Intravenous Cobinamide Versus Hydroxocobalamin for Acute Treatment of Severe Cyanide Poisoning in a Swine (Sus scrofa) Model
Intravenous Cobinamide Versus Hydroxocobalamin for Acute Treatment of Severe Cyanide Poisoning in a Swine (Sus scrofa) Model
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DOI：
10.1016/j.annemergmed.2014.02.009
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发表时间：
2014-12-01
影响因子：
6.2
通讯作者：
Boss, Gerry R.
中科院分区：
文献类型：
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作者：
Bebarta, Vikhyat S.;Tanen, David A.;Boss, Gerry R.
研究目的：羟钴胺素是食品和药物管理局批准的氰化物中毒解毒剂。Cobinamide是一种潜在的解毒剂，含有2个氰化物结合位点。据我们所知，没有研究直接比较羟钴胺与钴胺在一个严重的，氰化物中毒的大动物模型。我们的目的是比较的时间恢复自主呼吸的猪急性氰化物引起的呼吸暂停治疗与静脉内羟钴胺，静脉内钴胺，或生理盐水溶液（control）。方法：33头猪（45至55公斤）插管，麻醉，仪器（连续平均动脉压和心输出量监测）。在实验过程中调整麻醉以允许自主呼吸，FiO（2）为21%。持续静脉输注氰化物，直至发生呼吸暂停并持续1分钟（时间零点）。然后将动物随机分配接受静脉内羟钴胺素（65 mg/kg）、可宾胺（12.5 mg/kg）或盐水溶液，并监测60分钟。根据获得80%的把握度、0.05的α和0.17的平均时间SD，选择每组11只动物的样本量，以检测自主呼吸时间差异20%。我们评估组间死亡时间的差异，使用Kaplan-Meier估计方法，并比较血清乳酸，血液pH值，心输出量，平均动脉压，呼吸频率和每分钟通气时间曲线与重复测量AN0VA.Results：基线体重和生命体征组间相似。呼吸暂停时间和达到呼吸暂停所需的氰化物剂量相似。在零时，平均氰化物血液和乳酸盐浓度以及平均动脉压较基线的降低相似。在生理盐水组中，11只动物中有2只存活，而羟钴胺和钴氨酰胺组中有10只存活（P
Study objective: Hydroxocobalamin is a Food and Drug Administration-approved antidote for cyanide poisoning. Cobinamide is a potential antidote that contains 2 cyanide-binding sites. To our knowledge, no study has directly compared hydroxocobalamin with cobinamide in a severe, cyanide-toxic large-animal model. Our objective is to compare the time to return of spontaneous breathing in swine with acute cyanide-induced apnea treated with intravenous hydroxocobalamin, intravenous cobinamide, or saline solution (control).Methods: Thirty-three swine (45 to 55 kg) were intubated, anesthetized, and instrumented (continuous mean arterial pressure and cardiac output monitoring). Anesthesia was adjusted to allow spontaneous breathing with FiO(2) of 21% during the experiment. Cyanide was continuously infused intravenously until apnea occurred and lasted for 1 minute (time zero). Animals were then randomly assigned to receive intravenous hydroxocobalamin (65 mg/kg), cobinamide (12.5 mg/kg), or saline solution and monitored for 60 minutes. A sample size of 11 animals per group was selected according to obtaining a power of 80%, an alpha of .05, and an SD of 0.17 in mean time to detect a 20% difference in time to spontaneous breathing. We assessed differences in time to death among groups, using Kaplan-Meier estimation methods, and compared serum lactate, blood pH, cardiac output, mean arterial pressure, respiratory rate, and minute ventilation time curves with repeated-measures ANOVA.Results: Baseline weights and vital signs were similar among groups. The time to apnea and cyanide dose required to achieve apnea were similar. At time zero, mean cyanide blood and lactate concentrations and reduction in mean arterial pressure from baseline were similar. In the saline solution group, 2 of 11 animals survived compared with 10 of 11 in the hydroxocobalamin and cobinamide groups (P