• T D Egan, S E Kern, K T Muir, and J White.
• Department of Anesthesiology, 3C444, University of Utah Health Sciences Center, 30 North 1900 East, Salt Lake City, UT 84132, USA. talmage.egan@hsc.utah.edu
• Br J Anaesth. 2004 Mar 1;92(3):335-43.

BackgroundAlthough 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.MethodsUsing 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.ResultsDose-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.ConclusionsBolus 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.

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