Mechanical ventilation, the use of a machine to help a person breathe, was not something many people thought about all that often—until the COVID pandemic struck. Stories of patients being put on ventilators, along with associated shortages of these machines, were blasted across the news, thrusting this decades-old treatment into the spotlight.
In the many years that modern ventilation has been in use, it has contended with a serious side effect: lung injury. While the patient needs air, pushing too much of it into the lungs in the wrong way can end up causing lasting harm, including multiorgan failure and death.
In research published in Science Translational Medicine Aug. 14, scientists explained how they carefully imaged sheep placed on ventilators to identify a setting that can optimize lung function while minimizing the risk of injury.
“It's sort of the sweet spot,” Arthur Slutsky, M.D., a pulmonary and critical care physician at Unity Health Toronto who was not involved with the research, told Fierce Medtech in an interview. “Not too big, not too small.”
In the early 1950s, a polio epidemic broke out in Denmark's capital of Copenhagen. Ironically, the outbreak was likely caused by a large conference on the virus that the city hosted the previous year. Machine ventilators didn’t exist, so patients had to be ventilated by hand using bags. This simple intervention dramatically reduced polio deaths, Slutsky said, and the episode gave birth to the modern intensive care unit.
But in recent decades, as mechanical ventilators have become more common, there’s been a growing understanding that the machines can damage the lungs.
“Mechanical ventilation, on one side, can save a lot of lives,” anesthesiologist and intensivist David Lagier, M.D., Ph.D., of Aix Marseille University in France, told Fierce in an interview. “But it's not physiological at all. It's something that is actually very bad for the lungs.”
During normal breathing, our diaphragm muscle contracts and allows the lungs to expand and fill evenly with air. With a ventilator, air is instead forced into the lungs of a patient who is often lying on their back, with their diaphragm pressed against the respiratory organs.
Lagier manages patients on ventilators every day and wanted to see if tweaking the settings of the machines could help limit the damage they cause. In order to capture what lungs look like on a ventilator in detail, he turned to our mammalian cousin the sheep.
Lagier took CT scans of sheep as they breathed over a range of different values of positive end-expiratory pressure (PEEP). PEEP is a measure of the strength of a burst of air that is pushed into the lungs after the patient exhales, so that the organ’s air sacs stay open and don’t collapse between breaths; it is one of the main settings on modern ventilators.
“The question over the last 60 years is: what is the best PEEP?” Slutsky said. Too little PEEP can leave the lungs at risk of collapse, while too much can cause the lungs to over-expand and become inflamed.
One measure commonly taken by ventilators is called the driving pressure, which tells physicians if the lungs are getting more air than they can handle; a high driving pressure is strongly linked with a greater risk of death in patients on ventilators. Because of this known data, Lagier decided to see how driving pressure changed at different PEEP values and the resulting effect on ventilator-induced lung injury.
Starting from a PEEP of 20 centimeters of water (the amount of pressure needed to move a column of water 20 centimeters, the standard unit used for pressure in ventilation), Lagier collected 256 detailed CT scans of sheep lungs while steadily decreasing the pressure to two centimeters of water.
For sheep with both healthy lungs and injured lungs, the PEEP that best kept the lungs functioning while minimizing damage was whichever value produced the lowest driving pressure. At higher driving pressures, sheep were more at risk of the two main sources of lung injury from ventilators—collapse and overdistension. The researchers call this value the PEEP of minimal driving pressure, or PEEPDP, and it is different for every patient—but easy to measure and adjust.
“This paper is interesting because it gets at the underlying mechanism by which optimizing driving pressure may improve outcomes,” Slutsky said. Continuously tweaking the PEEP so that driving pressure stays as low as possible, either manually or automatically, could protect patients' lungs from serious damage. Clinical trials comparing different PEEP values are currently ongoing.
In addition to ventilator settings like PEEPDP, Lagier is looking into other ways to prevent lung injury in patients on ventilators.
Tweaking settings is free and easy for physicians, “but it looks like what you can optimize with the ventilator settings is limited,” Lagier said. “Something out of the ventilator that may help patients—that is what I'm working on right now.”