Egan T D, Kern S E, Muir K T, White J
Department of Anesthesiology, 3C444, University of Utah Health Sciences Center, 30 North 1900 East, Salt Lake City, UT 84132, USA.
Br J Anaesth. 2004 Mar;92(3):335-43. doi: 10.1093/bja/aeh075.
Although remifentanil's short-acting pharmacokinetic profile makes it well suited for procedures during which a brief period of intense analgesia is required, setting up an infusion pump for brief procedures is inconvenient. The clinical pharmacology of remifentanil administered by bolus injection, a more convenient alternative, has not been explored in detail. The primary aim of this study was to examine the safety of single bolus doses of remifentanil in conscious, healthy, adult volunteers breathing room air. Secondary aims included the evaluation of remifentanil pharmacokinetics and analgesic effects after bolus injection and a comparison of these issues in younger vs older adults.
Using a randomized, double-blind, placebo-controlled, dose-escalation, crossover study design, 64 subjects (16 over 60 years old) received remifentanil or placebo by bolus injection in a fixed unit dose separated by a 1 h washout period. Respiratory effects were assessed using a respiratory intervention scale. Analgesic effects were assessed using pressure algometry. A population pharmacokinetic model was constructed using non-linear, mixed-effects modelling techniques based on arterial blood samples. Computer simulations were performed to illustrate the clinical application of the pharmacokinetic model.
Dose-related increases in both respiratory and analgesic effects were observed. In general, the respiratory depression observed was mild and easily treated with requests to breathe or the administration of oxygen, although the older cohort (and some younger subjects) experienced more substantial respiratory depression at lower doses. The pharmacokinetics of bolus-dose remifentanil were adequately described by a two-compartment model. The pharmacokinetic simulations illustrated the potential utility of bolus-dose remifentanil.
Bolus injection could potentially be a safe and effective means of administering remifentanil in clinical situations requiring a brief period of intense analgesia. Because some subjects, both old and young, experienced significant respiratory depression even at low doses, careful monitoring of respiratory function is essential.
尽管瑞芬太尼的短效药代动力学特性使其非常适合需要短时间强效镇痛的手术，但为短时间手术设置输液泵并不方便。通过静脉推注给药这种更方便的方式来使用瑞芬太尼的临床药理学尚未得到详细研究。本研究的主要目的是检验在呼吸室内空气的清醒、健康成年志愿者中单次静脉推注瑞芬太尼的安全性。次要目的包括评估静脉推注瑞芬太尼后的药代动力学和镇痛效果，以及比较年轻人和老年人在这些方面的差异。
采用随机、双盲、安慰剂对照、剂量递增、交叉研究设计，64名受试者（16名年龄超过60岁）接受静脉推注瑞芬太尼或安慰剂，固定单位剂量给药，间隔1小时洗脱期。使用呼吸干预量表评估呼吸效应。使用压力测痛法评估镇痛效果。基于动脉血样本，采用非线性混合效应建模技术构建群体药代动力学模型。进行计算机模拟以说明药代动力学模型的临床应用。
观察到呼吸和镇痛效果均呈剂量相关增加。总体而言，观察到的呼吸抑制较轻，通过要求患者呼吸或给予氧气很容易处理，尽管老年组（以及一些年轻受试者）在较低剂量时经历了更严重的呼吸抑制。静脉推注瑞芬太尼的药代动力学可用二室模型充分描述。药代动力学模拟说明了静脉推注瑞芬太尼的潜在效用。
在需要短时间强效镇痛的临床情况下，静脉推注可能是一种安全有效的瑞芬太尼给药方式。由于一些老年和年轻受试者即使在低剂量时也经历了显著的呼吸抑制，因此仔细监测呼吸功能至关重要。
