Grade B Recommendation
Early goal directed resuscitation for the treatment of severe sepsis and septic shock.
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Author info
Posted By: Gordon S. Doig and Brent Richards
Posted Date: 2 July 2003
Title: Early goal directed resuscitation for the treatment of severe sepsis and septic shock.
PubMed Resource Link: Click here to repeat the Medline search used to develop this EBR.
Evidence-based Recommendation
Best level of evidence
Well conducted Level II RCT
Target Population
Patients presenting to the Emergency Department with:
1) At least 2 of the 4 criteria for the Systemic Inflammatory Response Syndrome
  • Temperature greater than or equal to 38C or less than 36C
  • Heart rate greater than 90bpm
  • Respiratory rate greater than 20 or PaCO2 less than 32mm Hg
  • White blood cell count greater than 12 x 109/L or less than 4 x 109/L or the presence of more than 10 percent bands and
    2) systolic blood pressure < 90mmHg after a crystalloid fluid challenge of 20 to 30 ml per kg over a 30 minute period or
    a blood lactate concentration of 4 mmol per litre or more.
  • Purpose
    To reduce:
  • hospital discharge mortality by 15.1% (NNT 6.6, p=0.009)
  • 28 day mortality by 15.1% (NNT 6.6, p=0.01) and
  • 60 day mortality 14.2% (NNT 7.0, p=0.03).
  • Exclusion criteria
    Patients who may not be appropriate for early resuscitation include those with:
  • age < 18yo (due to applicability of hemodynamic parameters, goals and drug doses)
  • an acute cerebral vascular event
  • acute coronary syndrome
  • acute pulmonary oedema
  • status asthmaticus
  • cardiac dysrhythmias (as a primary diagnosis)
  • contraindication to central venous catheter
  • active GI hemorrhage
  • seizure
  • burn injury
  • trauma or other requirement for immediate surgery
  • drug overdose,
  • uncured cancer, immunosuppression or DNR.
  • Recommendation
    1) Place central venous catheter capable of measuring central venous oxygen saturation.
    2) 500ml bolus of crystalloid every 30 minutes to achieve CVP of 8 to 12 mmHg.
    3) Vasopressors as required, to maintain MAP > 65 mmHg.
    4) Vasodilators as required, to maintain MAP < 90 mmHg.
    5) If central venous oxygen saturation < 70 percent, transfuse red cells to achieve hematocrit of at least 0.30.
    If the CVP, MAP and hematocrit are optimized (see 2,3,4,5 above) then:
    6) If central venous oxygen saturation < 70 percent, adminster dobutamine at 2.5 mcg/kg/min, increasing the dose by 2.5 mcg/kg/min every 30 minutes until central venous oxygen saturation > 70 percent or until a maximum dose of 20 mcg/kg/min is reached.
  • Dobutamine should be discontinued if the MAP < 65 mmHg or if the heart rate > 120 bpm.
    7) To decrease oxygen consumption, patients in whom hemodynamic optimization cannot be achieved should be mechanically ventilated and sedated.
  • Potential harm
    Development Information
    Date EBR last updated
    July 3, 2003
    Literature source and search terms
    Pubmed was searched from 1966 to July 2, 2003 using a modified high specificity Therapy Clinical Query. The search terms used were:
    (fluid therapy sepsis) AND ((blind* [WORD]) OR placebo [WORD])
    This search yielded 6 results.

    The high specificity Therapy Clinical Query search uses the terms 'double AND blind* OR placebo'. Many trials that use multiple levels of blinding are precluded from the high specificity search due to its requirement for the term 'double'. When a high specificity search does not return any useful articles, we have found that the yield can often be improved simply by deleting the term 'double' from the search box of PubMed.

    Study selection
    Papers evaluating early hemodynamic treatment of sepsis and reporting clinically meaningful outcomes were selected.
    One level I paper was retrieved and reviewed.
  • Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77.

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    Page last modified on June 6, 2002