The Effect of Ketoconazole on Post-Burn Inflammation, Hypermetabolism and Clinical Outcomes
The Effect of Ketoconazole on Post-Burn Inflammation, Hypermetabolism and Clinical Outcomes
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DOI：
10.1371/journal.pone.0035465
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发表时间：
2012-05-11
期刊：
影响因子：
3.7
通讯作者：
Herndon, David N.
中科院分区：
文献类型：
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作者：
Jeschke, Marc G.;Williams, Felicia N.;Herndon, David N.
背景：高皮质醇血症已被认为是严重烧伤后全身痉挛的主要激素介质。抗真菌药酮康唑可抑制皮质醇的合成。因此，我们研究了酮康唑对烧伤后皮质醇水平和高分解代谢反应的影响，在一项前瞻性随机试验（区组随机化2：1）。方法/主要发现：55例严重烧伤的小儿患者，>30%的总体表面积（TBSA）烧伤被纳入本试验。患者随机接受标准治疗加安慰剂（对照组，n = 38）或酮康唑（n = 23）。在整个急性住院过程中获得人口统计学、临床数据、血清激素水平、血清细胞因子表达谱、器官功能、高代谢指标、肌肉蛋白合成、伤口感染脓毒症发生率和身体组成。使用Fisher精确检验、Student t检验以及参数和非参数双向重复测量方差分析（如适用）进行统计分析。患者在人口统计学、年龄和TBSA烧伤方面相似。酮康唑有效地阻断了皮质醇的产生，尿皮质醇水平的8倍升高正常化表明了这一点[F（1，376）= 85.34，p
Background: Hypercortisolemia has been suggested as a primary hormonal mediator of whole-body catabolism following severe burn injury. Ketoconazole, an anti-fungal agent, inhibits cortisol synthesis. We, therefore, studied the effect of ketoconazole on post-burn cortisol levels and the hyper-catabolic response in a prospective randomized trial (block randomization 2:1).Methodology/Principal Findings: Fifty-five severely burned pediatric patients with >30% total body surface area (TBSA) burns were enrolled in this trial. Patients were randomized to receive standard care plus either placebo (controls, n = 38) or ketoconazole (n = 23). Demographics, clinical data, serum hormone levels, serum cytokine expression profiles, organ function, hypermetabolism measures, muscle protein synthesis, incidence of wound infection sepsis, and body composition were obtained throughout the acute hospital course. Statistical analysis was performed using Fisher's exact test, Student's t-test, and parametric and non-parametric two-way repeated measures analysis of variance where applicable. Patients were similar in demographics, age, and TBSA burned. Ketoconazole effectively blocked cortisol production, as indicated by normalization of the 8-fold elevation in urine cortisol levels [F(1, 376) = 85.34, p