Risks and realities of single vial antivenom recommendations for envenoming by Australian elapid snakes

To the Editor: We read the perspective by Weinstein and colleagues1 with interest and agree that treatment of snake envenoming in Australia is complex, and that clinicians should seek expert advice in cases of severe or unusual envenoming. There is 24‐hour specialist clinical toxicologist support available through the national Poisons Information Centre network (13 11 26), which takes 300 calls annually regarding snakebite.

However, we are concerned that the authors argue for just one non‐evidenced‐based solution — higher doses of antivenom — despite the extensive evidence that this historical approach does not lead to better outcomes. They suggest that the reduction in antivenom doses is based on a study of snakebite data in Australia from 2005 to 2015,2 which concluded that as “the usual antivenom dose for all major snake groups has decreased to one vial, with no evidence of adverse consequences, this approach should be retained” (emphasis added).2 However, the evidence supporting the move to lower doses of antivenom was based on a series of around 15 earlier studies.2 Serial measurement of venom concentrations using enzyme immunoassays in patients with snake envenoming demonstrated complete neutralisation after any dose,2 and the time course of recovery was unaltered by antivenom dose. The evidence suggests benefits from earlier antivenom but not from higher doses.3 Weinstein and colleagues cite a study by O'Leary and colleagues4 when they state that using “samples from rodents injected with venom … inaccurately determines a true neutralising dose”. However, the cited study measured venom–antivenom complexes in vitro to determine the antivenom concentration at which every venom molecule is bound to at least one antivenom molecule, as a measure of efficacy.4 It showed that this was similar to the manufacturer's original recommendation of a dose of a single vial of antivenom.

Weinstein and colleagues criticise the use of data from the large multicentre prospective cohort, the Australian Snakebite Project, which reports both clinical and laboratory outcomes and measures venom concentrations. They provide no citations to support their contentions, other than single cases and opinion (often citing their own previous views). A coroner's case in which a person died after three vials of antivenom is strangely cited as highlighting concerns that a single vial of antivenom is insufficient. They suggest two vials may be sufficient, or even larger doses, but offer no research or studies to support this, and no guidance as to when larger doses are required. They also do not provide a useful or practical alternative approach to the treatment of snake envenoming.

Current national evidence‐based guidelines and Poisons Information Centres recommend that one vial of brown snake antivenom and one vial of tiger snake antivenom be given as soon as possible in most snake envenoming cases in Australia.5 This ensures that the most common snakes are covered, as snake venom detection kits are unreliable.2 It also means an equivalent of two vials of antivenom is administered, because Australian “monovalent” antivenoms are in fact polyvalent.6 Evidence‐based guidelines continuously evolve, and we believe the key to better outcomes is early identification of envenomed patients and prompt access to the latest evidence‐based advice by consulting a clinical toxicologist through the Poisons Information Centre.