Fluid overload, de-resuscitation, and outcomes in critically ill or injured patients: a systematic review with suggestions for clinical practice

Background: Sepsis is associated with generalised endothelial injury and capillary leak and has traditionally been treated with large volume fluid resuscitation. Some patients with sepsis will accumulate bodily fluids. The aim of this study was to systematically review the association between a positive fluid balance/fluid overload and outcomes in critically ill adults, and to determine whether interventions aimed at reducing fluid balance may be linked with improved outcomes. Methods: We searched MEDLINE, PubMed, EMBASE, Web of Science, The Cochrane Database, clinical trials registries, and bibliographies of included articles. Two authors independently reviewed citations and selected studies examining the association between fluid balance and outcomes or where the intervention was any strategy or protocol that attempted to obtain a negative or neutral cumulative fluid balance after the third day of intensive care compared to usual care. The primary outcomes of interest were the incidence of IAH and mortality. Results: Among all identified citations, one individual patient meta-analysis, 11 randomised controlled clinical trials, seven interventional studies, 24 observational studies, and four case series met the inclusion criteria. Altogether, 19,902 critically ill patients were studied. The cumulative fluid balance after one week of ICU stay was 4.4 L more positive in non-survivors compared to survivors. A restrictive fluid management strategy resulted in a less positive cumulative fluid balance of 5.6 L compared to controls after one week of ICU stay. A restrictive fluid management was associated with a lower mortality compared to patients treated with a more liberal fluid management strategy (24.7% vs 33.2%; OR, 0.42; 95% CI 0.32-0.55; P < 0.0001). Patients with intra-abdominal hypertension (IAH) had a more positive cumulative fluid balance of 3.4 L after one week of ICU stay. Interventions to decrease fluid balance resulted in a decrease in intra-abdominal pressure (IAP): an average total body fluid removal of 4.9 L resulted in a drop in IAP from 19.3 +/- 9.1 mm Hg to 11.5 +/- 3.9 mm Hg. Conclusions: A positive cumulative fluid balance is associated with IAH and worse outcomes. Interventions to limit the development of a positive cumulative fluid balance are associated with improved outcomes. In patients not transgressing spontaneously from the Ebb to Flow phases of shock, late conservative fluid management and late goal directed fluid removal (de-resuscitation) should be considered.