Acetazolamide in hypercapnic respiratory failure with concomitant metabolic alkalosis has no clear effect on mortality or ventilation duration in patients with chronic obstructive pulmonary disease (COPD) or obesity hypoventilation syndrome (OHS), according to systematic review and meta-analysis published in Thorax.
In patients with chronic hypercapnic respiratory disease, acute respiratory failure may be associated with metabolic alkalosis. Although acetazolamide reduces serum pH and may reduce ventilatory suppression in these patients, it’s unclear whether this therapy lowers mortality or ventilation duration. Investigators therefore conducted a systematic review to determine whether acetazolamide affects mortality and/or ventilation duration in patients with COPD or OHS who have acute respiratory failure and metabolic alkalosis.
The primary endpoint of the analysis was in-hospital death. Length of intensive care unit (ICU) admission, duration of ventilation (non-invasive or invasive), duration of weaning from ventilation, length of hospitalization, and adverse effects were secondary endpoints.
Investigators conducted a systematic review and meta-analysis searching Medline, EMBASE, and CENTRAL from inception to March 2022 for randomized controlled trials comparing acetazolamide to placebo in patients with COPD, OHS, or obstructive sleep apnea (OSA) who were hospitalized with acute respiratory deterioration complicated by metabolic alkalosis. The investigators identified 4 studies with 504 patients; of those, 99% had COPD and none had OSA, and half of the trials had patients requiring mechanical ventilation.
Acetazolamide may have little impact on mortality for patients with acute respiratory failure and metabolic alkalosis with a background of COPD or OHS, however, certainty of evidence is low and clinically significant benefit or harm cannot be excluded.
Investigators found that acetazolamide had no significant effect on mortality vs placebo (relative risk, 0.98; 95% CI, 0.28-3.46; P =.95; 3 studies, n=490; low certainty of evidence) or on the duration of ventilation (mean difference [MD], -0.8 days; 95% CI, -7.2 to 5.6; P =.36; 2 studies, n=427; low certainty).
Pooled estimates of control groups showed length of ICU admission as 11.9 days vs 11.1 days for participants on acetazolamide vs placebo with no statistical significance (MD, -0.86; 95% CI, -14.01 to 12.30; P =.56; low certainty). Pooled estimates showed duration of ventilation weaning as 1.0 day(s) for each group with no statistical significance (MD, -0.03; 95% CI, -1.85 to 1.80; P =.88; low certainty).
Pooled estimates of control groups also showed hospital length of stay as 16.0 days vs 15.2 days for participants on acetazolamide vs placebo with no statistical significance (MD, -0.78; 95% CI, -26.1 to 24.5; P =.76; low certainty). Overall, studies showed inconsistent adverse effects ranging from 0% to 42% for participants treated with acetazolamide and from 0% to 30% for participants taking placebo and very low certainty of evidence.
Review and meta-analysis limitations include the small number of trials included and clinical heterogeneity regarding cause of respiratory deterioration in study participants.
“Acetazolamide may have little impact on mortality for patients with acute respiratory failure and metabolic alkalosis with a background of COPD or OHS, however, certainty of evidence is low and clinically significant benefit or harm cannot be excluded,” investigators concluded. “Larger well-powered clinical trials are required to confirm whether the use of acetazolamide has any significant benefits or harm for patients with acute respiratory failure and metabolic alkalosis in the context of chronic hypercapnic respiratory disease,” the study authors added.