|Year : 2018 | Volume
| Issue : 1 | Page : 2-5
Steroid therapy in swine flu: Beneficial or harmful
Department of Critical Care Medicine, Indraprastha Apollo Hospitals, New Delhi, India
|Date of Web Publication||2-Apr-2018|
C/O Tapan Kumar Samui, Jilipi Bagan Near, Atachaki, P.O. - Sripally, Burdwan - 713 103, West Bengal
Source of Support: None, Conflict of Interest: None
H1N1 influenza virus is responsible for respiratory illness that may range from mild symptoms of common cold to severe disease on presentation that needs hospitalization and management in intensive care. Corticosteroids are used to treat disease of immunity, inflammation or salt, and water balance. Here, the role of corticosteroid in swine flu is reviewed in various literatures. It is found that result of corticosteroid use in the management of swine flu patients is unsatisfactory. Instead of benefit, it is potentially harmful. It causes to develop higher duration of hospital stay, prolonged mechanical ventilation and ultimately increased mortality.
Keywords: Hospital stay, influenza, mortality, ventilation
|How to cite this article:|
Samui K. Steroid therapy in swine flu: Beneficial or harmful. Apollo Med 2018;15:2-5
| Introduction|| |
The first cases of swine flu virus during pandemic were reported on April 21 in California and in Mexico on April 23, 2009. The first case in India was reported on May 13, 2009, in Hyderabad. The World Health Organization declared influenza A (H1N1) as pandemic influenza in mid-year of 2009.,, Seasonal influenza infects in children, but it causes less mortality. However, it predominantly infects people older than 65 years of age. However, children were disproportionately infected by pandemic influenza A (H1N1) more than older age-groups in 2009. Risk factors for severe pandemic H1N1 infection and seasonal influenza are similar except younger age and obesity which have the highest risk of severe outcomes. Influenza has a notable mortality burden worldwide.,,, Clinical features include fever, cough, sore throat, hoarseness, malaise, muscular pain, loose motion and vomiting, arthralgia, chills and headaches with ophthalmalgia, photophobia, etc. Complications may happen such as bronchitis, pneumonia, myocarditis, pericarditis, encephalitis, and shock affecting mainly in people with immune system compromise. Delayed antiviral treatment, severe hypoxemia, and multisystem organ failure significantly affect critically ill patients with influenza. In the recent years, oseltamivir, a neuraminidase inhibitor, is being extensively used after being stockpiled by multiple governments. Using randomized controlled trials, it is found that the drug had very limited benefit on preventing complications and viral transmission., It also reduces the duration of clinical symptoms by about half a day only. Corticosteroid is a class of drug based on hormones formed from adrenal gland, which is used to reduce inflammatory activity. However, steroid can cause increased appetite, weight gain, neuropsychiatric change, muscle weakness, blurred vision, increased growth of body hair, easy bruising, lower resistance to infection, puffy face, acne, osteoporosis, worsening of diabetes, high blood pressure, stomach irritation, nervousness, restlessness, difficulty in sleeping, cataracts or glaucoma, water retention, swelling, etc., Here, we will discuss about the role of steroid therapy in patients of H1N1 influenza whether it is beneficial or harmful.
| Methods|| |
In clinical practice, it is found that some clinicians prefer to give steroid in the management of selective patients who are normal individuals and have developed swine flu pneumonia. Some clinicians do not prefer to give steroid at all in the management of isolated H1N1 pneumonia without any known comorbidity. A fair number of standard literatures on the role of steroid therapy in swine flu are studied. Their results have been discussed here, and a conclusion is drawn based on literature review.
| Discussion|| |
Corticosteroids favor spread of infections because of decreased capacity of defensive cells to kill microorganisms. They also interfere with healing and scar formation, peptic ulcer with asymptomatic perforation. Indiscriminate use of this group of drugs is hazardous. They suppress cell-mediated immunity in which T-cells are primarily involved. There may be inhibition of interleukin-1 (IL-1) release from macrophages, inhibition of lL-2 formation, inhibition of T-cell proliferation, and suppression of natural killer cells. Immunosuppression in the body has many adverse effects. Hence, it should be used cautiously in clinical practice. Study by Rewar et al. reported that high dose corticosteroids, in particular, did not cause any benefit, rather it harmed patients. However, low-dose corticosteroids (hydrocortisone 200–400 mg/day) might be used in persisting septic shock (systolic blood pressure <90 mm hg). Rodrigo et al. found that adjunctive corticosteroid therapy increased mortality. They did not find sufficient evidence to determine the effectiveness of corticosteroids for patients with influenza. Brun-Buisson et al. studied 208 acute respiratory failure patients. On receiving corticosteroid, mortality and the risk of hospital-acquired pneumonia increased to develop particularly, an early receiving group within 3 days after mechanical ventilation. Linko et al. prospectively found the same mortality of two groups of patients who received and did not receive corticosteroid among the influenza confirmed patients in intensive care unit during the pandemic influenza in 2009. Mady et al. study observed increased mortality of three times in pandemic influenza patients admitted to intensive care unit in 2009. A study by the European Society of Intensive Care Medicine showed that corticosteroid use resulted in the development of high risk of hospital-acquired pneumonia. Study by Kawashima et al. in Japan reported no benefit on steroid therapy among pediatric influenza encephalopathy patients. In a lot of clinical case series and reports, critically ill patients developing pneumonia and encephalopathy improved with administration of corticosteroid.,,,,,,,,,, Interesting thing was that all the studies showed negative result in patients of pandemic swine flu in 2009. Maraví-Poma et al. reported higher mortality in corticosteroid administration group compared to nonadministration group among severe influenza diseased pregnant women although this difference was not very statistically significant. Han et al. observed higher mortality in the early administration group of corticosteroid (within 72 h of influenza symptoms) compared to delayed receiving and nonreceiving group of corticosteroid. Diaz et al. study on viral pneumonia did not find any beneficial effect for steroid. As per Kudo et al. study, systemic administration of corticosteroids along with early administration of antiviral agents may prevent progression to severe pneumonia in a population of H1N1 pneumonia irrespective of the presence of wheeze. Delaney et al. found significant increased risk of death associated with corticosteroids in patients with H1N1 influenza. Yang et al. observed that management with corticosteroid for patients with influenza virus infection has no better outcomes and may increase mortality and nosocomial infections. It also prolongs the duration of mechanical ventilation and intensive care unit stay. Brun-Buisson et al. study provided no evidence of a beneficial effect of steroids in patients with acute respiratory distress syndrome secondary to influenza pneumonia. It also suggested the harmfulness of early corticosteroid therapy. Meta-analysis by Zhang et al. did not support to use corticosteroids as standard care for patients with severe influenza. As per Kim et al. study, adjuvant corticosteroids significantly increased higher mortality in critically ill patients with H1N1 influenza. A study by Nedel et al. concluded that beneficial effects of corticosteroid therapy did not exist at all. It increased overall mortality. It might be associated with higher chances of development of hospital-acquired pneumonia, longer duration of mechanical ventilation, and intensive care unit stay.
Corticosteroid drugs have anti-inflammatory action. They can reduce exudation, increased capillary permeability, cellular infiltration, phagocytic activity, and also the late responses such as capillary proliferation, collagen deposition, activation of fibroblast, and scar formation. Quispe-Laime et al. suggested the use of a low to moderate dose of a steroid. Logic was that it may significantly improve lung injuries. However, this study was done with small size of the study populations. Sohn et al. reported that the corticosteroid therapy increased recovery to all 37 pediatric patients presenting exacerbating influenza pneumonia after administering within 48 h of presentation. Kil et al. also observed that the duration of fever decreased, the necessity of oxygen therapy were significantly less and the number of cure rate from severe influenza pneumonia was greater in pediatric group of patients where steroid was administered. However, the sample of the study population of both these two studied was small and the patients were limited to pediatric age group.
However, it is difficult to say fairly about the effect according to the dose, giving time and baseline of steroid use. Steroid usage is variable by physicians. Only a few numbers of previous studies have been found to give information in detail. Hence, further randomized clinical study is needed to specify the matter.
| Conclusion|| |
Corticosteroid should not be used routinely in patients with swine flu except in conditions like associated obstructive airway disease, adrenal insufficiency where the therapeutic effect of steroid has already been proven. The use of steroid in normal individuals developed swine flu may increase prolongation of mechanical ventilation, duration of intensive care unit stay, and mortality.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Chowell G, Bertozzi SM, Colchero MA, Lopez-Gatell H, Alpuche-Aranda C, Hernandez M, et al.
Severe respiratory disease concurrent with the circulation of H1N1 influenza. N
Engl J Med 2009;361:674-9.
Garten RJ, Davis CT, Russell CA, Shu B, Lindstrom S, Balish A, et al.
Antigenic and genetic characteristics of swine-origin 2009 A (H1N1) influenza viruses circulating in humans. Science 2009;325:197-201.
Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team, Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, et al.
Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N
Engl J Med 2009;360:2605-15.
New influenza A (H1N1) virus: WHO guidance on public health measures, 11 June 2009. Wkly Epidemiol Rec 2009;84:261-4.
Pitman RJ, Melegaro A, Gelb D, Siddiqui MR, Gay NJ, Edmunds WJ, et al.
Assessing the burden of influenza and other respiratory infections in England and wales. J Infect 2007;54:530-8.
Miller E, Hoschler K, Hardelid P, Stanford E, Andrews N, Zambon M, et al.
Incidence of 2009 pandemic influenza A H1N1 infection in England: A cross-sectional serological study. Lancet 2010;375:1100-8.
Van Kerkhove MD, Vandemaele KA, Shinde V, Jaramillo-Gutierrez G, Koukounari A, Donnelly CA, et al.
Risk factors for severe outcomes following 2009 influenza A (H1N1) infection: A global pooled analysis. PLoS Med 2011;8:e1001053.
Feng L, Shay DK, Jiang Y, Zhou H, Chen X, Zheng Y, et al.
Influenza-associated mortality in temperate and subtropical Chinese cities, 2003-2008. Bull World Health Organ 2012;90:279-88B.
Wong CM, Chan KP, Hedley AJ, Peiris JS. Influenza-associated mortality in Hong Kong. Clin Infect Dis 2004;39:1611-7.
Yang L, Ma S, Chen PY, He JF, Chan KP, Chow A, et al.
Influenza associated mortality in the subtropics and tropics: Results from three Asian cities. Vaccine 2011;29:8909-14.
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.
Witczak A, Prystupa A, Kurys-Denis E, Borys M, Czuczwar M, Niemcewicz M, et al.
Acute respiratory distress syndrome (ARDS) complicating influenza A/H1N1v infection – A clinical approach. Ann Agric Environ Med 2013;20:820-2.
Chowell G, Bertozzi SM, Colchero MA, Lopez-Gatell H, Alpuche-Aranda C, Hernandez M, et al
. Severe respiratory disease concurrent with the circulation of H1N1 influenza. N
Engl J Med 2009;361:674-9
Jefferson T, Jones M, Doshi P, Spencer EA, Onakpoya I, Heneghan CJ, et al.
Oseltamivir for influenza in adults and children: Systematic review of clinical study reports and summary of regulatory comments. BMJ 2014;348:g2545.
Dobson J, Whitley RJ, Pocock S, Monto AS. Oseltamivir treatment for influenza in adults: A meta-analysis of randomised controlled trials. Lancet 2015;385:1729-37.
Heneghan CJ, Onakpoya I, Thompson M, Spencer EA, Jones M, Jefferson T, et al.
Zanamivir for influenza in adults and children: Systematic review of clinical study reports and summary of regulatory comments. BMJ 2014;348:g2547.
Rewar S, Mirdha D, Rewar P. Treatment and prevention of pandemic H1N1 influenza. Ann Glob Health 2015;81:645-53.
Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam J, Lim WS. Corticosteroids as adjunctive therapy in the treatment of influenza. Cochrane Database Syst Rev 2016;3:CD010406.
Brun-Buisson C, Richard JC, Mercat A, Thiébaut AC, Brochard L; REVA-SRLF A/H1N1v 2009 Registry Group, et al.
Early corticosteroids in severe influenza A/H1N1 pneumonia and acute respiratory distress syndrome. Am J Respir Crit Care Med 2011;183:1200-6.
Linko R, Pettilä V, Ruokonen E, Varpula T, Karlsson S, Tenhunen J, et al.
Corticosteroid therapy in Intensive Care Unit patients with PCR-confirmed influenza A (H1N1) infection in Finland. Acta Anaesthesiol Scand 2011;55:971-9.
Mady A, Ramadan OS, Yousef A, Mandourah Y, Amr AA, Kherallah M, et al.
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.
Martin-Loeches I, Lisboa T, Rhodes A, Moreno RP, Silva E, Sprung C, et al.
Use of early corticosteroid therapy on ICU admission in patients affected by severe pandemic (H1N1) v influenza A infection. Intensive Care Med 2011;37:272-83.
Kawashima H, Morichi S, Okumara A, Nakagawa S, Morishima T; Collaborating Study Group on Influenza-Associated Encephalopathy in Japan, et al.
Treatment of pandemic influenza A (H1N1) 2009-associated encephalopathy in children. Scand J Infect Dis 2012;44:941-7.
Athauda D, Andrews TC, Holmes PA, Howard RS. Multiphasic acute disseminated encephalomyelitis (ADEM) following influenza type A (swine specific H1N1). J Neurol 2012;259:775-8.
Roberts C, Nirmalan M, O'Shea S. Steroid-sensitive post-viral inflammatory pneumonitis (PVIP). Am J Respir Crit Care Med 2010;182:1089-90.
Samejima T, Takayanagi N, Ishiguro T, Miyahara Y, Yanagisawa T, Sugita Y, et al.
Case of novel influenza A (H1N1) pneumonia with shrinkage of a pulmonary lesion. Nihon Kokyuki Gakkai Zasshi 2010;48:930-7.
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.
Sakurai T, Kimura A, Tanaka Y, Hozumi I, Ogura S, Inuzuka T, et al.
Case of adult influenza type A virus-associated encephalopathy successfully treated with primary multidisciplinary treatments. Rinsho Shinkeigaku 2007;47:639-43.
Ohtsuki N, Kimura S, Nezu A, Aihara Y. Effects of mild hypothermia and steroid pulse combination therapy on acute encephalopathy associated with influenza virus infection: Report of two cases. No To Hattatsu 2000;32:318-22.
Ando M, Miyazaki E, Hiroshige S, Ashihara Y, Okubo T, Ueo M, et al.
Virus associated hemophagocytic syndrome accompanied by acute respiratory failure caused by influenza A (H3N2). Intern Med 2006;45:1183-6.
Hibino M, Akazawa K, Hikino K, Oe M. A case of acute respiratory distress syndrome associated with pandemic influenza A (H1N1) pneumonia which was aggravated by the cessation of corticosteroid therapy. Nihon Kokyuki Gakkai Zasshi 2011;49:955-63.
Wang Y, Lu YY, Zheng J, Da W, Ping C, Da DZ, et al.
Treatment of critically ill influenza A H1N1 patients in plateau region. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2010;22:153-5.
Djibré M, Berkane N, Salengro A, Ferrand E, Denis M, Chalumeau-Lemoine L, et al.
Non-invasive management of acute respiratory distress syndrome related to influenza A (H1N1) virus pneumonia in a pregnant woman. Intensive Care Med 2010;36:373-4.
Kawashima H, Togashi T, Yamanaka G, Nakajima M, Nagai M, Aritaki K, et al.
Efficacy of plasma exchange and methylprednisolone pulse therapy on influenza-associated encephalopathy. J Infect 2005;51:E53-6.
Maraví-Poma E, Martin-Loeches I, Regidor E, Laplaza C, Cambra K, Aldunate S, et al.
Severe 2009 A/H1N1v influenza in pregnant women in Spain. Crit Care Med 2011;39:945-51.
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 pH 1N1 infection. Clin Infect Dis 2011;53:326-33.
Diaz E, Martin-Loeches I, Canadell L, Vidaur L, Suarez D, Socias L, et al.
Corticosteroid therapy in patients with primary viral pneumonia due to pandemic (H1N1) 2009 influenza. J Infect 2012;64:311-8.
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.
Delaney JW, Pinto R, Long J, Lamontagne F, Adhikari NK, Kumar A, et al.
The influence of corticosteroid treatment on the outcome of influenza A (H1N1pdm09)-related critical illness. Crit Care 2016;20:75.
Yang JW, Fan LC, Miao XY, Mao B, Li MH, Lu HW, et al.
Corticosteroids for the treatment of human infection with influenza virus: A systematic review and meta-analysis. Clin Microbiol Infect 2015;21:956-63.
Zhang Y, Sun W, Svendsen ER, Tang S, MacIntyre RC, Yang P, et al.
Do corticosteroids reduce the mortality of influenza A (H1N1) infection? A meta-analysis. Crit Care 2015;19:46.
Kim SH, Hong SB, Yun SC, Choi WI, Ahn JJ, Lee YJ, et al.
Corticosteroid 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.
Nedel WL, Nora DG, Salluh JI, Lisboa T, Póvoa P. Corticosteroids for severe influenza pneumonia: A critical appraisal. World J Crit Care Med 2016;5:89-95.
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 corticosteroid treatment. Intensive Care Med 2010;36:33-41.
Sohn YR, Kim JH, Ma SH, Lee KY, Kang JH. Severe pneumonia caused by 2009 pandemic influenza A (H1N1) virus in children and corticosteroid treatment. Korean J Pediatr Infect Dis 2011;18:193-200.
Kil HR, Lee JH, Lee KY, Rhim JW, Youn YS, Kang JH, et al.
Early corticosteroid treatment for severe pneumonia caused by 2009 H1N1 influenza virus. Crit Care 2011;15:413.