Propofol, Fentanyl in high demand as COVID-19 has yet to peak in Wisconsin
During a pandemic that leaves the hardest hit patients in respiratory failure and in need of a ventilator in order to breath, the drugs required to keep them comfortable and sedated are dwindling in supply.
Pharmacists in Wisconsin are now increasingly concerned that cases worldwide and larger outbreaks in places like New York are creating a shortage of propofol, midazolam and fentanyl at a time when the outbreak has yet to peak in Wisconsin.
“On any given day there are 150-200 drugs that are hard to get in the United States, and those drugs are among them,” said Philip Trapskin, chair of the state’s Pharmacy Examining Board and the program director for medication use strategy and innovation with UW Health in Madison. “The shortage of these drugs is the other shoe that is about to drop.”
Even prior to the COVID-19 pandemic reaching the United States the drugs used to treat ventilated patients were in short supply, according to the American Society of Hospital Pharmacists.
Now the number of patients suffering from the same virus and requiring the same medications at the same time is straining a drug supply chain that was already struggling to meet demand.
Nationally, roughly 427,469 people have contracted the coronavirus and 14,696 have died, according to the Centers for Disease Control and Prevention. In Wisconsin, 2,885 people have contracted the virus and 113 have died, according to state and county health departments.
According to the organization, 166 drugs were in short supply in 2019, with nearly 40 percent of those drugs in the “injectables” category. This includes drugs like propofol, midazolam and fentanyl that are administered to patients through intravenous lines rather than in a pill form when they are connected to a ventilator.
Patients are connected to a ventilator – a device that mimics the actions their lungs should be capable of making on their own – by inserting a tube through the vocal cords and into the lungs after they are sedated.
It is a painful, panic-inducing experience for many patients. It is not uncommon for patients to have to be physically restrained to prevent them from trying to remove the tube on their own due to the pain and discomfort they are experiencing.
Sedatives like propofol or midazolam keep patients’ limbs lifeless. Pain is treated with fentanyl. It is the nurse’s job to constantly assess the proper dose of each to keep the patient calm and comfortable.
“It’s not like you can be on a ventilator without a paralytic,” Trapskin said. “It is uncomfortable. It is irritating. You have a plastic tube in your throat.”
Trapskin estimates that for each patient on a ventilator, 5,000 to 7,000 milligrams of propofol are needed per day. There are currently roughly 440 people hospitalized statewide due to the coronavirus, with 196 of them on a ventilator, according to the Wisconsin Hospital Association.
Multiply the number of Wisconsin’s ventilated patients by the number of patients on ventilators across the country and it is easy to understand why he is concerned.
“The world does not keep that quantity of medications around,” he said. “Yes, I am absolutely concerned.”
He said reports from New York show the amount of drugs increased fivefold when the surge hit, there.
“Obviously our surge will not be as large but we are trying to plan for that five-fold increase,” Trapskin said. “We have the supply on hand to treat the patients we have now, but we are trying to plan for that unknown and everyone is doing this at the same time. It is creating a spike in demand that the supply chain is not ready to handle.”
UWHealth, which includes UW Hospital, American Family Children’s Hospital, UnityPoint Meriter and numerous other hospitals and clinical locations, a majority of which are in Dane County, is one of the largest healthcare systems in the state.
As of Thursday, 310 people have tested positive for the virus and 11 have died due to the virus, according to the Dane County Health Department. Many of the patients have been hospitalized within the UWHealth system.
Tim Olsen, a spokesperson for Froedtert West Bend Hospital, said securing sufficient resources to care for patients remains a top priority, including for the pharmacy.
“Our pharmacy supplies vary day to day due to national medication demands that have affected health care providers everywhere,” said Olsen in a statement. “Thanks to mitigation strategies to find alternative medications, secure additional products through our supply channels, and adjust clinical practice guidelines when needed, we have been able to continue to meet our patients’ needs.”
Froedtert Hospital is locally in an area of the state hit hardest by the virus. On Thursday, Milwaukee County had 1,500 confirmed COVID-19 cases and 67 deaths, the most in the state, according to the Milwaukee County Health Department.
Vizient is the nation’s largest member-driven healthcare performance improvement company. Based in Texas, it provides group purchasing services for hospital systems, including UW Health.
On Tuesday, it released a report detailing the increasing demand and decreasing fill rate for drugs vital to treating ventilated patients.
According to the report, the demand for lorazepam, midazolam and propofol has increased by 91 percent in March for Vizient member hospitals across the nation. The fill rate, or how much of an order a hospital actually receives from their pharmaceutical distributor, dropped to 48 percent.
The demand for analgesics like hydromorphone, fentanyl and morphine to relieve pain increased by 79 percent, with the fill rate dropping to 71 percent, according to the report.
Steven Lucio, Vizient’s vice president of pharmacy solutions, said in an interview Thursday, that with some drugs like blood pressure medications there are numerous options available for physicians and pharmacists to choose from when treating patients.
That is not the case when it comes to the medications needed to keep ventilated patients remain calm and sedated.
“If you are on a ventilator and you don’t have fentanyl, you are really putting physicians, nurses and pharmacists in a tough position,” Lucio said. “And what is the impact, the outcomes for the patient? That is the most important thing.”
He said it is not possible to quickly increase the supply of injectable medications, either. To comply with federal regulations, drugs in this class require a 21-day waiting period to ensure they are sterile before being available for distribution to hospitals. In addition, the three-week turnaround time assumes the manufacturer has the raw materials and extra manufacturing capacity.
The opioid epidemic is also playing a role in the ability to ramp up production of pain medications. However, Lucio said the company has been working with the Drug Enforcement Administration and on Tuesday it announced it was increasing the systemwide quota for the production of fentanyl, hydromorphone and morphine by 15 percent.
He said the DEA and the U.S. Food and Drug Administration have been receptive to feedback and are “trying their best to address the hurdles to needed medications.”
Transparency, in terms of where drugs are being manufactured and where the raw materials are coming from, is also an issue.
The company is urging the Trump Administration to take steps to expand access to medications associated with ventilator use and is recommending the FDA work with entities like FEMA, the Drug Enforcement Administration and Centers for Disease Control and Prevention, wholesale distributors and hospitals to identify allocation strategies that better match current and future demands as COVID-19 spreads across the country.
“There is not one single clog in the system,” Lucio said. “The healthcare system, whether it’s ventilators, personal protective equipment or drugs, is not built to handle this unprecedented level of surge in demand. It takes a lot of effort to turn things on a dime and ramp up production.”
Jill Michaud is the pharmacy director for Aspirus Wausau Hospital. In that role, she is tasked with monitoring the supply of medications for the 10 hospital system that includes the system’s largest, the 250-bed hospital in Wausau, and nine community hospitals in north-central Wisconsin and Michigan’s upper peninsula.
Michaud said the hospital’s supply of propofol is sufficient for its current number of patients. In stock, the hospital has enough for a 20 to 30 percent increase in need, “and that is with our allocation,” Michaud said.
This allocation of medicine, especially for drugs needed for ventilated patients, is higher for larger hospitals as they are equipped with more intensive care units and capable of treating higher acuity patients than smaller, community hospitals.
“When the allocation stops is when the creativity kicks in,” she said.
For example, if propofol is in short supply, a pharmacist would start pairing a pain reliever with a drug like midazolam. In New York, doctors and pharmacists are being forced to treat ventilated patients with third- and fourth-line pain agents.
“They are using oral agents and pain patches because they are running out of IV medications,” Trapskin said.
She said the system has treated a few COVID-19 patients, yet still comparatively lower than other areas of the state.
Marathon County, where the Wausau Hospital is located, has 12 confirmed cases and no deaths, according to the state Department of Health Services.
Michaud said to ensure all resources reach patients, the pharmacy management teams meet at least three times a week. They discuss whether it is necessary to share drug supplies or staff. So far, they have not needed to move staff, she said.
She said her hope is the curve flats in Wisconsin before infecting people further up north.
“It is almost like watching the hurricane swirl toward the coast. You know it’s coming and then comes the moment you realize it’s here,” she said. “Being on the tail end of this pandemic is a good thing for us. We can learn from other communities. But from a drug supply standpoint it’s probably not such a good thing.”