Effect of Mechanical Ventilation Strategy on Lung Injury in Patients With Less Severe Acute Respiratory Distress Syndrome: Targeted on RAGE

This study is not yet open for participant recruitment.
Verified November 2012 by National Taiwan University Hospital
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT01301872
First received: February 18, 2011
Last updated: December 26, 2012
Last verified: November 2012
  Purpose

During the past two decades, there current concept has evolved significantly that ventilator-induced lung injury (VILI) may not only impose a direct mechanical stress and subsequent injury to the lungs, but may also induce local as well as systemic inflammation responses, generally referred as biotrauma.1 Patients with ARDS often die of severe systemic inflammatory response syndrome (SIRS) and multiorgan dysfunction2 rather than refractory hypoxemia. Ranieri et al found that patients with less severe ARDS, i.e., a lung injury score of 2.5 or less, receiving ventilation with lung protective strategy involving low tidal volume (7.5 mL/kg PBW) and high PEEP could attenuate the pulmonary and systemic cytokine response compared with conventional ventilation with high tidal volume.3 Stuber et al found an increase in pro-inflammatory cytokines in the lung and plasma of patients with ARDS within 1 hour after switching the patients from a protective to non-protective ventilator strategy.4 The receptor for advanced glycation end-products (RAGE) was recently identified as a marker of injury to the alveolar type I epithelial cells5. Clinical studies showed that the plasma level of RAGE was associated with severity of lung injury and clinical outcome, and low tidal volume strategy ventilation accelerated the decline in plasma RAGE levels. These results suggest plasma RAGE level might be a reliable biomarker of alveolar epithelial injury in acute lung injury and may associated with ventilator induced lung injury6. Although, current approach to mechanical ventilation of a patient with ARDS emphasizes the use of lower tidal volumes with lower plateau pressures to avoid causing lung overdistension and ventilator associated lung injury (VILI)7; however, in the real world, some studies showed that strictly reduction of tidal volume to 6ml/kg PBW was modest in modern time, and was noticed only in patients with greater lung injury scores8. The benefit of VT strictly reduction to 6ml/kgPBW and its effect on VILI in patients with less severe ARDS whose Pplat are already below 30 cmH2O are controversy9. One of the possible solutions is to look at the biomarkers of injury to alveolar epithelial cells. Of these potentially promising markers, the receptor for advanced glycation end-product (RAGE) is of great interest.

We hypothesize that a strategy with strict low tidal volume in less severe ARDS and ALI patients with good compliance may be beneficial to this patient population. Therefore, we wish to propose a prospective single-center study to investigate the effect of mechanical ventilation strategy on the plasma level of RAGE in patients with less severe ARDS and acute lung injury.


Condition Intervention
Acute Respiratory Distress Syndrome
Other: check biomarker :RAGE

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Effect of Mechanical Ventilation Strategy on Lung Injury in Patients With Less Severe Acute Respiratory Distress Syndrome: Targeted on RAGE

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • the effect of mechanical ventilation strategy on the plasma level of RAGE in patients with less severe ARDS and acute lung injury. [ Time Frame: 7 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: December 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1
All patients meet ALI/less severe ARDS criteria
Other: check biomarker :RAGE
We will check RAGE for all patients who have ARDS included in our study

Detailed Description:

During the past two decades, there current concept has evolved significantly that ventilator-induced lung injury (VILI) may not only impose a direct mechanical stress and subsequent injury to the lungs, but may also induce local as well as systemic inflammation responses, generally referred as biotrauma.1 Patients with ARDS often die of severe systemic inflammatory response syndrome (SIRS) and multiorgan dysfunction2 rather than refractory hypoxemia. Ranieri et al found that patients with less severe ARDS, i.e., a lung injury score of 2.5 or less, receiving ventilation with lung protective strategy involving low tidal volume (7.5 mL/kg PBW) and high PEEP could attenuate the pulmonary and systemic cytokine response compared with conventional ventilation with high tidal volume.3 Stuber et al found an increase in pro-inflammatory cytokines in the lung and plasma of patients with ARDS within 1 hour after switching the patients from a protective to non-protective ventilator strategy.4 The receptor for advanced glycation end-products (RAGE) was recently identified as a marker of injury to the alveolar type I epithelial cells5. Clinical studies showed that the plasma level of RAGE was associated with severity of lung injury and clinical outcome, and low tidal volume strategy ventilation accelerated the decline in plasma RAGE levels. These results suggest plasma RAGE level might be a reliable biomarker of alveolar epithelial injury in acute lung injury and may associated with ventilator induced lung injury6. Although, current approach to mechanical ventilation of a patient with ARDS emphasizes the use of lower tidal volumes with lower plateau pressures to avoid causing lung overdistension and ventilator associated lung injury (VILI)7; however, in the real world, some studies showed that strictly reduction of tidal volume to 6ml/kg PBW was modest in modern time, and was noticed only in patients with greater lung injury scores8. The benefit of VT strictly reduction to 6ml/kgPBW and its effect on VILI in patients with less severe ARDS whose Pplat are already below 30 cmH2O are controversy9. One of the possible solutions is to look at the biomarkers of injury to alveolar epithelial cells. Of these potentially promising markers, the receptor for advanced glycation end-product (RAGE) is of great interest.

We hypothesize that a strategy with strict low tidal volume in less severe ARDS and ALI patients with good compliance may be beneficial to this patient population. Therefore, we will to propose a prospective single-center study to investigate the effect of mechanical ventilation strategy on the plasma level of RAGE in patients with less severe ARDS and acute lung injury.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All intubated and mechanically ventilated patients who meet the criteria of American-European Consensus Conference (AECC) criteria for ALI/ ARDS:

Acute onset of illness Bilateral (patchy, diffuse, or homogeneous) infiltrates consistent with pulmonary edema PaO2/FiO2 <= 300 (corrected for altitude): (P/F <300 for ALI and P/F <200 for ARDS) No clinical evidence of left atrial hypertension

Exclusion Criteria:

  • 1. Age <18 years 2. Enrolled in other clinical trials 3. Had confirmed alternative diagnoses that would have different clinical course than ARDS/ALI, e.g., diffuse alveolar hemorrhage, vasculitis, interstitial pneumonitis, etc.

    4. Congestive heart failure related pulmonary edema 5. Acute myocardial infarction 6. Pregnancy 7. Patients with definite contraindication to the use of low-tidal volume ventilation, e.g., increased intracranial pressure, tricyclic antidepressant overdose, etc.

    8. The patient who meets inclusion criteria initially but rapidly improved within 24 hours of diagnosis of ARDS/ALI

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01301872

Contacts
Contact: Jih-Shuin Jerng, MD,PhD 0972651075 jsjerng@ntu.edu.tw

Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Jih-Shuin Jerng, MD,PhD National Taiwan University Hospital
  More Information

No publications provided

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT01301872     History of Changes
Other Study ID Numbers: 201012005RB
Study First Received: February 18, 2011
Last Updated: December 26, 2012
Health Authority: Taiwan: Department of Health

Additional relevant MeSH terms:
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Lung Injury
Wounds and Injuries
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Thoracic Injuries

ClinicalTrials.gov processed this record on April 16, 2014