de Leon-Casasola O A, Lema M J
Department of Anesthesiology and Critical Care Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263.
Anesthesiology. 1994 Feb;80(2):303-9. doi: 10.1097/00000542-199402000-00010.
Opioids are thought to have equal analgesic effects when equivalent doses are used. However, sufentanil may achieve maximum effect while occupying fewer spinal opioid receptors (higher intrinsic efficacy). Therefore, sufentanil may be more effective than morphine when administered intraspinally in opioid-tolerant patients.
This study evaluated 20 chronic cancer pain patients who underwent abdominal surgery for tumor resection. All patients used large doses of morphine (> 250 mg/day-1) preoperatively for 3 months or longer. Intraoperatively, patients received combined general-epidural anesthesia with 0.5% bupivacaine and 0.02% morphine at 8 ml/h-1. Postoperative continuous epidural analgesia with 0.1% bupivacaine and 0.02% morphine at 5 ml/h-1 plus intravenous patient-controlled analgesia morphine (3 mg every 6 min) was given. Epidural infusions were increased every 30 min by 1 ml/h-1 to achieve a dynamic (during coughing) visual analog pain score (VAPS) of less than 5/10. If the desired VAPS was not achieved after 6 h or the epidural morphine infusion was increased to 2 mg/h-1, 50 micrograms of sufentanil in 10 ml of normal saline was given as an epidural bolus dose. The epidural infusion then was switched to 0.0002% sufentanil (2 micrograms/ml-1) and 0.1% bupivacaine (1 mg/ml-1) at 7 ml/h-1. Further titration to maintain a dynamic VAPS of less than 5/10 occurred every 4 h.
Mean preoperative daily oral morphine use was 380 +/- 97 mg (range 290-490) for 4 +/- 1 months. Before the switch to sufentanil, patients had received a mean maximum morphine dose of 8.8 +/- 0.2 mg intraoperatively plus 9.0 +/- 1.2 mg during 4.2 +/- 0.3 h postoperatively (1.8 +/- 0.4 mg/h-1), at which point VAPS ranged between 7-10/10. All patients experienced adequate analgesia within 1 h of starting sufentanil therapy. The mean sufentanil dose during the first 4 h of treatment was 17 +/- 0.2 micrograms/h-1. At this time, VAPS ranged from 0-3/10. Satisfactory analgesia was achieved with sufentanil at a lower than a calculated equally potent dose of morphine (23 micrograms/h-1 vs. 17 micrograms/h-1, P < 0.01). Intravenous patient-controlled analgesia morphine requirements were also lower (7.8 mg/h-1 vs. 2.0 mg/h-1, P < 0.01). Length of morphine and sufentanil therapies were 5 +/- 3 h and 10 +/- 2 days, respectively. No patient experienced signs or symptoms of opioid withdrawal.
These results suggest that sufentanil can be used successfully in opioid-tolerant patients who do not experience adequate pain control in the early postoperative period despite a large dose of epidural morphine. Moreover, sufentanil should be considered an effective alternative therapy for postoperative pain control in chronic opioid users using high doses of oral opioids before surgical intervention.
人们认为当使用等效剂量时，阿片类药物具有同等的镇痛效果。然而，舒芬太尼可能在占据较少脊髓阿片受体的情况下达到最大效应（内在效能更高）。因此，在对阿片类药物耐受的患者中进行脊髓给药时，舒芬太尼可能比吗啡更有效。
本研究评估了20例因肿瘤切除而接受腹部手术的慢性癌症疼痛患者。所有患者术前使用大剂量吗啡（>250mg/天 -1）达3个月或更长时间。术中，患者接受0.5%布比卡因和0.02%吗啡以8ml/h -1的速度进行的全麻与硬膜外联合麻醉。术后给予0.1%布比卡因和0.02%吗啡以5ml/h -1的速度进行持续硬膜外镇痛，外加静脉自控镇痛吗啡（每6分钟3mg）。硬膜外输注每30分钟增加1ml/h -1，以达到咳嗽时视觉模拟疼痛评分（VAPS）小于5/10的动态效果。如果6小时后未达到所需的VAPS，或硬膜外吗啡输注量增加到2mg/h -1，则给予10ml生理盐水中含50μg舒芬太尼作为硬膜外推注剂量。然后硬膜外输注改为0.0002%舒芬太尼（2μg/ml -1）和0.1%布比卡因（1mg/ml -1），速度为7ml/h -1。每4小时进一步滴定以维持动态VAPS小于5/10。
术前平均每日口服吗啡用量为380±97mg（范围290 - 490mg），持续4±1个月。在改用舒芬太尼之前，患者术中平均最大吗啡剂量为8.8±0.2mg，术后4.2±0.3小时内为9.0±1.2mg（1.8±0.4mg/h -1），此时VAPS在7 - 10/10之间。所有患者在开始舒芬太尼治疗后1小时内均获得了充分的镇痛效果。治疗的前4小时内舒芬太尼的平均剂量为17±0.2μg/h -1。此时，VAPS范围为0 - 3/10。舒芬太尼在低于计算得出的等效效量吗啡剂量（23μg/h -1对17μg/h -1，P<0.01）时即实现了满意的镇痛效果。静脉自控镇痛所需的吗啡量也更低（7.8mg/h -1对2.0mg/h -1，P<0.01）。吗啡和舒芬太尼治疗的时长分别为5±3小时和10±2天。没有患者出现阿片类药物戒断的体征或症状。
这些结果表明，尽管给予了大剂量的硬膜外吗啡，但在术后早期疼痛控制不佳的阿片类药物耐受患者中，舒芬太尼可以成功使用。此外，对于术前使用高剂量口服阿片类药物的慢性阿片类药物使用者，舒芬太尼应被视为术后疼痛控制的一种有效替代疗法。
