A new study published 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 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.”

Low Tidal Volume, Varied Sigh Rate

The researchers divided mice into three experimental groups. All three groups received positive end-expiratory pressure (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 those of the mice in the LV and HV groups.
    •     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 2 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 [that] it’s possible to give deep breaths too frequently and too seldom,” Bates explained. In short, he found that the middle ground—two deep inflations per minute—provided the most benefit to the mice he studied without injuring the lungs.

“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

The authors believe their findings have obvious implications for the recruitment of the injured human lung during low tidal ventilation. However, they cautioned that one must be careful when extrapolating the results to the clinical situation in humans. “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,” they pointed out.

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.


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