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To the Editor: In their study on the effectiveness of antivenom for redback spider bite, Isbister and Gray cast doubt on the current method of administering antivenom intramuscularly.1
Any study on the outcome of treating bites by venomous animals is limited by factors beyond the control of the investigator. These include the variability of the venom content in the animal’s venom apparatus, uncertainty regarding how much and where venom has been injected, and the delay before treatment.
Between 1955 and 1957, I dissected the venom glands of 590 redback spiders for the production of antivenom.2 The yield of freeze dried venom per spider varied from 0.08 mg to 0.32 mg. Based on these findings, and to allow for dilution of antivenom by body fluids, “it was considered that 500 units of antivenene would constitute a suitable initial dose for the treatment of a bite by L. hasseltii”.3 This amount of antivenom will neutralise 5 mg of venom in vitro, and the antivenom is still issued in this strength by CSL Ltd.
No fatalities have occurred from redback spider bite since antivenom became available in 1956,4 and reports from doctors have confirmed its efficacy and safety.5 If symptoms persist after the initial dose, or if diagnosis has been delayed, the initial dose of 500 units may have to be repeated. As Banham et al have wisely stated “treatment should be titrated against response”.6
Because of the risk of anaphylaxis, intramuscular injection, which has stood the test of time, is safer than the intravenous route.
Geoffrey K Isbister
Clinical Envenoming Research Group, University of Newcastle, Newcastle Mater Misericordiae Hospital, Locked Bag 7, Hunter Region Mail Centre, NSW 2310 gsbiteATferntree.com
In reply: We thank Wiener for his comments on our study. Although we challenge the use of intramuscular redback spider antivenom (RBS AV) in the article, we only suggested that the use of intramuscular antivenom needs review and that randomised controlled trials comparing intravenous and intramuscular RBS AV should be undertaken. Two such trials, in Western Australia and Newcastle, are currently in progress.
There are no pharmacokinetic studies of RBS AV, but studies of other antivenoms suggest that the intramuscular route is less effective.1 In Tunisia, the intramuscular use of scorpion antivenom, which is also an F(ab')2 antivenom, similar to RBS AV, has been questioned for similar reasons.2,3 Studies in a rabbit model demonstrated that intramuscular antivenom induced only partial and delayed neutralisation of circulating toxins.3 More importantly, in a study of scorpion stings of children, the intramuscular administration of antivenom had far less effect on plasma venom concentrations and patient recovery times.2
We do not dispute that repeated doses of antivenom may be required, but the implication that only an initial dose was used in our study is incorrect. Half of the treated patients required repeat doses (6 ampoules in one patient). In a recent series of four patients with redback spider bites, intramuscular antivenom was ineffective, even though three patients received two or three ampoules. Subsequent intravenous antivenom was effective in all cases.4 There is no evidence that appropriately administered intravenous RBS AV (diluted in 200 mL of normal saline, over 20–30 minutes) is less safe than intramuscular antivenom. There is insufficient reason to prevent the use of intravenous antivenom if it is shown to be more effective than intramuscular antivenom. Although it is too early to change recommendations for the administration of RBS AV, it is essential that controlled trials be done.
©The Medical Journal of Australia 2003 www.mja.com.au ISSN: 0025-729X
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