title: Intravenous bolus of ultra-low-dose naloxone added to morphine does not enhance analgesia in emergency department patients.
abstract: There is some evidence from in vitro, animal, and postoperative clinical studies that low doses of opioid antagonists combined with morphine increase analgesia. The theoretical model of this effect posits that ultra-low doses of opioid antagonists selectively antagonize excitatory, but not inhibitory, opioid receptor-mediated signaling. To determine whether this effect occurs in emergency department patients presenting with severe acute pain, we conducted a randomized, double-blind placebo-controlled trial to assess the relative analgesic effect of morphine administered with 3 different doses of naloxone versus morphine alone. Patients received 0.1 mg/kg morphine intravenously (IV) over 2 min plus one of 3 different doses of naloxone (0.1 ng/kg, 0.01 ng/kg, or 0.001 ng/kg) or normal saline. A 0 to 10 numerical rating scale (NRS) was used to measure pain intensity at baseline and every 30 min up to 4 hours. One hundred fifty-six patients with a median NRS of 10 (IQR: 8-10) were studied. There were no clinically or statistically significant differences in the mean pain intensity of patients in the 4 treatment groups over the 4-hour study period, nor were there differences in the administration of additional analgesics or incidence of side effects.
  
  
  CONCLUSIONS
  Ultra-low doses of naloxone in the 0.001 ng/kg to 0.1 ng/kg range do not enhance the analgesia provided by morphine alone among emergency department patients with acute, severe pain. This suggests that naloxone in these doses is not an effective adjunct to morphine for control of acute pain.
authors.affiliation: Department of Emergency Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA. bijur@aecom.yu.edu
authors.forename: Polly E
authors.initials: PE
authors.lastname: Bijur
authors.forename: Clyde
authors.initials: C
authors.lastname: Schechter
authors.forename: David
authors.initials: D
authors.lastname: Esses
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Chang
authors.forename: E John
authors.initials: EJ
authors.lastname: Gallagher
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004636:Emergency Service, Hospital; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage*; D009270:Naloxone / Q000008:administration & dosage*; D009292:Narcotic Antagonists / Q000008:administration & dosage*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D017211:Treatment Failure
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009270:Naloxone; D009020:Morphine