Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Critical Care
Published in: Critical Care 1/2015

Open Access 01-12-2015 | Research

Do corticosteroids reduce the mortality of influenza A (H1N1) infection? A meta-analysis

Authors: Yi Zhang, Wenjie Sun, Erik R Svendsen, Song Tang, Raina C MacIntyre, Peng Yang, Daitao Zhang, Quanyi Wang

Published in: Critical Care | Issue 1/2015

Login to get access

Abstract

Introduction

Corticosteroids are used empirically in influenza A (H1N1) treatment despite lack of clear evidence for effective treatment. This study aims to assess the efficacy of corticosteroids treatment for H1N1 infection.

Methods

Systematic review and meta-analysis were used to estimate the efficacy of corticosteroids for the prevention of mortality in H1N1 infection. Databases searched included MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Clinical Trials and so on, and bibliographies of retrieved articles, from April 2009 to October 2014. We included both cohort studies and case-control studies reported in English or Chinese that compared treatment effects between corticosteroids and non-corticosteroids therapy in inpatients with H1N1 virus infection. Cohort studies employed mortality as outcome, and case-control studies employed deaths as cases and survivors as controls; both were assessed in this meta-analysis.

Results

In total twenty-three eligible studies were included. Both cohort studies (nine studies, n = 1,405) and case-control studies (14 studies, n = 4,700) showed a similar trend toward increased mortality (cohort studies relative risk was 1.85 with 95% confidence interval (CI) 1.46 to 2.33; case-control studies odds ratio was 4.22 with 95% CI 3.10 to 5.76). The results from both subgroup analyses and sensitive analyses were consistent with each other, showing that steroid treatment is associated with mortality. However, considering the fact that corticosteroids were tend to be used in sickest case-patients and heterogeneity was observed between studies, we cannot make a solid conclusion.

Conclusions

Available evidence did not support the use of corticosteroids as standard care for patients with severe influenza. We conclude that further research is required.
Appendix
Available only for authorised users
Literature
1.
Libster R, Bugna J, Coviello S, Hijano DR, Dunaiewsky M, Reynoso N, et al. Pediatric hospitalizations associated with 2009 pandemic influenza A (H1N1) in Argentina. N Engl J Med. 2010;362:45–55.PubMed
2.
Louie J, Acosta M, Winter K, Jean C, Gavali S, Schechter R, et al. Factors associated with death or hospitalization due to pandemic 2009 influenza A(H1N1) infection in California. J Am Med Assoc. 2009;302:1896–902.
3.
Jain S, Kamimoto L, Bramley AM, Schmitz AM, Benoit SR, Louie J, et al. Hospitalized patients with 2009 H1N1 influenza in the United States, April–June 2009. N Engl J Med. 2009;361:1935–44.PubMed
4.
Dominguez-Cherit G, Lapinsky SE, Macias AE, Pinto R, Espinosa-Perez L, de la Torre A, et al. Critically Ill patients with 2009 influenza A(H1N1) in Mexico. J Am Med Assoc. 2009;302:1880–7.
5.
Kumar A, Zarychanski R, Pinto R, Cook DJ, Marshall J, Lacroix J, et al. Critically ill patients with 2009 influenza A(H1N1) infection in Canada. J Am Med Assoc. 2009;302:1872–9.
6.
Dawood FS, Iuliano AD, Reed C, Meltzer MI, Shay DK, Cheng PY, et al. Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study. Lancet Infect Dis. 2012;12:687–95.PubMed
7.
Barker CI, Snape MD. Pandemic influenza A H1N1 vaccines and narcolepsy: vaccine safety surveillance in action. Lancet Infect Dis. 2014;14:227–38.PubMed
8.
Hui DS, Lee N, Chan PK. Adjunctive therapies and immunomodulatory agents in the management of severe influenza. Antiviral Res. 2013;98:410–6.PubMedPubMedCentral
9.
Annane D. Pro: the illegitimate crusade against Corticosteroids for severe H1N1 pneumonia. Am J Respir Crit Care Med. 2011;183:1125–6.PubMed
10.
Confalonieri M, Urbino R, Potena A, Piattella M, Parigi P, Puccio G, et al. Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study. Am J Respir Crit Care Med. 2005;171:242–8.PubMed
11.
Meduri GU, Marik PE, Annane D. Prolonged glucocorticoid treatment in acute respiratory distress syndrome: evidence supporting effectiveness and safety. Crit Care Med. 2009;37:1800–3.PubMed
12.
Tang BM, Craig JC, Eslick GD, Seppelt I, McLean AS. Use of corticosteroids in acute lung injury and acute respiratory distress syndrome: a systematic review and meta-analysis. Crit Care Med. 2009;37:1594–603.PubMed
13.
Nie W, Zhang Y, Cheng J, Xiu Q. Corticosteroids in the treatment of community-acquired pneumonia in adults: a meta-analysis. PloS One. 2012;7:e47926.PubMedPubMedCentral
14.
Viasus D, Pano-Pardo JR, Pachon J, Campins A, Lopez-Medrano F, Villoslada A, et al. Factors associated with severe disease in hospitalized adults with pandemic (H1N1) 2009 in Spain. Clin Microbiol Infect. 2011;17:738–46.PubMed
15.
Rios FG, Estenssoro E, Villarejo F, Valentini R, Aguilar L, Pezzola D, et al. Lung function and organ dysfunctions in 178 patients requiring mechanical ventilation during the 2009 influenza A (H1N1) pandemic. Crit Care. 2011;15:R201.PubMedPubMedCentral
16.
Nin N, Soto L, Hurtado J, Lorente JA, Buroni M, Arancibia F, et al. Clinical characteristics and outcomes of patients with 2009 influenza A(H1N1) virus infection with respiratory failure requiring mechanical ventilation. J Crit Care. 2011;26:186–92.PubMed
17.
Zheng Y, He Y, Deng J, Lu Z, Wei J, Yang W, et al. Hospitalized children with 2009 influenza A (H1N1) infection in Shenzhen, China, November–December 2009. Pediatr Pulmonol. 2011;46:246–52.PubMed
18.
Choi WS, Baek JH, Seo YB, Kee SY, Jeong HW, Lee HY, et al. Severe influenza treatment guideline. Korean J Intern Med. 2014;29:132–47.PubMedPubMedCentral
19.
Kil HR, Lee JH, Lee KY, Rhim JW, Youn YS, Kang JH. Early corticosteroids treatment for severe pneumonia caused by 2009 H1N1 influenza virus. Criti Care. 2011;15:413.
20.
Quispe-Laime AM, Bracco JD, Barberio PA, Campagne CG, Rolfo VE, Umberger R, et al. H1N1 influenza A virus-associated acute lung injury: response to combination oseltamivir and prolonged corticosteroids treatment. Intensive Care Med. 2010;36:33–41.PubMed
21.
Rhim JW, Lee KY, Youn YS, Kang JH, Kim JC. Epidemiological and clinical characteristics of childhood pandemic 2009 H1N1 virus infection: an observational cohort study. BMC Infect Dis. 2011;11:225.PubMedPubMedCentral
22.
Confalonieri M, Cifaldi R, Dreas L, Viviani M, Biolo M, Gabrielli M. Methylprednisolone infusion for life-threatening H1N1-virus infection. Ther Adv Respir Dis. 2010;4:233–7.PubMed
23.
Confalonieri M, D'Agaro P, Campello C. Corticosteroids do not cause harmful increase of viral load in severe H1N1 virus infection. Intensive Care Med. 2010;36:1780–1.PubMedPubMedCentral
24.
Roberts C, Nirmalan M, O'Shea S. Steroid-sensitive post-viral inflammatory pneumonitis (PVIP). Am J Respir Crit Care Med. 2010;182:1089–90.PubMed
25.
Centers for Disease Control and Prevention. Intensive-care patients with severe novel influenza A (H1N1) virus infection – Michigan, June 2009. Morb Mortal Weekly Rep. 2009;58:749–52.
26.
WHO. WHO Guidelines for Pharmacological Management of Pandemic Influenza A(H1N1) 2009 and Other Influenza Viruses. Geneva: WHO Guidelines Approved by the Guidelines Review Committee; 2010.
27.
Writing Committee of the WHOCoCAoPI, Bautista E, Chotpitayasunondh T, Gao Z, Harper SA, Shaw M, et al. Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection. N Engl J Med. 2010;362:1708–19.
28.
Korean Journal of Infectious Diseases, Won SC, Ji HB, Yu BS, Sae YK, Hye WJ, et al. Severe influenza treatment guideline. Korean J Intern Med. 2014;29:132–47.
29.
30.
Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.PubMed
31.
Chawla R, Kansal S, Chauhan M, Jain A, Jibhkate BN. Predictors of mortality and length of stay in hospitalized cases of 2009 influenza A (H1N1): experiences of a tertiary care center. Indian J Crit Care Med. 2013;17:275–82.PubMedPubMedCentral
32.
Hong SB, Choi EY, Kim SH, Suh GY, Park MS, Lee MG, et al. Epidemiological analysis of critically ill adult patients with pandemic influenza A(H1N1) in South Korea. Epidemiol Infect. 2013;141:1070–9.PubMed
33.
Jose G-M, Antonio G-P, Marquez JA, Rafael Z, Rosa G, Sergio R-S, et al. Epidemiology, clinical features, and prognosis of elderly adults with severe forms of influenza A (H1N1). J Am Geriatr Soc. 2013;61:350–6.
34.
Jung JY, Park BH, Hong SB, Koh Y, Suh GY, Jeon K, et al. Acute kidney injury in critically ill patients with pandemic influenza A pneumonia 2009 in Korea: a multicenter study. J Crit Care. 2011;26:577–85.PubMed
35.
Kinikar AA, Kulkarni RK, Valvi CT, Mave V, Gupte N, Khadse S, et al. Predictors of mortality in hospitalized children with pandemic H1N1 influenza 2009 in Pune. India Indian J Pediatr. 2012;79:459–66.PubMed
36.
Xl L, Cao B, Liang LR, Gu L, Yang SG, Hu K, et al. Clinical features among severe and critical children admitted to hospital with 2009 pandemic influenza A(H1N1) in Mainland China. Chin J Clin. 2012;6:2663–8.
37.
Perez-Padilla R, De La Rosa-Zamboni D. Ponce De Leon S, Hernandez M, Quinones-Falconi F, Bautista E, et al. Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med. 2009;361:680–9.PubMed
38.
Sertogullarindan B, Ozbay B, Gunini H, Sunnetcioglu A, Arisoy A, Bilgin HM, et al. Clinical and prognostic features of patients with pandemic 2009 influenza A (H1N1) virus in the intensive care unit. Afr Health Sci. 2011;11:163–70.PubMedPubMedCentral
39.
Sun JJ, Li C, Wu DW, Li CH, Qin WH, Li YL, et al. Eighteen cases of 2009 influenza A H1N1 associated with respiratory failure in adults. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2010;22:156–60.PubMed
40.
Torres SF, Iolster T, Schnitzler EJ, Farias JA, Bordogna AC, Rufach D, et al. High mortality in patients with influenza A pH1N1 2009 admitted to a pediatric intensive care unit: a predictive model of mortality. Pediatr Crit Care Med. 2012;13:e78–83.PubMed
41.
Xi X, Xu Y, Jiang L, Li A, Duan J, Du B. Hospitalized adult patients with 2009 influenza A(H1N1) in Beijing. China: risk factors for hospital mortality BMC Infect Dis. 2010;10:256.PubMed
42.
Yu HT, Yang YJ, Zhang QX, Jia JG, Chen QS, Zang JP, et al. Clinical characteristics and risk factors of severe patients with novel pandemic influenza A H1N1. Chin J TCM WM Crit Care. 2011;18:142–5.
43.
Peng-jun ZHANG, Bin CAO, Xiao-li LI, Li-rong LIANG, Shi-gui YANG, Li GU, et al. Risk factors for adult death due to 2009 pandemic influenza A (H1N1)virus infection: a 2151 severe and critical cases analysis. Chin Med J. 2013;126:2222–8.
44.
Zhang X, Chen W, YIN X, Zhang C, Li R, Li G. Retrospective analysis of 146 severe of critically ill patients with influenza A/H1N1. J Kunming Med Univ. 2011:136–41.
45.
Viasus D, Pano-Pardo JR, Cordero E, Campins A, Lopez-Medrano F, Villoslada A, et al. Effect of immunomodulatory therapies in patients with pandemic influenza A (H1N1) 2009 complicated by pneumonia. J Infect. 2011;62:193–9.PubMed
46.
Patel KK, Patel AK, Mehta PM, Amin RP, Patel KP, Chuhan PC, et al. Clinical outcome of novel H1N1 (swine flu)-infected patients during 2009 pandemic at tertiary referral hospital in Western India. J Glob Infect Dis. 2013;5:93–7.PubMedPubMedCentral
47.
Martin-Loeches I, Lisboa T, Rhodes A, Moreno RP, Silva E, Sprung C, et al. Use of early Corticosteroids therapy on ICU admission in patients affected by severe pandemic (H1N1)v influenza A infection. Intensive Care Med. 2011;37:272–83.PubMed
48.
Mady A, Ramadan OS, Yousef A, Mandourah Y, Amr AA, Kherallah M. Clinical experience with severe 2009 H1N1 influenza in the intensive care unit at King Saud Medical City. Saudi Arabia J Infect Public Health. 2012;5:52–6.PubMed
49.
Diaz E, Martin-Loeches I, Canadell L, Vidaur L, Suarez D, Socias L, et al. Corticosteroids therapy in patients with primary viral pneumonia due to pandemic (H1N1) 2009 influenza. J Infect. 2012;64:311–8.PubMed
50.
Chen K, Li YJ, Li KZ, Wu ZX, Ning B, Yu LJ. Glucocorticoid treatment on severe A/H1N1 influenza. Chin J Nosocomiol. 2010;20:3149–51.
51.
Brun-Buisson C, Richard JC, Mercat A, Thiebaut AC, Brochard L. Early corticosteroids in severe influenza A/H1N1 pneumonia and acute respiratory distress syndrome. Am J Respir Crit Care Med. 2011;183:1200–6.PubMed
52.
Linko R, Pettila V, Ruokonen E, Varpula T, Karlsson S, Tenhunen J, et al. Corticosteroids therapy in intensive care unit patients with PCR-confirmed influenza A(H1N1) infection in Finland. Acta Anaesthesiol Scand. 2011;55:971–9.PubMed
53.
Kudo K, Takasaki J, Manabe T, Uryu H, Yamada R, Kuroda E, et al. Systemic corticosteroids and early administration of antiviral agents for pneumonia with acute wheezing due to influenza A(H1N1)pdm09 in Japan. PloS One. 2012;7:e32280.PubMedPubMedCentral
54.
Balaganesakumar SR, Murhekar MV, Swamy KK, Kumar MR, Manickam P, Pandian PRT. Risk factors associated with death among influenza A (H1N1) patients, Tamil Nadu, India, 2010. J Postgrad Med. 2013;59:9–14.PubMed
55.
Kim SH, Hong SB, Yun SC, Choi WI, Ahn JJ, Lee YJ, et al. Corticosteroids treatment in critically ill patients with pandemic influenza A/H1N1 2009 infection: analytic strategy using propensity scores. Am J Respir Crit Care Med. 2011;183:1207–14.PubMed
56.
Chudasama RK, Patel UV, Verma PB. Hospitalizations associated with 2009 influenza A (H1N1) and seasonal influenza in Saurashtra region. India J Infect Dev Ctries. 2010;4:834–41.PubMed
57.
Han K, Ma H, An X, Su Y, Chen J, Lian Z, et al. Early use of glucocorticoids was a risk factor for critical disease and death from pH1N1 infection. Clin Infect Dis. 2011;53:326–33.PubMed
58.
Lapinsky SE. H1N1 novel influenza A in pregnant and immunocompromised patients. Crit Care Med. 2010;38:e52–7.PubMed
59.
Lee N, Allen Chan KC, Hui DS, Ng EK, Wu A, Chiu RW, et al. Effects of early corticosteroids treatment on plasma SARS-associated coronavirus RNA concentrations in adult patients. J Clin Virol. 2004;31:304–9.PubMedPubMedCentral
60.
Lee N, Chan PK, Hui DS, Rainer TH, Wong E, Choi KW, et al. Viral loads and duration of viral shedding in adult patients hospitalized with influenza. J Infect Dis. 2009;200:492–500.PubMed
61.
Li C, Yang P, Zhang Y, Sun Y, Wang W, Zou Z, et al. Corticosteroids treatment ameliorates acute lung injury induced by 2009 swine origin influenza A (H1N1) virus in mice. PloS One. 2012;7:e44110.PubMedPubMedCentral
62.
Bai L, Gu L, Cao B, Zhai XL, Lu M, Lu Y, et al. Clinical features of pneumonia caused by 2009 influenza A(H1N1) virus in Beijing. China Chest. 2011;139:1156–64.PubMed
Metadata
Title
Do corticosteroids reduce the mortality of influenza A (H1N1) infection? A meta-analysis
Authors
Yi Zhang
Wenjie Sun
Erik R Svendsen
Song Tang
Raina C MacIntyre
Peng Yang
Daitao Zhang
Quanyi Wang
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2015
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-015-0764-5

Other articles of this Issue 1/2015

Critical Care 1/2015 Go to the issue

Research

A positive fluid balance is an independent prognostic factor in patients with sepsis

Commentary

Acute respiratory distress syndrome: does histology matter?

Commentary

How to understand the results of studies of glutamine supplementation

Research

Multicenter evaluation of a lateral-flow device test for diagnosing invasive pulmonary aspergillosis in ICU patients

Research

Copeptin levels are associated with organ dysfunction and death in the intensive care unit after out-of-hospital cardiac arrest

Commentary

Bioelectrical impedance vector analysis in the critically ill: cool tool or just another ‘toy’?