Inhaled Remifentanil in Rodents

Bevans, Tatjana CRNA, MSN; Deering-Rice, Cassandra PhD; Stockmann, Chris PhD, MSc; Light, Alan PhD; Reilly, Christopher PhD; Sakata, Derek J. MD

doi: 10.1213/ANE.0000000000001228
Anesthetic Pharmacology: Research Report

BACKGROUND: Remifentanil is an injectable opioid that is metabolized rapidly at a constant rate by plasma esterases. This supports its use as an analgesic for short-term, but painful, procedures in a wide range of patients. The aim of this study was to explore the feasibility and safety of administering remifentanil via inhalation. Our hypothesis was that inhaled remifentanil would be absorbed rapidly, pharmacologically active, rapidly cleared, and noninjurious to rodent airways and lungs.

METHODS: Rats were exposed to remifentanil aerosol (100–2000 μg/mL) for varying times (1–5 minutes). Analgesia was quantified as a function of dose and time by measuring time to tail flick in response to a painful stimulus. Remifentanil was measured in blood using liquid chromatography-tandem mass spectrometry. Pulmonary mechanics and histology were assessed in mice for the evidence of adverse effects after acute and repeated (subacute) dosing.

RESULTS: Exposure of rats to remifentanil aerosols produced dose-dependent analgesia within 2 minutes, which was sustained for the exposure period. Subsequently, the rats experienced rapid and complete recovery with a return to baseline tail flick response to a painful stimulus within 5 minutes. Analgesia mirrored the concentration profile of remifentanil in blood, and the animals were not affected adversely by repeated dosing. Pulmonary mechanics measurements in mice indicated that remifentanil was nonirritating and that the nasal and respiratory tissues of rats were free of significant morphological changes.

CONCLUSIONS: Remifentanil delivered by inhalation is rapidly absorbed, pharmacologically active, rapidly cleared, and noninjurious to respiratory tissues in rodents.

Published ahead of print March 11, 2016

From the Departments of *Pharmacology/Toxicology, Pediatrics, and Anesthesiology, University of Utah, Salt Lake City, Utah.

Accepted for publication January 14, 2016.

Published ahead of print March 11, 2016

Funding: Leland O. and Avanelle W. Learned Endowed Professorship in Anesthesiology fund, Derek J. Sakata, MD, Anesthesiology Departmental Grant, University of Utah and the AANA Foundation (Park Ridge, IL).

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website.

Reprints will not be available from the authors.

Address correspondence to Derek J. Sakata, MD, Department of Anesthesiology, University of Utah, School of Medicine, 30 N 1900 E Rm 3C444, Salt Lake City, Utah. Address e-mail to Derek.Sakata@hsc.utah.edu.

© 2016 International Anesthesia Research Society