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Australian Taipan (Oxyuranus Spp.) Envenoming: Clinical Effects and Potential Benefits of Early Antivenom Therapy – Australian Snakebite Project (ASP-25)

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Australian Taipan (Oxyuranus Spp.) Envenoming: Clinical Effects and Potential Benefits of Early Antivenom Therapy – Australian Snakebite Project (ASP-25) Clinical Toxicology ISSN: 1556-3650 (Print) 1556-9519 (Online) Journal homepage: http://www.tandfonline.com/loi/ictx20 Australian taipan (Oxyuranus spp.) envenoming: clinical effects and potential benefits of early antivenom therapy – Australian Snakebite Project (ASP-25) Christopher I. Johnston, Nicole M. Ryan, Margaret A. O’Leary, Simon G. A. Brown & Geoffrey K. Isbister To cite this article: Christopher I. Johnston, Nicole M. Ryan, Margaret A. O’Leary, Simon G. A. Brown & Geoffrey K. Isbister (2016): Australian taipan (Oxyuranus spp.) envenoming: clinical effects and potential benefits of early antivenom therapy – Australian Snakebite Project (ASP-25), Clinical Toxicology, DOI: 10.1080/15563650.2016.1250903 To link to this article: http://dx.doi.org/10.1080/15563650.2016.1250903 View supplementary material Published online: 30 Nov 2016. Submit your article to this journal Article views: 46 View related articles View Crossmark data Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ictx20 Download by: [UQ Library] Date: 21 December 2016, At: 20:43 CLINICAL TOXICOLOGY, 2016 http://dx.doi.org/10.1080/15563650.2016.1250903 CLINICAL RESEARCH Australian taipan (Oxyuranus spp.) envenoming: clinical effects and potential benefits of early antivenom therapy – Australian Snakebite Project (ASP-25) Christopher I. Johnstona, Nicole M. Ryana , Margaret A. O’Learya, Simon G. A. Brownb and Geoffrey K. Isbistera,c aClinical Toxicology Research Group, University of Newcastle, Newcastle, Australia; bCentre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Royal Perth Hospital and the University of Western Australia, Perth, Australia; cDepartment of Clinical Toxicology and Pharmacology, Calvary Mater Newcastle, Newcastle, Australia ABSTRACT ARTICLE HISTORY Context: Taipans (Oxyuranus spp.) are medically important venomous snakes from Australia and Papua Received 29 August 2016 New Guinea. The objective of this study was to describe taipan envenoming in Australian and its Revised 13 October 2016 response to antivenom. Accepted 15 October 2016 Methods: Confirmed taipan bites were recruited from the Australian Snakebite Project. Data were col- Published online 30 Novem- lected prospectively on all snakebites, including patient demographics, bite circumstances, clinical ber 2016 effects, laboratory results, complications and treatment. Blood samples were taken and analysed by KEYWORDS venom specific immunoassay to confirm snake species and measure venom concentration pre- and Australia; snakebite; taipan; post-antivenom. envenoming; antivenom Results: There were 40 confirmed taipan bites: median age 41 years (2–85 years), 34 were males and 21 were snake handlers. Systemic envenoming occurred in 33 patients with neurotoxicity (26), com- plete venom induced consumption coagulopathy (VICC) (16), partial VICC (15), acute kidney injury (13), myotoxicity (11) and thrombocytopenia (7). Venom allergy occurred in seven patients, three of which had no evidence of envenoming and one died. Antivenom was given to 34 patients with a median ini- tial dose of one vial (range 1–4), and a median total dose of two vials (range 1–9). A greater total anti- venom dose was associated with VICC, neurotoxicity and acute kidney injury. Early antivenom administration was associated with a decreased frequency of neurotoxicity, acute kidney injury, myo- toxicity and intubation. There was a shorter median time to discharge of 51 h (19–432 h) in patients given antivenom <4 h post-bite, compared to 175 h (27–1104 h) in those given antivenom >4 h. Median peak venom concentration in 25 patients with systemic envenoming and a sample available was 8.4 ng/L (1–3212 ng/L). No venom was detected in post-antivenom samples, including 20 patients given one vial initially and five patients bitten by inland taipans. Discussion: Australian taipan envenoming is characterised by neurotoxicity, myotoxicity, coagulopathy, acute kidney injury and thrombocytopenia. One vial of antivenom binds all measurable venom and early antivenom was associated with a favourable outcome. Introduction described include a descending flaccid paralysis that may require intubation and mechanical ventilation, venom Taipans (Oxyuranus spp.) are highly venomous elapids that induced consumption coagulopathy (VICC), myotoxicity, early inhabit Australia and Papua New Guinea. Long revered for cardiovascular collapse and an acute kidney injury associated the lethality of their venom in mice,[1] three distinct species with microangiopathic haemolytic anaemia (MAHA).[3–9] of taipan are now recognised; the coastal taipan (Oxyuranus scutellatus), the inland taipan (Oxyuranus microlepidotus) and There is less information on the frequency of each of these the central ranges taipan (Oxyuranus temporalis). The snakes clinical syndromes or their severity, particularly in comparison are distributed along the northern coastline of Australia and to other Australian elapids. southern coast of Papua New Guinea (O. scutellatus), semi- Seqirus Ltd. taipan antivenom is currently the only specific arid central east Australia (O. microlepidodus) and the western treatment for taipan envenoming in Australia, which is also desert (O. temporalis).[2] frequently used in Papua New Guinea. It is raised against Most reports of taipan envenoming come from Papua Australian coastal taipan (O. scutellatus) venom but is recom- New Guinea, with a small number of cases from mended and used in cases of suspected taipan envenoming Australia.[3–5] In many, they are unconfirmed cases, with from any taipan species.[10,11] In vitro studies have shown only one previous study reporting venom concentrations, but efficacy of antivenom at preventing neurotoxicity from the limited clinical information.[5] Clinical effects that have been venoms of Australian and Papua New Guinean coastal CONTACT Geoffrey K. Isbister [email protected] Calvary Mater Newcastle, Edith Street, Waratah, NSW 2298, Australia. Supplemental data for this article can be accessed here: http://dx.doi.org/10.1080/15563650.2016.1250903 ß 2016 Informa UK Limited, trading as Taylor & Francis Group 2 C. I. JOHNSTON ET AL. taipans, as well as the inland taipan, when venom and anti- with every additional clinical blood collection (recommended venom are pre-mixed.[12] Clinical studies in Papua New 6, 12, 18, 24 h and daily thereafter). Blood is centrifuged and Guinea by Trevett et al. demonstrate a favourable outcome the serum aliquoted and frozen for subsequent analysis in patients treated with early antivenom, based on a lower according to a faxed protocol to the hospital laboratory. rate of endotracheal intubation and more rapid recovery Previously defined clinical syndromes were used to from neurotoxicity.[13] This is because the neurotoxicity from describe clinical effects (Supplementary Table 1).[19] VICC taipan venom appears to be mainly presynaptic,[14] and was defined as undetectable fibrinogen and/or a raised D- therefore irreversible. Dimer (at least 10 upper limit of normal or >2.5 mg/L) and  Dosing guidelines in the form of the approved Australian an international normalised ratio (INR) > 3. Partial VICC was product information and the CSL Antivenom Handbook pro- defined as low but detectable fibrinogen/elevated D-Dimer vide somewhat unclear instruction on antivenom therapy, and a maximum INR <3. Systemic hypersensitivity reactions with doses of one vial, three vials and up to eight vials rec- to antivenom administration were defined as anaphylaxis per ommended based upon the presence of mild envenoming or NIAID-FAAN consensus criteria and graded according to grad- “severe defibrination” and a confusing and potentially harm- ing system of Brown.[20,21] ful guide that “children may become critically ill and may A venom specific enzyme immunoassay is used to identify need more antivenom”.[10,11] Other clinical guidelines rec- venom type (and species) and quantify venom present in ommend a single vial for treatment which is not based on pre-antivenom samples. The assay measures only the venom arbitrary measures of severity or subjective responses to ther- antigens that generate specific antibodies, but the term apy.[15,16] A clear understanding of the frequency and sever- venom concentrations is used throughout. Venom measure- ity of different clinical syndromes in taipan envenoming and ment in post-antivenom samples is used to determine if suffi- their response to antivenom therapy is required. cient antivenom has been administered to bind all free The aims of this study were to better describe the clin- venom. If no pre-antivenom samples are available, the post- ical effects resulting from confirmed taipan bites in Australia antivenom samples are subjected to a previously described and the response of taipan envenoming to antivenom heat dissociation treatment and then venom is measured treatment. with the enzyme immunoassay.[22] For this study, the Australian snakebite project database was searched from May 2003 to April 2016 for potential Methods cases of taipan bites. Potential cases were defined by either expert identification of the snake in question, a posi- This study was a prospective cohort study of patients with tive Seqirus snake venom detection kit (sVDK) result for definite taipan (Oxyuranus spp.) bites recruited to the taipan, or snake envenoming of unknown type with sug- Australian Snakebite Project (ASP). The Australia snakebite gestive clinical features
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