Methods to Assess Breathlessness in Healthy Subjects: A Critical Evaluation and Application to Analyse the Acute Effects of Diazepam and Promethazine on Breathlessness Induced by Exercise or by Exposure to Raised Levels of Carbon Dioxide

Abstract

1. Methods were devised and evaluated for inducing breathlessness by submaximal graded exercise in healthy subjects while objective measurements of cardiorespiratory function were made. Breathlessness was assessed with serial visual analogue scales (VAS), but with various measures to enhance repeatability. 2. A high level of reproducibility was obtained in spite of the subjective nature of the assessment. Individual responses were described by the relationship between breathlessness and ventilation. The sensitivity of the method was demonstrated by the use of inspiratory resistances which disturbed this relationship and caused greater breathlessness for a given level of ventilation. 3. These methods were applied to six healthy subjects to analyse the effects of acute doses of diazepam and promethazine on breathlessness induced by graded exercise or by rebreathing carbon dioxide in a double-blind study. 4. During exercise, diazepam and promethazine did not reduce breathlessness, although there was a minor trend with promethazine. During exposure to elevated levels of carbon dioxide, diazepam and promethazine had no effect on breathlessness. Diazepam and promethazine produced similar levels of sedation, but neither drug had significant effects on the ventilatory response to carbon dioxide. These preliminary findings contrast with those reported for chronic diazepam in 'pink puffers'. 5. Raised levels of carbon dioxide caused greater breathlessness in relation to ventilation than did exercise.

The effects of ICI 118,587 and atenolol on the responses to exercise and on breathlessness in healthy subjects.

“…The test was similar to that described in detail previously (Stark et al, 1981). Sub-maximal exercise was undertaken by walking on an inclined treadmill at three speeds (2 kph for 2 min, 4 kph for 2 min and 6 kph for 2 min) to achieve a range of values for ventilation rather than a steady state.…”

“…The latter was assessed using methods we have described and validated (Stark et al, 1981(Stark et al, , 1983a). …”

Chlorpromazine‐a specific effect on breathlessness?

“…The test was similar to that described in detail previously (Stark et al, 1981). In brief, submaximal exercise was undertaken on a treadmill to achieve a range of values of minute ventilation and breathlessness was assessed with visual analogue scales (VAS) at intervals of 1 min.…”

“…MitchellHeggs et al (1980) reported that diazepam reduced dyspnoea in patients with the 'pink puffer' syndrome but the larger study of Woodcock et al (1981) failed to confirm this effect in similar patients. Any benefit of diazepam might be secondary to sedation and for this reason Stark et al (1981), in their investigation in healthy subjects, included promethazine as a control treatment. Surprisingly, breathlessness during exercise was reduced but this effect did not achieve statistical significance.…”

Assessing unconsciousness in livestock at slaughter

“…Exposure to CO 2 stimulates respiration and pigs start to hyperventilate (Raj and Gregory, 1996). In humans, this is described as breathlessness which is known to increase with blood carbon dioxide levels (Stark et al, 1981). Moreover, CO 2 is an acidic gas with a high solubility that together with water forms carbonic acid.…”