Coagulopathy

Neurotoxicity

Paralysis is a classic effect of snakebite and is due to either presynaptic or postsynaptic neurotoxins. 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 takes days to weeks to resolve. Postsynaptic neurotoxins competitively block acetylcholine receptors and this type of neurotoxicity is reported to be reversed by antivenom. 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 damage

Renal impairment or acute renal failure can occur secondary to severe myolysis, in association with thrombotic microangiopathy or, more rarely and to a minor degree, in isolation with brown snake envenoming. Thrombotic microangiopathy occurs in a small proportion of brown snakebites and is characterized by severe thrombocytopenia worse 3 to 4 days after the bite, acute renal failure often lasting 2 to 8 weeks and requiring dialysis, and microangiopathic haemolytic anaemia. This is also reported less commonly with taipan and tiger snakebites.

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. Delayed deaths are now uncommon and mainly due to major haemorrhage from the VICC from brown snake, the tiger snake group or taipan. 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.³ 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.⁴ Transport should be brought to the patient and walking must be avoided. Prompt, properly applied first aid probably prevents significant absorption of venom for many hours although there is only anecdotal evidence to support this. Pressure bandaging is clearly impractical for bites that are not on the limbs but direct pressure with a pad and immobilization may be useful. The bite site should not be washed so that it can be swabbed for venom detection.

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

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.

Figure 30.1.1 Early management of snakebite

¹ A toxicologist can be contacted at anytime via the Poison Information Centre 131126.

² Cardiac arrest, respiratory failure secondary to paralysis or major haemorrhage (intracranial, major gastrointestinal or other life-threatening bleeding).

³ Blood tests include: coagulation tests (INR/PT, aPTT, D-dimer, fibrinogen), FBC and blood film for fragments red cells, EUC, CK and LDH.

⁴ Any 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.

PIB, pressure immobilization bandaging; INR, international normalized ratio; WBCT, whole blood clotting time; ED, Emergency Department.

(modified from Therapeutic Guidelines Emergency Medicine, March 2008 with permission)

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:

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 one hour after bandage removal, and at 6 and 12 h after the bite (see Figure 30.1.1).

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 the 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 three factors allows determination of the correct monovalent snake antivenom required. If it is unclear which snake is involved then one vial of polyvalent antivenom should be administered. This contains sufficient antivenom for an initial dose for all types of snakes. In some parts of Australia, such as Victoria and Perth, a combination of brown and tiger snake antivenom can be administered in preference to polyvalent. 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 or Hartmann’s solution and administered over 15 min. In patients with cardiac arrest or life-threatening effects, undiluted antivenom may be administered more rapidly.

The initial dose of antivenom for children is the same as for adults and is provided in Table 30.1.1. Further doses are usually not required and recovery is determined by the reversibility of effects and the time it takes for recovery once venom is neutralized. The benefits of antivenom are listed in Table 30.1.2, which underlines the importance of waiting for recovery after antivenom administration, particularly with VICC.⁵ Although there is controversy over the dose of antivenom, recent studies have demonstrated that previously recommended large doses are not required. For brown snake envenoming an initial dose of two vials binds all venom and sufficient time must then be allowed for resynthesis of clotting factors.^1,2

Table 30.1.2 The benefits of antivenom for different effects of envenoming (Modified from Therapeutic Guidelines Emergency Medicine, March 2008 with permission)

Premedication for snake antivenom administration has previously been controversial but is no longer recommended in Australia. One randomized controlled trial suggested that adrenaline was an effective premedication for snake antivenom.⁶ However, the trial was for an antivenom with a much higher reaction rate and was too small to assess the safety of adrenaline.⁷ Promethazine has been shown to be ineffective as a premedication,⁸ and often leads to drowsiness that makes neurological assessment difficult. Immediate-type hypersensitivity reactions occur in about a quarter of antivenom administrations in Australia, but are only severe (mainly hypotension) in 5% of administrations.⁹ Reactions are more common with tiger snake antivenom and polyvalent antivenom compared to brown snake antivenom. 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 and a course of oral steroids (prednisolone 50 mg/day for 5 days) may be considered in patients receiving large amounts of antivenom. However, there is no evidence that prophylactic corticosteroids will reduce the risk of serum sickness. A similar course of steroids should be used for treatment in patients who re-present with serum sickness.

Other treatments

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

Preliminary clinical studies have shown that the use of fresh frozen plasma (FFP) appears to speed the recovery of VICC if administered early (after antivenom), but whether the decreased risk of bleeding is large enough to balance the risk of blood products remains unclear. Previously the theoretical concern was that the administration of clotting factors would worsen the consumptive process, but there is no evidence to support this. Until further evidence is available FFP should be reserved for patients with coagulopathy and active bleeding.

Snake venom detection kit

It is important to note that the SVDK is designed to confirm which major snake group is responsible and therefore which antivenom to be given. It does not confirm or exclude envenoming and should only be included in the assessment of envenomed patients. It is best done by laboratory staff. In all patients with suspected snake envenoming a bite site swab must be collected and stored. The bandage should not be removed to swab the wound: a window should be cut to obtain access. Controversy remains as to whether this should be tested immediately or left to be tested if the patient becomes envenomed.

In non-envenomed patients the SVDK has a high false positive rate, especially in the brown snake well. This is even more problematic for urine testing so a bite site swab is preferred if available. A positive VDK on urine does not indicate systemic toxicity and in asymptomatic patients with normal laboratory studies this is most likely a false positive. The test should not be done on blood. If the snake responsible for the bite accompanies the patient, a swab of the fangs can be tested except that this may require considerable dilution because it will be too concentrated and overwhelms the SVDK with all wells changing colour.