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Fluid Resuscitation in Sepsis: A Systematic Review and Network Meta-Analysis


Clinical question: Is there any difference between different resuscitative fluids (crystalloids or colloids) on mortality in critically ill sepsis patients?

Background: Fluid resuscitation, in addition to antibiotics and source control, is a cornerstone of initial management of sepsis. Resuscitation with crystalloids compared with colloids for critically ill patients has been evaluated in large randomized controlled trials and meta-analyses; however, whether any of these fluid properties translates into a survival advantage, particularly regarding the optimal fluid for resuscitation in critically ill sepsis patients, remains unclear.

Study design: Systematic review, network meta-analysis (NMA).

Setting: Database search in MEDLINE, Embase, ACP Journal Club, Cumulative Index to Nursing and Allied Health Literature (CINAHL), HealthSTAR, the Allied and Complementary Medicine Database (AMED), and the Cochrane Central Register of Controlled Trials (CENTRAL).

Synopsis: Of 9,875 records that involved adult (age =16 years) critically ill patients with severe sepsis or septic shock who required fluid resuscitation, with no restrictions on language or publication date, 14 randomized controlled trials were considered eligible. Interventions studied included any fluid or fluid strategy used for resuscitation compared with another fluid or fluid strategy. The endpoint was 90-day mortality or, if not available, 30-day intensive care unit or hospital mortality, whichever was longest.

The analysis classified fluids as crystalloids or colloids. The relevant analyses were a four-node NMA (crystalloids versus albumin versus hydroxyethyl starch [HES] versus gelatin) and a six-node NMA (crystalloids versus albumin versus HES versus gelatin, with crystalloids divided into balanced or unbalanced and HES divided into low or high molecular weight), and a conventional fixed-effects meta-analytic comparison of crystalloids versus colloids.

In the four-node analysis, the results suggested higher mortality with starches (versus crystalloids) and lower mortality with albumin (versus crystalloids and starches). In the six-node analysis, the results suggested that albumin is superior to saline and low-molecular-weight starch and that balanced crystalloids are superior to saline and starch (both high and low molecular weight).

These results highlight potentially important differences in mortality among solutions; they suggest an advantage of balanced crystalloids versus saline and low- or high-molecular-weight starch, with similar mortality results for balanced crystalloids and albumin. These differences were not detectable using a standard meta-analytic approach directly comparing “any crystalloids versus any colloids.” Biological rationale is consistent with the findings of lower mortality with balanced crystalloid solutions than with saline as it mimics the homeostatic composition of body fluids to a greater extent than unbalanced fluids. These results raise concerns about using unbalanced crystalloids in the acute resuscitation of patients with sepsis.

Bottom line: Among patients with sepsis, resuscitation with balanced crystalloids or albumin is associated with reduced mortality compared to other fluids.

Citation: Rochwerg B, Alhazzani W, Sindi A, et al; Fluids in Sepsis and Septic Shock Group. Fluid resuscitation in sepsis: a systematic review and network meta-analysis. Ann Intern Med. 2014;161(5):347-355.

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