COPD Exacerbation, Enoximone, Phosphodiesterase Inhibitor
Conditions
Brief summary
Introduction: The pharmacodynamic properties of enoximone could be beneficial for patients with an Acute Exacerbation COPD (AE-COPD). This research will focus on patients suffering of a severe AE-COPD and the bronchodilatory and inotropic effects of lower doses of enoximone. The main objective of the pilot study is to investigate if there is a bronchodilatory effect of enoximone in patients with AE-COPD. Secondary objective is to investigate a dose responsiveness in a range between 0.5 and 1.5 mg/kg enoximone. Methods: The study design is a prospective interventional non-randomized clinical series study involving patients admitted and intubated at the Intensive Care Unit (ICU) with an AE-COPD. Patients will receive three times a dose of 0.5 mg/kg enoximone with a one-hour-interval. The primary objective is a reduction in auto-positive end-expiratory pressure (PEEP) after enoximone compared to baseline. A dose-titration will test for dose dependency. Secondary objectives are a reduction in ventilator pressures, a reduction in pulmonary artery pressures and an increase in cardiac output.
Detailed description
Ventilator will be set during the study period at Volume Controle, 6 ml/kg, 5 PEEP and a respiratory rate of 15 bpm with an I:E-ratio of 1:2. Salbutamol/ipratropium bromide and magnesium sulphate will be administered at baseline (t=0h) and measurements will be made for an hour. At T=1h the first dose of 0.5 mg/kg enoximone will be administered and will be repeated at T=2h and T=3h. Ventilator derived variables will be obtained every fifteen minutes and echocardiography, arterial and central venous bloodgas analyses every hour until t=6h.
Interventions
DRUGEnoximone
Patients will receive three times a dose of 0.5 mg/kg enoximone with a one-hour-interval.
Sponsors
Rijnstate Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with an AE-COPD for which intubation occurred within 24 hours before enrolment.
Exclusion criteria
* Patients with known asthma or interstitial lung disease (ILD) * Known neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), Guillain-Barre and Dementia * Hypertrophic obstructive cardiomyopathy (HOCM) * Severe aortic stenosis with aortic valve area \< 1cm2 * Known ventricular arrhythmias * Severe kidney disorders with Glomerular Filtration Rate (GFR) \< 30 * Severe liver insufficiency with spontaneous PT/INR \> 1.5 * Pregnancy * Lactation * High dose-diuretics use (daily dose of \>480 mg furosemide)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PEEP | within 6 hoursmeasured every 15 minutes | Reduction in intrinsic PEEP, in cmH2O |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Airway resistence | within 6 hours, measured every hour | cmH2O/L/sec |
| VEI | within 6 hours, measured every hour | ml |
| VCO2 | within 6 hours, measured every hour | ml/min |
| etCO2 | within 6 hours, measured every hour | kPa |
| Vd/Vt | within 6 hours, measured every hour | Measured by Bohr-equation, in percentage |
| FiO2 | within 6 hours, measured every hour | percentage |
| Lung compliance | within 6 hours, measured every hour | ml/H2O |
| Cardiac Output | within 6 hours, measured every hour | Measured by echocardiography (LVOT VTI), ml/hr |
| RVSP | within 6 hours, measured every hour | Measured by echocardiography, in mmHg |
| TAPSE | within 6 hours, measured every hour | Measured by echocardiography, in mm |
| MAPSE | within 6 hours, measured every hour | Measured by echocardiography, in mm |
| LV Ejection Fraction | within 6 hours, measured every hour | Measured by echocardiography, in percentage |
| Bloodgas analysis | within 6 hours, measured every hour | Arterial bloodgas analysis and central venous gas analysis (through catheter placed in superior vena cava) |
| Shunt fraction | within 6 hours, measured every hour | measured by Fick-equation, using the SvO2, in percentage |
Countries
Netherlands
Outcome results
None listed