Niemi G, Breivik H
Department of Anaesthesiology, National Hospital (Rikshospitalet), Oslo, Norway.
Acta Anaesthesiol Scand. 1998 Sep;42(8):897-909. doi: 10.1111/j.1399-6576.1998.tb05348.x.
Basic pharmacological research indicates that there are synergistic antinociceptive effects at the spinal cord level between adrenaline, fentanyl and bupivacaine. Our clinical experience with such a mixture in a thoracic epidural infusion after major surgery confirms this. The objectives of the present study were to evaluate the effects on postoperative pain intensity, pain relief and side effects when removing adrenaline from this triple epidural mixture.
A prospective, randomised, double-blind, cross-over study was carried out in 24 patients after major thoracic or abdominal surgery. Patients with only mild pain when coughing during a titrated thoracic epidural infusion of about 10 ml.h-1 of bupivacaine 1 mg.ml-1, fentanyl 2 micrograms.ml-1, and adrenaline 2 micrograms.ml-1 were included. On the 1st and 2nd postoperative days each patient was given a double-blind epidural infusion, at the same rate, with or without adrenaline. The effect was observed for 4 h or until pain when coughing became unacceptable in spite of a rescue analgesic procedure. Rescue analgesia consisted of up to two epidural bolus injections per hour and i.v. morphine if necessary. All patients received rectal paracetamol 1 g, every 8 h. Fentanyl serum concentrations were measured with a radioimmunoassay technique at the start and end of each study period. Main outcome measures were extent of sensory blockade and pain intensity at rest and when coughing, evaluated by a visual analogue scale, a verbal categorical rating scale, the Prince Henry Hospital pain score, and an overall quality of pain relief score.
The number of hypaesthetic dermatomal segments decreased (P < 0.001) and pain intensity at rest and when coughing increased (P < 0.001) when adrenaline was omitted from the triple epidural mixture. This change started within the first hour after removing adrenaline. After 3 h pain intensity when coughing had increased to unacceptable levels in spite of rescue analgesia (epidural bolus injections and i.v. morphine). Within 15-20 min after restarting the triple epidural mixture with adrenaline, pain intensity was again reduced to mild pain when coughing. Serum concentration of fentanyl doubled from 0.22 to 0.45 ng.ml-1 (P < 0.01), and there was more sedation during the period without adrenaline.
Adrenaline increases sensory block and improves the pain-relieving effect of a mixture of bupivacaine and fentanyl infused epidurally at a thoracic level after major thoracic or abdominal surgery. Serum fentanyl concentrations doubled and sedation increased when adrenaline was removed from the epidural infusion, indicating more rapid vascular absorption and systemic effects of fentanyl.
基础药理学研究表明，肾上腺素、芬太尼和布比卡因在脊髓水平具有协同镇痛作用。我们在大手术后经胸段硬膜外输注这种混合液的临床经验证实了这一点。本研究的目的是评估从这种三联硬膜外混合液中去除肾上腺素后对术后疼痛强度、疼痛缓解及副作用的影响。
对24例接受胸段或腹部大手术的患者进行了一项前瞻性、随机、双盲、交叉研究。纳入在以约10 ml.h-1的速度滴定输注1 mg.ml-1布比卡因、2 μg.ml-1芬太尼和2 μg.ml-1肾上腺素的胸段硬膜外输注过程中咳嗽时仅轻度疼痛的患者。在术后第1天和第2天，每位患者接受一次双盲硬膜外输注，输注速度相同，一种含肾上腺素，另一种不含肾上腺素。观察效果4小时，或直至尽管采取了补救镇痛措施但咳嗽时疼痛变得难以忍受。补救镇痛包括每小时最多两次硬膜外推注，必要时静脉注射吗啡。所有患者每8小时直肠给予1 g对乙酰氨基酚。在每个研究期开始和结束时，采用放射免疫测定技术测量芬太尼血清浓度。主要观察指标为感觉阻滞范围以及静息和咳嗽时的疼痛强度，通过视觉模拟评分、语言分类评分、亨利王子医院疼痛评分和总体疼痛缓解质量评分进行评估。
从三联硬膜外混合液中去除肾上腺素后，感觉减退皮节数量减少（P < 0.001），静息和咳嗽时的疼痛强度增加（P < 0.001）。这种变化在去除肾上腺素后的第一小时内开始。3小时后，尽管采取了补救镇痛措施（硬膜外推注和静脉注射吗啡），咳嗽时的疼痛强度仍增加到难以忍受的程度。在重新开始含肾上腺素的三联硬膜外混合液输注后15 - 20分钟内，咳嗽时的疼痛强度再次降至轻度疼痛。芬太尼血清浓度从0.22 ng.ml-1增加一倍至0.45 ng.ml-1（P < 0.01），且在不含肾上腺素的期间镇静作用更强。
肾上腺素可增强感觉阻滞，并改善大胸段或腹部手术后经胸段硬膜外输注布比卡因和芬太尼混合液的镇痛效果。从硬膜外输注中去除肾上腺素后，芬太尼血清浓度增加一倍且镇静作用增强，表明芬太尼的血管吸收更快且全身作用更强。
