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吗啡消耗与异基因造血干细胞移植儿童的全身炎症有关。

Morphine consumption is associated with systemic inflammation in children undergoing allogeneic hematopoietic stem cell transplantation.

机构信息

a Department of Pediatrics and Adolescent Medicine , Copenhagen University Hospital, Rigshospitalet , Copenhagen , Denmark.

b Department of Anesthesiology , Copenhagen University Hospital, Rigshospitalet , Copenhagen , Denmark.

出版信息

Immunopharmacol Immunotoxicol. 2019 Apr;41(2):285-291. doi: 10.1080/08923973.2019.1590846. Epub 2019 Mar 20.

Abstract

The majority of children undergoing allogenic hematopoietic stem cell transplantation (HSCT) experience severe pain due to chemotherapy-induced gastrointestinal toxicity. Inter-individual differences in pain perceived and opioid consumption remain unexplained, limiting the possibility for individualized pain control. The aim of this study was to investigate the associations between opioid consumption and markers of gastrointestinal toxicity (plasma citrulline) and systemic inflammation (plasma CRP and IL-6) in these patients. We retrospectively included 38 children undergoing HSCT in Denmark in 2010-2012. Opioids doses on days 0-21 post-HSCT were registered as intravenous morphine equivalents (MEs). CRP was measured daily on days 0-21. IL-6 was measured on day 7. Citrulline was measured before conditioning, on days 7 and 21. Out of 38 children, 37 (97%) received opioids during days 0-21. CRP level and ME dose peaked on days 9-10 while citrulline level reached a nadir on day 7 indicating maximum enterocyte loss. CRP was associated with ME dose, with an estimated increase of 0.030 mg/kg (95% CI 0.024-0.035) in ME for a 50% increase in CRP level on the same day ( < .001). IL-6 was correlated with ME on day 7 (rho = 0.55,  = .002). Citrulline did not correlate with ME. Opioid consumption in the early post-HSCT period is associated with the degree of chemotherapy-induced systemic inflammation and not with the extent of enterocyte loss. These findings contribute to our understanding of mucositis-related pain and may be of interest for future studies on therapeutic strategies.

摘要

大多数接受异基因造血干细胞移植 (HSCT) 的儿童因化疗引起的胃肠道毒性而经历严重疼痛。个体间对疼痛的感知和阿片类药物消耗的差异仍未得到解释,限制了个体化疼痛控制的可能性。本研究旨在探讨这些患者中阿片类药物消耗与胃肠道毒性标志物(血浆瓜氨酸)和全身炎症标志物(血浆 CRP 和 IL-6)之间的相关性。

我们回顾性纳入了 2010 年至 2012 年在丹麦接受 HSCT 的 38 名儿童。HSCT 后 0-21 天的阿片类药物剂量记录为静脉注射吗啡当量 (ME)。CRP 每天在 0-21 天测量。IL-6 在第 7 天测量。瓜氨酸在预处理前、第 7 天和第 21 天测量。

在 38 名儿童中,37 名(97%)在 0-21 天期间接受了阿片类药物。CRP 水平和 ME 剂量在第 9-10 天达到峰值,而瓜氨酸水平在第 7 天达到最低点,表明最大的肠细胞丢失。CRP 与 ME 剂量相关,CRP 水平升高 50%,ME 剂量估计增加 0.030mg/kg(95%CI 0.024-0.035)( < .001)。第 7 天 IL-6 与 ME 相关(rho=0.55, = .002)。瓜氨酸与 ME 不相关。HSCT 后早期阿片类药物消耗与化疗引起的全身炎症程度相关,而与肠细胞丢失程度无关。这些发现有助于我们了解与粘膜炎相关的疼痛,并可能对未来的治疗策略研究感兴趣。

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