Severe frostbite receives treatment that can prevent amputation

The first time Dr. Peter Hackett saw a patient with frostbite, the man died from his injuries. It was in Chicago in 1971, and the man had gotten drunk and passed out in the snow, his fingers so frozen that eventually gangrene developed.

Dr. Hackett later worked at Mount Everest Basecamp, in Denali, Alaska, and now in Colorado, where he became an expert in treating cold weather injuries. The experience was often the same: there was not much to do about frostbite other than warm the patient, give aspirin, amputate in severe cases, and, more often, wait and accept that the patient’s body might automatically amputate six months later. shed a dead finger or toe naturally.

His mentor in Anchorage used to say, “Frostbite in January, amputation in July,” Dr. Hackett, clinical professor at the Altitude Research Center on the University of Colorado Anschutz Medical Campus. “For centuries there was nothing else to do.”

This month, the Food and Drug Administration has approved this the first therapy for the treatment of severe frostbite in the country. The drug, iloprost, is administered intravenously for several hours a day for just over a week. It works by opening blood vessels to improve circulation, limit inflammation, and stop the formation of platelet clots that can stop circulation and kill tissue. A person’s toes, fingers, ears, cheeks and nose are most at risk.

The approval of the treatment is both a scientific novelty and a money grab for the pharmaceutical industry. Experts say there is no good data on how many people have frostbite severe enough to receive this therapy. But according to Dr. Norman Stockbridge, chief of the FDA’s division of cardiology and nephrology at the FDA’s Center for Drug Evaluation and Research, which approved the drug, cases in the United States may number only a few dozen people per year.

“When you’re dealing with people who are really frozen and really at risk of losing grades, that’s quite unusual,” said Dr. Stockbridge. Still, “it’s better to have a cure for this than nothing.”

In fact, the approval of the freeze medication highlights an unspoken reality of the severity of the injury: it is rare.

Most at risk are high-altitude mountain climbers, people who work outdoors without proper equipment, and people who are homeless, especially those with poor circulation. Frostbite occurs at ‘extremely cold temperatures’ according to the Centers for Disease Control and Prevention, with injury often occurring during the thawing process as blood vessels become damaged by clots and inflammation, choking blood flow.

About two-thirds of total frostbite cases are milder, also known as frost nip, and are not likely candidates for this drug, according to Allison Widlitz, the vice president of medical affairs for Eicos Sciences, a startup in San Mateo, California. that received FDA approval to sell the drug. She estimated that the U.S. market for iloprost would employ fewer than 1,000 people per year.

“Although it is a small market, this is an important new option,” she said. Eicos, which has seven employees, has not yet set a price for the drug, Ms. Widlitz said.

Many infusion therapies for such rare conditions are very expensive. Treatment with iloprost requires infusions for six hours a day, for up to eight days.

Ms. Widlitz added that the company was founded to research iloprost and medications for other unmet medical needs.

This is not the first use of the drug. An inhaled version of iloprost was first approved by the FDA in 2004 for the treatment of pulmonary hypertension. Over the past decade, the IV version has been approved in many European countries for severe frostbite after a French doctor, Dr. Emmanuel Cauchy, had demonstrated its effectiveness in treating frozen mountain climbers.

Last year one article in The International Journal of Circumpolar Health, a publication dedicated to health issues affecting people in the Arctic Circle, found similar results in follow-up research. It noted that the use of iloprost “demonstrated a reduction in the number of amputations compared to untreated patients.”

As an example: an article from 2018, published in Wilderness and environmental medicine, examined iloprost treatment in five Himalayan climbers and found that the drug prevented tissue loss in two of them and limited tissue loss in two others. Those case studies found that the drug was effective when given 48 to 72 hours after the onset of the injury, an important wrinkle because climbers often cannot get immediate treatment.

In cases where frostbite is noticed more quickly, an anti-stroke medication, tissue plasminogen activator, or tPA, may be used to limit clot formation and reduce the risk of amputation. However, if that drug is not administered within hours, it can lead to serious complications and death. Unlike iloprost, tPA is not approved by the FDA for severe frostbite, but doctors have resorted to it in an off-label manner.

Dr. Hackett said the universe of people who suffer from severe frostbite includes “mountain climbers, snowmobilers who get stuck, mushers, the military” and other people who work in frigid conditions, along with those who are homeless and “people with drug and alcohol problems who are exposed to the cold for a long time.”

This is how Jennifer Livovich, a resident of Boulder, Colorado, who was homeless, suffered severe frostbite on an extremely cold night in December 2016.

She recalled drinking heavily and the weather being fine the day before: “Then I woke up the next day, covered in snow, and my shoe had come off while I was sleeping – maybe I took it off – and my left foot was stuck to the ground.”

“I kept walking around and I noticed my foot felt different, but I just thought I was cold,” she said. Five days later, she ended up in a detox unit, where, as she warmed and thawed her foot, she experienced “excruciating pain.”

In the thawing phase, damage begins to manifest and the capillaries deteriorate, sometimes irreversibly. “Several parts of my foot went from black to light blue,” she said.

Under the care of a doctor, she tried to soak in lukewarm water and raised her foot, putting gauze between her toes so that rejuvenating skin cells did not fuse. Chunks of skin fell off and she lost all her toenails. When the doctors were finally satisfied that the foot had healed as best as possible, “they shaved – that’s what they call it, ‘shaved’ – a quarter of an inch off my big toe,” she said.

The shearing took place in the summer, which roughly corresponded to the six-month timeline in Dr. Hackett’s mentor: injuries in early winter and amputation in summer.

So no matter how small the market for the new drug is, Dr. Hackett hopes it can save a few numbers.

“It’s fantastic,” he said. “It might change the old saying.”