COVID-19: Ventilators

A friend told me of this story: An older man contracted COVID-19 and became quite ill. As he became increasingly short of breath he despaired, because he knew that if he was placed on a ventilator he would die. Happily he was able to self rescue with breathing exercises he’d learned somewhere in his long life, ended up not needing a ventilator, and survived.

As a former surgeon who has taken care of thousands of patients on ventilators, listening to this tale caused my skepticism alarms to go off. How could the old guy know that his exercises were what saved him? And why was he so sure that a ventilator was a death sentence?

But, I got to thinking, just what is COVID-19 doing to people’s lungs? And just how much does a ventilator help? The answers alarmed me.

A little background: The living lung is a remarkable thing to see in the operating room. It’s soft and a beautiful shade of pink, it fills the entire chest, expanding and contracting with every breath delivered by the anesthesia machine. Amazingly, with slight pressure an entire lung can be gently squeezed until it exhales all it’s air, shrinking until it is small enough to fit in the palm of one hand- now a blue and apparently lifeless blob. But then, with a few quick breaths pushed into the lung by the anesthesia team, the lung springs back to normal size and shape and color, no worse for the wear. It’s amazing, really, just how tough the lung is.

“We’re not going to ventilate our way out of this problem.”

Surgeon General Jerome Adams

At the cellular level your lungs are still more amazing: a delicate mousse of air, blood, and lung tissue- an arrangement that allows air to come and go with every breath, and allows the blood to come into intimate contact with the air (within 0.2 micrometers (0.0000007 inches(!)). This close contact is essential, because it allows the blood to pick up oxygen and off load carbon dioxide into the lung’s air spaces. If this amazing arrangement is disturbed by, say, swelling of the thin layer of tissue that separates the air sacks from capillaries, well, you can’t get oxygen into your blood, and you die in short order.

So, how does COVID-19 fit into this picture? Well, the coronavirus selectively attaches to the ACE2 receptor, and because the air sacs of the lung (aveolae) are richly covered in ACE2 receptors, the coronavirus selectively attacks the lung. This is bad, because we don’t have an antiviral agent effective against the coronavirus- at least not yet.

With more established viruses, it’s not usually catastrophic because the body’s immune system can deal with viral attacks. Unfortunately, for reasons that we don’t yet understand, some people’s immune systems go over the top. In these people, the collateral damage to their lung tissue by their own immune system can be devastating. When the damage is so great that a patient’s lungs can’t keep up with the oxygen needs of their body, a ventilator can buy time through providing higher concentrations of oxygen, and bigger and faster breaths than a patient can muster on his/her own.

So, the ventilator can buy time, but time for what? In ordinary circumstances, the lung is damaged by some reversible insult- most commonly a bacterial infection. If bacteria are the problem, well, antibiotics are the solution. Once the infection is routed, the patient’s lung can heal and soon enough, the ventilator isn’t needed and can be removed.

Diagram source: Azuravesta Design

But if, as is sometimes the case in COVID-19 patients, the lung is subject to ongoing attack by the patient’s own immune system, the lung may never heal. The lung becomes a solid mass of tissue, with little air within it and scant air flow in and out, despite the ventilator’s maximal settings of oxygen concentration and pressure. Worse yet, by subjecting the lung to high oxygen concentrations and high pressures the lung is further injured, and the downward spiral of ARDS (Adult Respiratory Distress Syndrome) begins. In this scenario the ventilator is no longer prolonging life; it is simply prolonging death.

And here’s the thing: although good, data driven estimates are not yet available, it seems that the mortality for COVID-19 patients who require mechanical ventilation is very high- likely over 50%, and perhaps a good deal higher.

This is a lot more detail about the care of acute lung injury than anyone really needs, but here’s the point: by the time you’re on a ventilator it may be too late for a good outcome. The effort, discomfort, and substantial risk of an ICU admission are far better avoided than endured. Ventilators have been oversold as a solution, because the lung injury caused by COVID-19 often isn’t amenable to our usual tools of ICU care. Once you’re in the ICU, the die is cast. Far better to never find yourself in the ICU in the first

… but it only takes one drug to stop a pandemic.

Dr. Turner Osler

Hope?
A drug to treat COVID-19 before things get so grim would of course, make ventilators irrelevant. It turns out that many anti-RNA viral agents are available from earlier viral epidemics. Because these drugs have already been developed and in some cases even evaluated in clinical trials, the time to clinical deployment can be very quick.

Remdesivir is one such drug. Originally developed a decade ago, Remdesivir failed as treatment for hepatitis C, but worked better when it was repurposed as an anti-Ebola agent a few years later. Remdesivir seems to have hit its stride with COVID-19, however. Results leaked from the University of Chicago of a phase 3 trial have shown rapid improvement in almost all of 113 patients severely ill with COVID-19; only two patients died. So, a game changer? Maybe.

How does Remdesivir work? This molecule is an analog of a base that COVID-19 normally uses in the long chain of bases that is its RNA. That is, Remdesivir closely resembles a base that COVID-19 ordinarily uses in reproducing its DNA. Crucially, however, Remdesivir is different enough from the base that COVID-19’s assembly mechanism is expecting, that it gums up the machinery of RNA synthesis, abruptly halting viral RNA replication. No replication- end of infection. Very cool. And it only takes one effective drug to completely change the course of a pandemic.

Doctors on the frontline are aware of all this, of course. With no explicit treatment available, they have been repurposing drugs designed for other problems but which could plausibly help with the lung failure caused by COVID-19. For example, tolicizumab is a drug used by rheumatologists to tone down the immune systems of patients who are attacking their own joints. So, it makes sense that toning down the immune systems of COVID-19 patients could protect their lungs and possibly improve survival. The last three ventilated COVID-19 patients treated with tocilizumab at UVM have done well, so there’s some reason to be optimistic. But tocilizumab is still just a “definite maybe”: something that can be tried, but can’t be relied upon.

I write this in hopes of recasting the COVID-19 problem from: “We need more ventilators” to “We need scrupulous, and more uncompromising social distancing”. I’m dismayed by the amount of air time spent on counting ventilators, ordering ventilators, fighting over ventilators; ventilators, which in the end may not do much to change outcomes. Bandwidth and resources would be far better spent emphasizing and creatively explaining social distancing. Like this:

We humans generally prefer easy, after-the-fact fixes for problems: a treatment, a pill, a machine. However, it’s usually the less glamorous approach involving some simple behavioral tweak that’s more successful, and this is especially true for COVID-19.

So, “Do your part and stay apart”. Pass it on so you won’t pass it on.

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