WASHINGTON (NYTIMES) - Across the United States, as hospitals confront a harrowing surge in coronavirus cases, they are also beginning to report shortages of critical medications - especially those desperately needed to ease the disease's assault on patients' respiratory systems.
The most commonly reported shortages include drugs that are used to keep patients' airways open, antibiotics, antivirals and sedatives. They are all part of a standard cocktail of medications that help patients on mechanical ventilators, control secondary lung infections, reduce fevers, manage pain and resuscitate those who go into cardiac arrest.
Demand for these drugs significantly increased in March as the pandemic took hold in the United States.
Orders for antibiotics like azithromycin and antiviral medicines like ribavirin nearly tripled. Medicines used for sedation and pain management, including fentanyl, midazolam and propofol, increased by 100 per cent, 70 per cent and 60 per cent respectively.
Demand for albuterol, a common asthma inhaler medication, has also risen significantly, given its importance in easing the breathing of patients with severe infection.
At the same time, the rate at which these prescriptions are filled and shipped to hospitals has dropped considerably, down by half to more than three-fourths in the past month, according to data collected by Premier Inc., a health care improvement company that provides group purchasing, analytics, consulting and various services to more than 4,000 hospitals and approximately 175,000 other providers in the United States.
"Just like we're seeing shortages of other materials, like masks and ventilators, medications are right there in the mix of things that we don't always have enough of on hand," said Erin Fox, a drug shortage expert at the University of Utah.
"So we were not prepared for this kind of surge."
Hospitals in particular are feeling the pinch in supplies. In a recent survey of 377 hospitals and 100 long-term care, home infusion and retail pharmacies, Premier found that drug shortages were pervasive in acute care settings, where 70 per cent of respondents reported at least one shortage for coronavirus drugs.
Among long-term care facilities, home care settings and retail pharmacies, 48 per cent reported shortages.
Demand is even higher in coronavirus hot spots like New York, California and Washington. And with the peak in cases and resource use still projected to be several weeks away, the run on these drugs only highlights weaknesses in the current supply chain.
"The pharmaceutical supply chain is one of just-in-time production," Fox said.
"Manufacturers tend to make just enough product, and they forecast out their manufacturing cycles based on how much they sold in the past. Nobody expects to sell, you know, 10 times the amount of something, and so nobody has that on hand."
Even before this crisis emerged, the Food and Drug Administration noted shortages of well more than 100 drugs in the United States. And factory shutdowns in China, India and other countries may have exacerbated the shortage of some ingredients and generic drugs during the pandemic.
"Out of 21 antibiotics that would be critical for treating secondary infections in Covid-19 patients, 18 antibiotics have greater than 80 per cent of their supply coming out of either China, India or Italy - all places that have had production disruptions," said Stephen Schondelmeyer, a professor at the University of Minnesota's College of Pharmacy who is a co-leader of the Resilient Drug Supply Project, which aims to provide a detailed map of the supply chain for important drugs used in the United States.
The US government could provide incentives to drug manufacturers to increase domestic production to solve some of the supply problems. But ramping up production may take two to three months and would not be able to fill immediate gaps, Schondelmeyer said.
"It's not a process where we could have the tablets next Friday," he said.
Increasing production is also dependent on quotas for controlled substances and ingredients that are set by the Drug Enforcement Administration.
On Tuesday (March 31), the American Hospital Association and four other medical groups sent a letter requesting that the DEA temporarily increase quotas to add flexibility for domestic manufacturing, but the agency has not done so yet, Fox said.
Hospitals have to start looking for alternatives that work almost as well as the current standard treatments.
"Many places are already shifting to using medications that we tried to avoid," said Dr Lewis J. Kaplan, president of the Society of Critical Care Medicine, a nonprofit involved in research and advocacy for patients.
"We had cut down tremendously on the amount of benzodiazepines, which you may be familiar with as Ativan or Valium, because they may induce delirium, especially in people who are having trouble sleeping. But we're now using those medications where our standard sedatives are running low."
Some hospitals are purchasing alternative antibiotics, crushing up pills instead of using IV fluids, and reducing nonessential surgeries and treatments to prioritize patients with coronavirus infections, Kaplan said.
"There isn't a hard-and-fast rule," he said. "It is, what do I have? Can this work for this patient? And do I need to ask someone about whether or not the drugs that are mixing are reasonably safe?"
One change that has further strained drug supplies is a switch to buying albuterol inhalers for individual patients rather than using nebulisers, a shift that doctors hope will decrease the spread of the virus through the air. But that move heightens the problem of depleting supplies for people with asthma and chronic obstructive pulmonary disease, who routinely rely on the inhalers and have been encouraged to buy 90-day supplies of their medicine.
"In general, that's good advice up front," Schondelmeyer said. "But with drugs like albuterol, we're not going to be able to sustain that because we're already on short supply."
Kelley Dougherty, a spokeswoman for Teva Pharmaceuticals, one of the drugmakers that manufactures albuterol inhalers, said the company was facing unprecedented demand but did not have any supply chain issues at the moment.
"Overall, our supply chain supporting our key products, brand and generics and API remains largely uninterrupted," she said, referring to active pharmaceutical ingredients. She added that the company was "producing as much albuterol as possible as quickly as possible."
Pharmacy benefit managers, such as CVS Caremark, are also trying to balance the growing interest in prescription medications for the coronavirus response with the needs of patients who take them for chronic conditions like asthma, HIV, rheumatoid arthritis and lupus.
"Our goal is to limit stockpiling of medication that could result in future shortages and gaps in care," said Mike DeAngelis, a spokesman for CVS.
Retail pharmacies are following state dispensing guidelines, and limiting the dispensing for coronavirus treatments to a 10-day supply in states without set recommendations, DeAngelis said. People who already take these medications for approved uses will be able to bypass any new quantity limits agreed to by their plan sponsor.
Experts still advise that patients avoid hoarding medications because the regional shortages could soon turn into national shortages as coronavirus infections continue to spread.