Avramov M N, Smith I, White P F
Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas 75235, USA.
Anesthesiology. 1996 Dec;85(6):1283-9. doi: 10.1097/00000542-199612000-00009.
Remifentanil, an ultra-short-acting opioid analgesic, may be useful as an intravenous adjuvant to local anesthesia for treating patient discomfort and pain during monitored anesthesia care (MAC). However, the remifentanil dose requirements, interactions with other commonly used sedative drugs (such as midazolam), and recovery characteristics after ambulatory procedures have not been determined. Therefore, this study was designed to evaluate the safety and efficacy of remifentanil alone and in combination with different doses of midazolam during MAC.
Eighty-one healthy consenting women scheduled for elective breast biopsy procedures were randomly assigned to one of four treatment groups according to an institutional review board-approved, double-blind, placebo-controlled protocol. The study medication (containing either saline or 2 mg, 4 mg, or 8 mg of midazolam) was administered intravenously 5 min before starting an infusion of remifentanil at 0.1 microgram.kg-1.min-1. The remifentanil infusion was subsequently adjusted in 0.025- and 0.05-microgram.kg-1.min-1 increments to maintain patient comfort and adequate ventilation during the operation. The level of sedation was assessed at 1- to 10-min intervals during the procedure using the inverted observer's assessment of alertness/sedation (OAA/S) scale, with a score of 1 = awake, alert to 5 = asleep, unarousable. Discomfort and pain were assessed using numerical rating scales. Hemoglobin oxygen saturation, respiratory rate, blood pressure (systolic, diastolic, mean), and heart rate were monitored at 1- to 5-min intervals. Intraoperative amnesia was assessed by asking patients to recall a picture shown 5 min after the study medication was administered. Recovery was evaluated using the Aldrete score and the times to "home readiness" and actual discharge. Side effects and patient satisfaction were assessed in a follow-up telephone interview on the first postoperative day.
Midazolam produced dose-dependent increases in the median level of sedation. Remifentanil produced a greater reduction in respiratory rate in the 4-mg and 8-mg midazolam groups. However, there were no significant differences in the hemodynamic variables or discharge times. Patients with OAA/S scores of 1 to 3 ("light" sedation) 5 min after the study medication experienced a greater incidence of intraoperative pruritus and postoperative nausea and vomiting (PONV) compared with those with OAA/S scores of 4 to 5 ("deep" sedation). Discharge times were prolonged for patients in the light sedation group in whom PONV developed.
Use of remifentanil alone for MAC did not provide optimal sedation during local anesthesia. However, 0.05 to 0.1 microgram.kg-1.min-1 remifentanil in combination with 2 mg midazolam given intravenously, provided effective sedation and analgesia during MAC in healthy patients classified as American Society of Anesthesiologists status 1 to 2. Midazolam also produced dose-dependent potentiation of remifentanil's depressant effect on respiratory rate. In outpatients receiving a combination of midazolam and remifentanil during local anesthesia, the level of sedation appears to influence the incidence of both intraoperative pruritus and PONV.
瑞芬太尼是一种超短效阿片类镇痛药，作为局部麻醉的静脉辅助用药，可能有助于在麻醉监护（MAC）期间治疗患者的不适和疼痛。然而，瑞芬太尼的剂量需求、与其他常用镇静药物（如咪达唑仑）的相互作用以及门诊手术后的恢复特征尚未确定。因此，本研究旨在评估瑞芬太尼单独使用以及与不同剂量咪达唑仑联合使用在MAC期间的安全性和有效性。
81名计划进行择期乳房活检手术且同意参与的健康女性，根据机构审查委员会批准的双盲、安慰剂对照方案，随机分配至四个治疗组之一。在以0.1微克·千克⁻¹·分钟⁻¹的速度开始输注瑞芬太尼前5分钟，静脉注射研究药物（含生理盐水或2毫克、4毫克或8毫克咪达唑仑）。随后以0.025微克·千克⁻¹·分钟⁻¹和0.05微克·千克⁻¹·分钟⁻¹的增量调整瑞芬太尼输注速度，以在手术期间维持患者舒适和充分通气。在手术过程中，每隔1至10分钟使用反向观察者警觉/镇静评分（OAA/S）量表评估镇静水平，评分1 = 清醒、警觉至5 = 入睡、无法唤醒。使用数字评分量表评估不适和疼痛。每隔1至5分钟监测血红蛋白氧饱和度、呼吸频率、血压（收缩压、舒张压、平均压）和心率。通过询问患者回忆在研究药物给药后5分钟展示的图片来评估术中遗忘。使用Aldrete评分以及“准备回家”时间和实际出院时间评估恢复情况。在术后第一天通过电话随访评估副作用和患者满意度。
咪达唑仑使镇静中位数水平呈剂量依赖性增加。瑞芬太尼在4毫克和8毫克咪达唑仑组中使呼吸频率降低幅度更大。然而，血流动力学变量和出院时间无显著差异。与OAA/S评分为4至5（“深度”镇静）的患者相比，研究药物给药后5分钟OAA/S评分为1至3（“轻度”镇静）的患者术中瘙痒和术后恶心呕吐（PONV）的发生率更高。发生PONV的轻度镇静组患者出院时间延长。
单独使用瑞芬太尼用于MAC在局部麻醉期间未提供最佳镇静效果。然而，0.05至0.1微克·千克⁻¹·分钟⁻¹的瑞芬太尼与静脉注射2毫克咪达唑仑联合使用，在被分类为美国麻醉医师协会1至2级状态的健康患者的MAC期间提供了有效的镇静和镇痛。咪达唑仑还使瑞芬太尼对呼吸频率的抑制作用呈剂量依赖性增强。在局部麻醉期间接受咪达唑仑和瑞芬太尼联合治疗的门诊患者中，镇静水平似乎影响术中瘙痒和PONV的发生率。
