High first dose quinine regimen for treating severe malaria

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Abstract
Quinine is used for treating severe malaria. There are arguments for giving an initial high dose. We examined the evidence for and against this policy. To assess the clinical outcomes and adverse events of a high first (loading) dose regimen of quinine compared with a uniform (no loading) dose regimen in people with severe malaria. We searched the Cochrane Infectious Diseases Group Specialized Register (February 2009), CENTRAL (The Cochrane Library Issue 1, 2009), MEDLINE (1966 to February 2009), EMBASE (1974 to February 2009), LILACS (1982 to February 2009), and conference proceedings for relevant abstracts. We also contacted researchers working in the field and checked the reference lists of all studies. Randomized controlled trials comparing a high first (loading) dose of intravenous quinine with a uniform (no loading) dose of intravenous quinine in people with severe malaria. Two reviewers independently assessed the risk of bias in the trials and extracted data (including adverse event data). We used Review Manager 5.0 to analyse the data: risk ratio (RR) for binary data and mean difference (MD) for continuous data with 95% confidence intervals (CI). We contacted study authors for additional information. Four trials (n = 144) met the inclusion criteria. Loading dose was associated with fewer deaths, but this was not statistically significant (RR 0.62, 95% CI 0.19 to 2.04; 3 trials). Loading dose was associated with faster clearance of parasites (WMD ‐7.44 hours, 95% CI ‐13.24 to ‐1.64 hours; 2 trials), resolution of fever (WMD ‐11.11 hours, 95% CI ‐20.04 to ‐2.18 hours; 2 trials). No statistically significant difference was detected for recovery of consciousness, neurological sequelae, or convulsions, but the numbers were small. Quinine loading dose reduced fever clearance time and parasite clearance time. Data are insufficient to directly demonstrate an impact of loading dose on risk of death. 高初始劑量奎寧使用於嚴重瘧疾之治療 奎寧被用來治療嚴重瘧疾。但給予高初始劑量的奎寧仍有爭議。我們檢視這方面的證據以作為政策上的依據。 評估罹患嚴重瘧疾者使用高初始(初載)劑量奎寧與相同(無初載)劑量奎寧之臨床結果及不良事件之比較。 我們搜尋了the Cochrane Infectious Diseases Group's trials register (2006年七月), CENTRAL (The Cochrane Library Issue3, 2006), MEDLINE (1966 年至 2006年七月), EMBASE (1974 年至 2006年七月), LILACS (1982年至 2006年七月)，以及會議報告的相關摘要。我們也聯絡了在該領域工作的研究學者，並檢視了所有研究的參考文獻目錄。 隨機對照試驗，靜脈給予罹患嚴重瘧疾病人高初始(初載)劑量奎寧與給予相同(無初載)劑量奎寧之比較。 兩位審查員獨立評估所有試驗的方法學品質以及擷取資料(包括不良事件資料)。我們使用Review Manager 4.2來分析數據：類別變項的數據(dichotomous data)是以相對風險(relative risk, RR)來計算；連續變項的數據(continuous data)則是以加權平均數差(weighted mean difference, WMD)及95%信賴區間(95% confidence intervals, CI)來表示。 共4個試驗(n = 144)符合納入標準。初載劑量(loading dose)組死亡人數較少，但統計上並無顯著差別 (RR 0.62， CI 0.19 to 2.04，3個試驗)。初載劑量組對寄生蟲的清除較快(WMD −7.44 小時，CI −13.24 to −1.64小時，2 個試驗)，發燒緩解較快(WMD −11.11小時，CI −20.04 to2.18小時，2 個試驗)。但在意識恢復、神經後遺症或是痙攣上並無統計學上的顯著差異，不過個案數並不多。 使用初載劑量奎寧能減少發燒緩解時間及寄生蟲清除時間。所得數據尚不足以直接呈現初載劑量對於死亡風險的影響。 本摘要由三軍總醫院洪乃勻翻譯。 此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。 無總結

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