Background
Objective
Methods
Eligibility criteria
Search strategy
Selection process
Data extraction
Assessment of risk of bias
Data analysis
Assessment of certainty of the evidence
Results
Search results
Included studies
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 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 |
Risk of bias in included trials
Study name | Random sequence generation | Allocation concealment | Blinding | Completeness of data | Selective outcome reporting | Other bias |
---|---|---|---|---|---|---|
Faisy et al., 2016 [6] | Low risk “The randomization sequence was programmed in advance and generated by a statistician independent of the study” | Low risk “Patients were randomized via a computer-generated assignment sequence in a centralized blinded fashion” | Low risk “Double-blind placebo-controlled trial” No details provided on which specific groups were blinded | Low risk “One patient from each group was excluded” | Low risk All outcomes listed in the methods section are reported in the results section | High risk Means and standard deviations were extrapolated from medians and interquartile ranges |
Rialp Cervera et al., 2017 [8] | Low risk “Randomization was based on computer-generated random numbers” | Low risk “Treatment and placebo capsules were prepared, packaged and blinded in a centralized hospital pharmacy and distributed to all ICUs” | Low risk “Double-blind study” “Investigators, patients and caregivers were unaware of the randomization list” | Low risk “All enrolled patients completed the trial and were included in the final analysis” | Low risk All outcomes listed in the methods section are reported in the results section | Low risk |
Nelson and Wallace, 1965 [12] | Unclear risk Method of random sequence generation not specified | Unclear risk Method of allocation concealment not specified | Low risk “Active and placebo tablets were identical in appearance, and their identity was unknown to the patients and to the assessors during the trial” | High risk “Nineteen patients began the trial, but only 12 were included in the final analysis” | Low risk All outcomes listed in the methods section are reported in the results section | Low risk |
Haecki et al., 1983 [15] | Unclear risk Method of random sequence generation not specified | Unclear risk Method of allocation concealment not specified | Low risk “Double blind trial” No details provided on which specific groups were blinded | Low risk “One patient refused follow-up” | Low risk All outcomes listed in the methods section are reported in the results section | Low risk |
Vos et al., 1994 [29] | Unclear risk Method of random sequence generation not specified | Unclear risk Method of allocation concealment not specified | Low risk of bias “Double blind trial” No details provided on which specific groups were blinded | Low risk “All patients were studied during three nights” | Low risk All outcomes listed in the methods section are reported in the results section | Low risk |
Gulsvik et al., 2013 [28] | Low risk “Randomization was based on computer-generated random numbers” | Low risk “Patients were allocated randomly on a 1:1 basis to a sealed and numbered box containing either acetazolamide or placebo tablets with similar size and colour” | Low risk “placebo controlled and double-blind parallel group trial” | Low risk All enrolled patients were included in the final analysis | Low risk All outcomes listed in the methods section are reported in the results section | Low risk |
Effects of the intervention
Mortality
Outcomes | Anticipated absolute effects (95% CI) | Relative effect (95% CI) | No. of participants (studies) | Certainty of the evidence (GRADE) | |
---|---|---|---|---|---|
Risk with control | Risk with carbonic anhydrase | ||||
Duration of hospital stay (days) | The mean duration of hospital stay in the intervention group was 0.42 days more (4.82 fewer to 5.66 more) | – | 117 (2 RCTs) | ⨁⨁◯◯ LOWa | |
Duration of mechanical ventilation (h) | The mean duration of mechanical ventilation in the intervention group was 27.09 h lower (50.11 lower to 4.08 lower) | – | 427 (2 RCTs) | ⨁⨁◯◯ LOWb,c | |
Mortality | 130 per 1000 | 122 per 1000 (74 to 202) | RR 0.94 (0.57 to 1.56) | 427 (2 RCTs) | ⨁⨁◯◯ LOWa |
Adverse events | 78 per 1000 | 133 per 1000 (76 to 232) | RR 1.71 (0.98 to 2.99) | 508 (5 RCTs) | ⨁⨁⨁◯ MODERATEa |