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Abstract
BackgroundChronic obstructive pulmonary disease (COPD) patients may develop metabolic alkalosis during weaning from mechanical ventilation. Acetazolamide is one of the treatments used to reverse metabolic alkalosis.Methods619 time-respiratory (minute ventilation, tidal volume and respiratory rate) and 207 time-PaCO2 observations were obtained from 68 invasively ventilated COPD patients. We modeled respiratory responses to acetazolamide in mechanically ventilated COPD patients and then simulated the effect of increased amounts of the drug.ResultsThe effect of acetazolamide on minute ventilation and PaCO2 levels was analyzed using a nonlinear mixed effect model. The effect of different ventilatory modes was assessed on the model. Only slightly increased minute ventilation without decreased PaCO2 levels were observed in response to 250 to 500 mg of acetazolamide administered twice daily. Simulations indicated that higher acetazolamide dosage (>1000 mg daily) was required to significantly increase minute ventilation (P<.001 vs pre-acetazolamide administration). Based on our model, 1000 mg per day of acetazolamide would increase minute ventilation by >0.75 L min−1 in 60% of the population. The model also predicts that 45% of patients would have a decrease of PaCO2>5 mmHg with doses of 1000 mg per day.ConclusionsSimulations suggest that COPD patients might benefit from the respiratory stimulant effect after the administration of higher doses of acetazolamide.
Highlights
Acetazolamide is a non selective carbonic anhydrase (CA) inhibitor
Acetazolamide is commonly used in the intensive care unit (ICU) for reversing metabolic alkalosis [3]
We subsequently modeled the effect of acetazolamide on minute ventilation and PaCO2 and using Markov Chain Monte Carlo computations, simulated the effect of higher doses of acetazolamide on these respiratory parameters
Summary
Acetazolamide is a non selective carbonic anhydrase (CA) inhibitor. Acetazolamide is commonly used in the intensive care unit (ICU) for reversing metabolic alkalosis [3]. Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Severe exacerbations might lead to the need to establish mechanical invasive ventilation. Ventilated COPD patients are at high risk of prolonged mechanical ventilation and persistent weaning failure [9]. Prolonged invasive mechanical ventilation is in turn associated with increased hospital mortality [10,11]. Acetazolamide appears to increase respiratory drive and might be beneficial in obtaining a faster weaning from mechanical ventilation, especially in COPD patients who have developed metabolic alkalosis. Chronic obstructive pulmonary disease (COPD) patients may develop metabolic alkalosis during weaning from mechanical ventilation. Acetazolamide is one of the treatments used to reverse metabolic alkalosis
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