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 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.


METHODS
Double-blind, placebo-controlled, crossover trial with four periods.


METHODS
Clinical research referral center.


METHODS
29 pruritic patients with liver diseases of various causes.


METHODS
Each patient received as many as two naloxone and two placebo solution infusions consecutively in random order. Each infusion lasted 24 hours.


METHODS
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 < 0.01). Furthermore, the ratio of the geometric mean hourly scratching activity during 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 patients.


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 hypothesis that a mechanism underlying the pruritus of cholestasis is modulated by endogenous opioids and suggest that opiate antagonists may have a role in the management of this complication of cholestasis.
Bergasa
N V
NV
National Institutes of Health, Bethesda, Maryland, USA.
Alling
D W
DW
Talbot
T L
TL
Swain
M G
MG
Yurdaydin
C
C
Turner
M L
ML
Schmitt
J M
JM
Walker
E C
EC
Jones
E A
EA
D000328:Adult; D000368:Aged; D002779:Cholestasis / Q000150:complications*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D009270:Naloxone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011537:Pruritus / Q000188:drug therapy* / Q000209:etiology; D016896:Treatment Outcome
D009270:Naloxone