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Title: Mediators of the Impact of Hourly Net Ultrafiltration Rate on Mortality in Critically Ill Patients Receiving Continuous Renal Replacement Therapy.
Austin Authors: Naorungroj, Thummaporn ;Neto, Ary Serpa;Zwakman-Hessels, Lara;Yanase, Fumitaka ;Eastwood, Glenn M ;Murugan, Raghavan;Kellum, John A;Bellomo, Rinaldo 
Affiliation: Centre for Integrated Critical Care, Department of Medicine and Radiology, The University of Melbourne, Melbourne, VIC, Australia
ANZICS-Research Centre, Monash University Division and School of Public Health and Preventive Medicine, Melbourne, VIC, Australia
Data Analytics Research and Evaluation (DARE) Centre
Intensive Care
Department of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
Department of Intensive Care, Faculty of Medicine, Mahidol University, Bangkok, Thailand
The Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA
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
Department of Critical Care Medicine, Hospital Israelita Albert Einstein, São Paulo, Brazil
Department of Intensive Care, Academic Medical Center, Amsterdam, The Netherlands
Clinical Informatics
Issue Date: Oct-2020
Publication information: Critical Care Medicine 2020; 48(10): e934-e942
Abstract: 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. Retrospective, observational study. Mixed medical and surgical ICUs at Austin hospital, Melbourne, Australia. Critically ill patients treated with continuous renal replacement therapy within 14 days of ICU admission who survived greater than 48 hours. None. 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). 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.
DOI: 10.1097/CCM.0000000000004508
PubMed URL: 32885938
Type: Journal Article
Appears in Collections:Journal articles

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