サイトカインストームへのステロイドの適用は脳症と鳥インフルで異なる。

ここでは、「サイトカインストームへのステロイドの適用は脳症と鳥インフルで異なる。」 に関する記事を紹介しています。
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新しい記事を書く事で広告が消せます。


サイトカインストームの治療に関して、訂正します。


申し訳ありません。

鳥インフルエンザに関してのWHOからの臨床取り扱い指針が2007年に出ていました。


その中に、ステロイドの大量投与療法は有効性が認められない、

二次感染などの良くない影響を引き起こすことが多いとの記述がありました。


季節性インフルエンザに感染した日本の小児患者に引き起こされた

インフルエンザ脳症に対応する治療方法と、

鳥インフルエンザに感染した急性肺炎の状態の患者への治療方法とでは、

ステロイドの使い方に対する考え方など、

全然異なる対応が必要だということです。


そうすると、豚インフルエンザ感染の治療方法も

まだ手探りで進むしかないということですね。

鳥インフルエンザ感染による急性肺炎に近い状況だとすると、

ステロイドパルスセラピーなんてとんでもないということになります。


以下がWHOのガイドラインです。


Clinical management of human infection with avian influenza
A (H5N1) virus
Updated advice 15 August 2007

部分抜粋です。

Systemic corticosteroids. Systemic corticosteroids have often been used for treatment of acute
lung injury (ALI)/ARDS due to A(H5N1) disease, presumably for their anti-inflammatory and
anti-fibrotic effects. (4, 41, 42, 43). However, there has been no clear clinical benefit observed,
and most A(H5N1) virus-infected patients receiving corticosteroids have died, although the
incompleteness of reporting, the variable dosage and timing of administration, and other
confounding factors limit interpretation of these findings. One small randomized study of
A(H5N1) virus-infected patients in Viet Nam found that all 4 corticosteroid recipients died (4).
No studies of these agents in relevant animal models of A(H5N1) virus infection have been
published to date. Consequently, recommendations about the use of corticosteroids can only be
derived from data and publications describing their use in associated syndromes such as ARDS,
sepsis, and SARS.

Corticosteroids have been used in the treatment of other respiratory viral diseases. Despite the
extensive use of corticosteroids, no clear evidence of clinical benefit was evident in SARS
patients (44), and one study found that plasma SARS-CoV RNA concentrations were higher in
the second and third weeks of the illness in SARS patients given intravenous hydrocortisone than
in those given placebo during the first week of the illness (45). Other randomized, controlled
studies have found that corticosteroids are associated with delayed viral clearance in RSV1 and
rhinovirus illness (46, 47, 48, 49). These studies suggested that early use of corticosteroids may
prolong viral replication in some respiratory viral illnesses. In addition, corticosteroid use in
SARS and other conditions has been associated with adverse effects including avascular bone
necrosis and psychosis (50, 51).

Numerous clinical trials have examined the efficacy of corticosteroids in preventing acute lung
injury (ALI) / ARDS unrelated to A(H5N1) virus infection (52, 53) and in the treatment of both
early stage and late-stage (fibrotic) ALI/ARDS. To date no consistent survival benefit has been
found (54, 55). High-dose corticosteroids increase the risks of secondary infections (56, 57) and
related mortality (52). One recent, small trial reported that prolonged, lower dose
methylprednisolone therapy might be beneficial in early ARDS, although no significant increase
in long-term survival was found (58). However, these findings require confirmation by studies
conducted on a larger numbers of patients. The National Heart, Lung and Blood Institute
(NHLBI)2 of USA ARDS Network recently examined the role of methylprednisolone (MP) in the
treatment of ARDS patients of at least 7 days duration in a randomized placebo-controlled study.
MP therapy increased the number of ventilator-free days, shock-free days and ICU-free days in
the first month but was also associated with increased 60-day and 180-day mortality rates among
patients enrolled for more than 13 days after the onset of ARDS. MP recipients were more likely
to return to assisted ventilation after extubation than those on placebo and also experienced
neuromuscular weakness. Overall, the available evidence does not support the use of MP in
treating early or late ALI/ARDS (59).
Hypotension and septic shock have been reported in patients with A(H5N1) virus infection (42,
43). High dose corticosteroids have not been shown to be beneficial in septic shock unrelated to

A(H5N1) virus infection (52, 60). However, several studies have reported relative adrenal
insufficiency with septic shock, defined as SBP1 < 90 mmHg despite adequate fluid resuscitation,
requiring support with inotropic or vasoconstrictor drugs (61, 62, 63). A retrospective analysis of
one prospective study found that low doses of corticosteroids for 7 days were associated with
lower 28-day mortality in the subpopulation of septic shock patients with early ARDS and nonresponse
to a short corticotrophin test, but no difference was seen in test responders (61, 64).
Therefore, replacement dose corticosteroids (equivalent of hydrocortisone 200–300mg/day in
divided doses, often combined with 50 μg fludrocortisone daily, in adults) should be considered
for treatment of persisting septic shock in A(H5N1) virus-infected patients.

In summary, there is no clear benefit in treating A(H5N1) virus-associated pneumonia or ARDS
with high-dose corticosteroids while there is the potential for significant harm, particularly in
terms of immunosuppression leading to enhanced A(H5N1) viral replication or secondary
infections, and musculoskeletal side effects. It is recommended that high dose steroids should not
be given for treatment of A(H5N1) disease. Lower dose steroids should be considered in the
treatment of refractory septic shock according to current best-practice guidelines, but the benefit
in paediatric septic shock is unknown (65).


上記内容に関する文献です。

41. Yuen K et al. Clinical features and rapid viral diagnosis of human disease associated with
avian influenza A H5N1 virus. Lancet, 1998, 351:467–471.
42. Chotpitayasunondh T et al. Human disease from influenza A (H5N1), Thailand, 2004.
Emerging Infectious Diseases, 2005, 11:201-209.
43. Hien TT et al. Avian influenza A (H5N1) in 10 patients in Vietnam. New England Journal of
Medicine, 2004, 350:1179–1188.
44. Stockman L, Bellamy R, Garner P. SARS: systematic review of treatment effects. PLoS
Medicine, 2006, 3:e343.
45. Lee N et al. Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus
RNA concentrations in adult patients. Journal of Clinical Virology, 2004, 31:304–309.
46. Buckingham S et al. A randomized, double-blind, placebo-controlled trial of dexamethasone
in severe respiratory syncytial virus (RSV) infection: effects on RSV quantity and clinical
outcome. Journal of Infectious Diseases, 2002,185:1222–1228.
47. Gustafson L et al. Oral prednisone therapy in experimental rhinovirus infections. Journal of
Allergy and Clinical Immunology, 1996, 97:1009–1014.
48. Puhakka T et al. The common cold: effects of intranasal fluticasone propionate treatment.
Journal of Allergy and Clinical Immunology, 1998, 101:726–731.
49. Domachowske J et al. Glucocorticoid administration accelerates mortality of pneumovirusinfected
mice. Journal of Infectious Diseases,184:1518–1523.
50. Hong N, Du X. Avascular necrosis of bone in severe acute respiratory syndrome. Clinical
Radiology, 2004, 59:602–608.
51. Lee D et al. Factors associated with psychosis among patients with severe acute respiratory
syndrome: a case-control study. Clinical Infectious Diseases, 2004, 39:1247–1249.
52. Bone R et al. Early methylprednisolone treatment for septic syndrome and the adult
respiratory distress syndrome. Chest, 1987, 92:1032–1036.
53. Luce J et al. Ineffectiveness of high-dose methylprednisolone in preventing parenchymal lung
injury and improving mortality in patients with septic shock. American Review of Respiratory
Disease, 1988, 138:62–68.
54. Bernard G et al. High-dose corticosteroids in patients with the adult respiratory distress
syndrome. New England Journal of Medicine,1987, 317:1565–1570.
55. Meduri G et al. Effect of prolonged methylprednisolone therapy in unresolving acute
respiratory distress syndrome: a randomized controlled trial. Journal of the American Medical
Association, 1998, 280:159–165.
56. Sprung C et al. The effects of high-dose corticosteroids in patients with septic shock. A
prospective, controlled study. New England Journal of Medicine,1984, 311:1137–1143.
57. Wang H et al. Fatal aspergillosis in a patient with SARS who was treated with corticosteroids.
New England Journal of Medicine, 2003, 349:507–508.
58. Meduri G et al. Methylprednisolone influsion in early severe ARDS results of a randomized
controlled trial. Chest, 2007, 131:954–963.
59. Steinberg K et al. Efficacy and safety of corticosteroids for persistent acute respiratory
distress syndrome. New England Journal of Medicine, 2006, 354:1671–1684.
60. Cronin L et al. Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of
the literature. Critical Care Medicine, 1995, 23:1430–1439.
61. Annane D et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on
mortality in patients with septic shock. Journal of the American Medical Association, 2002,
288:862–871.
62. Keh D et al. Immunologic and hemodynamic effects of "low-dose" hydrocortisone in septic
shock: a double-blind, randomized, placebo-controlled, crossover study. American Journal of
Respiratory and Critical Care Medicine, 2003, 167:512–520.
63. Annane D et al. Corticosteroids for severe sepsis and septic shock: a systematic review and
meta-analysis. British Medical Journal, 2004, 329:480.
64. Annane D, Sebille V, Bellissant E, for the Ger-Inf-05 Study group. Effect of low doses of
corticosteroids in septic shock patients with or without early respiratory distress syndrome.
Critical Care Medicine, 2006, 34:22–30.
65. Dellinger R et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and
septic shock. Critical Care Medicine, 2004, 32:858–873.


WHOのガイドラインのページは以下です。

Clinical management of human infection with avian influenza A (H5N1) virus

混乱を招く記述内容で失礼いたしました。




関連タグ : 鳥インフルエンザ, WHO, 治療のガイドライン, ステロイド大量投与, 二次感染, インフルエンザ脳症, サイトカインストーム,

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