- 學位論文
比較高海拔疾病用藥之預防效果：網絡整合分析
Comparing Prevention Efficacy of Drugs for High Altitude Illness: A Network Meta-analysis
摘要
研究背景: 高海拔疾病包括3種形式：急性高山症、高海拔腦水腫及 高海拔肺水腫。高海拔腦水腫與急性高山症的預防可同時處理。只有 處於發生高海拔疾病的中高度風險，才需要使用預防藥物。 研究目的: 比較不同急性高山症與高海拔肺水腫用藥之預防效果。 研究方法: 在PubMed、Embase、Clinicalkey與Cochrane Library搜尋隨機臨床試驗。針對發生高海拔疾病的中高度風險，定義爬升高度的 納入條件為(1)一日內自海拔低於1200公尺爬升至高於2800公尺(2) 自海拔3000公尺後爬升速率大於500公尺/日。研究對象為年齡18歲至65歲的健康成年人。套用工具是以NetMetaXL為介面導入WinBUGS執行的貝氏網狀統合分析。 主要結果評估: 評估急性高山症發生率的依據是露易絲湖急性高山症指數：總分大於或等於3分且合併出現頭痛症狀。而評估高海拔肺水腫發生率的依據是臨床檢查與胸部X光攝影。 研究結果: (1)急性高山症發生率：有5個隨機臨床試驗共838人被納入研究。在8種介入成對比較中(以勝算比與95%信賴區間表示)，與安慰劑相比，急性高山症發生率較低且有統計學上顯著差異之4種藥物介入有口服125 mg Acetazolamide一日兩次(0.12, 0.02-0.56)、吸入200 μg Budesonide一日兩次(0.17, 0.06-0.45)、口服4 mg Dexamethasone一日兩次(0.27, 0.08-0.83)、口服250 mg Acetazolamide一日兩次(0.42, 0.20-0.89)。急性高山症發生率較低但無統計學上顯著差異之2種藥物介入有口服25 μg Procaterol一日兩次(0.45, 0.11-1.85)、吸入160 μg Budesonide / 4.5 μg Formoterol一日兩次(0.46, 0.11-1.82)。口服50 mg Spironolactone一日兩次預防急性高山症的效果卻劣於安慰劑。口服125 mg或250 mg Acetazolamide一日兩次的急性高山症發生率則無統計學上顯著差異(0.29, 0.05-1.55)。(2)高海拔肺水腫發生率：有3個隨機臨床試驗共85人被納入研究。在5種介入成對比較中(以勝算比與95%信賴區間表示)，與安慰劑相比，發生率較低且有統計學上顯著差異的藥物介入有口服8 mg Dexamethasone一日兩次(0.00, 0.00-0.11)、口服10 mg Tadalafil一日兩次(0.03, 0.00-0.45)、口服20 mg Nifedipine每8小時一次(0.04, 0.00-0.50)、吸入125μg Salmeterol每12小時一次(0.17, 0.03-0.93)。在隨機效應模式中，4個藥物介入之間的比較均無統計學上顯著差異。 結論: 有效預防急性高山症且將副作用降至最低的Acetazolamide劑 量為125 mg一日兩次。Dexamethasone可能成為同時降低發生急性高 山症與高海拔肺水腫風險的理想預防選擇。
並列摘要
Background: There were 3 forms of high altitude illness (HAI): acute mountain sickness (AMS), high altitude cerebral edema (HACE), and high altitude pulmonary edema (HAPE). HACE and AMS can be addressed simultaneously. Prophylaxis medicines should only be considered for individuals with moderate-to-high risk of HAI. Aims: Comparing prevention efficacy of AMS ans HAPE between different medicines. Methods: PubMed, Embase, Clinicalkey, and Cochrane Library were searched for randomized controlled trials. The inclusion criteria about ascent profile in moderate-to-high risk of HAI were: (1) ascending form < 1200 m to > 2800 m in 1 day (2) ascending > 500 m/d at altitudes above 3000 m. Study subjects were healthy adults aged 18-65. NetMetaXL provided an interface for conducting a Bayesian network meta-analysis with WinBUGS. Main Outcome Measure: AMS incidence was based on Lake Louise Acute Mountain Sickness Score: A total score ≥ 3, in the presence of a headache. HAPE incidence was assessed by clinical examination and chest radiography. Results: (1) AMS incidence: 5 RCTs and 838 subjects were included. In pairwise comparisons between 8 arms, 4 pharmacy arms showed significantly lower AMS incidence compared with placebo, showed as odds ratio(OR) and 95% credible interval(CRI), oral 125 mg Acetazolamide BID: 0.12(0.02-0.56), inhaled 200 μg Budesonide BID: 0.17(0.06-0.45), oral 4 mg Dexamethasone BID: 0.27(0.08-0.83), oral 250 mg Acetazolamide BID: 0.42(0.20-0.89). 2 pharmacy arms showed no significant difference in AMS incidence: oral 25 μg Procaterol BID: 0.45(0.11-1.85), inhaled 160 μg Budesonide / 4.5 μg Formoterol BID: 0.46(0.11-1.82). However, oral 50 mg Spironolactone BID was inferior to placebo in reducing AMS incidence. There were no significant differences about AMS incidence between oral 125 mg Acetazolamide BID and 250 mg Acetazolamide BID: 0.29(0.05-1.55). (2) HAPE incidence: 3 RCTs and 85 subjects were included. In pairwise comparisons between 5 arms, 4 pharmacy arms showed significantly lower HAPE incidence compared with placebo, showed as OR and 95% CRI, oral 8 mg Dexamethasone twice daily: 0.00(0.00-0.11), oral 10 mg Tadalafil twice daily: 0.03(0.00-0.45), oral 20 mg Nifedipine every 8 hours: 0.04(0.00-0.50), inhaled 125 μg Salmeterol every 12 hours: 0.17(0.03-0.93). There were no significant difference between 4 pharmacy arms in the random effects model. Conclusion: The effective preventive dose of Acetazolamide that also minimizes side effects was 125mg BID. Dexamethasone may be the ideal prophylaxis to reduce the risk of both AMS and HAPE.