A pilot clinical study of the neuromuscular blocker rocuronium to reduce the duration of ventilation after organophosphorus insecticide poisoning.
A pilot clinical study of the neuromuscular blocker rocuronium to reduce the duration of ventilation after organophosphorus insecticide poisoning.
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神经肌肉阻滞剂罗库溴铵减少有机磷杀虫剂中毒后通气时间的初步临床研究。
DOI：
10.1080/15563650.2019.1643467
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Dhanarisi J
中科院分区：
文献类型：
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作者：
Dhanarisi J
背景：有机磷杀虫剂自身中毒的一个常见表现是由于神经肌肉接头功能障碍和可能的烟碱受体过度刺激引起的长时间呼吸衰竭。我们的目的是收集初步的数据，是否增加竞争性烟碱拮抗剂罗库溴铵的标准早期治疗可能是临床可行的，并与减少持续时间的ventilation.Methods：一个试点三臂剂量反应第二阶段试验成立，比较团注剂量的罗库溴铵滴定产生初始>95%或50%的抑制神经肌肉功能，测量使用加速度肌电描记术，加上标准治疗，与标准治疗单独。达到抑制后，接受罗库溴铵推注的患者再接受罗库溴铵输注，最长持续120小时。主要结局是插管持续时间;次要结局是病例死亡率。在整个住院期间测量血浆丁酰胆碱酯酶活性。结果：45例患者随机接受：罗库溴铵最初达到95%的抑制（ROC>95，n= 15），罗库溴铵最初达到50%的抑制（ROC 50，n= 14），或没有罗库溴铵（对照，n= 16）。最常摄入的农药是丙溴磷（29/45，64.4%）。在研究期间，大多数患者的丁酰胆碱酯酶活性仍然受到严重抑制。病例死亡率为9/45（20%），各研究组相似：对照组3/16（18.8%），Roc 50组4/14（28.6%），Roc>95组2/15（13.3%）（p= .5842）。当排除死亡患者时，Roc 50中的插管中位[IQR]持续时间显着更长（259.5 [176-385] h）和ROC>95（226.8 [186-355] h）组与对照组相比（88.5 [47-160] h，分别为p= .0162和p = .0016）。在这个初步的剂量反应研究中，我们没有发现罗库溴铵加用标准治疗可以减少插管时间的证据。它可能使神经肌肉接头功能恶化。在烟碱拮抗剂用于OP中毒的临床治疗之前，需要进行进一步的临床研究，包括对较短持续时间方案的测试。
Background:A common manifestation of organophosphorus insecticide self-poisoning is prolonged respiratory failure due to neuromuscular junction dysfunction and likely nicotinic receptor overstimulation. We aimed at collecting preliminary data on whether addition of the competitive nicotinic antagonist rocuronium to standard early therapy might be clinically feasible and associated with reduced duration of ventilation.Methods:A pilot three-arm dose–response phase II trial was set up to compare bolus doses of rocuronium bromide titrated to produce initial >95% or 50% inhibition of neuromuscular function, measured using acceleromyography, plus standard treatment, versus standard treatment alone. After attaining inhibition, patients receiving bolus rocuronium then received rocuronium infusions for a maximum of 120 h. Primary outcome was duration of intubation; secondary outcome was case fatality. Plasma butyrylcholinesterase activity was measured throughout the inpatient stay. Blood was analysed to confirm the organophosphorus insecticide ingested.Results:Forty-five patients were randomised to receive: rocuronium to initially attain 95% inhibition (Roc>95,n= 15), rocuronium to initially attain 50% inhibition (Roc50,n= 14), or no rocuronium (control,n= 16). The most commonly ingested pesticide was profenofos (29/45, 64.4%). Butyrylcholinesterase activity remained severely inhibited for the duration of the study for most patients. Case fatality was 9/45 (20%) and similar across study arms: control 3/16 (18.8%), Roc50 4/14 (28.6%) and Roc>95 2/15 (13.3%) (p= .5842). When excluding patients who died, median [IQR] duration of intubation was significantly longer in the Roc50 (259.5 [176–385] h) and Roc>95 (226.8 [186–355] h) groups compared to controls (88.5 [47–160] h,p= .0162 andp= .0016, respectively).Conclusions:In this pilot dose–response study, we found no evidence that rocuronium in addition to standard therapy reduced the duration of intubation. It is possible that it worsened neuromuscular junction function. Further clinical research, including testing of shorter duration regimens, needs to be performed before nicotinic antagonists can be used in the clinical management of OP poisoning.