Airway Pressure Release Ventilation in Acute Lung Injury

NCT ID: NCT00750204

Last Updated: 2017-05-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2008-10-15

Brief Summary

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.

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.

Conditions

Acute Lung Injury; Acute Respiratory Distress Syndrome; Mechanical Ventilation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

APRV

Intervention Type: DEVICE

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.

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.

Group Type: ACTIVE_COMPARATOR

Conventional MV

Intervention Type: DEVICE

Low tidal-volume mechanical ventilation

Interventions

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.

Intervention Type: DEVICE

Conventional MV

Low tidal-volume mechanical ventilation

Intervention Type: DEVICE

Other Intervention Names

Lung-protective ventilation; Airway Pressure Release Ventilation; Lung protective ventilation; conventional mechanical ventilation

Eligibility Criteria

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.

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.

Exclusion Criteria

1. FiO2 > 70% or PaO2/FiO2 < 125 or arterial pH < 7.25

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roy G Brower, M.D.

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins Hospital Medical Intensive Care Unit

Baltimore, Maryland, United States

Countries

United States

References

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Thille AW, Rodriguez P, Cabello B, Lellouche F, Brochard L. Patient-ventilator asynchrony during assisted mechanical ventilation. Intensive Care Med. 2006 Oct;32(10):1515-22. doi: 10.1007/s00134-006-0301-8. Epub 2006 Aug 1.

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Ranieri VM, Suter PM, Tortorella C, De Tullio R, Dayer JM, Brienza A, Bruno F, Slutsky AS. Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. JAMA. 1999 Jul 7;282(1):54-61. doi: 10.1001/jama.282.1.54.

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PMID: 10404912 (View on PubMed)

Other Identifiers

NA_00017371

Identifier Type: -

Identifier Source: org_study_id