Effects of Naloxone Infusions in Patients with the Pruritus of Cholestasis: A Double-Blind, Randomized, Controlled Trial

Abstract

Objective To determine whether endogenous opioids contribute to the pruritus 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-controlled, crossover trial with four periods. Setting Clinical research referral center. Patients 29 pruritic patients with liver diseases of various causes. Intervention Each patient received as many as two naloxone and two placebo solution infusions consecutively in random order. Each infusion lasted 24 hours. Measurements During the infusions, visual analog scores of pruritus were recorded every 4 hours while patients were awake; scratching activity independent of limb movements was recorded continuously. Results One patient had a mild reaction consistent with a naloxone-precipitated syndrome similar to opiate withdrawal. A significant 24-hour rhythm of scratching activity was seen in 7 of 11 patients for whom complete 96-hour data were collected. The mean of a visual analog score of the perception of pruritus (maximum, 10.0) recorded during naloxone infusions was 0.582 lower than that recorded during placebo infusions (95% CI, 0.176 to 0.988; P Conclusions Naloxone administration is associated with amelioration of the perception of pruritus and reduction of scratching activity in cholestatic patients. Because of the opioid receptor specificity of the action of naloxone, these findings support the hypo…