Surge forces doctors to ration life-saving drugs

Ontario hospitals are facing shortages of critical drugs to treat COVID -19 patients amid a surge of cases, forcing some physicians to choose which patients receive potentially life-saving care, while others don’t have access to the drugs at all.

In anticipation of an Omicron-fuelled rise in cases, many hospitals in December had already started to ration key COVID therapeutics — in short supply across many regions — for patients who would benefit the most.

But drug shortages have escalated in the last week alongside a crush of COVID patients needing care on medical wards and in intensive care units, with at least one Torontoarea hospital instituting a lottery system to determine which patients will receive a dose of a potentially life-saving medication.

Networks of pharmacists and physicians are sharing information on how to access therapeutics and how to share any available doses, prioritizing hard-hit hospitals.

But with limited available stock from drug manufacturers and low provincial supply, little can be done, said Dr. Menaka Pai, co-chair of the Ontario COVID-19 Science Advisory Table’s working group that publishes clinical practice guidelines on COVID drugs and therapeutics.

Currently, many hospitals are primarily relying on a widely available steroid, dexamethasone, to care for COVID patients; the drug is considered “the most basic level of care,” said Pai, who is also an associate professor of medicine at McMaster University.

Last week she fielded messages from distraught hospital physicians and pharmacists across the province looking for advice on how best to care for COVID patients amid the worsening drug shortage.

“There is a unique moral injury happening now when there is actual evidence showing there are good drugs that can save people’s lives and help prevent this onslaught of patients coming to the ICU, and to know these drugs are just out of reach,” said Pai. “It’s a uniquely awful thing happening right now in the pandemic.

“I think the public doesn’t quite appreciate that we don’t have these (drug) options. But what if you’re that patient and the doctor is saying we don’t have the medications to save your life or that are proven to keep you off a breathing tube? That is very tough.”

In an email response to the Star, an Ontario Ministry of Health spokesperson confirmed “the current supply of COVID treatments is limited in Ontario and across Canada given global demands for these products and the increased use as a result of Omicron.”

The statement said the Public Health Agency of Canada is working “with manufacturers to secure additional supply of drugs.”

The Ontario COVID-19 Science Advisory Table on Jan. 8 published clinical guidance on recommended drugs and biologics for adult COVID patients. The document outlines which drugs should be used for mildly, moderately and severely ill patients based on the best available evidence, and lists drugs that can be used, should those medications be unavailable.

It also provides guidance on which types of patients should be prioritized for each of the recommended drugs when they are in short supply.

Pai said drugs — if available — are currently being rationed to patients most at risk of getting severely ill and dying from COVID, primarily those who are immunocompromised or unvaccinated.

“It’s all based on: what’s your risk of getting really sick. That’s what we want to stop. If you’re fully vaccinated, you are automatically ineligible for any of these treatments.”

But that recommendation gets murky when clinicians are presented with patients with the same level of risk, but different conditions.

“If you have, for example, an unvaccinated woman who is 28 weeks pregnant, and a patient who is fully vaccinated but had a bone-marrow transplant, and no longer has an immune system, those patients are on the same tier,” Pai said. “But if you only have one dose of this drug, which is the patient you will ration care to?”

Key drugs to treat hospitalized patients include tocilizumab and sarilumab — types of monoclonal antibodies used to treat inflammatory conditions — which reduce the risk of mechanical ventilation and death. The drugs work by shutting off the body’s inflammatory response, stopping dangerous inflammation that can lead to breathing troubles and organ failure, Pai said.

Tocilizumab, which is being used off-label for COVID patients, is typically used to prevent severe side effects after some types of cancer treatment and for patients with severe arthritis. The supply for this drug — in its on-label use — is stable in Ontario, according to the Ministry of Health.

But for COVID patients, tocilizumab and sarilumab are either all gone in Ontario or in extremely short supply right now,” said Pai.

The Ontario Science Advisory Table recommends another drug, baricitinib, that can be used if either tocilizumab or sarilumab is unavailable.

During the current COVID patient surge, baricitinib is largely unavailable to most hospitals, Pai said.

At Scarborough Health Network (SHN), in a region hit hard during the pandemic, a recent COVID patient surge has forced its clinicians to institute a lottery-type system to determine which patients will get these key drugs.

In the past two weeks, staff have contacted hospitals within about a four-hour drive for additional supply, with several smaller hospitals donating their drugs to SHN, said Dr. Martin Betts, the hospital’s chief and medical director of critical care.

But supplies are now so limited that it’s unlikely smaller hospitals can continue to donate any extra doses, he said. As of Jan. 13, SHN did not have any tocilizumab or sarilumab but had recently procured an order of baricitinib — the recommended alternative — that is being rationed to patients.

“This really is a form of triage because we don’t have the resources to treat the number of patients that would qualify,” Betts said.

“Physicians are now having to choose between four and six patients a day that you’d want to give the medication to, knowing there’s maybe one, two or three doses. That’s nothing any physician wants to do.”

SHN recently instituted a lotterytype system — based on the clinical guidelines from the Ontario science table — to ensure there is no bias in allocating doses across its three hospital sites.

Each day, infectious diseases physicians and critical care doctors identify patients that could benefit from the drugs, Betts said. Those patients’ health numbers are submitted to SHN’s infectious diseases pharmacist, who then uses a randomization program to allocate drugs to qualifying patients based on the supplies available that day.

“It’s a really tough thing to do,” Betts said. “This is the least bad way we feel we can allocate a really scarce resource at this present time.”

Dr. Bram Rochwerg, a critical care physician and site lead for the intensive care unit at Juravinski Hospital, part of Hamilton Health Sciences, said tocilizumab has largely been unavailable in Hamilton hospitals since about Jan. 1.

“Every so often, we hear that there’s a couple of doses that somebody found, and we’d give those doses and then we’d go back to not having any.”

Since large research trials showed tocilizumab improved outcomes of hospitalized COVID patients, the drug has become the standard of care, Rochwerg said, noting for roughly every 20 COVID patients who receive the drug, one life is saved.

“That’s not insignificant,” he said. “Here’s a life-saving intervention in severely ill COVID patients that we’re now just not able to get.”

Rochwerg said the current shortage of key therapeutics combined with escalating numbers of COVID patients makes clinicians worry about supplies for other drugs, including sedation medications and antibiotics. But for those more common drugs, there are readily available alternatives, unlike for most COVID therapeutics.

“We have the luxury of working in a health-care system where we always have access to drugs that would show benefit,” Rochwerg said. “I've never before faced a time where we didn't have access to a drug that can save lives. It's the reality of how many critically ill patients with COVID there are.”

Among the other COVID drugs in limited supply is the antiviral drug remdesivir, which is recommended for mildly to moderately ill hospitalized patients who may need oxygen support but not intensive care. Pai said the drug works by stopping the virus from proliferating and attacking more tissues in the body, preventing the progression of the disease.

“It basically keeps a sick patient from getting sicker,” she said. “We’ve already restricted its use to the highest risk mildly ill and moderately ill (hospitalized) patients. We don’t have enough. We’re running out as we speak.”

It’s a really tough thing to do. This is the least bad way we feel we can allocate a really scarce resource at this present time.

DR. MARTIN BETTS SCARBOROUGH HEALTH NETWORK MEDICAL DIRECTOR OF CRITICAL CARE