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Therapeutics |

Early goal-directed therapy reduced mortality and multiorgan dysfunction in severe sepsis or septic shock

Charles Natanson, MD; and Robert L. Danner, MD
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*See Glossary.

†Information provided by author.

Sources of funding: Henry Ford Health Systems Fund for Research; Weatherby Healthcare Resuscitation Fellowship; Edwards Lifesciences; Nova Biomedical.

For correspondence: Dr. E. Rivers, Henry Ford Hospital, Detroit, MI, USA. E-mail erivers1@hfhs.org.

Ann Intern Med. 2002;136(3):90. doi:10.7326/ACPJC-2002-136-3-090
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Question: In patients with severe sepsis or septic shock, does early goal-directed therapy (EGDT) before admission to the intensive-care unit (ICU) reduce mortality and multiorgan dysfunction?

Design: Randomized {allocation concealed*}†, blinded (clinicians),* controlled trial with 60-day follow-up.

Setting: Emergency department (ED) of a U.S. academic tertiary-care hospital.

Patients: 263 adults (mean age 66 y, 51% men) who met 2 of 4 criteria for the systemic inflammatory response syndrome (based on temperature, leukocyte count, tachycardia, and hyperventilation) and had systolic blood pressure ≤ 90 mm Hg (after crystalloid-fluid challenge of 20 to 30 mL/kg of body weight over 30 min) or a blood lactate level ≥ 4 mmol/L. Exclusion criteria included mostly the presence of such acute disorders as seizure, stroke, status asthmaticus, or burn. Follow-up was 100%.

Intervention: Patients were allocated to EGDT for ≥ 6 hours (n = 130) or to standard therapy in the ED (n = 133). All patients received a central venous catheter; however, patients in the EGDT group received a central venous catheter capable of continuously monitoring venous oxygen saturation (VOS). Both groups received a 500-mL bolus of crystalloid every 30 minutes to achieve a central venous pressure (CVP) of 8 to 12 mm Hg. Vasopressors were given if the mean arterial pressure (MAP) was < 65 mm Hg, and vasodilators were given if the MAP was > 90 mm Hg. In the EGDT group, if central VOS was < 70%, erythrocytes were transfused to achieve a hematocrit of ≥ 30%; if central VOS was still < 70%, dobutamine was given (2.5 µg/kg per min and titrated every 30 min up to 20 µg/kg per min unless the MAP was < 65 mm Hg or the heart rate was > 120 beats/min).

Main outcome measures: In-hospital death. Secondary outcomes included death and organ-dysfunction scores (24-point Multiple Organ Dysfunction score).

Main results: Analysis was by intention to treat. During the first 6 hours of treatment, both groups met the goals for CVP and MAP, although the control group received less fluid (mean 3.5 vs 5.0 L) and fewer blood transfusions (19% vs 64%). Later, in the ICU, the control group received more fluid, erythrocyte transfusions, vasopressors, mechanical ventilation, and pulmonary-artery catheterization. Fewer patients in the EGDT group than in the standard-therapy group died in the hospital (P = 0.009) or by 60 days (P = 0.03) (Table). Organ dysfunction scores were lower in the EGDT group than in the standard-therapy group (P < 0.001) (mean score difference 0.9, 95% CI 0.0 to 1.8 at 6 h; 1.3, CI 0.3 to 2.3 at 7 to 72 h).

Conclusions: In patients with severe sepsis or septic shock, early goal-directed therapy reduced mortality and organ dysfunction.

Early goal-directed therapy (EGDT) vs standard therapy for severe sepsis or septic shock‡

OutcomesEGDTStandard therapyRRR (95% CI)NNT (CI)
In-hospital mortality31%47%42% (13 to 62)6 (4 to 17)
Mortality at 60 d44%57%33% (4 to 54)6 (4 to 44)§

‡Abbreviations defined in Glossary; NNT and CI calculated from data in article.

§A correction was made at this point in the table. See Notices and Corrections for details.





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