The 60-day temperature-dependent degradation of midazolam and Lorazepam in the prehospital environment.
The 60-day temperature-dependent degradation of midazolam and Lorazepam in the prehospital environment.
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DOI：
10.3109/10903127.2012.722177
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发表时间：
2013-01
影响因子：
2.4
通讯作者：
Neurological Emergencies Treatment Trials investigators
中科院分区：
文献类型：
--
作者：
McMullan JT;Pinnawin A;Jones E;Denninghoff K;Siewart N;Spaite DW;Zaleski E;Silbergleit R;Neurological Emergencies Treatment Trials investigators
治疗院前癫痫持续状态的最佳苯二氮卓类药物的选择尚不清楚。劳拉西泮在急诊科是首选，但对非冷藏储存的担忧限制了紧急医疗服务（EMS）的使用。咪达唑仑越来越受欢迎，但其热稳定性没有记录。本研究评价了劳拉西泮和咪达唑仑在EMS环境中放置60天后的温度依赖性降解。劳拉西泮或咪达唑仑样品收集之前（n = 139）或之后（n = 229）60天的EMS部署在春夏月份在美国的14个大都市地区。根据当地机构政策，将药物储存在每分钟记录温度的研究盒中，并储存在EMS装置中。推导出每个样本的平均动力学温度（MKT）暴露量。在中心实验室通过高效液相色谱法测定药物浓度。通过线性回归分析浓度作为MKT的函数。展开前，两种苯二氮卓类药物的实测浓度相对于标示浓度均<1.0。60天后，咪达唑仑未显示降解（平均相对浓度1.00，95%置信区间[CI] 1.00-1.00），并且在温度暴露期间保持稳定（校正R2 -0.008）。劳拉西泮几乎没有降解（平均相对浓度0.99，95% CI 0.98-0.99），但降解与MKT增加相关（校正R2 0.278）。咪达唑仑和劳拉西泮降解的温度依赖性差异具有统计学显著性（T =-5.172，p < 0.001）。在EMS环境中60天后，劳拉西泮经历了小但具有统计学显著性的温度依赖性降解。需要进行额外的研究，以评估60天后是否发生临床显著恶化。咪达唑仑在这段时间内没有降解，即使在高温条件下也是如此。
The choice of the optimal benzodiazepine to treat prehospital status epilepticus is unclear. Lorazepam is preferred in the emergency department, but concerns about nonrefrigerated storage limits emergency medical services (EMS) use. Midazolam is increasingly popular, but its heat stability is undocumented. This study evaluated temperature-dependent degradation of lorazepam and midazolam after 60 days in the EMS environment. Lorazepam or midazolam samples were collected prior to (n = 139) or after (n = 229) 60 days of EMS deployment during spring–summer months in 14 metropolitan areas across the United States. Medications were stored in study boxes that logged temperature every minute and were stored in EMS units per local agency policy. Mean kinetic temperature (MKT) exposure was derived for each sample. Drug concentrations were determined in a central laboratory by high-performance liquid chromatography. Concentration as a function of MKT was analyzed by linear regression. Prior to deployment, measured concentrations of both benzodiazepines were 1.0 relative to labeled concentration. After 60 days, midazolam showed no degradation (mean relative concentration 1.00, 95% confidence interval [CI] 1.00–1.00) and was stable across temperature exposures (adjusted R2 –0.008). Lorazepam experienced little degradation (mean relative concentration 0.99, 95% CI 0.98–0.99), but degradation was correlated to increasing MKT (adjusted R2 0.278). The difference between the temperature dependence of degradation of midazolam and lorazepam was statistically significant (T = −5.172, p < 0.001). Lorazepam experiences small but statistically significant temperature-dependent degradation after 60 days in the EMS environment. Additional study is needed to evaluate whether clinically significant deterioration occurs after 60 days. Midazolam shows no degradation over this duration, even in high-heat conditions.
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影响因子：
4.4
作者：
McMullan, Jason;Sasson, Comilla;Silbergleit, Robert
通讯作者：
Silbergleit, Robert
影响因子：
3.6
作者：
Gottwald, MD;Akers, LC;Alldredge, BK
通讯作者：
Alldredge, BK
DOI：
10.1056/nejmoa1107494
发表时间：
2012-02-16
期刊：
The New England journal of medicine
影响因子：
--
作者：
Silbergleit R;Durkalski V;Lowenstein D;Conwit R;Pancioli A;Palesch Y;Barsan W;NETT Investigators
通讯作者：
NETT Investigators
DOI：
10.1016/j.prehos.2003.12.017
发表时间：
2004-04-01
期刊：
Prehospital emergency care : official journal of the National Association of EMS Physicians and the National Association of State EMS Directors
影响因子：
--
作者：
Brown, Lawrence H;Krumperman, Kurt;Fullagar, Christopher J
通讯作者：
Fullagar, Christopher J
影响因子：
158.5
作者：
Alldredge, BK;Gelb, AM;Lowenstein, DH
通讯作者：
Lowenstein, DH