Kurita G P, Lundström S, Sjøgren P, Ekholm O, Christrup L, Davies A, Kaasa S, Klepstad P, Dale O
Department of Oncology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark.
Multidisciplinary Pain Centre, Department of Neuroanaesthesiology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark.
Acta Anaesthesiol Scand. 2015 Sep;59(8):1049-59. doi: 10.1111/aas.12521. Epub 2015 May 5.
Renal impairment and the risk of toxicity caused by accumulation of opioids and/or active metabolites is an under-investigated issue. This study aimed at analysing if symptoms/adverse effects in opioid-treated patients with cancer were associated with renal function.
Cross-sectional multicentre study (European Pharmacogenetic Opioid Study, 2005-2008), in which 1147 adult patients treated exclusively with only one of the most frequently reported opioids (morphine/oxycodone/fentanyl) for at least 3 days were analysed. Fatigue, nausea/vomiting, pain, loss of appetite, constipation and cognitive dysfunction were assessed (EORTC QLQ-C30). Glomerular filtration rate (GFR) was estimated using Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI Creatinine) equations.
Mild to severe low GFR was observed among 40-54% of patients. CG equation showed that patients with mild and moderate/severe low GFR on morphine treatment had higher odds of having severe constipation (P < 0.01) than patients with normal GFR. In addition, patients with moderate/severe low GFR on morphine treatment were more likely to have loss of appetite (P = 0.04). No other significant associations were found.
Only severe constipation and loss of appetite were associated with low GFR in patients treated with morphine. Oxycodone and fentanyl, in relation to the symptoms studied, seem to be safe as used and titrated in routine cancer pain care.
肾功能损害以及阿片类药物和/或活性代谢产物蓄积所致的毒性风险是一个研究不足的问题。本研究旨在分析接受阿片类药物治疗的癌症患者的症状/不良反应是否与肾功能相关。
横断面多中心研究（欧洲药物基因组学阿片类药物研究，2005 - 2008年），分析了1147例成年患者，这些患者仅接受一种最常报告的阿片类药物（吗啡/羟考酮/芬太尼）治疗至少3天。评估了疲劳、恶心/呕吐、疼痛、食欲减退、便秘和认知功能障碍（欧洲癌症研究与治疗组织核心问卷QLQ - C30）。使用Cockcroft - Gault（CG）、肾脏病饮食改良（MDRD）和慢性肾脏病流行病学协作组（CKD - EPI肌酐）方程估算肾小球滤过率（GFR）。
40% - 54%的患者观察到轻度至重度低GFR。CG方程显示，接受吗啡治疗的轻度和中度/重度低GFR患者发生严重便秘的几率高于GFR正常的患者（P < 0.01）。此外，接受吗啡治疗的中度/重度低GFR患者更易出现食欲减退（P = 0.04）。未发现其他显著相关性。
在接受吗啡治疗的患者中，仅严重便秘和食欲减退与低GFR相关。就所研究的症状而言，羟考酮和芬太尼在常规癌症疼痛治疗中按常规使用和滴定似乎是安全的。
