Lewin Matthew R, Samuel Stephen P, Wexler David S, Bickler Philip, Vaiyapuri Sakthivel, Mensh Brett D
Center for Exploration and Travel Health, California Academy of Sciences, 55 Music Concourse Drive, San Francisco, CA 94118, USA.
Department of Clinical Medicine, Trinity College Dublin, Dublin 2, Ireland.
J Trop Med. 2014;2014:131835. doi: 10.1155/2014/131835. Epub 2014 May 14.
Objective. Most snakebite deaths occur prior to hospital arrival; yet inexpensive, effective, and easy to administer out-of-hospital treatments do not exist. Acetylcholinesterase inhibitors can be therapeutic in neurotoxic envenomations when administered intravenously, but nasally delivered drugs could facilitate prehospital therapy for these patients. We tested the feasibility of this idea in experimentally envenomed mice. Methods. Mice received intraperitoneal injections of Naja naja venom 2.5 to 10 times the estimated LD50 and then received 5 μ L neostigmine (0.5 mg/mL) or 5 μ L normal saline by nasal administration. Animals were observed up to 12 hours and survivors were euthanized. Results. 100% of control mice died. Untreated mice injected with 2.5× LD50 Naja naja died at average 193 minutes after injection, while 10 of 15 (67%) of treated mice survived and were behaviorally normal by 6 hours (P < 0.02). In the 5× LD50 group, survival was prolonged from 45 minutes to 196 minutes (P = 0.01) and for 10× LD50 mice, survival increased from 30 to 175 minutes (P < 0.02). Conclusion. This pilot suggests that intranasal drugs can improve survival and is the first direct demonstration that such an approach is plausible, suggesting means by which treatment could be initiated before reaching the hospital. Further investigation of this approach to neurotoxic and other types of envenomation is warranted.
目的。大多数蛇咬伤致死事件发生在到达医院之前；然而，目前尚无廉价、有效且易于在院外使用的治疗方法。乙酰胆碱酯酶抑制剂静脉给药时对神经毒性蛇伤具有治疗作用，但经鼻给药的药物可为这些患者的院前治疗提供便利。我们在实验性蛇伤小鼠中测试了这一想法的可行性。方法。小鼠腹腔注射印度眼镜蛇毒液，剂量为估计半数致死量（LD50）的2.5至10倍，然后经鼻给予5μL新斯的明（0.5mg/mL）或5μL生理盐水。观察动物长达12小时，对存活者实施安乐死。结果。100%的对照小鼠死亡。注射2.5×LD50印度眼镜蛇毒液的未治疗小鼠在注射后平均193分钟死亡，而15只接受治疗的小鼠中有10只（67%）存活，6小时后行为正常（P<0.02）。在5×LD50组中，存活时间从45分钟延长至196分钟（P = 0.01）；对于10×LD50的小鼠，存活时间从30分钟增加到175分钟（P<0.02）。结论。这项初步研究表明，经鼻给药可提高存活率，并且首次直接证明了这种方法是可行的，为在到达医院之前启动治疗提供了途径。有必要对这种治疗神经毒性及其他类型蛇伤的方法进行进一步研究。
