Preventing ventilation induced lung injury depends on giving the right number of 'sighs'

Bethesda, MD. (July 25, 2006) Ventilation therapy burst into the public consciousness more than 60 years ago with the "iron lung" and the polio epidemic. Mechanical ventilation has come a long way since then and is used today with patients who cannot breathe on their own because of trauma, lung injuries and chronic lung disease.

But ventilation demands a delicate balance between over inflating and under inflating the lungs, either of which can lead to further injury. Researchers have found that pumping too much air overdistends the lung, leading to ventilator-induced lung injury (VILI).

Doctors currently use small amounts of air (low tidal volume) to protect against VILI. But low tidal volumes can lead to progressive closure of the lungs' air cells, called alveoli, reducing the lung's ability to exchange gases. One way to reverse closure of the alveoli is to periodically give a more robust puff of air, known as deep inflation.

A new study in the online edition of the American Journal of Physiology-Lung Cellular and Molecular Physiology shows that low tidal volume combined with periodic deep inflation provides the best balance between keeping the lung open and preventing VILI in mice. And, using mice, these researchers have shown for the first time that although deep inflation is necessary, it can be overdone.

"There is still a lot of controversy and uncertainty about how best to ventilate the lung," said the study's senior author, Jason HT Bates of the University of Vermont. "One controversy is whether deep inflations, the "sighs" that each of us takes periodically, should ever be given, and if so, how frequently."

Researchers find optimal range

"This study demonstrates that an optimal frequency range of deep inflation delivery exists, at which point the potentially injurious effects of overdistention are outweighed by the protective benefits of maintaining a predominantly open lung," wrote Gilman B. Allen, Benjamin T. Suratt, Lisa Rinaldi, Joseph M. Petty and Bates in the AJP-Lung paper entitled "Choosing the frequency of deep inflation in mice: balancing recruitment against ventilator-induced lung injury."

Allen, a medical doctor with Fletcher Allen Health Care and the University of Vermont department of medicine, has treated patients on ventilation. Bates is a University of Vermont department of medicine researcher interested in lung physiology.

Ventilators are commonly used in hospital intensive care units with a variety of patients, including those with acute lung injury, acute respiratory distress syndrome, pneumonia, septic shock, trauma, aspiration of vomit and chemical inhalation. As a result of these conditions, fluid can build up in the lungs, blocking the alveoli. This causes the body to mount an inflammatory response, which injures the lung's epithelial lining, Bates said. At that point, doctors provide mechanical ventilation in the intensive care unit until the body heals itself.

Bates explains the difficulty of treating the injured lung this way: "Imagine you have two balloons which you fill by pumping in air. Now imagine you have only one balloon, and you must drive the same volume of air into the one balloon as you did into two," Bates explained. The same thing happens in the lungs. When parts of the lungs are no longer working, it places greater pressure on the portions of the lung that are working, with the remaining lung handling the air pressure that two lungs had handled.

Doctors consider tidal volume (the amount of air an individual normally inhales and exhales), deep inflation frequency (the number of deep breaths given) and PEEP (positive end-expiratory pressure), which helps keep lungs from collapsing by preventing the airways from emptying completely. PEEP also helps improve gas exchange within the lungs.

Low tidal volume, varied sigh rate

The researchers divided mice into three experimental groups. All three groups received PEEP and low tidal volume air. Each group was ventilated for two hours. The experimental groups differed according to how many deep inflations they received. They were as follows:

  • HV (high volume) received one deep inflation each breath
  • LV (low volume) received two deep inflations each hour
  • LVDI (low volume deep inflation) received two deep inflations each minute

In addition, there were two control groups -- a surgical sham, which received no ventilation, and a group that received deep inflation every breath and no PEEP.

The study found that:

  • The lungs of the mice given two big breaths every minute (LVDI) remained more open and functioned better than the LV and HV.
  • The lungs of the mice that received only two deep breaths per hour (LV) became stiff and portions of the lungs collapsed. However, lung function returned briefly to normal when the mice received their infrequent deep inflations. This suggests that the lungs self-repair after the deep inflation, at least over the course of the first two hours.
  • The lungs of the mice that received deep inflation every breath (HV) suffered overdistention injury to their lungs. This group was akin to a high tidal volume group, once again demonstrating that low tidal volume is safer.
  • The control group that received high tidal volume but no PEEP showed the highest evidence of injury, even higher than the high tidal volume group. This indicates that PEEP helps reduce the negative effects of frequent deep inflation.

"We demonstrated it's possible to give deep breaths too frequently and too seldom," Bates explained. The middle ground -- two deep inflations per minute -- provides the most benefit to the mice we studied without injuring the lungs, he said.

"We conclude that frequent deep inflation can safely improve gas exchange and lung mechanics and may confer protection from biotrauma," the authors wrote. "Differences between LVDI and HV suggest that an optimal frequency range of deep inflation exists, within which the benefits of maintaining an open lung outweigh injury incurred from over-distention."

Next step

"Our findings have obvious implications for the recruitment of the injured human lung during low tidal ventilation," the authors wrote. "However, extrapolating our results to the clinical situation must be done guardedly. In the present study we employed uninjured mice, whereas it is known that the injured lung is more prone to atelectasis (collapse) than a normal lung."

Bates' team hopes to move to a human trial in the near future, now that they have established that deep inflation is beneficial and can be delivered with an optimal frequency.

Source

"Choosing the frequency of deep inflation in mice: balancing recruitment against ventilator-induced lung injury," by Gilman B. Allen, Benjamin T. Suratt, Lisa Rinaldi and Joseph M. Petty and Jason HT Bates, Vermont Lung Center, Department of Medicine, University of Vermont, Burlington. Allen, Suratt and Bates are also affiliated with the Fletcher Allen Health Care, Burlington. The study appears in the online edition of American Journal of Physiology Lung Cellular and Molecular Physiology published by The American Physiological Society.

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Funding

The study was funded by grants from the National Institutes of Health's Centers of Biomedical Research Excellence and GlaxoSmithKline.

Editor's notes

The media may obtain a copy of Allen et al. by contacting Christine Guilfoy, American Physiological Society, (301) 634-7253 or cguilfoy@the-aps.org.

Want to learn the latest on lung disease research? Consider attending the APS conference examining how genomics, proteomics and bioinformatics are driving new discoveries about lung disease. Researchers and clinicians will examine how to use this information to benefit patients at "Physiological Genomics and Proteomics of Lung Disease," Nov. 2-5, Fort Lauderdale, FL. Allen Cowley Jr., editor of Physiological Genomics, and David A. Schwartz, NIH, are featured speakers.

The American Physiological Society was founded in 1887 to foster basic and applied bioscience. The Bethesda, Maryland-based society has 10,500 members and publishes 14 peer-reviewed journals containing almost 4,000 articles annually.

APS provides a wide range of research, educational and career support and programming to further the contributions of physiology to understanding the mechanisms of diseased and healthy states. In 2004, APS received the Presidential Award for Excellence in Science, Mathematics and Engineering Mentoring (PAESMEM).


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