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Peer-reviewed literature - 03 February 2012 (WHO, edited): Corticosteroids and influenza pneumonia
[Source: World Health Organization, full page: (LINK).]
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Peer-reviewed literature - 03 February 2012
Use of corticosteroids in patients with influenza pneumonia
The January 2012 issue of Journal of Infection contains a report by Diaz et al.[1] which assessed the effect of treatment with corticosteroids on survival among patients with primary viral pneumonia due to influenza A(H1N1)pdm09. The study was conducted as a prospective, observational, multicenter study in 148 intensive care units (ICU) in Spain.
The inclusion criteria were influenza-like symptoms, acute respiratory failure requiring ICU admission, and microbiological confirmation of influenza A(H1N1)pdm09. ICU admission criterion was determined by the need for intubation. Primary viral pneumonia was defined as acute respiratory distress and unequivocal alveolar opacities involving two or more lobes, a positive reaction for influenza by real time polymerase chain reaction on a respiratory specimen, and negative bacterial cultures of respiratory tract and blood during the acute phase of influenza virus infection. Administration of corticosteroid, antibiotic, antiviral medicine, and intubation were not standardized. From a total of 968 patients with confirmed influenza A(H1N1)pdm09 virus infection, 372 with the diagnosis of primary viral pneumonia were analyzed. Of those, 136 patients (36.6%) received corticosteroids.
A Cox regression analysis adjusted for severity and potential confounding factors demonstrated that the use of corticosteroid therapy was not significantly associated with mortality (RR=1.06, 95% CI 0.63-1.80; p = 0.82).
The authors concluded that corticosteroid therapy in patients with primary viral pneumonia due to influenza A(H1N1)pdm09 does not improve survival.
Comment:
Corticosteroids and other immune modulators have often been tried in the setting of influenza pneumonia and acute respiratory distress syndrome (ARDS) in an attempt to moderate the damage caused by the immune response.
Other investigators have found that corticosteroid administration may have deleterious effects. Martin-Loeches et al. found that early use of corticosteroids in patients admitted to the ICU due to influenza A(H1N1)pdm09 virus infection did not result in better outcomes and was associated with an increased risk of superinfections.[2]
Brun-Buisson et al. also found no beneficial effect of corticosteroids in patients with ARDS secondary to influenza pneumonia and that very early corticosteroids therapy may be harmful.[3]
Han et al reported early use of parenteral corticosteroids for pneumonia prevention increased the risk of critical disease or death from influenza A(H1N1)pdm09 infection.[4]
Kim et al concluded that adjuvant corticosteroid therapy among patients admitted to ICU or requiring mechanical ventilation with influenza A(H1N1)pdm09 infection was associated with higher mortality and risk of superinfections.[5]
Based on available data, WHO does not currently recommend the use of systemic high-dose corticosteroids for influenza-associated pneumonia. However, physiological replacement doses may be indicated in adrenocortical deficiency states and septic shock when hypotension is poorly responsive to fluid and vasopressor therapy.[6]
Prolonged use of systemic high-dose corticosteroids can result in serious adverse events in influenza virus-infected patients, including opportunistic infection and possibly prolong viral replication.
However, it should be noted that there may be other influenza associated complications, such as influenza associated encephalopathy, where the benefit of corticosteriods may outweigh the risk. [7-9]
Further work is needed to define the role of corticosteroids in these conditions and until definitive studies are available, clinical judgment should be used in weighing the risks and benefits of corticosteroid use in treating influenza associated complications. For more information on management of influenza complications, please see the WHO revised guidance on Clinical Management of human infection with pandemic (H1N1) 2009.[10]
Reference:
1. 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.
2. 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(2): 272-83.
3. 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(9): 1200-6.
4. 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(4): 326-33.
5. 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(9): 1207-14.
6. Surviving Sepsis Campaign. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008.
7. Ito S, Shima S, Ueda A, Kawamura N, Asakura K, Mutoh T. Transient splenial lesion of the corpus callosum in H1N1 influenza virus-associated encephalitis/encephalopathy. Intern Med. 2011; 50(8): 915-8.
8. 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(2): E53-6.
9. Munakata M, Kato R, Yokoyama H, Haginoya K, Tanaka Y, Kayaba J, et al. Combined therapy with hypothermia and anticytokine agents in influenza A encephalopathy. Brain Dev. 2000; 22(6): 373-7.
10. WHO Clinical management of human infection with pandemic (H1N1) 2009: revised guidance.
-Use of corticosteroids in patients with influenza pneumonia
The January 2012 issue of Journal of Infection contains a report by Diaz et al.[1] which assessed the effect of treatment with corticosteroids on survival among patients with primary viral pneumonia due to influenza A(H1N1)pdm09. The study was conducted as a prospective, observational, multicenter study in 148 intensive care units (ICU) in Spain.
The inclusion criteria were influenza-like symptoms, acute respiratory failure requiring ICU admission, and microbiological confirmation of influenza A(H1N1)pdm09. ICU admission criterion was determined by the need for intubation. Primary viral pneumonia was defined as acute respiratory distress and unequivocal alveolar opacities involving two or more lobes, a positive reaction for influenza by real time polymerase chain reaction on a respiratory specimen, and negative bacterial cultures of respiratory tract and blood during the acute phase of influenza virus infection. Administration of corticosteroid, antibiotic, antiviral medicine, and intubation were not standardized. From a total of 968 patients with confirmed influenza A(H1N1)pdm09 virus infection, 372 with the diagnosis of primary viral pneumonia were analyzed. Of those, 136 patients (36.6%) received corticosteroids.
A Cox regression analysis adjusted for severity and potential confounding factors demonstrated that the use of corticosteroid therapy was not significantly associated with mortality (RR=1.06, 95% CI 0.63-1.80; p = 0.82).
The authors concluded that corticosteroid therapy in patients with primary viral pneumonia due to influenza A(H1N1)pdm09 does not improve survival.
Comment:
Corticosteroids and other immune modulators have often been tried in the setting of influenza pneumonia and acute respiratory distress syndrome (ARDS) in an attempt to moderate the damage caused by the immune response.
Other investigators have found that corticosteroid administration may have deleterious effects. Martin-Loeches et al. found that early use of corticosteroids in patients admitted to the ICU due to influenza A(H1N1)pdm09 virus infection did not result in better outcomes and was associated with an increased risk of superinfections.[2]
Brun-Buisson et al. also found no beneficial effect of corticosteroids in patients with ARDS secondary to influenza pneumonia and that very early corticosteroids therapy may be harmful.[3]
Han et al reported early use of parenteral corticosteroids for pneumonia prevention increased the risk of critical disease or death from influenza A(H1N1)pdm09 infection.[4]
Kim et al concluded that adjuvant corticosteroid therapy among patients admitted to ICU or requiring mechanical ventilation with influenza A(H1N1)pdm09 infection was associated with higher mortality and risk of superinfections.[5]
Based on available data, WHO does not currently recommend the use of systemic high-dose corticosteroids for influenza-associated pneumonia. However, physiological replacement doses may be indicated in adrenocortical deficiency states and septic shock when hypotension is poorly responsive to fluid and vasopressor therapy.[6]
Prolonged use of systemic high-dose corticosteroids can result in serious adverse events in influenza virus-infected patients, including opportunistic infection and possibly prolong viral replication.
However, it should be noted that there may be other influenza associated complications, such as influenza associated encephalopathy, where the benefit of corticosteriods may outweigh the risk. [7-9]
Further work is needed to define the role of corticosteroids in these conditions and until definitive studies are available, clinical judgment should be used in weighing the risks and benefits of corticosteroid use in treating influenza associated complications. For more information on management of influenza complications, please see the WHO revised guidance on Clinical Management of human infection with pandemic (H1N1) 2009.[10]
Reference:
1. 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.
2. 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(2): 272-83.
3. 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(9): 1200-6.
4. 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(4): 326-33.
5. 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(9): 1207-14.
6. Surviving Sepsis Campaign. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008.
7. Ito S, Shima S, Ueda A, Kawamura N, Asakura K, Mutoh T. Transient splenial lesion of the corpus callosum in H1N1 influenza virus-associated encephalitis/encephalopathy. Intern Med. 2011; 50(8): 915-8.
8. 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(2): E53-6.
9. Munakata M, Kato R, Yokoyama H, Haginoya K, Tanaka Y, Kayaba J, et al. Combined therapy with hypothermia and anticytokine agents in influenza A encephalopathy. Brain Dev. 2000; 22(6): 373-7.
10. WHO Clinical management of human infection with pandemic (H1N1) 2009: revised guidance.
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