Characterization of the analgesic actions of adenosine: comparison of adenosine and remifentanil infusions in patients undergoing major surgical procedures
Characterization of the analgesic actions of adenosine: comparison of adenosine and remifentanil infusions in patients undergoing major surgical procedures
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DOI：
10.1016/s0304-3959(02)00321-4
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发表时间：
2003-01-01
期刊：
影响因子：
7.4
通讯作者：
Stark, CW
中科院分区：
文献类型：
--
作者：
Fukunaga, AF;Alexander, GE;Stark, CW
围手术期疼痛仍然是一个主要问题，应该探索新的药理学手段来减轻这种疼痛。腺苷是一种普遍存在的内源性物质；当外源性给药时，它提供了许多有益的作用，包括神经调节、镇痛和细胞保护作用。本研究的目的是表征术中腺苷输注的围手术期抗伤害镇痛作用，确定术后的作用持续时间，并在双盲研究中将其与瑞芬太尼对接受大手术的患者进行比较。62 名患者被随机分配接受两种治疗中的一种。标准麻醉诱导后，对肺部进行机械通气。用恒定肺泡浓度的吸入麻醉剂（3% 地氟烷和 65% 一氧化二氮的氧气溶液）维持麻醉。皮肤切口前5 min开始可变速率静脉输注腺苷（50-500 mug kg(-1) min(-1)）或瑞芬太尼（0.05-0.5 mug kg(-1) min(-1)），并滴定至术中维持收缩压和心率在基线值的20%以内。术后评估包括镇静水平、疼痛严重程度、阿片类镇痛药（芬太尼、吗啡）用量以及48小时心肺指标。术中腺苷或瑞芬太尼可以同样实现对手术刺激的心血管反应的抑制，并且两者都可以保持良好的血流动力学稳定性。然而，术后却存在显着差异：（1）与瑞芬太尼组相比，腺苷组的初始疼痛评分降低了60%（P < 0.001），并且在整个48小时恢复期内始终保持较低水平； (2)腺苷组术后前0.25、2和48小时的吗啡需求量始终低于瑞芬太尼组（分别为78%、71%和42%，P < 0.001）； (3) 在所有评估中，腺苷患者的镇静效果仍然明显较差； (4)当患者入住麻醉后监护室时，瑞芬太尼组的呼气末和动脉二氧化碳值显着升高。任何时候都没有观察到腺苷的不良反应。术中腺苷输注有助于从麻醉中恢复，并显着且持续地缓解术后疼痛。与瑞芬太尼相比，腺苷显着减少了阿片类药物的需求，并最大限度地减少了术后恢复期间的副作用，包括长期镇静、心肺不稳定、恶心和呕吐。 (C) 2002 年国际疼痛研究协会。由 Elsevier Science B.V. 出版。保留所有权利。
Perioperative pain is still a major problem, and new pharmacological means should be explored to mitigate such pain. Adenosine is an ubiquitous endogenous substance; when exogenously administered, it provides a number of salutary effects including neuromodulation, antinociception, and cytoprotective actions. The aim of this study was to characterize the perioperative antinociceptive-analgesic effects of intraoperative adenosine infusion and determine the duration of actions in the postoperative period, and compare them to those of remifentanil in patients undergoing major surgical procedures in a double-blind study.Sixty-two patients were randomly assigned to one of the two treatments. After standard induction of anesthesia, the lungs were mechanically ventilated. Anesthesia was maintained with a constant alveolar concentration of inhaled anesthetics (3% desflurane and 65% nitrous oxide in oxygen). A variable-rate of intravenous infusion of adenosine (50-500 mug kg(-1) min(-1)) or remifentanil (0.05-0.5 mug kg(-1) min(-1)) was initiated 5 min before the skin incision and was titrated to maintain systolic blood pressure and heart rate within 20% of baseline values during surgery. Postoperative evaluations included the level of sedation, degree of pain severity, opioid analgesic (fentanyl, morphine) consumption, and cardiorespiratory variables for 48 h.Intraoperative inhibition of the cardiovascular responses to surgical stimulation could be equally achieved by adenosine or remifentanil, and both could maintain excellent hemodynamic stability. Postoperatively, however, there were striking differences: (1) initial pain score was reduced by 60% (P < 0.001) in the adenosine group compared to the remifentanil group and it remained lower throughout the 48 h recovery period; (2) postoperative morphine requirements during the first 0.25, 2 and 48 h were consistently lower in the adenosine group as compared to the remifentanil group (78, 71 and 42%, P < 0.001, respectively); (3) adenosine patients remained significantly less sedated at all evaluations; (4) the end-tidal and arterial carbon dioxide values in the remifentanil group were significantly higher when patients were admitted to the postanesthesia care unit. No adverse effect of adenosine was observed at any time.Intraoperative adenosine infusion provided a salutary recovery from anesthesia associated with a pronounced and sustained postoperative pain relief. Compared to remifentanil, adenosine significantly reduced the opioid requirements and minimized the side effects including protracted sedation, cardiorespiratory instability, nausea, and vomiting in the postoperative recovery period. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.