Fluid Overload and Mortality in Adult Critical Care Patients—A Systematic Review and Meta-Analysis of Observational Studies*

Abstract

Objective: Fluid administration in combination with the increase in vasopermeability induced by critical illness often results in significant fluid overload in critically ill patients. Recent research indicates that mortality is increased in patients who have received large volumes of fluids. We have systematically reviewed and synthesized the evidence on fluid overload and mortality in critically ill patients and have performed a meta-analysis of available data from observational studies. Data Sources: A systematic search was performed on PubMed, EmBase, and the Cochrane Library databases. Study Selection and Data Extraction: All studies were eligible that investigated the impact of fluid overload (defined by weight gain > 5%) or positive cumulative fluid balance on mortality in adult critical care patients. We excluded animal studies and trials in pediatric populations (age < 16 years old), pregnant women, noncritically ill patients, very specific subpopulations of critically ill patients, and on early goal-directed therapy. Randomized controlled trials were only evaluated in the section on systematic review. Assessment followed the Cochrane/meta-analysis of observational trials in epidemiology guidelines for systematic reviews. Data Synthesis: A total of 31 observational and three randomized controlled trials including 31,076 ICU patients met the inclusion criteria. Only observational studies were included in the meta-analysis. Fluid overload and cumulative fluid balance were both associated with pooled mortality: after 3 days of ICU stay, adjusted relative risk for fluid overload was 8.83 (95% CI, 4.03-19.33), and for cumulative fluid balance 2.15 (95% CI, 1.51-3.07), at any time point, adjusted relative risk for fluid overload was 2.79 (95% CI, 1.55-5.00) and 1.39 (95% CI, 1.15-1.69) for cumulative fluid balance.Fluid overload was associated with mortality in patients with both acute kidney injury (adjusted relative risk, 2.38; 95% CI, 1.75-2.98) and surgery (adjusted relative risk, 6.17; 95% CI, 4.81-7.97). Cumulative fluid balance was linked to mortality in patients with sepsis (adjusted relative risk, 1.66; 95% CI, 1.39-1.98), acute kidney injury (adjusted relative risk, 2.63; 95% CI, 1.30-5.30), and respiratory failure (adjusted relative risk, 1.19; 95% CI, 1.03-1.43). The risk of mortality increased by a factor of 1.19 (95% CI, 1.11-1.28) per liter increase in positive fluid balance. Conclusions: This systematic review and meta-analysis of observational studies reporting adjusted risk estimates suggests that fluid overload and positive cumulative fluid balance are associated with increased mortality in a general population and defined subgroups of critically ill patients.

COVID-19-associated acute respiratory distress syndrome (CARDS): Current knowledge on pathophysiology and ICU treatment – A narrative review

“…Fluid overload is a crucial contributor to ICU mortality in the critically ill [ 128 ], particularly in patients with respiratory failure/ARDS [ 129 , 130 ]. Two recently published trials imply that fluid restriction in patients with ARDS results in improved pulmonary function and less ventilator days [ 131 , 132 ].…”

“…Two recently published trials imply that fluid restriction in patients with ARDS results in improved pulmonary function and less ventilator days [ 131 , 132 ]. However, the impact on mortality currently remains unclear [ 128 ]. In patients with ARDS, fluid administration to increase tissue oxygenation must be carefully balanced against the potential impact on pulmonary edema and risk of impaired gas exchange [ 133 ].…”

Restrictive fluid management versus usual care in acute kidney injury (REVERSE-AKI): a pilot randomized controlled feasibility trial

“…10 Australian National University Medical School, Canberra, Australia. 11 Intensive Care Unit, Canberra Hospital, Canberra, Australia. 12 Critical Care and Preoperative Medicine Research Group, Centre for Translational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, London, UK.…”

“…While fluid therapy is the traditional cornerstone of AKI prevention and treatment [6], patients with AKI are also especially prone to develop fluid overload [7]. Such fluid overload is associated with increased mortality [7][8][9][10][11] and progression of AKI [12,13]. Thus, a more restrictive fluid management approach among adequately resuscitated patients with AKI might improve outcomes by reducing congestion and improving kidney and other organ function.…”

Efficacy and safety of early target-controlled plasma volume replacement with a balanced gelatine solution versus a balanced electrolyte solution in patients with severe sepsis/septic shock: study protocol, design, and rationale of a prospective, randomized, controlled, double-blind, multicentric, international clinical trial

“…Early initial plasma volume replacement is recommended in septic patients to maintain appropriate cardiac output and tissue oxygenation [ 6 , 7 ]. Plasma volume replacement should be target-controlled and individualized to minimize the risk of harmful fluid overload associated with worse outcomes [ 8 – 10 ]. Therefore, as recent data suggest, plasma volume replacement should be guided by flow-based parameters or passive leg raising (PLR), which are useful bedside tests for volume depletion and/or volume responsiveness [ 11 ].…”