Abstract

Inhibition of ventilatory drive may improve the sensation of dyspnea, because heightened ventilatory demand contributes to dyspnea. Tris-hydroxymethyl aminomethane (THAM) is an alkalizing agent that does not increase CO 2 production and exerts a depressant effect on respiration. The purpose of this study was to clarify the effect of THAM on dyspnea associated with increases in respiratory drive. We investigated the effects of THAM on dyspneic sensation produced by a combination of hypercapnia (mean PaCO 2 = 52 mm Hg) and elastic loading (30 cm H 2O/L) in 14 healthy subjects. The subjects were asked to rate their dyspneic sensation using a visual analogue scale (VAS) during the loaded breathing while monitoring ventilation using a pneumotachograph. THAM was infused at a rate of 0.4 mL/kg/minute for 10 minutes, and the effects of THAM on dyspnea and ventilation were evaluated by comparing the steady-state values of ventilatory variables and VAS score obtained before and after THAM administration. Administration of THAM corrected respiratory acidosis and was associated with significant improvements in VAS score and significant decreases in minute ventilation, respiratory frequency, and ventilatory drive. THAM administration greatly alleviates dyspneic sensation associated with the increase in respiratory drive and could be an effective therapy for treating severe dyspnea in patients with hypercapnia.

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