激素在細菌性腦膜炎中的應用

1、激素在細菌性腦膜炎中的應用第1頁，共29頁，2022年，5月20日，13點50分，星期四臨床問題P (patient) : Becterial meningitisI (intervention) : SteroidC (comparison) : PlaceboO (outcome) : Efficacy第2頁，共29頁，2022年，5月20日，13點50分，星期四背景說明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(nèi)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

2、突破的瓶頸。 第3頁，共29頁，2022年，5月20日，13點50分，星期四背景說明感染性疾病有著強烈的地域性特色，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

3、善癥狀，但對於減少後遺癥則很難說。 第4頁，共29頁，2022年，5月20日，13點50分，星期四期待目標提供有用的文獻資料，期待進一步釐清Steroid 使用於Bacterial meningitis的角色及療效。 第5頁，共29頁，2022年，5月20日，13點50分，星期四搜尋步驟- 1Cochrane Library：Key Word： Combine bacterial meningitis AND steroid Found：【Reviews：1篇】【DARE：1篇】 【CENTRAL：7篇】 Combine bacterial meningitis AND dexamethaso

4、ne Found：【Reviews：1篇】【DARE：3篇】 【CENTRAL：23篇】第6頁，共29頁，2022年，5月20日，13點50分，星期四搜尋步驟- 2EBMR- ACP Journal ClubKey Word： Combine bacterial meningitis AND steroid Found：0篇 Combine bacterial meningitis AND dexamethasone Found：2篇第7頁，共29頁，2022年，5月20日，13點50分，星期四搜尋步驟- 3NGC（National Guideline Clearinghouse） Key W

5、ord： Combine bacterial meningitis AND steroid Found：1篇 Combine bacterial meningitis AND dexamethasone Found：1篇第8頁，共29頁，2022年，5月20日，13點50分，星期四搜尋步驟- 4PubMedKey Word： Combine bacterial meningitis AND steroid Found：9篇 Combine bacterial meningitis AND dexamethasone Found：8篇 第9頁，共29頁，2022年，5月20日，13點50分，星期

6、四搜尋步驟- 5MEDLINEKey Word： Combine bacterial meningitis AND steroid Found：10篇 Combine bacterial meningitis AND dexamethasone Found：8篇第10頁，共29頁，2022年，5月20日，13點50分，星期四搜尋步驟- 6EBM ONLINEKey Word： Combine bacterial meningitis AND steroid Found：2篇Combine bacterial meningitis AND dexamethasone Found：2篇第11頁，共

7、29頁，2022年，5月20日，13點50分，星期四結(jié)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)

8、 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 0

9、.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.第12頁，共29頁，2022年，5月20日，13點50分，星期四結(jié)果摘要In adults, there was a reduction in case-fatality (RR 0.38, 95% CI 0.18 to 0.78), however there

10、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 trend in favour of adjuvant corticosteroids but a denite recom

11、mendation 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.第13頁，共29頁，2022年，5月20日，13點50分，星期四結(jié)果摘要7 RCTs（848 pt in total）：1. In Haemophilus influenzae type b meningitis, dexa

12、methasone 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.第14頁，共29頁，2022年，5月20日，13點50分，星期四結(jié)果摘要7 RCTs（848 pt in total）：4. The a

13、vailable 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 Kanra, C M

14、 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 第15頁，共29頁，2022年，5月20日，13點50分，星期四結(jié)果摘要1 RCT（301 pt ）:1. Early treatment with dexamethasone improves the o

15、utcome in adults 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 fi

16、rst dose dose of ceftriaxone.3. Neurological complications and hearing loss were more common and severe in placebo group as compared to the dexamethasone group (p0.05).第16頁，共29頁，2022年，5月20日，13點50分，星期四結(jié)果摘要1 Controlled Clinical Trial (68 pt):1. Dexamethasone was given in dose of 0.6mg/kg/day in divide

17、d dose, for first 4 days of therapy.2. 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.第17頁，共29頁，2022年，5月20日，13點50分，星期四NeonatesAt present,

18、there are insufficient data to make a recommendation on the use of adjunctive dexamethasone in neonates with bacterial meningitis. (C-I) 結(jié)果摘要第18頁，共29頁，2022年，5月20日，13點50分，星期四結(jié)果摘要Infants and Children1. Despite some variability in result of published trials, the Practice Guideline Committee believes th

19、e 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 concomitant with, the first antimicrobial dose, at 0.15 mg/kg every 6 h for 2-4 days.第19頁，共29頁，202

20、2年，5月20日，13點50分，星期四結(jié)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 improve patient outcome. (A-I)4. In infants and children wit

21、h pneumococcal meningitis, there is controversy concerning the use of adjunctive dexamethasone therapy. (C-II)第20頁，共29頁，2022年，5月20日，13點50分，星期四結(jié)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 be

22、fore, 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 Scale score 11). 第21頁，共29頁，2022年，5月

23、20日，13點50分，星期四結(jié)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 o

24、nly be continued if the CSF Gram stain reveals gram-positive diplococci, or if blood or CSF cultures are positive for S. pneumoniae. 第22頁，共29頁，2022年，5月20日，13點50分，星期四結(jié)果摘要Adults4. Adjunctive dexamethasone should not be given to adult patients who have already received antimicrobial therapy, because ad

25、ministration of dexamethasone 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, becaus

26、e the etiology of meningitis is not always ascertained at initial evaluation. (B-III)第23頁，共29頁，2022年，5月20日，13點50分，星期四結(jié)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

27、 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 associated with adverse clinical outcome. 第24頁，共29頁，2022年，5月20日，13點50分，星期四結(jié)果摘要Pneumococcal Meningitis 3. For data on

28、 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 patients with suspected pneumococcal meningitis who receive adjunctive dexamethasone, addition

29、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).第25頁，共29頁，2022年，5月20日，13點50分，星期四後記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)Dexamethasone in adults with the adjunc