severe sepsis & mods - christiannurse.christian.ac.th/pdf/sepsis and multiorgan...

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06/03/56 1 Severe sepsis & MODS: Assessment and management DR. PONGDHEP THEERAWIT M.D. PULMONARY AND CRITICAL CARE RAMATHIBODI HOSPITAL Understanding shock state Inadequate tissue perfusion Low perfusion pressure Low CO Low oxygen Inadequate tissue perfusion in hypovolemic and septic shock Hypovolemic Septic Perfusion pressure Low Low Cardiac output Low High Oxygen Low Low Stroke volume in shock Oxygen transport CaO2 DO2 = CO x CaO2 VO2 = CO x (SaO2-SvO2) SvO2 Normal microcirculation DO2 = 100 VO2 = 30 SvO2 = 70

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Page 1: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

1

Severe sepsis

amp MODS Assessment and managementDR PONGDHEP THEERAWIT MD

PULMONARY AND CRITICAL CARE

RAMATHIBODI HOSPITAL

Understanding shock state

Inadequate

tissue perfusion

Low perfusion pressure

Low CO

Low oxygen

Inadequate tissue perfusion in hypovolemic and septic shock

Hypovolemic Septic

Perfusion pressure Low Low

Cardiac output Low High

Oxygen Low Low

Stroke volume in shock

Oxygen transport

CaO2

DO2 =CO x CaO2VO2 = CO x (SaO2-SvO2)SvO2

Normal microcirculation

DO2 = 100

VO2 = 30

SvO2 = 70

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2

Microcirculation in sepsis

DO2 = 100

VO2 = 10

SvO2 = 90

Understanding shock state

Inadequate

tissue perfusion

Low perfusion

Pressure by

low vascular resistance

High CO

Microcirculation dysfunction

Mortality outcome of decrease vascular density in septic shock

De Backer D etal AJRCCM 2002 Sakr etal Crit Care Med 2004

Mean arterial pressure and perfused capillaries density by OPS

For all vessels and for large vessels there was NOsignificant relationship between the proportion of perfused vessels

and MAP CI pH SvO2 Hb conc

De Backer et al AJRCCM 2002

Cardiac index MAP and Microcirculation dysfunction

Characteristics of septic shock

Even high CO -gt low perfusion

Low vascular resistance -gt low perfusion pressure

Microcirculation obstruction -gt cellular

hypoxia

Even rising of MAP (higher perfusion

pressure)-gt cellular hypoxemia due

to microcirculation dysfunction

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3

Multiple organs dysfunction syndrome

Persistence of low

perfusion pressure

SIRS

Endothelial dysfunction

Microcirculation dysfunction

Mitochondrial dysfunction

Definition of sepsis (SSC 2012)

Severe sepsis (SSC 2012) Hemodynamic

parameters in 4 shocks

CVP PAP PCWP CO SVR

Hypovolemic Low Low Low Low High

Cardiogenic High High High Low High

Obstructive High Very high Normal Low High

Septic Not high Not high Not high High Low

Clinical signs in 4 shocks

JVP P2 CM PP DiasBP

Hypovolemic Low Soft No Narrow Low

Cardiogenic High Not loud Yes Narrow Low

Obstructive High Very loud Yes Narrow Low

Septic Not high Normal No Wide Very low

Clinical characteristics of different shocks

Clinical

Pulse pressure

Tachycardia

Extremity

Capillary refill

Bleeding

Narrow

Present

Cold

Impaired

AMI

Narrow

Present

Cold

Impaired

AMPE

Narrow

Present

Cold

Impaired

Absent

Low

Soft

Cardiomegaly

JVP

P2

Ltside

High

Loud

Rtside

High

Vloud

Sepsis

Wide

Present

Warm

Preserve

Absent

Not high

Not loud

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4

Assessment amp Management

Site of infection

Local

Lungs

Abdomen

Genito-urinary

Soft tissue

Systemic

Leptospirosis

Mellioidosis

Salmonellosis

Organisms

bull Gram positive

bull Gram negative

bull Community basedbull Hospital based

Gram positive bull

Gram negative bull

Primary peritonitis bullSecondary peritonitis bull

Appropriate antibiotic ASAP within 1 hr (SSC 2012)

Hemodynamic assessment

Assess cardiac output

Assess fluid responsiveness

Assess pulmonary leakage

Assess tissue perfusion

Cardiac output monitoring

Intermittent

PA catheter

ICU-US

Continuous

Thermodilution

Pulse contour analysis

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5

PA catheter

bull Proximal ndash cold injectate ScvO2

bull Distal ndash Draw SvO2

bull Thermistor ndash Temperature

bull Balloon inflation and deflation

Wave form

Waveform In place PA catheter

Joining Zeroing

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6

Others parameter calculated from PAC parameters

SVR = ( MAP - CVP CO ) x 80

PVR = ( PAP - PAOP CO ) x 80

CO = VO2 ( CaO2 - CvO2 )

DO2 = CO x Ca O2 x 10

VO2 = ( Ca O2 - Cv O2 ) x CO x10

Ca O2 = ( 139 x Hb x SaO2 ) + ( 0003 x PaO2 ) - Arterial

O2 content

Cv O2 = ( 139 x Hb x SvO2 ) + ( 0003 x PvO2 ) - Venous

O2 content

O2 extraxtion = VO2 DO2

QsQt = ( PA-a O2 ) ( PA-a O2 ) ( Ca-v O2 )

Cardiac output measurement

Fickrsquos formular

CO = VO2

CaO2-CvO2

Poor feasibility

Indicator dilution method

Indocyanine green

More accurate and reproducible

Require blood sampling

Recirculation of dye can disturb measurement

Thermodilution

More efficient

Thermo dilution method

Inject 5-10 cc of cold water

Tem

pera

ture

change (

)

Time

Stewart ndashHamilton equation

CO = ( TB ndash TI )xK

0 TB(t) dt

Hemodynamic

parameters in 4 shocks

CVP PAP PCWP CO SVR

Hypovolemic Low Low Low Low High

Cardiogenic High High High Low High

Obstructive High Very high Normal Low High

Septic Not high Not high Not high High Low

Ultrasound CO by ultrasound

A mount of blood flow going through a fixed orifice =

CSA x Flow-Velocity

SV = CSA x LVOTTVI

CSA = LVOTd2 x 078540

SV = LVOTd2 x 078540 x LVOTTVI

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7

LVOT diameter

LVOT VTI

good correlation between the thermodilutiontechnique and

Simpsons two-chamber method (r = 091)

Simpsons four-chamber method (r = 077)

the LVOT Doppler method (r = 094)

the LVOT Doppler method demonstrated acceptable agreement with a mean of 02

litresminute standard deviation of 082 litresminute and 95 limits of agreement of -15 to +19 litresminute

CCO-thermodilution methods Model for CCOtd

Agreement between CCO and BCO

in cardio-thoracic surgeryIntensive Care Med 199925166

Compare CCO and BCO in 20 medical ptsJ Crit Care 199813184

Conditions Number

MV 15

Vasopressor 15

Malignancy 12

Aplastic anemia

5

SLE 1

Cushing 1

CGD 1

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8

Good correlation between

CCO and BCO in sepsisIntensive Care Med 2002281276

Good correlation between CCO and BCO in sepsisIntensive Care Med 2002281276

Poor correlation of

CCO during hypothermia

Conclusions

Despite an excellent correlation accuracy and

precision between CCO and ICO before CPB and more than 45 minutes after hypothermic CPB a lack

of correlation in the early phase after CPB has been

found Further investigation is needed to elucidate the underlying cause of these findings and to clarify

whether ICO or CCO or both fail to represent the

real cardiac output up to 45 minutes after weaning from hypothermic CPB

19959405

Response time after sudden reduction of COAnesthesiology 199889(6)1592

Response time after sudden reduction of COCrit Care Med 1995 23 860 Advantages over IBCO

Provide continuous trend

Reduce contamination

Less time consuming

Unnecessary fluid

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9

Limitations

Immediate CO measurement may not be done due to average time for reduce thermal noise

Transpulmoanry thermodilution method (TPTD)

Compare TPTD and IBTDAnesthesia amp Analgesia 2010

The respiratory variation affect IBTD rather than TPTD

IBTD

TPTD

Advantages over IBTD

Less invasive

Decrease complications result from PA catheter

GEDV and EVLW can be measuredAm J Physiol Lung Cell Mol Physiol 291 L1118ndashL1131 2006

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10

Limitations

Canrsquot assess PA pressure and its trend

Canrsquot assess SvO2

Pulse contour analysis

Non-calibrated

Calibrated

Basic Principles

Traditional CO = HR SV

FloTrac system CO = PR x (AP )

Where = M (HR AP C(P) BSA MAP 3ap 4ap)

Validation ICOCCOAPCOCrit Care 200711R105

Validation ICOCCOAPCOCrit Care 200711R105

FloTrac amp PACCrit Care 201014R212

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11

FloTrac amp PACCrit Care 201014R212

FloTrac in sepsisIntensive Care 201137233

FloTrac in sepsisIntensive Care 201137233

FloTrac Vigileo G3

Advantages

Real time

Less invasive

Non-calibrated

Informative

CO CI

PPV

SvO2

SVR

Disadvantages

Algorithm-gtnot real

Accuracy

Can not assess RV

derived parameters

Require new version software

PiCCO system Need calibration

060356

12

PAC and PiCCO (AP)Crit Care 201014R212

PiCCO

Advantages

Continuos monitoring

More accurate

Informative

COCI

SVV

SVR

GEDV

EVLW

AP

Disadvantages

Require calibration q 8 hrs

Femoral site risky to

CRBSI

Early goal directed therapy

What is the CVP

CVP = Central Venous Pressure

Frank Starling amp venous return line

Stroke volume

CVP0

Frank-Starling curve

Stroke volume or EDV

JVP or CVP or PCWP

ΔSV or Δ EDV

a

b

Responders

Non-responders

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13

b

CVP tells us who responders

Stroke volume or EDV

CVP or PCWP

ΔSV or Δ EDV

a

Good

Bad

CVP vs Fluid responders

Crit Care Med 20073564-8

39 cases25 cases

Does Central Venous Pressure Predict

Fluid ResponsivenessA Systematic Review of the Literature

CHEST 2008 134172ndash178

Fluid resuscitation in septic shock a positive fluid balance and elevated central venous pressure are associated with increased mortalityBoyd JH Forbes J Nakada TA Walley KR Russell JA

OBJECTIVE

To determine whether central venous pressure and fluid balance after resuscitation for septic shock are associated

with mortality

PATIENTS

The Vasopressin in Septic Shock Trial (VASST) study enrolled 778 patients who had septic shock and who were

receiving a minimum of 5 μg of norepinephrine per minute

MEASUREMENTS AND MAIN RESULTS

Based on net fluid balance we determined whether ones fluid balance quartile was correlated with 28-day

mortality We also analyzed whether fluid balance was predictive of central venous pressure and furthermore

whether a guideline-recommended central venous pressure of 8-12 mm Hg yielded a mortality advantage At

enrollment which occurred on average 12 hrs after presentation the average fluid balance was +42 L By day 4 the

cumulative average fluid balance was +11 L After correcting for age and Acute Physiology and Chronic Health

Evaluation II score a more positive fluid balance at both at 12 hrs and day 4 correlated significantly with increased

mortality Central venous pressure was correlated with fluid balance at 12 hrs whereas on days 1-4 there was no

significant correlation At 12 hrs patients with central venous pressure lt8 mm Hg had the lowest mortality rate

followed by those with central venous pressure 8-12 mm Hg The highest mortality rate was observed in those with

central venous pressure gt12 mm Hg Contrary to the overall effect patients whose central venous pressure was lt8

mm Hg had improved survival with a more positive fluid balance

CONCLUSIONS

A more positive fluid balance both early in resuscitation and cumulatively over 4 days is associated with an increased

risk of mortality in septic shock Central venous pressure may be used to gauge fluid balance le 12 hrs into septic

shock but becomes an unreliable marker of fluid balance thereafter Optimal survival in the VASST study occurred

with a positive fluid balance of approximately 3 L at 12 hrs

Functional hemodynamic for predicting fluidresponsiveness

Spontaneous respiration

CVP variation gt 1 mmHg

PLR cCO gt 15 ( can be used in arrhythmia)

On mechanical ventilation

PPV gt 13

IVCd variation gt 12 ( can be used in arrhythmia)

IVC distensibility index gt 18 ( can be used in arrhythmia)

Brachail peak velocity gt 10

PLR cCO gt 15 ( can be used in arrhythmia)

PLR ET-CO2 gt 5

060356

14

PP variation predict fluid responsiveness

PPV = PPmax-PPmin x 100

(PPmax+PPmin)2

PPV gt 13 indicate fluid

responsiveness

PPV 94

NPV 96

Reference Year of

publication

Clinical setting PPV threshold value()

Michard etal

Viellard-Baron etal

Kramer etal

Preisman etal

Hofer etal

Feissel etal

De Backer etal

Cannesson etal

Solus-Biguenet etal

Lafanechere etal

Monnet etal

Charron etal

Natalini etal

Feissel etal

Cannesson etal

2000

2004

2004

2005

2005

2005

2005

2006

2006

2006

2006

2006

2006

2007

2007

Medical ICU

Medical ICU

CABG

CABG

CABG

Surgical and medical ICU

Surgical and medical ICU

CABG

Hepatic resection

Medical ICU

Medical ICU

Surgical ICU

Surgical and medical ICU

Medical ICU

CABG

13

12

11

9

13

17

12

12

14

12

12

10

15

12

11

Limitations

Controlled mechanical ventilation

Tidal volume ge 8 mlkg

Sinus rhythm

How to assess lung leakage

Clinical assessment

More dyspneic

Crepitation increase

Gas exchange

Desaturation

Lower pO2

Lung mechanic

Decrease lung compliance

CXR

May be difficult to determine in ARDS

The lung compliance

Respiratory system compliance

119862119877119878 =119879119907

119875119901119897119886119905119890119886119906minus119875119864119864119875

Bedside measurement of CRS

Pressure

Time

PEEP

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15

Bedside measurement of CRS

Pressure

Time

PEEP

Pplateau

PIP

After set Plateau time

Monitoring CRS (Volume mode)

Parameters Time 0 1 hour

PaO2 80 85

PaCO2 40 44

SaO2 96 97

PIP 35 45

Pplateau 30 36

PEEP 12 12

Exhaled TV 400 400

CRS222 167

FiO2 05 09

Fluid (ml) 0 1200

The EGDTPuzzle of formula

SvO2 Cellular oxygen

Good SvO2 means good cellular oxygenation (Low flow)

DO2 = 100

VO2 = 30

SvO2 = 70

Good SvO2 means good cellular oxygenation (heterogeneous flow)

DO2 = 100

VO2 = 10

SvO2 = 90

060356

16

Correlation between perfused capillary and blood lactateDe Backer etal Crit Care Med 2006

Prognostic value of hyperlactatemia in many

different critical care conditionsBlood lactate levels are superior to oxygen-derived

variables in predicting outcome in human septic shock

J Bakker M Coffernils M Leon P Gris and J L Vincent Chest 199199956-962

plt 005

plt 0001

Lactate level after 4 hrs of resuscitationS-W Lee etal Emerg Med J 200825659-665

Prognostic value of blood lactate levels in the ED

Shapiro NI et al Serum lactate as a predictor of mortality in emergency department patients with infection Ann Emerg Med 2005 45(5) p 524-8

490

900

2840

150

450

2240

000

500

1000

1500

2000

2500

3000

0-24 25-39 gt4

28 day in hospital mortality Death

Mo

rta

lity

ra

te

Lactate

Serum lactate as a predictor of mortalityin patients with infection

S Trzeciak et alIntensive Care Med (2007) 33970ndash977

Prognostic value of blood lactate levels

in the Critical care unit at Ramathibodihospital

Survivors 27

Non-survivors

5

0

1

2

3

4

5

6

Art

eri

al la

cta

te (

mm

ol

L)

p=NS

The Correlation Between Arterial Lactate and Venous Lactate in Patients With Sepsis and

Septic Shock (unpublished data)

Na Petvicharn C MD Theerawit P MD

Department of Internal Medicine the Faculty of Medicine Ramathibodi Hospital MahidolUniversity

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17

LACtime the predictor of organ failureJan Bakker et alAJS 1996171221-6

Lactate

Time

Lactime

AUC

Survivors

Non-survivors

P lt 005

2 mmolL

Serial blood lactate levels can predict the

development of multiple organ failure following septic shock

MD Jan Bakker MD Philippe Gris MD Michel Coffernils MD Robert J Kahn MD PhD Jean-

Louis Vincent The American Journal of surgery Volume 171 Issue 2 Pages 221-226 February 1996

plt005

plt 001

plt005 vs initial

blood lactate

Lactate clearance and mortalityArnold RC Shock 2008

0

10

20

30

40

50

60

70

LC gt 10 LC lt 10

Mortality rate

SvO2 gt 70

P lt 0001

Odds ratio for death 49(15-159)

Early lactate clearance is associated with

improved outcome in severe sepsis and

septic shock

H Bryant Nguyen MD MS Emanuel P Rivers MD MPH Bernhard P Knoblich MD

Gordon Jacobsen MS Alexandria Muzzin BS Julie A Ressler BS Michael C Tomlanovich

MDCrit Care Med 2004 Vol 32 No 8

Lactate clearance

= (Lactate ED presentation ndash Lactate Hour 6)x100Lactate ED presentation

There was an approximately

11 decrease likelihood of mortality for each 10 increase in lactate clearance

Association between blood lactate levels Sequential Organ Failure

Assessment subscores and 28-day mortality during

early and late ICU stay A retrospective observational study

Tim C Jansen Jasper van Bommel Roger Woodward Paul G H Mulder Jan Bakker Crit Care Med 2009 Vol 37 No 8

Dynamic Lactate Indices as

Predictors of Outcome in Critically Ill Patients

Admission lactate (LACADM)

Maximum lactate (LACMAX24)

Minimum lactate (LACMIN24)

Time weighted lactate (LACTW24)

Absolute change in (delta) lactate (LACΔ24)

Percentage change in lactate (LACΔ24)

Nichol A Bailey M Egi M Pettila V French C Hart GK Stachowski E Reade MCCooper

DJ Bellomo RCrit Care 2011 15R242

060356

18

Tissue perfusion

Lactate is better than SvO2 for assessment of tissue perfusion

The higher initial lactate the higher mortality

Lactate changing over time is better than a single value for monitoring

The higher lactate clearance the better

outcome

At least 10 reduction of lactate during resuscitation should be achieved

Type of fluid

Colloids or Crystalloids

26 Randomized trials

BMJ 1998316961-4

RR of death

Trauma 130(095-177)

Burn 121(088-166)

Sepsis 108(073-161)

Pooled 119(098-145)

Crystalloid and colloid infusion over 90 min in sepsis and non sepsis cases with

fluid responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid Colloid P value

CI before

CI after

EVLW

beforeEVLW after

39(24-55)

41(25-59)

71(19-339)75(16-299)

34(20-82)

38(23-69)

71(26-213)71(25-196)

Plt001

Pgt005

P value between before and after

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

060356

19

Crystalloid VS Colloid

No difference in

PLI

EVLW

Gas exchange

If fluid is administered in septic

patients with

fluid responsiveness even in ALI

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

Correction of albumin in ARDS

Refresher course ICM December 2008

Correction of albumin in ARDS

Refresher course ICM December 2008

Colloid solution

Albumin Artificial

Gelatins

Dextran

HES

Poor effective

Allergic reactionAltered hemostasis

Allergic reactionRenal dysfucntion

060356

20

Colloid solutions

Hypoalbuminemia tends to increase the incidence of ARDS and mortality in sepsis patients

More fluid required for correct hemodynamic abnormality

Poor response to Furosemide

More potential leakage at capillary site may lead to more lung injury

Correction of hypoalbuminemia in ARDS may be benefitial in terms of mortality but it must be used carefully

HES may cause renal failure and high dosage may lead to bleeding tendency

The benefit of artificial colloid solution over albumin is not known

Case

60 YO male patient 60 Kg

Pneumonia with septic shock on MV

VS BP 8040 mmHg HR 120 RR 26 BT 39oC

Heart normal S1S2 no murmur

Lungs crepitation RLL lingular segment

Liver and spleen not palpable

No edema

Neuro WNL

Case

Load NSS 1500 ml -gt PPV 14 -gt lung crepitation

BP 9040 mmHg (MAP = 57 mmHg)

Increase Nor-epinephrine

BP 8545 mmHg (MAP = 55 mmHg)

HR 90 -gt 110 min lactate 3 to 6 mmolL

Re-assessment

ABG

pH 71

pCO2 35 mmHg

pO2 70 mmHg

HCO3 15 mmolL

We corrected acidosis and start dobutamine

Can decrease dosage of NorE and lactate 41

The

EGDT

We need re-

assessment

here

These are causes of no

response to pressor

Acidosis

Poor LV contraction

RV dysfunction +- PE

Pneumothorax

Concealed hemorrhage

Relative adrenal insufficiency

Electrolyte imbalance

Severe sepsis

060356

21

Norepinephrine in septic shock

Study Baseline CI(normal 25-4)

EM Redl-Wenzl et al 1993Claude Martin et al 1993BLevy et al 1997Daniel De Backer et al 2003

Jacques Albane`se et al 2004Franccedilois Lauzier et al 2006

38+1153+1340+134+1

47+0244+14

Blood transfusion in septic shockJean-Louis Vincent Pongdhep Theerawit Davide Simeon

Basic Principles of Oxygen Transport and Calculations

Alternatives to Blood Transfusion in Transfusion Medicine 2nd Ed

Chapter 17 Published Online 4 SEP 2010

Transfusions will obviously have opposite effects to

anemia increasing blood viscosity and reducing the adrenergic response It is intriguing to consider

that transfusions may result in a decrease in

myocardial contractility Hence cardiac output often decreases following transfusions in the

nomovolemic patient and the increase in DO2

can be minor or even absent For example Shah et al observed in resuscitated trauma patients

that blood transfusion of one unit of RBC increased hemoglobin from 92 plusmn 03 to 102 plusmn 03

gdL but decreased cardiac output so that DO2

did not change

Hb lt 10 gL goal 10-12 gL

Hb lt 7 gL goal 7-9 gL

N=418

N=420

A MULTICENTER RANDOMIZED CONTROLLED CLINICAL

TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CAREPAULC HEacuteBERT MD GEORGEWELLS PHD MORRISA BLAJCHMAN MD JOHNMARSHALL MD CLAUDIOMARTIN MD GIUSEPPEPAGLIARELLO MD MARTINTWEEDDALE MD PHD IRWINSCHWEITZER MSC ELIZABETHYETISIR MSC ANDTHETRANSFUSIONREQUIREMENTSINCRITICALCAREINVESTIGATORSFORTHECANADIANCRITICALCARETRIALSGROUP

NEJM 1999

(normovolemia)

Red blood cell transfusion during septic shock in the ICUA Perner etal Acta Anaesthesiol Scand 2012 56 718ndash723

The CRIT Study Anemia and blood transfusion in the critically illmdashCurrent clinical practice in the United States

(Observational study 284 ICU 4892 patients)

Crit Care Med 2004 3239 ndash52

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 2: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

2

Microcirculation in sepsis

DO2 = 100

VO2 = 10

SvO2 = 90

Understanding shock state

Inadequate

tissue perfusion

Low perfusion

Pressure by

low vascular resistance

High CO

Microcirculation dysfunction

Mortality outcome of decrease vascular density in septic shock

De Backer D etal AJRCCM 2002 Sakr etal Crit Care Med 2004

Mean arterial pressure and perfused capillaries density by OPS

For all vessels and for large vessels there was NOsignificant relationship between the proportion of perfused vessels

and MAP CI pH SvO2 Hb conc

De Backer et al AJRCCM 2002

Cardiac index MAP and Microcirculation dysfunction

Characteristics of septic shock

Even high CO -gt low perfusion

Low vascular resistance -gt low perfusion pressure

Microcirculation obstruction -gt cellular

hypoxia

Even rising of MAP (higher perfusion

pressure)-gt cellular hypoxemia due

to microcirculation dysfunction

060356

3

Multiple organs dysfunction syndrome

Persistence of low

perfusion pressure

SIRS

Endothelial dysfunction

Microcirculation dysfunction

Mitochondrial dysfunction

Definition of sepsis (SSC 2012)

Severe sepsis (SSC 2012) Hemodynamic

parameters in 4 shocks

CVP PAP PCWP CO SVR

Hypovolemic Low Low Low Low High

Cardiogenic High High High Low High

Obstructive High Very high Normal Low High

Septic Not high Not high Not high High Low

Clinical signs in 4 shocks

JVP P2 CM PP DiasBP

Hypovolemic Low Soft No Narrow Low

Cardiogenic High Not loud Yes Narrow Low

Obstructive High Very loud Yes Narrow Low

Septic Not high Normal No Wide Very low

Clinical characteristics of different shocks

Clinical

Pulse pressure

Tachycardia

Extremity

Capillary refill

Bleeding

Narrow

Present

Cold

Impaired

AMI

Narrow

Present

Cold

Impaired

AMPE

Narrow

Present

Cold

Impaired

Absent

Low

Soft

Cardiomegaly

JVP

P2

Ltside

High

Loud

Rtside

High

Vloud

Sepsis

Wide

Present

Warm

Preserve

Absent

Not high

Not loud

060356

4

Assessment amp Management

Site of infection

Local

Lungs

Abdomen

Genito-urinary

Soft tissue

Systemic

Leptospirosis

Mellioidosis

Salmonellosis

Organisms

bull Gram positive

bull Gram negative

bull Community basedbull Hospital based

Gram positive bull

Gram negative bull

Primary peritonitis bullSecondary peritonitis bull

Appropriate antibiotic ASAP within 1 hr (SSC 2012)

Hemodynamic assessment

Assess cardiac output

Assess fluid responsiveness

Assess pulmonary leakage

Assess tissue perfusion

Cardiac output monitoring

Intermittent

PA catheter

ICU-US

Continuous

Thermodilution

Pulse contour analysis

060356

5

PA catheter

bull Proximal ndash cold injectate ScvO2

bull Distal ndash Draw SvO2

bull Thermistor ndash Temperature

bull Balloon inflation and deflation

Wave form

Waveform In place PA catheter

Joining Zeroing

060356

6

Others parameter calculated from PAC parameters

SVR = ( MAP - CVP CO ) x 80

PVR = ( PAP - PAOP CO ) x 80

CO = VO2 ( CaO2 - CvO2 )

DO2 = CO x Ca O2 x 10

VO2 = ( Ca O2 - Cv O2 ) x CO x10

Ca O2 = ( 139 x Hb x SaO2 ) + ( 0003 x PaO2 ) - Arterial

O2 content

Cv O2 = ( 139 x Hb x SvO2 ) + ( 0003 x PvO2 ) - Venous

O2 content

O2 extraxtion = VO2 DO2

QsQt = ( PA-a O2 ) ( PA-a O2 ) ( Ca-v O2 )

Cardiac output measurement

Fickrsquos formular

CO = VO2

CaO2-CvO2

Poor feasibility

Indicator dilution method

Indocyanine green

More accurate and reproducible

Require blood sampling

Recirculation of dye can disturb measurement

Thermodilution

More efficient

Thermo dilution method

Inject 5-10 cc of cold water

Tem

pera

ture

change (

)

Time

Stewart ndashHamilton equation

CO = ( TB ndash TI )xK

0 TB(t) dt

Hemodynamic

parameters in 4 shocks

CVP PAP PCWP CO SVR

Hypovolemic Low Low Low Low High

Cardiogenic High High High Low High

Obstructive High Very high Normal Low High

Septic Not high Not high Not high High Low

Ultrasound CO by ultrasound

A mount of blood flow going through a fixed orifice =

CSA x Flow-Velocity

SV = CSA x LVOTTVI

CSA = LVOTd2 x 078540

SV = LVOTd2 x 078540 x LVOTTVI

060356

7

LVOT diameter

LVOT VTI

good correlation between the thermodilutiontechnique and

Simpsons two-chamber method (r = 091)

Simpsons four-chamber method (r = 077)

the LVOT Doppler method (r = 094)

the LVOT Doppler method demonstrated acceptable agreement with a mean of 02

litresminute standard deviation of 082 litresminute and 95 limits of agreement of -15 to +19 litresminute

CCO-thermodilution methods Model for CCOtd

Agreement between CCO and BCO

in cardio-thoracic surgeryIntensive Care Med 199925166

Compare CCO and BCO in 20 medical ptsJ Crit Care 199813184

Conditions Number

MV 15

Vasopressor 15

Malignancy 12

Aplastic anemia

5

SLE 1

Cushing 1

CGD 1

060356

8

Good correlation between

CCO and BCO in sepsisIntensive Care Med 2002281276

Good correlation between CCO and BCO in sepsisIntensive Care Med 2002281276

Poor correlation of

CCO during hypothermia

Conclusions

Despite an excellent correlation accuracy and

precision between CCO and ICO before CPB and more than 45 minutes after hypothermic CPB a lack

of correlation in the early phase after CPB has been

found Further investigation is needed to elucidate the underlying cause of these findings and to clarify

whether ICO or CCO or both fail to represent the

real cardiac output up to 45 minutes after weaning from hypothermic CPB

19959405

Response time after sudden reduction of COAnesthesiology 199889(6)1592

Response time after sudden reduction of COCrit Care Med 1995 23 860 Advantages over IBCO

Provide continuous trend

Reduce contamination

Less time consuming

Unnecessary fluid

060356

9

Limitations

Immediate CO measurement may not be done due to average time for reduce thermal noise

Transpulmoanry thermodilution method (TPTD)

Compare TPTD and IBTDAnesthesia amp Analgesia 2010

The respiratory variation affect IBTD rather than TPTD

IBTD

TPTD

Advantages over IBTD

Less invasive

Decrease complications result from PA catheter

GEDV and EVLW can be measuredAm J Physiol Lung Cell Mol Physiol 291 L1118ndashL1131 2006

060356

10

Limitations

Canrsquot assess PA pressure and its trend

Canrsquot assess SvO2

Pulse contour analysis

Non-calibrated

Calibrated

Basic Principles

Traditional CO = HR SV

FloTrac system CO = PR x (AP )

Where = M (HR AP C(P) BSA MAP 3ap 4ap)

Validation ICOCCOAPCOCrit Care 200711R105

Validation ICOCCOAPCOCrit Care 200711R105

FloTrac amp PACCrit Care 201014R212

060356

11

FloTrac amp PACCrit Care 201014R212

FloTrac in sepsisIntensive Care 201137233

FloTrac in sepsisIntensive Care 201137233

FloTrac Vigileo G3

Advantages

Real time

Less invasive

Non-calibrated

Informative

CO CI

PPV

SvO2

SVR

Disadvantages

Algorithm-gtnot real

Accuracy

Can not assess RV

derived parameters

Require new version software

PiCCO system Need calibration

060356

12

PAC and PiCCO (AP)Crit Care 201014R212

PiCCO

Advantages

Continuos monitoring

More accurate

Informative

COCI

SVV

SVR

GEDV

EVLW

AP

Disadvantages

Require calibration q 8 hrs

Femoral site risky to

CRBSI

Early goal directed therapy

What is the CVP

CVP = Central Venous Pressure

Frank Starling amp venous return line

Stroke volume

CVP0

Frank-Starling curve

Stroke volume or EDV

JVP or CVP or PCWP

ΔSV or Δ EDV

a

b

Responders

Non-responders

060356

13

b

CVP tells us who responders

Stroke volume or EDV

CVP or PCWP

ΔSV or Δ EDV

a

Good

Bad

CVP vs Fluid responders

Crit Care Med 20073564-8

39 cases25 cases

Does Central Venous Pressure Predict

Fluid ResponsivenessA Systematic Review of the Literature

CHEST 2008 134172ndash178

Fluid resuscitation in septic shock a positive fluid balance and elevated central venous pressure are associated with increased mortalityBoyd JH Forbes J Nakada TA Walley KR Russell JA

OBJECTIVE

To determine whether central venous pressure and fluid balance after resuscitation for septic shock are associated

with mortality

PATIENTS

The Vasopressin in Septic Shock Trial (VASST) study enrolled 778 patients who had septic shock and who were

receiving a minimum of 5 μg of norepinephrine per minute

MEASUREMENTS AND MAIN RESULTS

Based on net fluid balance we determined whether ones fluid balance quartile was correlated with 28-day

mortality We also analyzed whether fluid balance was predictive of central venous pressure and furthermore

whether a guideline-recommended central venous pressure of 8-12 mm Hg yielded a mortality advantage At

enrollment which occurred on average 12 hrs after presentation the average fluid balance was +42 L By day 4 the

cumulative average fluid balance was +11 L After correcting for age and Acute Physiology and Chronic Health

Evaluation II score a more positive fluid balance at both at 12 hrs and day 4 correlated significantly with increased

mortality Central venous pressure was correlated with fluid balance at 12 hrs whereas on days 1-4 there was no

significant correlation At 12 hrs patients with central venous pressure lt8 mm Hg had the lowest mortality rate

followed by those with central venous pressure 8-12 mm Hg The highest mortality rate was observed in those with

central venous pressure gt12 mm Hg Contrary to the overall effect patients whose central venous pressure was lt8

mm Hg had improved survival with a more positive fluid balance

CONCLUSIONS

A more positive fluid balance both early in resuscitation and cumulatively over 4 days is associated with an increased

risk of mortality in septic shock Central venous pressure may be used to gauge fluid balance le 12 hrs into septic

shock but becomes an unreliable marker of fluid balance thereafter Optimal survival in the VASST study occurred

with a positive fluid balance of approximately 3 L at 12 hrs

Functional hemodynamic for predicting fluidresponsiveness

Spontaneous respiration

CVP variation gt 1 mmHg

PLR cCO gt 15 ( can be used in arrhythmia)

On mechanical ventilation

PPV gt 13

IVCd variation gt 12 ( can be used in arrhythmia)

IVC distensibility index gt 18 ( can be used in arrhythmia)

Brachail peak velocity gt 10

PLR cCO gt 15 ( can be used in arrhythmia)

PLR ET-CO2 gt 5

060356

14

PP variation predict fluid responsiveness

PPV = PPmax-PPmin x 100

(PPmax+PPmin)2

PPV gt 13 indicate fluid

responsiveness

PPV 94

NPV 96

Reference Year of

publication

Clinical setting PPV threshold value()

Michard etal

Viellard-Baron etal

Kramer etal

Preisman etal

Hofer etal

Feissel etal

De Backer etal

Cannesson etal

Solus-Biguenet etal

Lafanechere etal

Monnet etal

Charron etal

Natalini etal

Feissel etal

Cannesson etal

2000

2004

2004

2005

2005

2005

2005

2006

2006

2006

2006

2006

2006

2007

2007

Medical ICU

Medical ICU

CABG

CABG

CABG

Surgical and medical ICU

Surgical and medical ICU

CABG

Hepatic resection

Medical ICU

Medical ICU

Surgical ICU

Surgical and medical ICU

Medical ICU

CABG

13

12

11

9

13

17

12

12

14

12

12

10

15

12

11

Limitations

Controlled mechanical ventilation

Tidal volume ge 8 mlkg

Sinus rhythm

How to assess lung leakage

Clinical assessment

More dyspneic

Crepitation increase

Gas exchange

Desaturation

Lower pO2

Lung mechanic

Decrease lung compliance

CXR

May be difficult to determine in ARDS

The lung compliance

Respiratory system compliance

119862119877119878 =119879119907

119875119901119897119886119905119890119886119906minus119875119864119864119875

Bedside measurement of CRS

Pressure

Time

PEEP

060356

15

Bedside measurement of CRS

Pressure

Time

PEEP

Pplateau

PIP

After set Plateau time

Monitoring CRS (Volume mode)

Parameters Time 0 1 hour

PaO2 80 85

PaCO2 40 44

SaO2 96 97

PIP 35 45

Pplateau 30 36

PEEP 12 12

Exhaled TV 400 400

CRS222 167

FiO2 05 09

Fluid (ml) 0 1200

The EGDTPuzzle of formula

SvO2 Cellular oxygen

Good SvO2 means good cellular oxygenation (Low flow)

DO2 = 100

VO2 = 30

SvO2 = 70

Good SvO2 means good cellular oxygenation (heterogeneous flow)

DO2 = 100

VO2 = 10

SvO2 = 90

060356

16

Correlation between perfused capillary and blood lactateDe Backer etal Crit Care Med 2006

Prognostic value of hyperlactatemia in many

different critical care conditionsBlood lactate levels are superior to oxygen-derived

variables in predicting outcome in human septic shock

J Bakker M Coffernils M Leon P Gris and J L Vincent Chest 199199956-962

plt 005

plt 0001

Lactate level after 4 hrs of resuscitationS-W Lee etal Emerg Med J 200825659-665

Prognostic value of blood lactate levels in the ED

Shapiro NI et al Serum lactate as a predictor of mortality in emergency department patients with infection Ann Emerg Med 2005 45(5) p 524-8

490

900

2840

150

450

2240

000

500

1000

1500

2000

2500

3000

0-24 25-39 gt4

28 day in hospital mortality Death

Mo

rta

lity

ra

te

Lactate

Serum lactate as a predictor of mortalityin patients with infection

S Trzeciak et alIntensive Care Med (2007) 33970ndash977

Prognostic value of blood lactate levels

in the Critical care unit at Ramathibodihospital

Survivors 27

Non-survivors

5

0

1

2

3

4

5

6

Art

eri

al la

cta

te (

mm

ol

L)

p=NS

The Correlation Between Arterial Lactate and Venous Lactate in Patients With Sepsis and

Septic Shock (unpublished data)

Na Petvicharn C MD Theerawit P MD

Department of Internal Medicine the Faculty of Medicine Ramathibodi Hospital MahidolUniversity

060356

17

LACtime the predictor of organ failureJan Bakker et alAJS 1996171221-6

Lactate

Time

Lactime

AUC

Survivors

Non-survivors

P lt 005

2 mmolL

Serial blood lactate levels can predict the

development of multiple organ failure following septic shock

MD Jan Bakker MD Philippe Gris MD Michel Coffernils MD Robert J Kahn MD PhD Jean-

Louis Vincent The American Journal of surgery Volume 171 Issue 2 Pages 221-226 February 1996

plt005

plt 001

plt005 vs initial

blood lactate

Lactate clearance and mortalityArnold RC Shock 2008

0

10

20

30

40

50

60

70

LC gt 10 LC lt 10

Mortality rate

SvO2 gt 70

P lt 0001

Odds ratio for death 49(15-159)

Early lactate clearance is associated with

improved outcome in severe sepsis and

septic shock

H Bryant Nguyen MD MS Emanuel P Rivers MD MPH Bernhard P Knoblich MD

Gordon Jacobsen MS Alexandria Muzzin BS Julie A Ressler BS Michael C Tomlanovich

MDCrit Care Med 2004 Vol 32 No 8

Lactate clearance

= (Lactate ED presentation ndash Lactate Hour 6)x100Lactate ED presentation

There was an approximately

11 decrease likelihood of mortality for each 10 increase in lactate clearance

Association between blood lactate levels Sequential Organ Failure

Assessment subscores and 28-day mortality during

early and late ICU stay A retrospective observational study

Tim C Jansen Jasper van Bommel Roger Woodward Paul G H Mulder Jan Bakker Crit Care Med 2009 Vol 37 No 8

Dynamic Lactate Indices as

Predictors of Outcome in Critically Ill Patients

Admission lactate (LACADM)

Maximum lactate (LACMAX24)

Minimum lactate (LACMIN24)

Time weighted lactate (LACTW24)

Absolute change in (delta) lactate (LACΔ24)

Percentage change in lactate (LACΔ24)

Nichol A Bailey M Egi M Pettila V French C Hart GK Stachowski E Reade MCCooper

DJ Bellomo RCrit Care 2011 15R242

060356

18

Tissue perfusion

Lactate is better than SvO2 for assessment of tissue perfusion

The higher initial lactate the higher mortality

Lactate changing over time is better than a single value for monitoring

The higher lactate clearance the better

outcome

At least 10 reduction of lactate during resuscitation should be achieved

Type of fluid

Colloids or Crystalloids

26 Randomized trials

BMJ 1998316961-4

RR of death

Trauma 130(095-177)

Burn 121(088-166)

Sepsis 108(073-161)

Pooled 119(098-145)

Crystalloid and colloid infusion over 90 min in sepsis and non sepsis cases with

fluid responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid Colloid P value

CI before

CI after

EVLW

beforeEVLW after

39(24-55)

41(25-59)

71(19-339)75(16-299)

34(20-82)

38(23-69)

71(26-213)71(25-196)

Plt001

Pgt005

P value between before and after

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

060356

19

Crystalloid VS Colloid

No difference in

PLI

EVLW

Gas exchange

If fluid is administered in septic

patients with

fluid responsiveness even in ALI

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

Correction of albumin in ARDS

Refresher course ICM December 2008

Correction of albumin in ARDS

Refresher course ICM December 2008

Colloid solution

Albumin Artificial

Gelatins

Dextran

HES

Poor effective

Allergic reactionAltered hemostasis

Allergic reactionRenal dysfucntion

060356

20

Colloid solutions

Hypoalbuminemia tends to increase the incidence of ARDS and mortality in sepsis patients

More fluid required for correct hemodynamic abnormality

Poor response to Furosemide

More potential leakage at capillary site may lead to more lung injury

Correction of hypoalbuminemia in ARDS may be benefitial in terms of mortality but it must be used carefully

HES may cause renal failure and high dosage may lead to bleeding tendency

The benefit of artificial colloid solution over albumin is not known

Case

60 YO male patient 60 Kg

Pneumonia with septic shock on MV

VS BP 8040 mmHg HR 120 RR 26 BT 39oC

Heart normal S1S2 no murmur

Lungs crepitation RLL lingular segment

Liver and spleen not palpable

No edema

Neuro WNL

Case

Load NSS 1500 ml -gt PPV 14 -gt lung crepitation

BP 9040 mmHg (MAP = 57 mmHg)

Increase Nor-epinephrine

BP 8545 mmHg (MAP = 55 mmHg)

HR 90 -gt 110 min lactate 3 to 6 mmolL

Re-assessment

ABG

pH 71

pCO2 35 mmHg

pO2 70 mmHg

HCO3 15 mmolL

We corrected acidosis and start dobutamine

Can decrease dosage of NorE and lactate 41

The

EGDT

We need re-

assessment

here

These are causes of no

response to pressor

Acidosis

Poor LV contraction

RV dysfunction +- PE

Pneumothorax

Concealed hemorrhage

Relative adrenal insufficiency

Electrolyte imbalance

Severe sepsis

060356

21

Norepinephrine in septic shock

Study Baseline CI(normal 25-4)

EM Redl-Wenzl et al 1993Claude Martin et al 1993BLevy et al 1997Daniel De Backer et al 2003

Jacques Albane`se et al 2004Franccedilois Lauzier et al 2006

38+1153+1340+134+1

47+0244+14

Blood transfusion in septic shockJean-Louis Vincent Pongdhep Theerawit Davide Simeon

Basic Principles of Oxygen Transport and Calculations

Alternatives to Blood Transfusion in Transfusion Medicine 2nd Ed

Chapter 17 Published Online 4 SEP 2010

Transfusions will obviously have opposite effects to

anemia increasing blood viscosity and reducing the adrenergic response It is intriguing to consider

that transfusions may result in a decrease in

myocardial contractility Hence cardiac output often decreases following transfusions in the

nomovolemic patient and the increase in DO2

can be minor or even absent For example Shah et al observed in resuscitated trauma patients

that blood transfusion of one unit of RBC increased hemoglobin from 92 plusmn 03 to 102 plusmn 03

gdL but decreased cardiac output so that DO2

did not change

Hb lt 10 gL goal 10-12 gL

Hb lt 7 gL goal 7-9 gL

N=418

N=420

A MULTICENTER RANDOMIZED CONTROLLED CLINICAL

TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CAREPAULC HEacuteBERT MD GEORGEWELLS PHD MORRISA BLAJCHMAN MD JOHNMARSHALL MD CLAUDIOMARTIN MD GIUSEPPEPAGLIARELLO MD MARTINTWEEDDALE MD PHD IRWINSCHWEITZER MSC ELIZABETHYETISIR MSC ANDTHETRANSFUSIONREQUIREMENTSINCRITICALCAREINVESTIGATORSFORTHECANADIANCRITICALCARETRIALSGROUP

NEJM 1999

(normovolemia)

Red blood cell transfusion during septic shock in the ICUA Perner etal Acta Anaesthesiol Scand 2012 56 718ndash723

The CRIT Study Anemia and blood transfusion in the critically illmdashCurrent clinical practice in the United States

(Observational study 284 ICU 4892 patients)

Crit Care Med 2004 3239 ndash52

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 3: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

3

Multiple organs dysfunction syndrome

Persistence of low

perfusion pressure

SIRS

Endothelial dysfunction

Microcirculation dysfunction

Mitochondrial dysfunction

Definition of sepsis (SSC 2012)

Severe sepsis (SSC 2012) Hemodynamic

parameters in 4 shocks

CVP PAP PCWP CO SVR

Hypovolemic Low Low Low Low High

Cardiogenic High High High Low High

Obstructive High Very high Normal Low High

Septic Not high Not high Not high High Low

Clinical signs in 4 shocks

JVP P2 CM PP DiasBP

Hypovolemic Low Soft No Narrow Low

Cardiogenic High Not loud Yes Narrow Low

Obstructive High Very loud Yes Narrow Low

Septic Not high Normal No Wide Very low

Clinical characteristics of different shocks

Clinical

Pulse pressure

Tachycardia

Extremity

Capillary refill

Bleeding

Narrow

Present

Cold

Impaired

AMI

Narrow

Present

Cold

Impaired

AMPE

Narrow

Present

Cold

Impaired

Absent

Low

Soft

Cardiomegaly

JVP

P2

Ltside

High

Loud

Rtside

High

Vloud

Sepsis

Wide

Present

Warm

Preserve

Absent

Not high

Not loud

060356

4

Assessment amp Management

Site of infection

Local

Lungs

Abdomen

Genito-urinary

Soft tissue

Systemic

Leptospirosis

Mellioidosis

Salmonellosis

Organisms

bull Gram positive

bull Gram negative

bull Community basedbull Hospital based

Gram positive bull

Gram negative bull

Primary peritonitis bullSecondary peritonitis bull

Appropriate antibiotic ASAP within 1 hr (SSC 2012)

Hemodynamic assessment

Assess cardiac output

Assess fluid responsiveness

Assess pulmonary leakage

Assess tissue perfusion

Cardiac output monitoring

Intermittent

PA catheter

ICU-US

Continuous

Thermodilution

Pulse contour analysis

060356

5

PA catheter

bull Proximal ndash cold injectate ScvO2

bull Distal ndash Draw SvO2

bull Thermistor ndash Temperature

bull Balloon inflation and deflation

Wave form

Waveform In place PA catheter

Joining Zeroing

060356

6

Others parameter calculated from PAC parameters

SVR = ( MAP - CVP CO ) x 80

PVR = ( PAP - PAOP CO ) x 80

CO = VO2 ( CaO2 - CvO2 )

DO2 = CO x Ca O2 x 10

VO2 = ( Ca O2 - Cv O2 ) x CO x10

Ca O2 = ( 139 x Hb x SaO2 ) + ( 0003 x PaO2 ) - Arterial

O2 content

Cv O2 = ( 139 x Hb x SvO2 ) + ( 0003 x PvO2 ) - Venous

O2 content

O2 extraxtion = VO2 DO2

QsQt = ( PA-a O2 ) ( PA-a O2 ) ( Ca-v O2 )

Cardiac output measurement

Fickrsquos formular

CO = VO2

CaO2-CvO2

Poor feasibility

Indicator dilution method

Indocyanine green

More accurate and reproducible

Require blood sampling

Recirculation of dye can disturb measurement

Thermodilution

More efficient

Thermo dilution method

Inject 5-10 cc of cold water

Tem

pera

ture

change (

)

Time

Stewart ndashHamilton equation

CO = ( TB ndash TI )xK

0 TB(t) dt

Hemodynamic

parameters in 4 shocks

CVP PAP PCWP CO SVR

Hypovolemic Low Low Low Low High

Cardiogenic High High High Low High

Obstructive High Very high Normal Low High

Septic Not high Not high Not high High Low

Ultrasound CO by ultrasound

A mount of blood flow going through a fixed orifice =

CSA x Flow-Velocity

SV = CSA x LVOTTVI

CSA = LVOTd2 x 078540

SV = LVOTd2 x 078540 x LVOTTVI

060356

7

LVOT diameter

LVOT VTI

good correlation between the thermodilutiontechnique and

Simpsons two-chamber method (r = 091)

Simpsons four-chamber method (r = 077)

the LVOT Doppler method (r = 094)

the LVOT Doppler method demonstrated acceptable agreement with a mean of 02

litresminute standard deviation of 082 litresminute and 95 limits of agreement of -15 to +19 litresminute

CCO-thermodilution methods Model for CCOtd

Agreement between CCO and BCO

in cardio-thoracic surgeryIntensive Care Med 199925166

Compare CCO and BCO in 20 medical ptsJ Crit Care 199813184

Conditions Number

MV 15

Vasopressor 15

Malignancy 12

Aplastic anemia

5

SLE 1

Cushing 1

CGD 1

060356

8

Good correlation between

CCO and BCO in sepsisIntensive Care Med 2002281276

Good correlation between CCO and BCO in sepsisIntensive Care Med 2002281276

Poor correlation of

CCO during hypothermia

Conclusions

Despite an excellent correlation accuracy and

precision between CCO and ICO before CPB and more than 45 minutes after hypothermic CPB a lack

of correlation in the early phase after CPB has been

found Further investigation is needed to elucidate the underlying cause of these findings and to clarify

whether ICO or CCO or both fail to represent the

real cardiac output up to 45 minutes after weaning from hypothermic CPB

19959405

Response time after sudden reduction of COAnesthesiology 199889(6)1592

Response time after sudden reduction of COCrit Care Med 1995 23 860 Advantages over IBCO

Provide continuous trend

Reduce contamination

Less time consuming

Unnecessary fluid

060356

9

Limitations

Immediate CO measurement may not be done due to average time for reduce thermal noise

Transpulmoanry thermodilution method (TPTD)

Compare TPTD and IBTDAnesthesia amp Analgesia 2010

The respiratory variation affect IBTD rather than TPTD

IBTD

TPTD

Advantages over IBTD

Less invasive

Decrease complications result from PA catheter

GEDV and EVLW can be measuredAm J Physiol Lung Cell Mol Physiol 291 L1118ndashL1131 2006

060356

10

Limitations

Canrsquot assess PA pressure and its trend

Canrsquot assess SvO2

Pulse contour analysis

Non-calibrated

Calibrated

Basic Principles

Traditional CO = HR SV

FloTrac system CO = PR x (AP )

Where = M (HR AP C(P) BSA MAP 3ap 4ap)

Validation ICOCCOAPCOCrit Care 200711R105

Validation ICOCCOAPCOCrit Care 200711R105

FloTrac amp PACCrit Care 201014R212

060356

11

FloTrac amp PACCrit Care 201014R212

FloTrac in sepsisIntensive Care 201137233

FloTrac in sepsisIntensive Care 201137233

FloTrac Vigileo G3

Advantages

Real time

Less invasive

Non-calibrated

Informative

CO CI

PPV

SvO2

SVR

Disadvantages

Algorithm-gtnot real

Accuracy

Can not assess RV

derived parameters

Require new version software

PiCCO system Need calibration

060356

12

PAC and PiCCO (AP)Crit Care 201014R212

PiCCO

Advantages

Continuos monitoring

More accurate

Informative

COCI

SVV

SVR

GEDV

EVLW

AP

Disadvantages

Require calibration q 8 hrs

Femoral site risky to

CRBSI

Early goal directed therapy

What is the CVP

CVP = Central Venous Pressure

Frank Starling amp venous return line

Stroke volume

CVP0

Frank-Starling curve

Stroke volume or EDV

JVP or CVP or PCWP

ΔSV or Δ EDV

a

b

Responders

Non-responders

060356

13

b

CVP tells us who responders

Stroke volume or EDV

CVP or PCWP

ΔSV or Δ EDV

a

Good

Bad

CVP vs Fluid responders

Crit Care Med 20073564-8

39 cases25 cases

Does Central Venous Pressure Predict

Fluid ResponsivenessA Systematic Review of the Literature

CHEST 2008 134172ndash178

Fluid resuscitation in septic shock a positive fluid balance and elevated central venous pressure are associated with increased mortalityBoyd JH Forbes J Nakada TA Walley KR Russell JA

OBJECTIVE

To determine whether central venous pressure and fluid balance after resuscitation for septic shock are associated

with mortality

PATIENTS

The Vasopressin in Septic Shock Trial (VASST) study enrolled 778 patients who had septic shock and who were

receiving a minimum of 5 μg of norepinephrine per minute

MEASUREMENTS AND MAIN RESULTS

Based on net fluid balance we determined whether ones fluid balance quartile was correlated with 28-day

mortality We also analyzed whether fluid balance was predictive of central venous pressure and furthermore

whether a guideline-recommended central venous pressure of 8-12 mm Hg yielded a mortality advantage At

enrollment which occurred on average 12 hrs after presentation the average fluid balance was +42 L By day 4 the

cumulative average fluid balance was +11 L After correcting for age and Acute Physiology and Chronic Health

Evaluation II score a more positive fluid balance at both at 12 hrs and day 4 correlated significantly with increased

mortality Central venous pressure was correlated with fluid balance at 12 hrs whereas on days 1-4 there was no

significant correlation At 12 hrs patients with central venous pressure lt8 mm Hg had the lowest mortality rate

followed by those with central venous pressure 8-12 mm Hg The highest mortality rate was observed in those with

central venous pressure gt12 mm Hg Contrary to the overall effect patients whose central venous pressure was lt8

mm Hg had improved survival with a more positive fluid balance

CONCLUSIONS

A more positive fluid balance both early in resuscitation and cumulatively over 4 days is associated with an increased

risk of mortality in septic shock Central venous pressure may be used to gauge fluid balance le 12 hrs into septic

shock but becomes an unreliable marker of fluid balance thereafter Optimal survival in the VASST study occurred

with a positive fluid balance of approximately 3 L at 12 hrs

Functional hemodynamic for predicting fluidresponsiveness

Spontaneous respiration

CVP variation gt 1 mmHg

PLR cCO gt 15 ( can be used in arrhythmia)

On mechanical ventilation

PPV gt 13

IVCd variation gt 12 ( can be used in arrhythmia)

IVC distensibility index gt 18 ( can be used in arrhythmia)

Brachail peak velocity gt 10

PLR cCO gt 15 ( can be used in arrhythmia)

PLR ET-CO2 gt 5

060356

14

PP variation predict fluid responsiveness

PPV = PPmax-PPmin x 100

(PPmax+PPmin)2

PPV gt 13 indicate fluid

responsiveness

PPV 94

NPV 96

Reference Year of

publication

Clinical setting PPV threshold value()

Michard etal

Viellard-Baron etal

Kramer etal

Preisman etal

Hofer etal

Feissel etal

De Backer etal

Cannesson etal

Solus-Biguenet etal

Lafanechere etal

Monnet etal

Charron etal

Natalini etal

Feissel etal

Cannesson etal

2000

2004

2004

2005

2005

2005

2005

2006

2006

2006

2006

2006

2006

2007

2007

Medical ICU

Medical ICU

CABG

CABG

CABG

Surgical and medical ICU

Surgical and medical ICU

CABG

Hepatic resection

Medical ICU

Medical ICU

Surgical ICU

Surgical and medical ICU

Medical ICU

CABG

13

12

11

9

13

17

12

12

14

12

12

10

15

12

11

Limitations

Controlled mechanical ventilation

Tidal volume ge 8 mlkg

Sinus rhythm

How to assess lung leakage

Clinical assessment

More dyspneic

Crepitation increase

Gas exchange

Desaturation

Lower pO2

Lung mechanic

Decrease lung compliance

CXR

May be difficult to determine in ARDS

The lung compliance

Respiratory system compliance

119862119877119878 =119879119907

119875119901119897119886119905119890119886119906minus119875119864119864119875

Bedside measurement of CRS

Pressure

Time

PEEP

060356

15

Bedside measurement of CRS

Pressure

Time

PEEP

Pplateau

PIP

After set Plateau time

Monitoring CRS (Volume mode)

Parameters Time 0 1 hour

PaO2 80 85

PaCO2 40 44

SaO2 96 97

PIP 35 45

Pplateau 30 36

PEEP 12 12

Exhaled TV 400 400

CRS222 167

FiO2 05 09

Fluid (ml) 0 1200

The EGDTPuzzle of formula

SvO2 Cellular oxygen

Good SvO2 means good cellular oxygenation (Low flow)

DO2 = 100

VO2 = 30

SvO2 = 70

Good SvO2 means good cellular oxygenation (heterogeneous flow)

DO2 = 100

VO2 = 10

SvO2 = 90

060356

16

Correlation between perfused capillary and blood lactateDe Backer etal Crit Care Med 2006

Prognostic value of hyperlactatemia in many

different critical care conditionsBlood lactate levels are superior to oxygen-derived

variables in predicting outcome in human septic shock

J Bakker M Coffernils M Leon P Gris and J L Vincent Chest 199199956-962

plt 005

plt 0001

Lactate level after 4 hrs of resuscitationS-W Lee etal Emerg Med J 200825659-665

Prognostic value of blood lactate levels in the ED

Shapiro NI et al Serum lactate as a predictor of mortality in emergency department patients with infection Ann Emerg Med 2005 45(5) p 524-8

490

900

2840

150

450

2240

000

500

1000

1500

2000

2500

3000

0-24 25-39 gt4

28 day in hospital mortality Death

Mo

rta

lity

ra

te

Lactate

Serum lactate as a predictor of mortalityin patients with infection

S Trzeciak et alIntensive Care Med (2007) 33970ndash977

Prognostic value of blood lactate levels

in the Critical care unit at Ramathibodihospital

Survivors 27

Non-survivors

5

0

1

2

3

4

5

6

Art

eri

al la

cta

te (

mm

ol

L)

p=NS

The Correlation Between Arterial Lactate and Venous Lactate in Patients With Sepsis and

Septic Shock (unpublished data)

Na Petvicharn C MD Theerawit P MD

Department of Internal Medicine the Faculty of Medicine Ramathibodi Hospital MahidolUniversity

060356

17

LACtime the predictor of organ failureJan Bakker et alAJS 1996171221-6

Lactate

Time

Lactime

AUC

Survivors

Non-survivors

P lt 005

2 mmolL

Serial blood lactate levels can predict the

development of multiple organ failure following septic shock

MD Jan Bakker MD Philippe Gris MD Michel Coffernils MD Robert J Kahn MD PhD Jean-

Louis Vincent The American Journal of surgery Volume 171 Issue 2 Pages 221-226 February 1996

plt005

plt 001

plt005 vs initial

blood lactate

Lactate clearance and mortalityArnold RC Shock 2008

0

10

20

30

40

50

60

70

LC gt 10 LC lt 10

Mortality rate

SvO2 gt 70

P lt 0001

Odds ratio for death 49(15-159)

Early lactate clearance is associated with

improved outcome in severe sepsis and

septic shock

H Bryant Nguyen MD MS Emanuel P Rivers MD MPH Bernhard P Knoblich MD

Gordon Jacobsen MS Alexandria Muzzin BS Julie A Ressler BS Michael C Tomlanovich

MDCrit Care Med 2004 Vol 32 No 8

Lactate clearance

= (Lactate ED presentation ndash Lactate Hour 6)x100Lactate ED presentation

There was an approximately

11 decrease likelihood of mortality for each 10 increase in lactate clearance

Association between blood lactate levels Sequential Organ Failure

Assessment subscores and 28-day mortality during

early and late ICU stay A retrospective observational study

Tim C Jansen Jasper van Bommel Roger Woodward Paul G H Mulder Jan Bakker Crit Care Med 2009 Vol 37 No 8

Dynamic Lactate Indices as

Predictors of Outcome in Critically Ill Patients

Admission lactate (LACADM)

Maximum lactate (LACMAX24)

Minimum lactate (LACMIN24)

Time weighted lactate (LACTW24)

Absolute change in (delta) lactate (LACΔ24)

Percentage change in lactate (LACΔ24)

Nichol A Bailey M Egi M Pettila V French C Hart GK Stachowski E Reade MCCooper

DJ Bellomo RCrit Care 2011 15R242

060356

18

Tissue perfusion

Lactate is better than SvO2 for assessment of tissue perfusion

The higher initial lactate the higher mortality

Lactate changing over time is better than a single value for monitoring

The higher lactate clearance the better

outcome

At least 10 reduction of lactate during resuscitation should be achieved

Type of fluid

Colloids or Crystalloids

26 Randomized trials

BMJ 1998316961-4

RR of death

Trauma 130(095-177)

Burn 121(088-166)

Sepsis 108(073-161)

Pooled 119(098-145)

Crystalloid and colloid infusion over 90 min in sepsis and non sepsis cases with

fluid responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid Colloid P value

CI before

CI after

EVLW

beforeEVLW after

39(24-55)

41(25-59)

71(19-339)75(16-299)

34(20-82)

38(23-69)

71(26-213)71(25-196)

Plt001

Pgt005

P value between before and after

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

060356

19

Crystalloid VS Colloid

No difference in

PLI

EVLW

Gas exchange

If fluid is administered in septic

patients with

fluid responsiveness even in ALI

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

Correction of albumin in ARDS

Refresher course ICM December 2008

Correction of albumin in ARDS

Refresher course ICM December 2008

Colloid solution

Albumin Artificial

Gelatins

Dextran

HES

Poor effective

Allergic reactionAltered hemostasis

Allergic reactionRenal dysfucntion

060356

20

Colloid solutions

Hypoalbuminemia tends to increase the incidence of ARDS and mortality in sepsis patients

More fluid required for correct hemodynamic abnormality

Poor response to Furosemide

More potential leakage at capillary site may lead to more lung injury

Correction of hypoalbuminemia in ARDS may be benefitial in terms of mortality but it must be used carefully

HES may cause renal failure and high dosage may lead to bleeding tendency

The benefit of artificial colloid solution over albumin is not known

Case

60 YO male patient 60 Kg

Pneumonia with septic shock on MV

VS BP 8040 mmHg HR 120 RR 26 BT 39oC

Heart normal S1S2 no murmur

Lungs crepitation RLL lingular segment

Liver and spleen not palpable

No edema

Neuro WNL

Case

Load NSS 1500 ml -gt PPV 14 -gt lung crepitation

BP 9040 mmHg (MAP = 57 mmHg)

Increase Nor-epinephrine

BP 8545 mmHg (MAP = 55 mmHg)

HR 90 -gt 110 min lactate 3 to 6 mmolL

Re-assessment

ABG

pH 71

pCO2 35 mmHg

pO2 70 mmHg

HCO3 15 mmolL

We corrected acidosis and start dobutamine

Can decrease dosage of NorE and lactate 41

The

EGDT

We need re-

assessment

here

These are causes of no

response to pressor

Acidosis

Poor LV contraction

RV dysfunction +- PE

Pneumothorax

Concealed hemorrhage

Relative adrenal insufficiency

Electrolyte imbalance

Severe sepsis

060356

21

Norepinephrine in septic shock

Study Baseline CI(normal 25-4)

EM Redl-Wenzl et al 1993Claude Martin et al 1993BLevy et al 1997Daniel De Backer et al 2003

Jacques Albane`se et al 2004Franccedilois Lauzier et al 2006

38+1153+1340+134+1

47+0244+14

Blood transfusion in septic shockJean-Louis Vincent Pongdhep Theerawit Davide Simeon

Basic Principles of Oxygen Transport and Calculations

Alternatives to Blood Transfusion in Transfusion Medicine 2nd Ed

Chapter 17 Published Online 4 SEP 2010

Transfusions will obviously have opposite effects to

anemia increasing blood viscosity and reducing the adrenergic response It is intriguing to consider

that transfusions may result in a decrease in

myocardial contractility Hence cardiac output often decreases following transfusions in the

nomovolemic patient and the increase in DO2

can be minor or even absent For example Shah et al observed in resuscitated trauma patients

that blood transfusion of one unit of RBC increased hemoglobin from 92 plusmn 03 to 102 plusmn 03

gdL but decreased cardiac output so that DO2

did not change

Hb lt 10 gL goal 10-12 gL

Hb lt 7 gL goal 7-9 gL

N=418

N=420

A MULTICENTER RANDOMIZED CONTROLLED CLINICAL

TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CAREPAULC HEacuteBERT MD GEORGEWELLS PHD MORRISA BLAJCHMAN MD JOHNMARSHALL MD CLAUDIOMARTIN MD GIUSEPPEPAGLIARELLO MD MARTINTWEEDDALE MD PHD IRWINSCHWEITZER MSC ELIZABETHYETISIR MSC ANDTHETRANSFUSIONREQUIREMENTSINCRITICALCAREINVESTIGATORSFORTHECANADIANCRITICALCARETRIALSGROUP

NEJM 1999

(normovolemia)

Red blood cell transfusion during septic shock in the ICUA Perner etal Acta Anaesthesiol Scand 2012 56 718ndash723

The CRIT Study Anemia and blood transfusion in the critically illmdashCurrent clinical practice in the United States

(Observational study 284 ICU 4892 patients)

Crit Care Med 2004 3239 ndash52

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 4: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

4

Assessment amp Management

Site of infection

Local

Lungs

Abdomen

Genito-urinary

Soft tissue

Systemic

Leptospirosis

Mellioidosis

Salmonellosis

Organisms

bull Gram positive

bull Gram negative

bull Community basedbull Hospital based

Gram positive bull

Gram negative bull

Primary peritonitis bullSecondary peritonitis bull

Appropriate antibiotic ASAP within 1 hr (SSC 2012)

Hemodynamic assessment

Assess cardiac output

Assess fluid responsiveness

Assess pulmonary leakage

Assess tissue perfusion

Cardiac output monitoring

Intermittent

PA catheter

ICU-US

Continuous

Thermodilution

Pulse contour analysis

060356

5

PA catheter

bull Proximal ndash cold injectate ScvO2

bull Distal ndash Draw SvO2

bull Thermistor ndash Temperature

bull Balloon inflation and deflation

Wave form

Waveform In place PA catheter

Joining Zeroing

060356

6

Others parameter calculated from PAC parameters

SVR = ( MAP - CVP CO ) x 80

PVR = ( PAP - PAOP CO ) x 80

CO = VO2 ( CaO2 - CvO2 )

DO2 = CO x Ca O2 x 10

VO2 = ( Ca O2 - Cv O2 ) x CO x10

Ca O2 = ( 139 x Hb x SaO2 ) + ( 0003 x PaO2 ) - Arterial

O2 content

Cv O2 = ( 139 x Hb x SvO2 ) + ( 0003 x PvO2 ) - Venous

O2 content

O2 extraxtion = VO2 DO2

QsQt = ( PA-a O2 ) ( PA-a O2 ) ( Ca-v O2 )

Cardiac output measurement

Fickrsquos formular

CO = VO2

CaO2-CvO2

Poor feasibility

Indicator dilution method

Indocyanine green

More accurate and reproducible

Require blood sampling

Recirculation of dye can disturb measurement

Thermodilution

More efficient

Thermo dilution method

Inject 5-10 cc of cold water

Tem

pera

ture

change (

)

Time

Stewart ndashHamilton equation

CO = ( TB ndash TI )xK

0 TB(t) dt

Hemodynamic

parameters in 4 shocks

CVP PAP PCWP CO SVR

Hypovolemic Low Low Low Low High

Cardiogenic High High High Low High

Obstructive High Very high Normal Low High

Septic Not high Not high Not high High Low

Ultrasound CO by ultrasound

A mount of blood flow going through a fixed orifice =

CSA x Flow-Velocity

SV = CSA x LVOTTVI

CSA = LVOTd2 x 078540

SV = LVOTd2 x 078540 x LVOTTVI

060356

7

LVOT diameter

LVOT VTI

good correlation between the thermodilutiontechnique and

Simpsons two-chamber method (r = 091)

Simpsons four-chamber method (r = 077)

the LVOT Doppler method (r = 094)

the LVOT Doppler method demonstrated acceptable agreement with a mean of 02

litresminute standard deviation of 082 litresminute and 95 limits of agreement of -15 to +19 litresminute

CCO-thermodilution methods Model for CCOtd

Agreement between CCO and BCO

in cardio-thoracic surgeryIntensive Care Med 199925166

Compare CCO and BCO in 20 medical ptsJ Crit Care 199813184

Conditions Number

MV 15

Vasopressor 15

Malignancy 12

Aplastic anemia

5

SLE 1

Cushing 1

CGD 1

060356

8

Good correlation between

CCO and BCO in sepsisIntensive Care Med 2002281276

Good correlation between CCO and BCO in sepsisIntensive Care Med 2002281276

Poor correlation of

CCO during hypothermia

Conclusions

Despite an excellent correlation accuracy and

precision between CCO and ICO before CPB and more than 45 minutes after hypothermic CPB a lack

of correlation in the early phase after CPB has been

found Further investigation is needed to elucidate the underlying cause of these findings and to clarify

whether ICO or CCO or both fail to represent the

real cardiac output up to 45 minutes after weaning from hypothermic CPB

19959405

Response time after sudden reduction of COAnesthesiology 199889(6)1592

Response time after sudden reduction of COCrit Care Med 1995 23 860 Advantages over IBCO

Provide continuous trend

Reduce contamination

Less time consuming

Unnecessary fluid

060356

9

Limitations

Immediate CO measurement may not be done due to average time for reduce thermal noise

Transpulmoanry thermodilution method (TPTD)

Compare TPTD and IBTDAnesthesia amp Analgesia 2010

The respiratory variation affect IBTD rather than TPTD

IBTD

TPTD

Advantages over IBTD

Less invasive

Decrease complications result from PA catheter

GEDV and EVLW can be measuredAm J Physiol Lung Cell Mol Physiol 291 L1118ndashL1131 2006

060356

10

Limitations

Canrsquot assess PA pressure and its trend

Canrsquot assess SvO2

Pulse contour analysis

Non-calibrated

Calibrated

Basic Principles

Traditional CO = HR SV

FloTrac system CO = PR x (AP )

Where = M (HR AP C(P) BSA MAP 3ap 4ap)

Validation ICOCCOAPCOCrit Care 200711R105

Validation ICOCCOAPCOCrit Care 200711R105

FloTrac amp PACCrit Care 201014R212

060356

11

FloTrac amp PACCrit Care 201014R212

FloTrac in sepsisIntensive Care 201137233

FloTrac in sepsisIntensive Care 201137233

FloTrac Vigileo G3

Advantages

Real time

Less invasive

Non-calibrated

Informative

CO CI

PPV

SvO2

SVR

Disadvantages

Algorithm-gtnot real

Accuracy

Can not assess RV

derived parameters

Require new version software

PiCCO system Need calibration

060356

12

PAC and PiCCO (AP)Crit Care 201014R212

PiCCO

Advantages

Continuos monitoring

More accurate

Informative

COCI

SVV

SVR

GEDV

EVLW

AP

Disadvantages

Require calibration q 8 hrs

Femoral site risky to

CRBSI

Early goal directed therapy

What is the CVP

CVP = Central Venous Pressure

Frank Starling amp venous return line

Stroke volume

CVP0

Frank-Starling curve

Stroke volume or EDV

JVP or CVP or PCWP

ΔSV or Δ EDV

a

b

Responders

Non-responders

060356

13

b

CVP tells us who responders

Stroke volume or EDV

CVP or PCWP

ΔSV or Δ EDV

a

Good

Bad

CVP vs Fluid responders

Crit Care Med 20073564-8

39 cases25 cases

Does Central Venous Pressure Predict

Fluid ResponsivenessA Systematic Review of the Literature

CHEST 2008 134172ndash178

Fluid resuscitation in septic shock a positive fluid balance and elevated central venous pressure are associated with increased mortalityBoyd JH Forbes J Nakada TA Walley KR Russell JA

OBJECTIVE

To determine whether central venous pressure and fluid balance after resuscitation for septic shock are associated

with mortality

PATIENTS

The Vasopressin in Septic Shock Trial (VASST) study enrolled 778 patients who had septic shock and who were

receiving a minimum of 5 μg of norepinephrine per minute

MEASUREMENTS AND MAIN RESULTS

Based on net fluid balance we determined whether ones fluid balance quartile was correlated with 28-day

mortality We also analyzed whether fluid balance was predictive of central venous pressure and furthermore

whether a guideline-recommended central venous pressure of 8-12 mm Hg yielded a mortality advantage At

enrollment which occurred on average 12 hrs after presentation the average fluid balance was +42 L By day 4 the

cumulative average fluid balance was +11 L After correcting for age and Acute Physiology and Chronic Health

Evaluation II score a more positive fluid balance at both at 12 hrs and day 4 correlated significantly with increased

mortality Central venous pressure was correlated with fluid balance at 12 hrs whereas on days 1-4 there was no

significant correlation At 12 hrs patients with central venous pressure lt8 mm Hg had the lowest mortality rate

followed by those with central venous pressure 8-12 mm Hg The highest mortality rate was observed in those with

central venous pressure gt12 mm Hg Contrary to the overall effect patients whose central venous pressure was lt8

mm Hg had improved survival with a more positive fluid balance

CONCLUSIONS

A more positive fluid balance both early in resuscitation and cumulatively over 4 days is associated with an increased

risk of mortality in septic shock Central venous pressure may be used to gauge fluid balance le 12 hrs into septic

shock but becomes an unreliable marker of fluid balance thereafter Optimal survival in the VASST study occurred

with a positive fluid balance of approximately 3 L at 12 hrs

Functional hemodynamic for predicting fluidresponsiveness

Spontaneous respiration

CVP variation gt 1 mmHg

PLR cCO gt 15 ( can be used in arrhythmia)

On mechanical ventilation

PPV gt 13

IVCd variation gt 12 ( can be used in arrhythmia)

IVC distensibility index gt 18 ( can be used in arrhythmia)

Brachail peak velocity gt 10

PLR cCO gt 15 ( can be used in arrhythmia)

PLR ET-CO2 gt 5

060356

14

PP variation predict fluid responsiveness

PPV = PPmax-PPmin x 100

(PPmax+PPmin)2

PPV gt 13 indicate fluid

responsiveness

PPV 94

NPV 96

Reference Year of

publication

Clinical setting PPV threshold value()

Michard etal

Viellard-Baron etal

Kramer etal

Preisman etal

Hofer etal

Feissel etal

De Backer etal

Cannesson etal

Solus-Biguenet etal

Lafanechere etal

Monnet etal

Charron etal

Natalini etal

Feissel etal

Cannesson etal

2000

2004

2004

2005

2005

2005

2005

2006

2006

2006

2006

2006

2006

2007

2007

Medical ICU

Medical ICU

CABG

CABG

CABG

Surgical and medical ICU

Surgical and medical ICU

CABG

Hepatic resection

Medical ICU

Medical ICU

Surgical ICU

Surgical and medical ICU

Medical ICU

CABG

13

12

11

9

13

17

12

12

14

12

12

10

15

12

11

Limitations

Controlled mechanical ventilation

Tidal volume ge 8 mlkg

Sinus rhythm

How to assess lung leakage

Clinical assessment

More dyspneic

Crepitation increase

Gas exchange

Desaturation

Lower pO2

Lung mechanic

Decrease lung compliance

CXR

May be difficult to determine in ARDS

The lung compliance

Respiratory system compliance

119862119877119878 =119879119907

119875119901119897119886119905119890119886119906minus119875119864119864119875

Bedside measurement of CRS

Pressure

Time

PEEP

060356

15

Bedside measurement of CRS

Pressure

Time

PEEP

Pplateau

PIP

After set Plateau time

Monitoring CRS (Volume mode)

Parameters Time 0 1 hour

PaO2 80 85

PaCO2 40 44

SaO2 96 97

PIP 35 45

Pplateau 30 36

PEEP 12 12

Exhaled TV 400 400

CRS222 167

FiO2 05 09

Fluid (ml) 0 1200

The EGDTPuzzle of formula

SvO2 Cellular oxygen

Good SvO2 means good cellular oxygenation (Low flow)

DO2 = 100

VO2 = 30

SvO2 = 70

Good SvO2 means good cellular oxygenation (heterogeneous flow)

DO2 = 100

VO2 = 10

SvO2 = 90

060356

16

Correlation between perfused capillary and blood lactateDe Backer etal Crit Care Med 2006

Prognostic value of hyperlactatemia in many

different critical care conditionsBlood lactate levels are superior to oxygen-derived

variables in predicting outcome in human septic shock

J Bakker M Coffernils M Leon P Gris and J L Vincent Chest 199199956-962

plt 005

plt 0001

Lactate level after 4 hrs of resuscitationS-W Lee etal Emerg Med J 200825659-665

Prognostic value of blood lactate levels in the ED

Shapiro NI et al Serum lactate as a predictor of mortality in emergency department patients with infection Ann Emerg Med 2005 45(5) p 524-8

490

900

2840

150

450

2240

000

500

1000

1500

2000

2500

3000

0-24 25-39 gt4

28 day in hospital mortality Death

Mo

rta

lity

ra

te

Lactate

Serum lactate as a predictor of mortalityin patients with infection

S Trzeciak et alIntensive Care Med (2007) 33970ndash977

Prognostic value of blood lactate levels

in the Critical care unit at Ramathibodihospital

Survivors 27

Non-survivors

5

0

1

2

3

4

5

6

Art

eri

al la

cta

te (

mm

ol

L)

p=NS

The Correlation Between Arterial Lactate and Venous Lactate in Patients With Sepsis and

Septic Shock (unpublished data)

Na Petvicharn C MD Theerawit P MD

Department of Internal Medicine the Faculty of Medicine Ramathibodi Hospital MahidolUniversity

060356

17

LACtime the predictor of organ failureJan Bakker et alAJS 1996171221-6

Lactate

Time

Lactime

AUC

Survivors

Non-survivors

P lt 005

2 mmolL

Serial blood lactate levels can predict the

development of multiple organ failure following septic shock

MD Jan Bakker MD Philippe Gris MD Michel Coffernils MD Robert J Kahn MD PhD Jean-

Louis Vincent The American Journal of surgery Volume 171 Issue 2 Pages 221-226 February 1996

plt005

plt 001

plt005 vs initial

blood lactate

Lactate clearance and mortalityArnold RC Shock 2008

0

10

20

30

40

50

60

70

LC gt 10 LC lt 10

Mortality rate

SvO2 gt 70

P lt 0001

Odds ratio for death 49(15-159)

Early lactate clearance is associated with

improved outcome in severe sepsis and

septic shock

H Bryant Nguyen MD MS Emanuel P Rivers MD MPH Bernhard P Knoblich MD

Gordon Jacobsen MS Alexandria Muzzin BS Julie A Ressler BS Michael C Tomlanovich

MDCrit Care Med 2004 Vol 32 No 8

Lactate clearance

= (Lactate ED presentation ndash Lactate Hour 6)x100Lactate ED presentation

There was an approximately

11 decrease likelihood of mortality for each 10 increase in lactate clearance

Association between blood lactate levels Sequential Organ Failure

Assessment subscores and 28-day mortality during

early and late ICU stay A retrospective observational study

Tim C Jansen Jasper van Bommel Roger Woodward Paul G H Mulder Jan Bakker Crit Care Med 2009 Vol 37 No 8

Dynamic Lactate Indices as

Predictors of Outcome in Critically Ill Patients

Admission lactate (LACADM)

Maximum lactate (LACMAX24)

Minimum lactate (LACMIN24)

Time weighted lactate (LACTW24)

Absolute change in (delta) lactate (LACΔ24)

Percentage change in lactate (LACΔ24)

Nichol A Bailey M Egi M Pettila V French C Hart GK Stachowski E Reade MCCooper

DJ Bellomo RCrit Care 2011 15R242

060356

18

Tissue perfusion

Lactate is better than SvO2 for assessment of tissue perfusion

The higher initial lactate the higher mortality

Lactate changing over time is better than a single value for monitoring

The higher lactate clearance the better

outcome

At least 10 reduction of lactate during resuscitation should be achieved

Type of fluid

Colloids or Crystalloids

26 Randomized trials

BMJ 1998316961-4

RR of death

Trauma 130(095-177)

Burn 121(088-166)

Sepsis 108(073-161)

Pooled 119(098-145)

Crystalloid and colloid infusion over 90 min in sepsis and non sepsis cases with

fluid responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid Colloid P value

CI before

CI after

EVLW

beforeEVLW after

39(24-55)

41(25-59)

71(19-339)75(16-299)

34(20-82)

38(23-69)

71(26-213)71(25-196)

Plt001

Pgt005

P value between before and after

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

060356

19

Crystalloid VS Colloid

No difference in

PLI

EVLW

Gas exchange

If fluid is administered in septic

patients with

fluid responsiveness even in ALI

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

Correction of albumin in ARDS

Refresher course ICM December 2008

Correction of albumin in ARDS

Refresher course ICM December 2008

Colloid solution

Albumin Artificial

Gelatins

Dextran

HES

Poor effective

Allergic reactionAltered hemostasis

Allergic reactionRenal dysfucntion

060356

20

Colloid solutions

Hypoalbuminemia tends to increase the incidence of ARDS and mortality in sepsis patients

More fluid required for correct hemodynamic abnormality

Poor response to Furosemide

More potential leakage at capillary site may lead to more lung injury

Correction of hypoalbuminemia in ARDS may be benefitial in terms of mortality but it must be used carefully

HES may cause renal failure and high dosage may lead to bleeding tendency

The benefit of artificial colloid solution over albumin is not known

Case

60 YO male patient 60 Kg

Pneumonia with septic shock on MV

VS BP 8040 mmHg HR 120 RR 26 BT 39oC

Heart normal S1S2 no murmur

Lungs crepitation RLL lingular segment

Liver and spleen not palpable

No edema

Neuro WNL

Case

Load NSS 1500 ml -gt PPV 14 -gt lung crepitation

BP 9040 mmHg (MAP = 57 mmHg)

Increase Nor-epinephrine

BP 8545 mmHg (MAP = 55 mmHg)

HR 90 -gt 110 min lactate 3 to 6 mmolL

Re-assessment

ABG

pH 71

pCO2 35 mmHg

pO2 70 mmHg

HCO3 15 mmolL

We corrected acidosis and start dobutamine

Can decrease dosage of NorE and lactate 41

The

EGDT

We need re-

assessment

here

These are causes of no

response to pressor

Acidosis

Poor LV contraction

RV dysfunction +- PE

Pneumothorax

Concealed hemorrhage

Relative adrenal insufficiency

Electrolyte imbalance

Severe sepsis

060356

21

Norepinephrine in septic shock

Study Baseline CI(normal 25-4)

EM Redl-Wenzl et al 1993Claude Martin et al 1993BLevy et al 1997Daniel De Backer et al 2003

Jacques Albane`se et al 2004Franccedilois Lauzier et al 2006

38+1153+1340+134+1

47+0244+14

Blood transfusion in septic shockJean-Louis Vincent Pongdhep Theerawit Davide Simeon

Basic Principles of Oxygen Transport and Calculations

Alternatives to Blood Transfusion in Transfusion Medicine 2nd Ed

Chapter 17 Published Online 4 SEP 2010

Transfusions will obviously have opposite effects to

anemia increasing blood viscosity and reducing the adrenergic response It is intriguing to consider

that transfusions may result in a decrease in

myocardial contractility Hence cardiac output often decreases following transfusions in the

nomovolemic patient and the increase in DO2

can be minor or even absent For example Shah et al observed in resuscitated trauma patients

that blood transfusion of one unit of RBC increased hemoglobin from 92 plusmn 03 to 102 plusmn 03

gdL but decreased cardiac output so that DO2

did not change

Hb lt 10 gL goal 10-12 gL

Hb lt 7 gL goal 7-9 gL

N=418

N=420

A MULTICENTER RANDOMIZED CONTROLLED CLINICAL

TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CAREPAULC HEacuteBERT MD GEORGEWELLS PHD MORRISA BLAJCHMAN MD JOHNMARSHALL MD CLAUDIOMARTIN MD GIUSEPPEPAGLIARELLO MD MARTINTWEEDDALE MD PHD IRWINSCHWEITZER MSC ELIZABETHYETISIR MSC ANDTHETRANSFUSIONREQUIREMENTSINCRITICALCAREINVESTIGATORSFORTHECANADIANCRITICALCARETRIALSGROUP

NEJM 1999

(normovolemia)

Red blood cell transfusion during septic shock in the ICUA Perner etal Acta Anaesthesiol Scand 2012 56 718ndash723

The CRIT Study Anemia and blood transfusion in the critically illmdashCurrent clinical practice in the United States

(Observational study 284 ICU 4892 patients)

Crit Care Med 2004 3239 ndash52

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 5: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

5

PA catheter

bull Proximal ndash cold injectate ScvO2

bull Distal ndash Draw SvO2

bull Thermistor ndash Temperature

bull Balloon inflation and deflation

Wave form

Waveform In place PA catheter

Joining Zeroing

060356

6

Others parameter calculated from PAC parameters

SVR = ( MAP - CVP CO ) x 80

PVR = ( PAP - PAOP CO ) x 80

CO = VO2 ( CaO2 - CvO2 )

DO2 = CO x Ca O2 x 10

VO2 = ( Ca O2 - Cv O2 ) x CO x10

Ca O2 = ( 139 x Hb x SaO2 ) + ( 0003 x PaO2 ) - Arterial

O2 content

Cv O2 = ( 139 x Hb x SvO2 ) + ( 0003 x PvO2 ) - Venous

O2 content

O2 extraxtion = VO2 DO2

QsQt = ( PA-a O2 ) ( PA-a O2 ) ( Ca-v O2 )

Cardiac output measurement

Fickrsquos formular

CO = VO2

CaO2-CvO2

Poor feasibility

Indicator dilution method

Indocyanine green

More accurate and reproducible

Require blood sampling

Recirculation of dye can disturb measurement

Thermodilution

More efficient

Thermo dilution method

Inject 5-10 cc of cold water

Tem

pera

ture

change (

)

Time

Stewart ndashHamilton equation

CO = ( TB ndash TI )xK

0 TB(t) dt

Hemodynamic

parameters in 4 shocks

CVP PAP PCWP CO SVR

Hypovolemic Low Low Low Low High

Cardiogenic High High High Low High

Obstructive High Very high Normal Low High

Septic Not high Not high Not high High Low

Ultrasound CO by ultrasound

A mount of blood flow going through a fixed orifice =

CSA x Flow-Velocity

SV = CSA x LVOTTVI

CSA = LVOTd2 x 078540

SV = LVOTd2 x 078540 x LVOTTVI

060356

7

LVOT diameter

LVOT VTI

good correlation between the thermodilutiontechnique and

Simpsons two-chamber method (r = 091)

Simpsons four-chamber method (r = 077)

the LVOT Doppler method (r = 094)

the LVOT Doppler method demonstrated acceptable agreement with a mean of 02

litresminute standard deviation of 082 litresminute and 95 limits of agreement of -15 to +19 litresminute

CCO-thermodilution methods Model for CCOtd

Agreement between CCO and BCO

in cardio-thoracic surgeryIntensive Care Med 199925166

Compare CCO and BCO in 20 medical ptsJ Crit Care 199813184

Conditions Number

MV 15

Vasopressor 15

Malignancy 12

Aplastic anemia

5

SLE 1

Cushing 1

CGD 1

060356

8

Good correlation between

CCO and BCO in sepsisIntensive Care Med 2002281276

Good correlation between CCO and BCO in sepsisIntensive Care Med 2002281276

Poor correlation of

CCO during hypothermia

Conclusions

Despite an excellent correlation accuracy and

precision between CCO and ICO before CPB and more than 45 minutes after hypothermic CPB a lack

of correlation in the early phase after CPB has been

found Further investigation is needed to elucidate the underlying cause of these findings and to clarify

whether ICO or CCO or both fail to represent the

real cardiac output up to 45 minutes after weaning from hypothermic CPB

19959405

Response time after sudden reduction of COAnesthesiology 199889(6)1592

Response time after sudden reduction of COCrit Care Med 1995 23 860 Advantages over IBCO

Provide continuous trend

Reduce contamination

Less time consuming

Unnecessary fluid

060356

9

Limitations

Immediate CO measurement may not be done due to average time for reduce thermal noise

Transpulmoanry thermodilution method (TPTD)

Compare TPTD and IBTDAnesthesia amp Analgesia 2010

The respiratory variation affect IBTD rather than TPTD

IBTD

TPTD

Advantages over IBTD

Less invasive

Decrease complications result from PA catheter

GEDV and EVLW can be measuredAm J Physiol Lung Cell Mol Physiol 291 L1118ndashL1131 2006

060356

10

Limitations

Canrsquot assess PA pressure and its trend

Canrsquot assess SvO2

Pulse contour analysis

Non-calibrated

Calibrated

Basic Principles

Traditional CO = HR SV

FloTrac system CO = PR x (AP )

Where = M (HR AP C(P) BSA MAP 3ap 4ap)

Validation ICOCCOAPCOCrit Care 200711R105

Validation ICOCCOAPCOCrit Care 200711R105

FloTrac amp PACCrit Care 201014R212

060356

11

FloTrac amp PACCrit Care 201014R212

FloTrac in sepsisIntensive Care 201137233

FloTrac in sepsisIntensive Care 201137233

FloTrac Vigileo G3

Advantages

Real time

Less invasive

Non-calibrated

Informative

CO CI

PPV

SvO2

SVR

Disadvantages

Algorithm-gtnot real

Accuracy

Can not assess RV

derived parameters

Require new version software

PiCCO system Need calibration

060356

12

PAC and PiCCO (AP)Crit Care 201014R212

PiCCO

Advantages

Continuos monitoring

More accurate

Informative

COCI

SVV

SVR

GEDV

EVLW

AP

Disadvantages

Require calibration q 8 hrs

Femoral site risky to

CRBSI

Early goal directed therapy

What is the CVP

CVP = Central Venous Pressure

Frank Starling amp venous return line

Stroke volume

CVP0

Frank-Starling curve

Stroke volume or EDV

JVP or CVP or PCWP

ΔSV or Δ EDV

a

b

Responders

Non-responders

060356

13

b

CVP tells us who responders

Stroke volume or EDV

CVP or PCWP

ΔSV or Δ EDV

a

Good

Bad

CVP vs Fluid responders

Crit Care Med 20073564-8

39 cases25 cases

Does Central Venous Pressure Predict

Fluid ResponsivenessA Systematic Review of the Literature

CHEST 2008 134172ndash178

Fluid resuscitation in septic shock a positive fluid balance and elevated central venous pressure are associated with increased mortalityBoyd JH Forbes J Nakada TA Walley KR Russell JA

OBJECTIVE

To determine whether central venous pressure and fluid balance after resuscitation for septic shock are associated

with mortality

PATIENTS

The Vasopressin in Septic Shock Trial (VASST) study enrolled 778 patients who had septic shock and who were

receiving a minimum of 5 μg of norepinephrine per minute

MEASUREMENTS AND MAIN RESULTS

Based on net fluid balance we determined whether ones fluid balance quartile was correlated with 28-day

mortality We also analyzed whether fluid balance was predictive of central venous pressure and furthermore

whether a guideline-recommended central venous pressure of 8-12 mm Hg yielded a mortality advantage At

enrollment which occurred on average 12 hrs after presentation the average fluid balance was +42 L By day 4 the

cumulative average fluid balance was +11 L After correcting for age and Acute Physiology and Chronic Health

Evaluation II score a more positive fluid balance at both at 12 hrs and day 4 correlated significantly with increased

mortality Central venous pressure was correlated with fluid balance at 12 hrs whereas on days 1-4 there was no

significant correlation At 12 hrs patients with central venous pressure lt8 mm Hg had the lowest mortality rate

followed by those with central venous pressure 8-12 mm Hg The highest mortality rate was observed in those with

central venous pressure gt12 mm Hg Contrary to the overall effect patients whose central venous pressure was lt8

mm Hg had improved survival with a more positive fluid balance

CONCLUSIONS

A more positive fluid balance both early in resuscitation and cumulatively over 4 days is associated with an increased

risk of mortality in septic shock Central venous pressure may be used to gauge fluid balance le 12 hrs into septic

shock but becomes an unreliable marker of fluid balance thereafter Optimal survival in the VASST study occurred

with a positive fluid balance of approximately 3 L at 12 hrs

Functional hemodynamic for predicting fluidresponsiveness

Spontaneous respiration

CVP variation gt 1 mmHg

PLR cCO gt 15 ( can be used in arrhythmia)

On mechanical ventilation

PPV gt 13

IVCd variation gt 12 ( can be used in arrhythmia)

IVC distensibility index gt 18 ( can be used in arrhythmia)

Brachail peak velocity gt 10

PLR cCO gt 15 ( can be used in arrhythmia)

PLR ET-CO2 gt 5

060356

14

PP variation predict fluid responsiveness

PPV = PPmax-PPmin x 100

(PPmax+PPmin)2

PPV gt 13 indicate fluid

responsiveness

PPV 94

NPV 96

Reference Year of

publication

Clinical setting PPV threshold value()

Michard etal

Viellard-Baron etal

Kramer etal

Preisman etal

Hofer etal

Feissel etal

De Backer etal

Cannesson etal

Solus-Biguenet etal

Lafanechere etal

Monnet etal

Charron etal

Natalini etal

Feissel etal

Cannesson etal

2000

2004

2004

2005

2005

2005

2005

2006

2006

2006

2006

2006

2006

2007

2007

Medical ICU

Medical ICU

CABG

CABG

CABG

Surgical and medical ICU

Surgical and medical ICU

CABG

Hepatic resection

Medical ICU

Medical ICU

Surgical ICU

Surgical and medical ICU

Medical ICU

CABG

13

12

11

9

13

17

12

12

14

12

12

10

15

12

11

Limitations

Controlled mechanical ventilation

Tidal volume ge 8 mlkg

Sinus rhythm

How to assess lung leakage

Clinical assessment

More dyspneic

Crepitation increase

Gas exchange

Desaturation

Lower pO2

Lung mechanic

Decrease lung compliance

CXR

May be difficult to determine in ARDS

The lung compliance

Respiratory system compliance

119862119877119878 =119879119907

119875119901119897119886119905119890119886119906minus119875119864119864119875

Bedside measurement of CRS

Pressure

Time

PEEP

060356

15

Bedside measurement of CRS

Pressure

Time

PEEP

Pplateau

PIP

After set Plateau time

Monitoring CRS (Volume mode)

Parameters Time 0 1 hour

PaO2 80 85

PaCO2 40 44

SaO2 96 97

PIP 35 45

Pplateau 30 36

PEEP 12 12

Exhaled TV 400 400

CRS222 167

FiO2 05 09

Fluid (ml) 0 1200

The EGDTPuzzle of formula

SvO2 Cellular oxygen

Good SvO2 means good cellular oxygenation (Low flow)

DO2 = 100

VO2 = 30

SvO2 = 70

Good SvO2 means good cellular oxygenation (heterogeneous flow)

DO2 = 100

VO2 = 10

SvO2 = 90

060356

16

Correlation between perfused capillary and blood lactateDe Backer etal Crit Care Med 2006

Prognostic value of hyperlactatemia in many

different critical care conditionsBlood lactate levels are superior to oxygen-derived

variables in predicting outcome in human septic shock

J Bakker M Coffernils M Leon P Gris and J L Vincent Chest 199199956-962

plt 005

plt 0001

Lactate level after 4 hrs of resuscitationS-W Lee etal Emerg Med J 200825659-665

Prognostic value of blood lactate levels in the ED

Shapiro NI et al Serum lactate as a predictor of mortality in emergency department patients with infection Ann Emerg Med 2005 45(5) p 524-8

490

900

2840

150

450

2240

000

500

1000

1500

2000

2500

3000

0-24 25-39 gt4

28 day in hospital mortality Death

Mo

rta

lity

ra

te

Lactate

Serum lactate as a predictor of mortalityin patients with infection

S Trzeciak et alIntensive Care Med (2007) 33970ndash977

Prognostic value of blood lactate levels

in the Critical care unit at Ramathibodihospital

Survivors 27

Non-survivors

5

0

1

2

3

4

5

6

Art

eri

al la

cta

te (

mm

ol

L)

p=NS

The Correlation Between Arterial Lactate and Venous Lactate in Patients With Sepsis and

Septic Shock (unpublished data)

Na Petvicharn C MD Theerawit P MD

Department of Internal Medicine the Faculty of Medicine Ramathibodi Hospital MahidolUniversity

060356

17

LACtime the predictor of organ failureJan Bakker et alAJS 1996171221-6

Lactate

Time

Lactime

AUC

Survivors

Non-survivors

P lt 005

2 mmolL

Serial blood lactate levels can predict the

development of multiple organ failure following septic shock

MD Jan Bakker MD Philippe Gris MD Michel Coffernils MD Robert J Kahn MD PhD Jean-

Louis Vincent The American Journal of surgery Volume 171 Issue 2 Pages 221-226 February 1996

plt005

plt 001

plt005 vs initial

blood lactate

Lactate clearance and mortalityArnold RC Shock 2008

0

10

20

30

40

50

60

70

LC gt 10 LC lt 10

Mortality rate

SvO2 gt 70

P lt 0001

Odds ratio for death 49(15-159)

Early lactate clearance is associated with

improved outcome in severe sepsis and

septic shock

H Bryant Nguyen MD MS Emanuel P Rivers MD MPH Bernhard P Knoblich MD

Gordon Jacobsen MS Alexandria Muzzin BS Julie A Ressler BS Michael C Tomlanovich

MDCrit Care Med 2004 Vol 32 No 8

Lactate clearance

= (Lactate ED presentation ndash Lactate Hour 6)x100Lactate ED presentation

There was an approximately

11 decrease likelihood of mortality for each 10 increase in lactate clearance

Association between blood lactate levels Sequential Organ Failure

Assessment subscores and 28-day mortality during

early and late ICU stay A retrospective observational study

Tim C Jansen Jasper van Bommel Roger Woodward Paul G H Mulder Jan Bakker Crit Care Med 2009 Vol 37 No 8

Dynamic Lactate Indices as

Predictors of Outcome in Critically Ill Patients

Admission lactate (LACADM)

Maximum lactate (LACMAX24)

Minimum lactate (LACMIN24)

Time weighted lactate (LACTW24)

Absolute change in (delta) lactate (LACΔ24)

Percentage change in lactate (LACΔ24)

Nichol A Bailey M Egi M Pettila V French C Hart GK Stachowski E Reade MCCooper

DJ Bellomo RCrit Care 2011 15R242

060356

18

Tissue perfusion

Lactate is better than SvO2 for assessment of tissue perfusion

The higher initial lactate the higher mortality

Lactate changing over time is better than a single value for monitoring

The higher lactate clearance the better

outcome

At least 10 reduction of lactate during resuscitation should be achieved

Type of fluid

Colloids or Crystalloids

26 Randomized trials

BMJ 1998316961-4

RR of death

Trauma 130(095-177)

Burn 121(088-166)

Sepsis 108(073-161)

Pooled 119(098-145)

Crystalloid and colloid infusion over 90 min in sepsis and non sepsis cases with

fluid responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid Colloid P value

CI before

CI after

EVLW

beforeEVLW after

39(24-55)

41(25-59)

71(19-339)75(16-299)

34(20-82)

38(23-69)

71(26-213)71(25-196)

Plt001

Pgt005

P value between before and after

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

060356

19

Crystalloid VS Colloid

No difference in

PLI

EVLW

Gas exchange

If fluid is administered in septic

patients with

fluid responsiveness even in ALI

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

Correction of albumin in ARDS

Refresher course ICM December 2008

Correction of albumin in ARDS

Refresher course ICM December 2008

Colloid solution

Albumin Artificial

Gelatins

Dextran

HES

Poor effective

Allergic reactionAltered hemostasis

Allergic reactionRenal dysfucntion

060356

20

Colloid solutions

Hypoalbuminemia tends to increase the incidence of ARDS and mortality in sepsis patients

More fluid required for correct hemodynamic abnormality

Poor response to Furosemide

More potential leakage at capillary site may lead to more lung injury

Correction of hypoalbuminemia in ARDS may be benefitial in terms of mortality but it must be used carefully

HES may cause renal failure and high dosage may lead to bleeding tendency

The benefit of artificial colloid solution over albumin is not known

Case

60 YO male patient 60 Kg

Pneumonia with septic shock on MV

VS BP 8040 mmHg HR 120 RR 26 BT 39oC

Heart normal S1S2 no murmur

Lungs crepitation RLL lingular segment

Liver and spleen not palpable

No edema

Neuro WNL

Case

Load NSS 1500 ml -gt PPV 14 -gt lung crepitation

BP 9040 mmHg (MAP = 57 mmHg)

Increase Nor-epinephrine

BP 8545 mmHg (MAP = 55 mmHg)

HR 90 -gt 110 min lactate 3 to 6 mmolL

Re-assessment

ABG

pH 71

pCO2 35 mmHg

pO2 70 mmHg

HCO3 15 mmolL

We corrected acidosis and start dobutamine

Can decrease dosage of NorE and lactate 41

The

EGDT

We need re-

assessment

here

These are causes of no

response to pressor

Acidosis

Poor LV contraction

RV dysfunction +- PE

Pneumothorax

Concealed hemorrhage

Relative adrenal insufficiency

Electrolyte imbalance

Severe sepsis

060356

21

Norepinephrine in septic shock

Study Baseline CI(normal 25-4)

EM Redl-Wenzl et al 1993Claude Martin et al 1993BLevy et al 1997Daniel De Backer et al 2003

Jacques Albane`se et al 2004Franccedilois Lauzier et al 2006

38+1153+1340+134+1

47+0244+14

Blood transfusion in septic shockJean-Louis Vincent Pongdhep Theerawit Davide Simeon

Basic Principles of Oxygen Transport and Calculations

Alternatives to Blood Transfusion in Transfusion Medicine 2nd Ed

Chapter 17 Published Online 4 SEP 2010

Transfusions will obviously have opposite effects to

anemia increasing blood viscosity and reducing the adrenergic response It is intriguing to consider

that transfusions may result in a decrease in

myocardial contractility Hence cardiac output often decreases following transfusions in the

nomovolemic patient and the increase in DO2

can be minor or even absent For example Shah et al observed in resuscitated trauma patients

that blood transfusion of one unit of RBC increased hemoglobin from 92 plusmn 03 to 102 plusmn 03

gdL but decreased cardiac output so that DO2

did not change

Hb lt 10 gL goal 10-12 gL

Hb lt 7 gL goal 7-9 gL

N=418

N=420

A MULTICENTER RANDOMIZED CONTROLLED CLINICAL

TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CAREPAULC HEacuteBERT MD GEORGEWELLS PHD MORRISA BLAJCHMAN MD JOHNMARSHALL MD CLAUDIOMARTIN MD GIUSEPPEPAGLIARELLO MD MARTINTWEEDDALE MD PHD IRWINSCHWEITZER MSC ELIZABETHYETISIR MSC ANDTHETRANSFUSIONREQUIREMENTSINCRITICALCAREINVESTIGATORSFORTHECANADIANCRITICALCARETRIALSGROUP

NEJM 1999

(normovolemia)

Red blood cell transfusion during septic shock in the ICUA Perner etal Acta Anaesthesiol Scand 2012 56 718ndash723

The CRIT Study Anemia and blood transfusion in the critically illmdashCurrent clinical practice in the United States

(Observational study 284 ICU 4892 patients)

Crit Care Med 2004 3239 ndash52

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 6: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

6

Others parameter calculated from PAC parameters

SVR = ( MAP - CVP CO ) x 80

PVR = ( PAP - PAOP CO ) x 80

CO = VO2 ( CaO2 - CvO2 )

DO2 = CO x Ca O2 x 10

VO2 = ( Ca O2 - Cv O2 ) x CO x10

Ca O2 = ( 139 x Hb x SaO2 ) + ( 0003 x PaO2 ) - Arterial

O2 content

Cv O2 = ( 139 x Hb x SvO2 ) + ( 0003 x PvO2 ) - Venous

O2 content

O2 extraxtion = VO2 DO2

QsQt = ( PA-a O2 ) ( PA-a O2 ) ( Ca-v O2 )

Cardiac output measurement

Fickrsquos formular

CO = VO2

CaO2-CvO2

Poor feasibility

Indicator dilution method

Indocyanine green

More accurate and reproducible

Require blood sampling

Recirculation of dye can disturb measurement

Thermodilution

More efficient

Thermo dilution method

Inject 5-10 cc of cold water

Tem

pera

ture

change (

)

Time

Stewart ndashHamilton equation

CO = ( TB ndash TI )xK

0 TB(t) dt

Hemodynamic

parameters in 4 shocks

CVP PAP PCWP CO SVR

Hypovolemic Low Low Low Low High

Cardiogenic High High High Low High

Obstructive High Very high Normal Low High

Septic Not high Not high Not high High Low

Ultrasound CO by ultrasound

A mount of blood flow going through a fixed orifice =

CSA x Flow-Velocity

SV = CSA x LVOTTVI

CSA = LVOTd2 x 078540

SV = LVOTd2 x 078540 x LVOTTVI

060356

7

LVOT diameter

LVOT VTI

good correlation between the thermodilutiontechnique and

Simpsons two-chamber method (r = 091)

Simpsons four-chamber method (r = 077)

the LVOT Doppler method (r = 094)

the LVOT Doppler method demonstrated acceptable agreement with a mean of 02

litresminute standard deviation of 082 litresminute and 95 limits of agreement of -15 to +19 litresminute

CCO-thermodilution methods Model for CCOtd

Agreement between CCO and BCO

in cardio-thoracic surgeryIntensive Care Med 199925166

Compare CCO and BCO in 20 medical ptsJ Crit Care 199813184

Conditions Number

MV 15

Vasopressor 15

Malignancy 12

Aplastic anemia

5

SLE 1

Cushing 1

CGD 1

060356

8

Good correlation between

CCO and BCO in sepsisIntensive Care Med 2002281276

Good correlation between CCO and BCO in sepsisIntensive Care Med 2002281276

Poor correlation of

CCO during hypothermia

Conclusions

Despite an excellent correlation accuracy and

precision between CCO and ICO before CPB and more than 45 minutes after hypothermic CPB a lack

of correlation in the early phase after CPB has been

found Further investigation is needed to elucidate the underlying cause of these findings and to clarify

whether ICO or CCO or both fail to represent the

real cardiac output up to 45 minutes after weaning from hypothermic CPB

19959405

Response time after sudden reduction of COAnesthesiology 199889(6)1592

Response time after sudden reduction of COCrit Care Med 1995 23 860 Advantages over IBCO

Provide continuous trend

Reduce contamination

Less time consuming

Unnecessary fluid

060356

9

Limitations

Immediate CO measurement may not be done due to average time for reduce thermal noise

Transpulmoanry thermodilution method (TPTD)

Compare TPTD and IBTDAnesthesia amp Analgesia 2010

The respiratory variation affect IBTD rather than TPTD

IBTD

TPTD

Advantages over IBTD

Less invasive

Decrease complications result from PA catheter

GEDV and EVLW can be measuredAm J Physiol Lung Cell Mol Physiol 291 L1118ndashL1131 2006

060356

10

Limitations

Canrsquot assess PA pressure and its trend

Canrsquot assess SvO2

Pulse contour analysis

Non-calibrated

Calibrated

Basic Principles

Traditional CO = HR SV

FloTrac system CO = PR x (AP )

Where = M (HR AP C(P) BSA MAP 3ap 4ap)

Validation ICOCCOAPCOCrit Care 200711R105

Validation ICOCCOAPCOCrit Care 200711R105

FloTrac amp PACCrit Care 201014R212

060356

11

FloTrac amp PACCrit Care 201014R212

FloTrac in sepsisIntensive Care 201137233

FloTrac in sepsisIntensive Care 201137233

FloTrac Vigileo G3

Advantages

Real time

Less invasive

Non-calibrated

Informative

CO CI

PPV

SvO2

SVR

Disadvantages

Algorithm-gtnot real

Accuracy

Can not assess RV

derived parameters

Require new version software

PiCCO system Need calibration

060356

12

PAC and PiCCO (AP)Crit Care 201014R212

PiCCO

Advantages

Continuos monitoring

More accurate

Informative

COCI

SVV

SVR

GEDV

EVLW

AP

Disadvantages

Require calibration q 8 hrs

Femoral site risky to

CRBSI

Early goal directed therapy

What is the CVP

CVP = Central Venous Pressure

Frank Starling amp venous return line

Stroke volume

CVP0

Frank-Starling curve

Stroke volume or EDV

JVP or CVP or PCWP

ΔSV or Δ EDV

a

b

Responders

Non-responders

060356

13

b

CVP tells us who responders

Stroke volume or EDV

CVP or PCWP

ΔSV or Δ EDV

a

Good

Bad

CVP vs Fluid responders

Crit Care Med 20073564-8

39 cases25 cases

Does Central Venous Pressure Predict

Fluid ResponsivenessA Systematic Review of the Literature

CHEST 2008 134172ndash178

Fluid resuscitation in septic shock a positive fluid balance and elevated central venous pressure are associated with increased mortalityBoyd JH Forbes J Nakada TA Walley KR Russell JA

OBJECTIVE

To determine whether central venous pressure and fluid balance after resuscitation for septic shock are associated

with mortality

PATIENTS

The Vasopressin in Septic Shock Trial (VASST) study enrolled 778 patients who had septic shock and who were

receiving a minimum of 5 μg of norepinephrine per minute

MEASUREMENTS AND MAIN RESULTS

Based on net fluid balance we determined whether ones fluid balance quartile was correlated with 28-day

mortality We also analyzed whether fluid balance was predictive of central venous pressure and furthermore

whether a guideline-recommended central venous pressure of 8-12 mm Hg yielded a mortality advantage At

enrollment which occurred on average 12 hrs after presentation the average fluid balance was +42 L By day 4 the

cumulative average fluid balance was +11 L After correcting for age and Acute Physiology and Chronic Health

Evaluation II score a more positive fluid balance at both at 12 hrs and day 4 correlated significantly with increased

mortality Central venous pressure was correlated with fluid balance at 12 hrs whereas on days 1-4 there was no

significant correlation At 12 hrs patients with central venous pressure lt8 mm Hg had the lowest mortality rate

followed by those with central venous pressure 8-12 mm Hg The highest mortality rate was observed in those with

central venous pressure gt12 mm Hg Contrary to the overall effect patients whose central venous pressure was lt8

mm Hg had improved survival with a more positive fluid balance

CONCLUSIONS

A more positive fluid balance both early in resuscitation and cumulatively over 4 days is associated with an increased

risk of mortality in septic shock Central venous pressure may be used to gauge fluid balance le 12 hrs into septic

shock but becomes an unreliable marker of fluid balance thereafter Optimal survival in the VASST study occurred

with a positive fluid balance of approximately 3 L at 12 hrs

Functional hemodynamic for predicting fluidresponsiveness

Spontaneous respiration

CVP variation gt 1 mmHg

PLR cCO gt 15 ( can be used in arrhythmia)

On mechanical ventilation

PPV gt 13

IVCd variation gt 12 ( can be used in arrhythmia)

IVC distensibility index gt 18 ( can be used in arrhythmia)

Brachail peak velocity gt 10

PLR cCO gt 15 ( can be used in arrhythmia)

PLR ET-CO2 gt 5

060356

14

PP variation predict fluid responsiveness

PPV = PPmax-PPmin x 100

(PPmax+PPmin)2

PPV gt 13 indicate fluid

responsiveness

PPV 94

NPV 96

Reference Year of

publication

Clinical setting PPV threshold value()

Michard etal

Viellard-Baron etal

Kramer etal

Preisman etal

Hofer etal

Feissel etal

De Backer etal

Cannesson etal

Solus-Biguenet etal

Lafanechere etal

Monnet etal

Charron etal

Natalini etal

Feissel etal

Cannesson etal

2000

2004

2004

2005

2005

2005

2005

2006

2006

2006

2006

2006

2006

2007

2007

Medical ICU

Medical ICU

CABG

CABG

CABG

Surgical and medical ICU

Surgical and medical ICU

CABG

Hepatic resection

Medical ICU

Medical ICU

Surgical ICU

Surgical and medical ICU

Medical ICU

CABG

13

12

11

9

13

17

12

12

14

12

12

10

15

12

11

Limitations

Controlled mechanical ventilation

Tidal volume ge 8 mlkg

Sinus rhythm

How to assess lung leakage

Clinical assessment

More dyspneic

Crepitation increase

Gas exchange

Desaturation

Lower pO2

Lung mechanic

Decrease lung compliance

CXR

May be difficult to determine in ARDS

The lung compliance

Respiratory system compliance

119862119877119878 =119879119907

119875119901119897119886119905119890119886119906minus119875119864119864119875

Bedside measurement of CRS

Pressure

Time

PEEP

060356

15

Bedside measurement of CRS

Pressure

Time

PEEP

Pplateau

PIP

After set Plateau time

Monitoring CRS (Volume mode)

Parameters Time 0 1 hour

PaO2 80 85

PaCO2 40 44

SaO2 96 97

PIP 35 45

Pplateau 30 36

PEEP 12 12

Exhaled TV 400 400

CRS222 167

FiO2 05 09

Fluid (ml) 0 1200

The EGDTPuzzle of formula

SvO2 Cellular oxygen

Good SvO2 means good cellular oxygenation (Low flow)

DO2 = 100

VO2 = 30

SvO2 = 70

Good SvO2 means good cellular oxygenation (heterogeneous flow)

DO2 = 100

VO2 = 10

SvO2 = 90

060356

16

Correlation between perfused capillary and blood lactateDe Backer etal Crit Care Med 2006

Prognostic value of hyperlactatemia in many

different critical care conditionsBlood lactate levels are superior to oxygen-derived

variables in predicting outcome in human septic shock

J Bakker M Coffernils M Leon P Gris and J L Vincent Chest 199199956-962

plt 005

plt 0001

Lactate level after 4 hrs of resuscitationS-W Lee etal Emerg Med J 200825659-665

Prognostic value of blood lactate levels in the ED

Shapiro NI et al Serum lactate as a predictor of mortality in emergency department patients with infection Ann Emerg Med 2005 45(5) p 524-8

490

900

2840

150

450

2240

000

500

1000

1500

2000

2500

3000

0-24 25-39 gt4

28 day in hospital mortality Death

Mo

rta

lity

ra

te

Lactate

Serum lactate as a predictor of mortalityin patients with infection

S Trzeciak et alIntensive Care Med (2007) 33970ndash977

Prognostic value of blood lactate levels

in the Critical care unit at Ramathibodihospital

Survivors 27

Non-survivors

5

0

1

2

3

4

5

6

Art

eri

al la

cta

te (

mm

ol

L)

p=NS

The Correlation Between Arterial Lactate and Venous Lactate in Patients With Sepsis and

Septic Shock (unpublished data)

Na Petvicharn C MD Theerawit P MD

Department of Internal Medicine the Faculty of Medicine Ramathibodi Hospital MahidolUniversity

060356

17

LACtime the predictor of organ failureJan Bakker et alAJS 1996171221-6

Lactate

Time

Lactime

AUC

Survivors

Non-survivors

P lt 005

2 mmolL

Serial blood lactate levels can predict the

development of multiple organ failure following septic shock

MD Jan Bakker MD Philippe Gris MD Michel Coffernils MD Robert J Kahn MD PhD Jean-

Louis Vincent The American Journal of surgery Volume 171 Issue 2 Pages 221-226 February 1996

plt005

plt 001

plt005 vs initial

blood lactate

Lactate clearance and mortalityArnold RC Shock 2008

0

10

20

30

40

50

60

70

LC gt 10 LC lt 10

Mortality rate

SvO2 gt 70

P lt 0001

Odds ratio for death 49(15-159)

Early lactate clearance is associated with

improved outcome in severe sepsis and

septic shock

H Bryant Nguyen MD MS Emanuel P Rivers MD MPH Bernhard P Knoblich MD

Gordon Jacobsen MS Alexandria Muzzin BS Julie A Ressler BS Michael C Tomlanovich

MDCrit Care Med 2004 Vol 32 No 8

Lactate clearance

= (Lactate ED presentation ndash Lactate Hour 6)x100Lactate ED presentation

There was an approximately

11 decrease likelihood of mortality for each 10 increase in lactate clearance

Association between blood lactate levels Sequential Organ Failure

Assessment subscores and 28-day mortality during

early and late ICU stay A retrospective observational study

Tim C Jansen Jasper van Bommel Roger Woodward Paul G H Mulder Jan Bakker Crit Care Med 2009 Vol 37 No 8

Dynamic Lactate Indices as

Predictors of Outcome in Critically Ill Patients

Admission lactate (LACADM)

Maximum lactate (LACMAX24)

Minimum lactate (LACMIN24)

Time weighted lactate (LACTW24)

Absolute change in (delta) lactate (LACΔ24)

Percentage change in lactate (LACΔ24)

Nichol A Bailey M Egi M Pettila V French C Hart GK Stachowski E Reade MCCooper

DJ Bellomo RCrit Care 2011 15R242

060356

18

Tissue perfusion

Lactate is better than SvO2 for assessment of tissue perfusion

The higher initial lactate the higher mortality

Lactate changing over time is better than a single value for monitoring

The higher lactate clearance the better

outcome

At least 10 reduction of lactate during resuscitation should be achieved

Type of fluid

Colloids or Crystalloids

26 Randomized trials

BMJ 1998316961-4

RR of death

Trauma 130(095-177)

Burn 121(088-166)

Sepsis 108(073-161)

Pooled 119(098-145)

Crystalloid and colloid infusion over 90 min in sepsis and non sepsis cases with

fluid responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid Colloid P value

CI before

CI after

EVLW

beforeEVLW after

39(24-55)

41(25-59)

71(19-339)75(16-299)

34(20-82)

38(23-69)

71(26-213)71(25-196)

Plt001

Pgt005

P value between before and after

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

060356

19

Crystalloid VS Colloid

No difference in

PLI

EVLW

Gas exchange

If fluid is administered in septic

patients with

fluid responsiveness even in ALI

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

Correction of albumin in ARDS

Refresher course ICM December 2008

Correction of albumin in ARDS

Refresher course ICM December 2008

Colloid solution

Albumin Artificial

Gelatins

Dextran

HES

Poor effective

Allergic reactionAltered hemostasis

Allergic reactionRenal dysfucntion

060356

20

Colloid solutions

Hypoalbuminemia tends to increase the incidence of ARDS and mortality in sepsis patients

More fluid required for correct hemodynamic abnormality

Poor response to Furosemide

More potential leakage at capillary site may lead to more lung injury

Correction of hypoalbuminemia in ARDS may be benefitial in terms of mortality but it must be used carefully

HES may cause renal failure and high dosage may lead to bleeding tendency

The benefit of artificial colloid solution over albumin is not known

Case

60 YO male patient 60 Kg

Pneumonia with septic shock on MV

VS BP 8040 mmHg HR 120 RR 26 BT 39oC

Heart normal S1S2 no murmur

Lungs crepitation RLL lingular segment

Liver and spleen not palpable

No edema

Neuro WNL

Case

Load NSS 1500 ml -gt PPV 14 -gt lung crepitation

BP 9040 mmHg (MAP = 57 mmHg)

Increase Nor-epinephrine

BP 8545 mmHg (MAP = 55 mmHg)

HR 90 -gt 110 min lactate 3 to 6 mmolL

Re-assessment

ABG

pH 71

pCO2 35 mmHg

pO2 70 mmHg

HCO3 15 mmolL

We corrected acidosis and start dobutamine

Can decrease dosage of NorE and lactate 41

The

EGDT

We need re-

assessment

here

These are causes of no

response to pressor

Acidosis

Poor LV contraction

RV dysfunction +- PE

Pneumothorax

Concealed hemorrhage

Relative adrenal insufficiency

Electrolyte imbalance

Severe sepsis

060356

21

Norepinephrine in septic shock

Study Baseline CI(normal 25-4)

EM Redl-Wenzl et al 1993Claude Martin et al 1993BLevy et al 1997Daniel De Backer et al 2003

Jacques Albane`se et al 2004Franccedilois Lauzier et al 2006

38+1153+1340+134+1

47+0244+14

Blood transfusion in septic shockJean-Louis Vincent Pongdhep Theerawit Davide Simeon

Basic Principles of Oxygen Transport and Calculations

Alternatives to Blood Transfusion in Transfusion Medicine 2nd Ed

Chapter 17 Published Online 4 SEP 2010

Transfusions will obviously have opposite effects to

anemia increasing blood viscosity and reducing the adrenergic response It is intriguing to consider

that transfusions may result in a decrease in

myocardial contractility Hence cardiac output often decreases following transfusions in the

nomovolemic patient and the increase in DO2

can be minor or even absent For example Shah et al observed in resuscitated trauma patients

that blood transfusion of one unit of RBC increased hemoglobin from 92 plusmn 03 to 102 plusmn 03

gdL but decreased cardiac output so that DO2

did not change

Hb lt 10 gL goal 10-12 gL

Hb lt 7 gL goal 7-9 gL

N=418

N=420

A MULTICENTER RANDOMIZED CONTROLLED CLINICAL

TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CAREPAULC HEacuteBERT MD GEORGEWELLS PHD MORRISA BLAJCHMAN MD JOHNMARSHALL MD CLAUDIOMARTIN MD GIUSEPPEPAGLIARELLO MD MARTINTWEEDDALE MD PHD IRWINSCHWEITZER MSC ELIZABETHYETISIR MSC ANDTHETRANSFUSIONREQUIREMENTSINCRITICALCAREINVESTIGATORSFORTHECANADIANCRITICALCARETRIALSGROUP

NEJM 1999

(normovolemia)

Red blood cell transfusion during septic shock in the ICUA Perner etal Acta Anaesthesiol Scand 2012 56 718ndash723

The CRIT Study Anemia and blood transfusion in the critically illmdashCurrent clinical practice in the United States

(Observational study 284 ICU 4892 patients)

Crit Care Med 2004 3239 ndash52

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 7: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

7

LVOT diameter

LVOT VTI

good correlation between the thermodilutiontechnique and

Simpsons two-chamber method (r = 091)

Simpsons four-chamber method (r = 077)

the LVOT Doppler method (r = 094)

the LVOT Doppler method demonstrated acceptable agreement with a mean of 02

litresminute standard deviation of 082 litresminute and 95 limits of agreement of -15 to +19 litresminute

CCO-thermodilution methods Model for CCOtd

Agreement between CCO and BCO

in cardio-thoracic surgeryIntensive Care Med 199925166

Compare CCO and BCO in 20 medical ptsJ Crit Care 199813184

Conditions Number

MV 15

Vasopressor 15

Malignancy 12

Aplastic anemia

5

SLE 1

Cushing 1

CGD 1

060356

8

Good correlation between

CCO and BCO in sepsisIntensive Care Med 2002281276

Good correlation between CCO and BCO in sepsisIntensive Care Med 2002281276

Poor correlation of

CCO during hypothermia

Conclusions

Despite an excellent correlation accuracy and

precision between CCO and ICO before CPB and more than 45 minutes after hypothermic CPB a lack

of correlation in the early phase after CPB has been

found Further investigation is needed to elucidate the underlying cause of these findings and to clarify

whether ICO or CCO or both fail to represent the

real cardiac output up to 45 minutes after weaning from hypothermic CPB

19959405

Response time after sudden reduction of COAnesthesiology 199889(6)1592

Response time after sudden reduction of COCrit Care Med 1995 23 860 Advantages over IBCO

Provide continuous trend

Reduce contamination

Less time consuming

Unnecessary fluid

060356

9

Limitations

Immediate CO measurement may not be done due to average time for reduce thermal noise

Transpulmoanry thermodilution method (TPTD)

Compare TPTD and IBTDAnesthesia amp Analgesia 2010

The respiratory variation affect IBTD rather than TPTD

IBTD

TPTD

Advantages over IBTD

Less invasive

Decrease complications result from PA catheter

GEDV and EVLW can be measuredAm J Physiol Lung Cell Mol Physiol 291 L1118ndashL1131 2006

060356

10

Limitations

Canrsquot assess PA pressure and its trend

Canrsquot assess SvO2

Pulse contour analysis

Non-calibrated

Calibrated

Basic Principles

Traditional CO = HR SV

FloTrac system CO = PR x (AP )

Where = M (HR AP C(P) BSA MAP 3ap 4ap)

Validation ICOCCOAPCOCrit Care 200711R105

Validation ICOCCOAPCOCrit Care 200711R105

FloTrac amp PACCrit Care 201014R212

060356

11

FloTrac amp PACCrit Care 201014R212

FloTrac in sepsisIntensive Care 201137233

FloTrac in sepsisIntensive Care 201137233

FloTrac Vigileo G3

Advantages

Real time

Less invasive

Non-calibrated

Informative

CO CI

PPV

SvO2

SVR

Disadvantages

Algorithm-gtnot real

Accuracy

Can not assess RV

derived parameters

Require new version software

PiCCO system Need calibration

060356

12

PAC and PiCCO (AP)Crit Care 201014R212

PiCCO

Advantages

Continuos monitoring

More accurate

Informative

COCI

SVV

SVR

GEDV

EVLW

AP

Disadvantages

Require calibration q 8 hrs

Femoral site risky to

CRBSI

Early goal directed therapy

What is the CVP

CVP = Central Venous Pressure

Frank Starling amp venous return line

Stroke volume

CVP0

Frank-Starling curve

Stroke volume or EDV

JVP or CVP or PCWP

ΔSV or Δ EDV

a

b

Responders

Non-responders

060356

13

b

CVP tells us who responders

Stroke volume or EDV

CVP or PCWP

ΔSV or Δ EDV

a

Good

Bad

CVP vs Fluid responders

Crit Care Med 20073564-8

39 cases25 cases

Does Central Venous Pressure Predict

Fluid ResponsivenessA Systematic Review of the Literature

CHEST 2008 134172ndash178

Fluid resuscitation in septic shock a positive fluid balance and elevated central venous pressure are associated with increased mortalityBoyd JH Forbes J Nakada TA Walley KR Russell JA

OBJECTIVE

To determine whether central venous pressure and fluid balance after resuscitation for septic shock are associated

with mortality

PATIENTS

The Vasopressin in Septic Shock Trial (VASST) study enrolled 778 patients who had septic shock and who were

receiving a minimum of 5 μg of norepinephrine per minute

MEASUREMENTS AND MAIN RESULTS

Based on net fluid balance we determined whether ones fluid balance quartile was correlated with 28-day

mortality We also analyzed whether fluid balance was predictive of central venous pressure and furthermore

whether a guideline-recommended central venous pressure of 8-12 mm Hg yielded a mortality advantage At

enrollment which occurred on average 12 hrs after presentation the average fluid balance was +42 L By day 4 the

cumulative average fluid balance was +11 L After correcting for age and Acute Physiology and Chronic Health

Evaluation II score a more positive fluid balance at both at 12 hrs and day 4 correlated significantly with increased

mortality Central venous pressure was correlated with fluid balance at 12 hrs whereas on days 1-4 there was no

significant correlation At 12 hrs patients with central venous pressure lt8 mm Hg had the lowest mortality rate

followed by those with central venous pressure 8-12 mm Hg The highest mortality rate was observed in those with

central venous pressure gt12 mm Hg Contrary to the overall effect patients whose central venous pressure was lt8

mm Hg had improved survival with a more positive fluid balance

CONCLUSIONS

A more positive fluid balance both early in resuscitation and cumulatively over 4 days is associated with an increased

risk of mortality in septic shock Central venous pressure may be used to gauge fluid balance le 12 hrs into septic

shock but becomes an unreliable marker of fluid balance thereafter Optimal survival in the VASST study occurred

with a positive fluid balance of approximately 3 L at 12 hrs

Functional hemodynamic for predicting fluidresponsiveness

Spontaneous respiration

CVP variation gt 1 mmHg

PLR cCO gt 15 ( can be used in arrhythmia)

On mechanical ventilation

PPV gt 13

IVCd variation gt 12 ( can be used in arrhythmia)

IVC distensibility index gt 18 ( can be used in arrhythmia)

Brachail peak velocity gt 10

PLR cCO gt 15 ( can be used in arrhythmia)

PLR ET-CO2 gt 5

060356

14

PP variation predict fluid responsiveness

PPV = PPmax-PPmin x 100

(PPmax+PPmin)2

PPV gt 13 indicate fluid

responsiveness

PPV 94

NPV 96

Reference Year of

publication

Clinical setting PPV threshold value()

Michard etal

Viellard-Baron etal

Kramer etal

Preisman etal

Hofer etal

Feissel etal

De Backer etal

Cannesson etal

Solus-Biguenet etal

Lafanechere etal

Monnet etal

Charron etal

Natalini etal

Feissel etal

Cannesson etal

2000

2004

2004

2005

2005

2005

2005

2006

2006

2006

2006

2006

2006

2007

2007

Medical ICU

Medical ICU

CABG

CABG

CABG

Surgical and medical ICU

Surgical and medical ICU

CABG

Hepatic resection

Medical ICU

Medical ICU

Surgical ICU

Surgical and medical ICU

Medical ICU

CABG

13

12

11

9

13

17

12

12

14

12

12

10

15

12

11

Limitations

Controlled mechanical ventilation

Tidal volume ge 8 mlkg

Sinus rhythm

How to assess lung leakage

Clinical assessment

More dyspneic

Crepitation increase

Gas exchange

Desaturation

Lower pO2

Lung mechanic

Decrease lung compliance

CXR

May be difficult to determine in ARDS

The lung compliance

Respiratory system compliance

119862119877119878 =119879119907

119875119901119897119886119905119890119886119906minus119875119864119864119875

Bedside measurement of CRS

Pressure

Time

PEEP

060356

15

Bedside measurement of CRS

Pressure

Time

PEEP

Pplateau

PIP

After set Plateau time

Monitoring CRS (Volume mode)

Parameters Time 0 1 hour

PaO2 80 85

PaCO2 40 44

SaO2 96 97

PIP 35 45

Pplateau 30 36

PEEP 12 12

Exhaled TV 400 400

CRS222 167

FiO2 05 09

Fluid (ml) 0 1200

The EGDTPuzzle of formula

SvO2 Cellular oxygen

Good SvO2 means good cellular oxygenation (Low flow)

DO2 = 100

VO2 = 30

SvO2 = 70

Good SvO2 means good cellular oxygenation (heterogeneous flow)

DO2 = 100

VO2 = 10

SvO2 = 90

060356

16

Correlation between perfused capillary and blood lactateDe Backer etal Crit Care Med 2006

Prognostic value of hyperlactatemia in many

different critical care conditionsBlood lactate levels are superior to oxygen-derived

variables in predicting outcome in human septic shock

J Bakker M Coffernils M Leon P Gris and J L Vincent Chest 199199956-962

plt 005

plt 0001

Lactate level after 4 hrs of resuscitationS-W Lee etal Emerg Med J 200825659-665

Prognostic value of blood lactate levels in the ED

Shapiro NI et al Serum lactate as a predictor of mortality in emergency department patients with infection Ann Emerg Med 2005 45(5) p 524-8

490

900

2840

150

450

2240

000

500

1000

1500

2000

2500

3000

0-24 25-39 gt4

28 day in hospital mortality Death

Mo

rta

lity

ra

te

Lactate

Serum lactate as a predictor of mortalityin patients with infection

S Trzeciak et alIntensive Care Med (2007) 33970ndash977

Prognostic value of blood lactate levels

in the Critical care unit at Ramathibodihospital

Survivors 27

Non-survivors

5

0

1

2

3

4

5

6

Art

eri

al la

cta

te (

mm

ol

L)

p=NS

The Correlation Between Arterial Lactate and Venous Lactate in Patients With Sepsis and

Septic Shock (unpublished data)

Na Petvicharn C MD Theerawit P MD

Department of Internal Medicine the Faculty of Medicine Ramathibodi Hospital MahidolUniversity

060356

17

LACtime the predictor of organ failureJan Bakker et alAJS 1996171221-6

Lactate

Time

Lactime

AUC

Survivors

Non-survivors

P lt 005

2 mmolL

Serial blood lactate levels can predict the

development of multiple organ failure following septic shock

MD Jan Bakker MD Philippe Gris MD Michel Coffernils MD Robert J Kahn MD PhD Jean-

Louis Vincent The American Journal of surgery Volume 171 Issue 2 Pages 221-226 February 1996

plt005

plt 001

plt005 vs initial

blood lactate

Lactate clearance and mortalityArnold RC Shock 2008

0

10

20

30

40

50

60

70

LC gt 10 LC lt 10

Mortality rate

SvO2 gt 70

P lt 0001

Odds ratio for death 49(15-159)

Early lactate clearance is associated with

improved outcome in severe sepsis and

septic shock

H Bryant Nguyen MD MS Emanuel P Rivers MD MPH Bernhard P Knoblich MD

Gordon Jacobsen MS Alexandria Muzzin BS Julie A Ressler BS Michael C Tomlanovich

MDCrit Care Med 2004 Vol 32 No 8

Lactate clearance

= (Lactate ED presentation ndash Lactate Hour 6)x100Lactate ED presentation

There was an approximately

11 decrease likelihood of mortality for each 10 increase in lactate clearance

Association between blood lactate levels Sequential Organ Failure

Assessment subscores and 28-day mortality during

early and late ICU stay A retrospective observational study

Tim C Jansen Jasper van Bommel Roger Woodward Paul G H Mulder Jan Bakker Crit Care Med 2009 Vol 37 No 8

Dynamic Lactate Indices as

Predictors of Outcome in Critically Ill Patients

Admission lactate (LACADM)

Maximum lactate (LACMAX24)

Minimum lactate (LACMIN24)

Time weighted lactate (LACTW24)

Absolute change in (delta) lactate (LACΔ24)

Percentage change in lactate (LACΔ24)

Nichol A Bailey M Egi M Pettila V French C Hart GK Stachowski E Reade MCCooper

DJ Bellomo RCrit Care 2011 15R242

060356

18

Tissue perfusion

Lactate is better than SvO2 for assessment of tissue perfusion

The higher initial lactate the higher mortality

Lactate changing over time is better than a single value for monitoring

The higher lactate clearance the better

outcome

At least 10 reduction of lactate during resuscitation should be achieved

Type of fluid

Colloids or Crystalloids

26 Randomized trials

BMJ 1998316961-4

RR of death

Trauma 130(095-177)

Burn 121(088-166)

Sepsis 108(073-161)

Pooled 119(098-145)

Crystalloid and colloid infusion over 90 min in sepsis and non sepsis cases with

fluid responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid Colloid P value

CI before

CI after

EVLW

beforeEVLW after

39(24-55)

41(25-59)

71(19-339)75(16-299)

34(20-82)

38(23-69)

71(26-213)71(25-196)

Plt001

Pgt005

P value between before and after

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

060356

19

Crystalloid VS Colloid

No difference in

PLI

EVLW

Gas exchange

If fluid is administered in septic

patients with

fluid responsiveness even in ALI

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

Correction of albumin in ARDS

Refresher course ICM December 2008

Correction of albumin in ARDS

Refresher course ICM December 2008

Colloid solution

Albumin Artificial

Gelatins

Dextran

HES

Poor effective

Allergic reactionAltered hemostasis

Allergic reactionRenal dysfucntion

060356

20

Colloid solutions

Hypoalbuminemia tends to increase the incidence of ARDS and mortality in sepsis patients

More fluid required for correct hemodynamic abnormality

Poor response to Furosemide

More potential leakage at capillary site may lead to more lung injury

Correction of hypoalbuminemia in ARDS may be benefitial in terms of mortality but it must be used carefully

HES may cause renal failure and high dosage may lead to bleeding tendency

The benefit of artificial colloid solution over albumin is not known

Case

60 YO male patient 60 Kg

Pneumonia with septic shock on MV

VS BP 8040 mmHg HR 120 RR 26 BT 39oC

Heart normal S1S2 no murmur

Lungs crepitation RLL lingular segment

Liver and spleen not palpable

No edema

Neuro WNL

Case

Load NSS 1500 ml -gt PPV 14 -gt lung crepitation

BP 9040 mmHg (MAP = 57 mmHg)

Increase Nor-epinephrine

BP 8545 mmHg (MAP = 55 mmHg)

HR 90 -gt 110 min lactate 3 to 6 mmolL

Re-assessment

ABG

pH 71

pCO2 35 mmHg

pO2 70 mmHg

HCO3 15 mmolL

We corrected acidosis and start dobutamine

Can decrease dosage of NorE and lactate 41

The

EGDT

We need re-

assessment

here

These are causes of no

response to pressor

Acidosis

Poor LV contraction

RV dysfunction +- PE

Pneumothorax

Concealed hemorrhage

Relative adrenal insufficiency

Electrolyte imbalance

Severe sepsis

060356

21

Norepinephrine in septic shock

Study Baseline CI(normal 25-4)

EM Redl-Wenzl et al 1993Claude Martin et al 1993BLevy et al 1997Daniel De Backer et al 2003

Jacques Albane`se et al 2004Franccedilois Lauzier et al 2006

38+1153+1340+134+1

47+0244+14

Blood transfusion in septic shockJean-Louis Vincent Pongdhep Theerawit Davide Simeon

Basic Principles of Oxygen Transport and Calculations

Alternatives to Blood Transfusion in Transfusion Medicine 2nd Ed

Chapter 17 Published Online 4 SEP 2010

Transfusions will obviously have opposite effects to

anemia increasing blood viscosity and reducing the adrenergic response It is intriguing to consider

that transfusions may result in a decrease in

myocardial contractility Hence cardiac output often decreases following transfusions in the

nomovolemic patient and the increase in DO2

can be minor or even absent For example Shah et al observed in resuscitated trauma patients

that blood transfusion of one unit of RBC increased hemoglobin from 92 plusmn 03 to 102 plusmn 03

gdL but decreased cardiac output so that DO2

did not change

Hb lt 10 gL goal 10-12 gL

Hb lt 7 gL goal 7-9 gL

N=418

N=420

A MULTICENTER RANDOMIZED CONTROLLED CLINICAL

TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CAREPAULC HEacuteBERT MD GEORGEWELLS PHD MORRISA BLAJCHMAN MD JOHNMARSHALL MD CLAUDIOMARTIN MD GIUSEPPEPAGLIARELLO MD MARTINTWEEDDALE MD PHD IRWINSCHWEITZER MSC ELIZABETHYETISIR MSC ANDTHETRANSFUSIONREQUIREMENTSINCRITICALCAREINVESTIGATORSFORTHECANADIANCRITICALCARETRIALSGROUP

NEJM 1999

(normovolemia)

Red blood cell transfusion during septic shock in the ICUA Perner etal Acta Anaesthesiol Scand 2012 56 718ndash723

The CRIT Study Anemia and blood transfusion in the critically illmdashCurrent clinical practice in the United States

(Observational study 284 ICU 4892 patients)

Crit Care Med 2004 3239 ndash52

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 8: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

8

Good correlation between

CCO and BCO in sepsisIntensive Care Med 2002281276

Good correlation between CCO and BCO in sepsisIntensive Care Med 2002281276

Poor correlation of

CCO during hypothermia

Conclusions

Despite an excellent correlation accuracy and

precision between CCO and ICO before CPB and more than 45 minutes after hypothermic CPB a lack

of correlation in the early phase after CPB has been

found Further investigation is needed to elucidate the underlying cause of these findings and to clarify

whether ICO or CCO or both fail to represent the

real cardiac output up to 45 minutes after weaning from hypothermic CPB

19959405

Response time after sudden reduction of COAnesthesiology 199889(6)1592

Response time after sudden reduction of COCrit Care Med 1995 23 860 Advantages over IBCO

Provide continuous trend

Reduce contamination

Less time consuming

Unnecessary fluid

060356

9

Limitations

Immediate CO measurement may not be done due to average time for reduce thermal noise

Transpulmoanry thermodilution method (TPTD)

Compare TPTD and IBTDAnesthesia amp Analgesia 2010

The respiratory variation affect IBTD rather than TPTD

IBTD

TPTD

Advantages over IBTD

Less invasive

Decrease complications result from PA catheter

GEDV and EVLW can be measuredAm J Physiol Lung Cell Mol Physiol 291 L1118ndashL1131 2006

060356

10

Limitations

Canrsquot assess PA pressure and its trend

Canrsquot assess SvO2

Pulse contour analysis

Non-calibrated

Calibrated

Basic Principles

Traditional CO = HR SV

FloTrac system CO = PR x (AP )

Where = M (HR AP C(P) BSA MAP 3ap 4ap)

Validation ICOCCOAPCOCrit Care 200711R105

Validation ICOCCOAPCOCrit Care 200711R105

FloTrac amp PACCrit Care 201014R212

060356

11

FloTrac amp PACCrit Care 201014R212

FloTrac in sepsisIntensive Care 201137233

FloTrac in sepsisIntensive Care 201137233

FloTrac Vigileo G3

Advantages

Real time

Less invasive

Non-calibrated

Informative

CO CI

PPV

SvO2

SVR

Disadvantages

Algorithm-gtnot real

Accuracy

Can not assess RV

derived parameters

Require new version software

PiCCO system Need calibration

060356

12

PAC and PiCCO (AP)Crit Care 201014R212

PiCCO

Advantages

Continuos monitoring

More accurate

Informative

COCI

SVV

SVR

GEDV

EVLW

AP

Disadvantages

Require calibration q 8 hrs

Femoral site risky to

CRBSI

Early goal directed therapy

What is the CVP

CVP = Central Venous Pressure

Frank Starling amp venous return line

Stroke volume

CVP0

Frank-Starling curve

Stroke volume or EDV

JVP or CVP or PCWP

ΔSV or Δ EDV

a

b

Responders

Non-responders

060356

13

b

CVP tells us who responders

Stroke volume or EDV

CVP or PCWP

ΔSV or Δ EDV

a

Good

Bad

CVP vs Fluid responders

Crit Care Med 20073564-8

39 cases25 cases

Does Central Venous Pressure Predict

Fluid ResponsivenessA Systematic Review of the Literature

CHEST 2008 134172ndash178

Fluid resuscitation in septic shock a positive fluid balance and elevated central venous pressure are associated with increased mortalityBoyd JH Forbes J Nakada TA Walley KR Russell JA

OBJECTIVE

To determine whether central venous pressure and fluid balance after resuscitation for septic shock are associated

with mortality

PATIENTS

The Vasopressin in Septic Shock Trial (VASST) study enrolled 778 patients who had septic shock and who were

receiving a minimum of 5 μg of norepinephrine per minute

MEASUREMENTS AND MAIN RESULTS

Based on net fluid balance we determined whether ones fluid balance quartile was correlated with 28-day

mortality We also analyzed whether fluid balance was predictive of central venous pressure and furthermore

whether a guideline-recommended central venous pressure of 8-12 mm Hg yielded a mortality advantage At

enrollment which occurred on average 12 hrs after presentation the average fluid balance was +42 L By day 4 the

cumulative average fluid balance was +11 L After correcting for age and Acute Physiology and Chronic Health

Evaluation II score a more positive fluid balance at both at 12 hrs and day 4 correlated significantly with increased

mortality Central venous pressure was correlated with fluid balance at 12 hrs whereas on days 1-4 there was no

significant correlation At 12 hrs patients with central venous pressure lt8 mm Hg had the lowest mortality rate

followed by those with central venous pressure 8-12 mm Hg The highest mortality rate was observed in those with

central venous pressure gt12 mm Hg Contrary to the overall effect patients whose central venous pressure was lt8

mm Hg had improved survival with a more positive fluid balance

CONCLUSIONS

A more positive fluid balance both early in resuscitation and cumulatively over 4 days is associated with an increased

risk of mortality in septic shock Central venous pressure may be used to gauge fluid balance le 12 hrs into septic

shock but becomes an unreliable marker of fluid balance thereafter Optimal survival in the VASST study occurred

with a positive fluid balance of approximately 3 L at 12 hrs

Functional hemodynamic for predicting fluidresponsiveness

Spontaneous respiration

CVP variation gt 1 mmHg

PLR cCO gt 15 ( can be used in arrhythmia)

On mechanical ventilation

PPV gt 13

IVCd variation gt 12 ( can be used in arrhythmia)

IVC distensibility index gt 18 ( can be used in arrhythmia)

Brachail peak velocity gt 10

PLR cCO gt 15 ( can be used in arrhythmia)

PLR ET-CO2 gt 5

060356

14

PP variation predict fluid responsiveness

PPV = PPmax-PPmin x 100

(PPmax+PPmin)2

PPV gt 13 indicate fluid

responsiveness

PPV 94

NPV 96

Reference Year of

publication

Clinical setting PPV threshold value()

Michard etal

Viellard-Baron etal

Kramer etal

Preisman etal

Hofer etal

Feissel etal

De Backer etal

Cannesson etal

Solus-Biguenet etal

Lafanechere etal

Monnet etal

Charron etal

Natalini etal

Feissel etal

Cannesson etal

2000

2004

2004

2005

2005

2005

2005

2006

2006

2006

2006

2006

2006

2007

2007

Medical ICU

Medical ICU

CABG

CABG

CABG

Surgical and medical ICU

Surgical and medical ICU

CABG

Hepatic resection

Medical ICU

Medical ICU

Surgical ICU

Surgical and medical ICU

Medical ICU

CABG

13

12

11

9

13

17

12

12

14

12

12

10

15

12

11

Limitations

Controlled mechanical ventilation

Tidal volume ge 8 mlkg

Sinus rhythm

How to assess lung leakage

Clinical assessment

More dyspneic

Crepitation increase

Gas exchange

Desaturation

Lower pO2

Lung mechanic

Decrease lung compliance

CXR

May be difficult to determine in ARDS

The lung compliance

Respiratory system compliance

119862119877119878 =119879119907

119875119901119897119886119905119890119886119906minus119875119864119864119875

Bedside measurement of CRS

Pressure

Time

PEEP

060356

15

Bedside measurement of CRS

Pressure

Time

PEEP

Pplateau

PIP

After set Plateau time

Monitoring CRS (Volume mode)

Parameters Time 0 1 hour

PaO2 80 85

PaCO2 40 44

SaO2 96 97

PIP 35 45

Pplateau 30 36

PEEP 12 12

Exhaled TV 400 400

CRS222 167

FiO2 05 09

Fluid (ml) 0 1200

The EGDTPuzzle of formula

SvO2 Cellular oxygen

Good SvO2 means good cellular oxygenation (Low flow)

DO2 = 100

VO2 = 30

SvO2 = 70

Good SvO2 means good cellular oxygenation (heterogeneous flow)

DO2 = 100

VO2 = 10

SvO2 = 90

060356

16

Correlation between perfused capillary and blood lactateDe Backer etal Crit Care Med 2006

Prognostic value of hyperlactatemia in many

different critical care conditionsBlood lactate levels are superior to oxygen-derived

variables in predicting outcome in human septic shock

J Bakker M Coffernils M Leon P Gris and J L Vincent Chest 199199956-962

plt 005

plt 0001

Lactate level after 4 hrs of resuscitationS-W Lee etal Emerg Med J 200825659-665

Prognostic value of blood lactate levels in the ED

Shapiro NI et al Serum lactate as a predictor of mortality in emergency department patients with infection Ann Emerg Med 2005 45(5) p 524-8

490

900

2840

150

450

2240

000

500

1000

1500

2000

2500

3000

0-24 25-39 gt4

28 day in hospital mortality Death

Mo

rta

lity

ra

te

Lactate

Serum lactate as a predictor of mortalityin patients with infection

S Trzeciak et alIntensive Care Med (2007) 33970ndash977

Prognostic value of blood lactate levels

in the Critical care unit at Ramathibodihospital

Survivors 27

Non-survivors

5

0

1

2

3

4

5

6

Art

eri

al la

cta

te (

mm

ol

L)

p=NS

The Correlation Between Arterial Lactate and Venous Lactate in Patients With Sepsis and

Septic Shock (unpublished data)

Na Petvicharn C MD Theerawit P MD

Department of Internal Medicine the Faculty of Medicine Ramathibodi Hospital MahidolUniversity

060356

17

LACtime the predictor of organ failureJan Bakker et alAJS 1996171221-6

Lactate

Time

Lactime

AUC

Survivors

Non-survivors

P lt 005

2 mmolL

Serial blood lactate levels can predict the

development of multiple organ failure following septic shock

MD Jan Bakker MD Philippe Gris MD Michel Coffernils MD Robert J Kahn MD PhD Jean-

Louis Vincent The American Journal of surgery Volume 171 Issue 2 Pages 221-226 February 1996

plt005

plt 001

plt005 vs initial

blood lactate

Lactate clearance and mortalityArnold RC Shock 2008

0

10

20

30

40

50

60

70

LC gt 10 LC lt 10

Mortality rate

SvO2 gt 70

P lt 0001

Odds ratio for death 49(15-159)

Early lactate clearance is associated with

improved outcome in severe sepsis and

septic shock

H Bryant Nguyen MD MS Emanuel P Rivers MD MPH Bernhard P Knoblich MD

Gordon Jacobsen MS Alexandria Muzzin BS Julie A Ressler BS Michael C Tomlanovich

MDCrit Care Med 2004 Vol 32 No 8

Lactate clearance

= (Lactate ED presentation ndash Lactate Hour 6)x100Lactate ED presentation

There was an approximately

11 decrease likelihood of mortality for each 10 increase in lactate clearance

Association between blood lactate levels Sequential Organ Failure

Assessment subscores and 28-day mortality during

early and late ICU stay A retrospective observational study

Tim C Jansen Jasper van Bommel Roger Woodward Paul G H Mulder Jan Bakker Crit Care Med 2009 Vol 37 No 8

Dynamic Lactate Indices as

Predictors of Outcome in Critically Ill Patients

Admission lactate (LACADM)

Maximum lactate (LACMAX24)

Minimum lactate (LACMIN24)

Time weighted lactate (LACTW24)

Absolute change in (delta) lactate (LACΔ24)

Percentage change in lactate (LACΔ24)

Nichol A Bailey M Egi M Pettila V French C Hart GK Stachowski E Reade MCCooper

DJ Bellomo RCrit Care 2011 15R242

060356

18

Tissue perfusion

Lactate is better than SvO2 for assessment of tissue perfusion

The higher initial lactate the higher mortality

Lactate changing over time is better than a single value for monitoring

The higher lactate clearance the better

outcome

At least 10 reduction of lactate during resuscitation should be achieved

Type of fluid

Colloids or Crystalloids

26 Randomized trials

BMJ 1998316961-4

RR of death

Trauma 130(095-177)

Burn 121(088-166)

Sepsis 108(073-161)

Pooled 119(098-145)

Crystalloid and colloid infusion over 90 min in sepsis and non sepsis cases with

fluid responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid Colloid P value

CI before

CI after

EVLW

beforeEVLW after

39(24-55)

41(25-59)

71(19-339)75(16-299)

34(20-82)

38(23-69)

71(26-213)71(25-196)

Plt001

Pgt005

P value between before and after

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

060356

19

Crystalloid VS Colloid

No difference in

PLI

EVLW

Gas exchange

If fluid is administered in septic

patients with

fluid responsiveness even in ALI

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

Correction of albumin in ARDS

Refresher course ICM December 2008

Correction of albumin in ARDS

Refresher course ICM December 2008

Colloid solution

Albumin Artificial

Gelatins

Dextran

HES

Poor effective

Allergic reactionAltered hemostasis

Allergic reactionRenal dysfucntion

060356

20

Colloid solutions

Hypoalbuminemia tends to increase the incidence of ARDS and mortality in sepsis patients

More fluid required for correct hemodynamic abnormality

Poor response to Furosemide

More potential leakage at capillary site may lead to more lung injury

Correction of hypoalbuminemia in ARDS may be benefitial in terms of mortality but it must be used carefully

HES may cause renal failure and high dosage may lead to bleeding tendency

The benefit of artificial colloid solution over albumin is not known

Case

60 YO male patient 60 Kg

Pneumonia with septic shock on MV

VS BP 8040 mmHg HR 120 RR 26 BT 39oC

Heart normal S1S2 no murmur

Lungs crepitation RLL lingular segment

Liver and spleen not palpable

No edema

Neuro WNL

Case

Load NSS 1500 ml -gt PPV 14 -gt lung crepitation

BP 9040 mmHg (MAP = 57 mmHg)

Increase Nor-epinephrine

BP 8545 mmHg (MAP = 55 mmHg)

HR 90 -gt 110 min lactate 3 to 6 mmolL

Re-assessment

ABG

pH 71

pCO2 35 mmHg

pO2 70 mmHg

HCO3 15 mmolL

We corrected acidosis and start dobutamine

Can decrease dosage of NorE and lactate 41

The

EGDT

We need re-

assessment

here

These are causes of no

response to pressor

Acidosis

Poor LV contraction

RV dysfunction +- PE

Pneumothorax

Concealed hemorrhage

Relative adrenal insufficiency

Electrolyte imbalance

Severe sepsis

060356

21

Norepinephrine in septic shock

Study Baseline CI(normal 25-4)

EM Redl-Wenzl et al 1993Claude Martin et al 1993BLevy et al 1997Daniel De Backer et al 2003

Jacques Albane`se et al 2004Franccedilois Lauzier et al 2006

38+1153+1340+134+1

47+0244+14

Blood transfusion in septic shockJean-Louis Vincent Pongdhep Theerawit Davide Simeon

Basic Principles of Oxygen Transport and Calculations

Alternatives to Blood Transfusion in Transfusion Medicine 2nd Ed

Chapter 17 Published Online 4 SEP 2010

Transfusions will obviously have opposite effects to

anemia increasing blood viscosity and reducing the adrenergic response It is intriguing to consider

that transfusions may result in a decrease in

myocardial contractility Hence cardiac output often decreases following transfusions in the

nomovolemic patient and the increase in DO2

can be minor or even absent For example Shah et al observed in resuscitated trauma patients

that blood transfusion of one unit of RBC increased hemoglobin from 92 plusmn 03 to 102 plusmn 03

gdL but decreased cardiac output so that DO2

did not change

Hb lt 10 gL goal 10-12 gL

Hb lt 7 gL goal 7-9 gL

N=418

N=420

A MULTICENTER RANDOMIZED CONTROLLED CLINICAL

TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CAREPAULC HEacuteBERT MD GEORGEWELLS PHD MORRISA BLAJCHMAN MD JOHNMARSHALL MD CLAUDIOMARTIN MD GIUSEPPEPAGLIARELLO MD MARTINTWEEDDALE MD PHD IRWINSCHWEITZER MSC ELIZABETHYETISIR MSC ANDTHETRANSFUSIONREQUIREMENTSINCRITICALCAREINVESTIGATORSFORTHECANADIANCRITICALCARETRIALSGROUP

NEJM 1999

(normovolemia)

Red blood cell transfusion during septic shock in the ICUA Perner etal Acta Anaesthesiol Scand 2012 56 718ndash723

The CRIT Study Anemia and blood transfusion in the critically illmdashCurrent clinical practice in the United States

(Observational study 284 ICU 4892 patients)

Crit Care Med 2004 3239 ndash52

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 9: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

9

Limitations

Immediate CO measurement may not be done due to average time for reduce thermal noise

Transpulmoanry thermodilution method (TPTD)

Compare TPTD and IBTDAnesthesia amp Analgesia 2010

The respiratory variation affect IBTD rather than TPTD

IBTD

TPTD

Advantages over IBTD

Less invasive

Decrease complications result from PA catheter

GEDV and EVLW can be measuredAm J Physiol Lung Cell Mol Physiol 291 L1118ndashL1131 2006

060356

10

Limitations

Canrsquot assess PA pressure and its trend

Canrsquot assess SvO2

Pulse contour analysis

Non-calibrated

Calibrated

Basic Principles

Traditional CO = HR SV

FloTrac system CO = PR x (AP )

Where = M (HR AP C(P) BSA MAP 3ap 4ap)

Validation ICOCCOAPCOCrit Care 200711R105

Validation ICOCCOAPCOCrit Care 200711R105

FloTrac amp PACCrit Care 201014R212

060356

11

FloTrac amp PACCrit Care 201014R212

FloTrac in sepsisIntensive Care 201137233

FloTrac in sepsisIntensive Care 201137233

FloTrac Vigileo G3

Advantages

Real time

Less invasive

Non-calibrated

Informative

CO CI

PPV

SvO2

SVR

Disadvantages

Algorithm-gtnot real

Accuracy

Can not assess RV

derived parameters

Require new version software

PiCCO system Need calibration

060356

12

PAC and PiCCO (AP)Crit Care 201014R212

PiCCO

Advantages

Continuos monitoring

More accurate

Informative

COCI

SVV

SVR

GEDV

EVLW

AP

Disadvantages

Require calibration q 8 hrs

Femoral site risky to

CRBSI

Early goal directed therapy

What is the CVP

CVP = Central Venous Pressure

Frank Starling amp venous return line

Stroke volume

CVP0

Frank-Starling curve

Stroke volume or EDV

JVP or CVP or PCWP

ΔSV or Δ EDV

a

b

Responders

Non-responders

060356

13

b

CVP tells us who responders

Stroke volume or EDV

CVP or PCWP

ΔSV or Δ EDV

a

Good

Bad

CVP vs Fluid responders

Crit Care Med 20073564-8

39 cases25 cases

Does Central Venous Pressure Predict

Fluid ResponsivenessA Systematic Review of the Literature

CHEST 2008 134172ndash178

Fluid resuscitation in septic shock a positive fluid balance and elevated central venous pressure are associated with increased mortalityBoyd JH Forbes J Nakada TA Walley KR Russell JA

OBJECTIVE

To determine whether central venous pressure and fluid balance after resuscitation for septic shock are associated

with mortality

PATIENTS

The Vasopressin in Septic Shock Trial (VASST) study enrolled 778 patients who had septic shock and who were

receiving a minimum of 5 μg of norepinephrine per minute

MEASUREMENTS AND MAIN RESULTS

Based on net fluid balance we determined whether ones fluid balance quartile was correlated with 28-day

mortality We also analyzed whether fluid balance was predictive of central venous pressure and furthermore

whether a guideline-recommended central venous pressure of 8-12 mm Hg yielded a mortality advantage At

enrollment which occurred on average 12 hrs after presentation the average fluid balance was +42 L By day 4 the

cumulative average fluid balance was +11 L After correcting for age and Acute Physiology and Chronic Health

Evaluation II score a more positive fluid balance at both at 12 hrs and day 4 correlated significantly with increased

mortality Central venous pressure was correlated with fluid balance at 12 hrs whereas on days 1-4 there was no

significant correlation At 12 hrs patients with central venous pressure lt8 mm Hg had the lowest mortality rate

followed by those with central venous pressure 8-12 mm Hg The highest mortality rate was observed in those with

central venous pressure gt12 mm Hg Contrary to the overall effect patients whose central venous pressure was lt8

mm Hg had improved survival with a more positive fluid balance

CONCLUSIONS

A more positive fluid balance both early in resuscitation and cumulatively over 4 days is associated with an increased

risk of mortality in septic shock Central venous pressure may be used to gauge fluid balance le 12 hrs into septic

shock but becomes an unreliable marker of fluid balance thereafter Optimal survival in the VASST study occurred

with a positive fluid balance of approximately 3 L at 12 hrs

Functional hemodynamic for predicting fluidresponsiveness

Spontaneous respiration

CVP variation gt 1 mmHg

PLR cCO gt 15 ( can be used in arrhythmia)

On mechanical ventilation

PPV gt 13

IVCd variation gt 12 ( can be used in arrhythmia)

IVC distensibility index gt 18 ( can be used in arrhythmia)

Brachail peak velocity gt 10

PLR cCO gt 15 ( can be used in arrhythmia)

PLR ET-CO2 gt 5

060356

14

PP variation predict fluid responsiveness

PPV = PPmax-PPmin x 100

(PPmax+PPmin)2

PPV gt 13 indicate fluid

responsiveness

PPV 94

NPV 96

Reference Year of

publication

Clinical setting PPV threshold value()

Michard etal

Viellard-Baron etal

Kramer etal

Preisman etal

Hofer etal

Feissel etal

De Backer etal

Cannesson etal

Solus-Biguenet etal

Lafanechere etal

Monnet etal

Charron etal

Natalini etal

Feissel etal

Cannesson etal

2000

2004

2004

2005

2005

2005

2005

2006

2006

2006

2006

2006

2006

2007

2007

Medical ICU

Medical ICU

CABG

CABG

CABG

Surgical and medical ICU

Surgical and medical ICU

CABG

Hepatic resection

Medical ICU

Medical ICU

Surgical ICU

Surgical and medical ICU

Medical ICU

CABG

13

12

11

9

13

17

12

12

14

12

12

10

15

12

11

Limitations

Controlled mechanical ventilation

Tidal volume ge 8 mlkg

Sinus rhythm

How to assess lung leakage

Clinical assessment

More dyspneic

Crepitation increase

Gas exchange

Desaturation

Lower pO2

Lung mechanic

Decrease lung compliance

CXR

May be difficult to determine in ARDS

The lung compliance

Respiratory system compliance

119862119877119878 =119879119907

119875119901119897119886119905119890119886119906minus119875119864119864119875

Bedside measurement of CRS

Pressure

Time

PEEP

060356

15

Bedside measurement of CRS

Pressure

Time

PEEP

Pplateau

PIP

After set Plateau time

Monitoring CRS (Volume mode)

Parameters Time 0 1 hour

PaO2 80 85

PaCO2 40 44

SaO2 96 97

PIP 35 45

Pplateau 30 36

PEEP 12 12

Exhaled TV 400 400

CRS222 167

FiO2 05 09

Fluid (ml) 0 1200

The EGDTPuzzle of formula

SvO2 Cellular oxygen

Good SvO2 means good cellular oxygenation (Low flow)

DO2 = 100

VO2 = 30

SvO2 = 70

Good SvO2 means good cellular oxygenation (heterogeneous flow)

DO2 = 100

VO2 = 10

SvO2 = 90

060356

16

Correlation between perfused capillary and blood lactateDe Backer etal Crit Care Med 2006

Prognostic value of hyperlactatemia in many

different critical care conditionsBlood lactate levels are superior to oxygen-derived

variables in predicting outcome in human septic shock

J Bakker M Coffernils M Leon P Gris and J L Vincent Chest 199199956-962

plt 005

plt 0001

Lactate level after 4 hrs of resuscitationS-W Lee etal Emerg Med J 200825659-665

Prognostic value of blood lactate levels in the ED

Shapiro NI et al Serum lactate as a predictor of mortality in emergency department patients with infection Ann Emerg Med 2005 45(5) p 524-8

490

900

2840

150

450

2240

000

500

1000

1500

2000

2500

3000

0-24 25-39 gt4

28 day in hospital mortality Death

Mo

rta

lity

ra

te

Lactate

Serum lactate as a predictor of mortalityin patients with infection

S Trzeciak et alIntensive Care Med (2007) 33970ndash977

Prognostic value of blood lactate levels

in the Critical care unit at Ramathibodihospital

Survivors 27

Non-survivors

5

0

1

2

3

4

5

6

Art

eri

al la

cta

te (

mm

ol

L)

p=NS

The Correlation Between Arterial Lactate and Venous Lactate in Patients With Sepsis and

Septic Shock (unpublished data)

Na Petvicharn C MD Theerawit P MD

Department of Internal Medicine the Faculty of Medicine Ramathibodi Hospital MahidolUniversity

060356

17

LACtime the predictor of organ failureJan Bakker et alAJS 1996171221-6

Lactate

Time

Lactime

AUC

Survivors

Non-survivors

P lt 005

2 mmolL

Serial blood lactate levels can predict the

development of multiple organ failure following septic shock

MD Jan Bakker MD Philippe Gris MD Michel Coffernils MD Robert J Kahn MD PhD Jean-

Louis Vincent The American Journal of surgery Volume 171 Issue 2 Pages 221-226 February 1996

plt005

plt 001

plt005 vs initial

blood lactate

Lactate clearance and mortalityArnold RC Shock 2008

0

10

20

30

40

50

60

70

LC gt 10 LC lt 10

Mortality rate

SvO2 gt 70

P lt 0001

Odds ratio for death 49(15-159)

Early lactate clearance is associated with

improved outcome in severe sepsis and

septic shock

H Bryant Nguyen MD MS Emanuel P Rivers MD MPH Bernhard P Knoblich MD

Gordon Jacobsen MS Alexandria Muzzin BS Julie A Ressler BS Michael C Tomlanovich

MDCrit Care Med 2004 Vol 32 No 8

Lactate clearance

= (Lactate ED presentation ndash Lactate Hour 6)x100Lactate ED presentation

There was an approximately

11 decrease likelihood of mortality for each 10 increase in lactate clearance

Association between blood lactate levels Sequential Organ Failure

Assessment subscores and 28-day mortality during

early and late ICU stay A retrospective observational study

Tim C Jansen Jasper van Bommel Roger Woodward Paul G H Mulder Jan Bakker Crit Care Med 2009 Vol 37 No 8

Dynamic Lactate Indices as

Predictors of Outcome in Critically Ill Patients

Admission lactate (LACADM)

Maximum lactate (LACMAX24)

Minimum lactate (LACMIN24)

Time weighted lactate (LACTW24)

Absolute change in (delta) lactate (LACΔ24)

Percentage change in lactate (LACΔ24)

Nichol A Bailey M Egi M Pettila V French C Hart GK Stachowski E Reade MCCooper

DJ Bellomo RCrit Care 2011 15R242

060356

18

Tissue perfusion

Lactate is better than SvO2 for assessment of tissue perfusion

The higher initial lactate the higher mortality

Lactate changing over time is better than a single value for monitoring

The higher lactate clearance the better

outcome

At least 10 reduction of lactate during resuscitation should be achieved

Type of fluid

Colloids or Crystalloids

26 Randomized trials

BMJ 1998316961-4

RR of death

Trauma 130(095-177)

Burn 121(088-166)

Sepsis 108(073-161)

Pooled 119(098-145)

Crystalloid and colloid infusion over 90 min in sepsis and non sepsis cases with

fluid responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid Colloid P value

CI before

CI after

EVLW

beforeEVLW after

39(24-55)

41(25-59)

71(19-339)75(16-299)

34(20-82)

38(23-69)

71(26-213)71(25-196)

Plt001

Pgt005

P value between before and after

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

060356

19

Crystalloid VS Colloid

No difference in

PLI

EVLW

Gas exchange

If fluid is administered in septic

patients with

fluid responsiveness even in ALI

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

Correction of albumin in ARDS

Refresher course ICM December 2008

Correction of albumin in ARDS

Refresher course ICM December 2008

Colloid solution

Albumin Artificial

Gelatins

Dextran

HES

Poor effective

Allergic reactionAltered hemostasis

Allergic reactionRenal dysfucntion

060356

20

Colloid solutions

Hypoalbuminemia tends to increase the incidence of ARDS and mortality in sepsis patients

More fluid required for correct hemodynamic abnormality

Poor response to Furosemide

More potential leakage at capillary site may lead to more lung injury

Correction of hypoalbuminemia in ARDS may be benefitial in terms of mortality but it must be used carefully

HES may cause renal failure and high dosage may lead to bleeding tendency

The benefit of artificial colloid solution over albumin is not known

Case

60 YO male patient 60 Kg

Pneumonia with septic shock on MV

VS BP 8040 mmHg HR 120 RR 26 BT 39oC

Heart normal S1S2 no murmur

Lungs crepitation RLL lingular segment

Liver and spleen not palpable

No edema

Neuro WNL

Case

Load NSS 1500 ml -gt PPV 14 -gt lung crepitation

BP 9040 mmHg (MAP = 57 mmHg)

Increase Nor-epinephrine

BP 8545 mmHg (MAP = 55 mmHg)

HR 90 -gt 110 min lactate 3 to 6 mmolL

Re-assessment

ABG

pH 71

pCO2 35 mmHg

pO2 70 mmHg

HCO3 15 mmolL

We corrected acidosis and start dobutamine

Can decrease dosage of NorE and lactate 41

The

EGDT

We need re-

assessment

here

These are causes of no

response to pressor

Acidosis

Poor LV contraction

RV dysfunction +- PE

Pneumothorax

Concealed hemorrhage

Relative adrenal insufficiency

Electrolyte imbalance

Severe sepsis

060356

21

Norepinephrine in septic shock

Study Baseline CI(normal 25-4)

EM Redl-Wenzl et al 1993Claude Martin et al 1993BLevy et al 1997Daniel De Backer et al 2003

Jacques Albane`se et al 2004Franccedilois Lauzier et al 2006

38+1153+1340+134+1

47+0244+14

Blood transfusion in septic shockJean-Louis Vincent Pongdhep Theerawit Davide Simeon

Basic Principles of Oxygen Transport and Calculations

Alternatives to Blood Transfusion in Transfusion Medicine 2nd Ed

Chapter 17 Published Online 4 SEP 2010

Transfusions will obviously have opposite effects to

anemia increasing blood viscosity and reducing the adrenergic response It is intriguing to consider

that transfusions may result in a decrease in

myocardial contractility Hence cardiac output often decreases following transfusions in the

nomovolemic patient and the increase in DO2

can be minor or even absent For example Shah et al observed in resuscitated trauma patients

that blood transfusion of one unit of RBC increased hemoglobin from 92 plusmn 03 to 102 plusmn 03

gdL but decreased cardiac output so that DO2

did not change

Hb lt 10 gL goal 10-12 gL

Hb lt 7 gL goal 7-9 gL

N=418

N=420

A MULTICENTER RANDOMIZED CONTROLLED CLINICAL

TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CAREPAULC HEacuteBERT MD GEORGEWELLS PHD MORRISA BLAJCHMAN MD JOHNMARSHALL MD CLAUDIOMARTIN MD GIUSEPPEPAGLIARELLO MD MARTINTWEEDDALE MD PHD IRWINSCHWEITZER MSC ELIZABETHYETISIR MSC ANDTHETRANSFUSIONREQUIREMENTSINCRITICALCAREINVESTIGATORSFORTHECANADIANCRITICALCARETRIALSGROUP

NEJM 1999

(normovolemia)

Red blood cell transfusion during septic shock in the ICUA Perner etal Acta Anaesthesiol Scand 2012 56 718ndash723

The CRIT Study Anemia and blood transfusion in the critically illmdashCurrent clinical practice in the United States

(Observational study 284 ICU 4892 patients)

Crit Care Med 2004 3239 ndash52

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 10: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

10

Limitations

Canrsquot assess PA pressure and its trend

Canrsquot assess SvO2

Pulse contour analysis

Non-calibrated

Calibrated

Basic Principles

Traditional CO = HR SV

FloTrac system CO = PR x (AP )

Where = M (HR AP C(P) BSA MAP 3ap 4ap)

Validation ICOCCOAPCOCrit Care 200711R105

Validation ICOCCOAPCOCrit Care 200711R105

FloTrac amp PACCrit Care 201014R212

060356

11

FloTrac amp PACCrit Care 201014R212

FloTrac in sepsisIntensive Care 201137233

FloTrac in sepsisIntensive Care 201137233

FloTrac Vigileo G3

Advantages

Real time

Less invasive

Non-calibrated

Informative

CO CI

PPV

SvO2

SVR

Disadvantages

Algorithm-gtnot real

Accuracy

Can not assess RV

derived parameters

Require new version software

PiCCO system Need calibration

060356

12

PAC and PiCCO (AP)Crit Care 201014R212

PiCCO

Advantages

Continuos monitoring

More accurate

Informative

COCI

SVV

SVR

GEDV

EVLW

AP

Disadvantages

Require calibration q 8 hrs

Femoral site risky to

CRBSI

Early goal directed therapy

What is the CVP

CVP = Central Venous Pressure

Frank Starling amp venous return line

Stroke volume

CVP0

Frank-Starling curve

Stroke volume or EDV

JVP or CVP or PCWP

ΔSV or Δ EDV

a

b

Responders

Non-responders

060356

13

b

CVP tells us who responders

Stroke volume or EDV

CVP or PCWP

ΔSV or Δ EDV

a

Good

Bad

CVP vs Fluid responders

Crit Care Med 20073564-8

39 cases25 cases

Does Central Venous Pressure Predict

Fluid ResponsivenessA Systematic Review of the Literature

CHEST 2008 134172ndash178

Fluid resuscitation in septic shock a positive fluid balance and elevated central venous pressure are associated with increased mortalityBoyd JH Forbes J Nakada TA Walley KR Russell JA

OBJECTIVE

To determine whether central venous pressure and fluid balance after resuscitation for septic shock are associated

with mortality

PATIENTS

The Vasopressin in Septic Shock Trial (VASST) study enrolled 778 patients who had septic shock and who were

receiving a minimum of 5 μg of norepinephrine per minute

MEASUREMENTS AND MAIN RESULTS

Based on net fluid balance we determined whether ones fluid balance quartile was correlated with 28-day

mortality We also analyzed whether fluid balance was predictive of central venous pressure and furthermore

whether a guideline-recommended central venous pressure of 8-12 mm Hg yielded a mortality advantage At

enrollment which occurred on average 12 hrs after presentation the average fluid balance was +42 L By day 4 the

cumulative average fluid balance was +11 L After correcting for age and Acute Physiology and Chronic Health

Evaluation II score a more positive fluid balance at both at 12 hrs and day 4 correlated significantly with increased

mortality Central venous pressure was correlated with fluid balance at 12 hrs whereas on days 1-4 there was no

significant correlation At 12 hrs patients with central venous pressure lt8 mm Hg had the lowest mortality rate

followed by those with central venous pressure 8-12 mm Hg The highest mortality rate was observed in those with

central venous pressure gt12 mm Hg Contrary to the overall effect patients whose central venous pressure was lt8

mm Hg had improved survival with a more positive fluid balance

CONCLUSIONS

A more positive fluid balance both early in resuscitation and cumulatively over 4 days is associated with an increased

risk of mortality in septic shock Central venous pressure may be used to gauge fluid balance le 12 hrs into septic

shock but becomes an unreliable marker of fluid balance thereafter Optimal survival in the VASST study occurred

with a positive fluid balance of approximately 3 L at 12 hrs

Functional hemodynamic for predicting fluidresponsiveness

Spontaneous respiration

CVP variation gt 1 mmHg

PLR cCO gt 15 ( can be used in arrhythmia)

On mechanical ventilation

PPV gt 13

IVCd variation gt 12 ( can be used in arrhythmia)

IVC distensibility index gt 18 ( can be used in arrhythmia)

Brachail peak velocity gt 10

PLR cCO gt 15 ( can be used in arrhythmia)

PLR ET-CO2 gt 5

060356

14

PP variation predict fluid responsiveness

PPV = PPmax-PPmin x 100

(PPmax+PPmin)2

PPV gt 13 indicate fluid

responsiveness

PPV 94

NPV 96

Reference Year of

publication

Clinical setting PPV threshold value()

Michard etal

Viellard-Baron etal

Kramer etal

Preisman etal

Hofer etal

Feissel etal

De Backer etal

Cannesson etal

Solus-Biguenet etal

Lafanechere etal

Monnet etal

Charron etal

Natalini etal

Feissel etal

Cannesson etal

2000

2004

2004

2005

2005

2005

2005

2006

2006

2006

2006

2006

2006

2007

2007

Medical ICU

Medical ICU

CABG

CABG

CABG

Surgical and medical ICU

Surgical and medical ICU

CABG

Hepatic resection

Medical ICU

Medical ICU

Surgical ICU

Surgical and medical ICU

Medical ICU

CABG

13

12

11

9

13

17

12

12

14

12

12

10

15

12

11

Limitations

Controlled mechanical ventilation

Tidal volume ge 8 mlkg

Sinus rhythm

How to assess lung leakage

Clinical assessment

More dyspneic

Crepitation increase

Gas exchange

Desaturation

Lower pO2

Lung mechanic

Decrease lung compliance

CXR

May be difficult to determine in ARDS

The lung compliance

Respiratory system compliance

119862119877119878 =119879119907

119875119901119897119886119905119890119886119906minus119875119864119864119875

Bedside measurement of CRS

Pressure

Time

PEEP

060356

15

Bedside measurement of CRS

Pressure

Time

PEEP

Pplateau

PIP

After set Plateau time

Monitoring CRS (Volume mode)

Parameters Time 0 1 hour

PaO2 80 85

PaCO2 40 44

SaO2 96 97

PIP 35 45

Pplateau 30 36

PEEP 12 12

Exhaled TV 400 400

CRS222 167

FiO2 05 09

Fluid (ml) 0 1200

The EGDTPuzzle of formula

SvO2 Cellular oxygen

Good SvO2 means good cellular oxygenation (Low flow)

DO2 = 100

VO2 = 30

SvO2 = 70

Good SvO2 means good cellular oxygenation (heterogeneous flow)

DO2 = 100

VO2 = 10

SvO2 = 90

060356

16

Correlation between perfused capillary and blood lactateDe Backer etal Crit Care Med 2006

Prognostic value of hyperlactatemia in many

different critical care conditionsBlood lactate levels are superior to oxygen-derived

variables in predicting outcome in human septic shock

J Bakker M Coffernils M Leon P Gris and J L Vincent Chest 199199956-962

plt 005

plt 0001

Lactate level after 4 hrs of resuscitationS-W Lee etal Emerg Med J 200825659-665

Prognostic value of blood lactate levels in the ED

Shapiro NI et al Serum lactate as a predictor of mortality in emergency department patients with infection Ann Emerg Med 2005 45(5) p 524-8

490

900

2840

150

450

2240

000

500

1000

1500

2000

2500

3000

0-24 25-39 gt4

28 day in hospital mortality Death

Mo

rta

lity

ra

te

Lactate

Serum lactate as a predictor of mortalityin patients with infection

S Trzeciak et alIntensive Care Med (2007) 33970ndash977

Prognostic value of blood lactate levels

in the Critical care unit at Ramathibodihospital

Survivors 27

Non-survivors

5

0

1

2

3

4

5

6

Art

eri

al la

cta

te (

mm

ol

L)

p=NS

The Correlation Between Arterial Lactate and Venous Lactate in Patients With Sepsis and

Septic Shock (unpublished data)

Na Petvicharn C MD Theerawit P MD

Department of Internal Medicine the Faculty of Medicine Ramathibodi Hospital MahidolUniversity

060356

17

LACtime the predictor of organ failureJan Bakker et alAJS 1996171221-6

Lactate

Time

Lactime

AUC

Survivors

Non-survivors

P lt 005

2 mmolL

Serial blood lactate levels can predict the

development of multiple organ failure following septic shock

MD Jan Bakker MD Philippe Gris MD Michel Coffernils MD Robert J Kahn MD PhD Jean-

Louis Vincent The American Journal of surgery Volume 171 Issue 2 Pages 221-226 February 1996

plt005

plt 001

plt005 vs initial

blood lactate

Lactate clearance and mortalityArnold RC Shock 2008

0

10

20

30

40

50

60

70

LC gt 10 LC lt 10

Mortality rate

SvO2 gt 70

P lt 0001

Odds ratio for death 49(15-159)

Early lactate clearance is associated with

improved outcome in severe sepsis and

septic shock

H Bryant Nguyen MD MS Emanuel P Rivers MD MPH Bernhard P Knoblich MD

Gordon Jacobsen MS Alexandria Muzzin BS Julie A Ressler BS Michael C Tomlanovich

MDCrit Care Med 2004 Vol 32 No 8

Lactate clearance

= (Lactate ED presentation ndash Lactate Hour 6)x100Lactate ED presentation

There was an approximately

11 decrease likelihood of mortality for each 10 increase in lactate clearance

Association between blood lactate levels Sequential Organ Failure

Assessment subscores and 28-day mortality during

early and late ICU stay A retrospective observational study

Tim C Jansen Jasper van Bommel Roger Woodward Paul G H Mulder Jan Bakker Crit Care Med 2009 Vol 37 No 8

Dynamic Lactate Indices as

Predictors of Outcome in Critically Ill Patients

Admission lactate (LACADM)

Maximum lactate (LACMAX24)

Minimum lactate (LACMIN24)

Time weighted lactate (LACTW24)

Absolute change in (delta) lactate (LACΔ24)

Percentage change in lactate (LACΔ24)

Nichol A Bailey M Egi M Pettila V French C Hart GK Stachowski E Reade MCCooper

DJ Bellomo RCrit Care 2011 15R242

060356

18

Tissue perfusion

Lactate is better than SvO2 for assessment of tissue perfusion

The higher initial lactate the higher mortality

Lactate changing over time is better than a single value for monitoring

The higher lactate clearance the better

outcome

At least 10 reduction of lactate during resuscitation should be achieved

Type of fluid

Colloids or Crystalloids

26 Randomized trials

BMJ 1998316961-4

RR of death

Trauma 130(095-177)

Burn 121(088-166)

Sepsis 108(073-161)

Pooled 119(098-145)

Crystalloid and colloid infusion over 90 min in sepsis and non sepsis cases with

fluid responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid Colloid P value

CI before

CI after

EVLW

beforeEVLW after

39(24-55)

41(25-59)

71(19-339)75(16-299)

34(20-82)

38(23-69)

71(26-213)71(25-196)

Plt001

Pgt005

P value between before and after

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

060356

19

Crystalloid VS Colloid

No difference in

PLI

EVLW

Gas exchange

If fluid is administered in septic

patients with

fluid responsiveness even in ALI

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

Correction of albumin in ARDS

Refresher course ICM December 2008

Correction of albumin in ARDS

Refresher course ICM December 2008

Colloid solution

Albumin Artificial

Gelatins

Dextran

HES

Poor effective

Allergic reactionAltered hemostasis

Allergic reactionRenal dysfucntion

060356

20

Colloid solutions

Hypoalbuminemia tends to increase the incidence of ARDS and mortality in sepsis patients

More fluid required for correct hemodynamic abnormality

Poor response to Furosemide

More potential leakage at capillary site may lead to more lung injury

Correction of hypoalbuminemia in ARDS may be benefitial in terms of mortality but it must be used carefully

HES may cause renal failure and high dosage may lead to bleeding tendency

The benefit of artificial colloid solution over albumin is not known

Case

60 YO male patient 60 Kg

Pneumonia with septic shock on MV

VS BP 8040 mmHg HR 120 RR 26 BT 39oC

Heart normal S1S2 no murmur

Lungs crepitation RLL lingular segment

Liver and spleen not palpable

No edema

Neuro WNL

Case

Load NSS 1500 ml -gt PPV 14 -gt lung crepitation

BP 9040 mmHg (MAP = 57 mmHg)

Increase Nor-epinephrine

BP 8545 mmHg (MAP = 55 mmHg)

HR 90 -gt 110 min lactate 3 to 6 mmolL

Re-assessment

ABG

pH 71

pCO2 35 mmHg

pO2 70 mmHg

HCO3 15 mmolL

We corrected acidosis and start dobutamine

Can decrease dosage of NorE and lactate 41

The

EGDT

We need re-

assessment

here

These are causes of no

response to pressor

Acidosis

Poor LV contraction

RV dysfunction +- PE

Pneumothorax

Concealed hemorrhage

Relative adrenal insufficiency

Electrolyte imbalance

Severe sepsis

060356

21

Norepinephrine in septic shock

Study Baseline CI(normal 25-4)

EM Redl-Wenzl et al 1993Claude Martin et al 1993BLevy et al 1997Daniel De Backer et al 2003

Jacques Albane`se et al 2004Franccedilois Lauzier et al 2006

38+1153+1340+134+1

47+0244+14

Blood transfusion in septic shockJean-Louis Vincent Pongdhep Theerawit Davide Simeon

Basic Principles of Oxygen Transport and Calculations

Alternatives to Blood Transfusion in Transfusion Medicine 2nd Ed

Chapter 17 Published Online 4 SEP 2010

Transfusions will obviously have opposite effects to

anemia increasing blood viscosity and reducing the adrenergic response It is intriguing to consider

that transfusions may result in a decrease in

myocardial contractility Hence cardiac output often decreases following transfusions in the

nomovolemic patient and the increase in DO2

can be minor or even absent For example Shah et al observed in resuscitated trauma patients

that blood transfusion of one unit of RBC increased hemoglobin from 92 plusmn 03 to 102 plusmn 03

gdL but decreased cardiac output so that DO2

did not change

Hb lt 10 gL goal 10-12 gL

Hb lt 7 gL goal 7-9 gL

N=418

N=420

A MULTICENTER RANDOMIZED CONTROLLED CLINICAL

TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CAREPAULC HEacuteBERT MD GEORGEWELLS PHD MORRISA BLAJCHMAN MD JOHNMARSHALL MD CLAUDIOMARTIN MD GIUSEPPEPAGLIARELLO MD MARTINTWEEDDALE MD PHD IRWINSCHWEITZER MSC ELIZABETHYETISIR MSC ANDTHETRANSFUSIONREQUIREMENTSINCRITICALCAREINVESTIGATORSFORTHECANADIANCRITICALCARETRIALSGROUP

NEJM 1999

(normovolemia)

Red blood cell transfusion during septic shock in the ICUA Perner etal Acta Anaesthesiol Scand 2012 56 718ndash723

The CRIT Study Anemia and blood transfusion in the critically illmdashCurrent clinical practice in the United States

(Observational study 284 ICU 4892 patients)

Crit Care Med 2004 3239 ndash52

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 11: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

11

FloTrac amp PACCrit Care 201014R212

FloTrac in sepsisIntensive Care 201137233

FloTrac in sepsisIntensive Care 201137233

FloTrac Vigileo G3

Advantages

Real time

Less invasive

Non-calibrated

Informative

CO CI

PPV

SvO2

SVR

Disadvantages

Algorithm-gtnot real

Accuracy

Can not assess RV

derived parameters

Require new version software

PiCCO system Need calibration

060356

12

PAC and PiCCO (AP)Crit Care 201014R212

PiCCO

Advantages

Continuos monitoring

More accurate

Informative

COCI

SVV

SVR

GEDV

EVLW

AP

Disadvantages

Require calibration q 8 hrs

Femoral site risky to

CRBSI

Early goal directed therapy

What is the CVP

CVP = Central Venous Pressure

Frank Starling amp venous return line

Stroke volume

CVP0

Frank-Starling curve

Stroke volume or EDV

JVP or CVP or PCWP

ΔSV or Δ EDV

a

b

Responders

Non-responders

060356

13

b

CVP tells us who responders

Stroke volume or EDV

CVP or PCWP

ΔSV or Δ EDV

a

Good

Bad

CVP vs Fluid responders

Crit Care Med 20073564-8

39 cases25 cases

Does Central Venous Pressure Predict

Fluid ResponsivenessA Systematic Review of the Literature

CHEST 2008 134172ndash178

Fluid resuscitation in septic shock a positive fluid balance and elevated central venous pressure are associated with increased mortalityBoyd JH Forbes J Nakada TA Walley KR Russell JA

OBJECTIVE

To determine whether central venous pressure and fluid balance after resuscitation for septic shock are associated

with mortality

PATIENTS

The Vasopressin in Septic Shock Trial (VASST) study enrolled 778 patients who had septic shock and who were

receiving a minimum of 5 μg of norepinephrine per minute

MEASUREMENTS AND MAIN RESULTS

Based on net fluid balance we determined whether ones fluid balance quartile was correlated with 28-day

mortality We also analyzed whether fluid balance was predictive of central venous pressure and furthermore

whether a guideline-recommended central venous pressure of 8-12 mm Hg yielded a mortality advantage At

enrollment which occurred on average 12 hrs after presentation the average fluid balance was +42 L By day 4 the

cumulative average fluid balance was +11 L After correcting for age and Acute Physiology and Chronic Health

Evaluation II score a more positive fluid balance at both at 12 hrs and day 4 correlated significantly with increased

mortality Central venous pressure was correlated with fluid balance at 12 hrs whereas on days 1-4 there was no

significant correlation At 12 hrs patients with central venous pressure lt8 mm Hg had the lowest mortality rate

followed by those with central venous pressure 8-12 mm Hg The highest mortality rate was observed in those with

central venous pressure gt12 mm Hg Contrary to the overall effect patients whose central venous pressure was lt8

mm Hg had improved survival with a more positive fluid balance

CONCLUSIONS

A more positive fluid balance both early in resuscitation and cumulatively over 4 days is associated with an increased

risk of mortality in septic shock Central venous pressure may be used to gauge fluid balance le 12 hrs into septic

shock but becomes an unreliable marker of fluid balance thereafter Optimal survival in the VASST study occurred

with a positive fluid balance of approximately 3 L at 12 hrs

Functional hemodynamic for predicting fluidresponsiveness

Spontaneous respiration

CVP variation gt 1 mmHg

PLR cCO gt 15 ( can be used in arrhythmia)

On mechanical ventilation

PPV gt 13

IVCd variation gt 12 ( can be used in arrhythmia)

IVC distensibility index gt 18 ( can be used in arrhythmia)

Brachail peak velocity gt 10

PLR cCO gt 15 ( can be used in arrhythmia)

PLR ET-CO2 gt 5

060356

14

PP variation predict fluid responsiveness

PPV = PPmax-PPmin x 100

(PPmax+PPmin)2

PPV gt 13 indicate fluid

responsiveness

PPV 94

NPV 96

Reference Year of

publication

Clinical setting PPV threshold value()

Michard etal

Viellard-Baron etal

Kramer etal

Preisman etal

Hofer etal

Feissel etal

De Backer etal

Cannesson etal

Solus-Biguenet etal

Lafanechere etal

Monnet etal

Charron etal

Natalini etal

Feissel etal

Cannesson etal

2000

2004

2004

2005

2005

2005

2005

2006

2006

2006

2006

2006

2006

2007

2007

Medical ICU

Medical ICU

CABG

CABG

CABG

Surgical and medical ICU

Surgical and medical ICU

CABG

Hepatic resection

Medical ICU

Medical ICU

Surgical ICU

Surgical and medical ICU

Medical ICU

CABG

13

12

11

9

13

17

12

12

14

12

12

10

15

12

11

Limitations

Controlled mechanical ventilation

Tidal volume ge 8 mlkg

Sinus rhythm

How to assess lung leakage

Clinical assessment

More dyspneic

Crepitation increase

Gas exchange

Desaturation

Lower pO2

Lung mechanic

Decrease lung compliance

CXR

May be difficult to determine in ARDS

The lung compliance

Respiratory system compliance

119862119877119878 =119879119907

119875119901119897119886119905119890119886119906minus119875119864119864119875

Bedside measurement of CRS

Pressure

Time

PEEP

060356

15

Bedside measurement of CRS

Pressure

Time

PEEP

Pplateau

PIP

After set Plateau time

Monitoring CRS (Volume mode)

Parameters Time 0 1 hour

PaO2 80 85

PaCO2 40 44

SaO2 96 97

PIP 35 45

Pplateau 30 36

PEEP 12 12

Exhaled TV 400 400

CRS222 167

FiO2 05 09

Fluid (ml) 0 1200

The EGDTPuzzle of formula

SvO2 Cellular oxygen

Good SvO2 means good cellular oxygenation (Low flow)

DO2 = 100

VO2 = 30

SvO2 = 70

Good SvO2 means good cellular oxygenation (heterogeneous flow)

DO2 = 100

VO2 = 10

SvO2 = 90

060356

16

Correlation between perfused capillary and blood lactateDe Backer etal Crit Care Med 2006

Prognostic value of hyperlactatemia in many

different critical care conditionsBlood lactate levels are superior to oxygen-derived

variables in predicting outcome in human septic shock

J Bakker M Coffernils M Leon P Gris and J L Vincent Chest 199199956-962

plt 005

plt 0001

Lactate level after 4 hrs of resuscitationS-W Lee etal Emerg Med J 200825659-665

Prognostic value of blood lactate levels in the ED

Shapiro NI et al Serum lactate as a predictor of mortality in emergency department patients with infection Ann Emerg Med 2005 45(5) p 524-8

490

900

2840

150

450

2240

000

500

1000

1500

2000

2500

3000

0-24 25-39 gt4

28 day in hospital mortality Death

Mo

rta

lity

ra

te

Lactate

Serum lactate as a predictor of mortalityin patients with infection

S Trzeciak et alIntensive Care Med (2007) 33970ndash977

Prognostic value of blood lactate levels

in the Critical care unit at Ramathibodihospital

Survivors 27

Non-survivors

5

0

1

2

3

4

5

6

Art

eri

al la

cta

te (

mm

ol

L)

p=NS

The Correlation Between Arterial Lactate and Venous Lactate in Patients With Sepsis and

Septic Shock (unpublished data)

Na Petvicharn C MD Theerawit P MD

Department of Internal Medicine the Faculty of Medicine Ramathibodi Hospital MahidolUniversity

060356

17

LACtime the predictor of organ failureJan Bakker et alAJS 1996171221-6

Lactate

Time

Lactime

AUC

Survivors

Non-survivors

P lt 005

2 mmolL

Serial blood lactate levels can predict the

development of multiple organ failure following septic shock

MD Jan Bakker MD Philippe Gris MD Michel Coffernils MD Robert J Kahn MD PhD Jean-

Louis Vincent The American Journal of surgery Volume 171 Issue 2 Pages 221-226 February 1996

plt005

plt 001

plt005 vs initial

blood lactate

Lactate clearance and mortalityArnold RC Shock 2008

0

10

20

30

40

50

60

70

LC gt 10 LC lt 10

Mortality rate

SvO2 gt 70

P lt 0001

Odds ratio for death 49(15-159)

Early lactate clearance is associated with

improved outcome in severe sepsis and

septic shock

H Bryant Nguyen MD MS Emanuel P Rivers MD MPH Bernhard P Knoblich MD

Gordon Jacobsen MS Alexandria Muzzin BS Julie A Ressler BS Michael C Tomlanovich

MDCrit Care Med 2004 Vol 32 No 8

Lactate clearance

= (Lactate ED presentation ndash Lactate Hour 6)x100Lactate ED presentation

There was an approximately

11 decrease likelihood of mortality for each 10 increase in lactate clearance

Association between blood lactate levels Sequential Organ Failure

Assessment subscores and 28-day mortality during

early and late ICU stay A retrospective observational study

Tim C Jansen Jasper van Bommel Roger Woodward Paul G H Mulder Jan Bakker Crit Care Med 2009 Vol 37 No 8

Dynamic Lactate Indices as

Predictors of Outcome in Critically Ill Patients

Admission lactate (LACADM)

Maximum lactate (LACMAX24)

Minimum lactate (LACMIN24)

Time weighted lactate (LACTW24)

Absolute change in (delta) lactate (LACΔ24)

Percentage change in lactate (LACΔ24)

Nichol A Bailey M Egi M Pettila V French C Hart GK Stachowski E Reade MCCooper

DJ Bellomo RCrit Care 2011 15R242

060356

18

Tissue perfusion

Lactate is better than SvO2 for assessment of tissue perfusion

The higher initial lactate the higher mortality

Lactate changing over time is better than a single value for monitoring

The higher lactate clearance the better

outcome

At least 10 reduction of lactate during resuscitation should be achieved

Type of fluid

Colloids or Crystalloids

26 Randomized trials

BMJ 1998316961-4

RR of death

Trauma 130(095-177)

Burn 121(088-166)

Sepsis 108(073-161)

Pooled 119(098-145)

Crystalloid and colloid infusion over 90 min in sepsis and non sepsis cases with

fluid responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid Colloid P value

CI before

CI after

EVLW

beforeEVLW after

39(24-55)

41(25-59)

71(19-339)75(16-299)

34(20-82)

38(23-69)

71(26-213)71(25-196)

Plt001

Pgt005

P value between before and after

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

060356

19

Crystalloid VS Colloid

No difference in

PLI

EVLW

Gas exchange

If fluid is administered in septic

patients with

fluid responsiveness even in ALI

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

Correction of albumin in ARDS

Refresher course ICM December 2008

Correction of albumin in ARDS

Refresher course ICM December 2008

Colloid solution

Albumin Artificial

Gelatins

Dextran

HES

Poor effective

Allergic reactionAltered hemostasis

Allergic reactionRenal dysfucntion

060356

20

Colloid solutions

Hypoalbuminemia tends to increase the incidence of ARDS and mortality in sepsis patients

More fluid required for correct hemodynamic abnormality

Poor response to Furosemide

More potential leakage at capillary site may lead to more lung injury

Correction of hypoalbuminemia in ARDS may be benefitial in terms of mortality but it must be used carefully

HES may cause renal failure and high dosage may lead to bleeding tendency

The benefit of artificial colloid solution over albumin is not known

Case

60 YO male patient 60 Kg

Pneumonia with septic shock on MV

VS BP 8040 mmHg HR 120 RR 26 BT 39oC

Heart normal S1S2 no murmur

Lungs crepitation RLL lingular segment

Liver and spleen not palpable

No edema

Neuro WNL

Case

Load NSS 1500 ml -gt PPV 14 -gt lung crepitation

BP 9040 mmHg (MAP = 57 mmHg)

Increase Nor-epinephrine

BP 8545 mmHg (MAP = 55 mmHg)

HR 90 -gt 110 min lactate 3 to 6 mmolL

Re-assessment

ABG

pH 71

pCO2 35 mmHg

pO2 70 mmHg

HCO3 15 mmolL

We corrected acidosis and start dobutamine

Can decrease dosage of NorE and lactate 41

The

EGDT

We need re-

assessment

here

These are causes of no

response to pressor

Acidosis

Poor LV contraction

RV dysfunction +- PE

Pneumothorax

Concealed hemorrhage

Relative adrenal insufficiency

Electrolyte imbalance

Severe sepsis

060356

21

Norepinephrine in septic shock

Study Baseline CI(normal 25-4)

EM Redl-Wenzl et al 1993Claude Martin et al 1993BLevy et al 1997Daniel De Backer et al 2003

Jacques Albane`se et al 2004Franccedilois Lauzier et al 2006

38+1153+1340+134+1

47+0244+14

Blood transfusion in septic shockJean-Louis Vincent Pongdhep Theerawit Davide Simeon

Basic Principles of Oxygen Transport and Calculations

Alternatives to Blood Transfusion in Transfusion Medicine 2nd Ed

Chapter 17 Published Online 4 SEP 2010

Transfusions will obviously have opposite effects to

anemia increasing blood viscosity and reducing the adrenergic response It is intriguing to consider

that transfusions may result in a decrease in

myocardial contractility Hence cardiac output often decreases following transfusions in the

nomovolemic patient and the increase in DO2

can be minor or even absent For example Shah et al observed in resuscitated trauma patients

that blood transfusion of one unit of RBC increased hemoglobin from 92 plusmn 03 to 102 plusmn 03

gdL but decreased cardiac output so that DO2

did not change

Hb lt 10 gL goal 10-12 gL

Hb lt 7 gL goal 7-9 gL

N=418

N=420

A MULTICENTER RANDOMIZED CONTROLLED CLINICAL

TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CAREPAULC HEacuteBERT MD GEORGEWELLS PHD MORRISA BLAJCHMAN MD JOHNMARSHALL MD CLAUDIOMARTIN MD GIUSEPPEPAGLIARELLO MD MARTINTWEEDDALE MD PHD IRWINSCHWEITZER MSC ELIZABETHYETISIR MSC ANDTHETRANSFUSIONREQUIREMENTSINCRITICALCAREINVESTIGATORSFORTHECANADIANCRITICALCARETRIALSGROUP

NEJM 1999

(normovolemia)

Red blood cell transfusion during septic shock in the ICUA Perner etal Acta Anaesthesiol Scand 2012 56 718ndash723

The CRIT Study Anemia and blood transfusion in the critically illmdashCurrent clinical practice in the United States

(Observational study 284 ICU 4892 patients)

Crit Care Med 2004 3239 ndash52

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 12: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

12

PAC and PiCCO (AP)Crit Care 201014R212

PiCCO

Advantages

Continuos monitoring

More accurate

Informative

COCI

SVV

SVR

GEDV

EVLW

AP

Disadvantages

Require calibration q 8 hrs

Femoral site risky to

CRBSI

Early goal directed therapy

What is the CVP

CVP = Central Venous Pressure

Frank Starling amp venous return line

Stroke volume

CVP0

Frank-Starling curve

Stroke volume or EDV

JVP or CVP or PCWP

ΔSV or Δ EDV

a

b

Responders

Non-responders

060356

13

b

CVP tells us who responders

Stroke volume or EDV

CVP or PCWP

ΔSV or Δ EDV

a

Good

Bad

CVP vs Fluid responders

Crit Care Med 20073564-8

39 cases25 cases

Does Central Venous Pressure Predict

Fluid ResponsivenessA Systematic Review of the Literature

CHEST 2008 134172ndash178

Fluid resuscitation in septic shock a positive fluid balance and elevated central venous pressure are associated with increased mortalityBoyd JH Forbes J Nakada TA Walley KR Russell JA

OBJECTIVE

To determine whether central venous pressure and fluid balance after resuscitation for septic shock are associated

with mortality

PATIENTS

The Vasopressin in Septic Shock Trial (VASST) study enrolled 778 patients who had septic shock and who were

receiving a minimum of 5 μg of norepinephrine per minute

MEASUREMENTS AND MAIN RESULTS

Based on net fluid balance we determined whether ones fluid balance quartile was correlated with 28-day

mortality We also analyzed whether fluid balance was predictive of central venous pressure and furthermore

whether a guideline-recommended central venous pressure of 8-12 mm Hg yielded a mortality advantage At

enrollment which occurred on average 12 hrs after presentation the average fluid balance was +42 L By day 4 the

cumulative average fluid balance was +11 L After correcting for age and Acute Physiology and Chronic Health

Evaluation II score a more positive fluid balance at both at 12 hrs and day 4 correlated significantly with increased

mortality Central venous pressure was correlated with fluid balance at 12 hrs whereas on days 1-4 there was no

significant correlation At 12 hrs patients with central venous pressure lt8 mm Hg had the lowest mortality rate

followed by those with central venous pressure 8-12 mm Hg The highest mortality rate was observed in those with

central venous pressure gt12 mm Hg Contrary to the overall effect patients whose central venous pressure was lt8

mm Hg had improved survival with a more positive fluid balance

CONCLUSIONS

A more positive fluid balance both early in resuscitation and cumulatively over 4 days is associated with an increased

risk of mortality in septic shock Central venous pressure may be used to gauge fluid balance le 12 hrs into septic

shock but becomes an unreliable marker of fluid balance thereafter Optimal survival in the VASST study occurred

with a positive fluid balance of approximately 3 L at 12 hrs

Functional hemodynamic for predicting fluidresponsiveness

Spontaneous respiration

CVP variation gt 1 mmHg

PLR cCO gt 15 ( can be used in arrhythmia)

On mechanical ventilation

PPV gt 13

IVCd variation gt 12 ( can be used in arrhythmia)

IVC distensibility index gt 18 ( can be used in arrhythmia)

Brachail peak velocity gt 10

PLR cCO gt 15 ( can be used in arrhythmia)

PLR ET-CO2 gt 5

060356

14

PP variation predict fluid responsiveness

PPV = PPmax-PPmin x 100

(PPmax+PPmin)2

PPV gt 13 indicate fluid

responsiveness

PPV 94

NPV 96

Reference Year of

publication

Clinical setting PPV threshold value()

Michard etal

Viellard-Baron etal

Kramer etal

Preisman etal

Hofer etal

Feissel etal

De Backer etal

Cannesson etal

Solus-Biguenet etal

Lafanechere etal

Monnet etal

Charron etal

Natalini etal

Feissel etal

Cannesson etal

2000

2004

2004

2005

2005

2005

2005

2006

2006

2006

2006

2006

2006

2007

2007

Medical ICU

Medical ICU

CABG

CABG

CABG

Surgical and medical ICU

Surgical and medical ICU

CABG

Hepatic resection

Medical ICU

Medical ICU

Surgical ICU

Surgical and medical ICU

Medical ICU

CABG

13

12

11

9

13

17

12

12

14

12

12

10

15

12

11

Limitations

Controlled mechanical ventilation

Tidal volume ge 8 mlkg

Sinus rhythm

How to assess lung leakage

Clinical assessment

More dyspneic

Crepitation increase

Gas exchange

Desaturation

Lower pO2

Lung mechanic

Decrease lung compliance

CXR

May be difficult to determine in ARDS

The lung compliance

Respiratory system compliance

119862119877119878 =119879119907

119875119901119897119886119905119890119886119906minus119875119864119864119875

Bedside measurement of CRS

Pressure

Time

PEEP

060356

15

Bedside measurement of CRS

Pressure

Time

PEEP

Pplateau

PIP

After set Plateau time

Monitoring CRS (Volume mode)

Parameters Time 0 1 hour

PaO2 80 85

PaCO2 40 44

SaO2 96 97

PIP 35 45

Pplateau 30 36

PEEP 12 12

Exhaled TV 400 400

CRS222 167

FiO2 05 09

Fluid (ml) 0 1200

The EGDTPuzzle of formula

SvO2 Cellular oxygen

Good SvO2 means good cellular oxygenation (Low flow)

DO2 = 100

VO2 = 30

SvO2 = 70

Good SvO2 means good cellular oxygenation (heterogeneous flow)

DO2 = 100

VO2 = 10

SvO2 = 90

060356

16

Correlation between perfused capillary and blood lactateDe Backer etal Crit Care Med 2006

Prognostic value of hyperlactatemia in many

different critical care conditionsBlood lactate levels are superior to oxygen-derived

variables in predicting outcome in human septic shock

J Bakker M Coffernils M Leon P Gris and J L Vincent Chest 199199956-962

plt 005

plt 0001

Lactate level after 4 hrs of resuscitationS-W Lee etal Emerg Med J 200825659-665

Prognostic value of blood lactate levels in the ED

Shapiro NI et al Serum lactate as a predictor of mortality in emergency department patients with infection Ann Emerg Med 2005 45(5) p 524-8

490

900

2840

150

450

2240

000

500

1000

1500

2000

2500

3000

0-24 25-39 gt4

28 day in hospital mortality Death

Mo

rta

lity

ra

te

Lactate

Serum lactate as a predictor of mortalityin patients with infection

S Trzeciak et alIntensive Care Med (2007) 33970ndash977

Prognostic value of blood lactate levels

in the Critical care unit at Ramathibodihospital

Survivors 27

Non-survivors

5

0

1

2

3

4

5

6

Art

eri

al la

cta

te (

mm

ol

L)

p=NS

The Correlation Between Arterial Lactate and Venous Lactate in Patients With Sepsis and

Septic Shock (unpublished data)

Na Petvicharn C MD Theerawit P MD

Department of Internal Medicine the Faculty of Medicine Ramathibodi Hospital MahidolUniversity

060356

17

LACtime the predictor of organ failureJan Bakker et alAJS 1996171221-6

Lactate

Time

Lactime

AUC

Survivors

Non-survivors

P lt 005

2 mmolL

Serial blood lactate levels can predict the

development of multiple organ failure following septic shock

MD Jan Bakker MD Philippe Gris MD Michel Coffernils MD Robert J Kahn MD PhD Jean-

Louis Vincent The American Journal of surgery Volume 171 Issue 2 Pages 221-226 February 1996

plt005

plt 001

plt005 vs initial

blood lactate

Lactate clearance and mortalityArnold RC Shock 2008

0

10

20

30

40

50

60

70

LC gt 10 LC lt 10

Mortality rate

SvO2 gt 70

P lt 0001

Odds ratio for death 49(15-159)

Early lactate clearance is associated with

improved outcome in severe sepsis and

septic shock

H Bryant Nguyen MD MS Emanuel P Rivers MD MPH Bernhard P Knoblich MD

Gordon Jacobsen MS Alexandria Muzzin BS Julie A Ressler BS Michael C Tomlanovich

MDCrit Care Med 2004 Vol 32 No 8

Lactate clearance

= (Lactate ED presentation ndash Lactate Hour 6)x100Lactate ED presentation

There was an approximately

11 decrease likelihood of mortality for each 10 increase in lactate clearance

Association between blood lactate levels Sequential Organ Failure

Assessment subscores and 28-day mortality during

early and late ICU stay A retrospective observational study

Tim C Jansen Jasper van Bommel Roger Woodward Paul G H Mulder Jan Bakker Crit Care Med 2009 Vol 37 No 8

Dynamic Lactate Indices as

Predictors of Outcome in Critically Ill Patients

Admission lactate (LACADM)

Maximum lactate (LACMAX24)

Minimum lactate (LACMIN24)

Time weighted lactate (LACTW24)

Absolute change in (delta) lactate (LACΔ24)

Percentage change in lactate (LACΔ24)

Nichol A Bailey M Egi M Pettila V French C Hart GK Stachowski E Reade MCCooper

DJ Bellomo RCrit Care 2011 15R242

060356

18

Tissue perfusion

Lactate is better than SvO2 for assessment of tissue perfusion

The higher initial lactate the higher mortality

Lactate changing over time is better than a single value for monitoring

The higher lactate clearance the better

outcome

At least 10 reduction of lactate during resuscitation should be achieved

Type of fluid

Colloids or Crystalloids

26 Randomized trials

BMJ 1998316961-4

RR of death

Trauma 130(095-177)

Burn 121(088-166)

Sepsis 108(073-161)

Pooled 119(098-145)

Crystalloid and colloid infusion over 90 min in sepsis and non sepsis cases with

fluid responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid Colloid P value

CI before

CI after

EVLW

beforeEVLW after

39(24-55)

41(25-59)

71(19-339)75(16-299)

34(20-82)

38(23-69)

71(26-213)71(25-196)

Plt001

Pgt005

P value between before and after

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

060356

19

Crystalloid VS Colloid

No difference in

PLI

EVLW

Gas exchange

If fluid is administered in septic

patients with

fluid responsiveness even in ALI

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

Correction of albumin in ARDS

Refresher course ICM December 2008

Correction of albumin in ARDS

Refresher course ICM December 2008

Colloid solution

Albumin Artificial

Gelatins

Dextran

HES

Poor effective

Allergic reactionAltered hemostasis

Allergic reactionRenal dysfucntion

060356

20

Colloid solutions

Hypoalbuminemia tends to increase the incidence of ARDS and mortality in sepsis patients

More fluid required for correct hemodynamic abnormality

Poor response to Furosemide

More potential leakage at capillary site may lead to more lung injury

Correction of hypoalbuminemia in ARDS may be benefitial in terms of mortality but it must be used carefully

HES may cause renal failure and high dosage may lead to bleeding tendency

The benefit of artificial colloid solution over albumin is not known

Case

60 YO male patient 60 Kg

Pneumonia with septic shock on MV

VS BP 8040 mmHg HR 120 RR 26 BT 39oC

Heart normal S1S2 no murmur

Lungs crepitation RLL lingular segment

Liver and spleen not palpable

No edema

Neuro WNL

Case

Load NSS 1500 ml -gt PPV 14 -gt lung crepitation

BP 9040 mmHg (MAP = 57 mmHg)

Increase Nor-epinephrine

BP 8545 mmHg (MAP = 55 mmHg)

HR 90 -gt 110 min lactate 3 to 6 mmolL

Re-assessment

ABG

pH 71

pCO2 35 mmHg

pO2 70 mmHg

HCO3 15 mmolL

We corrected acidosis and start dobutamine

Can decrease dosage of NorE and lactate 41

The

EGDT

We need re-

assessment

here

These are causes of no

response to pressor

Acidosis

Poor LV contraction

RV dysfunction +- PE

Pneumothorax

Concealed hemorrhage

Relative adrenal insufficiency

Electrolyte imbalance

Severe sepsis

060356

21

Norepinephrine in septic shock

Study Baseline CI(normal 25-4)

EM Redl-Wenzl et al 1993Claude Martin et al 1993BLevy et al 1997Daniel De Backer et al 2003

Jacques Albane`se et al 2004Franccedilois Lauzier et al 2006

38+1153+1340+134+1

47+0244+14

Blood transfusion in septic shockJean-Louis Vincent Pongdhep Theerawit Davide Simeon

Basic Principles of Oxygen Transport and Calculations

Alternatives to Blood Transfusion in Transfusion Medicine 2nd Ed

Chapter 17 Published Online 4 SEP 2010

Transfusions will obviously have opposite effects to

anemia increasing blood viscosity and reducing the adrenergic response It is intriguing to consider

that transfusions may result in a decrease in

myocardial contractility Hence cardiac output often decreases following transfusions in the

nomovolemic patient and the increase in DO2

can be minor or even absent For example Shah et al observed in resuscitated trauma patients

that blood transfusion of one unit of RBC increased hemoglobin from 92 plusmn 03 to 102 plusmn 03

gdL but decreased cardiac output so that DO2

did not change

Hb lt 10 gL goal 10-12 gL

Hb lt 7 gL goal 7-9 gL

N=418

N=420

A MULTICENTER RANDOMIZED CONTROLLED CLINICAL

TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CAREPAULC HEacuteBERT MD GEORGEWELLS PHD MORRISA BLAJCHMAN MD JOHNMARSHALL MD CLAUDIOMARTIN MD GIUSEPPEPAGLIARELLO MD MARTINTWEEDDALE MD PHD IRWINSCHWEITZER MSC ELIZABETHYETISIR MSC ANDTHETRANSFUSIONREQUIREMENTSINCRITICALCAREINVESTIGATORSFORTHECANADIANCRITICALCARETRIALSGROUP

NEJM 1999

(normovolemia)

Red blood cell transfusion during septic shock in the ICUA Perner etal Acta Anaesthesiol Scand 2012 56 718ndash723

The CRIT Study Anemia and blood transfusion in the critically illmdashCurrent clinical practice in the United States

(Observational study 284 ICU 4892 patients)

Crit Care Med 2004 3239 ndash52

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 13: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

13

b

CVP tells us who responders

Stroke volume or EDV

CVP or PCWP

ΔSV or Δ EDV

a

Good

Bad

CVP vs Fluid responders

Crit Care Med 20073564-8

39 cases25 cases

Does Central Venous Pressure Predict

Fluid ResponsivenessA Systematic Review of the Literature

CHEST 2008 134172ndash178

Fluid resuscitation in septic shock a positive fluid balance and elevated central venous pressure are associated with increased mortalityBoyd JH Forbes J Nakada TA Walley KR Russell JA

OBJECTIVE

To determine whether central venous pressure and fluid balance after resuscitation for septic shock are associated

with mortality

PATIENTS

The Vasopressin in Septic Shock Trial (VASST) study enrolled 778 patients who had septic shock and who were

receiving a minimum of 5 μg of norepinephrine per minute

MEASUREMENTS AND MAIN RESULTS

Based on net fluid balance we determined whether ones fluid balance quartile was correlated with 28-day

mortality We also analyzed whether fluid balance was predictive of central venous pressure and furthermore

whether a guideline-recommended central venous pressure of 8-12 mm Hg yielded a mortality advantage At

enrollment which occurred on average 12 hrs after presentation the average fluid balance was +42 L By day 4 the

cumulative average fluid balance was +11 L After correcting for age and Acute Physiology and Chronic Health

Evaluation II score a more positive fluid balance at both at 12 hrs and day 4 correlated significantly with increased

mortality Central venous pressure was correlated with fluid balance at 12 hrs whereas on days 1-4 there was no

significant correlation At 12 hrs patients with central venous pressure lt8 mm Hg had the lowest mortality rate

followed by those with central venous pressure 8-12 mm Hg The highest mortality rate was observed in those with

central venous pressure gt12 mm Hg Contrary to the overall effect patients whose central venous pressure was lt8

mm Hg had improved survival with a more positive fluid balance

CONCLUSIONS

A more positive fluid balance both early in resuscitation and cumulatively over 4 days is associated with an increased

risk of mortality in septic shock Central venous pressure may be used to gauge fluid balance le 12 hrs into septic

shock but becomes an unreliable marker of fluid balance thereafter Optimal survival in the VASST study occurred

with a positive fluid balance of approximately 3 L at 12 hrs

Functional hemodynamic for predicting fluidresponsiveness

Spontaneous respiration

CVP variation gt 1 mmHg

PLR cCO gt 15 ( can be used in arrhythmia)

On mechanical ventilation

PPV gt 13

IVCd variation gt 12 ( can be used in arrhythmia)

IVC distensibility index gt 18 ( can be used in arrhythmia)

Brachail peak velocity gt 10

PLR cCO gt 15 ( can be used in arrhythmia)

PLR ET-CO2 gt 5

060356

14

PP variation predict fluid responsiveness

PPV = PPmax-PPmin x 100

(PPmax+PPmin)2

PPV gt 13 indicate fluid

responsiveness

PPV 94

NPV 96

Reference Year of

publication

Clinical setting PPV threshold value()

Michard etal

Viellard-Baron etal

Kramer etal

Preisman etal

Hofer etal

Feissel etal

De Backer etal

Cannesson etal

Solus-Biguenet etal

Lafanechere etal

Monnet etal

Charron etal

Natalini etal

Feissel etal

Cannesson etal

2000

2004

2004

2005

2005

2005

2005

2006

2006

2006

2006

2006

2006

2007

2007

Medical ICU

Medical ICU

CABG

CABG

CABG

Surgical and medical ICU

Surgical and medical ICU

CABG

Hepatic resection

Medical ICU

Medical ICU

Surgical ICU

Surgical and medical ICU

Medical ICU

CABG

13

12

11

9

13

17

12

12

14

12

12

10

15

12

11

Limitations

Controlled mechanical ventilation

Tidal volume ge 8 mlkg

Sinus rhythm

How to assess lung leakage

Clinical assessment

More dyspneic

Crepitation increase

Gas exchange

Desaturation

Lower pO2

Lung mechanic

Decrease lung compliance

CXR

May be difficult to determine in ARDS

The lung compliance

Respiratory system compliance

119862119877119878 =119879119907

119875119901119897119886119905119890119886119906minus119875119864119864119875

Bedside measurement of CRS

Pressure

Time

PEEP

060356

15

Bedside measurement of CRS

Pressure

Time

PEEP

Pplateau

PIP

After set Plateau time

Monitoring CRS (Volume mode)

Parameters Time 0 1 hour

PaO2 80 85

PaCO2 40 44

SaO2 96 97

PIP 35 45

Pplateau 30 36

PEEP 12 12

Exhaled TV 400 400

CRS222 167

FiO2 05 09

Fluid (ml) 0 1200

The EGDTPuzzle of formula

SvO2 Cellular oxygen

Good SvO2 means good cellular oxygenation (Low flow)

DO2 = 100

VO2 = 30

SvO2 = 70

Good SvO2 means good cellular oxygenation (heterogeneous flow)

DO2 = 100

VO2 = 10

SvO2 = 90

060356

16

Correlation between perfused capillary and blood lactateDe Backer etal Crit Care Med 2006

Prognostic value of hyperlactatemia in many

different critical care conditionsBlood lactate levels are superior to oxygen-derived

variables in predicting outcome in human septic shock

J Bakker M Coffernils M Leon P Gris and J L Vincent Chest 199199956-962

plt 005

plt 0001

Lactate level after 4 hrs of resuscitationS-W Lee etal Emerg Med J 200825659-665

Prognostic value of blood lactate levels in the ED

Shapiro NI et al Serum lactate as a predictor of mortality in emergency department patients with infection Ann Emerg Med 2005 45(5) p 524-8

490

900

2840

150

450

2240

000

500

1000

1500

2000

2500

3000

0-24 25-39 gt4

28 day in hospital mortality Death

Mo

rta

lity

ra

te

Lactate

Serum lactate as a predictor of mortalityin patients with infection

S Trzeciak et alIntensive Care Med (2007) 33970ndash977

Prognostic value of blood lactate levels

in the Critical care unit at Ramathibodihospital

Survivors 27

Non-survivors

5

0

1

2

3

4

5

6

Art

eri

al la

cta

te (

mm

ol

L)

p=NS

The Correlation Between Arterial Lactate and Venous Lactate in Patients With Sepsis and

Septic Shock (unpublished data)

Na Petvicharn C MD Theerawit P MD

Department of Internal Medicine the Faculty of Medicine Ramathibodi Hospital MahidolUniversity

060356

17

LACtime the predictor of organ failureJan Bakker et alAJS 1996171221-6

Lactate

Time

Lactime

AUC

Survivors

Non-survivors

P lt 005

2 mmolL

Serial blood lactate levels can predict the

development of multiple organ failure following septic shock

MD Jan Bakker MD Philippe Gris MD Michel Coffernils MD Robert J Kahn MD PhD Jean-

Louis Vincent The American Journal of surgery Volume 171 Issue 2 Pages 221-226 February 1996

plt005

plt 001

plt005 vs initial

blood lactate

Lactate clearance and mortalityArnold RC Shock 2008

0

10

20

30

40

50

60

70

LC gt 10 LC lt 10

Mortality rate

SvO2 gt 70

P lt 0001

Odds ratio for death 49(15-159)

Early lactate clearance is associated with

improved outcome in severe sepsis and

septic shock

H Bryant Nguyen MD MS Emanuel P Rivers MD MPH Bernhard P Knoblich MD

Gordon Jacobsen MS Alexandria Muzzin BS Julie A Ressler BS Michael C Tomlanovich

MDCrit Care Med 2004 Vol 32 No 8

Lactate clearance

= (Lactate ED presentation ndash Lactate Hour 6)x100Lactate ED presentation

There was an approximately

11 decrease likelihood of mortality for each 10 increase in lactate clearance

Association between blood lactate levels Sequential Organ Failure

Assessment subscores and 28-day mortality during

early and late ICU stay A retrospective observational study

Tim C Jansen Jasper van Bommel Roger Woodward Paul G H Mulder Jan Bakker Crit Care Med 2009 Vol 37 No 8

Dynamic Lactate Indices as

Predictors of Outcome in Critically Ill Patients

Admission lactate (LACADM)

Maximum lactate (LACMAX24)

Minimum lactate (LACMIN24)

Time weighted lactate (LACTW24)

Absolute change in (delta) lactate (LACΔ24)

Percentage change in lactate (LACΔ24)

Nichol A Bailey M Egi M Pettila V French C Hart GK Stachowski E Reade MCCooper

DJ Bellomo RCrit Care 2011 15R242

060356

18

Tissue perfusion

Lactate is better than SvO2 for assessment of tissue perfusion

The higher initial lactate the higher mortality

Lactate changing over time is better than a single value for monitoring

The higher lactate clearance the better

outcome

At least 10 reduction of lactate during resuscitation should be achieved

Type of fluid

Colloids or Crystalloids

26 Randomized trials

BMJ 1998316961-4

RR of death

Trauma 130(095-177)

Burn 121(088-166)

Sepsis 108(073-161)

Pooled 119(098-145)

Crystalloid and colloid infusion over 90 min in sepsis and non sepsis cases with

fluid responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid Colloid P value

CI before

CI after

EVLW

beforeEVLW after

39(24-55)

41(25-59)

71(19-339)75(16-299)

34(20-82)

38(23-69)

71(26-213)71(25-196)

Plt001

Pgt005

P value between before and after

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

060356

19

Crystalloid VS Colloid

No difference in

PLI

EVLW

Gas exchange

If fluid is administered in septic

patients with

fluid responsiveness even in ALI

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

Correction of albumin in ARDS

Refresher course ICM December 2008

Correction of albumin in ARDS

Refresher course ICM December 2008

Colloid solution

Albumin Artificial

Gelatins

Dextran

HES

Poor effective

Allergic reactionAltered hemostasis

Allergic reactionRenal dysfucntion

060356

20

Colloid solutions

Hypoalbuminemia tends to increase the incidence of ARDS and mortality in sepsis patients

More fluid required for correct hemodynamic abnormality

Poor response to Furosemide

More potential leakage at capillary site may lead to more lung injury

Correction of hypoalbuminemia in ARDS may be benefitial in terms of mortality but it must be used carefully

HES may cause renal failure and high dosage may lead to bleeding tendency

The benefit of artificial colloid solution over albumin is not known

Case

60 YO male patient 60 Kg

Pneumonia with septic shock on MV

VS BP 8040 mmHg HR 120 RR 26 BT 39oC

Heart normal S1S2 no murmur

Lungs crepitation RLL lingular segment

Liver and spleen not palpable

No edema

Neuro WNL

Case

Load NSS 1500 ml -gt PPV 14 -gt lung crepitation

BP 9040 mmHg (MAP = 57 mmHg)

Increase Nor-epinephrine

BP 8545 mmHg (MAP = 55 mmHg)

HR 90 -gt 110 min lactate 3 to 6 mmolL

Re-assessment

ABG

pH 71

pCO2 35 mmHg

pO2 70 mmHg

HCO3 15 mmolL

We corrected acidosis and start dobutamine

Can decrease dosage of NorE and lactate 41

The

EGDT

We need re-

assessment

here

These are causes of no

response to pressor

Acidosis

Poor LV contraction

RV dysfunction +- PE

Pneumothorax

Concealed hemorrhage

Relative adrenal insufficiency

Electrolyte imbalance

Severe sepsis

060356

21

Norepinephrine in septic shock

Study Baseline CI(normal 25-4)

EM Redl-Wenzl et al 1993Claude Martin et al 1993BLevy et al 1997Daniel De Backer et al 2003

Jacques Albane`se et al 2004Franccedilois Lauzier et al 2006

38+1153+1340+134+1

47+0244+14

Blood transfusion in septic shockJean-Louis Vincent Pongdhep Theerawit Davide Simeon

Basic Principles of Oxygen Transport and Calculations

Alternatives to Blood Transfusion in Transfusion Medicine 2nd Ed

Chapter 17 Published Online 4 SEP 2010

Transfusions will obviously have opposite effects to

anemia increasing blood viscosity and reducing the adrenergic response It is intriguing to consider

that transfusions may result in a decrease in

myocardial contractility Hence cardiac output often decreases following transfusions in the

nomovolemic patient and the increase in DO2

can be minor or even absent For example Shah et al observed in resuscitated trauma patients

that blood transfusion of one unit of RBC increased hemoglobin from 92 plusmn 03 to 102 plusmn 03

gdL but decreased cardiac output so that DO2

did not change

Hb lt 10 gL goal 10-12 gL

Hb lt 7 gL goal 7-9 gL

N=418

N=420

A MULTICENTER RANDOMIZED CONTROLLED CLINICAL

TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CAREPAULC HEacuteBERT MD GEORGEWELLS PHD MORRISA BLAJCHMAN MD JOHNMARSHALL MD CLAUDIOMARTIN MD GIUSEPPEPAGLIARELLO MD MARTINTWEEDDALE MD PHD IRWINSCHWEITZER MSC ELIZABETHYETISIR MSC ANDTHETRANSFUSIONREQUIREMENTSINCRITICALCAREINVESTIGATORSFORTHECANADIANCRITICALCARETRIALSGROUP

NEJM 1999

(normovolemia)

Red blood cell transfusion during septic shock in the ICUA Perner etal Acta Anaesthesiol Scand 2012 56 718ndash723

The CRIT Study Anemia and blood transfusion in the critically illmdashCurrent clinical practice in the United States

(Observational study 284 ICU 4892 patients)

Crit Care Med 2004 3239 ndash52

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 14: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

14

PP variation predict fluid responsiveness

PPV = PPmax-PPmin x 100

(PPmax+PPmin)2

PPV gt 13 indicate fluid

responsiveness

PPV 94

NPV 96

Reference Year of

publication

Clinical setting PPV threshold value()

Michard etal

Viellard-Baron etal

Kramer etal

Preisman etal

Hofer etal

Feissel etal

De Backer etal

Cannesson etal

Solus-Biguenet etal

Lafanechere etal

Monnet etal

Charron etal

Natalini etal

Feissel etal

Cannesson etal

2000

2004

2004

2005

2005

2005

2005

2006

2006

2006

2006

2006

2006

2007

2007

Medical ICU

Medical ICU

CABG

CABG

CABG

Surgical and medical ICU

Surgical and medical ICU

CABG

Hepatic resection

Medical ICU

Medical ICU

Surgical ICU

Surgical and medical ICU

Medical ICU

CABG

13

12

11

9

13

17

12

12

14

12

12

10

15

12

11

Limitations

Controlled mechanical ventilation

Tidal volume ge 8 mlkg

Sinus rhythm

How to assess lung leakage

Clinical assessment

More dyspneic

Crepitation increase

Gas exchange

Desaturation

Lower pO2

Lung mechanic

Decrease lung compliance

CXR

May be difficult to determine in ARDS

The lung compliance

Respiratory system compliance

119862119877119878 =119879119907

119875119901119897119886119905119890119886119906minus119875119864119864119875

Bedside measurement of CRS

Pressure

Time

PEEP

060356

15

Bedside measurement of CRS

Pressure

Time

PEEP

Pplateau

PIP

After set Plateau time

Monitoring CRS (Volume mode)

Parameters Time 0 1 hour

PaO2 80 85

PaCO2 40 44

SaO2 96 97

PIP 35 45

Pplateau 30 36

PEEP 12 12

Exhaled TV 400 400

CRS222 167

FiO2 05 09

Fluid (ml) 0 1200

The EGDTPuzzle of formula

SvO2 Cellular oxygen

Good SvO2 means good cellular oxygenation (Low flow)

DO2 = 100

VO2 = 30

SvO2 = 70

Good SvO2 means good cellular oxygenation (heterogeneous flow)

DO2 = 100

VO2 = 10

SvO2 = 90

060356

16

Correlation between perfused capillary and blood lactateDe Backer etal Crit Care Med 2006

Prognostic value of hyperlactatemia in many

different critical care conditionsBlood lactate levels are superior to oxygen-derived

variables in predicting outcome in human septic shock

J Bakker M Coffernils M Leon P Gris and J L Vincent Chest 199199956-962

plt 005

plt 0001

Lactate level after 4 hrs of resuscitationS-W Lee etal Emerg Med J 200825659-665

Prognostic value of blood lactate levels in the ED

Shapiro NI et al Serum lactate as a predictor of mortality in emergency department patients with infection Ann Emerg Med 2005 45(5) p 524-8

490

900

2840

150

450

2240

000

500

1000

1500

2000

2500

3000

0-24 25-39 gt4

28 day in hospital mortality Death

Mo

rta

lity

ra

te

Lactate

Serum lactate as a predictor of mortalityin patients with infection

S Trzeciak et alIntensive Care Med (2007) 33970ndash977

Prognostic value of blood lactate levels

in the Critical care unit at Ramathibodihospital

Survivors 27

Non-survivors

5

0

1

2

3

4

5

6

Art

eri

al la

cta

te (

mm

ol

L)

p=NS

The Correlation Between Arterial Lactate and Venous Lactate in Patients With Sepsis and

Septic Shock (unpublished data)

Na Petvicharn C MD Theerawit P MD

Department of Internal Medicine the Faculty of Medicine Ramathibodi Hospital MahidolUniversity

060356

17

LACtime the predictor of organ failureJan Bakker et alAJS 1996171221-6

Lactate

Time

Lactime

AUC

Survivors

Non-survivors

P lt 005

2 mmolL

Serial blood lactate levels can predict the

development of multiple organ failure following septic shock

MD Jan Bakker MD Philippe Gris MD Michel Coffernils MD Robert J Kahn MD PhD Jean-

Louis Vincent The American Journal of surgery Volume 171 Issue 2 Pages 221-226 February 1996

plt005

plt 001

plt005 vs initial

blood lactate

Lactate clearance and mortalityArnold RC Shock 2008

0

10

20

30

40

50

60

70

LC gt 10 LC lt 10

Mortality rate

SvO2 gt 70

P lt 0001

Odds ratio for death 49(15-159)

Early lactate clearance is associated with

improved outcome in severe sepsis and

septic shock

H Bryant Nguyen MD MS Emanuel P Rivers MD MPH Bernhard P Knoblich MD

Gordon Jacobsen MS Alexandria Muzzin BS Julie A Ressler BS Michael C Tomlanovich

MDCrit Care Med 2004 Vol 32 No 8

Lactate clearance

= (Lactate ED presentation ndash Lactate Hour 6)x100Lactate ED presentation

There was an approximately

11 decrease likelihood of mortality for each 10 increase in lactate clearance

Association between blood lactate levels Sequential Organ Failure

Assessment subscores and 28-day mortality during

early and late ICU stay A retrospective observational study

Tim C Jansen Jasper van Bommel Roger Woodward Paul G H Mulder Jan Bakker Crit Care Med 2009 Vol 37 No 8

Dynamic Lactate Indices as

Predictors of Outcome in Critically Ill Patients

Admission lactate (LACADM)

Maximum lactate (LACMAX24)

Minimum lactate (LACMIN24)

Time weighted lactate (LACTW24)

Absolute change in (delta) lactate (LACΔ24)

Percentage change in lactate (LACΔ24)

Nichol A Bailey M Egi M Pettila V French C Hart GK Stachowski E Reade MCCooper

DJ Bellomo RCrit Care 2011 15R242

060356

18

Tissue perfusion

Lactate is better than SvO2 for assessment of tissue perfusion

The higher initial lactate the higher mortality

Lactate changing over time is better than a single value for monitoring

The higher lactate clearance the better

outcome

At least 10 reduction of lactate during resuscitation should be achieved

Type of fluid

Colloids or Crystalloids

26 Randomized trials

BMJ 1998316961-4

RR of death

Trauma 130(095-177)

Burn 121(088-166)

Sepsis 108(073-161)

Pooled 119(098-145)

Crystalloid and colloid infusion over 90 min in sepsis and non sepsis cases with

fluid responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid Colloid P value

CI before

CI after

EVLW

beforeEVLW after

39(24-55)

41(25-59)

71(19-339)75(16-299)

34(20-82)

38(23-69)

71(26-213)71(25-196)

Plt001

Pgt005

P value between before and after

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

060356

19

Crystalloid VS Colloid

No difference in

PLI

EVLW

Gas exchange

If fluid is administered in septic

patients with

fluid responsiveness even in ALI

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

Correction of albumin in ARDS

Refresher course ICM December 2008

Correction of albumin in ARDS

Refresher course ICM December 2008

Colloid solution

Albumin Artificial

Gelatins

Dextran

HES

Poor effective

Allergic reactionAltered hemostasis

Allergic reactionRenal dysfucntion

060356

20

Colloid solutions

Hypoalbuminemia tends to increase the incidence of ARDS and mortality in sepsis patients

More fluid required for correct hemodynamic abnormality

Poor response to Furosemide

More potential leakage at capillary site may lead to more lung injury

Correction of hypoalbuminemia in ARDS may be benefitial in terms of mortality but it must be used carefully

HES may cause renal failure and high dosage may lead to bleeding tendency

The benefit of artificial colloid solution over albumin is not known

Case

60 YO male patient 60 Kg

Pneumonia with septic shock on MV

VS BP 8040 mmHg HR 120 RR 26 BT 39oC

Heart normal S1S2 no murmur

Lungs crepitation RLL lingular segment

Liver and spleen not palpable

No edema

Neuro WNL

Case

Load NSS 1500 ml -gt PPV 14 -gt lung crepitation

BP 9040 mmHg (MAP = 57 mmHg)

Increase Nor-epinephrine

BP 8545 mmHg (MAP = 55 mmHg)

HR 90 -gt 110 min lactate 3 to 6 mmolL

Re-assessment

ABG

pH 71

pCO2 35 mmHg

pO2 70 mmHg

HCO3 15 mmolL

We corrected acidosis and start dobutamine

Can decrease dosage of NorE and lactate 41

The

EGDT

We need re-

assessment

here

These are causes of no

response to pressor

Acidosis

Poor LV contraction

RV dysfunction +- PE

Pneumothorax

Concealed hemorrhage

Relative adrenal insufficiency

Electrolyte imbalance

Severe sepsis

060356

21

Norepinephrine in septic shock

Study Baseline CI(normal 25-4)

EM Redl-Wenzl et al 1993Claude Martin et al 1993BLevy et al 1997Daniel De Backer et al 2003

Jacques Albane`se et al 2004Franccedilois Lauzier et al 2006

38+1153+1340+134+1

47+0244+14

Blood transfusion in septic shockJean-Louis Vincent Pongdhep Theerawit Davide Simeon

Basic Principles of Oxygen Transport and Calculations

Alternatives to Blood Transfusion in Transfusion Medicine 2nd Ed

Chapter 17 Published Online 4 SEP 2010

Transfusions will obviously have opposite effects to

anemia increasing blood viscosity and reducing the adrenergic response It is intriguing to consider

that transfusions may result in a decrease in

myocardial contractility Hence cardiac output often decreases following transfusions in the

nomovolemic patient and the increase in DO2

can be minor or even absent For example Shah et al observed in resuscitated trauma patients

that blood transfusion of one unit of RBC increased hemoglobin from 92 plusmn 03 to 102 plusmn 03

gdL but decreased cardiac output so that DO2

did not change

Hb lt 10 gL goal 10-12 gL

Hb lt 7 gL goal 7-9 gL

N=418

N=420

A MULTICENTER RANDOMIZED CONTROLLED CLINICAL

TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CAREPAULC HEacuteBERT MD GEORGEWELLS PHD MORRISA BLAJCHMAN MD JOHNMARSHALL MD CLAUDIOMARTIN MD GIUSEPPEPAGLIARELLO MD MARTINTWEEDDALE MD PHD IRWINSCHWEITZER MSC ELIZABETHYETISIR MSC ANDTHETRANSFUSIONREQUIREMENTSINCRITICALCAREINVESTIGATORSFORTHECANADIANCRITICALCARETRIALSGROUP

NEJM 1999

(normovolemia)

Red blood cell transfusion during septic shock in the ICUA Perner etal Acta Anaesthesiol Scand 2012 56 718ndash723

The CRIT Study Anemia and blood transfusion in the critically illmdashCurrent clinical practice in the United States

(Observational study 284 ICU 4892 patients)

Crit Care Med 2004 3239 ndash52

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 15: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

15

Bedside measurement of CRS

Pressure

Time

PEEP

Pplateau

PIP

After set Plateau time

Monitoring CRS (Volume mode)

Parameters Time 0 1 hour

PaO2 80 85

PaCO2 40 44

SaO2 96 97

PIP 35 45

Pplateau 30 36

PEEP 12 12

Exhaled TV 400 400

CRS222 167

FiO2 05 09

Fluid (ml) 0 1200

The EGDTPuzzle of formula

SvO2 Cellular oxygen

Good SvO2 means good cellular oxygenation (Low flow)

DO2 = 100

VO2 = 30

SvO2 = 70

Good SvO2 means good cellular oxygenation (heterogeneous flow)

DO2 = 100

VO2 = 10

SvO2 = 90

060356

16

Correlation between perfused capillary and blood lactateDe Backer etal Crit Care Med 2006

Prognostic value of hyperlactatemia in many

different critical care conditionsBlood lactate levels are superior to oxygen-derived

variables in predicting outcome in human septic shock

J Bakker M Coffernils M Leon P Gris and J L Vincent Chest 199199956-962

plt 005

plt 0001

Lactate level after 4 hrs of resuscitationS-W Lee etal Emerg Med J 200825659-665

Prognostic value of blood lactate levels in the ED

Shapiro NI et al Serum lactate as a predictor of mortality in emergency department patients with infection Ann Emerg Med 2005 45(5) p 524-8

490

900

2840

150

450

2240

000

500

1000

1500

2000

2500

3000

0-24 25-39 gt4

28 day in hospital mortality Death

Mo

rta

lity

ra

te

Lactate

Serum lactate as a predictor of mortalityin patients with infection

S Trzeciak et alIntensive Care Med (2007) 33970ndash977

Prognostic value of blood lactate levels

in the Critical care unit at Ramathibodihospital

Survivors 27

Non-survivors

5

0

1

2

3

4

5

6

Art

eri

al la

cta

te (

mm

ol

L)

p=NS

The Correlation Between Arterial Lactate and Venous Lactate in Patients With Sepsis and

Septic Shock (unpublished data)

Na Petvicharn C MD Theerawit P MD

Department of Internal Medicine the Faculty of Medicine Ramathibodi Hospital MahidolUniversity

060356

17

LACtime the predictor of organ failureJan Bakker et alAJS 1996171221-6

Lactate

Time

Lactime

AUC

Survivors

Non-survivors

P lt 005

2 mmolL

Serial blood lactate levels can predict the

development of multiple organ failure following septic shock

MD Jan Bakker MD Philippe Gris MD Michel Coffernils MD Robert J Kahn MD PhD Jean-

Louis Vincent The American Journal of surgery Volume 171 Issue 2 Pages 221-226 February 1996

plt005

plt 001

plt005 vs initial

blood lactate

Lactate clearance and mortalityArnold RC Shock 2008

0

10

20

30

40

50

60

70

LC gt 10 LC lt 10

Mortality rate

SvO2 gt 70

P lt 0001

Odds ratio for death 49(15-159)

Early lactate clearance is associated with

improved outcome in severe sepsis and

septic shock

H Bryant Nguyen MD MS Emanuel P Rivers MD MPH Bernhard P Knoblich MD

Gordon Jacobsen MS Alexandria Muzzin BS Julie A Ressler BS Michael C Tomlanovich

MDCrit Care Med 2004 Vol 32 No 8

Lactate clearance

= (Lactate ED presentation ndash Lactate Hour 6)x100Lactate ED presentation

There was an approximately

11 decrease likelihood of mortality for each 10 increase in lactate clearance

Association between blood lactate levels Sequential Organ Failure

Assessment subscores and 28-day mortality during

early and late ICU stay A retrospective observational study

Tim C Jansen Jasper van Bommel Roger Woodward Paul G H Mulder Jan Bakker Crit Care Med 2009 Vol 37 No 8

Dynamic Lactate Indices as

Predictors of Outcome in Critically Ill Patients

Admission lactate (LACADM)

Maximum lactate (LACMAX24)

Minimum lactate (LACMIN24)

Time weighted lactate (LACTW24)

Absolute change in (delta) lactate (LACΔ24)

Percentage change in lactate (LACΔ24)

Nichol A Bailey M Egi M Pettila V French C Hart GK Stachowski E Reade MCCooper

DJ Bellomo RCrit Care 2011 15R242

060356

18

Tissue perfusion

Lactate is better than SvO2 for assessment of tissue perfusion

The higher initial lactate the higher mortality

Lactate changing over time is better than a single value for monitoring

The higher lactate clearance the better

outcome

At least 10 reduction of lactate during resuscitation should be achieved

Type of fluid

Colloids or Crystalloids

26 Randomized trials

BMJ 1998316961-4

RR of death

Trauma 130(095-177)

Burn 121(088-166)

Sepsis 108(073-161)

Pooled 119(098-145)

Crystalloid and colloid infusion over 90 min in sepsis and non sepsis cases with

fluid responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid Colloid P value

CI before

CI after

EVLW

beforeEVLW after

39(24-55)

41(25-59)

71(19-339)75(16-299)

34(20-82)

38(23-69)

71(26-213)71(25-196)

Plt001

Pgt005

P value between before and after

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

060356

19

Crystalloid VS Colloid

No difference in

PLI

EVLW

Gas exchange

If fluid is administered in septic

patients with

fluid responsiveness even in ALI

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

Correction of albumin in ARDS

Refresher course ICM December 2008

Correction of albumin in ARDS

Refresher course ICM December 2008

Colloid solution

Albumin Artificial

Gelatins

Dextran

HES

Poor effective

Allergic reactionAltered hemostasis

Allergic reactionRenal dysfucntion

060356

20

Colloid solutions

Hypoalbuminemia tends to increase the incidence of ARDS and mortality in sepsis patients

More fluid required for correct hemodynamic abnormality

Poor response to Furosemide

More potential leakage at capillary site may lead to more lung injury

Correction of hypoalbuminemia in ARDS may be benefitial in terms of mortality but it must be used carefully

HES may cause renal failure and high dosage may lead to bleeding tendency

The benefit of artificial colloid solution over albumin is not known

Case

60 YO male patient 60 Kg

Pneumonia with septic shock on MV

VS BP 8040 mmHg HR 120 RR 26 BT 39oC

Heart normal S1S2 no murmur

Lungs crepitation RLL lingular segment

Liver and spleen not palpable

No edema

Neuro WNL

Case

Load NSS 1500 ml -gt PPV 14 -gt lung crepitation

BP 9040 mmHg (MAP = 57 mmHg)

Increase Nor-epinephrine

BP 8545 mmHg (MAP = 55 mmHg)

HR 90 -gt 110 min lactate 3 to 6 mmolL

Re-assessment

ABG

pH 71

pCO2 35 mmHg

pO2 70 mmHg

HCO3 15 mmolL

We corrected acidosis and start dobutamine

Can decrease dosage of NorE and lactate 41

The

EGDT

We need re-

assessment

here

These are causes of no

response to pressor

Acidosis

Poor LV contraction

RV dysfunction +- PE

Pneumothorax

Concealed hemorrhage

Relative adrenal insufficiency

Electrolyte imbalance

Severe sepsis

060356

21

Norepinephrine in septic shock

Study Baseline CI(normal 25-4)

EM Redl-Wenzl et al 1993Claude Martin et al 1993BLevy et al 1997Daniel De Backer et al 2003

Jacques Albane`se et al 2004Franccedilois Lauzier et al 2006

38+1153+1340+134+1

47+0244+14

Blood transfusion in septic shockJean-Louis Vincent Pongdhep Theerawit Davide Simeon

Basic Principles of Oxygen Transport and Calculations

Alternatives to Blood Transfusion in Transfusion Medicine 2nd Ed

Chapter 17 Published Online 4 SEP 2010

Transfusions will obviously have opposite effects to

anemia increasing blood viscosity and reducing the adrenergic response It is intriguing to consider

that transfusions may result in a decrease in

myocardial contractility Hence cardiac output often decreases following transfusions in the

nomovolemic patient and the increase in DO2

can be minor or even absent For example Shah et al observed in resuscitated trauma patients

that blood transfusion of one unit of RBC increased hemoglobin from 92 plusmn 03 to 102 plusmn 03

gdL but decreased cardiac output so that DO2

did not change

Hb lt 10 gL goal 10-12 gL

Hb lt 7 gL goal 7-9 gL

N=418

N=420

A MULTICENTER RANDOMIZED CONTROLLED CLINICAL

TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CAREPAULC HEacuteBERT MD GEORGEWELLS PHD MORRISA BLAJCHMAN MD JOHNMARSHALL MD CLAUDIOMARTIN MD GIUSEPPEPAGLIARELLO MD MARTINTWEEDDALE MD PHD IRWINSCHWEITZER MSC ELIZABETHYETISIR MSC ANDTHETRANSFUSIONREQUIREMENTSINCRITICALCAREINVESTIGATORSFORTHECANADIANCRITICALCARETRIALSGROUP

NEJM 1999

(normovolemia)

Red blood cell transfusion during septic shock in the ICUA Perner etal Acta Anaesthesiol Scand 2012 56 718ndash723

The CRIT Study Anemia and blood transfusion in the critically illmdashCurrent clinical practice in the United States

(Observational study 284 ICU 4892 patients)

Crit Care Med 2004 3239 ndash52

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 16: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

16

Correlation between perfused capillary and blood lactateDe Backer etal Crit Care Med 2006

Prognostic value of hyperlactatemia in many

different critical care conditionsBlood lactate levels are superior to oxygen-derived

variables in predicting outcome in human septic shock

J Bakker M Coffernils M Leon P Gris and J L Vincent Chest 199199956-962

plt 005

plt 0001

Lactate level after 4 hrs of resuscitationS-W Lee etal Emerg Med J 200825659-665

Prognostic value of blood lactate levels in the ED

Shapiro NI et al Serum lactate as a predictor of mortality in emergency department patients with infection Ann Emerg Med 2005 45(5) p 524-8

490

900

2840

150

450

2240

000

500

1000

1500

2000

2500

3000

0-24 25-39 gt4

28 day in hospital mortality Death

Mo

rta

lity

ra

te

Lactate

Serum lactate as a predictor of mortalityin patients with infection

S Trzeciak et alIntensive Care Med (2007) 33970ndash977

Prognostic value of blood lactate levels

in the Critical care unit at Ramathibodihospital

Survivors 27

Non-survivors

5

0

1

2

3

4

5

6

Art

eri

al la

cta

te (

mm

ol

L)

p=NS

The Correlation Between Arterial Lactate and Venous Lactate in Patients With Sepsis and

Septic Shock (unpublished data)

Na Petvicharn C MD Theerawit P MD

Department of Internal Medicine the Faculty of Medicine Ramathibodi Hospital MahidolUniversity

060356

17

LACtime the predictor of organ failureJan Bakker et alAJS 1996171221-6

Lactate

Time

Lactime

AUC

Survivors

Non-survivors

P lt 005

2 mmolL

Serial blood lactate levels can predict the

development of multiple organ failure following septic shock

MD Jan Bakker MD Philippe Gris MD Michel Coffernils MD Robert J Kahn MD PhD Jean-

Louis Vincent The American Journal of surgery Volume 171 Issue 2 Pages 221-226 February 1996

plt005

plt 001

plt005 vs initial

blood lactate

Lactate clearance and mortalityArnold RC Shock 2008

0

10

20

30

40

50

60

70

LC gt 10 LC lt 10

Mortality rate

SvO2 gt 70

P lt 0001

Odds ratio for death 49(15-159)

Early lactate clearance is associated with

improved outcome in severe sepsis and

septic shock

H Bryant Nguyen MD MS Emanuel P Rivers MD MPH Bernhard P Knoblich MD

Gordon Jacobsen MS Alexandria Muzzin BS Julie A Ressler BS Michael C Tomlanovich

MDCrit Care Med 2004 Vol 32 No 8

Lactate clearance

= (Lactate ED presentation ndash Lactate Hour 6)x100Lactate ED presentation

There was an approximately

11 decrease likelihood of mortality for each 10 increase in lactate clearance

Association between blood lactate levels Sequential Organ Failure

Assessment subscores and 28-day mortality during

early and late ICU stay A retrospective observational study

Tim C Jansen Jasper van Bommel Roger Woodward Paul G H Mulder Jan Bakker Crit Care Med 2009 Vol 37 No 8

Dynamic Lactate Indices as

Predictors of Outcome in Critically Ill Patients

Admission lactate (LACADM)

Maximum lactate (LACMAX24)

Minimum lactate (LACMIN24)

Time weighted lactate (LACTW24)

Absolute change in (delta) lactate (LACΔ24)

Percentage change in lactate (LACΔ24)

Nichol A Bailey M Egi M Pettila V French C Hart GK Stachowski E Reade MCCooper

DJ Bellomo RCrit Care 2011 15R242

060356

18

Tissue perfusion

Lactate is better than SvO2 for assessment of tissue perfusion

The higher initial lactate the higher mortality

Lactate changing over time is better than a single value for monitoring

The higher lactate clearance the better

outcome

At least 10 reduction of lactate during resuscitation should be achieved

Type of fluid

Colloids or Crystalloids

26 Randomized trials

BMJ 1998316961-4

RR of death

Trauma 130(095-177)

Burn 121(088-166)

Sepsis 108(073-161)

Pooled 119(098-145)

Crystalloid and colloid infusion over 90 min in sepsis and non sepsis cases with

fluid responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid Colloid P value

CI before

CI after

EVLW

beforeEVLW after

39(24-55)

41(25-59)

71(19-339)75(16-299)

34(20-82)

38(23-69)

71(26-213)71(25-196)

Plt001

Pgt005

P value between before and after

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

060356

19

Crystalloid VS Colloid

No difference in

PLI

EVLW

Gas exchange

If fluid is administered in septic

patients with

fluid responsiveness even in ALI

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

Correction of albumin in ARDS

Refresher course ICM December 2008

Correction of albumin in ARDS

Refresher course ICM December 2008

Colloid solution

Albumin Artificial

Gelatins

Dextran

HES

Poor effective

Allergic reactionAltered hemostasis

Allergic reactionRenal dysfucntion

060356

20

Colloid solutions

Hypoalbuminemia tends to increase the incidence of ARDS and mortality in sepsis patients

More fluid required for correct hemodynamic abnormality

Poor response to Furosemide

More potential leakage at capillary site may lead to more lung injury

Correction of hypoalbuminemia in ARDS may be benefitial in terms of mortality but it must be used carefully

HES may cause renal failure and high dosage may lead to bleeding tendency

The benefit of artificial colloid solution over albumin is not known

Case

60 YO male patient 60 Kg

Pneumonia with septic shock on MV

VS BP 8040 mmHg HR 120 RR 26 BT 39oC

Heart normal S1S2 no murmur

Lungs crepitation RLL lingular segment

Liver and spleen not palpable

No edema

Neuro WNL

Case

Load NSS 1500 ml -gt PPV 14 -gt lung crepitation

BP 9040 mmHg (MAP = 57 mmHg)

Increase Nor-epinephrine

BP 8545 mmHg (MAP = 55 mmHg)

HR 90 -gt 110 min lactate 3 to 6 mmolL

Re-assessment

ABG

pH 71

pCO2 35 mmHg

pO2 70 mmHg

HCO3 15 mmolL

We corrected acidosis and start dobutamine

Can decrease dosage of NorE and lactate 41

The

EGDT

We need re-

assessment

here

These are causes of no

response to pressor

Acidosis

Poor LV contraction

RV dysfunction +- PE

Pneumothorax

Concealed hemorrhage

Relative adrenal insufficiency

Electrolyte imbalance

Severe sepsis

060356

21

Norepinephrine in septic shock

Study Baseline CI(normal 25-4)

EM Redl-Wenzl et al 1993Claude Martin et al 1993BLevy et al 1997Daniel De Backer et al 2003

Jacques Albane`se et al 2004Franccedilois Lauzier et al 2006

38+1153+1340+134+1

47+0244+14

Blood transfusion in septic shockJean-Louis Vincent Pongdhep Theerawit Davide Simeon

Basic Principles of Oxygen Transport and Calculations

Alternatives to Blood Transfusion in Transfusion Medicine 2nd Ed

Chapter 17 Published Online 4 SEP 2010

Transfusions will obviously have opposite effects to

anemia increasing blood viscosity and reducing the adrenergic response It is intriguing to consider

that transfusions may result in a decrease in

myocardial contractility Hence cardiac output often decreases following transfusions in the

nomovolemic patient and the increase in DO2

can be minor or even absent For example Shah et al observed in resuscitated trauma patients

that blood transfusion of one unit of RBC increased hemoglobin from 92 plusmn 03 to 102 plusmn 03

gdL but decreased cardiac output so that DO2

did not change

Hb lt 10 gL goal 10-12 gL

Hb lt 7 gL goal 7-9 gL

N=418

N=420

A MULTICENTER RANDOMIZED CONTROLLED CLINICAL

TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CAREPAULC HEacuteBERT MD GEORGEWELLS PHD MORRISA BLAJCHMAN MD JOHNMARSHALL MD CLAUDIOMARTIN MD GIUSEPPEPAGLIARELLO MD MARTINTWEEDDALE MD PHD IRWINSCHWEITZER MSC ELIZABETHYETISIR MSC ANDTHETRANSFUSIONREQUIREMENTSINCRITICALCAREINVESTIGATORSFORTHECANADIANCRITICALCARETRIALSGROUP

NEJM 1999

(normovolemia)

Red blood cell transfusion during septic shock in the ICUA Perner etal Acta Anaesthesiol Scand 2012 56 718ndash723

The CRIT Study Anemia and blood transfusion in the critically illmdashCurrent clinical practice in the United States

(Observational study 284 ICU 4892 patients)

Crit Care Med 2004 3239 ndash52

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 17: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

17

LACtime the predictor of organ failureJan Bakker et alAJS 1996171221-6

Lactate

Time

Lactime

AUC

Survivors

Non-survivors

P lt 005

2 mmolL

Serial blood lactate levels can predict the

development of multiple organ failure following septic shock

MD Jan Bakker MD Philippe Gris MD Michel Coffernils MD Robert J Kahn MD PhD Jean-

Louis Vincent The American Journal of surgery Volume 171 Issue 2 Pages 221-226 February 1996

plt005

plt 001

plt005 vs initial

blood lactate

Lactate clearance and mortalityArnold RC Shock 2008

0

10

20

30

40

50

60

70

LC gt 10 LC lt 10

Mortality rate

SvO2 gt 70

P lt 0001

Odds ratio for death 49(15-159)

Early lactate clearance is associated with

improved outcome in severe sepsis and

septic shock

H Bryant Nguyen MD MS Emanuel P Rivers MD MPH Bernhard P Knoblich MD

Gordon Jacobsen MS Alexandria Muzzin BS Julie A Ressler BS Michael C Tomlanovich

MDCrit Care Med 2004 Vol 32 No 8

Lactate clearance

= (Lactate ED presentation ndash Lactate Hour 6)x100Lactate ED presentation

There was an approximately

11 decrease likelihood of mortality for each 10 increase in lactate clearance

Association between blood lactate levels Sequential Organ Failure

Assessment subscores and 28-day mortality during

early and late ICU stay A retrospective observational study

Tim C Jansen Jasper van Bommel Roger Woodward Paul G H Mulder Jan Bakker Crit Care Med 2009 Vol 37 No 8

Dynamic Lactate Indices as

Predictors of Outcome in Critically Ill Patients

Admission lactate (LACADM)

Maximum lactate (LACMAX24)

Minimum lactate (LACMIN24)

Time weighted lactate (LACTW24)

Absolute change in (delta) lactate (LACΔ24)

Percentage change in lactate (LACΔ24)

Nichol A Bailey M Egi M Pettila V French C Hart GK Stachowski E Reade MCCooper

DJ Bellomo RCrit Care 2011 15R242

060356

18

Tissue perfusion

Lactate is better than SvO2 for assessment of tissue perfusion

The higher initial lactate the higher mortality

Lactate changing over time is better than a single value for monitoring

The higher lactate clearance the better

outcome

At least 10 reduction of lactate during resuscitation should be achieved

Type of fluid

Colloids or Crystalloids

26 Randomized trials

BMJ 1998316961-4

RR of death

Trauma 130(095-177)

Burn 121(088-166)

Sepsis 108(073-161)

Pooled 119(098-145)

Crystalloid and colloid infusion over 90 min in sepsis and non sepsis cases with

fluid responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid Colloid P value

CI before

CI after

EVLW

beforeEVLW after

39(24-55)

41(25-59)

71(19-339)75(16-299)

34(20-82)

38(23-69)

71(26-213)71(25-196)

Plt001

Pgt005

P value between before and after

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

060356

19

Crystalloid VS Colloid

No difference in

PLI

EVLW

Gas exchange

If fluid is administered in septic

patients with

fluid responsiveness even in ALI

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

Correction of albumin in ARDS

Refresher course ICM December 2008

Correction of albumin in ARDS

Refresher course ICM December 2008

Colloid solution

Albumin Artificial

Gelatins

Dextran

HES

Poor effective

Allergic reactionAltered hemostasis

Allergic reactionRenal dysfucntion

060356

20

Colloid solutions

Hypoalbuminemia tends to increase the incidence of ARDS and mortality in sepsis patients

More fluid required for correct hemodynamic abnormality

Poor response to Furosemide

More potential leakage at capillary site may lead to more lung injury

Correction of hypoalbuminemia in ARDS may be benefitial in terms of mortality but it must be used carefully

HES may cause renal failure and high dosage may lead to bleeding tendency

The benefit of artificial colloid solution over albumin is not known

Case

60 YO male patient 60 Kg

Pneumonia with septic shock on MV

VS BP 8040 mmHg HR 120 RR 26 BT 39oC

Heart normal S1S2 no murmur

Lungs crepitation RLL lingular segment

Liver and spleen not palpable

No edema

Neuro WNL

Case

Load NSS 1500 ml -gt PPV 14 -gt lung crepitation

BP 9040 mmHg (MAP = 57 mmHg)

Increase Nor-epinephrine

BP 8545 mmHg (MAP = 55 mmHg)

HR 90 -gt 110 min lactate 3 to 6 mmolL

Re-assessment

ABG

pH 71

pCO2 35 mmHg

pO2 70 mmHg

HCO3 15 mmolL

We corrected acidosis and start dobutamine

Can decrease dosage of NorE and lactate 41

The

EGDT

We need re-

assessment

here

These are causes of no

response to pressor

Acidosis

Poor LV contraction

RV dysfunction +- PE

Pneumothorax

Concealed hemorrhage

Relative adrenal insufficiency

Electrolyte imbalance

Severe sepsis

060356

21

Norepinephrine in septic shock

Study Baseline CI(normal 25-4)

EM Redl-Wenzl et al 1993Claude Martin et al 1993BLevy et al 1997Daniel De Backer et al 2003

Jacques Albane`se et al 2004Franccedilois Lauzier et al 2006

38+1153+1340+134+1

47+0244+14

Blood transfusion in septic shockJean-Louis Vincent Pongdhep Theerawit Davide Simeon

Basic Principles of Oxygen Transport and Calculations

Alternatives to Blood Transfusion in Transfusion Medicine 2nd Ed

Chapter 17 Published Online 4 SEP 2010

Transfusions will obviously have opposite effects to

anemia increasing blood viscosity and reducing the adrenergic response It is intriguing to consider

that transfusions may result in a decrease in

myocardial contractility Hence cardiac output often decreases following transfusions in the

nomovolemic patient and the increase in DO2

can be minor or even absent For example Shah et al observed in resuscitated trauma patients

that blood transfusion of one unit of RBC increased hemoglobin from 92 plusmn 03 to 102 plusmn 03

gdL but decreased cardiac output so that DO2

did not change

Hb lt 10 gL goal 10-12 gL

Hb lt 7 gL goal 7-9 gL

N=418

N=420

A MULTICENTER RANDOMIZED CONTROLLED CLINICAL

TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CAREPAULC HEacuteBERT MD GEORGEWELLS PHD MORRISA BLAJCHMAN MD JOHNMARSHALL MD CLAUDIOMARTIN MD GIUSEPPEPAGLIARELLO MD MARTINTWEEDDALE MD PHD IRWINSCHWEITZER MSC ELIZABETHYETISIR MSC ANDTHETRANSFUSIONREQUIREMENTSINCRITICALCAREINVESTIGATORSFORTHECANADIANCRITICALCARETRIALSGROUP

NEJM 1999

(normovolemia)

Red blood cell transfusion during septic shock in the ICUA Perner etal Acta Anaesthesiol Scand 2012 56 718ndash723

The CRIT Study Anemia and blood transfusion in the critically illmdashCurrent clinical practice in the United States

(Observational study 284 ICU 4892 patients)

Crit Care Med 2004 3239 ndash52

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 18: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

18

Tissue perfusion

Lactate is better than SvO2 for assessment of tissue perfusion

The higher initial lactate the higher mortality

Lactate changing over time is better than a single value for monitoring

The higher lactate clearance the better

outcome

At least 10 reduction of lactate during resuscitation should be achieved

Type of fluid

Colloids or Crystalloids

26 Randomized trials

BMJ 1998316961-4

RR of death

Trauma 130(095-177)

Burn 121(088-166)

Sepsis 108(073-161)

Pooled 119(098-145)

Crystalloid and colloid infusion over 90 min in sepsis and non sepsis cases with

fluid responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid Colloid P value

CI before

CI after

EVLW

beforeEVLW after

39(24-55)

41(25-59)

71(19-339)75(16-299)

34(20-82)

38(23-69)

71(26-213)71(25-196)

Plt001

Pgt005

P value between before and after

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

Crystalloid and colloid infusion over 90 min in

sepsis and non sepsis cases with fluid

responsivenessMelanie van der Heijden etal Crit Care Med 2009371275

060356

19

Crystalloid VS Colloid

No difference in

PLI

EVLW

Gas exchange

If fluid is administered in septic

patients with

fluid responsiveness even in ALI

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

Correction of albumin in ARDS

Refresher course ICM December 2008

Correction of albumin in ARDS

Refresher course ICM December 2008

Colloid solution

Albumin Artificial

Gelatins

Dextran

HES

Poor effective

Allergic reactionAltered hemostasis

Allergic reactionRenal dysfucntion

060356

20

Colloid solutions

Hypoalbuminemia tends to increase the incidence of ARDS and mortality in sepsis patients

More fluid required for correct hemodynamic abnormality

Poor response to Furosemide

More potential leakage at capillary site may lead to more lung injury

Correction of hypoalbuminemia in ARDS may be benefitial in terms of mortality but it must be used carefully

HES may cause renal failure and high dosage may lead to bleeding tendency

The benefit of artificial colloid solution over albumin is not known

Case

60 YO male patient 60 Kg

Pneumonia with septic shock on MV

VS BP 8040 mmHg HR 120 RR 26 BT 39oC

Heart normal S1S2 no murmur

Lungs crepitation RLL lingular segment

Liver and spleen not palpable

No edema

Neuro WNL

Case

Load NSS 1500 ml -gt PPV 14 -gt lung crepitation

BP 9040 mmHg (MAP = 57 mmHg)

Increase Nor-epinephrine

BP 8545 mmHg (MAP = 55 mmHg)

HR 90 -gt 110 min lactate 3 to 6 mmolL

Re-assessment

ABG

pH 71

pCO2 35 mmHg

pO2 70 mmHg

HCO3 15 mmolL

We corrected acidosis and start dobutamine

Can decrease dosage of NorE and lactate 41

The

EGDT

We need re-

assessment

here

These are causes of no

response to pressor

Acidosis

Poor LV contraction

RV dysfunction +- PE

Pneumothorax

Concealed hemorrhage

Relative adrenal insufficiency

Electrolyte imbalance

Severe sepsis

060356

21

Norepinephrine in septic shock

Study Baseline CI(normal 25-4)

EM Redl-Wenzl et al 1993Claude Martin et al 1993BLevy et al 1997Daniel De Backer et al 2003

Jacques Albane`se et al 2004Franccedilois Lauzier et al 2006

38+1153+1340+134+1

47+0244+14

Blood transfusion in septic shockJean-Louis Vincent Pongdhep Theerawit Davide Simeon

Basic Principles of Oxygen Transport and Calculations

Alternatives to Blood Transfusion in Transfusion Medicine 2nd Ed

Chapter 17 Published Online 4 SEP 2010

Transfusions will obviously have opposite effects to

anemia increasing blood viscosity and reducing the adrenergic response It is intriguing to consider

that transfusions may result in a decrease in

myocardial contractility Hence cardiac output often decreases following transfusions in the

nomovolemic patient and the increase in DO2

can be minor or even absent For example Shah et al observed in resuscitated trauma patients

that blood transfusion of one unit of RBC increased hemoglobin from 92 plusmn 03 to 102 plusmn 03

gdL but decreased cardiac output so that DO2

did not change

Hb lt 10 gL goal 10-12 gL

Hb lt 7 gL goal 7-9 gL

N=418

N=420

A MULTICENTER RANDOMIZED CONTROLLED CLINICAL

TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CAREPAULC HEacuteBERT MD GEORGEWELLS PHD MORRISA BLAJCHMAN MD JOHNMARSHALL MD CLAUDIOMARTIN MD GIUSEPPEPAGLIARELLO MD MARTINTWEEDDALE MD PHD IRWINSCHWEITZER MSC ELIZABETHYETISIR MSC ANDTHETRANSFUSIONREQUIREMENTSINCRITICALCAREINVESTIGATORSFORTHECANADIANCRITICALCARETRIALSGROUP

NEJM 1999

(normovolemia)

Red blood cell transfusion during septic shock in the ICUA Perner etal Acta Anaesthesiol Scand 2012 56 718ndash723

The CRIT Study Anemia and blood transfusion in the critically illmdashCurrent clinical practice in the United States

(Observational study 284 ICU 4892 patients)

Crit Care Med 2004 3239 ndash52

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 19: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

19

Crystalloid VS Colloid

No difference in

PLI

EVLW

Gas exchange

If fluid is administered in septic

patients with

fluid responsiveness even in ALI

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

ARDS development and mortality

in hypoproteinemic stateManglialardi etal Crit Care Med 2000283137-45

Correction of albumin in ARDS

Refresher course ICM December 2008

Correction of albumin in ARDS

Refresher course ICM December 2008

Colloid solution

Albumin Artificial

Gelatins

Dextran

HES

Poor effective

Allergic reactionAltered hemostasis

Allergic reactionRenal dysfucntion

060356

20

Colloid solutions

Hypoalbuminemia tends to increase the incidence of ARDS and mortality in sepsis patients

More fluid required for correct hemodynamic abnormality

Poor response to Furosemide

More potential leakage at capillary site may lead to more lung injury

Correction of hypoalbuminemia in ARDS may be benefitial in terms of mortality but it must be used carefully

HES may cause renal failure and high dosage may lead to bleeding tendency

The benefit of artificial colloid solution over albumin is not known

Case

60 YO male patient 60 Kg

Pneumonia with septic shock on MV

VS BP 8040 mmHg HR 120 RR 26 BT 39oC

Heart normal S1S2 no murmur

Lungs crepitation RLL lingular segment

Liver and spleen not palpable

No edema

Neuro WNL

Case

Load NSS 1500 ml -gt PPV 14 -gt lung crepitation

BP 9040 mmHg (MAP = 57 mmHg)

Increase Nor-epinephrine

BP 8545 mmHg (MAP = 55 mmHg)

HR 90 -gt 110 min lactate 3 to 6 mmolL

Re-assessment

ABG

pH 71

pCO2 35 mmHg

pO2 70 mmHg

HCO3 15 mmolL

We corrected acidosis and start dobutamine

Can decrease dosage of NorE and lactate 41

The

EGDT

We need re-

assessment

here

These are causes of no

response to pressor

Acidosis

Poor LV contraction

RV dysfunction +- PE

Pneumothorax

Concealed hemorrhage

Relative adrenal insufficiency

Electrolyte imbalance

Severe sepsis

060356

21

Norepinephrine in septic shock

Study Baseline CI(normal 25-4)

EM Redl-Wenzl et al 1993Claude Martin et al 1993BLevy et al 1997Daniel De Backer et al 2003

Jacques Albane`se et al 2004Franccedilois Lauzier et al 2006

38+1153+1340+134+1

47+0244+14

Blood transfusion in septic shockJean-Louis Vincent Pongdhep Theerawit Davide Simeon

Basic Principles of Oxygen Transport and Calculations

Alternatives to Blood Transfusion in Transfusion Medicine 2nd Ed

Chapter 17 Published Online 4 SEP 2010

Transfusions will obviously have opposite effects to

anemia increasing blood viscosity and reducing the adrenergic response It is intriguing to consider

that transfusions may result in a decrease in

myocardial contractility Hence cardiac output often decreases following transfusions in the

nomovolemic patient and the increase in DO2

can be minor or even absent For example Shah et al observed in resuscitated trauma patients

that blood transfusion of one unit of RBC increased hemoglobin from 92 plusmn 03 to 102 plusmn 03

gdL but decreased cardiac output so that DO2

did not change

Hb lt 10 gL goal 10-12 gL

Hb lt 7 gL goal 7-9 gL

N=418

N=420

A MULTICENTER RANDOMIZED CONTROLLED CLINICAL

TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CAREPAULC HEacuteBERT MD GEORGEWELLS PHD MORRISA BLAJCHMAN MD JOHNMARSHALL MD CLAUDIOMARTIN MD GIUSEPPEPAGLIARELLO MD MARTINTWEEDDALE MD PHD IRWINSCHWEITZER MSC ELIZABETHYETISIR MSC ANDTHETRANSFUSIONREQUIREMENTSINCRITICALCAREINVESTIGATORSFORTHECANADIANCRITICALCARETRIALSGROUP

NEJM 1999

(normovolemia)

Red blood cell transfusion during septic shock in the ICUA Perner etal Acta Anaesthesiol Scand 2012 56 718ndash723

The CRIT Study Anemia and blood transfusion in the critically illmdashCurrent clinical practice in the United States

(Observational study 284 ICU 4892 patients)

Crit Care Med 2004 3239 ndash52

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 20: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

20

Colloid solutions

Hypoalbuminemia tends to increase the incidence of ARDS and mortality in sepsis patients

More fluid required for correct hemodynamic abnormality

Poor response to Furosemide

More potential leakage at capillary site may lead to more lung injury

Correction of hypoalbuminemia in ARDS may be benefitial in terms of mortality but it must be used carefully

HES may cause renal failure and high dosage may lead to bleeding tendency

The benefit of artificial colloid solution over albumin is not known

Case

60 YO male patient 60 Kg

Pneumonia with septic shock on MV

VS BP 8040 mmHg HR 120 RR 26 BT 39oC

Heart normal S1S2 no murmur

Lungs crepitation RLL lingular segment

Liver and spleen not palpable

No edema

Neuro WNL

Case

Load NSS 1500 ml -gt PPV 14 -gt lung crepitation

BP 9040 mmHg (MAP = 57 mmHg)

Increase Nor-epinephrine

BP 8545 mmHg (MAP = 55 mmHg)

HR 90 -gt 110 min lactate 3 to 6 mmolL

Re-assessment

ABG

pH 71

pCO2 35 mmHg

pO2 70 mmHg

HCO3 15 mmolL

We corrected acidosis and start dobutamine

Can decrease dosage of NorE and lactate 41

The

EGDT

We need re-

assessment

here

These are causes of no

response to pressor

Acidosis

Poor LV contraction

RV dysfunction +- PE

Pneumothorax

Concealed hemorrhage

Relative adrenal insufficiency

Electrolyte imbalance

Severe sepsis

060356

21

Norepinephrine in septic shock

Study Baseline CI(normal 25-4)

EM Redl-Wenzl et al 1993Claude Martin et al 1993BLevy et al 1997Daniel De Backer et al 2003

Jacques Albane`se et al 2004Franccedilois Lauzier et al 2006

38+1153+1340+134+1

47+0244+14

Blood transfusion in septic shockJean-Louis Vincent Pongdhep Theerawit Davide Simeon

Basic Principles of Oxygen Transport and Calculations

Alternatives to Blood Transfusion in Transfusion Medicine 2nd Ed

Chapter 17 Published Online 4 SEP 2010

Transfusions will obviously have opposite effects to

anemia increasing blood viscosity and reducing the adrenergic response It is intriguing to consider

that transfusions may result in a decrease in

myocardial contractility Hence cardiac output often decreases following transfusions in the

nomovolemic patient and the increase in DO2

can be minor or even absent For example Shah et al observed in resuscitated trauma patients

that blood transfusion of one unit of RBC increased hemoglobin from 92 plusmn 03 to 102 plusmn 03

gdL but decreased cardiac output so that DO2

did not change

Hb lt 10 gL goal 10-12 gL

Hb lt 7 gL goal 7-9 gL

N=418

N=420

A MULTICENTER RANDOMIZED CONTROLLED CLINICAL

TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CAREPAULC HEacuteBERT MD GEORGEWELLS PHD MORRISA BLAJCHMAN MD JOHNMARSHALL MD CLAUDIOMARTIN MD GIUSEPPEPAGLIARELLO MD MARTINTWEEDDALE MD PHD IRWINSCHWEITZER MSC ELIZABETHYETISIR MSC ANDTHETRANSFUSIONREQUIREMENTSINCRITICALCAREINVESTIGATORSFORTHECANADIANCRITICALCARETRIALSGROUP

NEJM 1999

(normovolemia)

Red blood cell transfusion during septic shock in the ICUA Perner etal Acta Anaesthesiol Scand 2012 56 718ndash723

The CRIT Study Anemia and blood transfusion in the critically illmdashCurrent clinical practice in the United States

(Observational study 284 ICU 4892 patients)

Crit Care Med 2004 3239 ndash52

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 21: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

21

Norepinephrine in septic shock

Study Baseline CI(normal 25-4)

EM Redl-Wenzl et al 1993Claude Martin et al 1993BLevy et al 1997Daniel De Backer et al 2003

Jacques Albane`se et al 2004Franccedilois Lauzier et al 2006

38+1153+1340+134+1

47+0244+14

Blood transfusion in septic shockJean-Louis Vincent Pongdhep Theerawit Davide Simeon

Basic Principles of Oxygen Transport and Calculations

Alternatives to Blood Transfusion in Transfusion Medicine 2nd Ed

Chapter 17 Published Online 4 SEP 2010

Transfusions will obviously have opposite effects to

anemia increasing blood viscosity and reducing the adrenergic response It is intriguing to consider

that transfusions may result in a decrease in

myocardial contractility Hence cardiac output often decreases following transfusions in the

nomovolemic patient and the increase in DO2

can be minor or even absent For example Shah et al observed in resuscitated trauma patients

that blood transfusion of one unit of RBC increased hemoglobin from 92 plusmn 03 to 102 plusmn 03

gdL but decreased cardiac output so that DO2

did not change

Hb lt 10 gL goal 10-12 gL

Hb lt 7 gL goal 7-9 gL

N=418

N=420

A MULTICENTER RANDOMIZED CONTROLLED CLINICAL

TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CAREPAULC HEacuteBERT MD GEORGEWELLS PHD MORRISA BLAJCHMAN MD JOHNMARSHALL MD CLAUDIOMARTIN MD GIUSEPPEPAGLIARELLO MD MARTINTWEEDDALE MD PHD IRWINSCHWEITZER MSC ELIZABETHYETISIR MSC ANDTHETRANSFUSIONREQUIREMENTSINCRITICALCAREINVESTIGATORSFORTHECANADIANCRITICALCARETRIALSGROUP

NEJM 1999

(normovolemia)

Red blood cell transfusion during septic shock in the ICUA Perner etal Acta Anaesthesiol Scand 2012 56 718ndash723

The CRIT Study Anemia and blood transfusion in the critically illmdashCurrent clinical practice in the United States

(Observational study 284 ICU 4892 patients)

Crit Care Med 2004 3239 ndash52

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 22: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

22

Microvascular response to red blood cell

transfusion in patients with severe sepsisYasser Sakr MD PhDetal Crit Care Med 2007 351639ndash1644

Clinical practice guideline Red blood cell transfusion in

adult trauma and critical careLena M Napolitano MD Stanley Kurek DO Fred A Luchette MD Howard L Corwin MD

Philip S Barie MD Samuel A Tisherman MD Paul C Hebert MD MHSc Gary L Anderson DO

Michael R Bard MD William Bromberg MD William C Chiu MD Mark D Cipolle MD PhD

Keith D Clancy MD Lawrence Diebel MD William S Hoff MD K Michael Hughes DO

Imtiaz Munshi MD Donna Nayduch RN MSN ACNP Rovinder Sandhu MD Jay A Yelon MD

for the American College of Critical Care Medicine of the Society of Critical Care Medicine and the Eastern

Association for the Surgery of Trauma Practice Management Workgroup (Crit Care Med 2009)

we recommend that red blood cell transfusion occur

only when hemoglobin concentration decreases to

lt70 gdL to target a hemoglobin concentration of 70 ndash90 gdL in adults

The

EGDT

started at a dose of 25 microg per kilogram of body weight per

minute a dose that was increased by 25 microg per kilogram

per minute every 30 minutes until the central venous

oxygen saturation was 70 percent or higher or until a

maximal dose of 20 microg per kilogram per minute was given

Median max dose of dobutamine to reach CI gt 45 DO2 gt 600 VO2 gt 170

Control group 023 mcgkgmin (005-10)

Treatment group 12 mcgkgmin (002-166)

P = 0029

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion

Page 23: Severe sepsis & MODS - Christiannurse.christian.ac.th/PDF/Sepsis and multiorgan dysfunction.pdf · DO2 = SvO2 VO2 = CO x (SaO2-SvO2) ... Ca O2 = ( 1.39 x Hb x SaO2 ) + ( 0.003 x PaO2

060356

23

CI ge 45 CI = 25-35

in the presence of (a)myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output or

(b)ongoing signs of hypoperfusion