University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Faculty of Health: Medicine, Dentistry and Human Sciences, University of Plymouth, Plymouth, UK.
Paediatr Anaesth. 2020 Dec;30(12):1292-1298. doi: 10.1111/pan.14039. Epub 2020 Nov 4.
Total intravenous anesthesia (TIVA) using a mixture of propofol and remifentanil in the same syringe has become an accepted technique in Pediatric Anesthesia. A survey by a group of respected UK anesthetists demonstrated a low incidence of serious complications, related to the pharmacology and dose of the drugs. However, a current guideline for the safe use of TIVA recommends against this practice. Pharmaceutical concerns include the physical stability of the emulsion when remifentanil is mixed with propofol; changes in drug concentration over time; nonuniform mixing of propofol and remifentanil; the risk of bacterial contamination; and the potential for drug administration errors. Propofol and remifentanil have markedly different pharmacokinetic profiles. When remifentanil is mixed with propofol and delivered as a target-controlled infusion (TCI) of propofol, remifentanil delivery is not target-controlled but passively follows the variable infusion rates calculated by the syringe driver to deliver predicted plasma or effect-site concentrations of propofol. The pharmacokinetic consequences can be illustrated using pharmacokinetic modeling similar to that used in TCI pumps. The clinical consequences reflect the dose-dependent pharmacodynamics of remifentanil. Increasing the target propofol concentration produces a rapid increase and peak in remifentanil concentration that risks apnea, bradycardia, and hypotension, especially with higher concentrations of remifentanil. The faster decline in remifentanil concentration with falling propofol concentrations risks inadequate narcosis and unwanted responses to surgical stimuli. Remifentanil delivery is inflexible and dosing cannot be adjusted to the clinical need and responses of individual patients. The medicolegal considerations are stark. In UK and EU Law, mixing propofol and remifentanil creates a new, unlicensed drug and the person mixing takes on the responsibilities of manufacturer. If a patient receiving anesthesia in the form of a mixed propofol-remifentanil infusion suffered a critical incident or actual harm, the clinician's practice may come under scrutiny and criticism, potentially involving a legal challenge and the Medical Regulator.
全凭静脉麻醉（TIVA）在同一注射器中使用丙泊酚和瑞芬太尼混合物已成为小儿麻醉中的一种被接受的技术。一组受尊敬的英国麻醉师的调查显示，与药物的药理学和剂量相关的严重并发症发生率较低。然而，目前关于 TIVA 安全使用的指南建议反对这种做法。药物方面的顾虑包括瑞芬太尼与丙泊酚混合时乳液的物理稳定性；随着时间的推移药物浓度的变化；丙泊酚和瑞芬太尼混合不均匀；细菌污染的风险；以及药物给药错误的潜在风险。丙泊酚和瑞芬太尼具有明显不同的药代动力学特征。当瑞芬太尼与丙泊酚混合并作为丙泊酚的靶控输注（TCI）给予时，瑞芬太尼的给予不是靶控的，而是被动地遵循由注射器驱动器计算的可变输注率，以提供预测的丙泊酚血浆或效应部位浓度。可以使用类似于 TCI 泵中使用的药代动力学模型来说明药代动力学后果。临床后果反映了瑞芬太尼的剂量依赖性药效学。增加目标丙泊酚浓度会迅速增加并达到瑞芬太尼浓度峰值，从而有发生呼吸暂停、心动过缓和低血压的风险，尤其是在较高浓度的瑞芬太尼时。随着丙泊酚浓度的下降，瑞芬太尼浓度的快速下降会导致麻醉不足和对手术刺激的不必要反应。瑞芬太尼的给予缺乏灵活性，无法根据个体患者的临床需要和反应调整剂量。医学法律方面的考虑是严峻的。在英国和欧盟法律中，混合丙泊酚和瑞芬太尼会产生一种新的、未经许可的药物，混合药物的人承担制造商的责任。如果接受混合丙泊酚-瑞芬太尼输注麻醉的患者遭受严重事件或实际伤害，临床医生的实践可能会受到审查和批评，可能涉及法律挑战和医疗监管机构。
