Hello and welcome to Careviser, the weekly newsletter that cuts through the healthcare noise with a single focus: productization of the latest research and tech breakthroughs.
Have you ever been in an ICU? Have you ever heard the noise from all the machines and alerts, all the devices? It was not always this way. This week, we take a step back and explore the birth of the modern intensive care unit.
The Reign of the Ventilator: Acute Respiratory Distress Syndrome, COVID-19, and Technological Imperatives in Intensive Care, Yvan Prkachin, PhD, Annals of Internal Medicine
🗝️ Why it matters: when the covid-19 pandemic started, emergency department physicians and critical care physicians disagreed about whether covid-19 patients suffered from acute respiratory distress syndrome and thus needed to be put on a ventilator. Ventilators were in short supply making the need to allocate the right resources to a rising number of covid-19 patients even more urgent.
🔎 The story: Acute respiratory distress syndrome was born with modern intensive care and ventilators. It shows how new technologies (here ventilators) frame medical thinking.
It all started with a polio epidemic in Copenhagen in 1952. Patients experienced severe respiratory complications. A local anesthetist, Björn Ibsen, adapted a positive pressure procedure from surgical anesthesia. They ventilated patients using a bag that they manually squeezed through an opening in the trachea. They also brought together all critically-ill patients in the same unit. The modern ICU was born.
The Copenhagen ICU only relied on manual ventilation, however as its ICU organization started to be replicated in the following two decades, these included mechanical ventilators.
In 1967, an American physician, Thomas L. Petty, pioneered a new way of using ventilators. He used them for patients suffering from chronic obstructive pulmonary disease. Instead of using them temporarily, he would ventilate patients for lengthy periods of time while monitoring their blood gases in real time. However, as he treated patients who didn’t have pulmonary disorders but still required ventilation (e.g., a car accident patient), they found out that the common ventilators would not work. They found an older ventilator that could
“deliver ventilation at higher pressure and could maintain that pressure even when the patient exhaled—a procedure Petty and Ashbaugh eventually christened positive end-expiratory pressure (PEEP)”
When they autopsied the lungs of these patients, they had heavy lungs that had grown more and more resistant to ventilation over time. They called this disease:”Acute Respiratory Distress in Adults” and spread the word that positive end-expiratory pressure was the way to treat them.
So acute respiratory distress syndrome became a condition that could only be found in ICUs and needed to be treated with a specific type of ventilation (PEEP). In a way, acute respiratory distress syndrome was both a diagnosis and a cure in itself.
However, there was no evidence that PEEP led to better survival chances of patients, or that it was the only way to treat patients. PEEP itself seemed to create new types of injuries (ventilator-induced lung injury). As PEEP was now accepted as the new standard of care, it was ethically challenging to launch clinical studies to prove whether it worked or not, because it meant not giving the gold standard treatment to critically ill patients.
A study presented in 2000 found that aggressive ventilation used with PEEP was actually detrimental and recommended reduced ventilatory pressure. A new definition in 2012 defined a new rating of Acute Respiratory Distress Syndrome (mild, moderate, or severe) and tied a minimal level of PEEP to confirm the diagnosis. So more than ever the diagnosis depended on the machine.
🚀 Opportunities ahead: In a nutshell, the use of ventilators created a new type of disease that had to be cured by...ventilators. Measuring patient’s metrics through machines makes providers assess patients differently. The author claims that this sometimes blurs the picture and does not leave enough room for creativity.
Exvastat launched 2016 in Cambridge, UK with the objective to be the first company to develop pharmacotherapy for acute respiratory distress syndrome.
🤯 The problem: It is hard to administer drugs to patients suffering from acute respiratory distress syndrome. They are sometimes in a coma so they cannot swallow pills or digest them.
🤗 The solution: Exvastat is developing a formulation that can be delivered intravenously. It inhibits vascular leaks reducing mortality and morbidities. It’s a formulation of an existing oral drug, imatinib, used for leukemia. Repurposed drugs are highly attractive because their cost and risk profile are lower than new drugs as long as the IP stuff is sorted out. Human safety data is already available. We also know how to manufacture and control them.
📈 The traction: The pool size of patients suffering from acute respiratory distress syndrome has increased with covid-19. That’s how they were able to recruit hundreds of patients for two phase II clinical trials this year. Following these phases, they should be approved for compassionate use, and start a phase III. They raised a round of funding from Cambridge Innovation Capital this summer and received a €3.6m grant from the EU.
That’s a wrap for today! Don’t hesitate to reply to this email with comments, I read and answer all emails :)
Marie