Airway Pressure Release Ventilation (APRV) Compared to ARDSnet Ventilation (PRESSURE)

Primary Resuscitation Using Airway Pressure Release Ventilation Improves Recovery From Acute Lung Injury or Adult Respiratory Distress Syndrome and Reduces All Cause Mortality Compared to ARDS Net Low Tidal Volume-Cycled Ventilation.

Traditional modes of ventilation have failed to improve patient survival. Subsequent observations that elevated airway pressures observed in traditional forms of ventilation resulted in barotrauma and extension of ALI lead to the evolution of low volume cycled ventilation as a potentially better ventilatory modality for ARDS. Recent multicenter trials by the NIH-ARDS network have confirmed that low volume ventilation increases the number of ventilatory free days and improves overall patient survival. While reducing mean airway pressure has reduced barotrauma and improved patient survival, it has impaired attempts to improve alveolar recruitment. Alveolar recruitment is important as it improves V/Q mismatch, allows reduction in FIO2 earlier, and decreases the risk of oxygen toxicity. Airway pressure release ventilation (APRV) is a novel ventilatory modality that utilizes controlled positive airway pressure to maximize alveolar recruitment while minimizing barotrauma. In APRV, tidal ventilation occurs between the increase in lung volumes established by the application of CPAP and the relaxation of lung tissue following pressure release. Preliminary studies have suggested that APRV recruits collapsed alveoli and improves oxygenation through a restoration of pulmonary mechanics, but there are no studies indicating the potential overall benefit of APRV in recovery form ALI/ADRS.

Study Overview

• Status: Withdrawn
• Conditions: Acute Lung Injury; Kidney Injury; Adult Respiratory Distress Syndrome
• Intervention / Treatment: Device: Volume-Cycled Assist-Control (AC) mode; Device: Airway Pressure Release Ventilation (APRV) mode

Detailed Description

Low volume ventilation may increase number of ventilatory free days and may improve overall patient survival. While reducing mean airway pressure has reduced barotrauma and improved patient survival, it has impaired attempts to improve alveolar recruitment. Alveolar recruitment is important as it improves V/Q mismatch, allows reduction in FIO2 earlier, and decreases the risk of oxygen toxicity. Airway pressure release ventilation (APRV) is a novel ventilatory modality that utilizes controlled positive airway pressure to maximize alveolar recruitment while minimizing barotrauma. In APRV, tidal ventilation occurs between the increase in lung volumes established by the application of CPAP and the relaxation of lung tissue following pressure release. Preliminary studies have suggested that APRV recruits collapsed alveoli and improves oxygenation through a restoration of pulmonary mechanics, but there are no studies indicating the potential overall benefit of APRV in recovery form ALI/ADRS.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • James A. Tumlin, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients admitted to the Internal Medicine service at the Baroness Erlanger Hospital of the University of Tennessee College of Medicine with hypoxia (O2 saturation < 93%) and pulmonary distress, will be screened for study participation.
• Patients displaying all the following clinical criteria: acute onset of respiratory failure; hypoxia defined as a PaO2/FiO2 ratio of < 300 Torr; pulmonary capillary wedge pressure less or equal than 18 mm Hg, and/or no clinical evidence of left sided heart failure; and chest x-ray with diffuse bilateral pulmonary infiltrates.

Exclusion Criteria:

• Patients receiving conventional volume ventilation with or without PEEP for > 6 hours prior to study enrollment
• Patient's family or surrogate unwilling to give informed consent
• Patients requiring sedation or paralysis for effective ventilation
• Patients known pulmonary embolus within 72 hours of study enrollment
• Patients with close head injuries or evidence of increased intracranial pressure
• Patients with burns over 30% of total body surface area
• Pulmonary capillary wedge pressure greater than 18 mm Hg
• CVP > 15 cm H2O
• Patients with B type Naturetic peptide levels > 1000
• Patients with prior history of dilated cardiomyopathy with EF < 25%
• Patients receiving chronic outpatient peritoneal or hemodialysis
• Patients with severe liver disease (as defined by Child-Pugh class C)
• AIDS patients

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARDS Net Low Tidal Volume	Device: Volume-Cycled Assist-Control (AC) mode; Patients ventilated with volume-cycled assist-control mode with PEEP and goal FIO2 < 40%; Rate of mandatory time-cycled, pressure controlled breaths,initially at 12 per breaths/min; Initial tidal volume set at 8mL/kg using predicted body weight (PBW) with a goal of 6mL/kg & setting positive end-expiratory pressure (PEEP) based on level of initial FiO2; Inspiratory to Expiratory ratio set at 1:1 to 1:3; If frequency of triggered breaths increased greater than 10 per min sedation will be increased. If needed,rate of mandatory breaths increased; Mgmt of PEEP will be conducted as per the ARDSnet Protocol; Oxygenation goal PaO2: PaO2-55-80 mm Hg O2 Sat: 88-95%; Tidal volume and respiratory rate adjusted to the desired pH and plateau pressures per ARDSnet protocol; Other Names: Controlled Mechanical Ventilation (CMV)
Experimental: APRV Ventilation	Device: Airway Pressure Release Ventilation (APRV) mode; Ventilation uses Drager Model X1; Spontaneous breathing allowed throughout ventilatory cycle at 2 airway pressure levels; Time periods for the high & low pressure levels can be set independently; Duration of the lower pressure level will be adjusted to allow expiratory flow to decay to 75% of total volume; Duration of higher pressure levels will be adjusted to produce 12 pressure shifts per min; Spontaneous frequency will be targeted for 6 to 18 breaths/per min; If spontaneous breathing is achieved,level of sedation will be decreased; If spontaneous respirations are >20 breaths/min, sedation will be increased; If spontaneous breathing frequency increased greater than 20/per min, sedation was increased and if needed the mechanical frequency increased; Other Names: Controlled Mechanical Ventilation (CMV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
All cause mortality	28 days or prior to hospital discharge

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of ventilator-free days	28 days or prior to hospital discarge
Length of ICU stay and /or Total hospital days	28 days or prior to hospital discharge
To determine the effects of APRV ventilation versus ARDS net low volume-cycle ventilation on the incidence of of AKI	28 days or prior to hospital discharge
To determine the effects of APRV ventilation versus ARDS net low volume-cycle ventilation on the NGAL, KIM-1, and IL-18 urine biomarkers for AKI	28 days or prior to hospital discharge
To determine the effects of APRV ventilation versus ARDS net low volume-cycle ventilation in maintaining hourly urine output > 0.5 mls/kg/hr	28 days or prior to hospital discharge
Will determine urinary aquaporin-2 levels in patients randomized to APRV ventilation versus ARDS net low volume-cycle ventilation	28 days or prior to hospital discharge

Collaborators and Investigators

• Sponsor: University of Tennessee, Chattanooga
• Investigators: Principal Investigator: James A Tumlin, MD, University of Tennessee

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2020
• Primary Completion (Actual): November 2, 2020
• Study Completion (Actual): November 2, 2020

Study Registration Dates

• First Submitted: November 17, 2008
• First Submitted That Met QC Criteria: November 17, 2008
• First Posted (Estimate): November 18, 2008

Study Record Updates

• Last Update Posted (Actual): November 4, 2020
• Last Update Submitted That Met QC Criteria: November 2, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Airway Pressure Release Ventilation; Acute Kidney Injury; Acute Lung Injury; Adult Respiratory Distress Syndrome; Pressure Trial
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Infant, Premature, Diseases; Thoracic Injuries; Syndrome; Wounds and Injuries; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury
• Other Study ID Numbers: 123456789

Drug and device information, study documents

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