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Anand Kumar, MD; Ryan Zarychanski, MD; Ruxandra Pinto, PhD; Deborah J. Cook, MD, MSc; John Marshall, MD; Jacques Lacroix, MD; Tom Stelfox, MD, PhD; Sean Bagshaw, MD, MSc; Karen Choong, MD; Francois Lamontagne, MD; Alexis F. Turgeon, MD, MSc; Stephen Lapinsky, MD; Stéphane P. Ahern, MD; Orla Smith, MSc; Faisal Siddiqui, MD; Philippe Jouvet, MD, PhD; Kosar Khwaja, MD; Lauralyn McIntyre, MD, MSc; Kusum Menon, MD, MSc; Jamie Hutchison, MD; David Hornstein, MD; Ari Joffe, MD; Francois Lauzier, MD; Jeffrey Singh, MD, MSc; Tim Karachi, MD; Kim Wiebe, MD; Kendiss Olafson, MD; Clare Ramsey, MD; Sat Sharma, MD; Peter Dodek, MD, MHSc; Maureen Meade, MD, MSc; Richard Hall, MD; Robert A. Fowler, MD, MSc; for the Canadian Critical Care Trials Group H1N1 Collaborative

JAMA. 2009;302(17):1872-1879. Published online October 12, 2009 (doi:10.1001/jama.2009.1496).

Context  Between March and July 2009, the largest number of confirmed cases of 2009 influenza A(H1N1) infection occurred in North America.

Objective  To describe characteristics, treatment, and outcomes of critically ill patients in Canada with 2009 influenza A(H1N1) infection.

Design, Setting, and Patients  A prospective observational study of 168 critically ill patients with 2009 influenza A(H1N1) infection in 38 adult and pediatric intensive care units (ICUs) in Canada between April 16 and August 12, 2009.

Main Outcome Measures  The primary outcome measures were 28-day and 90-day mortality. Secondary outcomes included frequency and duration of mechanical ventilation and duration of ICU stay.

Results  Critical illness occurred in 215 patients with confirmed (n = 162), probable (n = 6), or suspected (n = 47) community-acquired 2009 influenza A(H1N1) infection. Among the 168 patients with confirmed or probable 2009 influenza A(H1N1), the mean (SD) age was 32.3 (21.4) years; 113 were female (67.3%) and 50 were children (29.8%). Overall mortality among critically ill patients at 28 days was 14.3% (95% confidence interval, 9.5%-20.7%). There were 43 patients who were aboriginal Canadians (25.6%). The median time from symptom onset to hospital admission was 4 days (interquartile range [IQR], 2-7 days) and from hospitalization to ICU admission was 1 day (IQR, 0-2 days). Shock and nonpulmonary acute organ dysfunction was common (Sequential Organ Failure Assessment mean [SD] score of 6.8 [3.6] on day 1). Neuraminidase inhibitors were administered to 152 patients (90.5%). All patients were severely hypoxemic (mean [SD] ratio of PaO₂ to fraction of inspired oxygen [FIO₂] of 147 [128] mm Hg) at ICU admission. Mechanical ventilation was received by 136 patients (81.0%). The median duration of ventilation was 12 days (IQR, 6-20 days) and ICU stay was 12 days (IQR, 5-20 days). Lung rescue therapies included neuromuscular blockade (28% of patients), inhaled nitric oxide (13.7%), high-frequency oscillatory ventilation (11.9%), extracorporeal membrane oxygenation (4.2%), and prone positioning ventilation (3.0%). Overall mortality among critically ill patients at 90 days was 17.3% (95% confidence interval, 12.0%-24.0%; n = 29).

Conclusion  Critical illness due to 2009 influenza A(H1N1) in Canada occurred rapidly after hospital admission, often in young adults, and was associated with severe hypoxemia, multisystem organ failure, a requirement for prolonged mechanical ventilation, and the frequent use of rescue therapies.

Author Affiliations: Section of Critical Care Medicine, Health Sciences Centre and St Boniface Hospital, Winnipeg, Manitoba, Canada (Drs Kumar, Siddiqui, Wiebe, Olafson, Ramsey, and Sharma); Department of Medical Oncology and Hematology, Cancercare Manitoba, Winnipeg (Dr Zarychanski); Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (Drs Pinto and Fowler); Departments of Clinical Epidemiology and Biostatistics (Drs Cook and Meade) and Medicine (Dr Karachi), McMaster Children's Hospital (Dr Choong), McMaster University, Hamilton, Ontario, Canada; Department of Critical Care Medicine, St Michael's Hospital, Toronto, Ontario, Canada (Dr Marshall and Ms Smith); Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montréal, Quebec, Canada (Drs Lacroix and Jouvet); Departments of Critical Care Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada (Dr Stelfox); Division of Critical Care Medicine, University of Alberta, Edmonton (Drs Bagshaw and Joffe); Department of Medicine, Centre Hospitalier, Université de Sherbrooke, Sherbrooke, Quebec, Canada (Dr Lamontagne); Centre de Recherche du CHA, Hôpital de l’Enfant-Jésus, Université Laval, Quebec City, Quebec, Canada (Drs Turgeon and Lauzier); Intensive Care Unit, Mount Sinai Hospital (Dr Lapinsky) and University Health Network (Dr Singh), University of Toronto, Toronto, Ontario, Canada; Department of Medicine, Hôpital Maisonneuve-Rosemont, University of Montréal, Montréal, Quebec, Canada (Dr Ahern); Trauma Services, McGill University Health Centre, Montréal, Quebec, Canada (Dr Khwaja); Clinical Epidemiology Unit, Ottawa Health Research Institute, Ottawa, Ontario, Canada (Dr McIntyre); Clinical Research Unit, Children's Hospital of Eastern Ontario, Ottawa (Dr Menon); Department of Critical Care Medicine, Hospital for Sick Children, Toronto, Ontario, Canada (Dr Hutchison); SMBD-Jewish General Hospital, Montréal, Québec, Canada (Dr Hornstein); University of British Columbia, Vancouver (Dr Dodek); and Department of Anesthesia, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada (Dr Hall).

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