SIRS

Dr. Jonathan R. GoodallM62 Coloproctology Course31st March 2006

SIRS

SIRS Definitions Recognising the patient with SIRS Management of the patient with

SIRS Activated Protein C Use of Steroids Glucose Control

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Definitions

Systemic Inflammatory Response Syndrome (SIRS)

Severe Sepsis Septic Shock Refractory Shock

Definitions

SIRS: 2 or more of:Temperature > 38°C or < 36°CHeart rate > 90 bpmResp rate > 20 breaths.min -1 or

PaCO2 < 4.3kPa (32mmg)WBCs > 12 or < 4 (or >10%

immature forms)

Definitions

Sepsis = SIRS with documented infection site

Severe Sepsis Sepsis + organ dysfunction,

hypoperfusion or hypotension Septic Shock

Severe sepsis (SBP < 90mmHg) despite adequate fluid resuscitation

Crit Care Med 2004 Vol. 32 No 3

Experts from 11 international organisations (2003)

Management guidelines that would be of practical use for the bedside clinician

International effort to increase awareness & improve outcome…

Dellinger et al, Crit Care Med 2004 Vol 32, No 3

Key Recommendations

Recommendations on groups of treatments

Total consensus reached on all but two of recommendations

Most of recommendations are not supported by ‘high-level’ evidence

Dellinger et al, Crit Care Med 2004 Vol 32, No 3

A. Initial Resuscitation

Resuscitation should begin as soon as condition is recognised

In first 6 hours should include all of the following: CVP 8-12mmHg MAP > 65mmHg UO > 0.5ml.kg-1.hr-1

CvO2 > 70%

Grade B: Early Goal Directed Therapy in the Treatment of Severe Sepsis. Rivers et al NEJM 2001; 345:1368-77

Dellinger et al, Crit Care Med 2004 Vol 32, No 3

B. Diagnosis

Appropriate cultures should always be obtained before antimicrobial therapy At least 2 blood cultures One from each IV device >48 hours old Other cultures as appropriate

Grade D/E

Dellinger et al, Crit Care Med 2004 Vol 32, No 3

C. Antibiotic Therapy

Appropriate antimicrobial therapy should be started within 1 hour of onset Grade E

Initial empirical therapy Grade D

Focussed after 48-72 hours ? Monotherapy 7-10 day course Grade E

Stop if non-infective cause found Grade E

Dellinger et al, Crit Care Med 2004 Vol 32, No 3

D. Source control

Evaluate all patients for the presence of a focus of infection amenable to ‘source control measures’ (SCM) (Grade E)

Method of SCM must weigh benefits & risks (Grade E)

Once a source of infection identified, SCM should be instituted as soon as possible (Grade E)

IV access devices should be removed promptly (Grade E)

Dellinger et al, Crit Care Med 2004 Vol 32, No 3

E. Fluid Therapy

Fluid resuscitation may consist of natural or artificial colloids or crystalloids. There is no evidence-based support for one type of fluid over another.

Rates: 500-1000ml crystalloids over 30 mins 300-500ml colloids over 30 minsGrade C

Dellinger et al, Crit Care Med 2004 Vol 32, No 3

F & G Vasopressors & Inotropes

Use when appropriate fluid resuscitation fails to restore adequate MAP

Noradrenaline or dopamine ± dobutamine (Grade D)

Low-dose (renal) dopamine should not be used. (Grade B) Bellomo et al Lancet 2000: 356:2139-2143

Dellinger et al, Crit Care Med 2004 Vol 32, No 3

H. Steroids

IV hydrocortisone (200-300mg/day) should be used for 7 days in patients requiring vasopressor therapy (Grade C)

> 300mg/day should not be used Steroids should not be for the

treatment of sepsis in the absence of shock (Grade E)

Dellinger et al, Crit Care Med 2004 Vol 32, No 3

I. Activated Protein C

Recommended in patients at high risk of death without contraindications (Grade B) Bernard GR

et al, N Engl J Med 2001;344:699-709

Dellinger et al, Crit Care Med 2004 Vol 32, No 3

Activated Protein C - properties

Anticoagulant Degrades factor Va & VIIIa thereby

inhibiting generation of thrombin Pro-fibrinolytic

Promoted fibrinolysis by inhibiting plasminogen activator inhibitor

Anti-inflammatory Direct effects on endothelium and

neutrophils

PROWESS Study Group

1690 patients with sepsis enrolled Mortality rate 30.8% in placebo

group vs 24.7% in APC group Relative risk of death reduction

19%; absolute risk reduction 6% (P=0.005)

Increased incidence serious bleeding (3.5 vs 2 %)

Bernard GR et al, N Engl J Med 2001;344:699-709

M. Glucose Control

Following initial stablisation maintain blood glucose < 8.3 mmol/l (Grade B) Intensive Insulin Therapy in Critically Ill Patients. van den Berghe et al N Engl J Med 2001;345:1359

Dellinger et al, Crit Care Med 2004 Vol 32, No 3

Intensive Insulin Therapy

1548 patients admitted to ICU Intensive Treatment Group

Insulin started if glucose > 6.1 mmol.l-1

Glucose controlled 4.4 - 6.1 mmol.l-1

Conventional Treatment Group Insulin started if glucose > 12 mmol.l-1

Glucose controlled 10.0 – 11.1mmol.l-1

van den Berghe NEJM 2001;345:1359

Intensive Insulin Therapy

Mortality Rates Treatment Group 4.6% Conventional Group 8.0%

Unbiased risk reduction 32% Also reduced incidence of

complications (eg septicaemia, acute renal failure)

van den Berghe NEJM 2001;345:1359

M. Glucose Control

…There is no reason to think these data are not generalisable to all severely septic patients…

Intensive Insulin Therapy in the Medical ICU. van den Berghe et al N Eng J Med 2006; 354: 449-461

Dellinger et al, Crit Care Med 2004 Vol 32, No 3

P. DVT Prophylaxis

Use unfractionated or LMW heparin For patients with contraindication to

heparin, use of a mechanical prophylactic device is recommended

In very high risk patients, use both pharmacological and mechanical prophylaxis

Grade ADellinger et al, Crit Care Med 2004 Vol 32, No 3

Q. Stress Ulcer Prophylaxis

H2 receptor antagonsists are more efficacious than sucralfate and are the preferred agents

Proton pump inhibitors have not been assessed in a direct comparison to H2 receptor antagonsists, and their relative efficacy is not known.

Grade A

Dellinger et al, Crit Care Med 2004 Vol 32, No 3

Summary

SIRS is very common SIRS is a difficult problem

It is a complex disease It is not easy to recognise

Steroids probably useful APC is useful Tight glucose control is useful (in

surgical patients)

www.survivingsepsis.org