Gosselin Sophie, Hoegberg Lotte C G, Hoffman Robert S, Graudins Andis, Stork Christine M, Thomas Simon H L, Stellpflug Samuel J, Hayes Bryan D, Levine Michael, Morris Martin, Nesbitt-Miller Andrea, Turgeon Alexis F, Bailey Benoit, Calello Diane P, Chuang Ryan, Bania Theodore C, Mégarbane Bruno, Bhalla Ashish, Lavergne Valéry
a Department of Emergency Medicine , McGill University Health Centre , Montréal , Québec , Canada.
b Centre Antipoison du Québec , Montréal , Québec , Canada.
Clin Toxicol (Phila). 2016 Dec;54(10):899-923. doi: 10.1080/15563650.2016.1214275. Epub 2016 Sep 8.
Although intravenous lipid emulsion (ILE) was first used to treat life-threatening local anesthetic (LA) toxicity, its use has expanded to include both non-local anesthetic (non-LA) poisoning and less severe manifestations of toxicity. A collaborative workgroup appraised the literature and provides evidence-based recommendations for the use of ILE in poisoning.
Following a systematic review of the literature, data were summarized in four publications: LA and non-LA poisoning efficacy, adverse effects, and analytical interferences. Twenty-two toxins or toxin categories and three clinical situations were selected for voting. Voting statements were proposed using a predetermined format. A two-round modified Delphi method was used to reach consensus on the voting statements. Disagreement was quantified using RAND/UCLA Appropriateness Method.
For the management of cardiac arrest, we recommend using ILE with bupivacaine toxicity, while our recommendations are neutral regarding its use for all other toxins. For the management of life-threatening toxicity, (1) as first line therapy, we suggest not to use ILE with toxicity from amitriptyline, non-lipid soluble beta receptor antagonists, bupropion, calcium channel blockers, cocaine, diphenhydramine, lamotrigine, malathion but are neutral for other toxins, (2) as part of treatment modalities, we suggest using ILE in bupivacaine toxicity if other therapies fail, but are neutral for other toxins, (3) if other therapies fail, we recommend ILE for bupivacaine toxicity and we suggest using ILE for toxicity due to other LAs, amitriptyline, and bupropion, but our recommendations are neutral for all other toxins. In the treatment of non-life-threatening toxicity, recommendations are variable according to the balance of expected risks and benefits for each toxin. For LA-toxicity we suggest the use of Intralipid 20% as it is the formulation the most often reported. There is no evidence to support a recommendation for the best formulation of ILE for non-LAs. The voting panel is neutral regarding ILE dosing and infusion duration due to insufficient data for non-LAs. All recommendations were based on very low quality of evidence.
Clinical recommendations regarding the use of ILE in poisoning were only possible in a small number of scenarios and were based mainly on very low quality of evidence, balance of expected risks and benefits, adverse effects, laboratory interferences as well as related costs and resources. The workgroup emphasizes that dose-finding and controlled studies reflecting human poisoning scenarios are required to advance knowledge of limitations, indications, adverse effects, effectiveness, and best regimen for ILE treatment.
尽管静脉脂质乳剂(ILE)最初用于治疗危及生命的局部麻醉药(LA)中毒,但它的应用已扩展到包括非局部麻醉药(非LA)中毒以及毒性较轻的表现。一个协作工作组评估了相关文献,并为ILE在中毒治疗中的应用提供基于证据的建议。
在对文献进行系统综述后,数据总结在四篇出版物中:LA和非LA中毒的疗效、不良反应及分析干扰。选择了22种毒素或毒素类别以及三种临床情况进行投票。投票声明采用预定格式提出。采用两轮改良德尔菲法就投票声明达成共识。使用兰德/加州大学洛杉矶分校适宜性方法对分歧进行量化。
对于心脏骤停的处理,我们建议在布比卡因中毒时使用ILE,而对于其在所有其他毒素中毒中的应用,我们的建议持中立态度。对于危及生命的毒性处理,(1)作为一线治疗,我们建议在阿米替林、非脂溶性β受体拮抗剂、安非他酮、钙通道阻滞剂、可卡因、苯海拉明、拉莫三嗪、马拉硫磷中毒时不使用ILE,而对于其他毒素持中立态度;(2)作为治疗方式的一部分,我们建议在其他治疗失败时,布比卡因中毒可使用ILE,而对于其他毒素持中立态度;(3)如果其他治疗失败,我们建议布比卡因中毒时使用ILE,对于其他局部麻醉药、阿米替林和安非他酮中毒建议使用ILE,而对于所有其他毒素我们的建议持中立态度。在治疗非危及生命的毒性时,根据每种毒素预期风险和益处的平衡,建议各不相同。对于LA中毒,我们建议使用20%的英脱利匹特,因为它是最常报告的制剂。没有证据支持针对非LA的ILE最佳制剂提出建议。由于非LA的数据不足,投票小组对于ILE的剂量和输注持续时间持中立态度。所有建议均基于非常低质量的证据。
关于ILE在中毒治疗中的临床建议仅在少数情况下可行,且主要基于非常低质量的证据、预期风险和益处的平衡、不良反应、实验室干扰以及相关成本和资源。工作组强调,需要进行反映人类中毒情况的剂量探索和对照研究,以增进对ILE治疗的局限性、适应证、不良反应、有效性和最佳方案的了解。