Washington — With federal and state officials rushing to secure ventilators for patients battling COVID-19, the disease caused by the coronavirus, doctors and pharmacists are warning that the supply of drugs needed to place patients on those ventilators is also dwindling.
“The correlation is 1 to 1,” said Dan Kistner, group senior vice president of pharmacy solutions for Vizient, a company that serves more than half the nation’s hospitals and negotiates lower drug prices. “There is a demand for ventilators that we’ve never seen before, and thus you’re going to have the same pressure on the drugs that support ventilators.”
The coronavirus pandemic has led to a surge in the number of patients on ventilators as they battle the respiratory illness, which has claimed the lives of more than 14,500 people in the U.S, according to Johns Hopkins University. In addition to the ventilator machines themselves, patients need specific drugs when they’re intubated and once they’re on the device.
For patients diagnosed with COVID-19 who develop what’s called acute respiratory distress syndrome due to fluid in the lungs, anesthesiologists are brought in to administer intravenous anesthetic agents or sedatives, Dr. Ed Mariano, a professor at the Stanford University School of Medicine, told CBS News.
Once a patient is unconscious, doctors insert a breathing tube into the patient’s trachea while peering into the airway using a specialized instrument, a procedure that Mariano said can be “incredibly stimulating.” Once the airway is isolated, doctors or respiratory therapists connect the tubing to the ventilator itself.
The paralytic drugs prevent the patient from involuntarily coughing during the process and showering the anesthesiologist with viral particles. Shortages of the medicines used to subdue a patient can present urgent problems for health care workers on the front lines.
“For mechanically ventilated, critically ill patients, we use a lot of sedatives and analgesics, and we have guidelines that tell us what drug you would want to use first and what is the second option,” said Dr. Sandra Kane-Gill, a pharmacist on the executive committee for the Society of Critical Care Medicine. “For the substantial increase in demand and as this continues to move across the country, that demand is going to increase and there’s definitely an opportunity for shortage in those agents.”
In the face of a dwindling supply, the Department of Health and Human Services last week posted a request for information to identify manufacturers with the capability to rapidly produce “priority ICU medicines.”
“Ventilators are a critical life-saving medical countermeasure for patients experiencing respiratory failure,” the solicitation states. “The United States has a critical need to procure priority medicines for ventilated ICU patients in response to COVID-19.”
The list of more than two dozen “Tier 1” priority medicines includes propofol and morphine, while the “Tier 2” priorities include fentanyl, lorazepam and midazolam.
Data compiled and made public by Vizient showed that the demand for these medications has spiked while manufacturers struggle to fully fill orders.
According to its most recent data, demand for sedatives and anesthetics like propofol and midazolam grew 91% in March, while the fill rate dropped to a low of 48%. Demand for pain medicines, meanwhile, rose 79% last month and the fill rate fell to 71%, while demand for paralytics increased 105% in March and the fill rate fell to 37%, Vizient found.
“Without having these drugs, it’s like having a bunch of cars with no gas,” Kistner said. “What keeps pharmacy leaders up at night, what we think about is we don’t want to get to a situation where we have the ventilators we need — I’m not saying that’s easy or something we can guarantee — but you don’t have the drugs to support it. That’s our biggest fear.”
Contributing to the heightened demand is not only the volume of COVID-19 patients on ventilators who require sedatives and pain medicines, but the length of the time they are on the machines.
“The demand is much greater because of the prolonged use,” Mariano said. “So it’s not just that we have increased use, it’s continuous use, 24 hours a day for the time that patient is ventilated.”
The shortages have been felt more intensely in hospitals in New York City, the epicenter of the coronavirus outbreak, where they are quickly exhausting their supplies, said Dr. Michael Ganio, director of pharmacy practice and quality at the American Society of Health-System Pharmacists.
“They’re counting their supply hours to days, getting replenished just in time and using package sizes that aren’t very efficient,” he said.
There are alternatives that doctors can turn to for patients on mechanical ventilators requiring sedation and pain management, but they present their own challenges.
“They may include drugs we typically use for surgeries that are very short-acting, so it’s not ideal in an intensive care setting where you’re keeping someone sedated around the clock,” Ganio said. “We can keep going to the next line of agents, but we run into the challenges of what the side effects may be.”
Mariano said while there are second- and third-line medications, certain classes “have a deeper bench” than others.
“What ends up happening is you start to look beyond the first-choice agents,” he said of health care providers. “They knowingly have to use drugs that maybe they wouldn’t have necessarily chosen, and I do think that contributes to the sense of moral injury, you know the right thing to do and you can’t.”
The U.S. is no stranger to drug shortages, and groups like the American Society of Health-System Pharmacists have databases that track which drugs have dwindled in supply.
But Mariano said he fears drug shortages are going to be worse than seen before, especially because there are few manufacturers and demand for these medications is not concentrated in the U.S., but worldwide.
“It’s a different world right now in so many ways, but when it comes to our typical backup plans for supplying needed drugs, some of our alternatives may not be readily available,” he said.
Most of the pharmaceutical supply chain is a just-in-time inventory model, where providers and wholesalers keep a week or two of supplies on hand, Ganio said.
“That gets depleted in a situation like this,” he said. “This is unprecedented.”
To address looming shortages, Kane-Gill said there should be more transparency associated with the supply chain.
“Each pharmaceutical company knows where their good comes but the public doesn’t,” she said. “It would be nice if that information was more transparent.”