Rygnestad T, Zahlsen K, Bergslien O, Dale O
Department of Anaesthesia, Regional and University Hospital, Trondheim, Norway.
Acta Anaesthesiol Scand. 1999 Apr;43(4):380-7. doi: 10.1034/j.1399-6576.1999.430403.x.
Epidural infusion of morphine, usually with bupivacaine, for postoperative pain relief has proved to be safe and effective. Lidocaine with its short duration of action and low toxicity may be an alternative to bupivacaine. The clinical importance of the choice of local anaesthetic drug on mobilisation after lower abdominal surgery has not been studied previously.
A total of 52 patients was randomised to epidural infusion of morphine (1.6-4.4 micrograms.kg-1.h-1) with either lidocaine (0.44-0.98 mg.kg-1.h-1) or bupivacaine (0.10-0.28 mg.kg-1.h-1) in a double-blind fashion. The time to mobilisation, degree of pain relief, blood pressure, respiration and motor function were recorded at regular intervals postoperatively for 40 h. Serum concentrations of lidocaine, its main metabolite monoethylglycinexylidide (MEGX) and bupivacaine were measured at 3, 15 and 40 h.
There were no significant differences in the clinical characteristics between the two patient groups. There were no significant differences in the time from the end of surgery to the time the patients were able to stand without support (bupivacaine: median 24 h (interquartile range (IQR): 22-31), lidocaine: median 28 h (IQR 23-40), P = 0.15) or were able to walk without support (bupivacaine: median 46 h (IQR 28-62), lidocaine: median 48 h (IQR 35-54), P = 0.78). No significant differences between the groups were recorded with respect to pain relief, blood pressure, respiration, sedation score and motor function. The plasma concentration of lidocaine and bupivacaine increased significantly during the treatment period (P < 0.01 for both drugs), but not the concentration of MEGX. The highest venous lidocaine concentration was 17.5 mumol/l and the highest bupivacaine concentration was 18.8 mumol/l. There was a significant correlation between the concentration of both lidocaine and bupivacaine and the concentration of alpha 1-acid glycoprotein (AAG) (lidocaine: r = 0.77, P < 0.001, bupivacaine: r = 0.60, P < 0.001), suggesting that the free fraction of the drugs did not increase. No patients showed serious signs of toxicity. The epidural infusion rates remained stable in both groups during the study period.
There were no clinically or statistically significant differences in the postoperative course after lower abdominal surgery in patients who received an epidural infusion of morphine combined with bupivacaine as compared to patients who received morphine with lidocaine. Further clinical studies to establish the place of lidocaine in postoperative epidural analgesia should be performed.
硬膜外输注吗啡（通常与布比卡因合用）用于术后镇痛已被证明是安全有效的。利多卡因作用时间短且毒性低，可能是布比卡因的一种替代药物。以往尚未研究局部麻醉药物的选择对下腹部手术后活动能力的临床重要性。
总共52例患者被随机分为两组，以双盲方式接受硬膜外输注吗啡（1.6 - 4.4微克·千克⁻¹·小时⁻¹），其中一组配伍利多卡因（0.44 - 0.98毫克·千克⁻¹·小时⁻¹），另一组配伍布比卡因（0.10 - 0.28毫克·千克⁻¹·小时⁻¹）。术后40小时内定期记录患者的活动时间、疼痛缓解程度、血压、呼吸及运动功能。在术后3小时、15小时和40小时测量血清利多卡因及其主要代谢产物单乙基甘氨酰二甲苯胺（MEGX）以及布比卡因的浓度。
两组患者的临床特征无显著差异。从手术结束到患者能够独立站立的时间（布比卡因组：中位数24小时（四分位间距（IQR）：22 - 31），利多卡因组：中位数28小时（IQR 23 - 40），P = 0.15）或能够独立行走的时间（布比卡因组：中位数46小时（IQR 28 - 62），利多卡因组：中位数48小时（IQR 35 - 54），P = 0.78）均无显著差异。两组在疼痛缓解、血压、呼吸、镇静评分及运动功能方面均无显著差异。治疗期间利多卡因和布比卡因的血浆浓度显著升高（两种药物P均< 0.01），但MEGX浓度未升高。利多卡因最高静脉浓度为17.5微摩尔/升，布比卡因最高浓度为18.8微摩尔/升。利多卡因和布比卡因的浓度与α1 - 酸性糖蛋白（AAG）浓度均存在显著相关性（利多卡因：r = 0.77，P < 0.001，布比卡因：r = 0.60，P < 0.001），提示药物的游离部分未增加。无患者出现严重毒性迹象。研究期间两组的硬膜外输注速率均保持稳定。
接受硬膜外输注吗啡联合布比卡因的患者与接受吗啡联合利多卡因的患者相比，下腹部手术后的病程在临床和统计学上均无显著差异。应开展进一步的临床研究以确定利多卡因在术后硬膜外镇痛中的地位。
