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.

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:

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.

Further management

Two major diagnostic and risk assessment issues exist for snakebite:

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:

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).

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:

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.

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.