Diaphragm Protective Ventilation in the Intensive Care Unit (DiaPro)

Diaphragm-protective Mechanical Ventilation in Critically Ill Patients: A Randomized Controlled Pilot Study

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.

Study Overview

• Status: Completed
• Conditions: Critical Illness; Muscle Weakness; Respiration, Artificial; Muscle Damage; Respiratory, Diaphragm
• Intervention / Treatment: Other: Titration of support level

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1081HV
      • VU University Medical Center

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2018
• Primary Completion (Actual): July 16, 2020
• Study Completion (Actual): October 18, 2020

Study Registration Dates

• First Submitted: April 24, 2018
• First Submitted That Met QC Criteria: May 16, 2018
• First Posted (Actual): May 17, 2018

Study Record Updates

• Last Update Posted (Actual): March 18, 2021
• Last Update Submitted That Met QC Criteria: March 17, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Critical illness; Mechanical ventilation; Critical illness associated diaphragm weakness; Respiratory muscle dysfunction
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Disease Attributes; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Muscle Weakness; Critical Illness
• Other Study ID Numbers: NL62486.029.17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No