Fernando G Zampieri1,2, Flávia R Machado2,3, Rodrigo S Biondi2,4, Flávio G R Freitas2,5, Viviane C Veiga2,6, Rodrigo C Figueiredo7, Wilson J Lovato8, Cristina P Amêndola9, Ary Serpa-Neto2,10, Jorge L R Paranhos11, Marco A V Guedes12, Eraldo A Lúcio13, Lúcio C Oliveira-Júnior14, Thiago C Lisboa2,15, Fábio H Lacerda16, Israel S Maia2,17, Cintia M C Grion2,18, Murillo S C Assunção10, Airton L O Manoel19, João M Silva-Junior20, Péricles Duarte21, Rafael M Soares1, Tamiris A Miranda1, Lucas M de Lima1, Rodrigo M Gurgel1, Denise M Paisani1, Thiago D Corrêa2,10, Luciano C P Azevedo2,22, John A Kellum23, Lucas P Damiani1, Nilton Brandão da Silva24, Alexandre B Cavalcanti1,2. 1. HCor Research Institute, São Paulo, Brazil. 2. Brazilian Research in Intensive Care Network, São Paulo, Brazil. 3. Department of Anesthesiology, Pain and Intensive Care, Universidade Federal de São Paulo, São Paulo, Brazil. 4. Instituto de Cardiologia do Distrito Federal, Brasília, Brazil. 5. Hospital SEPACO, São Paulo, Brazil. 6. BP-A Beneficência Portuguesa de São Paulo, São Paulo, Brazil. 7. Hospital Maternidade São José, Centro Universitário do Espírito Santo, Colatina, Brazil. 8. Hospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil. 9. Fundação Pio XII, Hospital de Câncer de Barretos, Barretos, Brazil. 10. Hospital Israelita Albert Einstein, São Paulo, Brazil. 11. Santa Casa de Misericórdia de São João Del Rei, São João Del Rei, Brazil. 12. Hospital Ana Nery, Salvador, Brazil. 13. Hospital São Francisco, Santa Casa de Porto Alegre, Porto Alegre, Brazil. 14. Hospital Geral Clériston Andrade, Feira de Santana, Brazil. 15. Hospital Santa Rita, Santa Casa de Porto Alegre, Porto Alegre, Brazil. 16. Hospital da Luz, São Paulo, Brazil. 17. Hospital Nereu Ramos, Florianópolis, Brazil. 18. Hospital Universitário Regional do Norte do Paraná, Universidade Estadual de Londrina, Londrina, Brazil. 19. Hospital Paulistano, São Paulo, Brazil. 20. Hospital do Servidor Público Estadual, São Paulo, Brazil. 21. Hospital Universitário de Cascavel, Cascavel, Brazil. 22. Hospital Sírio Libanês, São Paulo, Brazil. 23. Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. 24. School of Medicine, Federal University of Health Sciences, Porto Alegre, Brazil.
Abstract
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.
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.
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