Tighe K E, Webb A M, Hobbs G J
University Department of Anaesthesia, Queen's Medical Centre, Nottingham, United Kingdom.
Anesth Analg. 1999 May;88(5):1137-42. doi: 10.1097/00000539-199905000-00032.
We studied the time course of clinical and pharmacokinetic effects after the rectal administration of diclofenac 100 mg in seven patients using patient-controlled morphine (PCA) on the first postoperative day after major spinal surgery. Plots of plasma diclofenac concentrations and pain intensity difference (PID) demonstrated counterclockwise hysteresis consistent with distribution to a central effect compartment such as the central nervous system. Mean +/- SEM (range) maximum PID and its timing were 62%+/-10% (32%-98%) and 309+/-20 (210-360) min after the administration of diclofenac, respectively. Minimal respiratory rates were significantly slower after the administration of diclofenac (P < 0.001), occurring at 197+/-51.9 (60-360) min; arterial desaturations occurred in two patients without oxygen therapy. Plasma morphine and morphine-6-glucuronide (M6G) concentrations interpolated to the average time of minimal respiratory rate indicated decreases of 23%+/-13% (0%-79%) and 1%+/-9% (0%-32%) from their respective starting values. Plasma M6G concentrations were significantly different from baseline only 420 and 480 min after the administration of diclofenac. The potential opioid-sparing effects of a nonsteroidal antiinflammatory drug added during PCA morphine use may not be manifest for several hours. During this lag, plasma concentrations of M6G may reach and remain at levels high enough to increase the risk of respiratory depression and other opioid side effects for hours.
Plasma concentrations of morphine, morphine-6-glucuronide, and diclofenac were measured postoperatively after a single dose of rectal diclofenac 100 mg was added to morphine patient-controlled analgesia. Peak analgesia occurred 309 min and respiratory depression 197 min after diclofenac administration. Morphine consumption had decreased by 20%, but concentrations of the active metabolite morphine-6-glucuronide were unchanged. Vigilance is recommended in patients receiving patient-controlled analgesia opioids and nonsteroidal antiinflammatory drugs.
我们在7例接受大脊柱手术后第一天使用患者自控吗啡（PCA）的患者中，研究了直肠给予100mg双氯芬酸后的临床和药代动力学效应的时间过程。血浆双氯芬酸浓度和疼痛强度差值（PID）曲线显示出逆时针滞后，这与向中枢效应室（如中枢神经系统）分布一致。双氯芬酸给药后，平均±标准误（范围）最大PID及其出现时间分别为62%±10%（32%-98%）和309±20（210-360）分钟。双氯芬酸给药后最低呼吸频率显著减慢（P<0.001），出现在197±51.9（60-360）分钟；两名患者在未进行氧疗的情况下出现动脉血氧饱和度下降。根据最低呼吸频率的平均时间推算的血浆吗啡和吗啡-6-葡萄糖醛酸（M6G）浓度显示，与各自起始值相比分别下降了23%±13%（0%-79%）和1%±9%（0%-32%）。双氯芬酸给药后仅420和480分钟，血浆M6G浓度与基线有显著差异。在PCA吗啡使用期间添加非甾体抗炎药的潜在阿片类药物节省效应可能在数小时内不明显。在此延迟期间，M6G的血浆浓度可能会达到并在数小时内保持在足以增加呼吸抑制和其他阿片类药物副作用风险的高水平。
在吗啡患者自控镇痛中添加单次直肠给予100mg双氯芬酸后，术后测量了吗啡、吗啡-6-葡萄糖醛酸和双氯芬酸的血浆浓度。双氯芬酸给药后309分钟出现镇痛峰值，197分钟出现呼吸抑制。吗啡消耗量减少了20%，但活性代谢产物吗啡-6-葡萄糖醛酸的浓度未改变。建议对接受患者自控镇痛阿片类药物和非甾体抗炎药的患者保持警惕。
