In the February 13 issue of JAMA, several strategies were explored for patients with severe respiratory disorders. While there was little improvement in death rates, several promising results were obtained, and the resulting dialogue indicates a need for further research in the same vein.

New Lung Open Ventilation Strategy Compared to Mechanical Ventilation

A new study in the Februay 13 issue of JAMA compares two treatment methods for critically ill patients who display severe, rapid onset lung disorders — specifically, a new “lung open ventilation”strategy was compared to the classical mechanical ventilators. The risk of death appeared to be comparable in each of the strategies, but the newer method reduced the rates of severe persistent low oxygen levels and the need for additional “rescue” therapies.

Acute lung injury can be caused by severe pneumonia or trauma, and acute respiratory distress syndrome (ARDS) is its most critical form. As dangerous complications of critical illness, they are often treated with mechanical ventilation, which can provide life support but often at the expense of further lung injury. Ventilation that employs a low tidal volume inhaled in each breath reduces the risk of death in patients who are critically ill and have acute lung injury and ARDS. Additional therapies may be used to splint open collapsed lung segments, and these may reduce the risk of death even further, according to the authors.

Maureen O. Meade, M.D., M.Sc., of Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada, and colleagues explored the effect of an experimental “lung open ventilation”(LOV) strategy using a combination of: low tidal volumes; recruitment maneuvers, which attempt to open the lung through periodic sighs on the ventilator; and high positive end-expiratory pressure (PEEP) to help maintain the lung once open. This was compared to a previously established low-tidal-volume strategy as a control. This study, known as the Lung Open Ventilation (LOV) Study, tested 983 patients with moderate and severe lung injury in a randomized trial between August 2000 and March 2006 in 30 intensive care units in Canada, Australia, and Saudi Arabia.

The all-cause death rates were 36.4 percent in the experimental LOV group and 40.4 percent in the control low tidal volume group. Barotrauma, injury to the lung as a result of the pressure of the ventilator, was found to be 11.2 percent and 9.1 percent respectively.

Despite similar death and barotrauma rates, the authors summarize their conclusions to show a prediliction for the LOV strategy for other beneficial reasons. They write: “… for patients with acute lung injury and ARDS, we found similar mortality in patients with a multi-faceted protocolized lung-protective ventilation strategy designed to open the lung compared with an established low-tidal-volume protocolized ventilation strategy. We found no evidence of significant harm or increased risk of barotrauma despite the use of higher PEEP. In addition, the ‘open-lung’ strategy appeared to improve oxygenation, with fewer hypoxemia-related deaths and a lower use of rescue therapies by the treating clinicians. Our results, in combination with the two other major trials, justify use of higher PEEP levels as an alternative to the established low-PEEP, low-tidal-volume strategy.”

Ventilation Strategy Using Low Tidal Volumes, Recruitment Maneuvers, and High Positive End-Expiratory Pressure for Acute Lung Injury and Acute Respiratory Distress Syndrome
Maureen O. Meade, Deborah J. Cook, Gordon H. Guyatt, Arthur S. Slutsky, Yaseen M. Arabi, D. James Cooper, Andrew R. Davies, Lori E. Hand, Qi Zhou, Lehana Thabane, Peggy Austin, Stephen Lapinsky, Alan Baxter, James Russell, Yoanna Skrobik, Juan J. Ronco, Thomas E. Stewart
JAMA, February 13, 2008 – Vol 299, No. 6: 637-645
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Positive End-Expiratory Pressure Treatment Approach For Patients on Mechanical Ventilation

A therapy for patients on mechanical ventilation which set the Positive End-Expiratory Pressure (PEEP) at a certain level did not help attenuate the death rate. However, it did improve lung function and help reduce the length of time in organ failure, according to a study in the February 13 issue of JAMA.

Alain Mercat, M.D., of CHU d’Angers, Angers, France, and colleagues examined two strategies in a study known as the Express study, which was conducted in 767 patients with acute lung injury (ALI) in 37 intensive care units in France between September 2002 and December 2005. They compared an approach which limited PEEP levels in hopes of increasing alveolar recruitment in the air sacs of the lungs to one which minimized alveolar distention, or stretching.

It was found that the 28-day death rate in the group allowed minimal alveolar distention was 31.2 percent (a sample size of 119) while the increased alveolar recruitment group showed 27.8 percent (a sample size of 107.) The hospital mortality rates were 39.0 percent versus 35.6 percent, respectively. While these numbers are similar, the increased alveolar recruitment group had a higher median number of days when ventilators were not used (7 days compared to 3 days) and more organ-failure free days (6 compared to 2.) In addition, this new strategy was associated with higher compliance values, better oxygenation, less use of additional therapy measures, and larger fluid requirements, many of which could indicate better recovery.

Positive End-Expiratory Pressure Setting in Adults With Acute Lung Injury and Acute Respiratory Distress Syndrome: A Randomized Controlled Trial

Alain Mercat; Jean-Christophe M. Richard; Bruno Vielle; Samir Jaber; David Osman; Jean-Luc Diehl; Jean-Yves Lefrant; Gwenaël Prat; Jack Richecoeur; Ania Nieszkowska; Claude Gervais; Jérôme Baudot; Lila Bouadma; Laurent Brochard
JAMA, February 13, 2008-Vol 299, No. 6: 646-655
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Editorial: Ventilatory Treatment for Acute Lung Injury and Acute Respiratory Distress Syndrome

Luciano Gattinoni, M.D., F.R.C.P., and Pietro Caironi, M.D., of the Universita degli Studi di Milana, Milan, Italy, provided comments in an accompanying editorial in the February 13 issue of JAMA regarding the treatment of acute lung injury and acute respiratory distress syndrome (ARDS). They confirm the implications of the studies while calling for more specific research regarding these strategies.

“The LOV study and the Express study not only should conclude the era of comparing PEEP levels in unselected populations with ALI and ARDS, but also underscore the need for a new definition of ARDS aimed at identifying patients with greater lung edema [accumulation of fluid in the tissue] and larger recruitability. Higher and lower levels of PEEP should be tested in this more selective population to obtain a definitive answer. In the meantime, the data from these two studies favor the use of higher levels of PEEP in the early phase of ALI and ARDS.”

Refining Ventilatory Treatment for Acute Lung Injury and Acute Respiratory Distress Syndrome
Luciano Gattinoni, Pietro Caironi
JAMA, February 13, 2008-Vol 299, No. 6: 691-693
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Editorial: The Challenges of Testing Protocols in the Intensive Care Unit

Jean-Daniel Chiche, M.D., of the University Rene Descartes, Paris, and Derek C. Angus, M.D., M.P.H., of the University of Pittsburgh, and Contributing Editor, JAMA, wrote an accompanying editorial in the February 13 issue of JAMA. Specifically, they were concerned with the challenges of testing complex interventions in critically ill patients. They cite these studies as solid examples of how clinical trials can be rigorously and effectively performed.

“… both the Lung Open Ventilation Study and the Express Study demonstrated that is was possible to convert the physiologic principles on which experts base their care into a set of reproducible instructions and then test these instructions in a broad multicenter environment. Although neither study demonstrated a significant improvement in mortality, their findings appear to have implications for future practice. Finally, these studies made important steps toward increasingly rigorous assessment of increasingly sophisticated protocols for the best care of critically ill patients.”

Testing Protocols in the Intensive Care Unit
Jean-Daniel Chiche, Derek C. Angus
JAMA, February 13, 2008-Vol 299, No. 6: 693-695
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Written by Anna Sophia McKenney