title: Using laboratory models to test treatment: morphine reduces dyspnea and hypercapnic ventilatory response.
abstract: BACKGROUND
  Opioids are commonly used to relieve dyspnea, but clinical data are mixed and practice varies widely.
  
  
  OBJECTIVE
  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 CO(2) stimulus: (1) perceptual response (breathing discomfort; described by subjects as "air hunger") induced by increasing partial pressure of end-tidal carbon dioxide (Pet(CO2)) during restricted ventilation, measured with a visual analog scale (range, "neutral" to "intolerable"); and (2) ventilatory response, measured in separate trials during unrestricted breathing.
  
  
  RESULTS
  We determined the Pet(CO2) that produced a 60% breathing discomfort rating in each subject before morphine (median, 8.5 mm Hg above resting Pet(CO2)). At the same Pet(CO2) after morphine administration, median breathing discomfort was reduced by 65% of its pretreatment value; P < 0.001. Ventilation fell 28% at the same Pet(CO2); 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.
authors.affiliation: Division of Pulmonary and Critical Care, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA. rbanzett@bidmc.harvard.edu
authors.forename: Robert B
authors.initials: RB
authors.lastname: Banzett
authors.forename: Lewis
authors.initials: L
authors.lastname: Adams
authors.forename: Carl R
authors.initials: CR
authors.lastname: O'Donnell
authors.forename: Sean A
authors.initials: SA
authors.lastname: Gilman
authors.forename: Robert W
authors.initials: RW
authors.lastname: Lansing
authors.forename: Richard M
authors.initials: RM
authors.lastname: Schwartzstein
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D004417:Dyspnea / Q000188:drug therapy*; D005260:Female; D006801:Humans; D006935:Hypercapnia / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000494:pharmacology / Q000627:therapeutic use*; D012123:Pulmonary Ventilation / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine