Using Laboratory Models to Test Treatment: Morphine Reduces Dyspnea and Hypercapnic Ventilatory Response

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Title Using Laboratory Models to Test Treatment: Morphine Reduces Dyspnea and Hypercapnic Ventilatory Response
Author Banzett, Robert B.; Adams, Lewis; O'Donnell, Carl R.; Gilman, Sean A.; Lansing, Robert W.; Schwartzstein, Richard M.
Journal Name American Journal of Respiratory and Critical Care Medicine
Year Published 2011
Place of publication United States
Publisher American Thoracic Society
Abstract 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.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1164/rccm.201101-0005OC
Copyright Statement Self-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the authors for more information.
Volume 184
Issue Number 8
Page from 920
Page to 927
ISSN 1073-449X
Date Accessioned 2012-03-01; 2012-03-09T05:28:32Z
Date Available 2012-03-09T05:28:32Z
Research Centre Griffith Health Institute
Faculty Griffith Health Faculty
Subject Respiratory Diseases
URI http://hdl.handle.net/10072/43492
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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