title: The Dose Response Multicentre Investigation on Fluid Assessment (DoReMIFA) in critically ill patients.
abstract: BACKGROUND
  The previously published "Dose Response Multicentre International Collaborative Initiative (DoReMi)" study concluded that the high mortality of critically ill patients with acute kidney injury (AKI) was unlikely to be related to an inadequate dose of renal replacement therapy (RRT) and other factors were contributing. This follow-up study aimed to investigate the impact of daily fluid balance and fluid accumulation on mortality of critically ill patients without AKI (N-AKI), with AKI (AKI) and with AKI on RRT (AKI-RRT) receiving an adequate dose of RRT.
  
  
  METHODS
  We prospectively enrolled all consecutive patients admitted to 21 intensive care units (ICUs) from nine countries and collected baseline characteristics, comorbidities, severity of illness, presence of sepsis, daily physiologic parameters and fluid intake-output, AKI stage, need for RRT and survival status. Daily fluid balance was computed and fluid overload (FO) was defined as percentage of admission body weight (BW). Maximum fluid overload (MFO) was the peak value of FO.
  
  
  RESULTS
  We analysed 1734 patients. A total of 991 (57 %) had N-AKI, 560 (32 %) had AKI but did not have RRT and 183 (11 %) had AKI-RRT. ICU mortality was 22.3 % in AKI patients and 5.6 % in those without AKI (p < 0.0001). Progressive fluid accumulation was seen in all three groups. Maximum fluid accumulation occurred on day 2 in N-AKI patients (2.8 % of BW), on day 3 in AKI patients not receiving RRT (4.3 % of BW) and on day 5 in AKI-RRT patients (7.9 % of BW). The main findings were: (1) the odds ratio (OR) for hospital mortality increased by 1.075 (95 % confidence interval 1.055-1.095) with every 1 % increase of MFO. When adjusting for severity of illness and AKI status, the OR changed to 1.044. This phenomenon was a continuum and independent of thresholds as previously reported. (2) Multivariate analysis confirmed that the speed of fluid accumulation was independently associated with ICU mortality. (3) Fluid accumulation increased significantly in the 3-day period prior to the diagnosis of AKI and peaked 3 days later.
  
  
  CONCLUSIONS
  In critically ill patients, the severity and speed of fluid accumulation are independent risk factors for ICU mortality. Fluid balance abnormality precedes and follows the diagnosis of AKI.
authors.affiliation: Department of Nephrology Dialysis and Transplantation, San Bortolo Hospital, 37 Via Rodolfi, 36100, Vicenza, Italy. f.garzotto@gmail.com.|International Renal Research Institute of Vicenza (IRRIV), San Bortolo Hospital, 37 Via Rodolfi, 36100, Vicenza, Italy. f.garzotto@gmail.com.
authors.forename: F
authors.initials: F
authors.lastname: Garzotto
authors.affiliation: Department of Critical Care, King's College London, Guy's and St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH, UK.
authors.forename: M
authors.initials: M
authors.lastname: Ostermann
authors.affiliation: Servicio de Medicina Intensiva, Hospital Universitario del Vinalopo, Calle Tonico Sansano Mora, 14, 03283, Elche, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Martín-Langerwerf
authors.affiliation: Intensive Care, Hospital Universitario La Paz/Carlos III. IdiPAZ, Paseo Castellana 261, 28046, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Sánchez-Sánchez
authors.affiliation: Department of Nephrology, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Zhongshan Hospital, Fudan University, 180 Fenglin Road, 200032, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Teng
authors.affiliation: Medical Intensive Care, University of Poitiers; CHU Poitiers, 2, rue de la Milétrie, Poitiers, 86021, France.
authors.forename: R
authors.initials: R
authors.lastname: Robert
authors.affiliation: Intensive Care Service, St Antonio Hospital - Porto, Largo Prof. Abel Salazar, 4099-001, Porto, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Marinho
authors.affiliation: Intensive Care Unit, General University Hospital, Avd Carlos Haya s/n, Malaga, 29010, Spain.
authors.forename: M E
authors.initials: ME
authors.lastname: Herrera-Gutierrez
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, 210029, Nanjing, Jiangsu, China.
authors.forename: H J
authors.initials: HJ
authors.lastname: Mao
authors.affiliation: Department of Nephrology, Clinica Las Condes, Estoril 450, Las Condes, 7591283, Santiago, Chile.
authors.forename: D
authors.initials: D
authors.lastname: Benavente
authors.affiliation: Department of Anesthesiology and Critical Care, University Hospital, EA 7366, Lille, 59000, France.
authors.forename: E
authors.initials: E
authors.lastname: Kipnis
authors.affiliation: International Renal Research Institute of Vicenza (IRRIV), San Bortolo Hospital, 37 Via Rodolfi, 36100, Vicenza, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Lorenzin
authors.affiliation: Fresenius Medical Care, Else-Kröner-Straße 1, 61352 Bad, Homburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Marcelli
authors.affiliation: Fresenius Medical Care, Else-Kröner-Straße 1, 61352 Bad, Homburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Tetta
authors.affiliation: Department of Nephrology Dialysis and Transplantation, San Bortolo Hospital, 37 Via Rodolfi, 36100, Vicenza, Italy.|International Renal Research Institute of Vicenza (IRRIV), San Bortolo Hospital, 37 Via Rodolfi, 36100, Vicenza, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Ronco
mesh_terms: D058186:Acute Kidney Injury / Q000628:therapy; D000328:Adult; D000368:Aged; D016638:Critical Illness / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007362:Intensive Care Units / Q000458:organization & administration; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017582:Renal Replacement Therapy / Q000379:methods* / Q000592:standards; D012307:Risk Factors; D014883:Water-Electrolyte Imbalance
keywords: AKI; Critical illness; Fluid overload; ICU; RRT