Fluid resuscitation in sepsis: a systematic review and network meta-analysis

Ann Intern Med. 2014 Sep 2;161(5):347-55. doi: 10.7326/M14-0178.


Background: Fluid resuscitation is the cornerstone of sepsis treatment. However, whether balanced or unbalanced crystalloids or natural or synthetic colloids confer a survival advantage is unclear.

Purpose: To examine the effect of different resuscitative fluids on mortality in patients with sepsis.

Data sources: MEDLINE, EMBASE, ACP Journal Club, CINAHL, HealthSTAR, the Allied and Complementary Medicine Database, and the Cochrane Central Register of Controlled Trials through March 2014.

Study selection: Randomized trials that evaluated different resuscitative fluids in adult patients with sepsis or septic shock and death. No language restrictions were applied.

Data extraction: Two reviewers extracted data on study characteristics, methods, and outcomes. Risk of bias for individual studies and quality of evidence were assessed.

Data synthesis: 14 studies (18916 patients) were included with 15 direct comparisons. Network meta-analysis at the 4-node level showed higher mortality with starches than with crystalloids (high confidence) and lower mortality with albumin than with crystalloids (moderate confidence) or starches (moderate confidence). Network meta-analysis at the 6-node level showed lower mortality with albumin than with saline (moderate confidence) and low-molecular-weight starch (low confidence) and with balanced crystalloids than with saline (low confidence) and low- and high-molecular-weight starches (moderate confidence).

Limitations: These trials were heterogeneous in case mix, fluids evaluated, duration of fluid exposure, and risk of bias. Imprecise estimates for several comparisons in this network meta-analysis contribute to low confidence in most estimates of effect.

Conclusion: Among patients with sepsis, resuscitation with balanced crystalloids or albumin compared with other fluids seems to be associated with reduced mortality.

Primary funding source: The Hamilton Chapter of the Canadian Intensive Care Foundation and the Critical Care Medicine Residency Program and Critical Care Division Alternate Funding Plan at McMaster University.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Albumins / therapeutic use
  • Colloids / therapeutic use*
  • Crystalloid Solutions
  • Fluid Therapy*
  • Gelatin / therapeutic use
  • Humans
  • Hydroxyethyl Starch Derivatives / therapeutic use
  • Isotonic Solutions / therapeutic use*
  • Molecular Weight
  • Rehydration Solutions / chemistry
  • Rehydration Solutions / therapeutic use*
  • Saline Solution, Hypertonic / therapeutic use
  • Sepsis / therapy*
  • Shock, Septic / therapy


  • Albumins
  • Colloids
  • Crystalloid Solutions
  • Hydroxyethyl Starch Derivatives
  • Isotonic Solutions
  • Rehydration Solutions
  • Saline Solution, Hypertonic
  • Gelatin