Shortly after the Memorial Day floods in Houston, Brad Stodden saw a small tail emerging from below some debris in a drainage ditch by his Woodlands apartment. Thinking it was a lizard, he grabbed the tail only to find a black, red and yellow-banded snake, which promptly bit him on the finger.
As he tried to shake the snake loose, he struggled to recall the rhyme that would reveal whether it was a venomous coral snake.
“I didn’t really know it that well,” said Stodden, 21. “But I knew that red, black and yellow was bad.”
At the hospital, the tingling in his hand turned to sharp pain. Slowly, over the next few hours, the pins and needles crept up his arm. He had indeed been bitten by a coral snake and had received a good dose of venom. Concerned the neurotoxins in the venom could paralyze his diaphragm, suffocating him, doctors inserted a breathing tube and admitted him to the hospital. But even as his chest began to tighten, and his oxygen saturation levels began to drop, doctors never administered an antivenin. It would be used only as a last resort, they told him.
A shortage of coral snake antivenin has left physicians in Texas – where 25 to 30 coral snake bites are reported annually – and other Gulf Coast states more hesitant to use antivenin unless the patient is showing signs of paralysis. That has led to an ethical debate over the best way to treat coral snake bites. And while efforts are underway to produce a new supply of the antivenin, testing difficulties may prevent a safer, more effective antivenin from ever reaching the market.
Not year ‘to take risk’
“Most people who are bitten by coral snakes went towards the coral snake on purpose,” said Dr. Leslie Boyer, a venom expert at the University of Arizona. “If you are the kind of person who takes risks, because there is a shortage, this is not the year to take that risk.”
For the past five decades, coral snake bites have been treated primarily with an antivenin produced by Wyeth Pharmaceuticals. But the company, which was acquired by Pfizer in 2009, stopped producing it in 2003. The last two batches were due to expire in 2007.
As the expiration dates approached, Pfizer tested a few remaining vials, showing it was still effective, and FDA extended the dates for another year. Thereafter, each year on April 30 and Oct. 31, the FDA would extend the expiration date of those batches. By 2014, there were too few vials in the Halloween batch left to justify repeated testing, and some hospitals destroyed what remained. Many believe this year could be the last time the April 30 batch will be extended as well. Hospitals have been reluctant to stock the antivenin, at about $1,500 a vial, for fear it will expire before they can use it. And the shortage has raised the question of how quickly doctors should administer it.
“There is a case to be made, especially in Texas where we think that bites are on average milder, for waiting until you have at least some signs. A lot of people are in the mood to stretch the supply out,” Boyer said. “Then there are some doctors, especially pediatricians, who believe you should treat it right away because the stakes are so high.”
Some doctors will administer antivenin for any confirmed coral snake bite, while others may wait for signs – such as droopy eyelids or slurred speech- that the bite is having a systemic effect.
“We worry about neurotoxicity that would manifest as weakness,” said Dr. Spencer Greene, a toxicologist at Ben Taub General Hospital in Houston. “In the worst possible case, that would be respiratory weakness so they couldn’t breathe.”
Greene will assess patients repeatedly for any sign of muscle weakness before administering the antivenin. He’s seen only a handful of coral snake bites in his three years in Houston, and says none has required antivenin.
Some patients experience an acute allergic reaction to the antivenin. If patients can recover without the antivenin, Greene said, there’s no point in exposing them to those risks.
Other doctors will administer the antivenin if they know the patient has been bitten by coral snake.
“Sometimes the patients will show a picture to confirm it. Occasionally, the family will bring the snake in,” said Dr. Lillian Liao, director of the pediatric trauma and burn program at University Hospital in San Antonio. “That’s always fun, particularly if it’s live.”
Data from Florida show that the antivenin can reduce the mortality rate from 10 percent to 20 percent of patients to 1 percent to 2 percent. It’s unlikely those same percentages would apply to the less-potent Texas coral snake. One review of Texas bites from 2000 to 2004 found that only seven of 96 patients developed the type of systemic effects that would require treatment. But it’s unclear whether more patients would have developed systemic effects had they not received the antivenin.
“Honestly, I would have to say that in Texas, no one treats enough of these bites to say,” Liao said.
Florida accounts for about two-thirds of the national total of 100 to 150 coral snake bites a year. Even in Florida, however, not all doctors are quick to treat with antivenin, says Jack Facente, a venom producer from Orlando.
‘Ticking time bomb’
“Because 50 percent of bites are dry bites, where you get little to no venom, so they don’t want to waste the antivenin on you,” Facente said. “The problem that you have is now you’re sitting on a ticking time bomb.”
That’s because coral snake venom contains two types of neurotoxins that can cause paralysis: a reversible toxin that tends to affect the patient first, and an irreversible toxin that comes later.
“From a health standpoint, it makes a huge difference if you use it as a preventative instead of waiting until the person is severely ill,” Boyer said.
The Wyeth antivenin was made using only Eastern coral snake venom, and research performed by Elda Sanchez, of the National Natural Toxins Research Center in Kingsville, suggests it may be not be as effective in counteracting Texas coral snake venom.
When FDA officials could find no manufacturer to take up antivenin production, they turned to Boyer, who had just developed a new antivenin for scorpion bites. With funding from the National Institutes of Health, Boyer’s lab created a new coral snake antivenin from a mixture of Eastern and Texas coral snake venom, with additional processing designed to minimize allergic reactions.
“We haven’t proved that because we haven’t used it enough patients yet,” Boyer said. “But the technology in general is the same as for our scorpion study, and we know that has a very improved safety profile compared to the old product.”
Clinical trials started last year in a number of Florida hospitals, but so far only seven of the 55 snake bite patients needed for FDA approval have enrolled.
“We suspect that as long as there is a continuous supply of the old stuff, it’s going to be hard to get hospitals to sign-up,” Boyer said.
A Pfizer spokesman confirmed the company has resumed production of the old antivenin, using the Wyeth formulation.
Even without the antivenin, though, Stodden, the patient from The Woodlands, was none the worse for his experience other than some pain in his finger. He spent the night in the hospital and was released the next morning.
He did, however, finally remember that rhyme:
“Red on black, you’re OK Jack. Red on yellow, kill a fellow.”