The Effect of Doxapram Versus Theophylline on Diaphragmatic Function

The Effect of Doxapram Versus Theophylline on Diaphragmatic Function and Weaning From Mechanical Ventilation After Open Heart Surgery

Doxapram is licensed for drug-induced post-anesthesia respiratory depression , arousal effect and return airway protective reflexes caused by barbiturates, volatile anesthetics, nitrous oxide or benzodiazepines over dosage.

Value of theophylline to stimulate the respiratory neuronal network has been examined by previous studies and increases the activity of respiratory muscles, including the intercostal , transversus abdominis muscles and the diaphragm, it also has bronchodilator and anti-inflammatory effects.

Study Overview

• Status: Unknown
• Conditions: Weaning Failure
• Intervention / Treatment: Drug: Doxapram Hydrochloride; Drug: Theophylline

Detailed Description

This randomized comparative study will be conducted in the post-surgical cardio-thoracic intensive care unit in Beni -Suef University Hospital after approval of the department of anesthesiology, surgical ICU and pain management , and cardio thoracic department and the local ethics and research committee, and obtaining written informed consents from the patients to compare the effect of doxapram versus theophylline on diaphragmatic function using ultrasonography parameter: thickening fraction of the diaphragmatic muscle during respiration which defined as [(thickness at end-inspiration - thickness at end-expiration)/thickness at end-expiration] during spontaneous breathing trial as a primary outcome and its effect on weaning time and weaning success rate as secondary outcomes.

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Banī Suwayf, Egypt
    • Recruiting
    • Beni-Suef University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: Patients (males and females) in the age group 20 -60 scheduled for elective open heart surgery ( e.g. coronary artery bypass grafting, valve replacement ) under cardiopulmonary bypass .

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Exclusion Criteria:The preoperative exclusion criteria:

1. Age older than 60 years
2. Preoperative left ventricular ejection fraction less than 30%
3. Chronic obstructive pulmonary disease
4. Significant hepatic disease (alanine aminotransferase or aspartate aminotransferase >150 U/l).
5. Renal failure (creatinine >200 μm).
6. History of seizure, or stroke.
7. History of diaphragmatic palsy, cervical spine injury, or neuromuscular disease (eg, myasthenia gravis, Guillain-Barré syndrome).
8. Lesion adjacent to the diaphragm
9. Intra-abdominal hypertension (intra-abdominal pressure ≥12 mm Hg )
10. Known allergy to the study drugs.

The Post enrollment exclusion criteria:

1. Postoperative hemorrhage (chest tube drainage ≥ 200 ml/h).
2. Surgical complications necessitating reoperation.
3. Postoperative cardiac failure necessitating high-dose inotropes or intra -aortic balloon pump.
4. Refractory hypoxemia (ratio of arterial oxygen tension [PaO2] to fraction of inspired oxygen [FIO2] <150 mmHg).
5. Occurrence of neurologic deficit.
6. -Myocardial ischemia (ST-segment depression) lasting more than 30 min

7. Failure of spontaneous breathing trial.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: doxapram group (GROUP D); The patients in this group will receive loading dose of (1 mg/kg) followed by an infusion of (1mg/kg/h)	Drug: Doxapram Hydrochloride; the diaphragmatic function will be assessed measuring right and left diaphragmatic thickening fraction in the two groups to be compared as a primary outcome using ultrasound. following the administration of the selected drug; Other Names: Doxapram; Drug: Theophylline; the diaphragmatic function will be assessed measuring right and left diaphragmatic thickening fraction in the two groups to be compared as a primary outcome using ultrasound. following the administration of the selected drug
Active Comparator: theophylline group (GROUP T); the therapeutic loading dose (5mg/kg) followed by an infusion of (0.5 mg/kg/h)	Drug: Doxapram Hydrochloride; the diaphragmatic function will be assessed measuring right and left diaphragmatic thickening fraction in the two groups to be compared as a primary outcome using ultrasound. following the administration of the selected drug; Other Names: Doxapram; Drug: Theophylline; the diaphragmatic function will be assessed measuring right and left diaphragmatic thickening fraction in the two groups to be compared as a primary outcome using ultrasound. following the administration of the selected drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the effect of doxapram versus theophylline on diaphragmatic function	: thickening fraction of the diaphragmatic muscle during respiration which defined as [(thickness at end-inspiration - thickness at end-expiration)/thickness at end-expiration](18) (19) during spontaneous breathing trial as a primary outcome and its effect on weaning time and weaning success rate as secondary outcomes.	the study drugs will be infused for 1 hour,At the end of 60 min of SBT, the diaphragmatic function will be assessed measuring right and left diaphragmatic thickening fraction in the two groups to be compared as a primary outcome using ultrasound.

Collaborators and Investigators

• Sponsor: Beni-Suef University

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2019
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: March 23, 2019
• First Submitted That Met QC Criteria: March 27, 2019
• First Posted (Actual): March 28, 2019

Study Record Updates

• Last Update Posted (Actual): March 28, 2019
• Last Update Submitted That Met QC Criteria: March 27, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Theophylline; Doxapram
• Other Study ID Numbers: Faculty Of Medicine,Beni -Suef

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No