Effects of early administration of acetazolamide on the duration of mechanical ventilation in patients with chronic obstructive pulmonary disease: still far from the truth?

Abstract

In this study, Rialp Cervera et al.(1) have randomly assigned patients with chronic obstructive pulmonary disease (COPD) or obesity hypoventilation syndrome (OHS) with acute respiratory failure requiring mechanical ventilation (MV) <72 h to receive either acetazolamide 500 mg or placebo. All patients had initial bicarbonate >28 mmol/L and pH >7.35. Test-treatment, ACTZ 500 mg or placebo, was daily administered if pH >7.35 and bicarbonate >26 mmol/L. Clinical, respiratory and laboratory parameters were recorded on a daily basis.This was a multicenter, randomized, placebo-controlled, phase III, double-blind study held in seven intensive care units in Spain. Patients with COPD or OHS, requiring invasive MV due to acute respiratory failure for less than 72 h and who showed metabolic alkalosis with pH >7.35 and with plasmatic bicarbonate >28 mmol/L, while being on invasive MV, were consecutively included from November 2011 to February 2014. Forty seven patients (36 men) were randomized as ACTZ (+) or placebo: 23 patients in placebo group, and 24 in ACTZ (+) group. There were no significant differences between groups in comorbidities, baseline characteristics or arterial blood gases at inclusion. At inclusion, SOFA score, proportion of patients with noninvasive ventilation (NIV) failure before inclusion, reason of invasive MV, laboratory serum tests, blood gas analysis and respiratory parameters did not show any significant differences between groups.This study (1) showed no significant decreases in the duration of MV and weaning, or in the length of ICU and hospital stay with acetazolamide treatment compared with placebo in intubated patients with COPD or OHS and metabolic alkalosis. Moreover, patients treated with acetazolamide showed a significant reduction in bicarbonate concentration and PaCO 2 values at discontinuation of MV, with 33% of them having recovered from their metabolic alkalosis, whereas no patient in the placebo group did so. Moreover, respiratory rate and minute volume did not show any significant differences throughout the MV period although minute volume tended to increase over time in the acetazolamide group [minute volume 9.7 (8.9-10.4) vs. 10.6 (9.2-12.0) L/min, P=0.26].In conclusion, this study showed that in severe exacerbation of COPD or OHS requiring intensive care admission and invasive MV, despite the fact that acetazolamide is used to reverse metabolic alkalosis, this therapy does not help reduce the duration of MV and/or make the weaning process easier.Nevertheless, this study-as mentioned by authorssuffers from many limitations. First, a sample size of 98 patients was estimated to have a power of 80% with an alpha error of 5% to detect a 3-day difference between groups in the duration of MV. However, the study was stopped prematurely due to slow patient recruitment. In fact, only 47 patients were included in the study, 23 patients in the placebo group and 24 in the acetazolamide one. Consequently, this study did not detect any significant J Thorac Dis 2017;9(6):1393-1395 jtd.amegroups....

Post-Hypercapnic Alkalosis: A Brief Review

“…Upon diagnosing post-hypercapnic alkalosis (PHA), the presence of various co-existing conditions can complicate the correction of metabolic alkalosis. ECF deficits induced by diuretics or gastrointestinal loss, the use of steroids with mineralocorticoid effects, and electrolyte imbalances such as potassium and magnesium also can contribute to alkalosis, potentially delaying the diagnosis of PHA and impeding effective treatment 3 9) .…”