deSouza Ian S, Thode Henry C, Shrestha Pragati, Allen Robert, Koos Jessica, Singer Adam J
Department of Emergency Medicine, SUNY Downstate Health Sciences University and Kings County Hospital Center, Brooklyn, NY, USA.
Department of Emergency Medicine, Stony Brook University, NY, USA.
Am J Emerg Med. 2022 Jan;51:363-373. doi: 10.1016/j.ajem.2021.11.011. Epub 2021 Nov 14.
Safe and effective tranquilization of the acutely agitated patient is challenging, and head-to-head comparisons of medications are limited. We aimed to identify the most optimal agent(s) for rapid tranquilization of the severely agitated patient in the emergency department (ED).
The protocol for systematic review was registered (PROSPERO; CRD42020212534). We searched MEDLINE, Embase, PsycINFO, and Cochrane Database/CENTRAL from inception to June 2, 2021. We limited studies to randomized controlled trials that enrolled adult ED patients with severe agitation and compared drugs for rapid tranquilization. Predetermined outcomes were: 1) Adequate sedation within 30 min (effectiveness), 2) Immediate, serious adverse event - cardiac arrest, ventricular tachydysrhythmia, endotracheal intubation, laryngospasm, hypoxemia, hypotension (safety), and 3) Time to adequate sedation (effect onset). We extracted data according to PRISMA-NMA and appraised trials using Cochrane RoB 2 tool. We performed Bayesian network meta-analysis (NMA) using a Markov Chain Monte Carlo method with random-effects model and vague prior distribution to calculate odds ratios with 95% credible intervals for dichotomous outcomes and frequentist NMA to calculate mean differences with 95% confidence intervals for continuous outcomes. We assessed confidence in results using CINeMA. We used surface under the cumulative ranking (SUCRA) curves to rank agent(s) for each outcome.
Eleven studies provided data for effectiveness (1142 patients) and safety (1147 patients). Data was insufficient for effect onset. The NMA found that ketamine (SUCRA = 93.0%) is most likely to have superior effectiveness; droperidol-midazolam (SUCRA = 78.8%) is most likely to be safest. There are concerns with study quality and imprecision. Quality of the point estimates varied for effectiveness but mostly rated "very low" for safety.
Available evidence suggests that ketamine and droperidol have intermediate effectiveness for rapid tranquilization of the severely agitated patient in the ED. There is insufficient evidence to definitively determine which agent(s) may be safest or fastest-acting. Further, direct-comparison study of ketamine and droperidol is recommended.
对急性躁动患者进行安全有效的镇静具有挑战性，且药物之间的直接比较有限。我们旨在确定急诊科（ED）中用于严重躁动患者快速镇静的最佳药物。
系统评价方案已注册（PROSPERO；CRD42020212534）。我们检索了MEDLINE、Embase、PsycINFO以及Cochrane数据库/CENTRAL，检索时间从建库至2021年6月2日。我们将研究限制为纳入成年ED严重躁动患者并比较快速镇静药物的随机对照试验。预定结局为：1）30分钟内达到充分镇静（有效性），2）即刻严重不良事件——心脏骤停、室性快速心律失常、气管插管、喉痉挛、低氧血症、低血压（安全性），以及3）达到充分镇静的时间（起效时间）。我们根据PRISMA-NMA提取数据，并使用Cochrane RoB 2工具评估试验。我们使用马尔可夫链蒙特卡罗方法和随机效应模型以及模糊先验分布进行贝叶斯网络荟萃分析（NMA），以计算二分结局的比值比及95%可信区间，使用频率主义NMA计算连续结局的均值差及95%置信区间。我们使用CINeMA评估对结果的信心。我们使用累积排名曲线下面积（SUCRA）对每种结局的药物进行排名。
11项研究提供了有效性（1142例患者）和安全性（1147例患者）的数据。起效时间的数据不足。NMA发现氯胺酮（SUCRA = 93.0%）最有可能具有更好的有效性；氟哌利多 - 咪达唑仑（SUCRA = 78.8%）最有可能是最安全的。存在研究质量和不精确性方面的问题。有效性的点估计质量各不相同，但安全性大多评为“非常低”。
现有证据表明，氯胺酮和氟哌利多在ED中对严重躁动患者的快速镇静具有中等效果。没有足够的证据来明确确定哪种药物可能最安全或起效最快。此外，建议对氯胺酮和氟哌利多进行直接比较研究。
