Australia has a number of venomous snakes with some of the most potent venoms in the world. All the medically important snakes are elapids (front-fanged), although bites rarely occur from colubrids and non-venomous snakes. New Zealand has no snakes of medical importance. The risk of significant coagulopathy and uncommonly death, even after apparently trivial contact with Australian snakes, remains and must be appreciated by healthcare workers [1].

Epidemiology

It is thought that approximately 3000 suspected snakebites occur annually in Australia, but this figure is difficult to estimate and depends on how many suspected bites, non-venomous bites and non-envenomed cases are included. The number of envenomed cases is far less and probably in the order of 100–200 each year; the majority of which occur in rural and regional areas. Snakebite deaths continue to occur (about 1–5 per year) and are usually a result of early cardiac arrest in brown snakebites or major haemorrhage in coagulopathic patients [1].

The commonest clinical manifestation is coagulopathy which occurs in about three-quarters of envenomed cases, the majority in brown snake bites [2]. Neurotoxicity and myotoxicity are now uncommon and mechanical ventilation is rarely required for treatment [2]. The types of snakes causing major envenoming differ across Australia. Bites in snake handlers remain an important problem with about 10% of all bites being in snake handlers. However, they are almost all bites from Australian snakes, albeit the more uncommon and interesting snakes and exotic snakebite is very rare [3]. Although snake handlers often want to avoid antivenom, they should be treated like anyone else because there is little evidence to support they are at higher risk of antivenom reactions. Snake handlers and people working with snake venoms can develop systemic hypersensitivity reactions to venom itself, so venom anaphylaxis must be a differential diagnosis in these patients [3].

Prevention

Most snakebites are preventable and result from snake handling or interference with snakes in the wild, sometimes in the setting of alcohol consumption. Ideally, snakes should be left alone and those working with or keeping snakes should have appropriate training and licences. Simple precautions, such as wearing thick long pants and boots when walking in the bush or when working with snakes, can prevent most bites due to the short length of Australian elapid fangs. Snake handlers should carry and maintain first-aid kits that include at least four broad elastic bandages (15 cm; e.g. Ace) and have practised applying the bandage. If exotic snakes are being held, including Australasian snakes out of their geographical distribution, appropriate antivenoms should be available.

Clinical features

Systemic envenoming results when venom is injected subcutaneously and reaches the systemic circulation. Whether or not a snakebite results in systemic envenoming depends on a number of factors including fang length, average venom yield of the snake, effectiveness of the bite and bite site. Recent studies have suggested that only a small amount of the injected venom actually reaches the systemic circulation [1,4]. Most snakebites do not result in envenoming because either insufficient venom reaches the systemic circulation or the snake is non-venomous.

Envenoming is characterized by local and systemic effects, although Australasian elapids rarely cause major local effects, such as necrosis and local haemorrhage. The clinical features of envenoming depend on the particular toxins present in each snake’s venom but non-specific systemic symptoms (nausea, vomiting, headache, abdominal pain, diarrhoea and diaphoresis) occur in many cases. The major clinical syndromes are coagulopathy, neurotoxicity, myotoxicity and acute kidney injury [2]. Severe envenoming can result in early collapse associated with dizziness, loss of consciousness, apnoea and hypotension [1]. In the majority of cases, there is spontaneous recovery over 5–15 min but, in some case, this does not occur and multiorgan failure and death ensue if resuscitation is delayed [1].

The medically important Australian snakes and their associated clinical effects are listed in Table 30.1.1.

Table 30.1.1

Clinical syndromes associated with the major venomous Australian snakes and the recommended antivenom

Snake	Coagulopathy	Neurotoxicity	Myotoxicity	Systemic symptoms	Thrombotic microangiopathy	Cardiovascular effects	Antivenom
Brown snake	VICC¹	Rare and mild	–	<50%	10%	Collapse (25%) Cardiac arrest (5%)	Brown snake
Tiger snake group
Tiger snake	VICC	Uncommon	Uncommon	Common	5%	Rare	Tiger snake
Rough-scale snake	VICC	Uncommon	Uncommon	Common	<5%	Rare	Tiger snake
Hoplocephalus spp.²	VICC	–	–	<50%	–	–	Tiger or brown snake
Black snakes
Mulga snake	Anticoagulant	–	Common	Common	–	–	Black snake³
Red-bellied black snake	Anticoagulant	–	Uncommon	Common	–	–	Tiger snake⁴
Death adder	–	Common	–	Common	–	–	Death Adder³
Taipan	VICC	Common	Rare	Common	5%	Uncommon	Taipan³

¹VICC: venom-induced consumption coagulopathy;

²The Hoplocephalus genus/group includes Stephen’s banded snake (H. stephensi), the broad headed snake (H. bungaroides) and the pale-headed snake (H. bitorquatus);

³Polyvalent antivenom can be substituted for these large volume monovalent antivenom with no increase in risk or cost;

⁴Polyvalent or tiger snake antivenom cannot be used for sea snake envenoming.

Coagulopathy

Venom-induced consumption coagulopathy (VICC)

This is the commonest and most important clinical effect in Australian snake envenoming. Venom-induced consumption coagulopathy (VICC) results from a prothrombin activator in the snake venom converting prothrombin (Factor II) to thrombin which leads to consumption of Factors V, VIII and fibrinogen, associated with a massive increase in fibrinogen degradation products [5]. Most dangerous Australian snakes contain such a prothrombin activator including brown snakes, snakes in the tiger snake group and taipans [5]. VICC develops rapidly within 15–60 min and the onset may coincide with the initial collapse seen with major envenoming by brown snakes and taipans [1]. Recovery usually takes 12–18 h [5].

Anticoagulant coagulopathy

Anticoagulant coagulopathy occurs in black snake envenoming, including mulga and red-bellied black snakes and is characterized by an abnormal activated partial thromboplastin time (aPTT) [6,7]. It is unlikely to result in haemorrhage and of itself is rarely of clinical importance. However, anticoagulant coagulopathy is a useful marker of envenoming and is rapidly reversed with antivenom [6].

Neurotoxicity

Paralysis is a classic effect of snakebite and is due to mainly presynaptic neurotoxins that occur in almost all Australian elapids. Presynaptic neurotoxins disrupt neurotransmitter release from the terminal axon and are associated with cellular damage. This type of neurotoxicity does not respond to antivenom treatment and may take days to weeks to resolve in severe cases. Neurotoxic envenoming manifests as a progressive descending flaccid paralysis. The first sign is usually ptosis followed by facial and bulbar involvement and progressing to paralysis of the extraocular muscles, respiratory muscles and peripheral weakness in severe cases.

Myotoxicity

Some Australian snakes contain myotoxins that cause damage to skeletal muscles resulting in local and/or generalized muscle pain, tenderness and weakness, associated with a rapidly rising creatine kinase and myoglobinuria. In rare severe cases, secondary renal impairment can occur.

Renal toxicity

Renal impairment or acute kidney injury can occur in association with thrombotic microangiopathy, secondary to severe myolysis or, more rarely and to a minor degree, in isolation with brown snake envenoming. Thrombotic microangiopathy occurs in snakebites associated with VICC and is characterized by severe thrombocytopaenia worse 3–4 days after the bite, acute renal failure that may last 2–8 weeks and require dialysis and microangiopathic haemolytic anaemia [8]. It is most common with brown snake envenoming, but also reported with all snakes that cause VICC.

Local effects

Local effects vary from minimal effects with brown snakebites to local pain, swelling and, occasionally, tissue injury following black and tiger snakebites.

Most fatalities occur within hours of the bite from initial cardiac arrest and multiorgan failure [1]. Delayed deaths are now uncommon and mainly due to major haemorrhage from VICC in brown snake, tiger snake group or taipan envenoming. Respiratory failure from neurotoxicity remains a problem in Papua New Guinea where there continue to be large numbers of cases, mainly taipan bites, and a shortage of both antivenom and resources for mechanical ventilation.

Treatment

First aid

Australian snake venoms appear to be absorbed via the lymphatic system so absorption is likely to be increased by movement and exercise. The aim of first aid is to minimize movement of venom to the systemic circulation. This is achieved by a pressure bandage (elastic bandage, such as ACE) being applied over the bite site and then covering the whole limb with a similar pressure to that used for a limb sprain. The bitten limb must be immobilized as well as the whole patient or the first aid is ineffective. Immobilization consists of splinting and complete prevention of movement or exercise of the bitten part. It has been shown that movement of all limbs, not just the affected one, needs to be minimized for optimal effect [9]. Transport should be brought to the patient and walking must be avoided. Pressure bandaging is clearly impractical for bites that are not on the limbs but direct pressure with a pad and immobilization may be useful.

First aid must eventually be removed but this should take place in a resuscitation area of a facility with the means definitively to treat envenoming. The first aid is removed when:

ent thorough clinical and laboratory assessment fail to demonstrate any evidence of envenoming. In these patients, further clinical and laboratory evaluation for suspected envenoming is needed following removal of the bandage

ent there is definite clinical or laboratory evidence of envenoming. The bandage is removed after the completion of treatment with intravenous antivenom.

Initial assessment and treatment

Figure 30.1.1 provides a simple approach to the management of suspected and envenomed snakebite patients. The patient is managed in an area with full resuscitation facilities. Assessment and management proceed simultaneously. The airway, breathing and circulation are assessed and stabilized. The majority of patients are not critically unwell and can have a focused neurological examination for early signs of paralysis (e.g. ptosis, drooling), examination of draining lymph nodes and general examination for signs of bleeding (oozing from the bite site, gum bleeds). Intravenous access should be established and intravenous fluids commenced.

Fig. 30.1.1 Early management of snakebite *(from Therapeutic Guidelines Emergency Medicine, July 2012 with permission)*. 1A toxicologist can be contacted at anytime via the Poison Information Centre 131126. ²Cardiac arrest, respiratory failure secondary to paralysis or major haemorrhage (intracranial, major gastrointestinal or other life-threatening bleeding). ³Blood tests include: coagulation tests (INR/PT, aPTT, D-dimer, fibrinogen), FBC and blood film for fragments red cells, EUC, CK and LDH. ⁴Any improvement in coagulation studies, such as measurable but still abnormal aPTT or PT after 6 h, is sufficient evidence of resolving coagulopathy. Neurotoxicity and myotoxicity are usually irreversible and further antivenom is unlikely to help. ⁵Any patient given antivenom needs advice on discharge about possibility of serum sickness occurring 4 to 14 days later. PBI: pressure bandaging immobilization; INR: international normalized ratio; ED: emergency department.

Further management

Two major diagnostic and risk assessment issues exist for snakebite:

ent whether or not the patient is envenomed

ent in patients with envenoming, which snake is responsible and therefore which antivenom should be administered.

The majority of patients are not envenomed, but all patients must initially be assessed as if they are potentially envenomed. Asymptomatic patients, particularly those seen early after a brown snakebite, may still be severely envenomed with VICC. The diagnosis of envenoming is made on history, examination and the clinical investigations listed below. Although systemic envenoming can be ambiguous in patients with mild envenoming, the following definitions are useful for determining whether patients require antivenom:

ent VICC is defined as an elevated international normalized ratio (INR) or prothrombin time (PT) associated with an elevated D-dimer. A low or unrecordable fibrinogen will also occur but is not required for the diagnosis. In the majority of cases, there is complete consumption with unrecordable PT/INR, aPTT and undetectable fibrinogen and the decision to give antivenom is straightforward. Milder forms of coagulopathy may occur with elevated D-dimer and only minimally elevated INR. Antivenom is still indicated in most cases but these can be discussed with a clinical toxicologist.

ent Neurotoxicity is defined as at least ptosis, but may progress without antivenom to include bulbar palsy, extraocular ophthalmoplegia, respiratory muscle paralysis and limb paralysis.

ent Myotoxicity is defined as local or generalized myalgia and/or muscle weakness in association with an elevated creatine kinase (CK>1000 IU).

ent Non-specific symptoms include nausea, vomiting, abdominal pain, diarrhoea, diaphoresis and headache and may, in some cases, be an indication for antivenom depending on the type of snake.

Table 30.1.2 provides a list of relative and absolute contraindications for antivenom which can be discussed with a clinical toxicologist if there is any doubt. If there is no evidence of envenoming after clinical assessment and initial laboratory testing, the first-aid bandage can be removed. The patient requires ongoing close observation including repeated investigations 1 h after bandage removal and at 6 and 12 h after the bite (see Fig. 30.1.1).

Table 30.1.2

Absolute and relative indications for antivenom

Absolute indications

History of sudden collapse, cardiac arrest or seizure

An abnormal INR

Evidence of paralysis with ptosis and/or ophthalmoplegia being the earliest signs

Relative indications: (suggest consultation with clinical toxicologist)

Systemic symptoms (vomiting, headache, abdominal pain)

Abnormal aPTT

Creatinine kinase>1000 U/L

Leucocytosis/lymphopaenia

If the patient is envenomed, then management must proceed with antivenom. A small number of patients present in extremis, usually following collapse and in cardiac arrest and should have antivenom administered immediately as part of advanced life support.

The next step is to determine the snake group responsible for envenoming in order to allow the administration of the appropriate monovalent antivenom. This is done taking into account:

ent local geographical information on the potential snake species that could be responsible

ent clinical syndrome (see Table 30.1.1).

In the majority of cases, a combination of these two factors allows determination of the correct monovalent snake antivenom required. In some cases, an expert may be available to identify the snake. If the snake type cannot be determined based on geography and clinical syndrome, a snake venom detection kit (SVDK) may assist in identifying the snake. However, the results of an SVDK cannot be used in isolation from the geography, expert snake identification or clinical syndrome. If it is unclear which snake is involved then one vial of polyvalent antivenom should be administered or two vials of monovalent in regions (e.g. Victoria) where this will cover all medically important snakes – most commonly brown and tiger snake antivenoms. In Tasmania, only tiger snake antivenom is required.

Administration of antivenom

Snake antivenom should be administered by the intravenous route after being diluted 1 in 10 with normal saline and administered over 15 min. In patients with cardiac arrest or life-threatening effects, undiluted antivenom may be administered as a slow intravenous bolus. The dose of antivenom is one vial for all Australian snakes and the dose for children is the same as adults. Recovery is determined by the reversibility of effects and the time it takes for recovery once venom is neutralized. Repeat doses of antivenom are never required. Although there has been controversy over the dose of antivenom, recent studies have demonstrated that previously recommended large doses are not required [1,10].

Premedication for snake antivenom administration has previously been controversial but is no longer recommended in Australia. A recent randomized controlled trial has suggested that adrenaline is an effective premedication for snake antivenom [11], but this is more appropriate in resource poor settings where the risk of reactions is higher. Systemic hypersensitivity reactions occur in about one-fifth of antivenom administrations in Australia, but are only severe (mainly hypotension) in less than 5% of administrations [2,3]. Reactions are more common with tiger snake antivenom and polyvalent antivenom compared to brown snake antivenom [2,3]. Antivenom should always be administered in a critical care area with readily available adrenaline, intravenous fluids and resuscitation equipment.

The frequency of delayed-type reactions to antivenom or serum sickness is probably higher than acute reactions and likely to depend on the amount of horse protein administered. All patients given antivenom should be warned of serum sickness. There is no evidence for the prophylactic use of a course of oral steroids but they should be used for treatment in patients who present with serum sickness (prednisolone 50 mg/day for 5–7 days).

Other treatments

Tetanus prophylaxis should be given as appropriate but local wound care is rarely required with Australasian snakes due to minimal local effects.

A recent randomized controlled trial has shown that the use of fresh frozen plasma (FFP) appears to speed the recovery of VICC [12], but whether the decreased risk of bleeding is large enough to balance the risk of blood products remains unclear. The study also suggested that use of FFP within 6 h of the bite may be associated with a poor response to FFP. Until larger studies are undertaken, FFP should be reserved for patients with coagulopathy and active bleeding.

Clinical investigations

Assessment of the potentially envenomed requires the following investigations to be performed, usually serially:

ent coagulation profile: PT or INR, aPTT, cross-linked fibrinogen degradation products or D-dimers and fibrinogen

ent full blood count including a blood film looking for fragments, red cells and evidence of haemolysis

ent urea, creatinine, electrolytes, creatine kinase (CK) and lactate dehydrogenase

ent blood group and cross-match

ent snake venom detection kit: a swab should be taken from the bite site

ent urinalysis.

Repeat laboratory testing, particularly coagulation studies, should not be used to determine if sufficient antivenom has been given because one vial is sufficient in all cases. Such serial testing should be used to determine when the patient has recovered and can be discharged.

Snake venom detection kit

The SVDK is designed to confirm which major snake group is responsible and therefore which antivenom to give. It does not confirm or exclude envenoming and should only be included in the assessment of envenomed patients after considering geography and clinical/laboratory effects. It is best done by laboratory staff. In non-envenomed patients, the SVDK has a high false-positive rate, especially in the brown snake well and is problematic in regions where brown snakes are uncommon (e.g. Victoria) [10]. A positive SVDK on urine does not indicate systemic toxicity and, in asymptomatic patients with normal laboratory studies, it is a false-positive result. The test should not be done on blood.

Disposition

Patients with suspected snakebite but no evidence of envenoming 1 h after the removal of first aid may be admitted to an observation area. Blood tests including coagulation studies and a CK should be repeated at 1 h after first aid is removed, and 6 and 12 h post-bite and be observed for 12 h or overnight (see Fig. 30.1.1). Envenomed patients requiring ventilatory support should have continued management in ICU, but patients with coagulopathy only are commonly managed in ED observation wards.

Controversies

Indications for early antivenom therapy to prevent myotoxicity and neurotoxicity.

ent Factor replacement appears to speed the recovery of VICC, but whether the decreased risk of bleeding is large enough to balance the risk of blood products remains unclear.