1、Steroid for Bacterial meningitis高雄市立小港醫院 神經科1臨床問題P (patient) : Becterial meningitisI (intervention) : SteroidC (comparison) : PlaceboO (outcome) : Efficacy2背景說明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，且造成嚴重的後遺癥，不僅是一個衝擊，也是我們要去突破的瓶頸。 3背景說明感染性疾病有著強烈的地域性特色，在

2、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癥狀，但對於減少後遺癥則很難說。 4期待目標提供有用的文獻資料，期待進一步釐清Steroid 使用於Bacteria

3、l meningitis的角色及療效。 5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】6搜尋步驟- 2EBMR- ACP Journal ClubKey Word： Combine bacterial meningitis AND st

4、eroid Found：0篇 Combine bacterial meningitis AND dexamethasone Found：2篇7搜尋步驟- 3NGC（National Guideline Clearinghouse） Key Word： Combine bacterial meningitis AND steroid Found：1篇 Combine bacterial meningitis AND dexamethasone Found：1篇8搜尋步驟- 4PubMedKey Word： Combine bacterial meningitis AND steroid Foun

5、d：9篇 Combine bacterial meningitis AND dexamethasone Found：8篇 9搜尋步驟- 5MEDLINEKey Word： Combine bacterial meningitis AND steroid Found：10篇 Combine bacterial meningitis AND dexamethasone Found：8篇10搜尋步驟- 6EBM ONLINEKey Word： Combine bacterial meningitis AND steroid Found：2篇Combine bacterial meningitis A

6、ND dexamethasone Found：2篇11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% condence 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

7、) 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 0.62), as well as in meningitis caused by other bacteria than H. influenzae (RR 0.42, 95%CI

8、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 3.12結果摘要In adults, there was a reduction in case-fatality (RR 0.38, 95% CI 0.18 to 0.78), however there were few data. Adverse events

9、 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 trend in favour of adjuvant corticosteroids but a denite recommendation must await more stu

10、dies.van de Beek D, de Gans J, McIntyre P, Prasad K. Corticosteroids for acute bacterial meningitis. The Cochrane Database of Systematic Reviews 2003, Issue 3.13結果摘要7 RCTs（848 pt in total）：1. In Haemophilus influenzae type b meningitis, dexamethasone reduced severe hearing loss. (pooled OR0.31,95%CI

11、: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.14結果摘要7 RCTs（848 pt in total）：4. The available evidence on adjunctive dexamethasone therapy confirms benefit for Haemophilus in

12、fluenzae 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 Kanra, C M Perez.Dexamethasone as adjunctive therapy in bacterial meningitis: a meta- analysis of r

13、andomized clinical trials since 1988 (Structured abstract). The Cochrane Database of Systematic DARE . 2000 15結果摘要1 RCT（301 pt ）:1. Early treatment with dexamethasone improves the outcome in adults with acute bacterial meningitis and does not increase the risk of G-I bleeding.1 double blind placebo

14、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 ceftriaxone.3. Neurological complications and hearing loss were more common and severe in placebo grou

15、p as compared to the dexamethasone group (p0.05).16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. Mortality was lower in the group treated with dexamethasone but the difference was not statistically significa

16、nt.3. Dexamethasone should be administered to all adultes patients with acute bacterial meningitis.17NeonatesAt present, there are insufficient data to make a recommendation on the use of adjunctive dexamethasone in neonates with bacterial meningitis. (C-I) 結果摘要18結果摘要Infants and Children1. Despite s

17、ome variability in result of published trials, the Practice Guideline Committee believes the available evidence supports the use of adjunctive dexamethasone in infants and children with H. influenzae type b meningitis. (A-I)2. Dexamethasone should be initiated 10-20 min prior to, or at least concomi

18、tant with, the first antimicrobial dose, at 0.15 mg/kg every 6 h for 2-4 days.19結果摘要Infants and Children3. Adjunctive dexamethasone should not be given to infants and children who have already received antimicrobial therapy, because administration of dexamethasone in this circumstance is unlikely to

19、 improve patient outcome. (A-I)4. In infants and children with pneumococcal meningitis, there is controversy concerning the use of adjunctive dexamethasone therapy. (C-II)20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

20、 dose administered 10-20 min before, or at least concomitant with, the first dose of antimicrobial therapy) in adults with suspected or proven pneumococcal meningitis. (A-I)2. Some experts would only administer adjunctive dexamethasone if the patient had moderate-to-severe disease (Glasgow Coma Scal

21、e score 11). 21結果摘要Adults3. However, the Practice Guideline Committee thinks that adjunctive dexamethasone should be initiated in all adult patients with suspected or proven pneumococcal meningitis, because assessment of the score may delay initiation of appropriate therapy. 4. Dexamethasone should

22、only be continued if the CSF Gram stain reveals gram-positive diplococci, or if blood or CSF cultures are positive for S. pneumoniae. 22結果摘要Adults4. Adjunctive dexamethasone should not be given to adult patients who have already received antimicrobial therapy, because administration of dexamethasone

23、 in this circumstance is unlikely to improve patient outcome. (A-I)5. The data are inadequate to recommend adjunctive dexamethasone to adults with meningitis caused by other bacterial pathogens, although some authorities would initiate dexamethasone in all adults, because the etiology of meningitis

24、is not always ascertained at initial evaluation. (B-III)23結果摘要Pneumococcal Meningitis1. The Practice Guideline Committee recommends that adjunctive dexamethasone be administered to all adult patients with pneumococcal meningitis, even if the isolate is subsequently found to be highly resistant to pe

25、nicillin and cephalosporins (B-III). 2. Careful observation and follow-up are critical to determine whether dexamethasone is associated with adverse clinical outcome. 24結果摘要Pneumococcal Meningitis 3. For data on outcome in patients with meningitis caused by resistant pneumococcal isolates, case repo

26、rts and small case series may help ascertain whether dexamethasone is harmful to these patients. 4. Furthermore, in patients 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).25後記The available 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)Dex