Gustafsson L L, Wiesenfeld-Hallin Z
Department of Clinical Pharmacology, Karolinska Institute, Huddinge University Hospital.
Drugs. 1988 Jun;35(6):597-603. doi: 10.2165/00003495-198835060-00001.
Small spinal (intrathecal or extrathecal) doses of opioids induce a long-lasting and regional analgesic effect in various experimental animal models. Nowadays extrathecal morphine administration is considered an established method of controlling postoperative and cancer-induced pain conditions. The potency of morphine applied by the spinal route is higher than when the drug is applied by the intravenous (IV) route. Opioids which are more lipophilic than morphine will provide a marginally better analgesic effect when administered by the spinal route as compared with the IV route. Several controlled clinical trials in postoperative patients have demonstrated that a single dose of morphine administered by the spinal route gives a more long-lasting action than a similar IV dose. It is not known whether frequent patient-controlled administration of morphine may provide equally good analgesia without additional side effects. The use of spinal morphine in the treatment of cancer-related pain is based on clinical experience only. There are risks in replacing opioid administration by the oral or IV route with spinal opioids. Morphine should only be used in selected cases until the advantage of spinal opioid analgesia to control postoperative and cancer pain has been clearly defined in well-designed clinical studies. Spinal morphine dosages must be individualised according to the intensity of the nociceptive stimuli and should take into account intra-individual variability in drug responses due to pharmacokinetic and pharmacodynamic factors.
在各种实验动物模型中,小剂量脊髓内(鞘内或鞘外)给予阿片类药物可产生持久的局部镇痛效果。如今,鞘外注射吗啡被认为是控制术后疼痛和癌症所致疼痛的一种成熟方法。经脊髓途径应用吗啡的效力高于经静脉(IV)途径给药时。与吗啡相比,亲脂性更强的阿片类药物经脊髓途径给药时,与经静脉途径给药相比,镇痛效果略好。多项针对术后患者的对照临床试验表明,单次经脊髓途径给予吗啡的作用持续时间比类似静脉剂量更长。尚不清楚患者频繁自控给予吗啡是否能在无额外副作用的情况下提供同样良好的镇痛效果。脊髓内使用吗啡治疗癌症相关疼痛仅基于临床经验。用脊髓阿片类药物替代口服或静脉阿片类药物给药存在风险。在精心设计的临床研究明确脊髓阿片类药物镇痛在控制术后疼痛和癌症疼痛方面的优势之前,吗啡仅应在特定情况下使用。脊髓内吗啡剂量必须根据伤害性刺激的强度个体化,并应考虑由于药代动力学和药效学因素导致的个体内药物反应变异性。