Abstract
BackgroundIntravenous crystalloid solutions are administered commonly for critically ill patients. We performed this meta-analysis of randomized trials with trial sequential analysis (TSA) to evaluate effects of chloride content of intravenous crystalloid solutions on clinical outcomes among critically ill adult patients.MethodsElectronic databases were searched up to June 1, 2018, for randomized trials of use of balanced crystalloids versus 0.9% saline solutions in critically ill adult patients. The outcome variables included mortality, renal outcomes, serum content alterations and organ function. Subgroup analysis was conducted according to patient settings, types or volume of crystalloid fluid, or among sepsis versus non-sepsis, TBI versus non-TBI or subpopulations by the categories of baseline kidney function. Random errors were evaluated by trial sequential analysis.ResultsEight studies with 19,301 patients were analyzed. A trend of in-hospital survival benefit with no statistical difference could be observed with balanced crystalloids compared with 0.9% saline (RR 0.92, 95% CI 0.85–1.0, p = 0.06). The use of balanced crystalloid solutions was associated with longer RRT-free days (SMD 0.09, 95% CI 0.06–0.12, p < 0.001), less risk of increase in serum concentrations of chloride (SMD − 1.23, 95% CI − 1.59 to − 0.87, p < 0.001) and sodium (SMD − 1.28, 95% CI − 1.65 to − 0.92, p < 0.001), less risk of decline in serum base deficit (SMD − 0.58, 95% CI − 0.98 to − 0.18, p = 0.004), longer ventilator-free days (SMD 0.08, 95% CI 0.05–0.11, p < 0.001) and vasopressor-free days (SMD 0.04, 95% CI 0.00–0.07, p = 0.02). Subgroup analysis showed that balanced crystalloid solutions were associated with a reduced in-hospital mortality rate among septic patients (RR 0.86, 95% CI 0.75–0.98; p = 0.02) and non-traumatic brain injury patients (RR 0.90, 95% CI 0.82–0.99, p = 0.02), while the TSA results indicated a larger sample size is still in need.ConclusionsLimited evidence supported statistical survival benefit with balanced crystalloid solutions, while it benefited in reducing organ support duration and fluctuations in serum electrolyte and base excess and was associated with decreased in-hospital mortality in subpopulation with sepsis and non-TBI. Large-scale rigorous randomized trials with better designs are needed to provide robust evidence for clinical management.Trial registration The protocol for this meta-analysis was registered on PROSPERO: International prospective register of systematic reviews (CRD42018102661), https://www.crd.york.ac.uk/prospero/#recordDetails
Highlights
Intravenous crystalloid solutions are administered commonly for critically ill patients
Data suggest that 0.9% saline can increase the risk of hyperchloremic metabolic acidosis and related complications, such as acute kidney injury: One before and after prospective trial has shown the beneficial effects of chloride-restrictive intravenous fluid in the improvement of preventing acute kidney injury (AKI) and decreasing use of renal replacement therapy (RRT) in critically ill patients [6]
Inconsistent with the before and after treatment study in which balanced crystalloid solutions administration was associated with decreasing the incidence of AKI and RRT use [7], our meta-analysis showed no difference between balanced crystalloid and 0.9% saline fluid groups regarding development of stage 2 or higher AKI and new RRT use
Summary
Intravenous crystalloid solutions are administered commonly for critically ill patients. Crystalloid solutions as the fluid of choice for initial resuscitation and subsequent intravascular volume replacement in patients with sepsis and septic shock were recommended in guidelines for management of sepsis and septic shock published in 2016 [1]. Resuscitation with large volumes of crystalloid solutions with non-physiological content may lead to electrolyte disturbance and hyperchloremic metabolic acidosis which could result in severe renal, cardiac or hepatic disease. Data suggest that 0.9% saline can increase the risk of hyperchloremic metabolic acidosis and related complications, such as acute kidney injury: One before and after prospective trial has shown the beneficial effects of chloride-restrictive intravenous fluid in the improvement of preventing acute kidney injury (AKI) and decreasing use of renal replacement therapy (RRT) in critically ill patients [6]. 2016 Surviving Sepsis Campaign (SSC) guidelines could not provide recommendations for the use between normal saline of supraphysiological chloride content and balanced salt solution of low chloride content with indirect low-quality evidence from observational or retrospective studies [1, 8, 9]
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