Reversal of opioid-induced bladder dysfunction by intravenous naloxone and methylnaltrexone.
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.
Rosow
C E
CE
Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, Massachusetts, USA. crosow@partners.org
Gomery
P
P
Chen
T Y
TY
Stefanovich
P
P
Stambler
N
N
Israel
R
R
D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D015877:Miosis / Q000139:chemically induced / Q000188:drug therapy; D009119:Muscle Contraction / Q000187:drug effects; D009270:Naloxone / Q000008:administration & dosage / Q000627:therapeutic use*; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects*; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D000077208:Remifentanil; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000187:drug effects* / Q000503:physiopathology; D016055:Urinary Retention / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D014554:Urination / Q000187:drug effects
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D010880:Piperidines; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009270:Naloxone; D009271:Naltrexone; D000077208:Remifentanil