Whether the use of balanced multielectrolyte solution (BMES) in preference to 0.9% sodium chloride solution (saline) in critically ill patients reduces the risk of acute kidney injury or death is uncertain. 

Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults

Intravenous fluids are recommended for the treatment of patients who are in septic shock, but higher fluid volumes have been associated with harm in patients who are in the intensive care unit (ICU).In this international, randomized trial, we assigned patients with septic shock in the ICU who had received at least 1 liter of intravenous fluid to receive restricted intravenous fluid or standard intravenous fluid therapy; patients were included if the onset of shock had been within 12 hours before screening. The primary outcome was death from any cause within 90 days after randomization.We enrolled 1554 patients; 770 were assigned to the restrictive-fluid group and 784 to the standard-fluid group. Primary outcome data were available for 1545 patients (99.4%). In the ICU, the restrictive-fluid group received a median of 1798 ml of intravenous fluid (interquartile range, 500 to 4366); the standard-fluid group received a median of 3811 ml (interquartile range, 1861 to 6762). At 90 days, death had occurred in 323 of 764 patients (42.3%) in the restrictive-fluid group, as compared with 329 of 781 patients (42.1%) in the standard-fluid group (adjusted absolute difference, 0.1 percentage points; 95% confidence interval [CI], -4.7 to 4.9; P = 0.96). In the ICU, serious adverse events occurred at least once in 221 of 751 patients (29.4%) in the restrictive-fluid group and in 238 of 772 patients (30.8%) in the standard-fluid group (adjusted absolute difference, -1.7 percentage points; 99% CI, -7.7 to 4.3). At 90 days after randomization, the numbers of days alive without life support and days alive and out of the hospital were similar in the two groups.Among adult patients with septic shock in the ICU, intravenous fluid restriction did not result in fewer deaths at 90 days than standard intravenous fluid therapy. (Funded by the Novo Nordisk Foundation and others; CLASSIC ClinicalTrials.gov number, NCT03668236.). 

Restriction of Intravenous Fluid in ICU Patients with Septic Shock

Importance Intravenous fluids are used for almost all intensive care unit (ICU) patients. Clinical and laboratory studies have questioned whether specific fluid types result in improved outcomes, including mortality and acute kidney injury. Objective To determine the effect of a balanced solution vs saline solution (0.9% sodium chloride) on 90-day survival in critically ill patients. Design, Setting, and Participants Double-blind, factorial, randomized clinical trial conducted at 75 ICUs in Brazil. Patients who were admitted to the ICU with at least 1 risk factor for worse outcomes, who required at least 1 fluid expansion, and who were expected to remain in the ICU for more than 24 hours were randomized between May 29, 2017, and March 2, 2020; follow-up concluded on October 29, 2020. Patients were randomized to 2 different fluid types (a balanced solution vs saline solution reported in this article) and 2 different infusion rates (reported separately). Interventions Patients were randomly assigned 1:1 to receive either a balanced solution (n = 5522) or 0.9% saline solution (n = 5530) for all intravenous fluids. Main Outcomes and Measures The primary outcome was 90-day survival. Results Among 11 052 patients who were randomized, 10 520 (95.2%) were available for the analysis (mean age, 61.1 [SD, 17] years; 44.2% were women). There was no significant interaction between the 2 interventions (fluid type and infusion speed;P = .98). Planned surgical admissions represented 48.4% of all patients. Of all the patients, 60.6% had hypotension or vasopressor use and 44.3% required mechanical ventilation at enrollment. Patients in both groups received a median of 1.5 L of fluid during the first day after enrollment. By day 90, 1381 of 5230 patients (26.4%) assigned to a balanced solution died vs 1439 of 5290 patients (27.2%) assigned to saline solution (adjusted hazard ratio, 0.97 [95% CI, 0.90-1.05];P = .47). There were no unexpected treatment-related severe adverse events in either group. Conclusion and Relevance Among critically ill patients requiring fluid challenges, use of a balanced solution compared with 0.9% saline solution did not significantly reduce 90-day mortality. The findings do not support the use of this balanced solution. Trial Registration ClinicalTrials.gov Identifier:NCT02875873

Effect of Intravenous Fluid Treatment With a Balanced Solution vs 0.9% Saline Solution on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial

BackgroundThe comparative efficacy and safety of balanced crystalloid solutions and saline for fluid therapy in critically ill adults remain uncertain.MethodsWe systematically reviewed randomized clinical trials (RCTs) comparing the use of balanced crystalloids with saline in critically ill adults. The primary outcome was 90-day mortality after pooling data from low-risk-of-bias trials using a random-effects model. We also performed a Bayesian meta-analysis to describe the primary treatment effect in probability terms. Secondary outcomes included the incidence of acute kidney injury (AKI), new treatment with renal replacement therapy (RRT), and ventilator-free and vasopressor-free days to day 28.ResultsWe identified 13 RCTs, comprising 35,884 participants. From six trials (34,450 participants) with a low risk of bias, the risk ratio (RR) for 90-day mortality with balanced crystalloids versus saline was 0.96 (95% confidence interval [CI], 0.91 to 1.01; I2 = 12.1%); using vague priors, the posterior probability that balanced crystalloids reduce mortality was 89.5%. The RRs of developing AKI and of being treated with RRT with balanced crystalloids versus saline were 0.96 (95% CI, 0.89 to 1.02) and 0.95 (95% CI, 0.81 to 1.11), respectively. Ventilator-free days (mean difference, 0.18 days; 95% CI, −0.45 to 0.81) and vasopressor-free days (mean difference, 0.19 days; 95% CI, −0.14 to 0.51) were similar between groups.ConclusionsThe estimated effect of using balanced crystalloids versus saline in critically ill adults ranges from a 9% relative reduction to a 1% relative increase in the risk of death, with a high probability that the average effect of using balanced crystalloids is to reduce mortality. (PROSPERO number, CRD42021243399.) 

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Balanced Crystalloids versus Saline in Critically Ill Adults — A Systematic Review with Meta-Analysis

Importance Slower intravenous fluid infusion rates could reduce the formation of tissue edema and organ dysfunction in critically ill patients; however, there are no data to support different infusion rates during fluid challenges for important outcomes such as mortality. Objective To determine the effect of a slower infusion rate vs control infusion rate on 90-day survival in patients in the intensive care unit (ICU). Design, Setting, and Participants Unblinded randomized factorial clinical trial in 75 ICUs in Brazil, involving 11 052 patients requiring at least 1 fluid challenge and with 1 risk factor for worse outcomes were randomized from May 29, 2017, to March 2, 2020. Follow-up was concluded on October 29, 2020. Patients were randomized to 2 different infusion rates (reported in this article) and 2 different fluid types (balanced fluids or saline, reported separately). Interventions Patients were randomized to receive fluid challenges at 2 different infusion rates; 5538 to the slower rate (333 mL/h) and 5514 to the control group (999 mL/h). Patients were also randomized to receive balanced solution or 0.9% saline using a factorial design. Main Outcomes and Measures The primary end point was 90-day survival. Results Of all randomized patients, 10 520 (95.2%) were analyzed (mean age, 61.1 years [SD, 17.0 years]; 44.2% were women) after excluding duplicates and consent withdrawals. Patients assigned to the slower rate received a mean of 1162 mL on the first day vs 1252 mL for the control group. By day 90, 1406 of 5276 patients (26.6%) in the slower rate group had died vs 1414 of 5244 (27.0%) in the control group (adjusted hazard ratio, 1.03; 95% CI, 0.96-1.11;P = .46). There was no significant interaction between fluid type and infusion rate (P = .98). Conclusions and Relevance Among patients in the intensive care unit requiring fluid challenges, infusing at a slower rate compared with a faster rate did not reduce 90-day mortality. These findings do not support the use of a slower infusion rate. Trial Registration ClinicalTrials.gov Identifier:NCT02875873

Effect of Slower vs Faster Intravenous Fluid Bolus Rates on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial

RESUMO Objetivo: Relatar o plano de analise estatistica (primeira versao) para o estudo Balanced Solutions versus Saline in Intensive Care Study (BaSICS). Metodos: O estudo BaSICS e um ensaio multicentrico fatorial e randomizado que avaliara os efeitos da administracao dos fluidos Plasma-Lyte 148 em comparacao com solucao salina 0,9% como fluido de escolha em pacientes criticos, assim como os efeitos de uma velocidade de infusao lenta (333mL/hora) em comparacao com uma velocidade de infusao rapida (999mL/hora) durante desafios com volume, em importantes desfechos do paciente. O tipo de fluido sera mantido cego para os investigadores, pacientes e nas analises. Nao sera possivel, entretanto, ocultar dos investigadores a velocidade de infusao, mas os procedimentos de analise serao mantidos cegos quanto a esse aspecto. Resultados: O estudo BaSICS tera como parâmetro primario a mortalidade em 90 dias, que sera testada com utilizacao de modelos de risco proporcional de Cox de efeitos mistos, considerando os centros de estudo como variavel randomica (modelos de fragilidade) ajustada por idade, disfuncao de orgaos e tipo de admissao. Os parâmetros secundarios importantes incluem terapia de substituicao renal ate 90 dias, insuficiencia renal aguda, disfuncao de orgaos nos dias 3 e 7 e dias sem ventilacao mecânica em 28 dias. Conclusao: Este artigo fornece detalhes referentes a primeira versao do plano de analise estatistica para o estudo BaSICS e orientara a analise do estudo apos a conclusao do seguimento.

http://www.scielo.br/pdf/rbti/v32n4/en_0103-507X-rbti-20200081.pdf

Marco Antonio Vieira Guedes

Papers

Effect of Intravenous Fluid Treatment With a Balanced Solution vs 0.9% Saline Solution on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial

Plano de análise estatística para o estudo Balanced Solution versus Saline in Intensive Care Study (BaSICS)