Acetazolamide Facilitates Ventilator Weaning

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

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.

Study Overview

• Status: Unknown
• Conditions: Ventilator Weaning; Alkalosis, Metabolic
• Intervention / Treatment: Drug: acetazolamide; Drug: Saline

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eun Young Choi, fellow; Phone Number: +82-2-3010-3894; Email: letact@hanmail.net
• Study Contact Backup: Name: Chae-Man Lim, professor; Phone Number: +82-2-3010-3135; Email: cmlim@amc.seoul.kr

Study Locations

• Korea, Republic of
  • 388-1, Pungnap-dong, Songpa-gu
    • Seoul, 388-1, Pungnap-dong, Songpa-gu, Korea, Republic of, 138-736
      • Recruiting
      • AMC MICU; Asan medical center
      • Contact: Eun Young Choi, fellow; Phone Number: +82-2-3010-3894; Email: letact@hanmail.net
      • Contact: Chae-Man Lim, professor; Phone Number: +82-2-3010-3135; Email: cmlim@amc.seoul.kr
      • Principal Investigator: Eun Young Choi, fellow

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. Oxygenation

     • FiO2 ≤ 0.4 & PaO2 ≥ 60 mmHg

       • O2 index (PaO2/FiO2) ≥ 150

         • SaO2 > 90%

           • PEEP ≤ 5 cmH2O

             • MN ≤ 15 L/min

  2. 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

  3. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Acetazolamide; 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; 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.; Other Names: acetazolamide = Zoladin
PLACEBO_COMPARATOR: Placebo; This group will be managed with general metabolic alkalosis treatment such as electrolyte correction, hydration except acetazolamide.	Drug: Saline; They will receive saline 50ml via IV q 24h.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Investigators: Study Chair: Chae-Man Lim, professor, Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (ANTICIPATED): May 1, 2011
• Study Completion (ANTICIPATED): May 1, 2011

Study Registration Dates

• First Submitted: May 26, 2010
• First Submitted That Met QC Criteria: May 26, 2010
• First Posted (ESTIMATE): May 27, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): May 27, 2010
• Last Update Submitted That Met QC Criteria: May 26, 2010
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Keywords: mechanical ventilation weaning phase patients with metabolic alkalosis
• Additional Relevant MeSH Terms: Metabolic Diseases; Acid-Base Imbalance; Alkalosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Carbonic Anhydrase Inhibitors; Natriuretic Agents; Diuretics; Anticonvulsants; Acetazolamide
• Other Study ID Numbers: AMCAZM-150