Opioid-related side-effects after intrathecal morphine: a prospective, randomized, double-blind dose-response study
Opioid-related side-effects after intrathecal morphine: a prospective, randomized, double-blind dose-response study
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DOI：
10.1017/s026502150600038x
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发表时间：
2006-07-01
影响因子：
3.6
通讯作者：
Casati, A.
中科院分区：
文献类型：
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作者：
Raffaeli, W.;Marconi, G.;Casati, A.
背景和目的：这项前瞻性、随机、双盲研究的目的是评估阿片类药物初治、非手术患者鞘内注射小剂量吗啡（0.015至0.25 mg）后术后恶心和呕吐的剂量效应特征。研究方法：经伦理委员会批准和书面知情同意，144名患有非癌性慢性背痛并接受鞘内吗啡作为慢性疼痛诊断试验的阿片类药物初治患者被随机分配接受鞘内注射0.015 mg（组I，n = 25）、0.03 mg（组II，n = 30）、0.06 mg（组III，n = 31）或0.25 mg（组IV，n = 33）吗啡。对照组包括未纳入剂量效应研究的另外25名患者，这些患者在棘突间韧带中接受生理盐水安慰剂注射。设盲观察员记录注射后2、4和24 h瘙痒、恶心、呕吐、尿潴留和呼吸抑制（呼吸频率< 6 bpm）的发生情况。结果如下：在所有接受鞘内吗啡的患者中观察到临床显著的疼痛缓解，但对照组中只有6例患者（25%）（P = 0.0005）。第III组（6%）和第IV组（3%）患者的瘙痒发生率低于第I组（12%）和第II组（20%）（P = 0.002）。恶心和呕吐的发生率在2小时和4小时观察时间较高，鞘内注射后24小时下降。令人惊讶的是，第I组（56%）和第II组（50%）的恶心发生率高于第III组（33%）和第IV组（24%）（P = 0.0005）。吗啡组患者的呕吐次数高于对照组，但四种剂量之间无差异。在对照组中未观察到尿潴留，而鞘内注射后2 h，20-40%的病例观察到尿潴留，脊髓注射后24 h降至10%以下，四种剂量之间无差异。结论：鞘内吗啡给药后轻微阿片类药物相关副作用的发作和发生率不取决于其剂量，即使是非常小剂量的吗啡也会发生。因此，它们可以被认为是药物的患者依赖性效应，表明存在可能与阿片受体双峰激活理论相关的主要剂量非依赖性兴奋组分。严重呼吸抑制的发生率非常低，这使我们无法得出任何关于这种副作用的剂量-效应关系的结论，应该提倡进一步适当的研究来评估脊髓吗啡后的严重呼吸抑制。
Background and objective: The aim of this prospective, randomized, double-blind investigation was to assess the dose-effect characteristics of postoperative nausea and vomiting after intrathecal administration of small doses of morphine (from 0.015 to 0.25 mg) in opioid-naive, non-surgical patients. Methods: With Ethic Committee approval and written informed consent 144 opioid-naive patients suffering from non-cancerous chronic back-pain, and receiving intrathecal morphine as diagnostic test for their chronic pain, were randomly allocated to receive intrathecal injection of 0.015 mg (Group I, n = 25), 0.03 mg (Group II, n = 30), 0.06 mg (Group III, n = 31) or 0.25 mg (Group IV, n = 33) morphine. The control group consisted in 25 further patients not included in the dose-effect study and receiving a placebo injection of normal saline in the interspinous ligament. A blinded observer recorded the occurrence of pruritus, nausea, vomiting, urinary retention and respiratory depression (respiratory rate < 6 bpm) at 2, 4 and 24 h after injection. Results: Clinically significant pain relief was observed in all patients receiving intrathecal morphine but only six patients (25%) of the control group (P = 0.0005). The incidence of pruritus was lower in patients of Groups III (6%) and IV (3%) than in Groups I (12%) and II (20%) (P = 0.002). The incidence of nausea and vomiting was higher at 2- and 4-h observation times, and decreased 24 h after intrathecal injection. Surprisingly, nausea was more frequent in Groups I (56%) and II (50%) than in Groups III (33%) and IV (24%) (P = 0.0005). Vomiting was higher in patients receiving morphine than in control group, but without differences among the four doses. No urinary retention was observed in the control group, while 2 h after intrathecal injection urinary retention was observed in 20-40% of cases, and decreased to less than 10% 24 h after spinal injection without differences among the four doses. Conclusions: The onset and incidence of minor opioid-related side-effects after intrathecal morphine administration do not depend on its dose, occurring with even very small doses of morphine. Accordingly, they can be considered as a patient-dependent effect of the drug, suggesting the presence of a primary dose-independent excitatory component that might be related to the theory of the bimodal activation of opioid receptors. The very low incidence major respiratory depression prevents us from drawing any conclusion about the dose-effect relationship for this side-effect, and further properly powered studies should be advocated to evaluate major respiratory depression after spinal morphine.