EFFECTS OF NALOXONE INFUSIONS IN PATIENTS WITH THE PRURITUS OF CHOLESTASIS - A DOUBLE-BLIND, RANDOMIZED, CONTROLLED TRIAL

Objective: To determine whether endogenous opioids contribute to the p ruritus of cholestasis by studying the effect of the opiate antagonist naloxone on the perception of pruritus and on scratching activity in patients with this form of pruritus. Design: Double-blind, placebo-con trolled, crossover trial with four periods. Setting: Clinical research referral center. Patients: 29 pruritic patients with liver diseases o f various causes. Intervention: Each patient received as many as two n aloxone and two placebo solution infusions consecutively in random ord er. Each infusion lasted 24 hours.Measurements: During the infusions, visual analog scores of pruritus were recorded every 4 hours while pat ients were awake; scratching activity independent of limb movements wa s recorded continuously. Results: One patient had a mild reaction cons istent with a naloxone-precipitated syndrome similar to opiate withdra wal. A significant 24-hour rhythm of scratching activity was seen in 7 of 11 patients for whom complete 96-hour data were collected. The mea n of a visual analog score of the perception of pruritus (maximum, 10. 0) recorded during naloxone infusions was 0.582 lower than that record ed during placebo infusions (95% CI, 0.176 to 0.988; P < 0.01). Furthe rmore, the ratio of the geometric mean hourly scratching activity duri ng naloxone infusions to that during placebo infusions was 0.727 (CI, 0.612 to 0.842; P < 0.001) and was greater than 1.0 in only five patie nts. Conclusions: Naloxone administration is associated with ameliorat ion of the perception of pruritus and reduction of scratching activity in cholestatic patients. Because of the opioid receptor specificity o f the action of naloxone, these findings support the hypothesis that a mechanism underlying the pruritus of cholestasis is modulated by endo genous opioids and suggest that opiate antagonists may have a role in the management of this complication of cholestasis.