Mastenbroek Thierry C, Kramp-Hendriks Bianca J, Kallewaard Jan Willem, Vonk Johanna M
Department of Anaesthesiology, Pain and Palliative Medicine, Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.
Department of Anaesthesiology and Pain Management, Rijnstate Hospital, Wagnerlaan 55, 6815 AD, Arnhem, The Netherlands.
Scand J Pain. 2017 Jan;14:39-43. doi: 10.1016/j.sjpain.2016.10.002. Epub 2016 Nov 1.
Cancer pain treatment has improved over the last decades. The majority of this population can be treated effectively with analgesics following the Guidelines of the original World Health Organisation (WHO). Unfortunately 10-15% of these patients still suffer from severe and refractory cancer pain, especially in the terminal phases of disease and require additional pain management modalities. Therefore, end-stage clinical interventions are particularly needed to minimize the perception of pain. With intrathecal therapy (ITT), drugs are delivered close to their site of action in the central nervous system avoiding first-pass metabolism and blood-brain barrier. It may improve analgesia with a smaller dose and possibly achieve a reduction in systemic or cerebral side effects compared to oral supplied medication alone. Multimodal analgesia enables further dose reduction with improved analgesia and fewer side effects.
In this retrospective research we investigated the effectiveness and side-effect profile of intrathecal morphine, bupivacaine and clonidine. Patients were followed until death occurred. Pain scores and side effects were recorded before initiating ITT (T0), just after initiating ITT (T1), at hospital discharge (T2), in the ambulant setting (T3) and the last obtained scores before death occurred (T4).
Nine patients were included who suffered from severe and refractory cancer pain, not reacting to conventional pain management or had intolerable side effects. Primary tumour location was pancreatic (4), urothelial (3) and prostate (2). Primary pain was considered neuropathic or mixed neuropathic-nociceptive. The treatment team consisted of an anaesthetist, specialized nurse in coordination with primary physician, treating oncologist and specialized home care. All patients were free of pain after initiation of the intrathecal therapy. The average follow-up period was 11 weeks in which there was a slight increase in NRS-score. In the last days before death occurred, half the patients were still free of pain. There were no problems during insertion of the catheter, device malfunction or infection. No severe adverse events defined as hypotension requiring inotropes, respiratory depression or neurological deficits were observed. Three patients experienced mild hypotension which gradually decreased after clonidine dose adjustment. Lower extremity weakness occurred in three patients as well. After bupivacaine dose adjustment the weakness disappeared in two patients and in one patient the lower extremity weakness persisted as a result of conus compression by tumour.
Multimodal IT treatment with morphine, bupivacaine and clonidine is effective and safe for treating refractory cancer pain in the terminal phase of disease. The study offers an important contribution to literature where there is still lack of convincing evidence about the benefits and harms of this type of pain management in patients with otherwise refractory cancer pain.
在过去几十年中,癌症疼痛治疗有了改善。按照原世界卫生组织(WHO)的指南,这类患者中的大多数可以通过镇痛药得到有效治疗。不幸的是,这些患者中有10% - 15%仍遭受严重且难治的癌症疼痛,尤其是在疾病终末期,需要额外的疼痛管理方式。因此,特别需要终末期临床干预措施以尽量减少疼痛感受。通过鞘内治疗(ITT),药物在中枢神经系统中靠近其作用部位给药,避免了首过代谢和血脑屏障。与单独口服给药相比,它可能以较小剂量改善镇痛效果,并可能减少全身或脑部副作用。多模式镇痛可进一步减少剂量,同时改善镇痛效果并减少副作用。
在这项回顾性研究中,我们调查了鞘内注射吗啡、布比卡因和可乐定的有效性及副作用情况。对患者进行随访直至死亡。在开始鞘内治疗前(T0)、刚开始鞘内治疗后(T1)、出院时(T2)、门诊环境下(T3)以及死亡前最后一次获得的评分(T4)记录疼痛评分和副作用。
纳入了9例患有严重且难治性癌症疼痛、对传统疼痛管理无反应或有无法耐受的副作用的患者。原发肿瘤部位为胰腺(4例)、尿路上皮(3例)和前列腺(2例)。主要疼痛被认为是神经性或神经性 - 伤害性混合性疼痛。治疗团队由一名麻醉医生、与主治医生协调的专科护士、肿瘤内科医生和专科家庭护理人员组成。所有患者在开始鞘内治疗后均无疼痛。平均随访期为11周,在此期间数字疼痛评分量表(NRS)评分略有增加。在死亡前的最后几天,一半患者仍无疼痛。导管插入过程中、设备故障或感染方面均无问题。未观察到定义为需要使用血管活性药物的低血压、呼吸抑制或神经功能缺损等严重不良事件。3例患者出现轻度低血压,在调整可乐定剂量后逐渐减轻。3例患者也出现下肢无力。在调整布比卡因剂量后,2例患者的无力症状消失,1例患者因肿瘤压迫圆锥导致下肢无力持续存在。
吗啡、布比卡因和可乐定的多模式鞘内治疗对于治疗疾病终末期难治性癌症疼痛是有效且安全的。该研究为文献做出了重要贡献,因为对于这类难治性癌症疼痛患者的这种疼痛管理的利弊,仍缺乏令人信服的证据。