The influence of corticosteroid treatment on the outcome of influenza A(H1N1pdm09)-related critical illness

doi:10.1186/s13054-016-1230-8

Observational Study

. 2016 Mar 30:20:75.

doi: 10.1186/s13054-016-1230-8.

The influence of corticosteroid treatment on the outcome of influenza A(H1N1pdm09)-related critical illness

Jesse W Delaney^{1

2}, Ruxandra Pinto³, Jennifer Long³, François Lamontagne⁴, Neill K Adhikari^{1

5}, Anand Kumar^{6

7

8

9}, John C Marshall¹⁰, Deborah J Cook¹¹, Philippe Jouvet¹², Niall D Ferguson^{1

13

14

15

16}, Donald Griesdale¹⁷, Lisa D Burry¹⁸, Karen E A Burns^{1

19}, Jamie Hutchison²⁰, Sangeeta Mehta^{1

13

18}, Kusum Menon²¹, Robert A Fowler^{22

23}; Canadian Critical Care Trials Group H1N1 Collaborative

Collaborators, Affiliations

Collaborators

Canadian Critical Care Trials Group H1N1 Collaborative:
N Bandrauk, S Leonard, E Moores, J Barter, J Fiander, R Hall, R Green, D Heinzler, L Julien, D Wright, C Soder, R Earle, S King, F Lauzier, A Turgeon, C Roy, C Gagne, F Lellouche, M C Ferland, P Dussault, G Poirier, F Lamontagne, I Neas, V Masse, P Yale, M Albert, I Arsenault, P Deroy, D Laporta, D Hornstein, B Verhoef, K Khwaja, L Banici, S P Ahern, Y Skrobic, J Harvey, M Santschi, L Ducharme-Crevier, P Jouvet, J Lacroix, D Withington, T Al Otaibi, M A Dugas, L St-Pierre, J Cassista, L Gosselin, L McIntyre, C Gaudet, R Saginur, J Pagliarello, I Watpool, T McArdle, J Foxall, E Murphy, C Bergeron, M J Lewis, J Muscedere, N Godfrey, M Fleury, G Hollinger, E Malus, N Williams, M Hrytsyk, M Meade, C Spoto, A Freitag, K Choong, N Irwin, T Karachi, S Lapinsky, N Ferguson, C Ethier, T Stewart, S Lubchansky, D J Cook, E MacDonald, K Wilton, A Tkaczyk, M Kho, L Sivaloganathan, R Cirone, J Marshall, K Burns, O Smith, J Friedrich, B Fry, K Porretta, R Fowler, J Long, R Pinto, N K Adhikari, N Marinoff, A Maher, C Moran, J Delaney, J M Singh, M Herridge, J Granton, N Brockest, A Matte, C Tansey, L Chu, M Dennis, M di Nino, D McRitchie, J A Correa, C Martin, E Campbell, K Menon, D Creery, D Doherty, S Dhanani, R Ward, B Alsaati, K Choong, M Duffett, N Irwin, T L Caceres, J Hutchison, L Keating, R Gaiteiro, A M Krancevic, J Van Huyse, A Kornecki, J Foster, B Kukreti, D Boyle, K Kostiw, L Green, D Fung, N Jacko, J Herzog, G Berg, P Bettello, A Ross, N Marcello, R Agarwala, W Anderson, S Stoger, A Kumar, R Zarychanski, F Siddiqui, S Sharma, K Wiebe, C Ramsey, K Olafson, D Funk, A Garland, W Janz, N Marten, M Siddiqui, S Veroukis, M Kesselman, L Angelo, M WaliAhsan, C Penner, A Wong, S Shaw, J Friedt, G Wolffe, S Thomson, T Holt, B Andreychuk, T Stelfox, B Bobranska-Artiuch, M Heule, D Kutsogiannis, C Johnston, R Bartel, P Thompson, D Jossy, S Norris, D E Stollery, T MacLure, R Hardy-Joel, J Barchard, S M Bagshaw, M Irwin, A Joffe, C Sheppard, C Gresiuk, L Hodson, E Gilfoyle, K Menzies, P Dodek, B J Ashley, H Dunham, D Griesdale, D Foster, M Gardner, S Logie, S Reynolds, S Keenan, S Mans, J Palmer, M Svetik, G Wood, L Atkins, B Aldred-Portman, P Skippen, N Kissoon, G Krahn, J Burzynski, A Barclay, A Patel, K Kandola, K Pender, B Hanley, K D Braden, R Beckett, P Bilton

Affiliations

¹ Interdepartmental Division of Critical Care Medicine, Department of Medicine, University of Toronto, Toronto, ON, Canada.
² Rouge Valley Health System, Scarborough, ON, Canada.
³ Sunnybrook Hospital, Toronto, ON, Canada.
⁴ Centre de recherche clinique Étienne-Le Bel, Université de Sherbrooke, Sherbrooke, PQ, Canada.
⁵ Department of Critical Care Medicine, Sunnybrook Hospital, 2075 Bayview Avenue, Room D478, Toronto, ON, M4N 3M5, Canada.
⁶ Section of Critical Care Medicine, Department of Internal Medicine, Faculty of Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
⁷ Section of Infectious Diseases, Department of Internal Medicine, Faculty of Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
⁸ Department of Medical Microbiology, Faculty of Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
⁹ Department of, Faculty of Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
¹⁰ St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
¹¹ St. Joseph's Hospital, McMaster University, Hamilton, ON, Canada.
¹² CHU Sainte Justine, Université de Montréal, Montréal, PQ, Canada.
¹³ Department of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁴ Department of Physiology, University of Toronto, Toronto, ON, Canada.
¹⁵ Division of Respirology, Department of Medicine, University Health Network and Mount Sinai Hospital, Toronto, ON, Canada.
¹⁶ Critical Care Program, Department of Medicine, University Health Network and Mount Sinai Hospital, Toronto, ON, Canada.
¹⁷ Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
¹⁸ Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
¹⁹ Division of Critical Care, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
²⁰ Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
²¹ Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.
²² Interdepartmental Division of Critical Care Medicine, Department of Medicine, University of Toronto, Toronto, ON, Canada. rob.fowler@sunnybrook.ca.
²³ Department of Critical Care Medicine, Sunnybrook Hospital, 2075 Bayview Avenue, Room D478, Toronto, ON, M4N 3M5, Canada. rob.fowler@sunnybrook.ca.

PMID: 27036638
PMCID: PMC4818504
DOI: 10.1186/s13054-016-1230-8

Observational Study

The influence of corticosteroid treatment on the outcome of influenza A(H1N1pdm09)-related critical illness

Jesse W Delaney et al. Crit Care. 2016.

. 2016 Mar 30:20:75.

doi: 10.1186/s13054-016-1230-8.

Authors

Collaborators

Canadian Critical Care Trials Group H1N1 Collaborative:
N Bandrauk, S Leonard, E Moores, J Barter, J Fiander, R Hall, R Green, D Heinzler, L Julien, D Wright, C Soder, R Earle, S King, F Lauzier, A Turgeon, C Roy, C Gagne, F Lellouche, M C Ferland, P Dussault, G Poirier, F Lamontagne, I Neas, V Masse, P Yale, M Albert, I Arsenault, P Deroy, D Laporta, D Hornstein, B Verhoef, K Khwaja, L Banici, S P Ahern, Y Skrobic, J Harvey, M Santschi, L Ducharme-Crevier, P Jouvet, J Lacroix, D Withington, T Al Otaibi, M A Dugas, L St-Pierre, J Cassista, L Gosselin, L McIntyre, C Gaudet, R Saginur, J Pagliarello, I Watpool, T McArdle, J Foxall, E Murphy, C Bergeron, M J Lewis, J Muscedere, N Godfrey, M Fleury, G Hollinger, E Malus, N Williams, M Hrytsyk, M Meade, C Spoto, A Freitag, K Choong, N Irwin, T Karachi, S Lapinsky, N Ferguson, C Ethier, T Stewart, S Lubchansky, D J Cook, E MacDonald, K Wilton, A Tkaczyk, M Kho, L Sivaloganathan, R Cirone, J Marshall, K Burns, O Smith, J Friedrich, B Fry, K Porretta, R Fowler, J Long, R Pinto, N K Adhikari, N Marinoff, A Maher, C Moran, J Delaney, J M Singh, M Herridge, J Granton, N Brockest, A Matte, C Tansey, L Chu, M Dennis, M di Nino, D McRitchie, J A Correa, C Martin, E Campbell, K Menon, D Creery, D Doherty, S Dhanani, R Ward, B Alsaati, K Choong, M Duffett, N Irwin, T L Caceres, J Hutchison, L Keating, R Gaiteiro, A M Krancevic, J Van Huyse, A Kornecki, J Foster, B Kukreti, D Boyle, K Kostiw, L Green, D Fung, N Jacko, J Herzog, G Berg, P Bettello, A Ross, N Marcello, R Agarwala, W Anderson, S Stoger, A Kumar, R Zarychanski, F Siddiqui, S Sharma, K Wiebe, C Ramsey, K Olafson, D Funk, A Garland, W Janz, N Marten, M Siddiqui, S Veroukis, M Kesselman, L Angelo, M WaliAhsan, C Penner, A Wong, S Shaw, J Friedt, G Wolffe, S Thomson, T Holt, B Andreychuk, T Stelfox, B Bobranska-Artiuch, M Heule, D Kutsogiannis, C Johnston, R Bartel, P Thompson, D Jossy, S Norris, D E Stollery, T MacLure, R Hardy-Joel, J Barchard, S M Bagshaw, M Irwin, A Joffe, C Sheppard, C Gresiuk, L Hodson, E Gilfoyle, K Menzies, P Dodek, B J Ashley, H Dunham, D Griesdale, D Foster, M Gardner, S Logie, S Reynolds, S Keenan, S Mans, J Palmer, M Svetik, G Wood, L Atkins, B Aldred-Portman, P Skippen, N Kissoon, G Krahn, J Burzynski, A Barclay, A Patel, K Kandola, K Pender, B Hanley, K D Braden, R Beckett, P Bilton

Affiliations

¹ Interdepartmental Division of Critical Care Medicine, Department of Medicine, University of Toronto, Toronto, ON, Canada.
² Rouge Valley Health System, Scarborough, ON, Canada.
³ Sunnybrook Hospital, Toronto, ON, Canada.
⁴ Centre de recherche clinique Étienne-Le Bel, Université de Sherbrooke, Sherbrooke, PQ, Canada.
⁵ Department of Critical Care Medicine, Sunnybrook Hospital, 2075 Bayview Avenue, Room D478, Toronto, ON, M4N 3M5, Canada.
⁶ Section of Critical Care Medicine, Department of Internal Medicine, Faculty of Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
⁷ Section of Infectious Diseases, Department of Internal Medicine, Faculty of Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
⁸ Department of Medical Microbiology, Faculty of Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
⁹ Department of, Faculty of Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
¹⁰ St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
¹¹ St. Joseph's Hospital, McMaster University, Hamilton, ON, Canada.
¹² CHU Sainte Justine, Université de Montréal, Montréal, PQ, Canada.
¹³ Department of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁴ Department of Physiology, University of Toronto, Toronto, ON, Canada.
¹⁵ Division of Respirology, Department of Medicine, University Health Network and Mount Sinai Hospital, Toronto, ON, Canada.
¹⁶ Critical Care Program, Department of Medicine, University Health Network and Mount Sinai Hospital, Toronto, ON, Canada.
¹⁷ Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
¹⁸ Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
¹⁹ Division of Critical Care, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
²⁰ Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
²¹ Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.
²² Interdepartmental Division of Critical Care Medicine, Department of Medicine, University of Toronto, Toronto, ON, Canada. rob.fowler@sunnybrook.ca.
²³ Department of Critical Care Medicine, Sunnybrook Hospital, 2075 Bayview Avenue, Room D478, Toronto, ON, M4N 3M5, Canada. rob.fowler@sunnybrook.ca.

PMID: 27036638
PMCID: PMC4818504
DOI: 10.1186/s13054-016-1230-8

Abstract

Background: Patients with 2009 pandemic influenza A(H1N1pdm09)-related critical illness were frequently treated with systemic corticosteroids. While observational studies have reported significant corticosteroid-associated mortality after adjusting for baseline differences in patients treated with corticosteroids or not, corticosteroids have remained a common treatment in subsequent influenza outbreaks, including avian influenza A(H7N9). Our objective was to describe the use of corticosteroids in these patients and investigate predictors of steroid prescription and clinical outcomes, adjusting for both baseline and time-dependent factors.

Methods: In an observational cohort study of adults with H1N1pdm09-related critical illness from 51 Canadian ICUs, we investigated predictors of steroid administration and outcomes of patients who received and those who did not receive corticosteroids. We adjusted for potential baseline confounding using multivariate logistic regression and propensity score analysis and adjusted for potential time-dependent confounding using marginal structural models.

Results: Among 607 patients, corticosteroids were administered to 280 patients (46.1%) at a median daily dose of 227 (interquartile range, 154-443) mg of hydrocortisone equivalents for a median of 7.0 (4.0-13.0) days. Compared with patients who did not receive corticosteroids, patients who received corticosteroids had higher hospital crude mortality (25.5% vs 16.4%, p = 0.007) and fewer ventilator-free days at 28 days (12.5 ± 10.7 vs 15.7 ± 10.1, p < 0.001). The odds ratio association between corticosteroid use and hospital mortality decreased from 1.85 (95% confidence interval 1.12-3.04, p = 0.02) with multivariate logistic regression, to 1.71 (1.05-2.78, p = 0.03) after adjustment for propensity score to receive corticosteroids, to 1.52 (0.90-2.58, p = 0.12) after case-matching on propensity score, and to 0.96 (0.28-3.28, p = 0.95) using marginal structural modeling to adjust for time-dependent between-group differences.

Conclusions: Corticosteroids were commonly prescribed for H1N1pdm09-related critical illness. Adjusting for only baseline between-group differences suggested a significant increased risk of death associated with corticosteroids. However, after adjusting for time-dependent differences, we found no significant association between corticosteroids and mortality. These findings highlight the challenges and importance in adjusting for baseline and time-dependent confounders when estimating clinical effects of treatments using observational studies.

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Figures

**Fig. 1**
Study participant enrollment flow diagram. *ICU* intensive care unit

See this image and copyright information in PMC

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References

1. Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, et al. Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med. 2009;361:680–9. doi: 10.1056/NEJMoa0904252. - DOI - PubMed
1. World Health Organization. Pandemic (H1N1) 2009. Update 74. 13 November 2009. http://www.who.int/csr/don/2009_11_13/en/index.html. Accessed 22 February 2016.
1. World Health Organization, Global Influenza Surveillance and Response System (GISRS). Influenza laboratory surveillance information. http://gamapserver.who.int/gareports/Default.aspx?ReportNo=6. Accessed 22 February 2016.
1. Dominguez-Cherit G, Lapinsky SE, Macias AE, et al. Critically ill patients with 2009 influenza A(H1N1) in Mexico. JAMA. 2009;302:1880–7. doi: 10.1001/jama.2009.1536. - DOI - PubMed
1. Kumar A, Zarychanski R, Pinto R, et al. Critically ill patients with 2009 influenza A(H1N1) infection in Canada. JAMA. 2009;302:1872–9. doi: 10.1001/jama.2009.1496. - DOI - PubMed

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[1] Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, et al. Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med. 2009;361:680–9. doi: 10.1056/NEJMoa0904252. - DOI - PubMed

[2] Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, et al. Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med. 2009;361:680–9. doi: 10.1056/NEJMoa0904252. - DOI - PubMed

[3] World Health Organization. Pandemic (H1N1) 2009. Update 74. 13 November 2009. http://www.who.int/csr/don/2009_11_13/en/index.html. Accessed 22 February 2016.

[4] World Health Organization. Pandemic (H1N1) 2009. Update 74. 13 November 2009. http://www.who.int/csr/don/2009_11_13/en/index.html. Accessed 22 February 2016.

[5] World Health Organization, Global Influenza Surveillance and Response System (GISRS). Influenza laboratory surveillance information. http://gamapserver.who.int/gareports/Default.aspx?ReportNo=6. Accessed 22 February 2016.

[6] World Health Organization, Global Influenza Surveillance and Response System (GISRS). Influenza laboratory surveillance information. http://gamapserver.who.int/gareports/Default.aspx?ReportNo=6. Accessed 22 February 2016.

[7] Dominguez-Cherit G, Lapinsky SE, Macias AE, et al. Critically ill patients with 2009 influenza A(H1N1) in Mexico. JAMA. 2009;302:1880–7. doi: 10.1001/jama.2009.1536. - DOI - PubMed

[8] Dominguez-Cherit G, Lapinsky SE, Macias AE, et al. Critically ill patients with 2009 influenza A(H1N1) in Mexico. JAMA. 2009;302:1880–7. doi: 10.1001/jama.2009.1536. - DOI - PubMed

[9] Kumar A, Zarychanski R, Pinto R, et al. Critically ill patients with 2009 influenza A(H1N1) infection in Canada. JAMA. 2009;302:1872–9. doi: 10.1001/jama.2009.1496. - DOI - PubMed

[10] Kumar A, Zarychanski R, Pinto R, et al. Critically ill patients with 2009 influenza A(H1N1) infection in Canada. JAMA. 2009;302:1872–9. doi: 10.1001/jama.2009.1496. - DOI - PubMed

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The influence of corticosteroid treatment on the outcome of influenza A(H1N1pdm09)-related critical illness

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The influence of corticosteroid treatment on the outcome of influenza A(H1N1pdm09)-related critical illness

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