Effects of doxapram on hypercapnic response during weaning from mechanical ventilation in COPD patients

Failure of weaning from mechanical ventilation in COPD patients is often related to diaphragmatic fatigue. Whether there is a central respiratory drive fatigue and a reserve of excitability is still debated. The purpose of this study was to analyze the following in 13 COPD patients weaned from mechanical ventilation: (1) ventilatory (VE/PETCO2) and neuromuscular (P0.1/PETCO2) response to hypercapnia; (2) the maximum reserve capacity measured through changes in the VE/PETCO2 and P0.1/PETCO2 slopes after doxapram (DXP) infusion, which, given during the test, allows measurement of the maximum response capacity to overstimulation; and (3) analyze the influence of these changes on the outcome of weaning. The results show a variable P0.1/PETCO2 response and a low VE/PETCO2. DXP infusion does not change the slopes of these relations but increases the end-expiratory volume (delta FRCd); (p less than 0.02). Since there was no change in the VE/PETCO2, P0.1/PETCO2, and delta FRC values with or without DXP, there was no excitability reserve in patients who were successfully weaned. When weaning failed, DXP did not change VE/PETCO2 and P0.1/PETCO2 slope, but delta FRCd was greater the delta FRC (p less than 0.001). The excitability reserve in these patients leads to an increase in end-expiratory volume, probably worsening the diaphragm dysfunction.