Effects of Oral Morphine on Breathlessness and Exercise Tolerance in Patients with Chronic Obstructive Pulmonary Disease

Printed in UK -all rights reserved D Dy ys sp pn no oe ea a a an nd d f fl lo ow w--v vo ol lu um me e c cu ur rv ve e d du ur ri in ng g e ex xe er rc ci is se e i in n C CO OP PD D p pa at ti ie en nt ts s Copyright ERS Journals Ltd 1994 European Respiratory Journal ISSN 0903 -1936 A. Noseda*, J-P. Carpiaux*, J. Schmerber*, F. Valente**, J-C. Yernault*** ABSTRACT: The purpose of this study, in patients with chronic obstructive pulmonary disease (COPD), was to examine the relationship of dyspnoea, rated on a visual analogue scale (VAS), to 1) tidal ventilatory variables measured on exercise and 2) pre-exercise lung function. Twenty one patients (forced expiratory volume in one second (FEV 1 ) mean (SD) 1.19 (0.32) l) were studied. During a preliminary test, the maximal workload was assessed and the upper end of the VAS was anchored. On the study day, the tidal flow-volume curve on exercise was monitored and dyspnoea was assessed serially every minute. In each individual, the relationship of dyspnoea to various tidal ventilatory variables was studied using linear regression analysis; results were reported as squared correlation coefficients, slopes and dyspnoea thresholds. Subsequently, the relationship of slopes and thresholds to pre-exercise lung function was examined.In all patients, dyspnoea showed a close correlation with ventilation, tidal volume, breathing frequency and tidal flow. The tidal peak inspiratory flow was the best individual predictor of dyspnoea with a median r 2 of 0.91. Patients with the poorest pre-exercise lung function exhibited the highest rates of increase in dyspnoea and the lowest thresholds, the strongest correlation being observed between the dyspnoea/ventilation slope and pre-exercise maximal peak inspiratory flow (r 2 = 0.54).In conclusion, for individual COPD patients dyspnoea on exercise is closely related to inspiratory flow. The degree of pre-exercise ventilatory impairment accounts, at most, for only half of the variation in dyspnoea perception between subjects.

Section: Discussionmentioning

confidence: 93%

Dyspnoea and flow-volume curve during exercise in COPD patients

Noseda¹,

Carpiaux²,

Schmerber³

et al. 1994

“…In two studies published in the 1980s, a decrease in exercise-induced dyspnoea was obtained in COPD subjects following oral administration of either 15 mg dihydrocodeine [1], or 0.8 mg·kg -1 of a morphine solution [2]. However, serious side-effects occurred in the latter study.…”

Section: Discussionmentioning

confidence: 95%

“…Systemic treatment with opioids has been reported to reduce dyspnoea in some patients groups [1,2], but adverse effects are common and preclude their long-term use. Nebulized morphine is potentially attractive, since it is free of the adverse effects associated with systemic therapy and uncontrolled studies have suggested a beneficial effect on dyspnoea [3,4].…”

mentioning

confidence: 99%

Disabling dyspnoea in patients with advanced disease: lack of effect of nebulized morphine

Noseda¹,

Carpiaux²,

Markstein³

et al. 1997

The purpose of this placebo-controlled, double-blind, randomized study was to assess the effect of nebulized morphine on dyspnoea perceived at rest by patients with advanced disease.Seventeen hospital in-patients with disabling dyspnoea received isotonic saline or morphine via nebulization for 10 min through a mouthpiece, combined with oxygen via nasal prongs. On four consecutive days, they were given one of the four following treatments in random order: saline with 2 L·min -1 oxygen; 10 mg morphine with 2 L·min -1 oxygen; 20 mg morphine with 2 L·min -1 oxygen; and 10 mg morphine without oxygen (prongs fixed, no flow). Dyspnoea was assessed on a bipolar visual analogue scale (VAS) (-100% much more short of breath, +100% much less short of breath), and arterial oxygen saturation (Sa,O 2 ) and respiratory frequency (f R) were recorded at the end of nebulization and 10 min later.In 14 subjects who completed the study, mean VAS ratings 10 min after the end of nebulization ranged +30 to +43%, with no significant difference between the four study days (VAS 20 mg morphine minus VAS saline, 95% confidence interval (95% CI) -6 to +8%). Sa,O 2 significantly increased on the 3 days with supplemental oxygen, and remained stable on the zero flow day. Respiratory frequency significantly decreased on the 4 days, with a trend to correlation between VAS rating and parallel change in respiratory frequency (Spearman's rank correlation coefficient (r s )=-0.46; p=0.09).We conclude that the subjects benefited from saline or morphine via a placebo effect and/or a nonspecific effect, and that nebulized morphine had no specific effect on dyspnoea.

“…Treatment of breathlessness is most effective when the primary cause can be identified and modified, but in those conditions in which treatment currently has little to offer, it is logical to explore the feasibility of modifying the perception of breathlessness in order to relieve distress. Many drugs, such as hydrocodeine [52][53][54][55], morphine [56][57][58][59], diazepam [60][61][62][63] and promethazine [62,63], have been tested for their ability to relieve intractable breathlessness, with inconclusive results. Relief when obtained can, in most cases, be adequately explained by a reduction in respiratory work without the need to postulate any alteration in the perceptive mechanism or ability.…”

Section: The Use Of Drugs To Alter the Perception Of Breathlessnessmentioning

confidence: 99%

“…Using oral morphine (0.8 mg·kg -1 ) in patients with severe chronic airflow obstruction, LIGHT et al [58] have shown that exercise endurance was increased and breathlessness, assessed using a modified Borg scale, significantly decreased following oral morphine treatment. The reduction in breathlessness in this study was achieved at the expense of an increase in arterial carbon dioxide tension, a reduction in ventilatory drive (P 0.1 ), and was thought by the authors to be due to a combination of lowered ventilatory requirements for a given workload and also to altered perception.…”

Section: The Use Of Drugs To Alter the Perception Of Breathlessnessmentioning

confidence: 99%

Chronic lung diseases and the perception of breathlessness: a clinical perspective

Burdon¹,

Pain²,

Rubinfeld³

et al. 1994

Breathlessness is an extremely common symptom. Its genesis is incompletely understood but is known to be largely determined by many of the mechanical factors associated with the act of breathing. As with all subjective sensations various other factors including volition, behavioural style and other cortical and subcortical factors play a part in its genesis.The relief of breathlessness is primarily directed at the underlying disorder. In those conditions and situations where specific therapy has little to offer or little impact it is reasonable to consider ways of reducing the perception of breathlessness by pharmacological means. However, to date there is no convincing evidence that use of drugs in the pursuit of the relief of breathlessness has any specific effect in modifying the perception of this often distressing symptom. Any reduction in breathlessness achieved in this way can be adequately explained in terms of a reduction in ventilation and other indices of respiratory mechanics.