Effects of dihydrocodeine, alcohol, and caffeine on breathlessness and exercise tolerance in patients with chronic obstructive lung disease and normal blood gases

N Engl J Med. 1981 Dec 31;305(27):1611-6. 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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcoholic Beverages
  • Caffeine / pharmacology*
  • Carbon Dioxide / blood
  • Clinical Trials as Topic
  • Codeine / analogs & derivatives*
  • Codeine / pharmacology
  • Codeine / therapeutic use
  • Double-Blind Method
  • Drug Synergism
  • Dyspnea / prevention & control
  • Ethanol / pharmacology*
  • Female
  • Humans
  • Lung Diseases, Obstructive / drug therapy
  • Lung Diseases, Obstructive / physiopathology*
  • Male
  • Middle Aged
  • Oxygen / blood
  • Oxygen Consumption / drug effects
  • Oxygen Inhalation Therapy
  • Physical Exertion*
  • Respiration / drug effects*
  • Respiratory Function Tests


  • Carbon Dioxide
  • Caffeine
  • Ethanol
  • dihydrocodeine
  • Oxygen
  • Codeine