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Doctors push back on treating COVID-19 as HAPE


For Luanne Freer, MD, an expert in high-altitude pulmonary edema (HAPE) and founder and director of Everest ER, a nonprofit seasonal clinic at the Mt. Everest base camp in Nepal (elevation, 17,600 ft), a sudden flurry of messages and questions she received about a possible COVID-19/HAPE link was startling.

Dr. Luanne Freer is a HAPE expert and founder and director of Everest ER, a nonprofit seasonal clinic at the Mt. Everest base camp in Nepal. Courtesy Rowie Ververis

Dr. Luanne Freer

“That’s why it kind of poked me in the eye,” she said, referencing her extensive experience treating HAPE, which she described as a pressure-related phenomenon. “My goodness, they are so completely different.”

Dr. Freer, an emergency physician, reached out to several pulmonary intensivists with experience treating both HAPE and COVID-19 to gauge their reactions, and within 36 hours, they had drafted their response. In the commentary, published in High Altitude Medicine & Biology, the clinicians note that the comparison between HAPE and COVID-19 is potentially risky.

“As a group of physicians who have in some cases cared for patients with COVID-19 and in all cases cared for patients with HAPE and studied its pathophysiology and management, we feel it important to correct this misconception, as continued amplification of this message could have adverse effects on management of these patients,” they wrote.

The suggestion that COVID-19 lung injury sometimes looks more like HAPE than like acute respiratory distress syndrome (ARDS) appeared in a journal review article in late March and was put forth by medical professionals on social media where it gained traction in recent weeks and was amplified in multiple media outlets, including this one.

“With COVID, we don’t understand everything that’s going on, but we know for sure it’s an inflammatory process – not a pressure-related problem,” Dr. Freer said. “I thought ... this could be so dangerous to load the medicines that we use when we’re treating HAPE onto patients with COVID-19.”

The pathophysiological mechanisms in HAPE are different than those in other respiratory syndromes, including those associated with COVID-19, said Andrew M. Luks, MD, of the UW Medicine, Seattle, and the first author on the commentary.

“HAPE is a noncardiogenic form of pulmonary edema, as are ARDS due to bacteria or viral pneumonia, re-expansion pulmonary edema, immersion pulmonary edema, negative pressure pulmonary edema, and neurogenic pulmonary edema,” Dr. Luks, Dr. Freer, and colleagues wrote in the commentary, explaining that all of these entities cause varying degrees of hypoxemia and diffuse bilateral opacities on chest imaging. “Importantly, in all of these cases, edema accumulates in the interstitial and alveolar spaces of the lung as a result of imbalance in Starling forces.”

A difference between these entities, however, is “the mechanism by which that imbalance develops,” they noted.

The excessive and uneven hypoxic pulmonary vasoconstriction that leads to a marked increase in pulmonary artery pressure, subsequent lung overperfusion, increased pulmonary capillary hydrostatic pressure, and leakage of fluid from the vascular space into the alveolar space as seen in HAPE, is a “fundamentally different phenomenon than what is seen in COVID-19-related ARDS, which involves viral-mediated inflammatory responses as the primary pathophysiological mechanism,” they added.

The authors described several other differences between the conditions, ultimately noting that “understanding the distinction between the pathophysiological mechanisms of these entities is critical for patient management.”

In HAPE, supplemental oxygen alone may be sufficient; in COVID-19, it may improve hypoxemia but won’t resolve the underlying inflammation or injury, they explained, adding that “only good supportive care including mechanical ventilation, quite often for long periods of time, allows some patients to survive until their disease resolves.”

Further, HAPE can be prevented or treated with pulmonary vasodilators such a nifedipine or sildenafil, which decrease pulmonary artery pressure and, as a result lower pulmonary capillary hydrostatic pressure, they said.

Use of such medications for COVID-19 might decrease pulmonary artery pressure and improve right ventricular function in COVID-19, but “by releasing hypoxic pulmonary vasoconstriction and increasing perfusion to nonventilated regions of the lung, they could also worsen ventilation-perfusion mismatch” and thereby worsen hypoxemia, they explained, adding that the treatments can also cause or worsen hypotension.

Efforts to share observations and experience are important in medicine, but sometimes, as in this circumstance, “they get out there, spread around – like a brushfire almost – and get [unwarranted] face validity,” Dr. Luks said, noting that in response to information circulating about COVID-19 and HAPE, he has already heard medical professionals floating the idea of treating COVID-19 with treatments used for HAPE.

It’s true that some COVID-19 lung injury cases are behaving differently than typical ARDS, he said, adding that presentation can vary.

“But trying to equate HAPE and COVID-19 is just wrong,” he said. “HAPE and COVID-19 may share several features ...but those are features that are shared by a lot of different forms of respiratory failure.”

In a recent video interview, WebMD’s chief medical officer John Whyte, MD, spoke with a New York City physician trained in critical care and emergency medicine, Cameron Kyle-Sidell, MD, who raised the need to consider different respiratory protocols for COVID-19, noting that standard protocols were falling short in many cases.

“What we’re seeing ... is something unusual, it’s something that we are not used to,” Dr. Kyle-Sidell of Maimonides Medical Center said in that interview, stressing that the presentation differed from that seen in typical ARDS. “The patterns I was seeing did not make sense.”

Like others, he noted that COVID-19 patients were presenting with illness that clinically looked more like HAPE, but that the pathophysiology is not necessary similar to HAPE.

At around the same time, Luciano Gattinoni, MD, of the Medical University of Göttingen in Germany and colleagues, published a letter to the editor in the American Journal of Respiratory and Critical Care Medicine stressing that the ARDS presentation in COVID-19 patients is atypical and requires a patient physiology–driven treatment approach, rather than a standard protocol–driven approach. Dr. Gattinoni and colleagues suggested that instead of high positive end-expiratory pressure (PEEP), physicians should consider the lowest possible PEEP and gentle ventilation.

Dr. Luks agreed that “some patients with COVID-19 do not have the same physiologic derangements that we see in a lot of other people with ARDS.”

“[Dr. Gattinoni] is making the point that we need to treat these people differently ... and I think that’s a valid point, and honestly, that’s a point that applied even before COVID-19,” he said. “Most of the things that we see in clinical practice – there’s a lot of heterogeneity between patients, and you have to be prepared to tailor your therapy in light of the differences that you’re picking up from your observations at the bedside and other data that you’re getting on the patient.”

The main concern Dr. Luks and his coauthors wanted to convey, they said, is making sure that the anecdotal experiences and observations of clinicians struggling to find answers don’t spiral out of control without proper vetting, thereby leading to patient harm.

“In this challenging time, we must identify the best means to care for these critically ill patients. That approach should be grounded in sound pulmonary physiology, clinical experience and, when available, evidence from clinical studies,” they concluded.

Dr. Luks and Dr. Freer reported having no financial disclosures.

[email protected]

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