Airway Pressure Release Ventilation in Acute Lung Injury

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 dysynchrony between a patient's spontaneous respiratory efforts and the
ventilator's respiratory cycle (2;3). Dysynchrony causes discomfort, anxiety, and agitation.
To manage dysynchrony, 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 dysynchrony 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 dysynchrony.
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.

Inclusion Criteria:

Acute onset of:

1. 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 LPV, in the AC mode with 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. 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.