Snakebite treatment buys time

Indiana Jones, intrepid cinematic archaeologist, is famously afraid of snakes. Perhaps he wouldn’t need to be if he had a new ointment developed by scientists in Australia. Quickly applying a nitric oxide–containing ointment near the bite site slows the spread of some venoms, including the notorious eastern brown snake’s, the researchers report online June 26 in Nature Medicine.

“This treatment might make all the difference between dying on the road and getting to the hospital in time,” says physician and emeritus professor of tropical medicine David Warrell of the University of Oxford, who was not involved with the study. Worldwide, snakebite causes approximately 100,000 deaths and 400,000 limb amputations each year.

Physiologist Dirk van Helden at the University of Newcastle and his colleagues showed that in humans, applying an ointment containing nitric oxide within one minute of a simulated snakebite slows the transit of injected tracer molecules. Foot-to-groin venom travel times increased from an average of 13 minutes without the ointment to an average of 54 minutes with the ointment applied in a 5-centimeter diameter circle just up the limb from the bite site. The group also tested the effects of the cream on rats injected with venom from the brown snake (Pseudonaja textilis). Its potent venom travels through the body’s lymphatic system, eventually halting respiration and causing death.

“It’s particularly nasty, one of the most toxic things in the world,” says van Helden.

In the injected rats that were slathered with ointment, symptoms of toxicity set in after about 96 minutes, compared with about 65 minutes in untreated animals. And the poison’s effects were less severe in treated rats, suggesting that slowing venom delivery decreases the toxicity of a given dose by spreading it out, says van Helden.

The nitric oxide source in the ointment is glyceryl trinitrate, the same compound used to treat angina. When applied to the body, the ointment releases microscopic amounts of nitric oxide gas, which sink through the skin. There, the gas inhibits pumping of the lymphatic vessels — the primary roadway for molecules too big to squeeze through blood vessel walls and hitch a ride through the bloodstream.

But victims might be out of luck if bitten by a Black Mamba or cobra, since the ointment isn’t effective against venom containing smaller toxic proteins capable of directly entering the bloodstream.

Another potential snag is the need for bite victims to be quick on the draw. The scientists applied ointment within 20 seconds of snakebite in rats and within a minute in the human subjects. “The window of opportunity they’ve looked at is brief,” says Warrell.

Van Helden says the next steps include testing longer time intervals between bite and treatment and more distant application sites.

Still, this study represents a breakthrough in the treatment of snakebites, says Alan Harvey of the University of Strathclyde in Scotland, pointing out that in 2009 the World Health Organization added snakebite to its list of neglected tropical diseases.

Common methods for stopping the spread of venom rely on the sometimes tricky and painful application of pressure to the punctured body part, including a tourniquet-type ligature that can cause gangrene as well as a distributed pressure pad that’s difficult to apply correctly and requires immobilization of the limb.

Van Helden hypothesizes that a combination of ointment and pressure treatment might be the best way to slow the spread of snake venom. But, “If I had the ointment in my backpack,” he says. “That would be the first I’d put on.”