title: Fluid balance, intradialytic hypotension, and outcomes in critically ill patients undergoing renal replacement therapy: a cohort study.
abstract: BACKGROUND
  In this cohort study, we explored the relationship between fluid balance, intradialytic hypotension and outcomes in critically ill patients with acute kidney injury (AKI) who received renal replacement therapy (RRT).
  
  
  METHODS
  We analysed prospectively collected registry data on patients older than 16 years who received RRT for at least two days in an intensive care unit at two university-affiliated hospitals. We used multivariable logistic regression to determine the relationship between mean daily fluid balance and intradialytic hypotension, both over seven days following RRT initiation, and the outcomes of hospital mortality and RRT dependence in survivors.
  
  
  RESULTS
  In total, 492 patients were included (299 male (60.8%), mean (standard deviation (SD)) age 62.9 (16.3) years); 251 (51.0%) died in hospital. Independent risk factors for mortality were mean daily fluid balance (odds ratio (OR) 1.36 per 1000 mL positive (95% confidence interval (CI) 1.18 to 1.57), intradialytic hypotension (OR 1.14 per 10% increase in days with intradialytic hypotension (95% CI 1.06 to 1.23)), age (OR 1.15 per five-year increase (95% CI 1.07 to 1.25)), maximum sequential organ failure assessment score on days 1 to 7 (OR 1.21 (95% CI 1.13 to 1.29)), and Charlson comorbidity index (OR 1.28 (95% CI 1.14 to 1.44)); higher baseline creatinine (OR 0.98 per 10 μmol/L (95% CI 0.97 to 0.996)) was associated with lower risk of death. Of 241 hospital survivors, 61 (25.3%) were RRT dependent at discharge. The only independent risk factor for RRT dependence was pre-existing heart failure (OR 3.13 (95% CI 1.46 to 6.74)). Neither mean daily fluid balance nor intradialytic hypotension was associated with RRT dependence in survivors. Associations between these exposures and mortality were similar in sensitivity analyses accounting for immortal time bias and dichotomising mean daily fluid balance as positive or negative. In the subgroup of patients with data on pre-RRT fluid balance, fluid overload at RRT initiation did not modify the association of mean daily fluid balance with mortality.
  
  
  CONCLUSIONS
  In this cohort of patients with AKI requiring RRT, a more positive mean daily fluid balance and intradialytic hypotension were associated with hospital mortality but not with RRT dependence at hospital discharge in survivors.
authors.affiliation: Interdepartmental Division of Critical Care, University of Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. j.silversides@qub.ac.uk.|Centre for Infection and Immunity, Queens University Belfast, Health Sciences Building, 97 Lisburn Road, Belfast, BT9 7BL, UK. j.silversides@qub.ac.uk.|Division of Critical Care and Outreach, Belfast Health and Social Care Trust, Belfast City Hospital, Lisburn Road, Belfast, BT9 7AB, UK. j.silversides@qub.ac.uk.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Silversides
authors.affiliation: Programme in Trauma, Emergency, and Critical Care, Sunnybrook Health Sciences Centre, Room D1.08, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada. ruxandra.pinto@sunnybrook.ca.
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Pinto
authors.affiliation: Interdepartmental Division of Critical Care, University of Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. kuint@hadassah.org.il.
authors.forename: Rottem
authors.initials: R
authors.lastname: Kuint
authors.affiliation: Division of Nephrology, St Michael's Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. waldr@smh.ca.|Division of Nephrology, University of Toronto, 190 Elizabeth Street, Suite 3-805, Toronto, ON, M5G 2C4, Canada. waldr@smh.ca.
authors.forename: Ron
authors.initials: R
authors.lastname: Wald
authors.affiliation: Division of Nephrology, University of Toronto, 190 Elizabeth Street, Suite 3-805, Toronto, ON, M5G 2C4, Canada. michelle.hladunewich@sunnybrook.ca.|Division of Nephrology, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Room A206a, Toronto, ON, M4N 3M5, Canada. michelle.hladunewich@sunnybrook.ca.|Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Room D1.08, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada. michelle.hladunewich@sunnybrook.ca.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Hladunewich
authors.affiliation: Interdepartmental Division of Critical Care, University of Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. slapinsky@mtsinai.on.ca.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Lapinsky
authors.affiliation: Interdepartmental Division of Critical Care, University of Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. neill.adhikari@utoronto.ca.|Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Room D1.08, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada. neill.adhikari@utoronto.ca.
authors.forename: Neill K J
authors.initials: NK
authors.lastname: Adhikari
mesh_terms: D000368:Aged; D015331:Cohort Studies; D016638:Critical Illness / Q000401:mortality* / Q000628:therapy*; D005260:Female; D017052:Hospital Mortality / Q000639:trends; D006801:Humans; D007022:Hypotension / Q000175:diagnosis* / Q000401:mortality* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012042:Registries; D017582:Renal Replacement Therapy / Q000401:mortality* / Q000639:trends; D016896:Treatment Outcome; D014882:Water-Electrolyte Balance / Q000502:physiology*