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Cited by 10,743Sepsis Diagnosis and TreatmentHemodynamic Monitoring and TherapyAbdominal Surgery and Complications

Early goal-directed therapy in the treatment of severe sepsis and septic shock

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Rivers, Emanuel, Nguyen, Bryant, Havstad, Suzanne, Ressler, Julie, Muzzin, Alexandria, Knoblich, Bernhard, Peterson, Edward, Tomlanovich, Michael·2001·New England Journal of Medicine
DOI 10.1056/nejmoa010307
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Abstract

BACKGROUND: Goal-directed therapy has been used for severe sepsis and septic shock in the intensive care unit. This approach involves adjustments of cardiac preload, afterload, and contractility to balance oxygen delivery with oxygen demand. The purpose of this study was to evaluate the efficacy of early goal-directed therapy before admission to the intensive care unit. METHODS: We randomly assigned patients who arrived at an urban emergency department with severe sepsis or septic shock to receive either six hours of early goal-directed therapy or standard therapy (as a control) before admission to the intensive care unit. Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment. In-hospital mortality (the primary efficacy outcome), end points with respect to resuscitation, and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were obtained serially for 72 hours and compared between the study groups. RESULTS: Of the 263 enrolled patients, 130 were randomly assigned to early goal-directed therapy and 133 to standard therapy; there were no significant differences between the groups with respect to base-line characteristics. In-hospital mortality was 30.5 percent in the group assigned to early goal-directed therapy, as compared with 46.5 percent in the group assigned to standard therapy (P = 0.009). During the interval from 7 to 72 hours, the patients assigned to early goal-directed therapy had a significantly higher mean (+/-SD) central venous oxygen saturation (70.4+/-10.7 percent vs. 65.3+/-11.4 percent), a lower lactate concentration (3.0+/-4.4 vs. 3.9+/-4.4 mmol per liter), a lower base deficit (2.0+/-6.6 vs. 5.1+/-6.7 mmol per liter), and a higher pH (7.40+/-0.12 vs. 7.36+/-0.12) than the patients assigned to standard therapy (P < or = 0.02 for all comparisons). During the same period, mean APACHE II scores were significantly lower, indicating less severe organ dysfunction, in the patients assigned to early goal-directed therapy than in those assigned to standard therapy (13.0+/-6.3 vs. 15.9+/-6.4, P < 0.001). CONCLUSIONS: Early goal-directed therapy provides significant benefits with respect to outcome in patients with severe sepsis and septic shock.

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  • We identified direct evidence from 14 RCTs (n = 4,499 patients) that assessed use of procalcitonin to guide antimicrobial treatment duration in patients with sepsis.

    “We identified direct evidence from 14 RCTs (n = 4,499 patients) that assessed use of procalcitonin to guide antimicrobial treatment duration in patients with sepsis (two trials included critically ill patients in general) (308-321).”

    From Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. (2021) · cites this paper as [315]

    The Abstract and Base-Line Characteristics describe one trial of early goal-directed therapy versus standard therapy in 263 patients, not a trial of procalcitonin-guided antimicrobial duration. The paper therefore cannot serve as one of the cited procalcitonin trials; it also does not report evidence from 14 RCTs involving 4,499 patients. Page numbers were not available in our copy. (LLM, conf=0.88)

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  • Accurate screening for sepsis is crucial to identify patients at high risk of clinical deterioration so that preventive measures can be taken in a timely manner, which may reduce mortality.

    “Accurate screening for sepsis is crucial to identify patients at high risk of clinical deterioration so that preventive measures can be taken in a timely manner, which may reduce mortality.21”

    From Development and validation of a screening tool for sepsis without laboratory results in the emergency department: a machine learning study (2025) · cites this paper as [21]

    The Discussion (page unavailable) says early identification of patients at high risk of cardiovascular collapse enables early therapy, and the Abstract reports lower mortality with early goal-directed therapy. The trial enrolled patients who already had severe sepsis or septic shock; it did not assess the accuracy of sepsis screening or establish a mortality benefit from screening itself. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Early detection and appropriate treatment of sepsis are associated with a significant mortality benefit in hospitalized patients.

    “Early detection and appropriate treatment of sepsis have been associated with a significant mortality benefit in hospitalized patients.1,2,3”

    From External validation of a widely implemented proprietary sepsis prediction model in hospitalized patients (2021) · cites this paper as [1]

    The Mortality section reports significantly lower in-hospital mortality with early goal-directed therapy, and the Discussion links its benefits to early identification and intervention. The Eligibility section limits the trial to adults presenting to an emergency department with severe sepsis, septic shock, or sepsis syndrome; it does not establish a mortality benefit for hospitalized patients with sepsis generally or for early detection on its own. (LLM, conf=0.86)

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  • The four largest sepsis resuscitation trials administered moderate to large fluid volumes during the first 72 hours.

    “The four largest clinical trials in sepsis resuscitation used moderate to large amounts of fluids in the first 72 h.”

    From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [393]

  • In the Rivers trial, over 13 L of fluids were administered.

    “Although Rivers [393] administered over 13 L of fluids”

    From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [393]

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Cites

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Research works printed but not linked: 2

  1. [8]8. Elliott DC. An evaluation of the end points of resuscitation. J Am Coll Surg 1998;187:536-47.
  2. [17]17. Shoemaker WC. Goal-oriented hemodynamic therapy. N Engl J Med 1996;334:799-800.

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Authors
Rivers, E., Nguyen, B., Havstad, S., Ressler, J., Muzzin, A., Knoblich, B., Peterson, E., & Tomlanovich, M.
Affiliations
Henry Ford Health (US)
ORCID
Ressler, Julie
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2001-11-08
Volume
345
Issue
19
Pages
1368-1377
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa010307
OpenAlex
W2160691650
Cited by
10,743
References
39
Citations by year
2026: 154 · 2025: 196 · 2024: 231 · 2023: 247 · 2022: 241 · 2021: 325 · 2020: 335 · 2019: 439 · 2018: 417 · 2017: 452 · 2016: 559 · 2015: 573 · 2014: 642 · 2013: 609 · 2012: 586
FWCI
194.86
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
  • Health Sciences › Medicine › Surgery › Hemodynamic Monitoring and Therapy
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Abdominal Surgery and Complications
Keywords
early goal-directed therapy, severe sepsis, septic shock, emergency department, in-hospital mortality, fluid resuscitation, lactate, base deficit, central venous oxygen saturation, APACHE II score, organ dysfunction, intensive care unit admission, hypotension, hypoxemia, acidosis, hypothermia, hypoglycemia, hypokalemia
MeSH terms
Aged, Algorithms, Blood Pressure, Cardiovascular Agents, Emergency Service, Hospital, Female, Fluid Therapy, Health Resources, Hemodynamics, Hospitals, Urban, Humans, Male, Middle Aged, Monitoring, Physiologic, Oxygen, Prospective Studies, Shock, Septic, Single-Blind Method, Treatment Outcome, Hospital Mortality, Erythrocyte Transfusion, Systemic Inflammatory Response Syndrome, Sepsis, APACHE

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