A shortage of painkillers and sedatives for COVID-19 patients struggling to breathe is causing concerned hospital groups to seek changes to increase the supply of these drugs.
Patients with more severe cases of the viral respiratory illness may require ventilators, which are machines that help with breathing. But the process of inserting a plastic tube into a patient’s airway is painful and requires pain medicine and sedation.
Beverly Philip, the president-elect of the American Society of Anesthesiologists, said patients in the ICU that use a breathing tube for a ventilator often need medicines to help relax or ease pain, as well as muscle relaxants to help their bodies accept the ventilator.
“These are part of routine needs in the intensive care unit,” she said.
Drugs such as morphine, hydromorphone and the synthetic opioid fentanyl are used to relax COVID-19 patients. Cisatracurium, a commonly used muscle relaxant, and general anesthesia drugs like propofol are often in short supply. Many patients need a combination of these drugs.
“Although elective surgeries are dramatically down, the fact that you have to ventilate patients with COVID for sometimes as little as five to seven days, but sometimes for two weeks or longer, means that the total amount of drugs necessary would be greater than a hospital normally uses,” said Lee Fleisher, chairman of the Department of Anesthesiology and Critical Care at the University of Pennsylvania Health System, who has observed the shortages.
The Food and Drug Administration is working with the manufacturers of drugs such as fentanyl and morphine “on anything that can be done to increase supplies,” said Nathan Arnold, an agency spokesperson.
A spokeswoman for AbbVie, which makes Nimbex, a brand of cisatracurium, said the company “is working closely with the FDA on potential solutions to address the temporary shortage and is working in parallel to accelerate supply where possible.” The drugmaker has seen a significant spike in demand for the drug for ventilator-assisted treatments, spokeswoman Adelle Infante said.
Diprivan, a brand of propofol, is manufactured by Fresenius Kabi in Europe, and the company said the plants are running at maximum capacity.
Spokesman Matthew Kuhn said the European plants are “responding as best as possible to the recent, significant increase in demand” with continued regular shipments to North America, adding that the company is working with the Department of Health and Human Services, the FDA and the Federal Emergency Management Agency. “We are aware that hospitals are evaluating propofol-sparing protocols and alternative medicines, and we are fully committed to adjusting manufacturing schedules to help.”
The American Hospital Association has called the issue a major concern and is pushing for additional flexibility for compounding pharmacies and outsourcing facilities to make and distribute these drugs.
Philip said the ASA and others recently convinced the federal Drug Enforcement Administration to start addressing the shortage in another way: by increasing limits on certain drugs sold to hospitals, such as some potentially addictive painkillers. Earlier this month, the DEA raised the quotas for hospitals on fentanyl, morphine, hydromorphone, codeine, ephedrine, pseudoephedrine and other drugs by 15 percent.
Health care consulting company Premier Inc., which serves an alliance of 4,000 U.S. hospitals, cautioned that even with the increase in quotas, the finished products are not likely to enter the marketplace until May or June.
Data from Premier shared with CQ Roll Call showed that the use of propofol as a first-line sedative increased over 300 percent from 2019 to 2020. Demand is expected to increase as elective surgeries begin to resume.
The shortages of these drugs can be found nationwide, but hospitals in “hot spot” areas for the virus reported more difficulties.
The New Jersey Hospital Association told CQ Roll Call that the three drugs it is seeing shortages of are fentanyl, propofol and cisatracurium.
Nationally, the picture is similar.
“The most concerning shortages involved drugs used in intensive care units for patients on ventilators,” said Michael Ganio, senior director of pharmacy practice and quality at the American Society of Health-System Pharmacists. “For pain and sedation, that includes fentanyl, midazolam, propofol, ketamine, and dexmedetomidine.”
In an April survey of ASHP members, respondents whose ICUs are at least half full of COVID-19 patients reported several drugs with unusually low levels of inventory.
Twenty percent of those surveyed who met those conditions had less than a one-day supply of cisatracurium on hand, and 55 percent had less than a seven-day supply.
Those health system pharmacists and other survey respondents said vecuronium, a general anesthesia drug used for mechanical ventilation, was also scarce, with 8 percent of those respondents having less than a one-day supply and 40 percent less than a week’s supply.
Less than a day’s supply of fentanyl was available for 9 percent of respondents, and 63 percent had less than a week’s supply. Ketamine, used in anesthesia, was down to less than a day’s supply for 8 percent of respondents and less than a seven-day supply for 46 percent.
The shortages of these drugs doesn’t stem from COVID-19 alone, experts said. Many drugs were already in short supply because of slim profit margins and quotas, making this a convergence of two different problems.
Philip said the supply chain for these drugs is fragile because the drugs are cheap and the market has consolidated in recent years. The active pharmaceutical ingredients are also often sourced from India or China, where shipments were disrupted.
“The drugs that are in shortage are sterile, injectable drugs [and] generics,” she said.
Providers working in hospitals that are running low on necessary drugs have often started using alternatives, which they say are still effective.
“I want to emphasize these second-choice drugs, they are not bad,” Philip said. “You have a first choice because it has what we think is the most favorable balance of doing things well and doing less of what we don’t want done. These other drugs have a slightly different balance of side effects.”
Most commonly, this involves administering a pill instead of an injectable form of a drug. For patients on ventilators, the pill would be delivered down a nasogastric tube from the nostril to the stomach. Medical providers could also switch to a similar type of drug.
Fleisher said that as long as adjustments are made when administering these drugs, this can work in the interim.
He said the University of Pennsylvania Health System planned ahead and is using an oral version of fentanyl midazolam initially, then converting to an injectable version as a way to ration the drugs.
“We have had a moderate surge in patients, but we are able to strategically look at how to conserve the drugs that we need for the acute period and go into different strategies during surgery, the prolonged phase of patients on ventilators, and how do we manage them differently after the acute phase,” he said. “We’ve been able to adapt. And part of this is, ‘Will we continue to adapt as we restart surgery?’ is really the key question.”