吗啡和氢吗啡酮的药效、副作用和变异性：一项交叉研究

以下文章来源于罂粟花 ，作者anesthGH

本文由“罂粟花”授权转载

吗啡和氢吗啡酮的药效、副作用和变异性：一项交叉研究

背景：

如何更好地平衡阿片类镇痛药的效果与呼吸抑制在围手术期、急诊科和其他急性护理环境中仍是一大挑战。在美国，吗啡和氢吗啡酮是术后镇痛的标准用药。然而，到目前为止对两者的药效和副作用、时效和各自的变异性知之甚少。本研究假设静脉注射吗啡和氢吗啡酮在镇痛的起效时间、程度、持续时间、变异性和通气情况方面存在差异。

方法：

在健康志愿者中进行随机交叉研究。42名受试者间隔1至2周接受氢吗啡酮（0.05mg / kg）或吗啡（0.2mg / kg）持续输注2小时。结局指标为动脉内阿片类药物浓度、对热反应刺激疼痛的镇痛效果（最大耐受温度，以及在离散预设温度下的语言模拟疼痛评分，以确定半最大温度效应）、暗适应瞳孔直径和瞳孔缩小、呼气末二氧化碳和给药后12小时的呼吸频率。

结果：

与氢吗啡酮相比，吗啡治疗后的最大瞳孔缩小程度较小（3.9 [3.4至4.2]对4.6 mm [4.0至5.0]，P < 0.001；中位数和25%至75%分位数），发生较晚（开始输注后3.1±0.9h比2.3±0.7 h，P < 0.001；平均值±标准差）; 最大耐受温度较低（49±2°C比50±2°C，P < 0.001）;在输注氢吗啡酮结束后给予最大耐受温度（48.2°C）时的语言疼痛评分为59±3，最大呼气末二氧化碳分压为48 mmHg（46至51），在输注吗啡结束后给予最大耐受温度（48.2°C）时的语言疼痛评分为82±4（P < 0.001），最大呼气末CO2分压为47mmHg（45至50; P = 0.007），并且发生较晚（输注开始后5.5±2.8小时比3.0±1.5 小时，P < 0.001）；吗啡与氢吗啡酮最小呼吸频率分别为9±1次/分钟和11±2次/分钟（P < 0.001），发生时间相似。吗啡的温度耐受-时间曲线下面积（1.8°C-h [0.0，4.4]）小于氢吗啡酮（5.4°C-h [1.6，12.1] P < 0.001），该两种阿片类药物在临床效应方面不存在个体间差异。  

结论：

与氢吗啡酮相比，吗啡的镇痛相关呼吸抑制较少，瞳孔缩小和呼吸抑制发生较晚，呼吸抑制持续时间较长。对于每种阿片类药物的各种临床时效并不一致。本试验结果可能使阿片类药物选择更加合理，并表明氢吗啡酮可能具有更好的临床特征。

原始文献来源：

Konrad Meissner, Albert Dahan, Erik Olofsen,et al. Morphine and Hydromorphone Effects, Side Effects, and Variability: A Crossover Study in Human Volunteers. Anesthesiology 2023; 139:16–34.

英文原文：

Morphine and Hydromorphone Effects, Side Effects, and Variability: A Crossover Study in Human Volunteers

Background: Balancing between opioid analgesia and respiratory depression continues to challenge clinicians in perioperative, emergency department, and other acute care settings. Morphine and hydromorphone are postoperative analgesic standards. Nevertheless, their comparative effects and side effects, timing, and respective variabilities remain poorly understood. This study tested the hypothesis that IV morphine and hydromorphone differ in onset, magnitude, duration, and variability of analgesic and ventilatory effects. Methods: The authors conducted a randomized crossover study in healthy volunteers. Forty-two subjects received a 2-h IV infusion of hydromorphone (0.05 mg/kg) or morphine (0.2 mg/kg) 1 to 2 weeks apart. The authors measured arterial opioid concentrations, analgesia in response to heat pain (maximally tolerated temperature, and verbal analog pain scores at discrete preset temperatures to determine half-maximum temperature effect), dark-adapted pupil diameter and miosis, end-expired carbon dioxide, and respiratory rate for 12 h after dosing. Results: For morphine and hydromorphone, respectively, maximum miosis was less (3.9 [3.4 to 4.2] vs. 4.6 mm [4.0 to 5.0], P < 0.001; median and 25 to 75% quantiles) and occurred later (3.1 ± 0.9 vs. 2.3 ± 0.7 h after infusion start, P < 0.001; mean ± SD); maximum tolerated temperature was less (49 ± 2 vs. 50 ± 2°C, P < 0.001); verbal pain scores at end-infusion at the most informative stimulus (48.2°C) were 82 ± 4 and 59 ± 3 (P < 0.001); maximum end-expired CO2 was 47 (45 to 50) and 48 mmHg (46 to 51; P = 0.007) and occurred later (5.5 ± 2.8 vs. 3.0 ± 1.5 h after infusion start, P < 0.001); and respiratory nadir was 9 ± 1 and 11 ± 2 breaths/min (P < 0.001), and occurred at similar times. The area under the temperature tolerance-time curve was less for morphine (1.8 [0.0 to 4.4]) than hydromorphone (5.4°C-h [1.6 to 12.1] P < 0.001). Interindividual variability in clinical effects did not differ between opioids. Conclusions: For morphine compared to hydromorphone, analgesia and analgesia relative to respiratory depression were less, onset of miosis and respiratory depression was later, and duration of respiratory depression was longer. For each opioid, timing of the various clinical effects was not coincident. Results may enable more rational opioid selection, and suggest hydromorphone may have a better clinical profile. 

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本公众平台所刊载原创或转载内容不代表米勒之声的观点或立场。文中所涉及药物使用、疾病诊疗等内容仅供医学专业人士参考。

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编辑：MiSuper.米超

校对：Michel.米萱  

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