Using Laboratory Models to Test Treatment Morphine Reduces Dyspnea and Hypercapnic Ventilatory Response
Using Laboratory Models to Test Treatment Morphine Reduces Dyspnea and Hypercapnic Ventilatory Response
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DOI：
10.1164/rccm.201101-0005oc
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发表时间：
2011-10-15
影响因子：
24.7
通讯作者：
Schwartzstein, Richard M.
中科院分区：
文献类型：
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作者：
Banzett, Robert B.;Adams, Lewis;Schwartzstein, Richard M.
理由：阿片类药物常用于缓解呼吸困难，但临床数据参差不齐，实践差异很大。目的：在控制良好的实验室条件下评估吗啡对呼吸困难和通气驱动的影响。方法：六名健康志愿者在不同的日子静脉注射吗啡（0.07 mg/kg）和安慰剂（随机、盲法）。我们测量了对二氧化碳刺激的两种反应：（1）知觉反应（呼吸不适；被受试者描述为“空气饥饿”），在通气受限期间由呼气末二氧化碳分压（PETCO2）增加引起，用视觉模拟量表测量（范围，“中性”到“无法忍受”）； (2) 通气反应，在不受限制的呼吸期间在单独的试验中测量。测量和主要结果：我们确定了在吗啡之前每个受试者产生 60% 呼吸不适评级的 PETCO2（中位值，比静息 PETCO2 高 8.5 毫米汞柱）。吗啡给药后，在相同的 PETCO2 水平下，呼吸不适中位数比治疗前值减少了 65%； P < 0.001。在相同 PETCO2 条件下，通风量下降 28%； P<0.01。吗啡对呼吸不适的影响与对通气反应的影响不显着相关。安慰剂没有效果。结论：（1）中等吗啡剂量可显着缓解实验室呼吸困难，且通气量减少幅度较小。 (2) 与早期的呼吸努力实验室模型相比，这种空气饥饿实验室模型建立了非常显着的治疗效果，其程度与阿片类药物的临床研究一致。实验室研究需要较少的受试者，并且可以实现在临床环境中难以进行的生理测量。受试者对仔细控制的实验室刺激的反应进行比较可以成为临床试验前优化治疗的有效手段。
Rationale: Opioids are commonly used to relieve dyspnea, but clinical data are mixed and practice varies widely.Objectives: Evaluate the effect of morphine on dyspnea and ventilatory drive under well-controlled laboratory conditions.Methods: Six healthy volunteers received morphine (0.07 mg/kg) and placebo intravenously on separate days (randomized, blinded). We measured two responses to a CO2 stimulus: (1) perceptual response(breathing discomfort; described by subjects as "air hunger") induced by increasing partial pressure of end-tidal carbon dioxide (PETCO2) during restricted ventilation, measured with a visual analog scale (range, "neutral" to "intolerable"); and (2) ventilatory response, measured in separate trials during unrestricted breathing.Measurements and Main Results: We determined the PETCO2 that produced a 60% breathing discomfort rating in each subject before morphine (median, 8.5 mm Hg above resting PETCO2). At the same PETCO2 after morphine administration, median breathing discomfort was reduced by 65% of its pretreatment value; P < 0.001. Ventilation fell 28% at the same PETCO2; P < 0.01. The effect of morphine on breathing discomfort was not significantly correlated with the effect on ventilatory response. Placebo had no effect.Conclusions: (1) A moderate morphine dose produced substantial relief of laboratory dyspnea, with a smaller reduction of ventilation. (2) In contrast to an earlier laboratory model of breathing effort, this laboratory model of air hunger established a highly significant treatment effect consistent in magnitude with clinical studies of opioids. Laboratory studies require fewer subjects and enable physiological measurements that are difficult to make in a clinical setting. Within-subject comparison of the response to carefully controlled laboratory stimuli can be an efficient means to optimize treatments before clinical trials.