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First it was a critical shortage of personal protective equipment. Then pleas for more ventilators to sustain patients with COVID-19 and providers to care for them. Now, multiple sources are reporting deepening shortages of the drugs needed to help ventilate patients and keep them sedated.

Shortages are already evident for albuterol; neuromuscular blockers and sedatives, including fentanyl, midazolam, and propofol; and vasopressors for septic shock, even as orders increase exponentially.

The rates at which hospitals traditionally had been able to fill orders for ventilator-associated drugs was 95%, Dan Kistner, PharmD, told Medscape Medical News.

"These classes of drugs have dropped to 60 or 70% in the last month alone," said Kistner, senior vice president for pharmacy solutions at Vizient, a group purchasing organization that negotiates medicine contracts for about 3000 hospitals and healthcare facilities in the US.

"Every day it's dropping 2 or 3 additional percent," he continued.

Demand "Unprecedented"

The demand is simply "unprecedented," he said, adding that the shortages are piling up even after elective surgeries have been put on hold.

A California nurse's tweet in a nationwide thread of tweets under #WeNeedMeds poignantly described the consequences of severe shortages of some of these drugs. "Please do not put me on a vent if you can't keep me sedated," she writes. "I understand the alternative is death."

https://twitter.com/drannamvaldez/status/1245208738530611201

Esther Choo, MD, MPH, an emergency physician at Oregon Health & Science University in Portland, tweeted: "Those ventilators can't really be used without a similarly vast supply of coupled medications to get people *on* the vents — and keep them on humanely. Hospitals are already experiencing shortages, before we even hit disease apex."

https://twitter.com/choo_ek/status/1245192984582217728

15 Drugs at or Near Short Supply

Healthcare improvement company Premier, based in Charlotte, North Carolina, this week released a report that found 15 drugs used for COVID-19 care are in shortage or close to being in short supply at the same time demand is skyrocketing, particularly in New York.

Their data differ slightly from Vizient's but still show increasing numbers of orders going unfilled.

Among the drugs are several that are key for ventilating patients and keeping airways open.

Premier's data for albuterol, for example — which is also listed as "currently in shortage" on the US Food and Drug Administration's website — show that orders increased nationally by 53% in March and now only 80% of orders are able to be filled. In New York, albuterol orders increased this month by 1870%, according to Premier's data.

Similarly, orders for fentanyl doubled nationally in March and were up 533% in New York for the month. Only 61% of orders are now being filled, Premier reports.

Table. State of Ventilator Drug Shortages

Drug Indication % Order Increase (March) Current fill rate % Order Increase in NY (March) Albuterol Bronchodilator 53 80 1870 Cisatracurium Neuromuscular blocker 253 51 786 Rocuronium Neuromuscular blocker 84 80 Data Unavailable Fentanyl Sedative 100 61 533 Midazolam Sedative 70 79 4100 Propofol Sedative 60 82 123 Norepinephrine Vasopressor 50 67 53

Data from Premier Inc

The Premier data come from a survey that was fielded from March 20-25 and included responses from 377 acute care and 102 nonacute long-term care, home infusion, and retail pharmacy facilities.

Anesthetic Fill Rate Drops from 95% to 63%

Meanwhile, Vizient's Kistner said their data show that the combined fill rate for six ventilator-associated anesthetics together is now 63% (down from 95%). Those drugs include dexmedetomidine, etomidate, ketamine, lorazepam, midazolam, and propofol.

The analgesics (hydromorphone, fentanyl, and morphine) dropped to a 73% fill rate, he noted.

"In my career and in the career of all the pharmacists I talk with — the chief pharmacy officers for the largest healthcare institutions in the world — they've never seen demand like this," he said.

Kistner notes that while manufacturers have stepped up production to make ventilators and personal protective equipment, and distilleries are making hand sanitizer, "Not just anyone can make a drug."

"For someone to make propofol or hydromorphone or fentanyl, it usually takes about 5 weeks," he said.

And unlike the process for oral tablet drugs, "the sterility period for generic injectables is an additional 21 days at least."

What's Being Done

Kistner said Vizient is advocating for drug manufacturers to ramp up supply as well as pushing for the FDA to speed up additional supply approvals with manufacturers.

They are also working with the Drug Enforcement Administration to ease limits on narcotics put in place for the opioid crisis.

Michael Ganio, PharmD, senior director of pharmacy and quality for the American Society of Health-System Pharmacists (ASHP), told Medscape Medical News that quality issues are often behind drug shortages.

Compounding the current problem is that many of these drugs have been on the ASHP shortage database for a couple of years, Ganio said. Their tracking data suggest manufacturing quality issues have been common around the sterile, generic injectables such as fentanyl.

"Some of the root causes are tied to economics," he said. "When drugs are cheap there's not a lot of profit margin on them. Reinvesting in robust quality systems at the manufacturing plants is not very cost effective."

As frontline providers wait for production to increase, they will have to reach for alternatives, Ganio said.

As each drug gets harder to find, providers will turn to the next available one on the list, he said, but familiarity drops with each change.

"The challenge is that you're using drugs you're less familiar with, that have different side effect profiles," he said. "Every time you have to use something you're not used to, you're introducing a little more risk."

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