Medical Toxicology, University of Texas Health Sciences Center, San Antonio, TX, USA.
Ann Emerg Med. 2010 Apr;55(4):345-51. doi: 10.1016/j.annemergmed.2009.09.020. Epub 2009 Nov 27.
Cyanide can cause severe hypotension with acute toxicity. To our knowledge, no study has directly compared hydroxocobalamin and sodium nitrite with sodium thiosulfate in an acute cyanide toxicity model. Our objective is to compare the return to baseline of mean arterial blood pressure between 2 groups of swine with acute cyanide toxicity and treated with hydroxocobalamin with sodium thiosulfate or sodium nitrite with sodium thiosulfate.
Twenty-four swine were intubated, anesthetized, and instrumented (continuous arterial and cardiac output monitoring) and then intoxicated with a continuous cyanide infusion until severe hypotension. The animals were divided into 2 arms of 12 each and then randomly assigned to intravenous hydroxocobalamin (150 mg/kg)+sodium thiosulfate (413 mg/kg) or sodium nitrite (10 mg/kg)+sodium thiosulfate (413 mg/kg) and monitored for 40 minutes after start of antidotal infusion. Twenty animals were needed for 80% power to detect a significant difference in outcomes (alpha 0.05). Repeated measures of analysis of covariance and post hoc t test were used for determining significance.
Baseline mean weights, time to hypotension (31 minutes 3 seconds versus 28 minutes 6 seconds), and cyanide dose at hypotension (5.6 versus 5.9 mg/kg) were similar. One animal in the hydroxocobalamin group and 2 animals in the sodium nitrite group died during antidote infusion and were excluded from analysis. Hydroxocobalamin resulted in a faster return to baseline mean arterial pressure, with improvement beginning at 5 minutes and lasting through the conclusion of the study (P<.05). No statistically significant difference was detected between groups for cardiac output, pulse rate, systemic vascular resistance, or mortality at 40 minutes post intoxication. Mean cyanide blood levels (4.03 versus 4.05 microg/mL) and lactate levels (peak 7.9 versus 8.1 mmol/L) at hypotension were similar. Lactate levels (5.1 versus 4.48 mmol/L), pH (7.40 versus 7.37), and base excess (-0.75 versus 1.27) at 40 minutes were also similar.
Hydroxocobalamin with sodium thiosulfate led to a faster return to baseline mean arterial pressure compared with sodium nitrite with sodium thiosulfate; however, there was no difference between the antidote combinations in mortality, serum acidosis, or serum lactate.
氰化物可导致急性毒性的严重低血压。据我们所知，尚无研究直接比较高铁血红蛋白和亚硝酸钠与硫代硫酸钠在急性氰化物毒性模型中的疗效。我们的目的是比较两组急性氰化物中毒猪在接受高铁血红蛋白联合硫代硫酸钠或亚硝酸钠联合硫代硫酸钠治疗后，平均动脉血压恢复至基线的情况。
24 只猪被气管插管、麻醉和置管（连续动脉和心输出量监测），然后连续输注氰化物直至出现严重低血压。动物被分为两组，每组 12 只，然后随机分配静脉注射高铁血红蛋白（150mg/kg）+硫代硫酸钠（413mg/kg）或亚硝酸钠（10mg/kg）+硫代硫酸钠（413mg/kg），并在解毒剂输注开始后监测 40 分钟。需要 20 只动物进行 80%的功效检测（α0.05）。采用协方差重复测量的分析和事后 t 检验来确定显著性。
基线平均体重、低血压时间（31 分 3 秒与 28 分 6 秒）和低血压时的氰化物剂量（5.6 毫克/千克与 5.9 毫克/千克）相似。高铁血红蛋白组有 1 只动物和亚硝酸钠组有 2 只动物在解毒剂输注期间死亡，被排除在分析之外。高铁血红蛋白可更快地恢复至平均动脉压基线，从 5 分钟开始改善，并持续到研究结束（P<.05）。在中毒后 40 分钟时，两组之间的心脏输出、脉搏率、全身血管阻力或死亡率无统计学显著差异。低血压时的平均氰化物血水平（4.03 微克/毫升与 4.05 微克/毫升）和乳酸水平（峰值 7.9 毫摩尔/升与 8.1 毫摩尔/升）相似。40 分钟时的乳酸水平（5.1 毫摩尔/升与 4.48 毫摩尔/升）、pH 值（7.40 与 7.37）和碱剩余（-0.75 与 1.27）也相似。
高铁血红蛋白联合硫代硫酸钠可更快地恢复至平均动脉压基线，与亚硝酸钠联合硫代硫酸钠相比；然而，两种解毒剂组合在死亡率、血清酸中毒或血清乳酸方面没有差异。
