Reply to Isbister and Page: Further discussion of an illuminated case of presumed brown snake (Pseudonaja spp.) envenoming

In commenting about our reported case of presumed brown snake (Pseudonaja spp.) envenoming, Isbister and Page opined that some of our statements were not ‘‘evidence based’’. We strongly disagree that we ‘‘left the reader and the patient in the dark about the diagnosis’’. As stated, the circumstances and presentation strongly supported the diagnosis, as did the demonstrable improvement of the patient’s clinical condition and laboratory tests following administration of brown snake antivenom (BSAV). We also outlined the problems with venom immunoassays, and would not have hinged our diagnosis on the results of a given assay. Our overriding concern was managing the patient who showed signs of clinical decline. To the best of our knowledge, their recommended venom assay is not a real-time test, independently verified or commercially available, and so is not practical for management of acute cases across Australia. Our view that a single vial of BSAV is a ‘‘precariously narrow strategy’’ is based on individual clinical experience with a substantial number of cases. We support the principle of evidence-based medicine, as a set of recommendations derived from the combined evaluation of the best external clinical evidence, individual clinical experience/expertise and patient values, as well as expectations. The authors state that their studies demonstrate that ‘‘one vial’’ of BSAV is ‘‘more than sufficient for all brown snake bites’’ and that ‘‘low concentrations of venom detected post-AV are in fact bound venom’’. The authors’ study does not include all possible clinical circumstances including patient co-morbidities that could complicate effects of a prolonged defibrinating coagulopathy. The complications that occurred in our patient are a good example of this, thus our entitling it ‘‘an instructive case’’. The possible role of venom variability and related effects in patients is another unpredictable factor. It must be noted that one of the authors (GI) has also suggested, based on a computer-modeled analysis of selected cases, that ‘‘antivenom has little or no benefit’’ for treating Australian elapid coagulopathic envenoming. Also, while the authors’ data have suggested the presence of bound venom in their post-envenoming assays, recent transcriptomic analyses suggest that Pseudonaja spp. venom contains at least 113 different toxin transcripts, and this should raise questions about which and proportionally how many expressed components are ‘‘bound’’, and what is the in vivo fate/metabolism of many clinically relevant toxins and isotoxins. Although, our patient did not specifically report chest pain and cardiac monitoring remained unremarkable, her troponin levels suggested a NSTEMI (our precise words were, ‘‘consistent with a NSTEMI’’). NSTEMI in some patients (e.g. geriatric patients and women) may present atypically, for example as syncope, or fatigue. Her advanced age, hypertension, hyperlipidemia and smoking histories are all traditional risk factors for NSTEMI. Our patient had no evidence of pulmonary embolism, sepsis or any other significant cause for the markedly abnormal Troponin T, other than myocardial insult. The key term ‘‘infarction’’ is warranted as the designation for this patient’s clinical status because the clinical evidence was consistent with a recent consensus definition. The early pro-thrombotic effects of the consumption coagulopathy likely precipitated the myocardial insult. The patient was not a candidate for acute interventional therapy because of her coagulopathy and the absence of ischemic changes, as well as clinical improvement post-BSAV. A recent NSTEMI management guideline also suggested that, in all but the highest-risk patients, immediate cardiac catheterization or other interventional therapy does not offer benefit over initial medical stabilization and subsequent early cardiac catheterization/intervention Address for correspondence Scott A. Weinstein, PhD, MBBS, MD, Toxinology Department, Women’s and Children’s Hospital, North Adelaide, South Australia 5006, Australia. Tel: +61 8 8 161 8044. E-mail: herptoxmed@msn.com Received 28 August 2015; revised 3 September 2015; accepted 14 September 2015.