Tiger snakebite deaths reveal problems with antivenom dosing

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With snake season having begun early for Queensland a new paper published in the Medical Journal of Australia brings into focus ongoing controversy surrounding the treatment for snakebite.

Two deaths by tiger snake bites in Victoria over the summer spring and summer of 2014 and 2015 have caused some experts to question recommendations that one vial of any Australian snake antivenom is all that is required for treatment of an Australian snake’s bite.

Associate Professors Scott Weinstein and Julian White from the Women’s and Children’s Hospital in Adelaide, and Mr Peter Mirtschin from Venom Supplies Pty Ltd, wrote in the Medical Journal of Australia that “the Australian medical community should be aware that there is no consensus agreement that one vial of any Australian snake antivenom is all that is ever required for significant Australian elapid [a family of venomous snakes endemic to tropical and subtropical regions] envenoming”.

In the spring of 2014 a 27 year old man who received a prolonged bite from a 1.5 m tiger snake that had to be forcibly removed, received one vial of tiger snake antivenom about 1 hour after the bite. A vial of brown snake antivenom was provided early the next morning, but the patient died shortly thereafter.

The following January a 70-year-old woman who was bitten multiple times by a tiger snake died less than 24 hours after being bitten. About 2–3 hours after the bite, she received two vials of tiger snake antivenom but further deteriorated and was given an additional vial 6.5 hours later. She later died. An autopsy revealed massive bleeding and a detected tiger snake venom level of 697 ng/mL.

In 2018 two coronial investigations into the deaths have exposed controversy over exactly how much antivenom people should receive. Evidence presented said that while one dose of tiger snake antivenom was supported by research as being no better than repeated doses, it “was an area of considerable debate”. Testing would later reveal that the 27 year old man still had active venom in his body after he died.

That finding led Associate Professor Mark Little, a clinical toxicologist at Cairns Hospital, to conclude he had not received enough antivenom. “Whilst it is likely that for many patients envenomed by a snake in Australia, one ampoule may be enough, this case would suggest that a higher initial dose (possibly two ampoules) might be required for tiger snake envenomings,” Dr. Little said.

The coroner’s conclusions included reiteration of a consulted clinical toxinologist’s comments that “in treating an envenomed patient we need to successfully treat the ‘outlier’ case, not the ‘median’ case”, and the coroner stated that “in light of [the patient’s] death, the current recommendation to administer one ampoule of antivenom needs refinement”.

Weinstein and colleagues cited the controversial Australian Snakebite Project 2017 study (also published in the MJA) as having “concluded that one vial of antivenom was sufficient to effectively treat envenoming by all taxa of Australian elapids”.

“Inadequately treating patients with particularly high venom loads exposes them to unnecessary risk and decreases the likelihood of a positive outcome,” Weinstein and colleagues wrote.

“For example, for an envenomed patient with pre-existing medical comorbidities or older people or young children who are envenomed by a large amount of injected venom, the single vial recommendation may be a ‘precariously narrow therapeutic strategy’. The severity of envenoming is also unpredictable because of the marked variability of injected venom volume and individual venom sample properties that can be influenced by geographic origin, ontogeny, as well as individual genetic factors.”

There was no evidence that higher doses of antivenom were dangerous, they wrote.

“We do not suggest that multiple vial doses should routinely be used for all Australian snakebite patients requiring antivenom, but the patient-centred factors and biomedical reasons outlined [in our article] support our contention that recommendations for a uniform single vial treatment are inappropriate. Each envenomed patient should be individually assessed and provided with adequate antivenom in response to the envenoming severity and their individual clinical needs,” the authors concluded.