Heinonen Juho A, Litonius Erik, Salmi Tapani, Haasio Juhani, Tarkkila Pekka, Backman Janne T, Rosenberg Per H
Department of Anaesthesiology and Intensive Care Medicine, University of Helsinki, Helsinki, Finland.
Basic Clin Pharmacol Toxicol. 2015 Apr;116(4):378-83. doi: 10.1111/bcpt.12321. Epub 2014 Oct 7.
Intravenous lipid emulsion has been suggested as treatment for local anaesthetic toxicity, but the exact mechanism of action is still uncertain. Controlled studies on the effect of lipid emulsion on toxic doses of local anaesthetics have not been performed in man. In randomized, subject-blinded and two-phase cross-over fashion, eight healthy volunteers were given a 1.5 ml/kg bolus of 20% Intralipid(®) (200 mg/ml) or Ringer's acetate solution intravenously, followed by a rapid injection of lidocaine 1.0 mg/kg. Then, the same solution as in the bolus was infused at a rate of 0.25 ml/kg/min. for 30 min. Electroencephalography (EEG) was recorded, and 5 min. after lidocaine injection, the volunteers were asked to report subjective symptoms. Total and un-entrapped lidocaine plasma concentrations were measured from venous blood samples. EEG band power changes (delta, alpha and beta) after the lidocaine bolus were similar during lipid and during Ringer infusion. There were no differences between infusions in the subjective symptoms of central nervous system toxicity. Lidocaine was only minimally entrapped in the plasma by lipid emulsion, but the mean un-entrapped lidocaine area under concentration-time curve from 0 to 30 min. was clearly smaller during lipid than Ringer infusion (16.4 versus 21.3 mg × min/l, p = 0.044). Intravenous lipid emulsion did not influence subjective toxicity symptoms nor affect the EEG changes caused by lidocaine.
静脉注射脂质乳剂已被建议用于治疗局部麻醉药中毒，但其确切作用机制仍不确定。关于脂质乳剂对局部麻醉药中毒剂量影响的对照研究尚未在人体中进行。以随机、受试者盲法和两阶段交叉方式，给8名健康志愿者静脉注射1.5 ml/kg的20%英脱利匹特（Intralipid®）（200 mg/ml）或醋酸林格液，随后快速注射1.0 mg/kg利多卡因。然后，以0.25 ml/kg/min的速率输注与推注相同的溶液，持续30分钟。记录脑电图（EEG），并在注射利多卡因后5分钟，要求志愿者报告主观症状。从静脉血样本中测量总利多卡因和未被包裹的利多卡因血浆浓度。在脂质输注和林格液输注期间，利多卡因推注后的EEG频段功率变化（δ、α和β）相似。在中枢神经系统毒性的主观症状方面，两种输注之间没有差异。脂质乳剂仅使极少量的利多卡因滞留在血浆中，但从0到30分钟，脂质输注期间未被包裹的利多卡因浓度-时间曲线下的平均面积明显小于林格液输注期间（16.4对21.3 mg×min/l，p = 0.044）。静脉注射脂质乳剂既不影响主观毒性症状，也不影响利多卡因引起的EEG变化。
