Acetazolamide: a second wind for a respiratory stimulant in the intensive care unit?

Abstract

Patients with chronic obstructive pulmonary disease (COPD) are affected by episodes of respiratory exacerbations, some of which can be severe and may necessitate respiratory support. Prolonged invasive mechanical ventilation is associated with increased mortality rates. Persistent failure to discontinue invasive mechanical ventilation is a major issue in patients with COPD. Pure or mixed metabolic alkalosis is a common finding in the intensive care unit (ICU) and is associated with a worse outcome. In patients with COPD, the condition is called post-hypercapnic alkalosis and is a complication of mechanical ventilation. Reversal of metabolic alkalosis may facilitate weaning from mechanical ventilation of patients with COPD. Acetazolamide, a non-specific carbonic anhydrase inhibitor, is one of the drugs employed in the ICU to reverse metabolic alkalosis. The drug is relatively safe, undesirable effects being rare. The compartmentalization of the different isoforms of the carbonic anhydrase enzyme may, in part, explain the lack of evidence of the efficacy of acetazolamide as a respiratory stimulant. Recent findings suggest that the usually employed doses of acetazolamide in the ICU may be insufficient to significantly improve respiratory parameters in mechanically ventilated patients with COPD. Randomized controlled trials using adequate doses of acetazolamide are required to address this issue.

The effect of metabolic alkalosis on the ventilatory response in healthy subjects

“…Bicarbonate on the other hand is found to remain elevated in patients with posthypercapnic alkalosis (Banga and Khilnani, 2009). It is suggested that excreting bicarbonate could correct metabolic alkalosis and, subsequently, increase minute ventilation and improve oxygenation, facilitating weaning from mechanical ventilation in patients with COPD or other pulmonary diseases (Heming et al, 2012). Recently, Faisy et al showed in a randomized trial that the use of acetazolamide did not result in a significant reduction in the duration of mechanical ventilation compared to placebo (Faisy et al, 2016).…”

Acetazolamide and Invasive Mechanical Ventilation for Patients With COPD

“…2 The authors did not report on changes in daily fluid balance and urine output. Although the net diuretic effect is usually modest (sodium reabsorption in more distal nephron segments may offset proximal sodium losses), its quantification might have helped better understand the results of this trial.…”

“…2 Second, if the role of acetazolamide, according to the authors, is to assist in weaning, then what was the rationale for starting it at the initiation of mechanical ventilation? It could be considered at the time of initiation of the weaning process.…”

“…2 After discovery of SFTSV, we carried out an analysis of nosocomial transmission of SFTSV, which included the HGA cluster because the clinical manifestations of the HGA cluster were very similar to SFTSV infec-tion. We found that all secondary patients in the HGA cluster had antibody titers with 4-fold increases or seroconversion to SFTSV between acute and convalescent sera.…”

Epithelial Anion Transporter Pendrin Contributes to Inflammatory Lung Pathology in Mouse Models of Bordetella pertussis Infection

“…ACTZ is a carbonic anhydrase inhibitor that is in clinical use for treatment of a variety of medical conditions, including as a respiratory stimulant in patients with COPD and metabolic alkalosis (59). Treatment from the outset of bacterial infection, as in our study, is somewhat artificial, but in future work we will investigate the therapeutic potential of this drug by treatment of infected mice at later time points of infection and by different routes of administration, since systemic inhibition of pendrin activity may lead to unwanted deleterious effects on other organs.…”