Bebarta Vikhyat S, Tanen David A, Boudreau Susan, Castaneda Maria, Zarzabal Lee A, Vargas Toni, Boss Gerry R
Medical Toxicology, San Antonio Military Medical Center, San Antonio, TX.
David Geffen School of Medicine at UCLA, Harbor-UCLA Medical Center, Torrance, CA.
Ann Emerg Med. 2014 Dec;64(6):612-9. doi: 10.1016/j.annemergmed.2014.02.009. Epub 2014 Apr 18.
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).
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 FiO2 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 α 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.
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<.001 between the 2 treated groups and the saline solution group). Time to return of spontaneous breathing after antidote was similar between hydroxocobalamin and cobinamide (1 minute 48 seconds versus 1 minute 49 seconds, respectively). Blood cyanide concentrations became undetectable at the end of the study in both antidote-treated groups, and no statistically significant differences were detected between the 2 groups for mean arterial pressure, cardiac output, respiratory rate, lactate, or pH.
Both hydroxocobalamin and cobinamide rescued severely cyanide-poisoned swine from apnea in the absence of assisted ventilation. The dose of cobinamide was one fifth that of hydroxocobalamin.
羟钴胺素是一种经美国食品药品监督管理局批准用于氰化物中毒的解毒剂。钴胺酰胺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，尚无研究在严重氰化物中毒的大型动物模型中直接比较羟钴胺素和钴胺酰胺。我们的目的是比较静脉注射羟钴胺素、静脉注射钴胺酰胺或生理盐水（对照）治疗急性氰化物诱导呼吸暂停的猪恢复自主呼吸的时间。
33头猪（45至55千克）进行插管、麻醉并安装监测仪器（连续监测平均动脉压和心输出量）。在实验过程中调整麻醉，使猪在吸入21%氧气时能自主呼吸。持续静脉输注氰化物直至出现呼吸暂停并持续1分钟（时间零点）。然后将动物随机分为静脉注射羟钴胺素（65毫克/千克）、钴胺酰胺（12.5毫克/千克）或生理盐水组，并监测60分钟。根据检测到自主呼吸时间有20%差异时的功效为80%、α为0.05以及平均时间标准差为0.17，每组选择11只动物作为样本量。我们使用Kaplan-Meier估计方法评估各组之间的死亡时间差异，并通过重复测量方差分析比较血清乳酸、血液pH值、心输出量、平均动脉压、呼吸频率和分钟通气时间曲线。
各组之间的基线体重和生命体征相似。出现呼吸暂停的时间和导致呼吸暂停所需的氰化物剂量相似。在时间零点，平均氰化物血浓度和乳酸浓度以及平均动脉压相对于基线的降低相似。在生理盐水组中，11只动物中有2只存活，而羟钴胺素组和钴胺酰胺组中11只动物分别有10只存活（两个治疗组与生理盐水组之间P<0.001）。羟钴胺素和钴胺酰胺组在使用解毒剂后恢复自主呼吸的时间相似（分别为1分48秒和1分49秒）。在两个解毒剂治疗组中，研究结束时血液氰化物浓度均无法检测到，并且两组之间在平均动脉压、心输出量、呼吸频率、乳酸或pH值方面未检测到统计学上的显著差异。
在没有辅助通气的情况下，羟钴胺素和钴胺酰胺均可使严重氰化物中毒的猪从呼吸暂停中获救。钴胺酰胺的剂量是羟钴胺素的五分之一。
