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ANESTHETIC PHARMACOLOGY

Modulation of Remifentanil-Induced Postinfusion Hyperalgesia by Propofol

Boris Singler, MD^*, Andreas Tröster, MD^*, Neil Manering, Jürgen Schüttler, MD, Prof.^*, and Wolfgang Koppert, MD^*

From the *Department of Anesthesiology, University Hospital Erlangen, Erlangen, Germany; and Department of Anesthesia, Stanford University School of Medicine, Stanford, California.

Address correspondence and reprint requests to Prof. Dr. med. Wolfgang Koppert, Department of Anesthesiology, University Hospital Erlangen, Krankenhausstr. 12, D-91054 Erlangen, Germany. Address e-mail to koppert{at}kfa.imed.uni-erlangen.de.

BACKGROUND: Experimental and clinical studies suggest that brief opioid exposure can enhance pain sensitivity. During anesthesia, however, opioids are commonly administered in combination with either IV or inhaled hypnotic drugs. In this investigation we sought to determine the analgesic and antihyperalgesic properties of propofol in subhypnotic concentrations on remifentanil-induced postinfusion hypersensitivity in an experimental human pain model.

METHODS: Fifteen healthy volunteers were included in this randomized, double-blind, and placebo-controlled study in a cross-over design. Transcutaneous electrical stimulation at high current densities (41.7 ± 14.3 mA) induced spontaneous acute pain (numerical rating scale = 6 of 10) and stable areas of hyperalgesia. Pain intensities and areas of hyperalgesia were assessed before, during and after a 30 min target-controlled infusion of propofol (1.5 µg/mL) and remifentanil (0.05 µg · kg^–1 · min^–1), either alone or in combination (propofol 1.5 µg/mL with remifentanil 0.025 or 0.05 µg · kg^–1 · min^–1).

RESULTS: During infusion, propofol significantly reduced the electrically evoked pain to 72% ± 21% of control. Subhypnotic concentrations of propofol did not lead to any hyperalgesic effects. Coadministration of remifentanil led to synergistic analgesic effects (to 62% ± 26% and 58% ± 25% of control, for 0.025 or 0.05 µg · kg^–1 · min^–1, respectively), but upon withdrawal, pain and hyperalgesia increased above control level.

CONCLUSIONS: The results suggest clinically relevant interactions of propofol and remifentanil in humans, since propofol led to a delay and a weakening of remifentanil-induced postinfusion anti-analgesia in humans. Nevertheless, pronociceptive effects were not completely antagonized by propofol, which may account for the increased demand for analgesics after remifentanil-based anesthesia in clinical practice.

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