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Suppressive effects of remifentanil on hemodynamics in baro-denervated rabbits

Kenji Shinohara, MD^*,, Hiroshi Aono, MD^,, Gregory K. Unruh, MD, James D. Kindscher, MD and Hiroshi Goto, MD

From the Department of Anesthesiology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS, 66160-7415 USA.

Address correspondence to: Hiroshi Goto MD. Phone: 913-588-6670; Fax: 913-588-3365; E-mail:

Purpose: To elucidate mechanisms by which remifentanil, an ultra-short-acting µ-opioid receptor agonist, causes hypotension and bradycardia.

Methods: Mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were measured and recorded after bolus injections of 1, 2 or 5 µg•kg^–1 of remifentanil in neuraxis intact (n=6 for each dose) and baro-denervated rabbits (n=6 for each dose). Arterial baroreflex sensitivity was assessed by depressor tests. An additional six baro-denervated animals received remifentanil, 5 µg•kg^–1 after pretreatment with naloxone, 40 µg•kg^–1.

Results: All values were expressed in % change from baseline. In the neuraxis intact animals, MAP and HR were decreased briefly immediately after remifentanil injection. RSNA was increased dose-dependently: 137 ± 8% (mean ± SE), 170 ± 14% (P < 0.05) and 225 ± 29% (P < 0.05) after 1, 2 and 5 µg•kg^–1 remifentanil, respectively. RSNA was increased even after MAP and HR had returned to baseline values. The depressor tests revealed that remifentanil did not attenuate arterial baroreflex sensitivity. In the baro-denervated animals, MAP and HR decreased gradually to 77 ± 3% (P < 0.05) and 94 ± 1% (P < 0.05), respectively 300 sec after 5 µg•kg^–1 remifentanil. At that time, increased RSNA (159 ± 9%, P < 0.05) had returned to baseline. Pretreatment with naloxone in the baro-denervated animals abolished these changes.

Conclusion: Remifentanil decreases HR and MAP by its central vagotonic effect and by stimulating peripheral µ-opioid receptors. These effects appear to be counteracted and masked by its central sympathotonic effect and by maintaining arterial baroreflex integrity.

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