Biomarkers of Lung Injury With Low Tidal Volume Ventilation Compared With Airway Pressure Release Ventilation

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) represent a spectrum of clinical syndromes of rapid respiratory system deterioration that are associated with both pulmonary and systemic illness. These syndromes are associated with 30-40% mortality with our current standard of care and are responsible for approximately 75,000 deaths in the US yearly. Current evidence-based care of ALI consists of a strategy of mechanical ventilation utilizing low lung volumes (ARDSNet ventilation) intended to limit further stretch-induced lung injury exacerbated by the ventilator. However, this strategy has been shown to be associated with increased lung injury in a subset of patients and still is associated with about a 30% mortality rate. Airway pressure release ventilation (APRV) is a different, non-experimental strategy of mechanical ventilation currently in routine clinical use. APRV is a pressure-cycled ventilator mode that allows a patient a greater degree of autonomy in controlling his or her breathing pattern than ARDSNet ventilation. Use of APRV has been associated with better oxygenation, less sedative usage, and less ventilator-associated pneumonia in small studies compared with other ventilator modes. However, debate exists over whether APRV might result in decreased or increased ventilator-associated lung injury when compared with ARDSNet ventilation. We intend to implement a randomized, cross over study looking at biomarkers of lung injury in patients with acute lung injury during ventilation with APRV and using the ARDSNet protocol. Our hypothesis is that airway pressure release ventilation is associated with lower levels of lung injury biomarkers than ARDSNet ventilation.

Study Overview

• Status: Terminated
• Conditions: Acute Lung Injury; Adult Respiratory Distress Syndrome
• Intervention / Treatment: Other: low-tidal-volume ventilation; Other: APRV

Detailed Description

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) represent a spectrum of clinical syndromes of rapid respiratory system deterioration that are associated with both pulmonary and systemic illness. These syndromes are associated with 30-40% mortality with our current standard of care and are responsible for approximately 75,000 deaths in the US yearly. The current evidence-based care consists of a strategy of mechanical ventilation utilizing low lung volumes (ARDSNet ventilation) intended to limit further lung injury from overstretch of the lung induced by the ventilator. However, this strategy has been shown to be associated with continued lung injury in some studies and still is associated with about a 30% mortality rate. Airway pressure release ventilation (APRV) is a different, nonexperimental strategy of mechanical ventilation currently in routine clinical use. APRV allows a patient a greater degree of autonomy in controlling his/her breathing while achieving a higher mean airway pressure (at similar plateau pressures) than that typically achieved with ARDSNet. APRV has been associated with less ventilator-associated pneumonia, better oxygenation, and less sedative usage in small studies when compared with other methods of ventilation. However, debate exists over net effects of APRV with regard to ventilator-associated lung injury. Additionally, we recently completed a study showing that APRV was associated with lower ventilator associated pneumonia (VAP) rates, but this benefit did not appear to be mediated by sedation differences. We hypothesized that the VAP benefits might be mediated by greater lung recruitment and possibly less ventilator-induced lung injury with APRV. We propose a randomized, crossover study looking at biomarkers of lung injury in patients with acute lung injury ventilated with APRV and ARDSNet. Our hypothesis is that airway pressure release ventilation is associated with lower levels of lung injury biomarkers than ARDSNet ventilation.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston 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:

• Age > or equal to 18.
• On mechanical ventilation using a volume-controlled mode.
• Admitted to Boston Medical Center Surgical, Medical, or Coronary Intensive Care Unit.
• Meets American-European Consensus Criteria for Acute Lung Injury (ALI) or Acute Respiratory Distress Syndrome.
• Required mechanical ventilator for less than 14 days.
• Met ARDS or ALI criteria for less than 7 days prior to enrollment.
• Assent of primary care team

Exclusion Criteria:

• Do not resuscitate order.
• Increased intracranial pressure.
• Pregnancy (urine pregnancy test for all women of child-bearing age).
• Planned transport out of ICU during planned study protocol.
• Coagulopathy (INR>2.0 or PTT >50).
• Severe thrombocytopenia (platelets <20,000).
• History of obstructive lung disease (asthma and/or COPD).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: low-tidal-volume ventilation; Goal tidal volume is 6 cc/kg ideal body weight.	Other: low-tidal-volume ventilation; goal tidal volume of 6 cc/kg ideal body weight
Experimental: APRV; APRV allows spontaneous breathing.	Other: APRV; APRV is a time cycled, inverse-ratio, pressure controlled strategy that allows spontaneous breathing through the respiratory cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The study will be powered to detect a decrease in plasma IL-6 levels (pg/ml) from ARDSNet to APRV	6 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in dose of sedation medications	6 hours
Riker score	6 hours
Lung mechanics	6 hours
Oxygenation with APRV versus ARDSNet	6 hours

Collaborators and Investigators

• Sponsor: Boston Medical Center
• Investigators: Principal Investigator: George O'Connor, MD, Boston University Medical College

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: December 22, 2009
• First Submitted That Met QC Criteria: December 23, 2009
• First Posted (Estimate): December 24, 2009

Study Record Updates

• Last Update Posted (Estimate): December 19, 2016
• Last Update Submitted That Met QC Criteria: December 16, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Acute lung injury (ALI); Adult respiratory distress syndrome (ARDS); Low-tidal-volume strategy; airway pressure release ventilation (APRV); biomarkers of lung injury; ARDS Net
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Infant, Premature, Diseases; Thoracic Injuries; Wounds and Injuries; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury
• Other Study ID Numbers: H-28944