Towards rationalisation of antivenom use in funnel-web spider envenoming: enzyme immunoassays for venom concentrations

Context: Funnel-web spider (Atrax and Hadronyche spp.) envenoming is rare but causes severe neuromuscular, autonomic, and cardiac effects. A rabbit-derived IgG antivenom is available, but venom detection in patients has not been reported. Objective: To use serial venom and antivenom concentrations to better define envenoming and antivenom effectiveness. Materials and methods: Serum was collected from nine patients with suspected funnel-web spider bites and clinical effects were recorded. Venom-specific enzyme immunoassays were developed to measure funnel-web spider venom and antivenom concentrations. Goat anti-rabbit whole serum was coupled to UltraLink resin and added to samples to remove bound venom and measure free venom. Antivenom efficacy was defined as antivenom binding all free venom and antivenom effectiveness as resolution of clinical features. Results: Venom was detectable in samples from six of nine patients. In three patients without venom detected, there were only moderate effects, which did not completely respond to antivenom in all cases and no spider was identified. In five of six cases, a male Atrax spp. (Sydney funnel-web) spider was identified. Three patients had moderate envenoming which responded to antivenom. Three patients had severe envenoming and developed catecholamine-induced myocarditis and acute pulmonary oedema. Although cholinergic and non-specific clinical features appeared to respond to antivenom, myocarditis and pulmonary oedema lasted 2–4 days. Median venom concentration pre-antivenom in five patients with samples was 5.6 ng/ml (3–35 ng/ml), and immediately post-antivenom decreased to a median of 0 ng/ml (0–1.8 ng/ml). Post-antivenom venom concentrations decreased when bound venom was removed; median, 0 ng/ml (0–0.9 ng/ml), indicating that most venom detected post-antivenom was bound. There was recurrence of venom and clinical features in one patient when a pressure bandage was removed. Conclusions: Detection of venom in suspected funnel-web spider bites identified definite cases with characteristic envenoming and a spider was identified. Measurement of venom concentrations pre- and post-antivenom demonstrated that venom was bound by antivenom, but in severe cases cardiac toxicity was not reversed.     

Mulga snake (Pseudechis australis) envenoming: a spectrum of myotoxicity,anticoagulant coagulopathy,haemolysis and the role of early antivenom therapy – Australian Snakebite Project (ASP-19)

Context. Mulga snakes (Pseudechis australis) are venomous snakes with a wide distribution in Australia. Objective. The objective of this study was to describe mulga snake envenoming and the response of envenoming to antivenom therapy. Materials and methods. Definite mulga bites, based on expert identification or venom-specific enzyme immunoassay, were recruited from the Australian Snakebite Project. Demographics, information about the bite, clinical effects, laboratory investigations and antivenom treatment are recorded for all patients. Blood samples are collected to measure the serum venom concentrations pre- and post-antivenom therapy using enzyme immunoassay. Results. There were 17 patients with definite mulga snake bites. The median age was 37 years (6–70 years); 16 were male and six were snake handlers. Thirteen patients had systemic envenoming with non-specific systemic symptoms (11), anticoagulant coagulopathy (10), myotoxicity (7) and haemolysis (6). Antivenom was given to ten patients; the median dose was one vial (range, one–three vials). Three patients had systemic hypersensitivity reactions post-antivenom. Antivenom reversed the coagulopathy in all cases. Antivenom appeared to prevent myotoxicity in three patients with high venom concentrations, given antivenom within 2 h of the bite. Median peak venom concentration in 12 envenomed patients with samples was 29 ng/mL (range, 0.6–624 ng/mL). There was a good correlation between venom concentrations and the area under the curve of the creatine kinase for patients receiving antivenom after 2 h. Higher venom concentrations were also associated with coagulopathy and haemolysis. Venom was not detected after antivenom administration except in one patient who had a venom concentration of 8.3 ng/ml after one vial of antivenom, but immediate reversal of the coagulopathy. Discussion. Mulga snake envenoming is characterised by myotoxicity, anticoagulant coagulopathy and haemolysis, and has a spectrum of toxicity that is venom dose dependant. This study supports a dose of one vial of antivenom, given as soon as a systemic envenoming is identified, rather than waiting for the development of myotoxicity.     

Australian taipan (Oxyuranus spp.) envenoming: clinical effects and potential benefits of early antivenom therapy – Australian Snakebite Project (ASP-25)

Context: Taipans (Oxyuranus spp.) are medically important venomous snakes from Australia and Papua New Guinea. The objective of this study was to describe taipan envenoming in Australian and its response to antivenom.

Methods: Confirmed taipan bites were recruited from the Australian Snakebite Project. Data were collected prospectively on all snakebites, including patient demographics, bite circumstances, clinical effects, laboratory results, complications and treatment. Blood samples were taken and analysed by venom specific immunoassay to confirm snake species and measure venom concentration pre- and post-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), complete 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 initial dose of one vial (range 1–4), and a median total dose of two vials (range 1–9). A greater total antivenom dose was associated with VICC, neurotoxicity and acute kidney injury. Early antivenom administration was associated with a decreased frequency of neurotoxicity, acute kidney injury, myotoxicity 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.     

Neurotoxicity in Russell’s viper (Daboia russelii) envenoming in Sri Lanka: a clinical and neurophysiological study

Context: Russell’s viper is more medically important than any other Asian snake, due to number of envenoming’s and fatalities. Russell’s viper populations in South India and Sri Lanka (Daboia russelii) cause unique neuromuscular paralysis not seen in other Russell’s vipers. Objective: To investigate the time course and severity of neuromuscular dysfunction in definite Russell’s viper bites, including antivenom response. Methodology: We prospectively enrolled all patients (>16 years) presenting with Russell’s viper bites over 14 months. Cases were confirmed by snake identification and/or enzyme immunoassay. All patients had serial neurological examinations and in some, single fibre electromyography (sfEMG) of the orbicularis oculi was performed. Results: 245 definite Russell’s viper bite patients (median age: 41 years; 171 males) presented a median 2.5?h (interquartile range: 1.75–4.0?h) post-bite. All but one had local envenoming and 199 (78%) had systemic envenoming: coagulopathy in 166 (68%), neurotoxicity in 130 (53%), and oliguria in 19 (8%). Neurotoxicity was characterised by ptosis (100%), blurred vision (93%), and ophthalmoplegia (90%) with weak extraocular movements, strabismus, and diplopia. Neurotoxicity developed within 8?h post-bite in all patients. No bulbar, respiratory or limb muscle weakness occurred. Neurotoxicity was associated with bites by larger snakes (p?<?0.0001) and higher peak serum venom concentrations (p?=?0.0025). Antivenom immediately decreased unbound venom in blood. Of 52 patients without neurotoxicity when they received antivenom, 31 developed neurotoxicity. sfEMG in 27 patients with neurotoxicity and 23 without had slightly elevated median jitter on day 1 compared to 29 normal subjects but normalised thereafter. Neurological features resolved in 80% of patients by day 3 with ptosis and weak eye movements resolving last. No clinical or neurophysiological abnormality was detected at 6 weeks or 6 months. Conclusion: Sri Lankan Russell’s viper envenoming causes mild neuromuscular dysfunction with no long-term effects. Indian polyvalent antivenom effectively binds free venom in blood but does not reverse neurotoxicity.     

Suspected snakebite: One year prospective study of emergency department presentations

Aim: Snakebite is an uncommon, but potentially life‐threatening condition. The more common clinical scenario is suspected snake‐bite. Our aim was to characterise the epidemiology, diagnosis and management of patients with suspected snakebites. Methods: Prospective cohort study of patients presenting with suspected snakebites to a tertiary referral hospital serving a large rural region in tropical northern Australia where a standard admission protocol for suspected snakebites is used. Results: Of 70 suspected snakebite cases, there were 45 definite bites: three severe envenomings (two western brown snakes [Pseudonaja nuchalis] and one mulga snake [Pseudechis australis]); seven mild/moderate envenomings by other snakes, two non‐envenomings by identified P. nuchalis, five bites by identified non‐venomous snakes and 28 definite bites without envenoming. The remaining 25 cases were either suspected bites (8), unlikely bites (15) and two people hit by snakes. Definite snake‐bites occurred throughout the year, peaking in May and December. There were three severe envenomings (mainly coagulopathy), requiring antivenom treatment, but no deaths or major complications. Most patients had appropriate investigations. Of 47 venom detection kit swabs collected, 34 were not tested, venom was not detected in nine and was positive in the three envenomings with one false‐positive tiger snake. Whole blood clotting time was highly sensitive for procoagulant coagulopathy and envenoming in this study. Median length of time from the bite to discharge was 20 h (interquartile range: 12–27). Conclusions: The study shows that although suspected snakebite was common, severe envenoming occurred in less than 5% of cases. The study supports the proposition that a structured approach and admission policy of suspected snakebites leads to the appropriate management of severe envenoming, with no cases discharged early and no cases of non‐envenoming treated with antivenom.     

Cross neutralization of coral snake venoms by commercial Australian snake antivenoms

Context: Although rare, coral snake envenomation is a serious health threat in Brazil, because of the highly neurotoxic venom and the scarcely available antivenom. The major bottleneck for antivenom production is the low availability of venom. Furthermore, the available serum is not effective against all coral snake species found in Brazil. An alternative to circumvent the lack of venom for serum production and the restricted protection of the actually available antivenom would be of great value. We compared the Brazilian coral snake and mono and polyvalent Australian antivenoms in terms of reactivity and protection.

Methods: The immunoreactivity of venoms from 9 coral snakes species were assayed by ELISA and western blot using the Brazilian Micrurus and the Australian pentavalent as well as monovalent anti-Notechis, Oxyuranus and Pseudechis antivenoms. Neutralization assays were performed in mice, using 3 LD₅₀ of the venoms, incubated for 30 minutes with 100?μL of antivenom/animal.

Discussion: All the venoms reacted against the autologous and heterologous antivenoms. Nevertheless, the neutralization assays showed that the coral snake antivenom was only effective against M. corallinus, M. frontalis, M. fulvius, M. nigrocinctus and M. pyrrhocryptus venoms. On the other hand, the Australian pentavalent antivenom neutralized all venoms except the one from M. spixii. A combination of anti-Oxyuranus and Pseudechis monovalent sera, extended the protection to M. altirostris and, partially, to M. ibiboboca. By adding Notechis antivenom to this mixture, we obtained full protection against M. ibiboboca and partial neutralization against M. lemniscatus venoms.

Conclusions: Our findings confirm the limited effectiveness of the Brazilian coral snake antivenom and indicate that antivenoms made from Australian snakes venoms are an effective alternative for coral snake bites in South America and also in the United States were coral snake antivenom production has been discontinued.     

Collett's snake (Pseudechis colletti) envenoming in snake handlers

BACKGROUND: Collett's snake (Pseudechis colletti) is a member of the black snake genus and occurs in a warm temperate to sub-tropical region of central Queensland, Australia. There are no reports of bites occurring in the wild, and bites were previously thought to cause only minor effects. They are a popular snake among zoos and exotic snake keepers. AIM: To investigate the clinical effects of severe envenoming by Collett's snake, and possible treatment options. DESIGN: Case series. METHODS: Clinical and laboratory features are described for six bites, all in snake handlers. RESULTS: All six bites were from captive snakes, resulting in severe envenoming in four. Two patients were treated early with black snake antivenom, and only developed an anticoagulant coagulopathy and mild myolysis. Two developed anticoagulant coagulopathy and severe rhabdomyolysis associated with acute renal failure, requiring haemodialysis; both received antivenom >10 h after the bite, and initially received minimal fluid replacement. Other effects included thrombocytopenia, non-immune haemolytic anaemia and a marked leukocytosis. DISCUSSION: Collett's snake envenoming is characterized by early generalized systemic effects (nausea, vomiting, abdominal pain, diarrhoea and headache) and an anticoagulant coagulopathy, followed in some cases by rhabdomyolysis and acute renal failure in untreated patients within 24 h. Early initiation of fluid therapy and treatment with black snake antivenom should be undertaken in all envenomed patients.     

Early pathology in venom-induced consumption coagulopathy by Rhabdophis tigrinus (Yamakagashi snake) envenomation

Objective: Rhabdophis tigrinus (Yamakagashi in Japanese) is a venomous non-front-fanged colubroid snake capable of inflicting envenoming with life-threatening defibrinating coagulopathy. However, because of the uncommon incidence of bites and tendency for late development of symptoms/signs, the early effects of the venom on the coagulation system are poorly known.

Case report: We describe a boy bitten by a wild R. tigrinus and report his clinical course starting at 30?min after the bite.

Results: At 30?min after envenomation, only the thrombin-antithrombin complex (TAT) level was elevated. At 90?min after envenomation, laboratory data revealed a prolonged activated partial thromboplastin time (APTT) and increased prothrombin time international normalized ratio (PT-INR) with elevated fibrinogen degeneration product (FDP). At 5.5?h after envenomation, APTT and PT-INR increased beyond a measurable range, and fibrinogen levels dropped below the detection limit. We administered recombinant human soluble thrombomodulin and antivenom prepared against R. tigrinus antivenom. Venom-induced consumption coagulopathy (VICC), which is sometimes reported as disseminated intravascular coagulation (DIC), subsequently improved rapidly.

Discussion: We found that TAT is the earliest marker to detect R. tigrinus envenomation and subsequent VICC occurrence. Although rTM was effective in this case, further studies are necessary to prove its safety and efficacy.     

The emerging syndrome of envenoming by the New Guinea small-eyed snake Micropechis ikaheka

The New Guinea small-eyed or Ikaheka snake, <it>Micropechis ikaheka</it>, which occurs throughout New Guinea and some adjacent islands, is feared by the indigenes. The first proven human fatality was in the 1950s and this species has since been implicated in many other cases of severe and fatal envenoming. Reliable attribution of envenoming to this species in victims unable to capture or kill the snake recently became possible by the use of enzyme immunoassay. Eleven cases of proven envenoming by <it>M. ikaheka</it>, with two fatalities, were identified in Papua New Guinea and Irian Jaya. Five patients showed no clinical signs of envenoming by other Australasian elapids: mild local swelling, local lymphadenopathy, neurotoxicity, general myalgia, spontaneous systemic bleeding, incoagulable blood and passage of dark urine (haemoglobinuria or myoglobinuria). Two patients developed hypotension and two died of respiratory paralysis 19 and 38 h after being bitten. <it>In vitro</it> studies indicate that the venom is rich in phospholipase A2, is indirectly haemolytic, anticoagulant and inhibits platelets, but is not procoagulant or fibrinolytic. It shows predominantly post-synaptic neurotoxic and myotoxic activity. Anecdotally, Commonwealth Serum Laboratories' (CSL) death adder antivenom has proved ineffective whereas CSL polyvalent antivenom may be beneficial. Anticholinesterase drugs might prove effective in improving neuromuscular transmission and should be tested in patients with neurotoxic envenoming.      

Neurotoxicity, anticoagulant activity and evidence of rhabdomyolysis in patients bitten by death adders (Acanthophis sp.) in southern Papua New Guinea

Thirty-two patients with enzyme-immunoassay-proven death adder (Acanthophis sp.) bites were studied in Port Moresby, Papua New Guinea. Eighteen were envenomed; local signs were rare and none had incoagulable blood, but all except one had signs of neurotoxicity. Five (27.7%) envenomed patients required intubation and ventilation. One patient developed renal failure, previously undescribed following death adder bites. Laboratory investigations showed mild prolongation of prothrombin and partial thromboplastin times in some patients. In vitro studies showed that the venom contains anticoagulant activity, but does not cause fibrinogenolysis. In contrast to taipan envenoming, neurotoxicity did not progress after antivenom administration, and there was reversal of neurotoxicity, evident within 6 h, in three severely envenomed patients treated less than 12 h after the bite. One patient treated with antivenom and anticholinesterases had the most dramatic response to treatment; the optimum management of bites by this species may include prompt treatment with both antivenom and anticholinesterases in addition to effective first aid.      

Vipera ammodytes bites treated with antivenom ViperaTAb: a case series with pharmacokinetic evaluation

Context: In clinical practice it is difficult to differentiate between V. berus and V. ammodytes venomous bites. In the past this was not a concern, but due to the current shortage in Viperfav? and European viper venom antiserum availability, V. a. ammodytes venomous bites have recently been treated with ViperaTAb^®, which is a pharmaceutical formulation containing a monospecific ovine Fab fragments against the venom of V. berus.

Objective: To evaluate ViperaTAb^® in V. a. ammodytes envenomations.

Materials and methods: This is a prospective case series of three consecutive patients envenomed by V. a. ammodytes snakebite treated with ViperaTAb^®. V. ammodytes venom, neurotoxic ammodytoxins, and Fab fragment levels were determined in serum samples and a pharmacokinetic analysis of the antivenom Fab fragments was carried out.

Results: Three patients bitten by V. a. ammodytes with extensive local swelling, neurological symptoms and recurrent thrombocytopenia were treated with ViperaTAb^®. V. ammodytes venom was detected in serum of all three patients. Ammodytoxins were detected in the serum of only the most severely envenomed patient who developed neurological symptoms. In the presented moderate cases, a dose of 8?mL of ViperaTAb^® reduced swelling and improved systemic effects, such as thrombocytopenia. However, this dose of ViperaTAb^® was not effective in the most severely envenomed patient with the highest serum values of V. ammodytes venom. In this case ViperaTAb^® did not stop local swelling and it had no effect on neurological signs. ViperaTAb^®’s systemic clearance, distribution and elimination half-lives were 4.3–13.4?mL/h/kg, 1.2–3.2?h and 14.1–55.4?h, respectively.

Conclusions: In patients envenomed by V. a. ammodytes venom, ViperaTAb^® reduces moderate swelling and temporarily improves systemic effects, except neurological symptoms. ViperaTAb^® application induces a decrement of V. ammodytes venom level in the blood, but did not affect serum concentration of neurotoxic ammodytoxins in the one patient with measurable concentrations.     

Exotic snake bites in the Czech Republic—Epidemiological and clinical aspects during 15-year period (1999–2013)

Only one natural venomous snake—the adder viper—lives in the central European region and its bite is usually associated only with mild course of envenoming. Cases of envenoming caused by exotic snakes among their breeders are clinically more important. Objective. The aim of this study was to analyze the epidemiological and clinical aspects of registered venomous bites caused by exotic snakes in the Czech Republic over a period of 15 years (1999–2013). Materials and methods. This is an observational case series. Data have been collected retrospectively from a database and medical charts of the Toxinology Center belonging to the General University Hospital in Prague. Results. In total, 87 cases of exotic snakebites caused by 34 venomous snake species were registered during the study period, coming from 18 genera of Elapinae, Viperinae, and Crotalinae subfamilies. In the cohort, 29 patients (33.3%) developed systemic envenoming and 17 (19.5%) were treated with antivenom. Ten cases of envenoming (11.5%) were considered as potentially life threatening. No patient died due to envenoming caused by exotic snake bites during the study period. Four illustrative cases of envenoming (Echis pyramidum, Dendroaspis polylepis, Protobothrops mangshanensis, and Proatheris superciliaris) are described in detail. Conclusion. Bites caused by exotic snakes resulted in serious and life-threatening envenomings in some patients. Early transfer to the Center, antivenom administration, and support of failing organ functions contributed to favorable outcome of victims.     

Life-threatening envenoming by the Saharan horned viper (Cerastes cerastes) causing micro-angiopathic haemolysis, coagulopathy and acute renal failure: clinical cases and review

BACKGROUND: The desert horned vipers (Cerastes cerastes and C. gasperettii) are the most familiar snakes of the great deserts of North Africa and the Middle East, including the plains of Iraq. They are responsible for many human snake bites. In Western countries, they are popular among exotic-snake keepers. AIM: To investigate mechanisms of life-threatening envenoming and treatment. DESIGN: Clinical investigation. METHODS: Clinical and laboratory studies with measurement of serum venom antigen concentrations by enzyme immunoassay. RESULTS: Two men bitten while handling captive Saharan horned vipers (Cerastes cerastes) in Europe developed extensive local swelling and life-threatening systemic envenoming, characterized by coagulopathy, increased fibrinolysis, thrombocytopenia, micro-angiopathic haemolytic anaemia and acute renal failure. The clinical picture is explicable by the presence in C. cerastes venom of several thrombin-like, Factor-X-activating, platelet-aggregating, haemorrhagic and nephrotoxic components. In one case, prophylactic use of subcutaneous epinephrine may have contributed to intracranial haemorrhage. The roles in treatment of heparin (rejected) and specific antivenom (recommended) are discussed. DISCUSSION: Cerastes cerastes is capable of life-threatening envenoming in humans. Optimal treatment of envenoming is by early administration of specific antivenom, and avoidance of ineffective and potentially-dangerous ancillary methods.     

Bites by the King Cobra (Ophiophagus hannah) in Myanmar: Successful Treatment of Severe Neurotoxic Envenoming

Three patients bitten by the world's largest species of venomoussnake, the king cobra (Ophiophagus hannah), were observed inMyanmar (Burma). All three were involved in the famous snakedance in Yangon (Rangoon) Zoological Gardens. One patient showedno signs of envenoming despite a sustained bite, another developedonly signs of local envenoming, but in a third there was severeneurotoxic envenoming requiring mechanical ventilation for 64hours, episodes of hypotension and massive swelling of the bittenlimb. This patient showed some signs of recovery before delayedtreatment with specific antivenom. It is possible that all threepatients had some immunity to king cobra venom resulting fromtraditional ‘immunization’ achieved by seratchingvenom into the skin. The literature on king cobra bites is reviewedand recommendations given for antivenom and ancillary treatments.     

Effects of Envenoming by Comb‐Footed Spiders of the Genera Steatoda and Achaearanea (Family Theridiidae: Araneae) in Australia

Abstract

Background:?The family Theridiidae (comb‐footed spiders) contains the well‐known and medically important widow spider group (Latrodectus spp.). Little is known about the effects of envenoming by other common members of this family. Objective:?The objective of this study was to determine the clinical effects of bites by common theridiid spiders of the genera Steatoda and Achaearanea. Methods:?This was a prospective cohort study of calls to Australian poison information centers and presentations to emergency departments. Twenty‐eight persons with a definite bite by a spider of the family Theridiidae, excluding Latrodectus spp., were included where the spider was immediately collected and expertly identified from February 1999 to April 2002. Results:?There were 23 bites by Steatoda spp. and five bites by Achaearanea spp. Steatoda bites occurred across Australia, throughout the year, and the majority during waking hours. Seventy‐eight percent of bites occurred indoors and 48% while dressing indoors. Pain was universal and was severe in six (26%). Increasing pain in the first hour occurred in 30%, and the median duration of pain was 6 hr (interquartile range: 1–12 hr). Local or regional diaphoresis did not occur. Systemic effects occurred in 30% and included nausea, headache, lethargy, and malaise. The majority received no treatment: seven patients presented to a hospital (two patients received opiates for analgesia) and 1 patient inadvertently received intravenous redback spider (RBS) antivenom because the spider was initially misidentified as a RBS (Latrodectus). The pain and symptoms responded over 1 hr following antivenom administration. Bites by Achaeranea spp. caused moderate to severe persistent pain, but no systemic effects. Conclusions:?Steatoda spp. bites or “steatodism” may cause prolonged pain and systemic effects similar to Latrodectus bites, but less severe. In severe cases, the clinical effects were almost indistinguishable from Latrodectus, except diaphoresis was absent, and the spiders were often mistaken for Latrodectus. Intravenous RBS antivenom appears to be an effective treatment in isolated severe cases, consistent with in vitro work. Achaearanea bites caused pain similar to Latrodectus bites.     

Coagulopathy as the main systemic manifestation after envenoming by a juvenile South American rattlesnake (Crotalus durissus terrificus): Case report

Abstract

Context. Rattlesnake bites in Brazil are generally caused by adult individuals, with most of the envenomed patients showing systemic manifestations that include varying degrees of neurotoxicity (acute myasthenia), rhabdomyolysis and coagulopathy, with only mild or no local manifestations. We report a case of envenoming by a juvenile South American rattlesnake (Crotalus durissus terrificus) that involved coagulopathy as the main systemic manifestation. Case details. A 19-year-old male was admitted to our Emergency Department with coagulopathy (incoagulable PT, APTT and INR), no remarkable local manifestations and no signs/symptoms of myasthenia or rhabdomyolysis (serum CK, LDH, ALT and AST within reference levels) 5 days after being bitten by a small snake that was described as a rattlesnake but was not brought for identification at admission. The patient had already been treated in another Emergency Department with i.v. bothropic antivenom (AV) 1 h and 4 days post-bite. Based on the possibility of an unusual rattlesnake bite, crotalic AV was administered i.v., which improved the coagulation (9 h post-CroAV, INR = 2.11; 36 h post-CroAV, INR = 1.42). During hospitalization, relatives brought the snake that caused the bite, which was identified as a 38-cm long C. d. terrificus. Discussion. Little is known about the clinical manifestations after bites by juvenile C. d. terrificus. This case shows that systemic envenoming by juvenile C. d. terrificus may result in coagulopathy as the main systemic manifestation, without neuromyotoxic features normally associated with bites by adult specimens. Despite the delayed administration, crotalic AV was effective in improving the blood coagulation.     

Pharmacokinetics and pharmacodynamics of the myotoxic venom of Pseudechis australis (mulga snake) in the anesthetised rat

Context. Myotoxicity is a common clinical effect of snake envenoming and results from either local or systemic myotoxins in snake venoms. Although numerous myotoxins have been isolated from snake venoms, there has been limited study on the relationship between the time course of venom concentrations (pharmacokinetics) and the time course of muscle injury measured as a rise in creatine kinase (CK) (pharmacodynamics). Objective. The aim of this study was to develop an in vivo model of myotoxicity to investigate the time course of myotoxicity and the effect of antivenom. Materials and methods. Anesthetised rats were administered Pseudechis australis (mulga snake) venom either through i.v., i.m. or s.d. route, including a range of doses (5–100 μg/kg). Serial blood samples were collected for measurement of venom using enzyme immunoassay and measurement of CK and creatinine. Antivenom was administered before, 1 and 6 h after venom administration to investigate its effect on muscle injury. Plots of venom and CK versus time were made and the area under the curve (AUC) was calculated. Results. There was a significant dose-dependent increase in CK concentration after administration of P. australis venom, which was greatest for i.v. administration. Timed measurement of venom concentrations showed a rapid absorption through s.d. and i.m. routes and a delayed rise in CK concentrations following any route. Antivenom prevented myotoxicity shown by a decrease in the CK AUC, which was most effective if given earliest. There was a rise in creatinine following i.v. venom administration. Conclusion. The study shows the delayed relationship between venom absorption and the rise in CK, consistent with the delayed onset of myotoxicity in human envenoming. Antivenom prevented myotoxicity more effectively if given earlier.     

Snake bites by the jararacucu (Bothrops jararacussu): clinicopathological studies of 29 proven cases in Sao Paulo State, Brazil

The jararacucu, one of the most dreaded snakes of Brazil, southern Bolivia, Paraguay and northeastern Argentina, is a heavily-built pit viper which may grow to a length of 2.2 m. Up to 1000 mg (dry weight) of highly-lethal venom may be milked from its venom glands on a single occasion. It has accounted for 0.8% to 10% of series of snake bites in Sao Paulo State, Brazil. We examined 29 cases of proven jararacucu bites recruited over a 20-year period in two Sao Paulo hospitals. Severe signs of local and systemic envenoming, (local necrosis, shock, spontaneous systemic bleeding, renal failure) were seen only in patients bitten by snakes longer than 50 cm; bites by shorter specimens were more likely to cause incoagulable blood. Fourteen patients developed coagulopathy, six local necrosis (requiring amputation in one) and five local abscesses. Two became shocked and four developed renal failure. Three patients, aged 3, 11 and 65 years, died 18.75, 27.75 and 83 h after being bitten, with respiratory and circulatory failure despite large doses of specific antivenom and intensive-care- unit management. In two patients, autopsies revealed acute renal tubular necrosis, cerebral oedema, haemorrhagic rhabdomyolysis at the site of the bite and disseminated intravascular coagulation. In one survivor with chronic renal failure, renal biopsy showed bilateral cortical necrosis; the patient remains dependent on haemodialysis. Effects of polyspecific Bothrops antivenom were not impressive, and it has been suggested that anti-Bothrops and anti-Crotalus antivenoms should be given in combination.      

Snake Eyes: Coral Snake Neurotoxicity Associated With Ocular Absorption of Venom and Successful Treatment With Exotic Antivenom

Background

Coral snake bites from Micrurus fulvius and Micrurus tener account for < 1% of all snake bites in North America. Coral snake envenomation may cause significant neurotoxicity, including respiratory insufficiency, and its onset may be delayed up to 13 h.