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Table 1 Characteristics of included studies

From: Carbonic anhydrase inhibitors in patients with respiratory failure and metabolic alkalosis: a systematic review and meta-analysis of randomized controlled trials

Study name Study design Participants Intervention Control Outcomes assessed
Faisy et al., 2016 [6] Randomized double blind multicenter trial N = 382
Mean age = 69
Females = 29% (N = 110)
Country, France
Mechanically ventilated patients mostly secondary to community-acquired pneumonia 43% (N = 166), bronchitis 18% (N = 70), and left ventricular insufficiency 19% (N = 75),
and metabolic alkalosis (serum HCO3 > 26 meq/l and arterial PH ≥ 7.35 mmHg)
Acetazolamide 500 mg or 1000 mg (when loop diuretics were co-prescribed) intravenously twice per day for 28 days 10 ml normal saline twice daily for 28 days Duration of invasive ventilation
Changes in serum HCO3
Arterial blood gases
Weaning duration
Ventilator-associated pneumonia episodes
Use of noninvasive ventilation after extubation
Successful weaning
Duration of ICU stay
ICU mortality
Adverse events
Rialp Cervera et al., 2017 [8] Multicenter, randomized, controlled, double-blind study N = 47
Mean age 67
Females 23% (N = 11)
Country, Spain
COPD or OHS with invasive MV,
and metabolic alkalosis
(PH > 7.35 with plasma HCO3 > 28 mmol/l)
Capsules of 500 mg of acetazolamide by nasogastric tube for 28 days Placebo one tablet once daily by nasogastric tube for 28 days Duration of MV
Duration of weaning
Need for tracheostomy
Application of postextubation noninvasive ventilation,
Re-intubation in 48 h
Duration of ICU stay
Duration of hospital stay
Hospital mortality
Adverse effects
Acid base balance
Nelson and Wallace, 1965 [12] Double blind, controlled, cross-over design N = 12
Mean age: 52
Female = 16% (N = 2)
Country, Northern Ireland
Outpatient COPD with either an arterial oxygen saturation of less than 90% or PCO2 of 53 mmHg or more and metabolic alkalosis with CO2 content 31.6 at baseline.
Dichlorphenamide 50 mg four times per day for 3 consecutive fortnights Placebo 1 tablet four times per day for 3 consecutive fortnights Oxygen saturation
Blood gases parameters
Symptomatic effects
Adverse events
Hacki et al.,1983 [15] Randomized, double blind, controlled trial, sequential design (cross-over then parallel group) N = 14
Patients with COPD who met the following conditions:
PO2 < 60 mmHg, PCO2 > 45 mmHg, and pH > 7.38
Acute term intervention (cross-over design):
Acetazolamide 250 mg twice daily with cross-over between intervention and placebo at day 3,6,9,
Long-term intervention (parallel group design):
re-randomization at day 12 and treatment of one group with acetazolamide 250 mg twice daily for a median of 4.5 months
Placebo twice daily Acute phase of trial:
PaO2 and PCO2 levels by ABG on days 0, 3, 6, 9, and 12
Pulmonary function tests on days 0 and 12
Weight on days 0 and 12
Long-term phase:
blood gases after 4.5 months follow-up
Vos et al., 1994 [29] Randomized, double blind, placebo controlled N = 53
Mean age: 65
Females = 26% (N = 14)
Country, the Netherlands
Outpatient COPD with PaO2 < 8.5 kPa and metabolic alkalosis with base excess: 6.6 mmol/l at baseline
Acetazolamide 250 mg twice per day for one week Placebo tablets twice per day for one week PaO2, pH, PaCO2, base excess,
Hypercapnic ventilatory response
Hypoxic ventilatory response
Quality of sleep
Beneficial effects according to patients
Side effects
Gulsvik et al., 2013 [28] Randomized, placebo-controlled, double-blind, parallel group trial N = 70
Mean age: 73.5
Female: 63%, (N = 44)
Country, Norway
Hospitalized COPD patients with PaO2 ≤ 8 kPa and/or PaCO2 ≥ 7 kPa, and metabolic alkalosis with base excess ≥8 mmol/L
13 patients received noninvasive ventilation
Acetazolamide tablets 250 mg three times per day for 5 days Placebo tablets three times per day for 5 days Primary outcome: PaO2
Secondary outcomes: PaCO2, base excess, pH, total number of days in hospital, adverse effects
  1. ABG arterial blood gases, COPD chronic obstructive pulmonary disease, ICU intensive care unit, MV mechanical ventilation, OHS obesity-hypoventilation syndrome, PFT pulmonary function test