Thummaporn Naorungroj1,2, Ary Serpa Neto1,3,4,5,6, Lara Zwakman-Hessels1,7, Yanase Fumitaka1,5, Glenn Eastwood1, Raghavan Murugan8,9, John A Kellum8,9, Rinaldo Bellomo1,5,6,10. 1. Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia. 2. Department of Intensive Care, Faculty of Medicine, Mahidol University, Bangkok, Thailand. 3. Department of Critical Care Medicine, Hospital Israelita Albert Einstein, São Paulo, Brazil. 4. Department of Intensive Care, Academic Medical Center, Amsterdam, The Netherlands. 5. ANZICS-Research Centre, Monash University Division and School of Public Health and Preventive Medicine, Melbourne, VIC, Australia. 6. Data Analytics Research and Evaluation (DARE) Centre, Department of Clinical Informatics Austin Hospital and University of Melbourne, Melbourne, VIC, Australia. 7. Department of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 8. The Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA. 9. The Clinical Research, Investigation, and Systems Modelling of Acute Illness (CRISMA) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA. 10. Centre for Integrated Critical Care, Department of Medicine and Radiology, The University of Melbourne, Melbourne, VIC, Australia.
Abstract
OBJECTIVES: During continuous renal replacement therapy, a high net ultrafiltration rate has been associated with increased mortality. However, it is unknown what might mediate its putative effect on mortality. In this study, we investigated whether the relationship between early (first 48 hr) net ultrafiltration and mortality is mediated by fluid balance, hemodynamic instability, or low potassium or phosphate blood levels using mediation analysis and the primary outcome was hospital mortality. DESIGN: Retrospective, observational study. SETTING: Mixed medical and surgical ICUs at Austin hospital, Melbourne, Australia. PATIENTS: Critically ill patients treated with continuous renal replacement therapy within 14 days of ICU admission who survived greater than 48 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We studied 347 patients (median [interquartile range] age: 64 yr [53-71 yr] and Acute Physiology and Chronic Health Evaluation III score: 73 (54-90)]. After adjustment for confounders, compared with a net ultrafiltration less than 1.01 mL/kg/hr, a net ultrafiltration rate greater than 1.75 mL/kg/hr was associated with significantly greater mortality (adjusted odds ratio, 1.15; 95% CI, 1.03-1.29; p = 0.011). Adjusted univariable mediation analysis found no suggestion of a causal mediation pathway for this effect by blood pressure, vasopressor therapy, or potassium levels, but identified a possible mediation effect for fluid balance (average causal mediation effect, 0.95; 95% CI, 0.89-1.00; p = 0.060) and percentage of phosphate measurements with hypophosphatemia (average causal mediation effect, 0.96; 95% CI, 0.92-1.00; p = 0.055). However, on multiple mediator analyses, these two variables showed no significant effect. In contrast, a high net ultrafiltration rate had an average direct effect of 1.24 (95% CI, 1.11-1.40; p < 0.001). CONCLUSIONS: An early net ultrafiltration greater than 1.75 mL/kg/hr was independently associated with increased hospital mortality. Its putative effect on mortality was direct and not mediated by a causal pathway that included fluid balance, low blood pressure, vasopressor use, hypokalemia, or hypophosphatemia.
OBJECTIVES: During continuous renal replacement therapy, a high net ultrafiltration rate has been associated with increased mortality. However, it is unknown what might mediate its putative effect on mortality. In this study, we investigated whether the relationship between early (first 48 hr) net ultrafiltration and mortality is mediated by fluid balance, hemodynamic instability, or low potassium or phosphate blood levels using mediation analysis and the primary outcome was hospital mortality. DESIGN: Retrospective, observational study. SETTING: Mixed medical and surgical ICUs at Austin hospital, Melbourne, Australia. PATIENTS: Critically illpatients treated with continuous renal replacement therapy within 14 days of ICU admission who survived greater than 48 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We studied 347 patients (median [interquartile range] age: 64 yr [53-71 yr] and Acute Physiology and Chronic Health Evaluation III score: 73 (54-90)]. After adjustment for confounders, compared with a net ultrafiltration less than 1.01 mL/kg/hr, a net ultrafiltration rate greater than 1.75 mL/kg/hr was associated with significantly greater mortality (adjusted odds ratio, 1.15; 95% CI, 1.03-1.29; p = 0.011). Adjusted univariable mediation analysis found no suggestion of a causal mediation pathway for this effect by blood pressure, vasopressor therapy, or potassium levels, but identified a possible mediation effect for fluid balance (average causal mediation effect, 0.95; 95% CI, 0.89-1.00; p = 0.060) and percentage of phosphate measurements with hypophosphatemia (average causal mediation effect, 0.96; 95% CI, 0.92-1.00; p = 0.055). However, on multiple mediator analyses, these two variables showed no significant effect. In contrast, a high net ultrafiltration rate had an average direct effect of 1.24 (95% CI, 1.11-1.40; p < 0.001). CONCLUSIONS: An early net ultrafiltration greater than 1.75 mL/kg/hr was independently associated with increased hospital mortality. Its putative effect on mortality was direct and not mediated by a causal pathway that included fluid balance, low blood pressure, vasopressor use, hypokalemia, or hypophosphatemia.
Authors: Javier A Neyra; Joshua Lambert; Victor Ortiz-Soriano; Daniel Cleland; Jon Colquitt; Paul Adams; Brittany D Bissell; Lili Chan; Girish N Nadkarni; Ashita Tolwani; Stuart L Goldstein Journal: PLoS One Date: 2022-08-25 Impact factor: 3.752