April 7, 2020 — As doctors treat more patients who are severely ill from COVID-19, they’re noticing differences in how their lungs are damaged.

Some patients coming to the hospital have very low oxygen levels in their blood, but you wouldn’t necessarily know it from talking to them. They don’t seem starved of oxygen. They may be a little confused. But they aren’t struggling to breathe.

When doctors take pictures of their lungs — either with a CT scanner or an X-ray machine — those also look fairly healthy. The lungs may have a few areas of cloudiness and crazing, indicating spots of damage from their infection, but most of the lung is black, indicating that it is filled with air.

One doctor treating COVID-19 patients in New York says it was like altitude sickness. It was “as if tens of thousands of my fellow New Yorkers are stuck on a plane at 30,000 feet and the cabin pressure is slowly being let out. These patients are slowly being starved of oxygen,” said Cameron Kyle-Sidell, MD, an emergency room and critical care doctor at Maimonides Medical Center in Brooklyn who has been posting about his experience on social media.

“A whole bunch of these patients really have low oxygen, but their lungs don’t look all that bad,” says Todd Bull, MD, director for the Center of Lungs and Breathing at the University of Colorado School of Medicine, in Aurora.

Doctors in Italy have noticed the same thing. And in some cases, that might mean patients need to be treated a little differently to ensure the best outcome.

In an editorial in the journal Intensive Care Medicine, Luciano Gattinoni, MD, a guest professor of anesthesia and intensive care at the University of Gottingen in Germany, and one of the world’s experts in mechanical ventilation, says more than half the patients he and his colleagues have treated in Northern Italy have had this unusual symptom. They seem to be able to breathe just fine, but their oxygen is very low.

According to Gattinoni, about 30% of COVID-19 patients who come to the hospital have more classic symptoms of acute respiratory distress syndrome, or ARDS. Their lungs are cloudy on imaging scans, and they’re stiff and inflamed, showing that they aren’t working well. The patients also have low levels of oxygen in their blood, and they are struggling to breathe. They look like patients with severe pneumonia caused by a virus. This is the type of lung trouble doctors are more used to seeing with respiratory diseases like influenza and SARS.

Gattinoni says doctors need to pay attention to how COVID-19 has affected the lungs and breathing of each patient they’re treating before deciding on treatment. Patients with more classic ARDS-type COVID-19 often need mechanical ventilation right away, which forces air into the lungs to increase oxygen.

Patients with respiratory failure who can still breathe OK, but have still have very low oxygen, may improve on oxygen alone, or on oxygen delivered through a lower pressure setting on a ventilator.

Gattinoni thinks the trouble for these patients may not be swelling and stiffening of their lung tissue, which is what happens when an infection causes pneumonia. Instead, he thinks the problem may lie in the intricate web of blood vessels in the lungs.

Normally, when lungs become damaged, the vessels that carry blood through the lungs so it can be re-oxygenated constrict, or close down, so blood can be shunted away from the area that’s damaged to an area that’s still working properly. This protects the body from a drop in oxygen.

Gattinoni thinks some COVID-19 patients can’t do this anymore. So blood is still flowing to damaged parts of the lungs. People still feel like they’re taking good breaths, but their blood oxygen is dropping all the same.

This problem with the blood vessels is similar to what happens in a condition called high-altitude pulmonary edema, or HAPE, says Bull.

HAPE patients recover when you bring them down from a high altitude and give them oxygen. They are sometimes also placed on ventilators and treated with medicines including diuretics to remove fluid that’s flooded their lungs. More research is needed to know if any of those strategies may help COVID-19 patients. Steroids, in particular, have not been shown to help with ARDS and may make it worse.

“Is it possible that there’s a problem with how the blood vessels regulate blood flow? That is, I guess, a possibility, which would be different than what we usually see in ARDS,” Bull says.

“This is just a hypothesis at this point. It has to be proven,” he says.

It’s also important to note that patients with relatively normal-looking lungs can progress to ARDS as the virus attacks their lung tissue, Gattinoni says.

He says these patients with more normal-looking lungs, but low blood oxygen, may also be especially vulnerable to ventilator-associated lung injury, where pressure from the air that’s being forced into the lungs damages the thin air sacs that exchange oxygen with the blood.

In normal breathing, our lungs expand because of negative pressure. A large thin muscle at the bottom of the lungs, called the diaphragm, pulls down and our lungs expand to fill the increased space. But ventilators work by forcing air into the lungs, which is positive pressure, like what happens when you blow up a balloon. These machines can help people whose lungs have become too weak to work, but they can also cause damage because they force the lung to work in a way it wasn’t designed to.

“When those pressures get too high, you can cause trauma to those little air sacs. Those are very fragile,” says Michael Mohning, MD, a pulmonologist and critical care specialist at National Jewish Health in Denver.

Gattinoni says putting a patient like this on a ventilator under too high a pressure may cause lung damage that ultimately looks like ARDS.

So he cautions that doctors need to be aware of the COVID-19 patients’ symptoms  and need to use the ventilator carefully and sparingly.

In an interview with MDEdge, Gattinoni said one center in central Europe that had begun using different treatments for different types of COVID-19 patients had not seen any deaths among those patients in its intensive care unit. He said a nearby hospital that was treating all COVID-19 patients based on the same set of instructions had a 60% death rate in its ICU.

“This is a kind of disease in which you don’t have to follow the protocol — you have to follow the physiology,” Gattinoni said. “Unfortunately, many, many doctors around the world cannot think outside the protocol.”

Other experts agree.

“If you over-distend somebody’s lung on mechanical ventilation, you essentially generate more ARDS. You make the lung leaky,” Bull says.

He says pulmonologists have gotten much better at using ventilators to make them safer for patients. Doctors work to keep the pressure on the lung as low as possible, to prevent that damage.

Several recent studies have helped to cut the death rate for patients who need to be on a ventilator. The PROSEVA study, published in The New England Journal of Medicine, showed the death rate among ventilated patients could be as low as 16% under optimal care.

So far, death rates for ventilated patients with COVID-19 have been higher than that. That could be because some COVID-19 patients often need to be on ventilators for a long time, sometimes as long as 2 weeks. They also tend to have other conditions, so it’s possible that they are sicker to begin with. More research is needed to understand why, and doctors will continue to share best practices as they see things that need to be addressed.



Sources

Cameron Kyle-Sidell, MD, emergency room and critical care doctor, Maimonides Medical Center, Brooklyn, NY.

Todd Bull, MD, director, Center of Lungs and Breathing, University of Colorado School of Medicine, Aurora.

Michael Mohning, MD, pulmonologist and critical care specialist, National Jewish Health, Denver.

Intensive Care Medicine: “COVID-19 pneumonia: different respiratory treatment for different phenotypes?”

The New England Journal of Medicine: “Prone Positioning in Severe Acute Respiratory Distress Syndrome.”

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