Early goal directed therapy reduces sepsis mortality

							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  65 mmHg, and urine output  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  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 g.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
              In-hospital     0.444 0.292      34%           0.152         7
Mortality
                95% Confidence Intervals: 8% to 60% 0.037 to 0.267 4 to 27
                60-day        0.526 0.385      27%           0.141         8
Mortality
                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