Dataset Information

Using laboratory models to test treatment: morphine reduces dyspnea and hypercapnic ventilatory response.

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 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.

Measurements and main 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.

SUBMITTER: Banzett RB

PROVIDER: S-EPMC3208656 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Using laboratory models to test treatment: morphine reduces dyspnea and hypercapnic ventilatory response.

Banzett Robert B RB Adams Lewis L O'Donnell Carl R CR Gilman Sean A SA Lansing Robert W RW Schwartzstein Richard M RM

American journal of respiratory and critical care medicine 20110721 8

<h4>Rationale</h4>Opioids are commonly used to relieve dyspnea, but clinical data are mixed and practice varies widely.<h4>Objectives</h4>Evaluate the effect of morphine on dyspnea and ventilatory drive under well-controlled laboratory conditions.<h4>Methods</h4>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 a ...[more]

PMID: 21778294

Similar Datasets

Project description:AimsIntravenous iron therapy can improve symptoms in patients with heart failure, anaemia and iron deficiency. The mechanisms underlying such an improvement might involve chemoreflex sensing and nocturnal breathing patterns.Methods and resultsPatients with heart failure, reduced left ventricular ejection fraction, anaemia (haemoglobin <13 g/dl in men; <12 g/dl in women) and iron deficiency (ferritin <100 or 100-299 μg/L with transferrin saturation <20%) were 2:1 randomized to patient-tailored intravenous ferric carboxymaltose dose or placebo. Chemoreflex sensitivity cardiorespiratory sleep study, symptom assessment and cardiopulmonary exercise test were performed before and 2 weeks after the last treatment dose. Fifty-eight patients (38 active arm/20 placebo arm) completed the study. Intravenous iron was associated with less severe symptoms, higher haemoglobin (12.5 ± 1.4 vs. 11.7 ± 1.0 mg/dl, p < 0.05) and improved haematinic parameters. Ferric carboxymaltose improved the central hypercapnic ventilatory response (-25.8%, p < 0.05 vs. placebo), without changes in peripheral chemosensitivity. In particular, the central hypercapnic ventilatory responses passed from 4.6 ± 6.5 to 2.9 ± 2.9 L/min/mmHg after ferric carboxymaltose and from 4.4 ± 4.6 to 4.6 ± 3.9 L/min/mmHg after placebo (ptreatment*condition = 0.046). In patients presenting with sleep-related breathing disorder, apnoea-hypopnoea index was reduced with active treatment as compared to placebo (12 ± 11 vs. 19 ± 13 events/h, p < 0.05). After ferric carboxymaltose, but not after placebo, both peak oxygen uptake (VO2 ) increased (Δ1.1 ± 2.0 ml/kg/min, p < 0.05) and VO2 /workload slope was steeper (Δ0.67 ± 1.7 L/min/W, p < 0.01).ConclusionsIntravenous ferric carboxymaltose improves the hypercapnic ventilatory response and sleep-related breathing disorders in patients with heart failure, anaemia and iron deficiency. These newly described findings, along with improved oxygen delivery to exercising muscles, likely contribute to the favourable effects of ferric carboxymaltose in anaemic patients with heart failure.

Dataset Information

Using laboratory models to test treatment: morphine reduces dyspnea and hypercapnic ventilatory response.

Rationale

Objectives

Methods

Measurements and main results

Conclusions

Publications

Using laboratory models to test treatment: morphine reduces dyspnea and hypercapnic ventilatory response.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets