Acute kidney injury among critically ill patients with pandemic H1N1 influenza A in Canada: cohort study

Sean M Bagshaw 1 Manish M Sood 1 Jennifer Long 1 Robert A Fowler 0 1 2 Neill KJ Adhikari 0 1 Canadian Critical Care Trials Group H 1 N 1 Collaborative 1 2 0 Department of Critical Care Medicine and Sunnybrook Research Institute, Sunnybrook Health Sciences Centre and University of Toronto , 2075 Bayview Avenue, Room D1.08, Toronto, ON M4N 3M5 , Canada 1 Critical Care Medicine and Sunnybrook Research Institute, Sunnybrook Health Sciences Centre and University of Toronto , 2075 Bayview Avenue, Room D1.08, Toronto, ON M4N 3M5 , Canada 2 Department of Medicine, Sunnybrook Health Sciences Centre and University of Toronto , 2075 Bayview Avenue, Room D4.78, Toronto, ON M4N 3M5 , Canada Background: Canada's pandemic H1N1 influenza A (pH1N1) outbreak led to a high burden of critical illness. Our objective was to describe the incidence of AKI (acute kidney injury) in these patients and risk factors for AKI, renal replacement therapy (RRT), and mortality. Methods: From a prospective cohort of critically ill adults with confirmed or probable pH1N1 (16 April 2009-12 April 2010), we abstracted data on demographics, co-morbidities, acute physiology, AKI (defined by RIFLE criteria for Injury or Failure), treatments in the intensive care unit, and clinical outcomes. Univariable and multivariable logistic regression analyses were used to evaluate the associations between clinical characteristics and the outcomes of AKI, RRT, and hospital mortality. Results: We included 562 patients with pH1N1-related critical illness (479 [85.2%] confirmed, 83 [14.8%] probable]: mean age 48.0 years, 53.4% female, and 13.3% aboriginal. Common co-morbidities included obesity, diabetes, and chronic obstructive pulmonary disease. AKI occurred in 60.9%, with RIFLE categories of Injury (23.0%) and Failure (37.9%). Independent predictors of AKI included obesity (OR 2.94; 95%CI, 1.75-4.91), chronic kidney disease (OR 4.50; 95%CI, 1.46-13.82), APACHE II score (OR per 1-unit increase 1.06; 95%CI, 1.03-1.09), and PaO2/FiO2 ratio (OR per 10-unit increase 0.98; 95%CI, 0.95-1.00). Of patients with AKI, 24.9% (85/342) received RRT and 25.8% (85/329) died. Independent predictors of RRT were obesity (OR 2.25; 95% CI, 1.14-4.44), day 1 mechanical ventilation (OR 4.09; 95% CI, 1.21-13.84), APACHE II score (OR per 1-unit increase 1.07; 95% CI, 1.03-1.12), and day 1 creatinine (OR per 10 mol/L increase, 1.06; 95%CI, 1.03-1.10). Development of AKI was not independently associated with hospital mortality. Conclusion: The incidence of AKI and RRT utilization were high among Canadian patients with critical illness due to pH1N1. - Background In the spring of 2009, the world experienced a pandemic due to novel swine-origin influenza A (pH1N1) virus, with more than 17,000 deaths [16]. In Canada, there were two major waves of pH1N1 in the spring and fall of 2009 that led to 8,678 hospitalizations, of which 1,473 (17.0%) required intensive care unit (ICU) admission [7]. By April 2010, there were approximately 428 deaths (4.9%; 12.7 per million population) attributable to pH1N1 infection, the 12th highest pH1N1-attributable mortality worldwide [7]. Of particular concern among pH1N1 patients was the high risk of ICU admission for respiratory failure [7,8]. Several studies have described the impact of pH1N1 on ICU resources, with an emphasis on respiratory failure, mechanical ventilation, and extracorporeal life support (ECLS) [9,10]. Fewer studies have focused on nonpulmonary organ dysfunction, specifically acute kidney injury (AKI) and its resource implications. AKI commonly accompanies critical illness and independently increases risks of death, prolonged length of stay, and development of new chronic kidney disease (CKD) among survivors [11,12]. Recently, reports have described the incidence and outcomes of AKI among critically ill adult and pediatric pH1N1 patients [1328]. Many studies, however, were limited by design (case reports [14,17,20,22,24,28] or small case series [13,15,18,21,27]), small sample size [16,19,25], or single-center enrollment [13,15,16,18,21]. There have been few larger scale prospective multi-center cohorts [19,23,26], none of which described the Canadian pandemic. Accordingly, we examined a prospective multi-centre Canadian cohort of critically ill patients and confirmed or probable pH1N1 infection [2] to primarily describe the incidence and severity of AKI and secondarily determine the rates of RRT utilization along with risk factors for AKI, RRT, and mortality. Methods This study was approved by the Research Ethics Board at Sunnybrook Health Sciences Centre, Toronto on 30 April 2009 (file #130-2009), and at all participating sites. All Research Ethics Boards waived the requirement for individual informed consent. The reporting of this study follows recent guidelines [29]. Study design, setting, and participants This cohort study is a secondary analysis of prospectively collected data from a multi-centre inception cohort of all adults (age >18 years), admitted to any of 51 Canadian ICUs, with confirmed or probable influenza A (pH1N1)-related critical illness, from 16 April 2009 to 12 April 2010 [2]. Members of the Canadian Critical Care H1N1 Collaborative are listed in Additional file 1. The 51 ICUs that agreed to collect data for this study constituted a subset of the 286 Canadian ICUs that provide mechanical ventilation (R. Fowler, personal communication). Data on a subset of 50 patients in this cohort, all from Manitoba, Canada, were published previously [27]. Data collection Data from patients medical records were captured on standardized case-report forms, as described elsewhere [2]. Briefly, we collected data on dates and times of hospital and ICU admission and discharge, demographics, comorbid diseases, acute physiology, laboratory parameters, illness severity (APACHE II [Acute Physiology and Chronic Health Evaluation II] [30] and SOFA [Sequential Organ Failure Assessment] [31] scores), treatment intensity (including mechanical ventilation, inotrope and vasopressor support, and RRT, with each determined on days 1, 3, 7, 14, and 28 of ICU admission), and vital status at hospital discharge. The comorbid condition of obesity was defined as body mass index 30 kg/m2. Diagnostic tests, including scheduled serum creatinine levels, were not mandated by the study protocol. Cohort definitions Patients with pH1N1 were included if confirmed or probable according to case definitions of the World Health Organization and the Canadian National Microbiology Laboratory [32]. Critical illness was defined by: 1) admission to an ICU and either 2) receipt of mechanical ventilation (invasive or non-invasive) or 3) receipt of inotrope or vasopressor infusion [2]. Chronic kidney disease (CKD) was defined as pre-morbid baseline serum creatinine 1.5 times the upper limit of normal. End-stage kidney disease was defined as outpatient dialysis dependence preceding ICU admission. Outcome definitions The primary outcom (...truncated)