ArticlesRandomised crossover trial of naltrexone in uraemic pruritus
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.
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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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