Brown snakes are the leading cause of both snakebites and snakebite fatalities in Australia.1,2 The characteristic feature of significant envenomation by brown snakes is defibrination coagulopathy caused by potent procoagulants in the venom. However, the cause of cardiac arrest after this envenomation is unclear.

One hypothesis, derived from animal models, is that early massive thrombosis results in collapse, cardiac arrest and death. The brief thrombotic phase of envenomation occurs before the development of defibrination. It is hypothesised that coronary vessels become temporarily occluded, resulting in hypotension, collapse and cardiac arrest.3,4

We report a patient who was successfully resuscitated after cardiac arrest following brown snake envenomation. The clinical and laboratory evidence appears to support the above hypothesis.

A 44-year-old man found a snake (later identified as Pseudonaja nuchalis, also known as a gwardar) in his house in Toodyay (85 km east of Perth). He attempted to catch it and was bitten on the middle finger of the left hand. He was alone and placed a single compression bandage on his left upper limb extending from the fingers to the elbow. He then drove to his general practitioner, a journey of 15 km, taking about 10 minutes.

The GP observed no symptoms or signs of envenomation and referred the patient to Royal Perth Hospital by ambulance. In transit, several minutes from Swan District Hospital, the patient complained of feeling unwell with chest tightness, and rapidly became unresponsive. It was decided to seek medical attention at Swan District Hospital.

02:15 hours after the bite: On arrival at the hospital, the patient was in a tonic–clonic state and unresponsive. Electrocardiography (ECG) revealed a narrow complex rhythm with no cardiac output (ie, pulseless electrical activity). Standard advanced life support measures were commenced, including cardiopulmonary resuscitation, intubation, and administration of two 0.5 mg doses of adrenalin and one litre of normal saline. In addition, undiluted snake antivenom was given as an intravenous bolus, comprising one ampoule of polyvalent antivenom and two ampoules each of brown snake antivenom (2000 units) and tiger snake antivenom (6000 units). The situation was discussed with the on-call toxicologist at the local poisons information centre.

Once further antivenom supplies were obtained, another ampoule of polyvalent antivenom and three ampoules of brown snake antivenom (3000 units) were administered. Spontaneous circulation resumed within one minute of administration of these three ampoules. Total cardiopulmonary resuscitation time was 11 minutes. When the patient's condition was stabilised, he was transferred to Royal Perth Hospital. En route, the first signs of coagulopathy appeared, with bleeding lips and gingivae (Box 1). Results of laboratory investigations are shown in Box 2.

03:10 hours after the bite: On arrival at Royal Perth Hospital, the patient's heart rate was 105 bpm, blood pressure was 135/60 mm Hg, and pupils were equal at 4 mm diameter and briskly reactive. Examination revealed bleeding gingivae and nose, suffusion petechiae around the eyes, oozing from venepuncture sites, and rosé-coloured urine. ECG findings are shown in Box 3.

Initial management involved reinforcing the compression bandage and extending it to include the whole of the left upper limb, and infusion of 10 ampoules of brown snake antivenom in 100 mL 0.9% saline over 15 minutes. Following this infusion, no further oozing of blood was noted. The compression bandage was then removed. The patient's clinical condition remained stable. Cranial computed tomography revealed no evidence of intracranial haemorrhage, nor early evidence of arterial thrombosis or ischaemia.

05:00 hours after the bite: The patient was transferred to the intensive care unit, where his condition remained stable. Repeat coagulation studies at 05:53 hours after the bite revealed a plasma fibrinogen level still below 0.3 g/L (Box 2). A further five ampoules of brown snake antivenom were infused.

11:38 hours after the bite: Coagulation studies demonstrated the return of measurable clotting activity, with a fibrinogen titre < 0.3 g/L, but an international normalised ratio (INR) of 2.7, and an activated partial thromboplastin time (APTT) of 64.4 s. No further antivenom was given.

14:49 hours after the bite: Repeat coagulation studies revealed a rising fibrinogen titre of 0.5 g/L, INR of 1.8, and an APTT of 44.7 s. The patient was subsequently extubated, neurologically normal. No additional blood products, such as fresh frozen plasma or cryoprecipitate, were administered at any stage.

In view of the high antivenom load given to the patient and the consequent risk of serum sickness, the patient was commenced on a five-day course of oral prednisone (50 mg/day).

Day 2: The patient was transferred to the cardiology unit for investigation of the chest pain, collapse and subsequent rise in plasma troponin I level. He had no risk factors or previous history of cardiac disease, and experienced no further episodes of chest pain. An angiogram four days after envenomation revealed normal left ventricular function and normal coronary arteries. There were no abnormal neurological findings, and he was discharged after the angiogram.

At follow-up a month later: The patient was well but reported a mild flu-like illness with rash and sore joints between days 17 and 21 after envenomation.

Deaths after brown snake envenomation tend to be either early (within hours) or delayed (days after the bite). Early deaths have been thought to result from a primary cardiotoxic effect, anaphylaxis, or early massive thrombosis.3,4 Delayed deaths appear to result from secondary complications, such as intracranial haemorrhage.5,6

Our patient described chest tightness immediately before his sudden collapse, and the post-resuscitation ECG was non-specific, possibly consistent with diffuse myocardial ischaemia. These changes could be associated with short-lived coronary vessel occlusion by thrombi generated by venom procoagulants.3,4 The rise in serum troponin I level was consistent with the effects of cardiopulmonary resuscitation, but could also represent ischaemic injury to the myocardium.7

An in-vitro study showed that the venoms of three Pseudonaja spp. have strong coagulant activity.8 There is strong prothrombin activator activity (Factor Xa-like) converting prothrombin to thrombin, with no dependence on Factor V and little dependence on calcium and phospholipid. Intravenous injection of venom in dogs showed the potential for early thrombosis, resulting in hypotension, cardiac arrest and death.3,4

There have been previous reports of survival of patients in extremis after brown snake envenomation. In 1975, Sutherland described a 42-year-old woman who suddenly collapsed about 20 minutes after envenomation. She was said to be pulseless, but her condition improved within 30 seconds of receiving antivenom.9 In another report, a 52-year-old man became unconscious within 15 minutes of a bite by Pseudonaja textilis. He received 1000 units of brown snake antivenom intravenously 30 minutes after the bite, and his condition stabilised.10 However, in neither case did the patient require external cardiac compression or advanced life support measures, such as intubation and adrenalin. We believe that the more severe nature of our patient's condition makes this case notable.

Antivenom dosing is controversial and to some extent arbitrary. However, as a result of this case, we propose that cardiac arrest due to massive brown snake envenomation in Western Australia should be treated with an initial minimum bolus of at least five ampoules (5000 units) of undiluted brown snake antivenom. This contrasts with the usual slow infusion of diluted antivenom.

Even higher doses of antivenom may be required. A study in dogs found that the dose required to prevent cardiovascular depression and coagulopathy induced by P. textilis was 25 times the current recommended dose for clinical use.11 Other authors have also stated that the necessary dose of antivenom may be greater than current recommendations.5 In addition, the venom of the western brown snake (P. nuchalis, or gwardar) may be more potent than that of the eastern brown snake (P. textilis),12 while antivenom raised against P. textilis may be less effective in neutralising the venom components of Western Australia's P. nuchalis.13 It should be noted that antivenom is an increasingly scarce resource, and that stocks in many hospitals are limited.

Some clinicians might have considered administering adjuvant therapies, such as fresh frozen plasma, to our patient. However, our approach was consistent with the guidelines of the antivenom manufacturer, which state that fresh frozen plasma "is usually not needed and is contraindicated until all circulating venom has been neutralised with adequate antivenom, except if there is severe, life threatening haemorrhage".14 Our patient had acceptable INR and APTT readings within two hours of the last antivenom dose, and his fibrinogen level had returned to levels associated with haemostasis within five hours. He remained clinically stable, with no evidence of active haemorrhage.15

During the initial resuscitation, we chose a smaller than standard dose of adrenalin (0.5 mg v 1 mg) to avoid further increasing the risk of intracranial haemorrhage.6 As the cardiac arrest was witnessed, with only a short interval before resuscitation began, and as the cause was known, it was decided that a lower dose would provide the optimum balance between benefit and risk.

Our patient also illustrates the need to emphasise the public health message for the community — early application of appropriate first aid is effective in brown snake envenomation.16 Correct first aid comprises pressure immobilisation bandaging of the entire limb, keeping the patient still, splinting the limb and seeking medical attention. In many fatal cases, there has been a failure to apply correct first aid.17 Despite the development of antivenom, pressure immobilisation bandages and venom detection kits, brown snake envenomation still causes deaths, so consultation with an expert is always appropriate.

1: Coagulopathy after brown snake envenomation

The first signs of coagulopathy were bleeding lips and gingivae, which became apparent three hours after the snakebite.

3: Electrocardiogram after brown snake envenomation

Electrocardiogram 03:10 hours after the snakebite revealed sinus tachycardia, with a mild intraventricular conduction disturbance with a (pre-existing) right bundle branch block pattern (A), and mild generalised ST-segment depression (B).