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Our generation of physicians prides itself on the practice of evidence-based medicine. Ideally, this means making medical decisions based on peer-reviewed clinical studies and randomized, controlled clinical trials. It means getting away from the “this-is-the-way-you-do-it-because-this-is-the-way-we’ve-always-done-it” approach to medicine to ensure that patients get the best known treatment for any given medical condition.
But what happens when you face a disease and there are no peer-reviewed publications and randomized controlled clinical trials? In that situation, physicians’ definition of what constitutes evidence can vary considerably. Thus enters dogma and nowhere in recent memory has there been a greater pandemic of dogma than in our intensive care units managing patients with COVID-19. As critical care physicians, we hold our convictions about how to best treat patients with COVID-19 respiratory failure more tightly than we hold religious convictions or political convictions. And given that many of these convictions are diametrically opposed, we can’t all be right. Forty years ago, in my first week of medical school, one of the professors told me that 50% of everything I was about to learn was going to ultimately be proven to be wrong. I think those words could be just as easily applied to our approach to managing patients with COVID-19 in the ICU today.
To Ventilate or Not To Ventilate?
That is the question… or is it? For decades, we have defined patients as having ARDS (acute respiratory distress syndrome) if they have acute onset of diffuse pulmonary infiltrates with severe hypoxemia in the absence of heart failure and in the presence of something known to cause non-cardiogenic pulmonary edema, such as infection. And ever since 1967 when surgeon David Ashbaugh and pulmonologist Tom Petty first described the ARDS in the medical literature, it has been well-accepted that mechanical ventilation with PEEP (positive end-expiratory pressure) is the first line treatment.
But in the era of COVID-19, we read on-line news articles about a hospital in New York that reported 88% of their patients placed on mechanical ventilators died. And then all of a sudden, some critical care physicians are having second thoughts about intubating COVID-19 patients in respiratory failure and instead letting them be hypoxic. On the other hand, we read a blog post from a physician in Europe that he observed hospitalized COVID-19 patients develop sudden severe hypoxemia and go from needing 4 L oxygen by nasal cannula to having respiratory arrest despite 100% oxygen by face mask in just 30 minutes. And all of a sudden, some critical care physicians are intubating every COVID-19 patients who needs 4 L oxygen by nasal cannula.
Maybe COVID-19 really is different from ARDS from any other infection. But until someone proves that, I know that mechanical ventilation can bridge patients through life-threatening ARDS until time heals the lungs, that PEEP helps, and that low tidal volume ventilation is better than high tidal volume ventilation. We should not throw out everything that we’ve learned about the management of ARDS over the past 53 years because of a blog post.
Steroids Yes or Steroids No?
Over the past 35 years, the steroid pendulum has swung back and forth several times with respect to treating ARDS. First, studies showed steroids were beneficial, then studies showed they were not beneficial, and now studies again suggest they might be beneficial again. Similarly, you can find studies that show steroids improve the mortality rate of other coronaviruses and influenza; you can also find that steroids have no effect on the mortality rate of viral pneumonia. Some critical care physicians believe that steroids are the cure to the “cytokine storm” attendant to COVID-19 respiratory failure. Other critical care physicians believe that steroids paralyze the body’s immune defenses against COVID-19 resulting in increased viral replication. Our resident and fellow trainees are often caught in the middle, hearing that “You’re going to kill your patients if you don’t give then steroids” from one critical care attending physician on Monday and then hearing “You’re going to kill your patients if you give them steroids” from another critical care attending physician on Tuesday.
A non-randomized, non-placebo-controlled study from France suggested that 20 COVID-19 patients who got anti-malaria drug hydroxycholorquine had lower levels of detectable virus than patients previously published in the literature. This made immediate news in the lay press and the U.S. President called the drug a “game changer”. Within 3 days, pharmacies all across the country were sold out of hydroxychlorquine and I had patients calling in and asking me to prescribe it for them to prevent getting COVID-19 infection. Physicians throughout the world began prescribing it for any of their patients sick enough to be admitted to the intensive care unit. But then other studies showed that patients who received hydroxychloroquine actually did worse than those did not receive it because of potential fatal heart rhythm disturbances brought on by hydroxychloroquine. Once again, you’ll find critical care physicians who think it is the standard of care and others who think that it is nonsense.
Patients with COIVD-19 have high levels of the cytokine, IL-6. This occurs during the “cytokine storm” that these patients can get when their macrophages and monocytes produce enormous quantities of pro-inflammatory cytokines. This is also called the “macrophage activation syndrome”. Tocilizumab is an inhibitor of IL-6 and so some physicians believe that by inhibiting IL-6, the cytokine storm can be attenuated. It is one of those “makes sense, no data” treatments that might make patients better, might not do anything at all, or might actually make them worse. But in the absence of randomized, placebo-controlled clinical trials, you can find critical care physicians who are staunch proponents and others who are staunch opponents.
And Everything Else?
Across the United States, there are some critical care physicians who believe that because D-dimer levels are high, that anticoagulation helps by preventing clotting; other critical care physicians thing that empiric anticoagulation just makes patients bleed more. Some physicians believe that inhaled vasodilators such as nitric oxide or epoprostenol improve oxygenation in COVID-19 patients by redirecting blood flow to less affected parts of the lungs; other physicians believe that these drugs can cause patients to become hypotensive and develop cardiac arrest. Other treatments that might or might not work include transfusion of plasma from patients who recover from COVID-19 infection, the anti-viral drug lopinavir/ritonavir, another anti-viral drug remdesivir, and the complement inhibitor eculizumab.
As humans, for thousands of years we have sought ways to control nature. And we base a lot of our attempts at control on anecdotal experience that leads to superstition. For example, a child falls into a volcano and the next day it rains so the village starts throwing lots of children into the volcano the next year when there is a drought. As physicians, we are no different. We see or hear about a patient who got one treatment or another and got better and then that one patient or small group of patients becomes the evidence that we base our practice on when there is a vacuum of randomized, placebo-controlled clinical trials. COVID-19 has overtaken the world suddenly, too fast for science to give us direction about how to best treat patients and so we fall back on medical superstition. Some of those superstitions will ultimately be proven to be right and others will ultimately be proven to be wrong.
So, all of a sudden, what constitutes evidence in evidence-based medicine today is a lot different than what constituted evidence last year.
April 25, 2020