Effects of Dihydrocodeine, Alcohol, and Caffeine on Breathlessness and Exercise Tolerance in Patients with Chronic Obstructive Lung Disease and Normal Blood Gases

• Published in: The New England journal of medicine Vol. 305; no. 27; pp. 1611 - 1616
• Main Authors: Woodcock, Ashley A, Gross, Elizabeth R, Gellert, Andrew, Shah, Smita, Johnson, Margaret, Geddes, Duncan M
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 31.12.1981
• Subjects: Alcohol; Alcoholic Beverages; Asthma; Caffeine; Caffeine - pharmacology; Carbon dioxide; Carbon Dioxide - blood; Chronic obstructive pulmonary disease; Clinical Trials as Topic; Codeine - analogs & derivatives; Codeine - pharmacology; Codeine - therapeutic use; Double-Blind Method; Drug Synergism; Dyspnea - prevention & control; Ethanol - pharmacology; Exercise; Female; Fitness equipment; Gases; Hospitals; Humans; Lung diseases; Lung Diseases, Obstructive - drug therapy; Lung Diseases, Obstructive - physiopathology; Male; Middle Aged; Narcotics; Obstructive lung disease; Opioids; Oxygen - blood; Oxygen consumption; Oxygen Consumption - drug effects; Oxygen Inhalation Therapy; Physical Exertion; Respiration - drug effects; Respiratory Function Tests
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJM198112313052703

We measured breathlessness and exercise tolerance in 12 patients with chronic airways obstruction, moderate or severe breathlessness, and low or normal arterial carbon dioxide tension, after the patients received dihydrocodeine, alcohol, caffeine, or placebo (through double-blind administration). forty-five minutes after ingestion, dihydrocodeine had reduced breathlessness by 20 per cent and increased exercise tolerance by 18 per cent, with a reduction in ventilation and oxygen consumption at submaximal work loads but with no change in spirometric volumes. Oxygen also reduced breathlessness and provided additional benefit to that achieved with dihydrocodeine (at three hours after ingestion) when the two were given together: the reduction of breathlessness was 18 per cent with dihydrocodeine; 22 per cent with oxygen; and 32 per cent with dihydrocodeine plus oxygen. Alcohol increased forced vital capacity by 9 per cent, and exercise tolerance by 7 per cent. Caffeine had no deleterious effect on breathlessness or exercise tolerance, despite increasing ventilation during rest and exercise. We conclude that opiates may be valuable for the treatment of breathlessness in selected patients; further evaluation is needed, particularly of the long-term benefits and safety. (N Engl J Med. 1981; 305:1611–6.) BREATHLESSNESS and exercise tolerance in patients with chronic airways obstruction correlate poorly with lung function. 1 Thus "pink and puffing" patients maintain nearly normal levels of blood gases at rest for many years, at the cost of persistent breathlessness, in contrast to "blue and bloated" patients with arterial hypercapnia, hypoxemia, and consequent cor pulmonale. 2 3 4 Treatment aimed at improving lung function is at best only moderately effective. There is therefore a need for treatment aimed at the symptom of breathlessness itself. We have shown that oxygen 5 and promethazine 6 relieve breathlessness and improve exercise tolerance without changing lung function appreciably, whereas diazepam has . . .