Potential Treatment For Snakebites Leads To A Paralyzing Test

Jul 31, 2013
Originally published on August 9, 2013 6:38 am

Each year, as many as 125,000 people around the world die from venomous snakebites, often because they live in remote, rural areas and didn't get to a hospital in time to get treatment. Toxins in the venom of snakes like cobras and kraits slowly paralyze their victims, who ultimately die of suffocation.

A San Francisco emergency room physician says he may have the beginnings of a workaround that could fend off paralysis and save many of those lives.

Already, hospitals sometimes use an intravenous version of the drug neostigmine to buy time if they don't have the right antivenom. But it's a scary treatment for laypeople to have to use in the field. "In the IV form, neostigmine is a very tricky drug," says Matt Lewin, the San Francisco physician. "An overdose will stop the heart."

Lewin is medical adviser to international research expeditions for the California Academy of Sciences, so he has to worry about things like cobra bites. He kept noodling about how neostigmine might be used safely outside a hospital.

On a camping trip in Mongolia, Lewin was talking the problem over with longtime pal and mentor Philip Bickler, an anesthesiology professor at the University of California, San Francisco, when they suddenly realized that a neostigmine intranasal spray might work. It's been used to treat some paralytic symptoms of myasthenia gravis, they realized, and might be a safer way to reverse the paralysis of snakebite, too.

But to test their theory, they would need to partially paralyze someone — temporarily, and under controlled conditions. So they found a volunteer, "a healthy, 45-year-old male." (Lewin wouldn't divulge the volunteer's identity to Shots, but says, "You could say he's someone whose perspective I'm very familiar with.")

With emergency rescue treatments at the ready, a team of anesthesiologists at UCSF began by infusing the very much awake and alert volunteer with a steady drip of mivacurium, a curare-like drug similar to cobra venom.

Over the course of 90 minutes, the doctors watched as the volunteer's eyelids and cheeks began to droop — the same initial symptoms seen after a cobra's bite. His vision blurred. Then he began to have difficulty swallowing. By 115 minutes after the infusion started, he was having trouble lifting his head.

At that point — and before breathing got too difficult, Lewin rushes to say — the doctors gave the volunteer a carefully measured spritz of neostigmine through the nose.

It worked. The drug safely reversed the paralysis within minutes.

The experiment was "very safe" and approved beforehand by UCSF's safety committee on human research, Lewin says. The volunteer was "intensively monitored at all times by two anesthesiologists immediately before, during and for five hours after the study," he says. A third doctor collected data.

They published their study online this week in the journal Clinical Case Reports.

The next step, in addition to followup testing with actual venom in animals, will be to test other drugs to see if they work better, Lewin says. Many snake venoms are complicated mixtures with a variety of effects, and nasal neostigmine may not be the best solution ultimately. "We were just hoping with this to start the conversation," he says. "Can you think of another catastrophic condition like this for which there is no out-of-hospital treatment at all?"

Snakebite victims should still get to a trauma center as soon as possible after a bite. "The idea here isn't to replace antivenom," Lewin says. Nasal sprays with drugs like neostigmine would do only part of the job. But they could buy people the crucial time they need to get life-saving care.

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