Acetazolamide Facilitates Ventilator Weaning

Study Overview
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Brief Summary
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Metabolic alkalosis(MA) is common metabolic disorder in ICU setting. MA could be cause of weaning failure or delay by depression of respiratory center. The purpose of this study is to evaluate that correction of MA by administration of acetazolamide facilitates weaning of mechanical ventilation.

Official Title
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Acetazolamide Facilitates Ventilator Weaning Multicenter, Prospective, Double Blinded, Randomised Controlled Trial

Conditions
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Ventilator Weaning, Alkalosis, Metabolic

Intervention / Treatment
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* Drug: acetazolamide
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients on mechanical ventilation for at least 24 hours with an assisted mode and passed acute resuscitation and considered for weaning. (Definition of Weaning point: Oxygenation FiO2 ≤ 0.4 & PaO2 ≥ 60 mmHg O2 index (PaO2/FiO2) ≥ 150 SaO2 > 90% PEEP ≤ 5 cmH2O MN ≤ 15 L/min Vital sign Stable BP: MAP ≥ 60 mmHg ((i.e., no epinephrine or norepinephrine <0.2μg/kg/min, or equivalent dose vasopressin or phenylephrine) HR ≤ 140bpm 35 ≤ BT ≤ 38 ℃ RR ≤ 35/min Clinical status resolution of acute disease process no newly developed pulmonary infiltration Ramsay sedation score 2 4 Hb > 7, pH > 7.30, normal electrolyte no active bleeding, no IICP, no bronchospasm, no CAD no rescure or specific treatment (NO, prone, OP plan) ABGA : pH ≥ 7.43 and HCO3- ≥ 26mEq/L Exclusion Criteria: Permanent ventilator dependency due to brainstem disease, diffuse cerebral disease, severe respiratory or neuromuscular disease Active bleeding, IICP, unstable coronary artery disease, bronchospasm, and rescue treatment (inhaled NO, prone), pre-op condition Contraindication to acetazolamide: renal insufficiency (creatinine clearance <20 ml/min and/or renal replacement therapy), intolerance or allergy to acetazolamide or sulfonamides, hyperchloremic metabolic acidosis, hyponatremia (Na<130), hypokalemia (K<3.5), adrenal insufficiency. Diaphragm dysfunction : as diagnosed by fluoroscopy, nerve conduction velocity, USG, or overt paradoxical motion of the abdomen

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetazolamide<br>If ABGA is pH ≥ 7.43 & HCO3- ≥ 26mEq/L at 7am, they will receive acetazolamide 500mg via IV. If ABGA is pH ≤ 7.35 at 7am, acetazolamide will skip. | Drug: acetazolamide<br>* If ABGA is pH ≥ 7.43 & HCO3- ≥ 26mEq/L at 7am, they will receive acetazolamide 500mg via IV q 24h. If ABGA is pH ≤ 7.35 at 7am, acetazolamide will skip.<br>* Other names: acetazolamide = Zoladin;|
| Placebo Comparator: Placebo<br>This group will be managed with general metabolic alkalosis treatment such as electrolyte correction, hydration except acetazolamide. | Drug: Saline<br>* They will receive saline 50ml via IV q 24h.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| weaning time between two group | Weaning time : [total ventilation time] - [total controlled mode time] | hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful weaning rate between two group | Successful weaning : self respiration more than 48h after withdrawl mechanical ventilation |  | 
| total duration of mechanical ventilation between two group |  | hour | 
| length of ICU stay between two group |  | hour | 
| frequency of ventilator associated pneumonia between two group |  |  | 
| overall ICU mortality between two group |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mechanical ventilation weaning phase patients with metabolic alkalosis