Du Pen Stuart L, Kharasch Evan D, Williams Anna, Peterson Donald G, Sloan Dean C, Hasche-Klunder Hans, Krembs Alexander W
Pain Consultation Service, Swedish Hospital Medical Center, Seattle, WA 98104, USA Department of Anesthesiology, Swedish Hospital Medical Center, Seattle, WA 98104, USA Department of Anesthesiology, University of Washington, Seattle, WA 98195 USA Department of Anesthesiology and Medicinal Chemistry, University of Washington, Seattle, WA 98195 USA.
Pain. 1992 Jun;49(3):293-300. doi: 10.1016/0304-3959(92)90234-3.
This study examined the efficacy and toxicity associated with chronic epidural opioid-bupivacaine infusions. In a series of 68 patients with cancer pain refractory to epidural opioids alone, analgesia was effectively regained by infusing a opioid-bupivacaine combination. Sixty-one patients (90%) were considered treatment successes, according to conventional criteria. Median length of therapy was 60-120 days, with the longest infusion lasting 277 days. Chronic bupivacaine infusion concentrations ranged from 0.1 to 0.5% with infusion rates varying from 4 to 18 ml/h. The majority of patients experienced pain relief with little or no sympathetic or sensorimotor impairment after the first 24 h at bupivacaine concentrations of 0.125-0.25% and were managed in home or chronic care settings without the need for re-hospitalization. In patients receiving higher bupivacaine concentrations, sympathetic, sensory and motor blockade were well tolerated during chronic infusion. Sensory loss was consistently observed only at bupivacaine concentrations exceeding 0.25%, and motor impairment occurred only at concentrations exceeding 0.35%. Postural hypotension was observed in 6 patients (9%) for the first 24 h only, which supports the requirement for monitoring and fluid therapy during initiation of the bupivacaine infusion. No patient experienced CNS or systemic toxicity, despite plasma total bupivacaine concentrations as high as 10.8 micrograms/ml. Serial plasma bupivacaine levels were measured in 15 patients during chronic infusion. There was considerable inter- and intra-individual variability in plasma bupivacaine concentrations and bupivacaine clearance. We conclude that epidural opioid-bupivacaine infusion is an effective and safe technique for long-term administration of analgesics in the refractory cancer patient.
本研究考察了慢性硬膜外注射阿片类药物与布比卡因联用的疗效及毒性。在一组68例单独使用硬膜外阿片类药物无法缓解癌痛的患者中,通过输注阿片类药物与布比卡因的组合有效地恢复了镇痛效果。根据传统标准,61例患者(90%)被认为治疗成功。治疗的中位时长为60 - 120天,最长输注持续277天。慢性布比卡因输注浓度范围为0.1%至0.5%,输注速率为4至18毫升/小时。在布比卡因浓度为0.125 - 0.25%的情况下,大多数患者在最初24小时后疼痛缓解,几乎没有或没有交感神经或感觉运动功能障碍,并且在家庭或长期护理环境中接受治疗,无需再次住院。在接受更高布比卡因浓度的患者中,慢性输注期间对交感神经、感觉和运动阻滞的耐受性良好。仅在布比卡因浓度超过0.25%时持续观察到感觉丧失,而运动功能障碍仅在浓度超过0.35%时出现。仅在最初24小时内有6例患者(9%)出现体位性低血压,这支持在开始布比卡因输注期间进行监测和液体治疗的必要性。尽管血浆总布比卡因浓度高达10.8微克/毫升,但没有患者出现中枢神经系统或全身毒性。在15例患者慢性输注期间测量了系列血浆布比卡因水平。血浆布比卡因浓度和布比卡因清除率在个体间和个体内存在相当大的变异性。我们得出结论,硬膜外阿片类药物与布比卡因联用是为难治性癌症患者长期给予镇痛药的一种有效且安全的技术。