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Early goal directed therapy reduces sepsis mortality.

 

For every 7 patients with severe sepsis or septic shock treated with early goal-directed therapy, compared to conventional therapy, one less patient dies in hospital (95% CI 4 – 27).

 Level 1+ evidence

 

Citation/s: Early goal-directed therapy in the treatment of severe sepsis and septic shock. NEJM 2001;345:1368-77.
 

Lead author's name and fax: E Rivers, Department of Emergency Medicine, Case Western Reserve University, Detroit. erivers1@hfhs.org

 

Three-part Clinical Question:
 

Search Terms: 1. exp sepsis/ or severe sep$.tw or sept$.tw or sepsi$.tw (50301), 2. exp critical care/ or critical ca$.tw or intensive ca$.tw (22553), 3. exp oximetry/ or goal$.tw or hemodyn$.tw  (52901), 4. 1 and 2 and 3 (259), 5. therapy filter (652119), 6. 4 and 5 (147)

 

The Study: Non-blinded concealed randomised controlled trial with intention-to-treat.
 

The Study Patients: Patients presenting to US A+E department with sepsis, severe sepsis or septic shock. Included if 2 of 4 criteria for SIRS and SBP £ 90 mmHg (after 30 ml.kg-1 crystalloid fluid challenge) or lactate > 4 mmol.l-1. Excluded: < 18 y, pregnant, CVA, acute coronary syndrome, acute pulmonary oedema, status asthmaticus, pneumothorax, CI to CVP, gi bleed, seizure, burns, urgent surgery required, uncured cancer, advance directive, or DNR order.
 

Control group (N = 133; 133 analysed): Standard haemodynamic therapy to achieve CVP 8 - 12 mmHg, MAP ³ 65 mmHg, and urine output ³ 0.5 ml.kg-1.  Methods used to achieve this were at the clinician’s discretion, with critical-care consultation. Patients were admitted for inpatient care as soon as possible. Once transferred from A+E decisions were left to receiving team.
 

Experimental group (N = 130; 130 analysed): CVP line measured mixed venous oxygen saturation. Same targets as above, PLUS Svo2 ³ 70%. If after achievement of CVP, MAP and urine targets Svo2 remained < 70%: haematocrit was raised to 30% (= 100g.l-1) with red cell transfusion.   If Svo2 remained < 70%, dobutamine titrated to maximum dose of 20 mg.kg-1.min-1.    Dobutamine was decreased or discontinued if the MAP was <65mmHg or HR >120bpm.    To decrease oxygen consumption, patients in whom haemodynamic optimization could not be achieved were sedated, intubated and ventilated.

Patients remained in A&E receiving goal-directed therapy for at least six hours prior to being transferred to an inpatient bed. Once transferred treatment

decisions were left to the receiving team.

 

The Evidence:

Outcome

Time to Outcome

CER

EER

RRR

ARR

NNT

Mortality

In-hospital

0.444

0.292

34%

0.152

7

95% Confidence Intervals:

8% to 60%

0.037 to 0.267

4 to 27

Mortality

60-day

0.526

0.385

27%

0.141

8

95% Confidence Intervals:

4% to 49%

0.022 to 0.260

4 to 46

 

Comments:

1.        In each group 76% of patient culture positive. Pneumonia and urosepsis most common causes of sepsis.

2.        Control group had less fluid in emergency room, but more fluid in ICU.

3.        Greater mortality in control group from sudden cardiovascular collapse, no difference in death from multiple organ failure.

4.        This study is about cardiovascular support / resuscitation -what about timing of anti-biotic therapy?

Appraised by: Malcolm Daniel, Department of Anaesthesia, Glasgow Royal Infirmary; Wednesday, October 02, 2002     Email: md23s@udcf.gla.ac.uk

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