Peer G, Kivity S, Agami O, Fireman E, Silverberg D, Blum M, laina A
Department of Nephrology, Ichilov Hospital, Tel Aviv Medical Centre, Israel.
Lancet. 1996 Dec 7;348(9041):1552-4. doi: 10.1016/s0140-6736(96)04176-1.
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.
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 beta-endorphin levels were measured, and spontaneous and stimulated basophil histamine-release were determined.
The median pruritus scores at the end of the naltrexone treatment were 2.1 (interquartile range 1.5-2.15) for the naltrexone-placebo sequence and 1.0 (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 beta-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 1.8 [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.
Our data suggest short-term efficacy with few side-effects for the amelioration of uraemic pruritus with naltrexone.
大多数透析患者会出现瘙痒症状，目前的治疗方法并不令人满意。内源性阿片类物质可能与这种瘙痒有关。我们研究了阿片类拮抗剂纳曲酮对血液透析患者瘙痒的影响。
在一项随机、双盲、安慰剂对照的交叉试验中，对15例患有严重顽固性瘙痒的血液透析患者口服每日50毫克纳曲酮。纳曲酮或安慰剂治疗期各持续7天，两个治疗期之间有7天的洗脱期。患者通过视觉模拟量表从0（无瘙痒）到10（最严重）对瘙痒进行评估，并计算每日平均得分。测量血浆组胺和β-内啡肽水平，并测定自发和刺激的嗜碱性粒细胞组胺释放。
纳曲酮-安慰剂序列中纳曲酮治疗结束时瘙痒评分中位数为2.1（四分位间距1.5 - 2.15），安慰剂-纳曲酮序列为1.0（0.4 - 1.15）。给予纳曲酮前的相应值分别为9.9（9.85 - 9.95）和9.9（9.3 - 10.0）。血浆β-内啡肽水平正常，在研究期间保持不变。血浆组胺水平较高（平均2.32 [标准差0.11] ng/mL，正常<1.0），纳曲酮治疗后降低（降至1.8 [0.09]，p < 0.01）。白细胞介素-3加IgE抗体刺激的血液透析患者嗜碱性粒细胞释放大量组胺。与5名正常对照的26.6（16.3）%相比，增加了78.3（19.3）%（p < 0.01）。嗜碱性粒细胞与另一种阿片类拮抗剂纳洛酮孵育可防止这种作用。
我们的数据表明，纳曲酮改善尿毒症瘙痒具有短期疗效且副作用较少。
