Research Tiger snake (Notechis spp) envenoming: Australian Snakebite Project (ASP-13)

Geoffrey K Isbister iger snakes are one of the BSc, FACEM, MD, Abstract 1 most frequent causes of Associate Professor, and Objectives: To describe the clinical syndrome associated with definite tiger Clinical Toxicologist2 T envenoming in Australia, par- snake (Notechis spp) envenoming and to examine the ability of tiger snake Margaret A O’Leary ticularly in Victoria, and are the most antivenom (TSAV) to bind free venom in vivo. PhD, important venomous snake in Tas- Hospital Scientist2 Design, setting and participants: We conducted a prospective cohort study mania. There are two species of tiger within the Australian Snakebite Project, reviewing all definite tiger snake Matthew Elliott envenoming cases between October 2004 and June 2011. Definite cases were Medical Student3 snake — Notechis scutatus (mainland tiger snake) and Notechis ater (black identified by venom-specific enzyme immunoassay or expert snake identification. Simon G A Brown tiger snake) — although a recent MB BS, FACEM, PhD, Main outcome measures: Clinical effects of tiger snake envenoming; peak Professor,4 and taxonomic revision suggests the dis- 5 venom concentrations; number of vials of antivenom administered. Emergency Physician tinction may be somewhat arbitrary.1 Results: Fifty-six definite tiger snake envenomings were identified. Clinical Mainland tiger snakes average 1.2 effects included venom-induced consumption coagulopathy (VICC) (n =53), 1 Discipline of Clinical Pharmacology, University of metres in length and have significant systemic symptoms (n = 45), myotoxicity (n = 11) and neurotoxicity (n =17). Newcastle, variability in appearance, from the Thrombotic microangiopathy occurred in three patients, all of whom developed Newcastle, NSW. classical banded dark grey/black and acute renal failure. There were no deaths. A bite-site snake venom detection kit 2 Department of Clinical test was done in 44 patients, but was positive for tiger snake in only 33 cases. Toxicology and yellow skin to unbanded types with a Pharmacology, Calvary range of colours from black to light Fifty-three patients received TSAV and eight of these patients had immediate Mater Newcastle Hospital, 2 hypersensitivity reactions, severe enough in one case to satisfy diagnostic Newcastle, NSW. grey. criteria for severe anaphylaxis. The median peak venom concentration in 50 3 School of Medicine, Most previous reports on tiger patients with pretreatment blood samples available was 3.2 ng/mL University of Melbourne, (interquartile range [IQR], 1–12 ng/mL; range 0.17–152 ng/mL). In 49 patients Melbourne, VIC. snake bites have been case reports of 3-8 with post-treatment blood samples available, no venom was detected in serum 4 Centre for Clinical one or a few cases, but there have Research in Emergency been two case-series studies, one after the first antivenom dose. Ten patients were given 1 vial of TSAV; the Medicine, Western 9 median dose was 2 vials (range, 1–4 vials). Pretreatment serum venom Australian Institute for from South Australia and another concentrations did not vary significantly between patients given 1 vial of TSAV Medical Research and from Western Australia.10 Both series University of Western and those given 2 or more vials. Australia, were retrospective, with case confir- Conclusion: Tiger snake envenoming causes VICC, systemic symptoms, Perth, WA. mation based on clinical effects and neurotoxicity and myotoxicity. One vial of TSAV, the dose originally 5 Emergency Department, Royal Perth Hospital, Perth, on a positive result for tiger snake recommended when the antivenom was first made available, appears to be WA. venom using the commercially avail- sufficient to bind all circulating venom. Geoffrey.isbister@ able snake venom detection kit newcastle.edu.au (sVDK).10 The frequency of different have shown that far less antivenom is Demographic details, clinical infor- envenoming syndromes and the required to neutralise the effects of mation, laboratory results, treatments MJA 2012; 197: 173–177 severity of clinical effects in tiger Australian snake venoms13,14 and to and reactions are documented on doi: 10.5694/mja11.11300 snake envenoming has not been fully fully bind venom in vivo.15-17 clinical research forms by treating characterised. The aims of our study were to staff. Data are entered into a purpose- Tiger snake antivenom (TSAV) was report the clinical syndrome that built relational database. Blood sam- the first snake antivenom to be occurs with definite tiger snake ples from each patient are centrifuged The Medical Journalreleased of Australia by the thenISSN: Commonwealth 0025- envenoming and to examine the abil- and aliquoted, and the serum is stored 729X 6 August 2012Serum 197 Laboratories3 173-177 (which later ity of TSAV to bind free venom in at –80C for later analysis of venom ©The Medical becameJournal CSLof AustraliaLtd) in 1930. 2012 The initial vivo. concentrations. www.mja.com.audose was 1 vial. However, over the Research past few decades, the recommended Clinical syndromes 11 Methods dose has increased to 4 vials and, in Clinical envenoming syndromes were 10,12 some cases, many more are given. We conducted a prospective cohort defined for each patient based on the Recent laboratory and clinical studies study of tiger snake envenomings clinical and laboratory features, using recruited to the Australian Snakebite a previously developed classification: Abbreviations Project (ASP). The ASP is a prospec- venom-induced consumption coagu- tive multicentre study of suspected lopathy (VICC) (partial or complete), ASP Australian Snakebite Project snakebites or snake envenomings myotoxicity, neurotoxicity, thrombotic CK Creatine kinase from over 100 Australian hospitals. microangiopathy and systemic symp- EIA Enzyme immunoassay The study design, recruitment and toms.19 In complete VICC, there is INR International normalised ratio data collection have been described undetectable fibrinogen and/or a sVDK Snake venom detection kit previously,15,18 and approval has been raised D-dimer concentration in cit- TSAV Tiger snake antivenom obtained from 19 human research and rate plasma (either at least 10 times VICC Venom-induced consumption ethics committees covering all institu- the assay cut-off point or > 2.5 mg/L) coagulopathy tions involved. and an international normalised ratio

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(INR) > 3.0. In partial VICC there is a and there is variation from batch to The remaining 78 cases included 39 low but detectable fibrinogen level, batch.21 definite rough-scaled snakebites elevated D-dimer level and a maxi- (based on EIA), 17 probable tiger mum INR < 3.0. Myotoxicity is Enzyme immunoassay snake bites (based on geography and defined as an elevated creatine In patients with blood samples avail- sVDK tests without EIA confirma- kinase (CK) level (> 1000 U/L) asso- able before and/or after antivenom tion), 18 cases in which there was ciated with myalgia and/or muscle administration, the venom concentra- either no venom EIA confirmation or tenderness. tion was measured using a venom- the amount of venom detected by EIA The presence of any one of these specific EIA to detect venoms from was too low to distinguish between syndromes was considered indicative Notechis spp (tiger snake), Tropidechis tiger snake or rough-scaled snake of systemic envenoming. Clinical fea- carinatus (rough-scaled snake), Hoplo- venom, one definite brown snake tures of any hypersensitivity reactions cephalus spp (which includes the bite, and three inconclusive cases in were also documented and were broad-headed snake, pale-headed which no venom was detected. Of the graded according to Brown’s scale.20 snake and Stephens’ banded snake) 56 definite tiger snake envenomings, and Pseudonaja spp (brown snake). the majority occurred in southern Case identification Venom-specific antibodies were not Australia and nine involved bites by We reviewed all cases from October available for Austrelaps spp (copper- captive snakes (Box 1). 2004 to June 2011 and identified pos- head snake). Clinical effects sible tiger snake bites or envenoming The method uses polyclonal anti- cases on the basis of expert snake bodies (IgG) to each venom, raised in The patient demographic characteris- identification, a positive sVDK test for rabbits. Detection is by biotinylated tics and clinical effects of the 56 tiger tiger snake venom, or clinical suspi- antibodies followed by streptavidin snake envenoming cases are summa- cion (in geographical areas where horseradish peroxidase, as described rised in Box 2 and Box 3. All enven- 17,22 tiger snakes occur). These included elsewhere. The limit of detection omed patients developed VICC, cases of VICC, from areas where tiger for the assay is 0.15 ng/mL for individ- neurotoxicity or myotoxicity, alone or snakes occur, in which a urine or bite- ual venoms, and the assay is highly in combination (Box 4). There was no site sample initially tested positive for specific for each venom, except that relationship between the pattern of brown snake (Pseudonaja spp) venom Notechis and T. carinatus can only be clinical syndromes and geographical with sVDK, but was later found to be distinguished from one another at location of the bite. There were no 16 negative for brown snake venom concentrations above 2 ng/mL. This deaths. Five patients had an early col- using serum venom-specific enzyme quantitative and specific EIA differs lapse, including one associated with a immunoassay (EIA). Stored samples from the sVDK test, which is a quali- seizure. One of the patients had a were analysed for the presence of tative EIA based on visual inspection cardiac arrest, but also developed fea- venoms from snakes known to of colour changes in wells. The latter tures of anaphylaxis before receiving inhabit the relevant geographical area. is used to rapidly detect venom at the antivenom and had a history of previ- Definite tiger snake envenomings bite site or in urine. ous snakebites. Systemic symptoms were defined by either a serum The peak pre-antivenom tiger occurred in 45 patients (80%), with venom-specific EIA being positive for snake venom concentration was nausea, vomiting and headache being tiger snake venom and negative for all reported for each patient. most common (Box 3). other relevant venoms or by expert VICC was the commonest manifes- Statistical analysis identification of the snake that had tation of envenoming. Thirty-nine bitten a patient who showed features For descriptive statistics, median, patients had complete VICC. In these of envenoming. range and interquartile range (IQR) patients the median time until the were calculated for data not normally INR returned to < 2.0 was 14.5 hours Antivenom dose distributed. Proportions are given (IQR, 11.3–18.6 hours). Fourteen Antivenom dose was defined as the with 95% confidence intervals calcu- patients had partial VICC. Of the lated using the Wilson’s procedure remaining three envenomed patients, amount given before the first post- 23 antivenom blood collection for the with a continuity correction. Statisti- one presented 8 days after the bite, measurement of venom. For patients cal and graphical analyses were done one had a normal INR and a D-dimer given antivenom other than tiger using GraphPad Prism software, ver- level 10 times the upper limit of nor- snake antivenom, the following con- sion 5.03 for Windows (GraphPad mal, and the third had a normal INR versions were used (based on a previ- Software Inc, San Diego, Calif, USA). but fibrinogen and D-dimer levels ous study that showed that all were not tested. Bleeding occurred in terrestrial snake antivenoms pro- Results 17 patients, and two of these had duced by CSL Ltd are in fact haematemesis without evidence of polyvalent21): 1 vial of brown snake From 138 possible tiger snake bites major gastrointestinal haemorrhage. antivenom is equivalent to 0.6 vials of and an additional four cases initially There were no other major haemor- tiger snake antivenom, and 1 vial of classified as brown snake bites, we rhages. Thrombotic microangiopathy, polyvalent antivenom is equivalent to identified 56 definite tiger snake which occurred in three patients with 4 vials of tiger snake antivenom. envenoming cases and four definite VICC, was characterised by acute These are the average conversions, non-envenomed tiger snake bites. renal failure, thrombocytopenia and

174 MJA 197 (3) · 6 August 2012 Research

tenderness, six developed generalised brown snake antivenom (2, 2 and 5 1 Distribution of definite tiger snake envenoming cases, including bites myalgia or muscle tenderness, and vials, respectively). There was no dif- by snakes in the wild and captive one developed trismus. Acute renal ference in time to receipt of snakes failure did not develop in association antivenom between patients who with myotoxicity, except in one case developed neurotoxicity and those where thrombotic microangiopathy who did not. Eight patients had sys- was present. The patient with the temic hypersensitivity reactions: most severe case of myotoxicity (who seven had skin-only reactions (Brown also developed severe neurotoxicity) Grade 1) and one had severe anaphy- had a peak CK level of 203 110 U/L laxis (Brown Grade 3). but did not develop renal failure. Of the three envenomed patients Local pain was reported in 51 who did not receive antivenom, two patients, with associated bruising in had partial VICC alone, and one pre- 35 patients and swelling in 33. Of two sented 8 days after being bitten. patients who developed local necro- sis, one had an associated secondary Venom assays 2 Characteristics and demographic infection. In the 50 patients for whom pre- features of 56 patients with treatment blood samples were availa- definite tiger snake envenoming Venom detection kit results ble, the median peak venom concen- Number of In 44 of the 56 definite envenoming tration was 3.2 ng/mL (IQR, 1–12 ng/ Characteristic/feature patients* cases, a bite-site sVDK test was done. mL; range, 0.17–152 ng/mL). Pre- Median age in years 42 (29–52; 5–87) Of the 12 patients who did not have a treatment venom concentrations did (IQR; range) bite-site sVDK test, four had a posi- Sex (male) 41 not differ between patients who sub- tive urine sVDK test for tiger snake, sequently received more than 1 vial of State or territory four had an expert identification of antivenom (median, 3.1 ng/mL; IQR, Victoria 18 the snake at the time, and four were 0.9–13 ng/mL) and patients who Western Australia 10 in Tasmania, where sVDK tests are received only 1 vial of antivenom Queensland 6 not required because tiger snakes and (median, 3.7 ng/mL; IQR, 1–8 ng/mL). New South Wales 11 copperhead snakes are the only ven- In the 49 patients for whom post- South Australia 3 omous species present. antivenom blood samples were avail- Tasmania 6 The bite-site sVDK test was posi- able — including three given only Australian Capital 2 tive for tiger snake only in 33/44 cases, brown snake antivenom and 10 given Territory negative for all species in four cases only 1 vial of TSAV — the post- Bite site (subsequent urine sVDK tests were antivenom blood venom concentra- Upper limb 29 positive for tiger snake in three of tion was zero. Lower limb 25 these), positive for both brown snake PBI applied 48 and tiger snake in two cases, and Antivenom 53 positive for brown snake only in five Discussion administered cases. Of the five patients with a posi- Snake handler 11 tive sVDK test for brown snake, three Our study showed that tiger snake IQR = interquartile range. PBI = pressure received brown snake antivenom, one envenoming is characterised by VICC bandage with immobilisation. *All figures represent number of patients except those received 1 vial of brown snake and 2 in almost all cases, neurotoxicity in a relating to median age. ◆ vials of tiger snake antivenom, and third of cases and myotoxicity in a one presented with myotoxicity 8 days fifth of cases. Major bleeding and microangiopathic haemolytic anae- after being bitten by a captive snake thrombotic microangiopathy were mia (two of these cases have been and did not receive antivenom. In one uncommon. Bite-site sVDK tests were reported in detail elsewhere24). of the non-envenomed cases involv- negative for tiger snake antivenom in Neurotoxicity occurred in 17 ing an identified tiger snake, an sVDK a quarter of cases, and the incorrect patients (30%) and was severe in one test was positive for brown snake, but antivenom was administered in four patient, who had bulbar, respiratory a venom-specific EIA on serum was cases. In the 49 patients for whom and limb weakness requiring intuba- negative for tiger snake venom. post-antivenom blood samples were tion and ventilation. The remaining available, no venom was detected in 16 patients had mainly extraocular Antivenom treatment blood after antivenom administration. involvement (Box 3). Four of the 17 Of the 56 patients with definite tiger This included 10 patients who patients with neurotoxicity also had snake envenoming, 53 received received only 1 vial of TSAV. Patients myotoxicity. Myotoxicity occurred in antivenom, with a median dose of 2 given only 1 vial of antivenom had 11 patients and there was a raised CK vials (IQR, 1–2 vials; range, 1–4 vials). similar pre-treatment serum venom level (> 1000 U/L) in another five. The Eleven of these patients received only concentrations to patients given more median peak CK level was 4749 U/L 1 vial of TSAV. The remainder than 1 vial. (range, 1193–203 110 U/L). All 11 received 2 or more vials of TSAV, The clinical syndrome associated patients had local muscle pain and except for three patients who received with tiger snake envenoming has

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3 Clinical effects of definite tiger been previously based on expert anec- A possible limitation of our study snake envenoming in 56 patients dotal reports and case reports. was that serum samples were not Although our results are generally tested for all elapid snake venoms, Number of Clinical effects patients consistent with current understand- and potentially related snakes such as ing of tiger snake envenoming, they copperheads (Austrelaps spp) could VICC 53 provide an accurate description of not be excluded as being responsible Complete 39 tiger snake envenoming in a series of for bites where their distribution over- Partial 14 patients treated with early antivenom laps that of tiger snakes. However, Bleeding 17 therapy. Tiger snake and rough-scaled reports of bites by identified Aus- Bite site 14 snake envenoming syndromes were trelaps spp are exceedingly rare, and Intravenous cannula site 9 previously regarded as similar. Our there was no geographical variation in Gums 2 results show that neurotoxicity is the clinical syndromes reported for more common with tiger snake tiger snake envenoming that occurred Haematemesis 2 envenoming, occurring in almost a in areas where Austrelaps spp are Neurotoxicity 17 third of cases, compared with two out found compared with other areas. Ptosis 12 of 24 cases of rough-scaled snake Our study brings into question the Extraocular ophthalmoplegia 11 envenoming reported in a previous reliance on the sVDK test for deter- 16 Dilated pupils 5 study. mining appropriate antivenom treat- Myotoxicity 11 Scop and colleagues reported on a ment. The sVDK result was incorrect 16-year retrospective series of 23 tiger in 5/44 cases, giving a positive result Creatine kinase level >1000 U/L 16 snake envenoming cases.10 However, for brown snake venom, which led to Systemic symptoms 45 their inclusion criteria were based on the incorrect use of antivenom in four Nausea 44 a positive sVDK test, which we have of the five cases. The use of sVDK is Vomiting 35 shown here to be unreliable and thus thus problematic and may confuse Headache 34 unsuitable for the purpose of case clinical assessment. A “saving grace” Abdominal pain 15 definition in research studies. In addi- in this situation is that, because all tion, Scop and colleagues included commercial antivenoms are poly- Diaphoresis 24 only cases in which fibrinogen was valent,21 brown snake antivenom Diarrhoea 7 undetectable, which biased the series contains sufficient TSAV to neutralise Other effects towards patients with complete the procoagulant activity of tiger Early collapse/ 5 VICC.10 It is recognised that VICC can snake venom.26 However, this princi- hypotension occur with only partial coagulation ple cannot be extended to the treat- Acute renal failure* 3 factor consumption,25 and in our ment of bites from other snakes that Thrombotic microangiopathy 3 study almost a third of patients with need much higher-volume antiven- Change in taste 4 tiger snake envenoming had only par- oms, such as the mulga snake, death tial VICC. An earlier series reported adder and taipan. Although all com- VICC = venom-induced consumption coagulopathy. *All three cases of acute renal by White described 10 cases of tiger mercial antivenoms are polyvalent, failure were in association with thrombotic microangiopathy. ◆ snake envenoming in which there the low-volume monovalent antiven- was a similar range of effects.9 oms (for brown and tiger snake bites) may contain insufficient antivenom to

4 Number of patients with venom-induced consumption coagulopathy (VICC), treat bites from snakes that require neurotoxicity and myotoxicity higher-volume antivenoms. Knowl- edge about medically important VICC alone (21) snakes that occur in a region and the VICC and neurotoxicity (10) clinical syndromes they cause is VICC (39) required for the selection of appropri- VICC and myotoxicity (7) ate antivenom. The data presented here provide VICC, neurotoxicity and myotoxicity (1) further evidence that 1 vial of

Partial VICC alone (10) antivenom is sufficient to treat enven- oming, as initially recommended by Envenomed (56) Partial VICC (14) Partial VICC and neurotoxicity (2) CSL Ltd. Larger doses of antivenom have been recommended up until Partial VICC and myotoxicity (2) recently, based on in-vitro27 and clinical10 studies. An in-vitro study Neurotoxicity (1) used venom concentrations that were No VICC (3)* Myotoxicity (1) 10 000-fold those seen in human snake envenoming. The study by Neurotoxicity and myotoxicity (1) Sprivulis and colleagues27 used a serum tiger snake venom concentra- ◆ * VICC may have occurred in these three patients but could not be confirmed (see text). tion of 33 g/mL, compared with the

176 MJA 197 (3) · 6 August 2012 Research median serum concentration of 4 Sutherland SK, Coulter AR. Three instructive carinatus): a series of confirmed cases. Med J Aust cases of tiger snake (Notechis scutatus) 2009; 191: 183-186. 3.2 ng/mL found in our study. It is envenomation — and how a radioimmunoassay 17 Kulawickrama S, O’Leary MA, Hodgson WC, et al. therefore not surprising that this proved the diagnosis. Med J Aust 1977; 2: 177-180. Development of a sensitive enzyme study suggested that larger doses of 5 Penington A, Johnstone B. A case of local tissue immunoassay for measuring taipan venom in necrosis following a bite by the Australian tiger serum. Tox icon 2010; 55: 1510-1518. antivenom were required. Previous snake Notechis scutatus. Aust N Z J Surg 1997; 67: 18 Isbister GK, Brown SG, MacDonald E, et al; clinical studies may have had unreal- 385-388. Australian Snakebite Project Investigators. istic expectations about the time to 6 Ferguson LA, Morling A, Moraes C, Baker R. Current use of Australian snake antivenoms and Investigation of coagulopathy in three cases of frequency of immediate-type hypersensitivity recovery of clotting function and have tiger snake (Notechis ater occidentalis) reactions and anaphylaxis. Med J Aust 2008; 188: reported the amount of antivenom envenomation. Pathology 2002; 34: 157-161. 473-476. given to patients, rather than deter- 7 Hood VL, Johnson JR. Acute renal failure with 19 Isbister GK, White J, Currie BJ, et al; ASP myoglobinuria after tiger snake bite. Med J Aust Investigators. Clinical effects and treatment of mining the amount required to bind 1975; 2: 638-641. envenoming by Hoplocephalus spp. snakes in all antivenom in vivo, thus overesti- 8 Harvey PM, Tabrett DG, Solomons BJ, Thomas Australia: Australian Snakebite Project (ASP-12). mating the required dose of MA. Envenomation by a King Island tiger snake Toxicon 2011; 58: 634-640. (Notechis ater humphreysi). Med J Aust 1982; 2: 20 Brown SG. Clinical features and severity grading antivenom. Our study provides in- 192-193. of anaphylaxis. J Allergy Clin Immunol 2004; 114: vivo support for the claim that 1 vial of 9 Scop J, Little M, Jelinek GA, Daly FF. Sixteen years 371-376. antivenom is an adequate dose. This of severe tiger snake (Notechis) envenoming in 21 O’Leary MA, Isbister GK. Commercial monovalent Perth, Western Australia. Anaesth Intensive Care antivenoms in Australia are polyvalent. Tox ico n is consistent with studies on other 2009; 37: 613-618. 2009; 54: 192-195. 15-17 14 snakes and with in-vitro studies. 10 White J. A review of 105 cases of suspected 22 O’Leary MA, Isbister GK, Schneider JJ, et al. snakebite in South Australia. In: Acknowledgements: We would like to thank the ASP Enzyme immunoassays in brown snake clinical investigators who recruited patients to the study: Gopalakrishnakone P, Tan C, editors. Progress in (Pseudonaja spp.) envenoming: detecting Yusuf Nagree (Armadale Hospital and Fremantle venom and toxin research. Singapore: National venom, antivenom and venom–antivenom Hospital), Adam Coulson and Garry Wilkes (Bunbury University of Singapore, 1987: 15-19. complexes. Tox icon 2006; 48: 4-11. Hospital), Nick Buckley (The Canberra Hospital), Alan 11 White J. CSL antivenom handbook. Melbourne: 23 Newcombe RG. Two-sided confidence intervals Tankel (Coffs Harbour Hospital), David Spain (Gold Coast CSL, 2001. for the single proportion: comparison of seven Hospital), Andrew Dawson (Royal Prince Alfred Hospital), 12 Parkin JD, Ibrahim K, Dauer RJ, Braitberg G. methods. Stat Med 1998; 17: 857-872. Colin Page (Princess Alexandra Hospital), Ovidu Pascui Prothrombin activation in eastern tiger snake 24 Casamento AJ, Isbister GK. Thrombotic (Sir Charles Gairdner Hospital), Naren Gunja (Westmead bite. Pathology 2002; 34: 162-166. microangiopathy in two tiger snake Hospital), and the ASP laboratory investigators. We also 13 Isbister GK, Woods D, Alley S, et al. Endogenous envenomations. Anaesth Intensive Care 2011; 39: acknowledge the many referrals from poisons information thrombin potential as a novel method for the 1124-1127. centres and clinical toxicologists and the help of many other nurses, doctors and laboratory staff in recruiting characterization of procoagulant snake venoms 25 Isbister GK, Scorgie FE, O’Leary MA, et al; ASP patients and collecting samples. and the efficacy of antivenom. Toxico n 2010; 56: Investigators. Factor deficiencies in venom- 75-85. induced consumption coagulopathy resulting Competing interests: No relevant disclosures. 14 Isbister GK, O’Leary MA, Schneider JJ, et al. from Australian elapid envenomation: Australian Received 8 Oct 2011, accepted 1 Mar 2012. Efficacy of antivenom against the procoagulant Snakebite Project (ASP-10). J Thromb Haemost effect of Australian brown snake (Pseudonaja 2010; 8: 2504-2513. 1 Rawlinson PA. Taxonomy and distribution of the sp.) venom: in vivo and in vitro studies. Toxicon 26 O’Leary MA, Schneider JJ, Krishnan BP, et al. Australian tiger snakes (Notechis) and 2007; 49: 57-67. Cross-neutralisation of Australian brown and copperheads (Austrelaps) (Serpentes: Elapidae). 15 Churchman A, O’Leary MA, Buckley NA, et al. tiger snake venoms with commercial Proc R Soc Victoria 1991; 103: 125-135. Clinical effects of red-bellied black snake antivenoms: cross-reactivity or antivenom 2 Cogger HG. Reptiles and amphibians of Australia. (Pseudechis porphyriacus) envenoming and mixtures? Tox icon 2007; 50: 206-213. Sydney: Reed New Holland, 2000. correlation with venom concentrations: 27 Sprivulis P, Jelinek GA, Marshall L. Efficacy and 3 Tibballs J, Henning RD, Sutherland SK, Kerr AR. Australian Snakebite Project (ASP-11). Med J Aust potency of antivenoms in neutralizing the Fatal cerebral haemorrhage after tiger snake 2010; 193: 696-700. procoagulant effects of Australian snake venoms (Notechis scutatus) envenomation. Med J Aust 16 Gan M, O’Leary MA, Brown SG, et al. Envenoming in dog and human plasma. Anaesth Intensive 1991; 154: 275-276. by the rough-scaled snake (Tropidechis Care 1996; 24: 379-381. ❏

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