Table 1 Characteristics of included studies

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

PFTs

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