Bujedo Borja Mugabure, Santos Silvia González, Azpiazu Amaia Uría
Department of Anesthesiology, Donostia University Hospital, San Sebastián, Spain.
J Opioid Manag. 2012 May-Jun;8(3):177-92. doi: 10.5055/jom.2012.0114.
Opioids are the most potent centrally acting analgesic drugs for the treatment of pain. For the past years, since the discovery of spinal opioid receptors, the use of spinal opioids has been adopted in clinical practice in the hope of producing intense segmental analgesia that was devoid of the dose-limiting side effects associated with systemic opioid administration. Experimental studies have demonstrated that after their perispinal administration, liposolubility is inversely proportional to their spinal selectivity, which is higher for the most water-soluble drug, morphine, than for other more lipophilic drugs, such as fentanyl and sufentanil. Clinical trials have shown that epidural morphine in the form of extended-release liposome injections gives good analgesia for a period of 48 hours, with no need for epidural catheterization. Conversely, fentanyl is the most appropriate opioid in ambulatory surgery and seems to have the strongest effect at the spinal cord administered epidurally as a bolus and supraspinally using continuous epidural infusion. Epidural methadone and hydromorphone are suitable alternatives for analgesia in the postoperative period, given that they have intermediate pharmacokinetic characteristics with respect to the two aforementioned groups of opioids. All opioids administered intrathecally will produce some degree of spinally mediated analgesia. The main differences are related to their duration of action, rate of clearance, and the pathways by which the drugs reach their receptors in the brain. In general, lipophilic opioids produce short-term analgesia (1-4 hours), which is very useful for immediate postoperative pain. However, morphine produces intense analgesia for up to 24 hours with doses as low as 100 μg.
阿片类药物是治疗疼痛最有效的中枢性镇痛药。在过去的几年里，自从发现脊髓阿片受体以来，脊髓阿片类药物的使用已被应用于临床实践，以期产生强烈的节段性镇痛作用，而没有与全身应用阿片类药物相关的剂量限制性副作用。实验研究表明，在脊髓周围给药后，脂溶性与其脊髓选择性成反比，对于水溶性最高的药物吗啡来说，其脊髓选择性高于其他亲脂性更强的药物，如芬太尼和舒芬太尼。临床试验表明，缓释脂质体注射形式的硬膜外吗啡能提供长达48小时的良好镇痛效果，无需硬膜外置管。相反，芬太尼是门诊手术中最合适的阿片类药物，在硬膜外推注给药于脊髓时以及通过持续硬膜外输注给药于脊髓以上部位时，似乎具有最强的作用。硬膜外美沙酮和氢吗啡酮是术后镇痛的合适替代药物，因为它们在药代动力学特征方面介于上述两类阿片类药物之间。所有鞘内给药的阿片类药物都会产生一定程度的脊髓介导的镇痛作用。主要差异与它们的作用持续时间、清除率以及药物到达大脑中受体的途径有关。一般来说，亲脂性阿片类药物产生短期镇痛作用（1 - 4小时），这对术后即刻疼痛非常有用。然而，吗啡以低至100μg的剂量可产生长达24小时的强烈镇痛作用。
