Relative Survival Benefit and Morbidity with Fluids in Severe Sepsis - A Network Meta-Analysis of Alternative Therapies

BACKGROUND: Fluid resuscitation is widely practiced in intensive care units for the treatment of sepsis. A comparison of the evidence base of different fluids may inform therapeutic choice. METHODS: The risks of mortality and morbidity (the need for renal replacement therapies (RRT)) were assessed in patients with severe sepsis. A network meta-analysis compared trials for crystalloids, albumin and hydroxyethyl starch (HES). A literature search of human randomized clinical trials was conducted in databases, the bibliographies of other recent relevant systematic reviews and data reported at recent conferences. Mortality outcomes and RRT data with the longest follow up period were compared. A Bayesian network meta-analysis assessed the risk of mortality and a pair-wise meta-analysis assessed RRT using crystalloids as the reference treatment. RESULTS: 13 studies were identified. A fixed-effects meta-analysis of mortality data in the trials demonstrated an odds-ratio (OR) of 0.90 between crystalloids and albumin, 1.25 between crystalloids and HES and 1.40 between albumin and HES. The probability that albumin is associated with the highest survival was 96.4% followed by crystalloid at 3.6%, with a negligible probability for HES. Sub-group analyses demonstrated the robustness of this result to variations in fluid composition, study source and origin of septic shock. A random-effects pairwise comparison for the risk of RRT provided an OR of 1.52 favoring crystalloid over HES. CONCLUSION: Fluid therapy with albumin was associated with the highest survival benefit. The higher morbidity with HES may affect mortality and requires consideration by prescribers.