surviving sepsis campaign- 2012 to 2016

SURVIVING SEPSIS CAMPAIGN

OUTLINE

• Introduction• Definitions– SIRS– Sepsis– Severe sepsis– Septic shock

• Pathophysiology • Protocols for treatment• SURVIVING SEPSIS CAMPAIGN

INTRODUCTION• Major cause of morbidity and mortality worldwide.

• Leading cause of death in noncoronary ICU.• 11th leading cause of death overall.

• Mortality– Sepsis: 30% - 50%– Septic Shock: 50% - 60%

• For every hour delay in the administration of treatment, there is an associated 6% rise in mortality.

SIRS

• Widespread inflammatory response to a variety of severe clinical insults.

• Clinically recognized by the presence of 2 or more of the following:– Temperature >38C or < 36C– Heart Rate >90– Respiratory Rate > 20 or PaCO2 <32– WBC > 12,000, < 4000 or > 10% immature forms

Stages In the Development of SIRS (Bone, 1996)

• Stage 1. In response to injury / infection, the local environment produces cytokines.

• Stage 2. Small amounts of cytokines are released into the circulation:• Recruitment of inflammatory cells.• Acute Phase Response.• Normally kept in check by endogenous anti-inflammatory

mediators (IL-10, PGE2, Antibodies, Cytokine receptor antagonists).

Stages In the Development of SIRS

• Stage 3. Failure to control inflammatory cascade:• Loss of capillary integrity.• Stimulation of Nitric Oxide Production.• Maldistribution of microvascular blood flow.

• Organ injury and dysfunction.

SEPSIS

• SIRS criteria + evidence of infection, or:– White cells in normally sterile body fluid– Perforated viscus– Radiographic evidence of pneumonia– Syndrome associated with a high risk of infection

SEVERE SEPSIS• Sepsis criteria + evidence of organ dysfunction or tissue hypoperfusion, including:

– CV: Systolic BP < 90 mmHg, MAP < 70 mm Hg for at least 1 hour despite volume resuscitation, or the use of vasopressors.

– Renal: Urine output < 0.5 ml/kg body weight/hr for 1 hour despite volume resuscitation

– Pulmonary: PaO2/FiO2 < 250 in absence of pneumonia as infection source or < 200 in presence of pneumonia as infection source.

– Hematologic: Platelet count < 1L or decreased by 50% in 3 days

– Metabolic: pH < 7.3 and plasma lactate > upper normal

– INR > 1.5, S. Bil > 2 mg/dl, S. Creat >2 mg/dl

SEPTIC SHOCK

• Septic Shock– Hypotension secondary to Sepsis that is resistant to

adequate fluid administration.

PATHOPHYSIOLOGY

Pathophysiology of Sepsis-Induced Organ Injury

• Multiple Organ Dysfunction (MODS) and Multiple Organ Failure (MOF) result from diffuse cell injury / death resulting in compromised organ function.

• Mechanisms of cell injury / death:• Cellular Necrosis (ischemic injury).• Apoptosis.• Leukocyte-mediated tissue injury.• Cytopathic Hypoxia

Pathophysiology of Sepsis-Induced Ischemic Organ Injury

• Cytokine production leads to massive production of endogenous vasodilators.

• Structural changes in the endothelium result in extravasation of intravascular fluid into interstitium and subsequent tissue edema.

• Plugging of select microvascular beds with neutrophils, fibrin aggregates, and microthrombi impair microvascular perfusion.

• Organ-specific vasoconstriction.

Pathogenesis of Vasodilation in Sepsis

• Loss of Sympathetic Responsiveness:• Down-regulation of adrenergic receptor number and

sensitivity, possible altered signal transduction.

• Vasodilatory Inflammatory Mediators.

• Endotoxin has direct vasodilatory effects.

• Increased Nitric Oxide Production.

Infection

InflammatoryMediators

Endothelial DysfunctionVasodilation

Hypotension Vasoconstriction Edema

Maldistribution of Microvascular Blood Flow

Organ Dysfunction

Microvascular Plugging

Ischemia

Cell Death

MANAGEMENT

PIRO staging for sepsis

• Aims to describe the sepsis considering the relationship amongst premorbid factors, infection insult & host response and how it impacts on development of organ dysfuction & prognosis of septic patients

SEPSIS SIX• The Sepsis Six is the name given to a bundle of medical

therapies designed to reduce the mortality of patients with sepsis.

• The Sepsis Six consists of three diagnostic and three therapeutic steps – all to be delivered within one hour of the initial diagnosis of sepsis.– Deliver high-flow oxygen.– Take blood cultures.– Administer empiric intravenous antibiotics.– Measure serum lactate and send full blood count.– Start intravenous fluid resuscitation.– Commence accurate urine output measurement.

Daniels et al. The sepsis six and the severe sepsis resuscitation bundle: a prospective observational cohort study. Emerg Med J (2011) vol. 28 (6) pp. 507-12

• The Surviving Sepsis Campaign (SSC) - global initiative to bring together professional organizations in reducing mortality from sepsis.

• The Surviving Sepsis Campaign and the Institute for Healthcare Improvement teamed up to achieve a 25 percent reduction in sepsis mortality by 2009.

History of the guideline

• 2004– The initial SSC guidelines incorporated the evidence

available through the end of 2003• 2008– Publication analyzed evidence available through the

end of 2007• 2012– The most current iteration is based on updated

literature search incorporated into the evolving manuscript through fall 2012

Selection and Organization of Committee Members

• Appointed by the Society of Critical Care Medicine and European Society of Intensive Care Medicine

• Sepsis expertise• Four clinicians with experience in the GRADE

process application (referred as GRADE group or Evidence-Based Medicine [EBM] group)

GRADING

• Grading of Recommendations Assessment, Development and Evaluation (GRADE) system

• Quality of evidence– High (grade A)– Moderate (grade B)– Low (grade C)– Very low (grade D)

• Classification of recommendations– Strong (grade 1)– Weak (grade 2)

GRADING

• Strength of recommendation and quality of evidence assessed using GRADE criteria, presented in brackets after each guideline. For added clarity:

• Indicates a strong recommendation or “we recommend.”

o Indicates a weak recommendation or “we suggest.” UG means the evidence is ungraded

MANAGEMENT OF SEVERE SEPSIS

• Initial Resuscitation and Infection Issues • Hemodynamic Support and Adjunctive

Therapy • Supportive Therapy of Severe Sepsis

Initial Resuscitation and Infection Issues

WORLD SEPSIS DAY – 13 SEPTEMBER

Initial Resuscitation and Infection Issues

• A. Initial Resuscitation• B. Screening for Sepsis and Performance

Improvement• C. Diagnosis• D. Antimicrobial Therapy• E. Source Control• F. Infection Prevention

A. Initial Resuscitation• Resuscitation of patients with sepsis- induced tissue

hypoperfusion – defined as hypotension persisting after initial fluid challenge or

blood lactate concentration ≥ 4 mmol/L• 1.EGDT (first 6 hrs of resuscitation) – a) Central venous pressure (CVP) 8–12 mm Hg – b) Mean arterial pressure (MAP) ≥ 65 mm Hg – c) Urine output ≥ 0.5 mL/kg/hr – d) Scvo2 or Svo2 70% or 65%, respectively- 1C

2. If Elevated Lactate- target resuscitation to normalize lactate – 2C

How to Resuscitate

• Resuscitate with IVF to reduce lactate• Resuscitate early ( if <6h- mortality by 16%)• If Hypotension + Lactate – mortality 16%• if ScvO2 <70% / SvO2 <65% despite adequate

intravascular volume repletion with persisting tissue hypoperfusion- Dobutamine @ max 20 μg/kg/min OR PRBC- to achieve Hct >= 30%

How to Resuscitate

• Target CVP 12-25mm Hg – if known Ventricular compliance

• Don’t Use CVP guided IVF if known PAH

SEVERE SEPSIS INCIDENCE MORTALITY

Hypotension + Lactate >4mmol/l

16% 46

Hypotension Only 49% 36%

Only Lactate >4mmol/l 5.4% 30%

B. Screening for Sepsis and Performance Improvement

• Routine screening of seriously ill patients for severe sepsis to– increase the early identification of sepsis (1C)– allow implementation of early sepsis therapy

• Performance improvement efforts to improve patient outcomes and decrease sepsis-related mortality.

B. Screening for Sepsis and Performance Improvement*

• The SSC guidelines and bundles as the basis of a sepsis performance improvement program

• A bundle is a selected set of elements of care derived from evidence based practice guidelines– effect on outcomes beyond implementing the

individual elements alone.

SEVERE SEPSIS

SEPTIC SHOCK

2016- not mandatory if early recognition of sepsis & timely Abx given

How to Screen

• Use Sepsis screening tools

• Many tools eg. St. Joseph Mercy, Sepsis Surv Campaign etc

• Any can be used as per hospital requirements/equipment

C. Diagnosis• Cultures before antibiotic therapy

– Without causing significant delay

• At least 2 blood cultures (both aerobic and anaerobic)– percutaneous– drawn through each lumen of each vascular access device (if >48

hrs)

• Imaging studies in attempts to confirm a potential source of infection– Balancing risks & benefits

C. Diagnosiso Other Cultures if indicated- Urine, CSF, sputum etco Vol of blood sample > 10mlo Adjunct Methods- PCR, Mass Spectroscopy,

Microarrayso Procalcitonin & CRP – can’t differentiate b/w Sepsis &

other Inflammatory States (Not Recommended)o 1,3 β-d-glucan assay (2B), mannan and anti-mannan

antibody assays– If invasive candidiasis suspected

D. Antimicrobial Therapy

• Goal - Administration of effective i/v antibiotics within the first hour of recognition of septic shock (grade 1B) and severe sepsis (grade 1C).

• ? Premixed Abx Solutions• Abx Bolus vs Infusions• Initial empiric anti-infective therapy – one or more drugs – activity against all likely pathogens (bacterial and/or fungal

or viral) presumed to be the source of sepsis (grade 1B)


• Reassessed daily for potential de-escalation (grade 1B)– prevent the development of resistance– to reduce toxicity– to reduce costs

o Combination empiric therapy (>=2 classes of Abx)- o neutropenic patients with severe sepsis (grade 2B)o difficult-to-treat, multidrug-resistant bacterial

pathogens such as Acinetobacter and Pseudomonas spp.


o Extended spectrum beta-lactam + AGS/FQs for P. aeruginosa bacteremia

o Beta-lactam and macrolide for bacteremic Streptococcus pneumoniae infections

o Not for more than 3–5 dayso De-escalation to the most appropriate single

therapy as per susceptibility


o Duration of therapy 7–10 dayso Longer courses

o slow clinical responseo undrainable foci of infectiono bacteremia with S. aureuso some fungal and viral infections o immunologic deficiencies, including neutropenia

(grade 2C).


o Antiviral therapy – suspected to be viral origin (grade 2C).

• Should not be used in severe inflammatory states determined to be of non-infectious cause (UG)

How to Give Antibiotics

• Choice- based on – History– Previous Abx usage– Clinical Features– Community pathogenic susceptibility– Renal/ Hepatic function

• M/C Organisms- G+ > G- > Mixed

E. Source Control

• Specific anatomical diagnosis of infection requiring emergent source control- Imaging

• Intervention for source control within the first 12 hr of diagnosis.

• Source control with least physiological insult in severe sepsis.

E. Source Control

• Intravascular access suspected to be source of severe sepsis or septic shock – remove promptly after other vascular access has been established (UG).

• Surgical intervention done when minimally invasive approaches are inadequate / when diagnostic uncertainty persists despite imaging

F. Infection Preventiono Selective Oral decontamination(SOD)- 2% gentamicin, 2%

colstin, and 2% vancomycin paste has been shown to reduce VAP

o Oral CHG be used (2B)

o Selective digestive decontamination (SDD)-o oral cavity paste + GI tract solution, and IV antibiotics x 4 days. o Eliminates harmful bacteria & allows native flora to thrive. –

CONTOVERSIAL

HAEMODYNAMIC SUPPORT & ADJUNCTIVE THERAPY

HAEMODYNAMIC SUPPORT & ADJUNCTIVE THERAPY

• FLUID THERAPY

• VASOPRESSORS

• INOTROPIC SUPPORT

• CORTICOSTEROIDS

FLUID THERAPY

• Crystalloids* • Against the use of hydroxyethyl starcheso Albumin for fluid resuscitation when patients

require substantial amounts of crystalloids • Initial fluid challenge in patients with sepsis-

induced tissue hypoperfusion & suspected of hypovolemia @ 30 mL/kg of crystalloids (minimum)*

VASOPRESSORS

• Target a mean arterial pressure (MAP) of 65 mm Hg• Norepinephrine* as the first choice vasopressoro Epinephrine added when an additional agent is needed

to maintain adequate B.P.• Vasopressin 0.03 U/min added to NE for raising MAP or

decreasing NE dosage (UG)• Low dose vasopressin not recommended as the single

initial vasopressor for sepsis-induced hypotension (UG)• Vasopressin doses > 0.03-0.04 U/min reserved for

salvage therapy (UG)

VASOPRESSORS

• Dopamine as an alternative vasopressor agent to NE only in highly selected patients– with low risk of tachyarrhythmias – absolute or relative bradycardia

• Phenylephrine not recommended except when– NE associated with serious arrhythmias– cardiac output high and BP persistently low– as salvage therapy when combined

inotrope/vasopressor drugs and low dose vasopressin have failed to achieve MAP

VASOPRESSORS

• Low dose dopamine should not be used for renal protection

INOTROPIC THERAPY

• Trial of dobutamine infusion up to 20 mcg/kg/min be administered or added to vasopressor (if in use) (grade 1C)– myocardial dysfunction suggested by elevated

cardiac filling pressures and low cardiac output– ongoing signs of hypoperfusion, despite achieving

adequate intravascular volume and adequate MAP.

CORTICOSTEROID

o Not indicated if adequate fluid resuscitation and vasopressor therapy able to restore hemodynamic stability

o In case not achievable, iv hydrocortisone at a dose of 200 mg per day

• Corticosteroids not be administered for treatment of sepsis in the absence of shock

CORTICOSTEROID

o Not using the ACTH stimulation test to identify adults with septic shock who should receive hydrocortisone (grade 2B).

o In treated patients hydrocortisone tapered when vasopressors are no longer required

o Low-dose hydrocortisone to be given as continuous infusion rather than repetitive bolus injections

OTHER SUPPORTIVE THERAPY

OTHER SUPPORTIVE THERAPY• Blood products administration• Immunoglobulins*• Selenium*• Mechanical ventilation of sepsis induced ARDS• rhAPC*• Sedation, anaelgesia & neuromuscular blockade• Glucose control• Renal replacement therapy• Bicarbonate therapy• DVT prophylaxis• Stress ulcer prophylaxis• Nutrition*• Setting goals of care

BLOOD PRODUCT ADMINISTRATION

• PRBC transfusion only when Hb <7.0 g/dl– Target Hb of 7.0 –9.0 g/dl

• EPO not be used as specific treatment of anemia associated with severe sepsis

o FFP not be used to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures

• Not using antithrombin for the treatment of severe sepsis and septic shock

BLOOD PRODUCT ADMINISTRATION

o Platelet transfusion– <10,000/mm3 in the absence of apparent

bleeding*– < 20,000/mm3 if the patient has a significant risk

of bleeding– Higher platelet counts (≥50,000/mm3) advised for

active bleeding, surgery, or invasive procedures

IMMUNOGLOBULINS*

SELENIUM*

MECHANICAL VENTILATION OF SEPSIS INDUCED ARDS

• Target tidal volume of 6 mL/kg predicted body weight in patients with sepsis-induced ARDS

• Positive end-expiratory pressure (PEEP) be applied to avoid alveolar collapse at end expiration

• Mechanically ventilated sepsis patients be maintained with the head end elevation of 30-45o

– limit aspiration risk – prevent the development of VAP


• Weaning protocol to be in place• Spontaneous breathing trials regularly to evaluate the

ability to discontinue mechanical ventilation if– arousable– hemodynamically stable (without vasopressor agents)– no new potentially serious conditions– low ventilatory and end-expiratory pressure requirements– low Fio2 requirements which can be met safely delivered with a

face mask or nasal cannula. • If the spontaneous breathing trial is successful,

consideration should be given for extubation


• Beta 2-agonists not be used for sepsis-induced ARDS, in absence of bronchospasm

• Pulmonary artery catheter not to be used routinely for patients with sepsis-induced ARDS

• Conservative fluid strategy for patients with established sepsis-induced ARDS without evidence of tissue hypoperfusion

rhAPC (drotecogin alpha)*

• PROWESS trial (2001)– Included in 2004 SSC

• Downgraded to suggestion in 2008 SSC• PROWESS SHOCK trial (2011)– No benefit– Drug withdrawn from market– No recommendation in SSC 2012

SEDATION, ANAELGESIA & NEUROMUSCULAR BLOCKADE

• Continuous or intermittent sedation be minimized in mechanically ventilated sepsis patients– Morphine vs morphine + propofol/midazolam

• NMBAs avoided if possible in the septic patient without ARDS – risk of prolonged neuromuscular blockade following

discontinuation.– If required, either intermittent bolus or continuous

infusion with monitoring of the depth of blockade

GLUCOSE CONTROL

• Protocolised approach– Insulin when two consecutive blood glucose > 180

mg/dL– upper target blood glucose ≤180 mg/dL rather

than ≤ 110 mg/dL*• Blood glucose values every 1–2 hrs until

glucose values and insulin infusion rates stable and then every 4 hrs thereafter

RENAL REPLACEMENT THERAPY

o Continuous renal replacement therapies and intermittent hemodialysis equivalent in patients with severe sepsis and acute renal failure (grade 2B).

o Continuous therapies to facilitate management of fluid balance in hemodynamically unstable septic patients (grade 2D).

BICARBONATE THERAPY

o NaHCO3 therapy not useful for the purpose of improving hemodynamics or reducing vasopressor requirements in patients with hypoperfusion-induced lactic acidemia.

DVT PROPHYLAXIS

• VTE prophylaxis required using daily subcutaneous LMWH*

• If creatinine clearance <30 mL/min, use dalteparin or UFH

o Combination of pharmacologic therapy and intermittent pneumatic compression devices whenever possible

o C/I for heparin – use mechanical prophylaxis. Start pharmacological Rx when risk decreases.

STRESS ULCER PROPHYLAXIS

• Stress ulcer prophylaxis using H2 blocker or proton pump inhibitor in patients with GI bleeding risk factors– Coagulopathy– Mechanical ventilation for at least 48 hrs– Hypotension

o PPIs > H2RA*o Patients without risk factors do not receive

prophylaxis

NUTRITION*o Oral or enteral feeding, as tolerated, rather than

complete fasting or only i/v glucose within the first 48 hours after diagnosis of severe sepsis/septic shock

o Low dose feeding > full caloric feeding in the first week (upto 500 Calories/day, advancing as tolerated)

o Use i/v glucose + enteral nutrition rather than TPN alone or parenteral nutrition + enteral feeding in the first 7 days

• Nutrition without specific immunomodulating supplementation

SETTING GOALS OF CARE

• Discuss goals of care and prognosis with patients and families

• Goals of care to be incorporated into treatment and end-of-life care planning

CONCLUSION

• Optimum treatment of severe sepsis and septic shock is a dynamic and ever evolving process.

• SSC provides guidelines for evolving protocols at institution.

THANK YOU

surviving sepsis campaign- 2012 to 2016

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