Diaphragm Protective Ventilation in the Intensive Care Unit (DiaPro)

• ClinicalTrials.gov Identifier: NCT03527797
• Recruitment Status: Completed
• First Posted: May 17, 2018
• Last Update Posted: March 18, 2021
• Sponsor: VU University Medical Center
• Information provided by (Responsible Party): Prof.dr. L.M.A. Heunks, VU University Medical Center

Study Description

Brief Summary:

Due to an accident, pneumonia or surgery, patients can have severe shortness of breath or lung damage to such an extent that it compromises vital functions. At such times, mechanical ventilation can be lifesaving. The ventilator temporarily takes over the function of the respiratory muscles to ensure adequate uptake of oxygen and removal of carbon dioxide. Mechanical ventilation can usually be stopped quickly after the initial disease has been treated. Unfortunately, in up to 25-40% of ventilated patients it takes several days to weeks before mechanical ventilation can be discontinued, even after treatment of the initial disease. This phenomenon is termed weaning failure. Weakness of the respiratory muscles, such as the diaphragm, is one of the leading causes of weaning failure.

Like other skeletal muscles, the diaphragm can become weakened if it is used too little. This happens often during mechanical ventilation because of excessive assistance provided by the ventilator or use of sedative medication. Excessive activity of the diaphragm can also lead to damage and weakness, just like in other muscles that have to perform excessive amounts for a prolonged period of time. Additionally, excessive work by the diaphragm might have a direct damaging effect on the lungs, which leads to a vicious cycle. As such, it is very important to find a balance between resting the diaphragm (which may lead to weakness) and placing excessive work on the diaphragm (which can damage the diaphragm and possibly the lungs).

In this study, the investigators want to test whether insufficient activity and excessive activity of the diaphragm during mechanical ventilation can be prevented or reduced. The investigators plan to measure the diaphragm activity in 40 participants on mechanical ventilation. Participants will be randomly assigned to the intervention group or the control group. In the intervention group, ventilator support levels will be adjusted according to the observed diaphragm activity, in an attempt to ensure adequate diaphragm activity. The control group receives usual care. The hypothesis is that adjusting the level of support provided by the ventilator is a feasible method to improve the time that the diaphragm operates within acceptable levels of activity over a 24 hour period.

Condition or disease	Intervention/treatment	Phase
Critical Illness; Muscle Weakness; Muscle Damage; Respiration, Artificial; Respiratory, Diaphragm	Other: Titration of support level	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Diaphragm-protective Mechanical Ventilation in Critically Ill Patients: A Randomized Controlled Pilot Study
• Actual Study Start Date: May 16, 2018
• Actual Primary Completion Date: July 16, 2020
• Actual Study Completion Date: October 18, 2020

Arms and Interventions

Arm	Intervention/treatment
No Intervention: Control; Standard of care
Experimental: Intervention; Titration of support level	Other: Titration of support level; Increasing support in case diaphragm activity is too high. Decreasing support in case diaphragm activity is too low.

Outcome Measures

Primary Outcome Measures :

1. Adequate diaphragm loading [ Time Frame: 24 hours ]
   Percentage of time that the diaphragm operates within physiological levels of activity (Transdiaphragmatic pressure per breath between 3-12 cmH2O).

Secondary Outcome Measures :

1. Pressure-time product of diaphragm activity [ Time Frame: 24 hours ]
   Average pressure-time product of the diaphragm calculated as the time-integral of transdiaphragmatic pressure, reported and compared between intervention and control
2. Work of breathing [ Time Frame: 24 hours ]
   Average work per breath and work per minute, calculated as the volume-pressure integral of esophageal pressure, reported and compared between intervention and control
3. Markers for lung-protective ventilation [ Time Frame: 24 hours ]
   Average transpulmonary pressure, tidal volumes, plateau airway pressures, markers for systemic inflammation and mechanical power reported and compared between intervention and control
4. Patient ventilator interaction [ Time Frame: 24 hours ]
   Average percentage of asynchrony events, calculated as number of asynchronies / total breathing cycles * 100%, reported and compared between intervention and control

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Informed consent
• Receives partially supported mechanical ventilation
• Estimated duration of mechanical ventilation after inclusion of at least 24 hours, as estimated by the attending physician

Exclusion Criteria:

• Known neuromuscular disease
• Contra-indications for nasogastric intubation (upper airway surgery, bleeding disorders)
• Expected difficulties in obtaining reliable pressure measurements, such as known airleak into pleural space or diaphragmatic herniation

Contacts and Locations

Locations

Netherlands

VU University medical center

Amsterdam, Noord-Holland, Netherlands, 1081HV

Sponsors and Collaborators

VU University Medical Center

Investigators

• Principal Investigator: Leo M Heunks, MD, PhD; Professor of Experimental Intensive Care
• Study Chair: Angélique Spoelstra - de Man, MD, PhD; Intensivist

More Information

• Responsible Party: Prof.dr. L.M.A. Heunks, Prof. dr., VU University Medical Center
• ClinicalTrials.gov Identifier: NCT03527797
• Other Study ID Numbers: NL62486.029.17
• First Posted: May 17, 2018
• Last Update Posted: March 18, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Prof.dr. L.M.A. Heunks, VU University Medical Center:

Critical illness associated diaphragm weakness; Mechanical ventilation; Critical illness; Respiratory muscle dysfunction

Additional relevant MeSH terms:

Muscle Weakness; Critical Illness; Disease Attributes; Pathologic Processes; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases