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1、激素在细菌性脑膜炎中的应用本讲稿第一页，共二十九页臨床問題臨床問題P(patient):Becterial meningitisI (intervention):SteroidC(comparison):PlaceboO(outcome):Efficacy本讲稿第二页，共二十九页背景背景說說明明Steroid在臨床上已被廣泛地應用，它具有抗炎、止痛及減緩異常血腦障壁之微血管的通透，以及降低顱內壓等作用。治療細菌性腦膜炎，雖然有著抗生素的介入治療，但卻仍具高死亡率，且造成嚴重的後遺症，不僅是一個衝擊，也是我們要去突破的瓶頸。本讲稿第三页，共二十九页背景背景說說明明感染性疾病有著強烈的地域性特色，
2、在西方國家細菌性腦膜炎最常見到的致病菌是鏈球菌(Streptococcus Pneumoniae)、李斯特菌(Listeria monocytogenes)，或是奈瑟氏菌(Neisseria meningitids)；我國則是鏈球菌(Streptococcus Pneumoniae)和取而代之的克雷伯氏菌(Klebsiella Pneumoniae)為主。至於Steroid針對Bacterial meningitis的使用，目前仍受爭議，至今尚無定論，但在有些病人身上是可以加速改善症狀，但對於減少後遺症則很難說。本讲稿第四页，共二十九页期待目標期待目標提供有用的文獻資料，期待進一步釐清Ster
3、oid 使用於Bacterial meningitis的角色及療效。本讲稿第五页，共二十九页搜尋步驟搜尋步驟-1Cochrane Library：Key Word：Combine bacterial meningitis AND steroid Found：【Reviews：1篇】【DARE：1篇】【CENTRAL：7篇】Combine bacterial meningitis AND dexamethasone Found：【Reviews：1篇】【DARE：3篇】【CENTRAL：23篇】本讲稿第六页，共二十九页搜尋步驟搜尋步驟-2EBMR-ACP Journal ClubKey Word
4、：Combine bacterial meningitis AND steroid Found：0篇篇 Combine bacterial meningitis AND dexamethasone Found：2篇篇本讲稿第七页，共二十九页搜尋步驟搜尋步驟-3NGC（National Guideline Clearinghouse）Key Word：Combine bacterial meningitis AND steroid Found：1篇篇 Combine bacterial meningitis AND dexamethasone Found：1篇篇本讲稿第八页，共二十九页搜尋步驟搜
5、尋步驟-4PubMedKey Word：Combine bacterial meningitis AND steroid Found：9篇篇 Combine bacterial meningitis AND dexamethasone Found：8篇篇 本讲稿第九页，共二十九页搜尋步驟搜尋步驟-5MEDLINEKey Word：Combine bacterial meningitis AND steroid Found：10篇篇 Combine bacterial meningitis AND dexamethasone Found：8篇篇本讲稿第十页，共二十九页搜尋步驟搜尋步驟-6EBM
6、ONLINEKey Word：Combine bacterial meningitis AND steroid Found：2篇篇Combine bacterial meningitis AND dexamethasone Found：2篇篇本讲稿第十一页，共二十九页結果摘要結果摘要Eighteen studies involving 1853 people were included.Overall,adjuvant corticosteroids were associated with lower case fatality(relativerisk(RR)0.76,95%condenc
7、e intervals(CI)0.59 to 0.98)and lower rates of both severe hearing loss(RR 0.36,95%CI 0.22 to 0.60)and long-term neurological sequelae(RR 0.66,95%CI 0.44 to 0.99).In children,corticosteroids reduced severe hearing loss in bacterial meningitis caused by Haemophilus influenzae(RR 0.31,95%CI 0.15 to 0.
8、62),as well as in meningitis caused by other bacteria than H.influenzae(RR 0.42,95%CI 0.20 to 0.89).van de Beek D,de Gans J,McIntyre P,Prasad K.Corticosteroids for acute bacterial meningitis.The Cochrane Database of Systematic Reviews 2003,Issue 3.本讲稿第十二页，共二十九页結果摘要結果摘要In adults,there was a reduction
9、 in case-fatality(RR 0.38,95%CI 0.18 to 0.78),however there were few data.Adverse events were not increased signicantly with the use of corticosteroids.Adjuvant corticosteroids are benecial in the treatment of children with acute bacterial meningitis.The limited data available in adults shows a tren
10、d in favour of adjuvant corticosteroids but a denite recommendation must await more studies.van de Beek D,de Gans J,McIntyre P,Prasad K.Corticosteroids for acute bacterial meningitis.The Cochrane Database of Systematic Reviews 2003,Issue 3.本讲稿第十三页，共二十九页結果摘要結果摘要7 RCTs（848 pt in total）：）：1.In Haemophi
11、lus influenzae type b meningitis,dexamethasone reduced severe hearing loss.(pooled OR0.31,95%CI:0.14,0.69)2.In pneumoccal meningitis,the pooled odds ratio for severe hearing loss was 0.52.(95%CI:0.17,1.46)3.Limiting dexamethasone therapy to 2 days may be optimal.本讲稿第十四页，共二十九页結果摘要結果摘要7 RCTs（848 pt in
12、 total）：）：4.The available evidence on adjunctive dexamethasone therapy confirms benefit for Haemophilus influenzae type b meningitis and,if commenced with or before parenteral antibiotics,suggests benefit for pneumoccal meningitis in childhood.P B McIntyre,C S Berkey,S M King,U B Schaad,T Kilpi,G Y
13、Kanra,C M Perez.Dexamethasone as adjunctive therapy in bacterial meningitis:a meta-analysis of randomized clinical trials since 1988(Structured abstract).The Cochrane Database of Systematic DARE.2000 本讲稿第十五页，共二十九页結果摘要結果摘要1 RCT（301 pt）:1.Early treatment with dexamethasone improves the outcome in adul
14、ts with acute bacterial meningitis and does not increase the risk of G-I bleeding.1 double blind placebo control study(40 pt):1.Dexamethasone was given in dose of 0.6mg/kg/day in divided dose,for first 4 days of therapy.2.First dose of dexamethasone was given 15 minutes prior to first dose dose of c
15、eftriaxone.3.Neurological complications and hearing loss were more common and severe in placebo group as compared to the dexamethasone group(p0.05).本讲稿第十六页，共二十九页結果摘要結果摘要1 Controlled Clinical Trial(68 pt):1.Dexamethasone was given in dose of 0.6mg/kg/day in divided dose,for first 4 days of therapy.2.
16、Mortality was lower in the group treated with dexamethasone but the difference was not statistically significant.3.Dexamethasone should be administered to all adultes patients with acute bacterial meningitis.本讲稿第十七页，共二十九页NeonatesAt present,there are insufficient data to make a recommendation on the
17、use of adjunctive dexamethasone in neonates with bacterial meningitis.(C-I)結果摘要結果摘要本讲稿第十八页，共二十九页結果摘要結果摘要Infants and Children1.Despite some variability in result of published trials,the Practice Guideline Committee believes the available evidence supports the use of adjunctive dexamethasone in infant
18、s and children with H.influenzae type b meningitis.(A-I)2.Dexamethasone should be initiated 10-20 min prior to,or at least concomitant with,the first antimicrobial dose,at 0.15 mg/kg every 6 h for 2-4 days.本讲稿第十九页，共二十九页結果摘要結果摘要Infants and Children3.Adjunctive dexamethasone should not be given to inf
19、ants and children who have already received antimicrobial therapy,because administration of dexamethasone in this circumstance is unlikely to improve patient outcome.(A-I)4.In infants and children with pneumococcal meningitis,there is controversy concerning the use of adjunctive dexamethasone therap
20、y.(C-II)本讲稿第二十页，共二十九页結果摘要結果摘要Adults1.The Practice Guideline Committee recommends use of dexamethasone(0.15 mg/kg every 6 h for 2-4 days with the first dose administered 10-20 min before,or at least concomitant with,the first dose of antimicrobial therapy)in adults with suspected or proven pneumococc
21、al meningitis.(A-I)2.Some experts would only administer adjunctive dexamethasone if the patient had moderate-to-severe disease(Glasgow Coma Scale score 11).本讲稿第二十一页，共二十九页結果摘要結果摘要Adults3.However,the Practice Guideline Committee thinks that adjunctive dexamethasone should be initiated in all adult pat
22、ients with suspected or proven pneumococcal meningitis,because assessment of the score may delay initiation of appropriate therapy.4.Dexamethasone should only be continued if the CSF Gram stain reveals gram-positive diplococci,or if blood or CSF cultures are positive for S.pneumoniae.本讲稿第二十二页，共二十九页結
23、果摘要結果摘要Adults4.Adjunctive dexamethasone should not be given to adult patients who have already received antimicrobial therapy,because administration of dexamethasone in this circumstance is unlikely to improve patient outcome.(A-I)5.The data are inadequate to recommend adjunctive dexamethasone to ad
24、ults with meningitis caused by other bacterial pathogens,although some authorities would initiate dexamethasone in all adults,because the etiology of meningitis is not always ascertained at initial evaluation.(B-III)本讲稿第二十三页，共二十九页結果摘要結果摘要Pneumococcal Meningitis1.The Practice Guideline Committee reco
25、mmends that adjunctive dexamethasone be administered to all adult patients with pneumococcal meningitis,even if the isolate is subsequently found to be highly resistant to penicillin and cephalosporins(B-III).2.Careful observation and follow-up are critical to determine whether dexamethasone is asso
26、ciated with adverse clinical outcome.本讲稿第二十四页，共二十九页結果摘要結果摘要Pneumococcal Meningitis 3.For data on outcome in patients with meningitis caused by resistant pneumococcal isolates,case reports and small case series may help ascertain whether dexamethasone is harmful to these patients.4.Furthermore,in pat
27、ients with suspected pneumococcal meningitis who receive adjunctive dexamethasone,addition of rifampin to the empirical combination of vancomycin plus a third-generation cephalosporin may be reasonable pending culture results and in vitro susceptibility testing(B-III).本讲稿第二十五页，共二十九页後記後記The available
28、 evidence supports the use of adjunctive dexamethasone in infants and children with H.influenzae type b meningitis.(0.15 mg/kg every 6 h for 2-4 days)Dexamethasone in adults with the adjunctive dexamethasone be administered to all adult patients with suspected or proven pneumococcal meningitis.(0.15
29、 mg/kg every 6 h for 2-4 days)本讲稿第二十六页，共二十九页後記後記For children and adults with acute bacterial meningitis,adjuvant dexamethasone therapy reduces mortality,hearing loss,and long term neurological sequelae.In patients with acute bacterial meningitis,adjunctuve treatment with dexamethasone was more effec
30、tive than placebo in improving disability and reducing death.本讲稿第二十七页，共二十九页後記後記Dexamethasone should now be considered the standard of care,provided that it is initiated before or at the same as antibiotics.Adjunctive dexamethasone should not be given to infants,children and adult patients who have already received antimicrobial therapy,because administration of dexamethasone in this circumstance is unlikely to improve patient outcome.本讲稿第二十八页，共二十九页Thanks for your attention本讲稿第二十九页，共二十九页