ObjectiveThere is controversy about the effects of high plasma bicarbonate concentration ([HCO3−]) and the CO2 response test. We analyzed the relationship between [HCO3−] and the variation in hydrogen ion concentration (pH) for a given change in PaCO2, and its effects upon CO2 response. DesignA retrospective study was carried out. SettingTwo intensive care units. PatientsSubjects with and without chronic obstructive pulmonary disease (COPD), at the beginning of weaning from mechanical ventilation. InterventionsThe CO2 response was evaluated by the re-inhalation of expired air method, measuring the hypercapnic ventilatory response (ΔVE/ΔPaCO2) and hypercapnic drive response (ΔP01/ΔPaCO2), where VE is minute volume and P0.1 is airway occlusion pressure 0.1s after the initiation of inspiration. Main outcome measures[HCO3−] and CO2 response. ResultsA total of 120 patients in the non-COPD group and 48 in the COPD group were studied. COPD patients had higher mean [HCO3−] than non-COPD patients (33.2±5.4 vs. 25.7±3.7mmol/l, p<0.001). In both non-COPD and COPD patients we observed a significant inverse linear relationship between [HCO3−] and pH change per mmHg of PaCO2 (p<0.001), ΔVE/ΔPaCO2 (p<0.001) and ΔP0.1/ΔPaCO2 (p<0.001). ConclusionsThere is an inverse linear relationship between [HCO3−] and the variation of pH for a given change in PaCO2 and the CO2 response.