Airway Pressure Release Ventilation in Acute Lung Injury

April 6, 2017 updated by: Johns Hopkins University

The purpose of this study is to compare airway pressure release ventilation (APRV) to conventional mechanical ventilation (MV) in patients with acute lung injury (ALI) to determine if APRV can reduce agitation, delirium, and requirements for sedative medications. We will also compare markers of inflammation in the blood and lung to determine if APRV reduces ventilator-induced lung injury (VILI), compared to conventional mechanical ventilation.

The proposed study is a randomized, crossover trial. We plan to enroll 40 patients with ALI and randomize to APRV or conventional MV for 24 hours. After this time the patients will be switched to the alternative mode of ventilation (MV or APRV) for another 24 hours. To assess breathing comfort, at the end of each 24-hour period we will measure the amounts of sedative and analgesic medications used. We will also measure the concentrations of markers of inflammation in the blood and lung as measures of VILI. Finally, throughout the study we will compare the adequacy of gas exchange with APRV compared to conventional MV.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Acute respiratory failure is common in patients with acute lung injury. MV re-establishes adequate gas exchange; it allows time for administration of antibiotics, for the host's immune system to fight infections, and for natural healing. Approximately 60% of ALI patients survive to hospital discharge (1). However, conventional approaches to MV in ALI frequently cause dyssynchrony between a patient's spontaneous respiratory efforts and the ventilator's respiratory cycle (2;3). Dyssynchrony causes discomfort, anxiety, and agitation. To manage dyssynchrony, physicians frequently prescribe large doses of sedative and analgesic medications. These medications contribute to delirium and sleep deprivation during the critical illness, and may delay weaning from MV and discharge from the intensive care unit (2;4). They may also contribute significantly to neuromuscular and neurocognitive sequelae after recovery from ALI (5;6). Moreover, MV may itself cause additional lung injury (ventilator-induced lung injury, VILI) which could, paradoxically, delay or prevent recovery from respiratory failure in some ALI patients (7;9).

Airway pressure release ventilation (APRV) is a mode of MV that is designed to reduce patient-ventilator dyssynchrony and VILI. It differs from most other modes of MV in that it allows patients to breathe spontaneously at any time, independent of the ventilator's cycle. This feature may improve breathing comfort by minimizing patient-ventilator dyssynchrony. Improving comfort and reducing agitation may ultimately curtail the use of sedative and analgesic medications. Since a substantial proportion of ventilation results from the patient's spontaneous efforts independent of the ventilator cycle, the frequency of mechanically assisted breaths can be reduced. This may reduce VILI from the cyclic opening-closing of alveoli and small bronchioles that results from assisted MV breaths. Another feature of APRV that distinguishes it from other modes of MV is that it applies a sustained high pressure during inspiration and a brief period of lower pressure during exhalation. This approach may maximize and maintain alveolar recruitment throughout the ventilatory cycle while limiting high airway pressures, thus further reducing VILI. Moreover, spontaneous contractions of the diaphragm during APRV may open dependent atelectatic lung regions, improving ventilation-perfusion (V/Q) matching and gas exchange. However, these potential advantages of APRV are unproven.

Study Type

Interventional

Enrollment (Actual)

2

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Johns Hopkins Hospital Medical Intensive Care Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

Acute onset of:

  1. Arterial Pressure of Oxygen (PaO2) / FiO2 ≤ 300
  2. Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph. The infiltrates may be patchy, diffuse, homogeneous, or asymmetric
  3. Requirement for positive pressure ventilation via endotracheal tube, and
  4. No clinical evidence of left atrial hypertension.
  5. Receiving conventional MV, or lung-protective ventilation (LPV), in the assist control (AC) mode with positive end-expiratory pressure (PEEP) > 5 cm H2O Criteria 1-3 must occur within a 24-hour period. "Acute onset" is defined as follows: the duration of the hypoxemia criterion (#1) and the chest radiograph criterion (#2) must be < 7 days at the time of randomization.

Exclusion Criteria:

  1. FiO2 > 70% or PaO2/FiO2 < 125 or arterial pH < 7.25
  2. Greater than 6 days since all inclusion criteria are met
  3. Anticipated to begin weaning from MV within 48 hours
  4. Neuromuscular disease that prevents the ability to generate spontaneous tidal volumes.
  5. Glasgow Coma Scale (GCS) < 15 within 1 week of intubation
  6. Acute stroke (vascular occlusion or hemorrhage)
  7. Current alcoholism or previous daily use of opioids or benzodiazepines before hospitalization
  8. Acute meningitis or encephalitis
  9. Pregnancy (negative pregnancy test required for women of child-bearing potential) or breast-feeding.
  10. Severe chronic respiratory disease
  11. Previous barotraumas during the current hospitalization
  12. Clinical evidence of bronchoconstriction on bedside examination (i.e., wheezing).
  13. Patient, surrogate, or physician not committed to full support
  14. Severe chronic liver disease (Child-Pugh Score B or C)
  15. International Normalized Ratio (INR) > 2.0
  16. Platelet level < 50,000
  17. Mean arterial pressure < 65, or patient receiving intravenous vasopressors (any dose of epinephrine, norepinephrine, phenylephrine, or dopamine > 5 mcg/kg/min)
  18. Age < 16 years old
  19. Morbid obesity (greater than 1kg/cm body weight).
  20. No consent/inability to obtain consent
  21. Unwillingness of the clinical team to use conventional low tidal-volume protocol for MV.
  22. Moribund patient not expected to survive 24 hours.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: APRV
Patients will be randomized to either arm. After 24 hours they will crossover to the alternative arm of the study for an additional 24 hours. After a total of 48 hours (24 hours in each study arm) the study will conclude.
Device: APRV

APRV Protocol

  • Set fraction of inspired oxygen (FiO2) at 0.1 higher than the setting on conventional MV currently used
  • Tlow = 1.0 second (this setting shall remain unchanged throughout the trial).
  • Respiratory rate (RR) to equal 60-65% of RR on conventional MV.
  • P high = the inspiratory plateau pressure. Maximum P high = 30 cm H20.
  • Plow = 5 cm water (H2O). Adjust Plow to achieve pressure release volumes 5.5-6.5 ml/kg of percent body weight (PBW).
  • If release volumes on APRV are greater than desired, increase Plow by 2-4 cm H2O increments to a maximum of Plow = 12 cm H2O. If release volumes are larger than desired despite raising Plow to 12 cm H20, decrease P high in increments of 2-4 cm H20 to achieve desired release volumes (minimum P high = 12 cm H20). If release volumes on APRV still remain larger than desired,the participant will be excluded from the study and placed on conventional MV.
Other Names:
  • Lung-protective ventilation
  • Airway Pressure Release Ventilation
Active Comparator: Conventional MV
Patients will be randomized to either arm. After 24 hours they will crossover to the alternative arm of the study for an additional 24 hours. After a total of 48 hours (24 hours in each study arm) the study will conclude.
Device: Conventional MV
Low tidal-volume mechanical ventilation
Other Names:
  • conventional mechanical ventilation
  • Lung protective ventilation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Amount of Sedatives Used
Time Frame: 48 hours
48 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Investigators

  • Principal Investigator: Roy G Brower, M.D., Johns Hopkins University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2008

Primary Completion (Actual)

October 15, 2008

Study Completion (Actual)

October 15, 2008

Study Registration Dates

First Submitted

September 9, 2008

First Submitted That Met QC Criteria

September 9, 2008

First Posted (Estimate)

September 10, 2008

Study Record Updates

Last Update Posted (Actual)

May 15, 2017

Last Update Submitted That Met QC Criteria

April 6, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NA_00017371

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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