Elsevier

The Lancet

Volume 348, Issue 9041, 7 December 1996, Pages 1552-1554
The Lancet

Articles
Randomised crossover trial of naltrexone in uraemic pruritus

https://doi.org/10.1016/S0140-6736(96)04176-1Get rights and content

Summary

Background

Most dialysis patients develop pruritus, for which current treatment is unsatisfactory. Endogenous opioids may be involved in this pruritus. We studied the effect of the opioid antagonist naltrexone on the pruritus of haemodialysis patients.

Methods

Naltrexone 50 mg per day by mouth was given to 15 haemodialysis patients with severe resistant pruritus in a randomised, double-blind, placebo-controlled crossover trial. The naltrexone or placebo periods lasted 7 days each with a 7-day washout between the two periods. Pruritus was assessed by the patients on a visual analogue scale from 0 (no pruritus) to 10 (maximum), and mean daily scores were calculated. Plasma histamine and β-endorphin levels were measured, and spontaneous and stimulated basophil histamine-release were determined.

Findings

The median pruritus scores at the end of the naltrexone treatment were 21 (interquartile range 1·5–2·15) for the naltrexone-placebo sequence and 10 (0·4–1·15) for the placebo-naltrexone sequence. The respective values before naltrexone was given were 9·9 (9·85–9·95) and 9·9 (9·3–10·0). Plasma β-endorphin levels were normal and remained unchanged during the study. Plasma histamine levels were high (mean 2·32 [SD 0·11] ng/mL, normal <1·0) and decreased after naltrexone (to 18 [0·09], p <0·01). Basophils from haemodialysis patients stimulated by interleukin-3 plus IgE antibodies released high amounts of histamine. The increase was 78·3 (19·3)% compared with 26·6 (16·3)% for five normal controls (p <0·01). Incubation of the basophils with naloxone, another opioid antagonist, prevented this effect.

Interpretation

Our data suggest short-term efficacy with few side-effects for the amelioration of uraemic pruritus with naltrexone.

Introduction

The occurrence of pruritus increases as patients survive longer on renal dialysis, and can reach 80%.1, 2, 3 Treatment is unsatisfactory.4 The pain of pruritus is carried to the central nervous system by unmyelinated C fibres and spinothalamic tracts.5 Opioids bind to receptors situated on peripheral sensory nerve fibres or on dorsal root ganglia. This common pathway and association of an opioid-related pruritus of central origin6, 7, 8, 9, 10, 11, 12, 13 suggests involvement of opioids in the pathogenesis of pruritus. There is also an association between the pruritus of cholestasis and endogenous opioids, with amelioration by opioid antagonists.14, 15, 16, 17 In one case, naloxone briefly alleviated pruritus in a uraemic patient with glomerulonephritis.18 We aimed to study the effect of naltrexone in patients on chronic haemodialysis with severe intractable pruritus.

Section snippets

Patients

After approval by our ethical committee and obtaining signed informed consent, 15 patients on haemodialysis with severe generalised pruritus entered a randomised double-blind placebo-controlled crossover study (figure 1). The patients had persistent pruritus, resistant to treatments such as antihistamines, intravenous lignocaine, antipruritic lotions, ultraviolet therapy, ketotifen, and cholestyramine. All patients were examined by a dermatologist to exclude causes of pruritus other than renal

Results

The visual analogue score on the day before treatment was similar when the first test period was either naltrexone or placebo. The median pruritus scores at the end of the naltrexone treatment were 2·1 (IQR 1·5–2·15) for the naltrexone-placebo sequence and 1·0 (0·4–1·15) for the placebo-naltrexone sequence. These values were significantly different (p<0·001) from the respective values before naltrexone: 9·9 (9·85–9·95) and 9·9 (9·3–10·0) (figure 2). Pruritus was relieved in the first 48 h of

Discussion

We found that naltrexone administration in patients on chronic haemodialysis relieved severe intractable pruritus, with fewer side-effects.

Endogenous opioids have been implicated in the production of pruritus due to cholestasis. This condition is associated with increased blood levels of endogenous opioids in human beings and in animals, and treatment with opioid antagonists can relieve the pruritus.14, 15, 16, 17, 21 β-endorphin can be high in patients with chronic renal failure on dialysis,22

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