A review of 91 canine and feline red-bellied black snake (Pseudechis porphyriacus) envenomation cases and lessons for improved management.

INTRODUCTION: Most cases of red-bellied black snake (RBBS) envenomation in dogs respond favourably to treatment comprising of tiger-brown snake antivenom (TBAV), intravenous fluid therapy, analgesia and, if indicated, mechanical ventilation and/or blood transfusion. However, there remains a subset of patients who develop fatal complications despite intensive treatment and risk factors for these occurring remain unknown. Here we present a retrospective cross-sectional survey of 91 canine and feline RBBS envenomation cases. METHODS: Cases seen between June 2010 and June 2020 were retrieved from the databases of seven practices in South East and coastal Queensland. From the canine case population, logistic regression analysis was performed to assess the impact of potential risk factors at presentation on the likelihood of death. A final multivariable model was developed using a manual backwards elimination approach based on overall likelihood ratio tests and Wald chi-square P-values for each variable. Where model convergence failed due to quasi-complete separation, Firth's penalised maximum likelihood method was implemented. Such separation may occur when an outcome is completely predicted by an explanatory variable in one group. RESULTS: Of the 88 canine cases, 7 died (8.0%), all after prognosis-based euthanasia. Of the three feline cases, one died after unsuccessful resuscitation following cardiopulmonary arrest. Compared to survivors, dogs that died were older, exhibited pigmenturia, received antivenom later and had a higher total plasma protein (TPP), activated clotting time (ACT) and lower packed cell volume (PCV) at presentation.

Pathology of Fatal Australian Black Snake (Pseudechis sp) Envenomation in Two Adult Dogs.

Black snakes (Pseudechis spp) are a genus of venomous Australian elapid snakes that can cause major clinical envenomation in companion animals, which may be fatal, even with appropriate antivenom treatment. Despite its clinical significance, there is little published information on the pathology of black snake envenomation. We report the gross and microscopic lesions associated with black snake envenomation in two dogs, one with a definitive immunological species identification of red-bellied black snake (RBBS; Pseudechis porphyriacus), the other with a black snake immunotype on a venom detection kit. Both dogs were located in a geographical area where the RBBS is found. The prominent gross findings in both cases included icterus, localized facial oedema in the region of the presumed bite wound, pigmenturia and multicavitary serosanguineous effusions. Histopathology of the confirmed RBBS case revealed acute renal tubular necrosis with haemosiderosis, marked splenic haemosiderosis and centrilobular to midzonal hepatocellular necrosis with severe cholestasis. Defining the spectrum of lesions of elapid snake envenomation improves understanding of the pathogenesis, which may lead to improved patient outcomes and post-mortem diagnosis.

Population pharmacokinetics of Pseudechis porphyriacus (red-bellied black snake) venom in snakebite patients.

OBJECTIVES: Understanding the time course of venom exposure in snakebite patients is important for the optimisation of treatment including antivenom dose and timing. We aimed to investigate the pharmacokinetics of red-bellied black snake (RBBS; Pseudechis porphyriacus) venom in envenomed patients. METHODS: Timed venom concentration data were obtained from patients with RBBS envenomation recruited to the Australian Snakebite Project (ASP), including demographics and antivenom treatment. Venom concentrations were measured using an enzyme immunoassay. Data were modelled using NONMEM version 7.3. Uncertainty in venom "dose" was accounted for by arbitrarily fixing the average amount to 1 mg and incorporating between-subject variability on relative bioavailability. A scale parameter for venom clearance was implemented to account for the rapid venom clearance following antivenom dosing. A sensitivity analysis was performed to determine the magnitude of venom clearance amplification. RESULTS: There were 457 venom concentrations in 114 patients (median age 41, 2-90 y; 80 male). Antivenom was administered to 54 patients a median of 4.2 h post-bite (0.67 to 32 h). A one-compartment model with first-order absorption and elimination provided the best description of the data. The estimated clearance and volume of distribution were 5.21 L/h and 39.9 L, respectively. The calculated elimination half-life of P. porphyriacus venom from the final pharmacokinetic model was 5.35 ± 0.36 h. The variability in the relative dose of injected venom was 140%. Antivenom administration increased venom clearance by 40-fold. Ten patients showed evidence of a double peak in the absorption profile. CONCLUSION: The information on the exposure time of venom in the body following envenomation will help improve treatment and the timing of antivenom.

Venom of the Red-Bellied Black Snake Pseudechis porphyriacus Shows Immunosuppressive Potential.

Venoms act with remarkable specificity upon a broad diversity of physiological targets. Venoms are composed of proteins, peptides, and small molecules, providing the foundation for the development of novel therapeutics. This study assessed the effect of venom from the red-bellied black snake (Pseudechis porphyriacus) on human primary leukocytes using bead-based flow cytometry, mixed lymphocyte reaction, and cell viability assays. We show that venom treatment had a significant immunosuppressive effect, inhibiting the secretion of interleukin (IL)-2 and tumor necrosis factor (TNF) from purified human T cells by 90% or greater following stimulation with mitogen (phorbol 12-myristate 13-acetate and ionomycin) or via cluster of differentiation (CD) receptors, CD3/CD28. In contrast, venom treatment did not inhibit TNF or IL-6 release from antigen-presenting cells stimulated with lipopolysaccharide. The reduced cytokine release from T cells was not associated with inhibition of T cell proliferation or reduction of cell viability, consistent with an anti-inflammatory mechanism unrelated to the cell cycle. Deconvolution of the venom using reverse-phase HPLC identified four fractions responsible for the observed immunosuppressive activity. These data suggest that compounds from P. porphyriacus venom may be potential drug leads for T cell-associated conditions such as graft versus host disease, rheumatoid arthritis, and inflammatory bowel disease.

Red-bellied black snake (Pseudechis porphyriacus) envenomation in 17 dogs: clinical signs, coagulation changes, haematological abnormalities, venom antigen levels and outcomes following treatment with a tiger-brown snake antivenom.

BACKGROUND: This report describes 17 cases of red-bellied black snake envenomation (RBBS; Pseudechis porphyriacus) in dogs in south-eastern Queensland. Patients were prospectively enrolled for the treatment with a new tiger-brown snake antivenom 8000 units, (TBAV; Padula Serums Pty Ltd, VIC, Australia). CASE REPORT: Clinical diagnosis of RBBS envenomation was made by either snake venom detection kit, snake identification using scale counting, or owner observed dog-snake interaction in patients with clinical signs of envenomation. An RBBS venom antigen sandwich ELISA was used to retrospectively quantify venom levels in frozen serum and urine. Mechanical ventilation was required in 11% (2/17) patients, whole blood transfusion in 12% (2/17), tissue swelling at the bite site occurred in 53% (9/17) and facial palsy in 12% (2/17). One dog was euthanised, and overall, 94% (16/17) survived to hospital discharge. Clinicopathological changes pre-TBAV included variable haemolysis, increased CK, pigmenturia and mildly prolonged active clotting time with a median of 134 s (n = 13, range 91-206 s). Haematological profiles post envenomation revealed anaemia (6/6) and spherocytosis (5/5), which resolved without the use of corticosteroids. Pre-TBAV, median RBBS venom antigen concentration was 22.6 ng/mL (n = 15, range 2-128) in serum and 58 ng/mL (range 1-452) in urine; RBBS venom antigen was undetectable in serum post-TBAV in all patients. CONCLUSION: Some RBBS envenomed dogs required, critical care including mechanical ventilation, blood transfusion, additional antivenom and prolonged hospitalisation. TBAV was effective with excellent prognosis despite stated specificity for tiger and brown snake.

Local morbidity from red-bellied black snake (Pseudechis porphyriacus, Elapidae) envenoming: Two cases and a brief review of management.

The red-bellied black snake (Pseudechis porphyriacus, Elapidae) is one of several species of venomous snakes most commonly implicated in human and domestic animal envenoming in Australia. Human systemic envenoming can present with myotoxicity that may include myoglobinuria; hemoglobinuria and intravascular hemolysis; thrombocytopenia, anticoagulant coagulopathy, and, rarely, mild cranial nerve palsies. Pseudechis porphyriacus envenoming can also feature significant local morbidity such as ecchymoses, bleeding, pain and necrosis. Some envenomed patients may develop progressive thickness necrosis independent of secondary infection, and occasionally require surgical debridement. Uncommonly, some digital envenoming may cause more severe deeper tissue pathology that justifies dermotomy and/or distal phalangeal amputation. Presented are two patients with significant local morbidity from P. porphyriacus envenoming. An 18-month old girl received a protracted envenoming on her right foot, while a 38-year old male professional zoologist was envenomed on the third digit of his right hand. Each patient experienced myotoxicity, one had anticoagulant coagulopathy, and both developed clinically significant local morbidity including persistent bleeding, ecchymoses, local necrosis and pain; each required extensive treatment and variably prolonged admission. Noted also were transiently elevated D-dimer with low-normal or normal fibrinogen levels. The progressive necrosis and subsequent chronic pathologic changes with ischemia of the latter patient's digit eventually required a dermotomy and amputation of the distal phalanx. The pediatric patient did not require extensive wound debridement, but experienced prolonged difficulty in ambulation because of slowly resolving wound discomfort. Factors that may contribute to the severity of local morbidity of P. porphyriacus envenoming are considered, and management of envenoming by this taxon is briefly reviewed.

Severe haemolysis and spherocytosis in a dog envenomed by a red-bellied black snake (Pseudechis porphyriacus) and successful treatment with a bivalent whole equine IgG antivenom and blood transfusion.

This case report describes a dog envenomed by a red-bellied black snake (RBBS; Pseudechis porphriacus) that experienced severe and life-threatening haemolysis. The dog presented with hypersalivation, facial swelling, mildly prolonged activated clotting time and the absence of neurological deficits. Envenomation was confirmed by positive identification of the snake and retrospective measurement of RBBS specific venom antigen (24 ng/mL) in serum. The dog was initially hospitalised, treated with intravenous fluids and one vial of tiger-brown snake antivenom which is recommended for RBBS envenomation in Australia. However, after 3.5 d the dog's PCV had declined to 15% and the dog was dull and tachycardic. A second vial of tiger-brown antivenom followed by a packed red blood cell transfusion was administered. A rapid clinical improvement within 12 h was observed. No free RBBS venom was detected in serum at any time point after the first vial of antivenom. Longitudinal haematology and biochemical profiling was performed to 62 d post-envenomation and revealed a gradual recovery in the haematocrit to normal reference range. Spherocyte numbers on blood smear were highest at 5 d post-envenomation and gradually declined to undetectable after 62 d. This case highlights the potential for unpredictable, severe and life-threatening anaemia resulting from RBBS envenomation in dogs.

Severe neurotoxicity requiring mechanical ventilation in a dog envenomed by a red-bellied black snake (Pseudechis porphyriacus) and successful treatment with an experimental bivalent whole equine IgG antivenom.

Snakebite in dogs from Pseudechis porphyriacus (red-bellied black snake; RBBS) is a common envenomation treated by veterinarians in Australia where this snake occurs. This case report describes the successful treatment of a clinically severe RBBS envenomation in a dog with an experimental bivalent equine whole IgG antivenom and mechanical ventilation, following its presentation in a cyanotic state. The cause of the cyanosis and respiratory distress was considered due to paralysis from neurotoxins in RBBS venom. The dog was treated with two vials of bivalent antivenom, each containing sufficient antivenom to neutralise the lethal effects of 40 mg of tiger snake (Notechis sp) and 40 mg of brown snake (Pseudonaja sp) venom. Hypoxaemia (Sp02 of 75%) and hypercapnia (PaCO2 of 61 mmHg) indicated the need for mechanical ventilation (MV) to prevent imminent death. The dog was anaesthetised using total intravenous anaesthesia and MV used for 18 h. Following discontinuation of MV, it resumed spontaneous breathing thereafter and made a complete recovery. Serum biochemistry revealed a significant myopathy with elevated CK and AST levels, peaking approximately 48 h post-treatment. Elevated liver enzymes, suggestive of hypoxic liver injury, were detected during the period of hospitalisation. The dog represented approximately one week after hospital discharge because of inappetence and mild hepatopathy, which resolved spontaneously by 30 d post-treatment. A mild coagulopathy was initially present which resolved within 24 h following antivenom treatment. At initial presentation, RBBS venom antigen was detected by sandwich ELISA in urine and serum. Free RBBS venom antigen was not detected post-antivenom treatment. Human cases of RBBS requiring ventilatory support are rare. This unusual case of RBBS envenomation in a dog highlights its potential clinical severity in dogs, and the need for early, aggressive, MV to achieve a successful outcome in cyanosed and clinically severe cases.

Clinical features of serum sickness after Australian snake antivenom.

Serum sickness is a delayed immune reaction in which the immune system responds to a protein in antiserum as a potentially harmful substance and mounts an IgG-mediated antibody response. A 32 year-old female patient had systemic envenoming following a bite by a red-bellied black snake (Pseudechis porphyriacus). She was treated with Tiger snake antivenom and recovered over 24 h and did not develop myotoxicity. She then presented with local pain, itching and swelling, which was partially treated with antihistamines. Eleven days after the bite she presented again with symptoms of worsening serum sickness including rash on the upper legs, joint and muscle pain in arms, ankles and knees, and nausea. The patient was prescribed five days of prednisone 50 mg/day, antihistamine 10 mg/day and analgesia 1000 mg/day and improved over 2 days. She had no further problems on follow up at 4 months. This case highlights that serum sickness can cause significant effects after the treatment of snake envenoming. It develops 5-14 days after antivenom administration and has characteristic clinical and laboratory features. Severe cases of serum sickness can result in morbidity but it appears to respond well to corticosteroid treatment.