US Food & Drug Administration Approves New Sedative Product For Emergency Use In Ventilated COVID-19 Patients; Doctors Question Remdesivir Eligibility Criteria
A bottle of 10ug/mL propofol, a sedative used for COVID-19 patients on mechanical ventilation

Amidst the global shortage of ventilators, personal protective equipment, and diagnostics; sedatives, used to keep severe COVID-19 patients who require invasive ventilation continuously sedated, are in increasingly short supply around the United States.

The US Food and Drug Administration (FDA) on Monday issued an emergency use authorization (EUA) for Fresenius Propoven 2% (propofol 20 mg/mL) Emulsion 100 mL to maintain sedation via continuous infusion in COVID-19 patients  who require mechanical ventilation in an intensive care unit (ICU) setting. The product is already approved for use in Europe, but only a lower concentration, propofol 10mg/mL drug Diprivan is approved for use in the US.

Sedating patients who are on mechanical ventilation is necessary to keep them calm while the machine supports their breathing, according to guidelines from the American Academy of Surgeons. Patients who are not sedated properly may experience physiological stress and panic, leading to struggling to rip their breathing tubes from their throats.

But continuous sedation is a delicate process, and even a slight miscalculation of anesthetics can lead to death. The US FDA warns multiple times that the higher concentration of propofol in the newly approved Fresenius Propoven Emulsion could lead to unintentional overdose. The product approved under the EUA is only to be used in patients 16 years of age or older, who are not pregnant.

Propofol is the most common drug used to sedate patients on mechanical ventilation, according to the Academy. However, COVID-19 patients require an unusually high level of sedation, and are often on a combination of drugs.

As such, other injectable anesthetic drugs such as ketamine, etomidate, dexmedetomidine, and others are also listed in the US FDA’s Drug Shortage database as facing “current shortages” due to “demand increase for the drug.”

Doctors Question Remdesivir Elligibility Criteria

In a parallel development, physicians are questioning the federal government’s system for doling out remdesivir. After the US FDA issued emergency use authorization for the drug on 1 May, hospitals receiving the government’s drug shipments claim that the limited quantities and unclear guidance still force doctors to make harsh decisions about who gets the treatment.

The US Health and Human Services began shipping the drug in limited quantities to 13 different states on 9 May, after finalizing an agreement with Gilead Sciences, remdesivir’s producer, to provide approximately 607,000 vials of the experimental drug over the next six weeks to treat an estimated 78,000 hospitalized COVID-19 patients.

But doctors are saying that the federal guidance for who should be getting the limited donations is too vague. According to the guidelines, anyone with a room-air blood oxygen level at or below 94% who requires supplemental oxygen is eligible to receive the drug. However, this broad categorization runs the gamut from patients who require just a little extra oxygen, all the way to heavily sedated patients on mechanical ventilation who rely almost entirely on the machine to breathe.

“It’s very broad,” Erin Fox, director of drug information and support services at the University of Utah Medical Center told STAT News. “If you have 20 patients but only two vials, how do you decide which two patients get those vials?”

The drug was granted emergency use authorization following the early termination of a National Institutes of Allergies and Infectious Diseases (NIAID) trial that found patients on remdesivir recovered on average 4 days faster than those who did not receive the drug. Anthony Fauci, leading coronavirus expert on the federal COVID-19 taskforce and director of the NIAID, showed high optimism for the drug’s potential after seeing preliminary trial results.

Image Credits: Flickr: Dustin Hackert.