Clinical Trials Logo

Clinical Trial Details — Status: Withdrawn

Administrative data

NCT number NCT00961168
Other study ID # WOBARDS
Secondary ID
Status Withdrawn
Phase N/A
First received August 16, 2009
Last updated March 3, 2015
Start date September 2009
Est. completion date September 2013

Study information

Verified date March 2015
Source University of California, San Francisco
Contact n/a
Is FDA regulated No
Health authority United States: Institutional Review Board
Study type Interventional

Clinical Trial Summary

The primary goal of this study is to measure changes in biological markers of inflammation in critically-ill patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) while they are treated with different styles of lung-protective, artificial breathing assistance.

Secondary goals are to measure the breathing effort of patients using different artificial breathing patterns from the breathing machine.

The primary hypothesis is that volume-targeted artificial patterns will produce less inflammation. The secondary hypothesis is that volume-targeted artificial patterns will increase breathing effort compared to pressure-targeted artificial patterns.


Description:

Ventilator-induced lung injury contributes to the progression of ALI/ARDS,1 and is thought to occur partly from the unequal distribution of a super-normal tidal volume to normal areas of the lung.2 Alveolar overdistension causes alveolar-capillary membrane damage,3 increased-permeability pulmonary edema4 and hyaline membrane formation.5 Therefore, it is recommended that tidal volume should be reduced to 6-7 mL/kg, and that the peak alveolar pressure, or the end-inspiratory plateau pressure (PPLAT), should be limited to < 30 cm H2O.6 The National Heart Lung and Blood Institute's ARDS Network demonstrated a 22% reduction in mortality using a "lung-protective" (low tidal volume) ventilation strategy in patients with ALI/ARDS.7 High tidal volume ventilation causes a rapid and substantial increase plasma levels of proinflammatory mediators which decrease in response to lung protective ventilation.8,9 A consequence of lung-protective ventilation is dyspnea and increased work of breathing.10 Our recent study11 on work of breathing during lung-protective ventilation found that inspiratory pleural pressure changes were extraordinarily high, averaging 15-17 cm H2O. Whereas tidal volume was well controlled during volume ventilation, in contrast, it exceeded target levels in 40% of patients during pressure control ventilation.

High tidal volume-high negative pressure ventilation causes acute lung injury in animal models.12,13 Thus ventilator-induced lung injury results from excessive stress across lung tissue created by high transpulmonary (airway-pleural).pressure.14 This suggests the possibility that despite pressure control ventilation being set with a low positive airway pressure, "occult" high tidal volume-high transpulmonary pressure ventilation still may occur.11 However, during spontaneous breathing diaphragmatic contractions cause ventilation to be distributed preferentially to dorsal:caudal aspects of the lungs.15 Therefore, high transpulmonary pressures created by large negative swings in pleural pressure theoretically may not cause regional lung over-distension and ventilator-induced lung injury if tidal ventilation is preferentially distributed to dorsocaudal lung regions. However, a study16 examining the effects of diaphragmatic breathing during Pressure Control Ventilation found that dorsocaudal distribution of tidal volume was not necessarily improved compared to passive ventilation, as the amount of tidal ventilation distributed to areas of high ventilation/perfusion was unaltered. Regardless, during a recent conference on respiratory controversies in the critical care setting, it was noted that the effects of ventilator modes such as volume control, pressure control and airway pressure-release ventilation on proinflammatory cytokine expression during lung-protective ventilation has not been studied in humans.17 Thus it is unknown whether or not differences in transpulmonary pressure and tidal volume between these modes has a direct impact on lung inflammation.


Recruitment information / eligibility

Status Withdrawn
Enrollment 0
Est. completion date September 2013
Est. primary completion date September 2012
Accepts healthy volunteers No
Gender Both
Age group 18 Years to 85 Years
Eligibility Inclusion Criteria:

- Both medical and surgical patients undergoing mechanical ventilatory support who meet criteria for Acute Lung Injury (ALI) or Acute Respiratory Distress Syndrome (ARDS) as defined by the European-American Consensus Conference,

- Mechanical ventilation via an endotracheal or tracheotomy tube,

- PaO2/FiO2 < 300 mmHg with bilateral infiltrates on chest radiogram,

- Clinical management with lung protective ventilation (Tidal volume < 8 mL/kg).

Exclusion Criteria:

- Patients receiving "comfort care",

- High cervical spinal cord injury or other neuromuscular disease,

- Prisoners,

- Pregnancy,

- Less than 18 years of age,

- Facial fractures and coagulopathies,

- Patients placed on psychiatric hold.

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Supportive Care


Related Conditions & MeSH terms


Intervention

Other:
Volume Control Ventilation
Mechanical ventilation at a constant tidal volume of 6 mL/kg.
Pressure Control Ventilation
Mechanical ventilation at a constant airway pressure of 25-30 cm H2O

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
University of California, San Francisco

References & Publications (16)

1. Dreyfus D, Sauman G. Ventilation induced injury. In: Principles and Practice of Mechanical Ventilation. Tobin M J. Editor. New York: McGraw Hill Publishers; 1994: 793-811.

6. Tuxen DV. Permisive hypercapnia. In: Principles and Practice of Mechanical Ventilation. Tobin M J. Editor. New York: McGraw Hill Publishers; 1994: 371-392.

Carlton DP, Cummings JJ, Scheerer RG, Poulain FR, Bland RD. Lung overexpansion increases pulmonary microvascular protein permeability in young lambs. J Appl Physiol (1985). 1990 Aug;69(2):577-83. — View Citation

Dreyfuss D, Soler P, Basset G, Saumon G. High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure. Am Rev Respir Dis. 1988 May;137(5):1159-64. — View Citation

Froese AB, Bryan AC. Effects of anesthesia and paralysis on diaphragmatic mechanics in man. Anesthesiology. 1974 Sep;41(3):242-55. — View Citation

Fu Z, Costello ML, Tsukimoto K, Prediletto R, Elliott AR, Mathieu-Costello O, West JB. High lung volume increases stress failure in pulmonary capillaries. J Appl Physiol (1985). 1992 Jul;73(1):123-33. — View Citation

Gattinoni L, Pesenti A. The concept of "baby lung". Intensive Care Med. 2005 Jun;31(6):776-84. Epub 2005 Apr 6. — View Citation

Hickling KG. Ventilatory management of ARDS: can it affect the outcome? Intensive Care Med. 1990;16(4):219-26. Review. — View Citation

Kallet RH, Campbell AR, Dicker RA, Katz JA, Mackersie RC. Work of breathing during lung-protective ventilation in patients with acute lung injury and acute respiratory distress syndrome: a comparison between volume and pressure-regulated breathing modes. Respir Care. 2005 Dec;50(12):1623-31. — View Citation

Lachmann B, Jonson B, Lindroth M, Robertson B. Modes of artificial ventilation in severe respiratory distress syndrome. Lung function and morphology in rabbits after wash-out of alveolar surfactant. Crit Care Med. 1982 Nov;10(11):724-32. — View Citation

Mascheroni D, Kolobow T, Fumagalli R, Moretti MP, Chen V, Buckhold D. Acute respiratory failure following pharmacologically induced hyperventilation: an experimental animal study. Intensive Care Med. 1988;15(1):8-14. — View Citation

Myers TR, MacIntyre NR. Respiratory controversies in the critical care setting. Does airway pressure release ventilation offer important new advantages in mechanical ventilator support? Respir Care. 2007 Apr;52(4):452-8; discussion 458-60. — View Citation

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. — View Citation

Stüber F, Wrigge H, Schroeder S, Wetegrove S, Zinserling J, Hoeft A, Putensen C. Kinetic and reversibility of mechanical ventilation-associated pulmonary and systemic inflammatory response in patients with acute lung injury. Intensive Care Med. 2002 Jul;28(7):834-41. Epub 2002 Jun 15. — View Citation

Tuxen DV. Permissive hypercapnic ventilation. Am J Respir Crit Care Med. 1994 Sep;150(3):870-4. Review. — View Citation

Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000 May 4;342(18):1301-8. — View Citation

* Note: There are 16 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary proinflammatory cytokine expression in plasma 2 hours No
Secondary work of breathing 2 hours No
See also
  Status Clinical Trial Phase
Recruiting NCT03937947 - Traumatic Brain Injury Associated Radiological DVT Incidence and Significance Study
Completed NCT04247477 - Comparison of Different PEEP Titration Strategies Using Electrical Impedance Tomography in Patients With ARDS N/A
Completed NCT03315702 - Effect of Mechanical Ventilation on Plasma Concentration Level of R-spondin Proteins
Not yet recruiting NCT02693912 - Changes in Alveolar Macrophage Function During Acute Lung Injury N/A
Completed NCT01659307 - The Effect of Aspirin on REducing iNflammation in Human in Vivo Model of Acute Lung Injury Phase 2
Unknown status NCT01186874 - Epidemiology Research on Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) in Adult ICU in Shanghai N/A
Completed NCT01552070 - Recruitment on Extravascular Lung Water in Acute Respiratory Distress Syndrome (ARDS) Phase 2
Recruiting NCT00759590 - Comparison of Two Methods to Estimate the Lung Recruitment N/A
Completed NCT00736892 - Incidence of Acute Lung Injury: The Alien Study
Completed NCT02475694 - Acute Lung Injury After Cardiac Surgery: Pathogenesis N/A
Completed NCT00825357 - Biological Markers to Identify Early Sepsis and Acute Lung Injury N/A
Terminated NCT00263146 - Recruitment Maneuvers in ARDS: Effects on Respiratory Function and Inflammatory Markers. N/A
Completed NCT00188058 - Comparison of 2 Strategies of Adjustment of Mechanical Ventilation in Patients With Acute Respiratory Distress Syndrome N/A
Completed NCT00234767 - Study of the Economics of Pulmonary Artery Catheter Use in Patients With Acute Respiratory Distress Syndrome (ARDS) Phase 3
Recruiting NCT02598648 - Role and Molecular Mechanism of Farnesoid X Receptor(FXR) and RIPK3 in the Formation of Acute Respiratory Distress Syndrome in Neonates N/A
Recruiting NCT02948530 - Measurement of Lung Elastance and Transpulmonary Pressure Using Two Different Methods (Lungbarometry)
Completed NCT01532024 - Exploratory Clinical Study of Neutrophil Activation Probe (NAP) for Optical Molecular Imaging in Human Lungs Early Phase 1
Recruiting NCT01992237 - Measuring Energy Expenditure in ECMO (Extracorporeal Membrane Oxygenation) Patients N/A
Completed NCT01486342 - PET Imaging in Patients at Risk for Acute Lung Injury N/A
Not yet recruiting NCT01212640 - GROUP FOR TRALI STUDY. SEMICYUC. N/A