septic shock

Topic ReviewTopic ReviewSeptic Shock ManagementSeptic Shock Management

Piti Niyomsirivanich, MD.

10 Jan 2013

Take home message

• Adequate preload• Appropriate Antibiotic within 1 hr• Proper dose of vasopressors

• Consult

Outline• Definition• Pathophysiology• Early Goal Directed Therapy• Fluid Resuscitation• Vasopressors• Steroids• Antibiotics

• Glucose control• Blood product administration• Bicarbonate therapy• Stress ulcer prophylaxis

Definition• Bacteremia : Bacteria in blood• Septicemia : Bacteria + toxin in blood• SIRS : 2/4 of following conditions

– 1)Temp > 38 C or < 36 C– 2) Pulse rate > 90 /min– 3) RR > 20 /min or PaCO2 < 32 mmHg– 4) WBC > 12,000/ul or < 4000 /ul and/or Band form > 10%

• Sepsis = SIRS from infection• Severe sepsis = Sepsis+ end organ damage

– CVS , Renal , pulmonary , Hematologic ,Metabolic acidosis • Septic Shock = Sepsis + hypotension

Pathophysiology

Guideline

Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock:2008

Since 2001 10+ years ago!!!

Result of EGDT

N Engl J Med 2001; 345:1368-1377 November 8, 2001

Early goal directed therapySIRS

+SBP < 90 mmHg or MAP < 65 mmHg

-Or-Lactate > 4 mmol/L

After 20-30 ml/kg crystalloid IVF

CultureAntibiotic within 1 hourVolume accessment

Supplement oxygen or ET tube (if necessary)

Critical care consultation

ScvO2 ?

Goals achieved

Resuscitation complete

Vasopressor (NE/dopamine)

Blood transfusion to Hct > 30%

Inotropic agent

ONEHour

Five Hours

< 8-12 mmHg

8-12 mmHg

>/= 65 mmHg

< 65 mmHg

N Engl J Med 2001; 345:1368-1377November 8, 2001

Sedatives & muscle relaxants

Fluid Resusitation• Fluid therapy

– crystalloids or colloids (1B)

– Target a CVP of 8-12 mmHg (1C)

– Give fluid challenges of 1000 mL of crystalloids • or 300–500 mL of colloids over 30 mins.

Frank-Starling Law

• BP = CO X TVR• CO = HR X SV• SV = EDV – ESV • BP = ( EDV- ESV ) X HR X TVR

• BP = EF X HR X TVR X EDV

Volume

• Crystalloids– NSS– Ringer Lactate Solution

• Colloids– albumin– Dextrans– Gelatins e.g. Haemaccel– Hydroxyethylstarch e.g. Voluven

Low cost

edemaHemodilution

Hyperchloremic metabolic acidosis

Low cost

Lactate liverAcetate peripheral tissue

Potassium

SAFE Study * not differrent VS NSS

hypocalcemia expensive

*A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit

N ENGL J MED 2004; 350:2247-2256 May 27, 2004

Coagulopathy (inh. F VIII/ vWF)

Renal damage

Cross matching problem

Osmotic diuresis

Anaphylaxis 0.27%

GelofundolHaemaccel

30,000-35,000 kDa

Renal Excretion

Short half life

Anaphylaxis 0.34%

• MW 450-480 kDa Hetastarch Hespan

•MW 200 kDa •HAES-Steril 6%,10%

•MW 70 kDa •HES 70/0.5

•Voluven

Anaphylaxis 0.058%

Cochrane Database Syst. Rev. CD 001319,2003

Volume Assessment• Static VS dynamic

• Non-invasive– U/S IVC– Passive leg raising test– Pulse oximetry plethysmographic waveform amplitude variation

• Invasive– CVP– Fluid challenge test– CVP variation– Pulse pressure variation

Volume Assessment

• Require Endotracheal tube

• No Endotracheal tube • W/WO Endotracheal tube

CVP measurement

a= Atrial contractionc= Ventricular Contractionx= Atrial relaXationv= Venous fillingy = Tr”Y”cuspids opening

• CVP : poor predictor of fluid volume

CHEST. July 2008;134(1):172-178.

Fluid Challenge Test for CVP

Load IV fluid 200-250 ml in 10 min

CVP + </=2

CVP + >/=5

CVP + 2-5

Continue fluid therapy

Decrease rate of fluid therapy

Ultrasound IVC

Caval Index = 100 x (diam expiration - diam inspiration)/diam expiration

Caval Index > 50% suggest low CVP

Ann Emerg Med 2010; 55:290-295.

Passive leg raising test

Esophageal doppler : in cardiac output > 8% predict fluid responsiveness

Critical Care 2006, 10:170

Pulse oximetry plethysmographic waveform amplitude variation

CASE BCVP =5 cmH2O

CASE ACVP =15 cmH2O

Pulse oximetry plethysmographic waveform amplitude variation

POP max – POP min X 100

POP mean

%POP variation > 13%

Arterial Line

Pulse Pressure Variation

Vasopressor therapy

• Dopamine VS Norepinephrine

Kaplan–Meier Curves for 28-Day Survival in the Intention-to-Treat Population.

N Engl J Med 2010; 362:779-789

Vasopressure therapyDopamine

Low doseModerate dose (beta adrenergic receptor ) 5-10 ug/kg/minHigh dose (alpha adrenergic receptor)

>10 ug/kg/min Maximum dose 50 ug/kg/min

Norepinephrinestart 0.5 mcg/min

Harrison Int. Med edition 18 th

Vasopressor therapyExample

ผู้��หญิ�ง 64 ปี หนั�ก 70 kg มาด้�วย ไข้� หนัาวสั่��นั ปี�สั่สั่าวะแสั่บข้�ด้CBC : WBC 25000/ul N% 85 Band 2% Hb 12 g/dl Plt 200,000/ul UA WBC 50-100

BP 80/40 mmHg PR 95/min Temp 37.8 C RR 18/min

จงคำ�านัวณ dose ข้อง Dopamine ให� start 5 ug/kg/min

Rate (ml/min)60 X W (kg) X D (ug/kg/min)

C = Volume

Solute1,000

Rate (ml/min)60 X 70 X 5

C = 500

10001,000 = 2000

(Dopamine 1000 mg ผู้สั่ม 5%D/W 500 ml)

= 10.5 ml/hr

Early goal directed therapySIRS

+SBP < 90 mmHg or MAP < 65 mmHg

-Or-Lactate > 4 mmol/L

After 20-30 ml/kg crystalloid IVF

CultureAntibiotic within 1 hourVolume accessment

Supplement oxygen or ET tube (if necessary)

Critical care consultation

Goals achieved

Resuscitation complete

Vasopressor (NE/dopamine)

Blood transfusion to Hct > 30%

Inotropic agent

ONEHour

Five Hours

< 8-12 mmHg

8-12 mmHg

>/= 65 mmHg

< 65 mmHg

Sedatives & muscle relaxants

ScvO2ให�เง�นัไปีโรงเร$ยนั

ข้ากลั�บเหลั&อ 50 บาท

แปีลัว(าให�เง�นัไปีโรงเร$ยนัพอใช้�

ScvO2O2 content

O2 content เหลั&อ 70%

แปีลัว(าให�ออกซิ�เจนัไปีเนั&,อเย&�อพอใช้�

O2 delivery

• DO2 = [1.39 x Hb x SaO2 + (0.003 x PaO2)] x CO

• Depend on – Hemoglobin– O2 saturation– Cardiac output

– ScvO2 < 70%• target Hct > 30• Inotropic drug increase cardiac output

Goals achieved

Blood transfusion to Hct > 30

Inotropic agent> 70%

Contin Educ Anaesth Crit Care Pain (2004) 4 (4) 123-126

Alternative for ScvO2

• Lactate clearance– lactate clearance >10% or higher

• 6% lower in-hospital mortality than those resuscitated to an ScvO2 of at least 70%

– (95% CI, −3% to 15%)– noninferiority trial.

JAMA. 2010 Feb 24;303(8):739-46.

Antimicrobial Therapy• administration of broad-spectrum antibiotic therapy within 1

hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D);

• reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C);

• a usual 7–10 days of antibiotic therapy guided by clinical response (1D);

• source control with attention to the balance of risks and benefits of the chosen method (1C);

Survival Sepsis Guideline .Crit Care Med 2008

Empirical Antibiotic• Host

– Immunocompetent– Neutropenia– IVDU– Post Splenectomy– AIDS

• Risk factors & exposures• Site of infection

• Antibiotics of choice ??

Antibiotic therapy in patients with septic shock European Journal of Anaesthesiology (EJA). 28(5):318-324, May 2011

• every 10 min, survival is decreased by 1%.*

• First dose Full dose– Then renal adjustment

* Antibiotic therapy in patients with septic shock European Journal of Anaesthesiology (EJA). 28(5):318-324, May 2011

De-escalate Therapy

• De-escalate Empirical antimicrobial therapy in life-threatening situations– Start with Broad Spectrum

• ‘Broad-spectrum antibiotics’ refers to antibiotics with activity against Pseudomonas aeruginosa, including imipenem-cilastatin, piperacillin-tazobactam, ceftazidime or ciprofloxacin.

• Limited-spectrum antibiotics will only refer to β-lactam antibiotics without activity against P. aeruginosa (essentially, ceftriaxone and amoxicillin-clavulanate).

De-escalate Therapy : Life Threatening

• "สั่�,นัๆ แต่( aggressive" แลั�วปีร�บลังมา– Recurrent infections were more common in Group No

De-escalate (19% versus 5%, P = 0.01)– An inadequate empiric antibiotic therapy was more

frequent in Group No De-escalate (27.5% versus 7.7% P = 0.02)

– Mortality between the two groups 18.3% (D) vs 24.6% (ND)

Critical Care 2010, 14:R225

Steroids in CIRCI(critical illness related corticosteroid insufficiency)

•stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C)

•Survival Sepsis Guideline 2008

Serum cortisol•< 15 ug/dl definite adrenal insufficiency•13-35 ug/dl Suspected•>35 ug/dl no benefit

•สั่มาคำมเวช้บ�าบ�ด้ว�กฤต่�แห(งปีระเทศไทย

Steroids in CIRCI

Surge in cortisol (> 9 ug/dl) response to ACTH 250 ug stimulation

Benefit from steroids

JAMA. 2002 Aug 21;288(7):862-71

Baseline cortisol level < or = 35 microg/dl is a useful diagnostic threshold for diagnosis of steroid responsiveness in Thai patients with septic shock

ACTH stimulation test should not be used

sensitivity was 85%, the specificity was 62%

J Med Assoc Thai 2010 Jan;93 Suppl 1:S187-95

• Hydrocortisone 100 mg bolus then 200 mg V drip in 24 hr

• OR

• Hydrocortisone bolus q 4-6 hr NOT q 8 hr– e.g. Hydrocortisone 50 mg V q 6 hr

• Then taper off

Blood Sugar control

• NICE-SUGAR study– 3050 patients– Medicine & Surgery Ward– Multicenter randomized open label study– ICU & non ICU

– Intensive control 81-108 mg%– Conventional control 144-180 mg%

The NICE-SUGAR Study InvestigatorsN Engl J Med 2009; 360:1283-1297March 26, 2009

NICE-SUGAR Study

The NICE-SUGAR Study InvestigatorsN Engl J Med 2009; 360:1283-1297March 26, 2009

Sliding Scale Insulin

Basal Insulin with Scheduled Insulin (prandial insulin) with Correctional dose

• CBG (ก(อนัอาหาร) เช้�า กลัางว�นั เย1นั ก(อนันัอนั

Somchai Pathanaangkul ,Royal Thai Army Medical Journal Vol 57 No.4 Oct.-Dec. 2004

Blood Transfusion● Give red blood cells when hemoglobin decreases to 7.0 g/dL (70 g/L) to targe

t a hemoglobin of 7.0–9.0 g/dL in adults (1B). A higher hemoglobin level may be required in special circumstances (e.g., myocardial ischaemia, severe hypoxemia, acute hemorrhage, cyanotic heart disease, or lactic acidosis)

● Do not use erythropoietin to treat sepsis-related anemia. Erythropoietin may be used for other accepted reasons (1B) Do not use fresh frozen plasma to correct laboratory clotting abnormalities unless there is bleeding or planned invasive procedures (2D)

● Do not use antithrombin therapy (1B)Administer platelets when (2D) Counts are 5000/mm3 (5 109/L) regardless of bleeding

Counts are 5000–30,000/mm3 (5–30 109/L) and there is significant bleeding risk

Higher platelet counts (50,000/mm3 [50 109/L]) are required for surgery or invasive procedures

Blood Transfusion• TRICC Study

– Study design: Multicenter RCT– Setting: 25 ICUs across Canada– Hb

• 7-9 g/dl (Restrictive Strategy) • 10-12 g/dl (Liberal Strategy)

– Primary Outcome : mortality rate 30 days– Results

• Hb 7-9 g/dl group mortality rate 22.2%• Hb 10-12 g/dl mortality rate 28.1% • (P=0.05)

TRICC Study

Hb 7-9 g/dl

Hb 10-12 g/dl

Bicarbonate Therapy

• We recommend against the use of sodium bicarbonate therapy for the purpost of improving hemodynamics or reducing vasopressure requirement with hypoperfusion-induced lactic acidemia with pH > 7.15 (1B)

Hb O2 Dissociation curve

Stress Ulcer Prophylaxis

• We recommend that stress ulcer prophylaxis using H2 blocker (1A)

• Or PPI (1B) be given to patients with severe sepsis to prevent upper GI bleed.

• Weighted aginst the potential effect of an increased stomach pH on development of VAP

• Sucralfate*– Not associated with an increase in stress

ulceration.– Less impact gastric colonization Less VAP– Increase aspiration

• Enteral Feeding

*EAST Practice Management Guidelines Committee

Take home message

• Adequate preload• Antibiotic within 1 hr• Proper dose of vasopressors.

• Consult

Thank you

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