Reversal of opioid-induced bladder dysfunction by intravenous naloxone and methylnaltrexone.

Author(s): Rosow CE, Gomery P, Chen TY, Stefanovich P, Stambler N, Israel R

Affiliation(s): Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, Massachusetts, USA. crosow@partners.org

Publication date & source: 2007-07, Clin Pharmacol Ther., 82(1):48-53. Epub 2007 Mar 28.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

Peripheral mechanisms may be involved in opioid actions on the urinary bladder. This double-blind study investigated whether opioid inhibition of bladder function is reversed by methylnaltrexone, a peripheral opioid antagonist. Thirteen healthy male volunteers received an intravenous (i.v.) infusion of remifentanil, 0.15 mcg/kg/min, then a single i.v. dose of study medication (methylnaltrexone 0.3 mg/kg, naloxone 0.01 mg/kg, or saline). Urodynamics were measured with indwelling bladder and rectal catheters, and pupil size was assessed with infrared pupillometry. Remifentanil decreased detrusor pressure in 21/25 sessions and caused complete urinary retention in 18/25. Voiding was possible in 7/7, 5/12, and 0/6 sessions after naloxone, methylnaltrexone, and saline, respectively (P=0.0013). Remifentanil caused marked miosis that was reversed by naloxone, but not methylnaltrexone or placebo (P<0.0001). The pupil data confirm that methylnaltrexone did not reverse central opioid effects. Reversal of urinary retention by methylnaltrexone indicates that peripheral mechanisms may play a role in opioid-induced bladder dysfunction.