Introduction

Snakebite is the single most important cause of envenoming. Some experts have estimated more than 2.5 million venomous snakebites per year, with more than 125 000 deaths. Accurate data to confirm such estimates are unavailable, but small regional studies point to the broad veracity of such statements. It is not just the number of fatalities that are of concern in snakebite; many survivors are left with permanent physical impairment, sometimes severe. Paediatric cases represent 20–25% of the total, but a higher proportion of fatalities.

Snakes are ectothermic (‘coldblooded’) reptiles, comprising around 3000 species. Venomous snakes are restricted to just four families: Colubridae, Elapidae, Atractaspididae, Viperidae (Table 22.1.1 and Figs 22.1.1–22.1.4). Fang structures and venom types vary between families, but the common theme is a bite resulting in injection or inoculation of venom through a break in the victim’s skin. In most cases, venom is injected by fangs, paired teeth evolved to deliver venom, usually through a venom groove or enclosed channel, exiting near the tip. The act of biting can leave a variety of bite marks, which may be highly visible or almost invisible. Venom need not be injected (‘dry bites’).

Table 22.1.1 Families of venomous snakes and their principal characteristics

Fig. 22.1.1 Diagramatic representation of the head of an opisthoglyph (back fanged) snake.

Reproduced with permission of Dr Julian White.

Fig. 22.1.2 Diagramatic representation of the head of a proteroglyph (front fanged) snake of the cobra type.

Reproduced with permission of Dr Julian White.

Fig. 22.1.3 Diagramatic representation of the head of a side ‘fanged’ atractaspid snake.

Reproduced with permission of Dr Julian White.

Fig. 22.1.4 Diagramatic representation of the head of a solenoglyph (front fanged) snake of the viper type, with maxillary rotation to allow folding of the fang against the mouth.

Reproduced with permission of Dr Julian White.

Venom varies between snake families, within families, between genera, within genera, between species, within species, between individual snakes, and even over time for a particular snake. It follows that while broad patterns of envenoming can be stated, there is always the possibility of an atypical pattern of effects occurring, because of venom variability. This is just one aspect of the potential difficulties in diagnosing and treating snakebite.

Venom has evolved from digestive juices. It has a variety of functions, which vary between species, but, in broad terms, venom has evolved to fulfil one or more of the following:

As humans, we tend to focus on the last function, but it is the other three functions that cause major medical problems.

Venom actions are diverse. Some major actions are listed in Table 22.1.2. From a clinical perspective, venom effects can be divided into three major groups:

Local effects.

Non-specific general effects.

Specific systemic effects.

Table 22.1.2 Broad overview of major clinical actions of snake venoms

For many snakebites, in most regions of the world, local effects are a major, often the principal, medical problem. In these cases there may be local pain, swelling, which may be severe, involving much or all of the bitten limb, resulting in fluid shifts, secondary hypovolaemic shock and the risk of compartment syndrome. There may be local blistering, bruising or development of skin necrosis. Systemic coagulopathy may manifest locally as persistent oozing or bleeding from the bite or damaged areas of the affected limb. The extent of local necrosis may be significant, with potential, often realised, for long-term tissue injury and dysfunction. Secondary infection may develop in the injured limb. For some species (e.g. lance-headed vipers, such as Bothrops spp. in South America) there may be local abscess formation. Long-term disability is a frequent outcome. In some cases, amputation is required. In cases with ongoing skin damage, never fully healed, skin tumours can develop after some years. This range of major local effects and secondary systemic effects can be seen following bites by many, but not all, species of viper and atractaspids but not colubrids and only selected African and Asian cobras amongst the elapids. Such severe local effects are generally absent from snakebite in New Guinea and Australia, where the only medically important venomous snakes are all elapids.

The non-specific general effects of envenoming vary between species, but usually include one or more of the following:

As most of these can be the result of anxiety as well as envenoming, they may not be reliable indicators of systemic envenoming.

The specific systemic effects of snake venoms are the most intensely studied, partly because they can usually be ascribed to particular venom components that can be isolated and studied in detail. An overview of these components is listed in Table 22.1.2. Specific clinical findings for the effects of these components will be discussed in the sections on ‘history’, ‘examination’ and ‘investigations’.

History

There may be a clear history of snakebite, or an encounter with a snake, where an actual bite is uncertain, or no history of a snake or bite. Particularly in young children, there may be no possibility of obtaining a history. Listen carefully to the story from young children, because relevant information may be disguised by rudimentary language. Some key points are listed in Table 22.1.3.

The environment and circumstances can be of great importance in deciding if a snakebite is likely. Do not assume that bites are unlikely indoors; snakes do enter houses, commonly in the rural tropics, but even in temperate urban areas such as Australian cities.

If there is a history of an encounter with a snake, note if the snake struck, how many times, if bites were through clothing, as well as noting the apparent length and colouration of the snake. For selected cobra attacks in Africa and Asia, the snake may spit first, particularly aiming for the eyes, before either retreating or pressing home an attack with actual bites. A chewing bite, where the snake hangs on is also important, as there is more opportunity for venom injection. Similarly, multiple bites are associated with higher rates of major envenoming.

A description of the snake and geographical location may help narrow the range of possible culprit species. This can be combined with clinical features to assist in identifying the most likely culprits using diagnostic algorithms (Figs 22.1.5 and 22.1.6).

Fig. 22.1.5 Diagnostic algorithm for Australian snakes using the bite site effects.

Reproduced with permission of Dr Julian White.

Fig. 22.1.6 Diagnostic algorithm for Australian snakes using the systemic effects of the bite.

Reproduced with permission of Dr Julian White.

It is important to ask about any local, general or specific symptoms that might indicate developing significant envenoming (see Table 22.1.3).

In children it may prove difficult, even impossible, to obtain any history from the child; however, parents, siblings or bystanders may have useful information. For instance, a small child seeking a parent because they are upset, then collapsing, having a convulsion, then recovering, but remaining miserable is a classic presentation for significant snakebite in some regions (e.g. Australia).

Examination

While examination must be thorough, time is of the essence in major envenoming. Therefore, if snakebite is suspected, examination should be directed initially to determine if there is evidence for snakebite and the extent of any envenoming.

It is clearly important to look at the bite site, or look for a bite, if no site is indicated from the history. Snakebites may result in single or paired fang punctures, multiple teeth punctures or even scratches, as fangs are dragged through the skin during release (Figs 22.1.7–22.1.10). If there is a bandage over the bite site, as first aid, cut a window only to inspect. Keep the removed bandage portion, if in Australia, for possible venom detection later. If venom detection is available (Australia, New Guinea), swab the bite site with the stick provided in the test kit. Do not allow anyone to clean the bite area until it has been swabbed for venom. Look for bite marks and particularly for multiple bites. Observe for local bruising, bleeding, blistering, swelling or necrosis. If there is significant local tissue injury or swelling, check pulses, etc., to exclude compartment syndrome in affected compartments. Compartment syndrome, if suspected clinically, must be confirmed by measuring intracompartmental pressure, before any consideration of surgical intervention.

Fig. 22.1.7 Brown snake bite. Note scratches rather than punctures and lack of local reaction.

Reproduced with permission of Dr Julian White.

Fig. 22.1.8 Tiger snake bite. Multiple bite with two sets of marks and local bruising.

Reproduced with permission of Dr Julian White.

Fig. 22.1.9 Persistent bleeding from bite site, a sign of coagulopathy.

Reproduced with permission of Dr Julian White.

Fig. 22.1.10 Extensive bruising of bitten limb. Typical of viper bites causing coagulopathy (green pit viper bite).

Reproduced with permission of Dr Julian White.

Check draining lymph nodes; if they are tender or swollen it may indicate venom absorption and movement.

Examine for specific effects, notably neurotoxicity (flaccid paralysis; check for cranial nerve paralysis first, starting with ptosis; Figs 22.1.11, 22.1.12), myolysis (muscle tenderness and weakness), coagulopathy (persistent bleeding from bite site, needle punctures, etc.; Fig. 22.1.13) or deep vein thrombosis (DVT, pulmonary embolism; Martinique crotalids only), cardiotoxicity (arrhythmias), ‘allergy’ (angioneurotic oedema; particularly European vipers).

Fig. 22.1.11 Early stage flaccid neurotoxic paralysis with mild ptosis. An important early sign, easily missed (tiger snake bite).

Reproduced with permission of Dr Julian White.

Fig. 22.1.12 Flat facial appearance. Caused by progressive involvement of cranial nerves in flaccid neurotoxic paralysis. Ptosis is also present (tiger snake bite).

Reproduced with permission of Dr Julian White.

Fig. 22.1.13 Persistent blood ooze from IV site indicative of coagulopathy (taipan bite).

Reproduced with permission of Dr Julian White.

Investigations

The most specific investigation is venom detection, but currently this is only routinely available in Australia (most reliable sample is bite site swab; urine can be tested if there is systemic envenoming; blood is unreliable). However, venom detection will not always provide a useful answer, even if available, so it is important to be aware of other diagnostic tools in determining the type of bite and clinical effects. These are discussed further under ‘differential diagnosis’.

Laboratory or similar investigations are often crucial to the management of snakebite. The key areas are coagulation, renal function and muscle integrity.

Many snakes, especially vipers but also some colubrids and many Australian elapids, can cause coagulopathy, which in many cases is potentially lethal. Coagulopathy can develop early or gradually over many hours. The type of coagulopathy is determined by the type of venom components, but just a few tests are adequate in most situations to determine the extent of pathology. For rural areas or hospitals without laboratory facilities, including outback Australia, the whole blood clotting test (WBCT) is the only practical test. 5–10 mL of venous blood is placed in a glass test tube or similar and allowed to clot. If possible, the time to clot is measured. Normal blood should clot in under 10 minutes. If there is minimal or no clot at 20 minutes, this strongly suggests a coagulopathy. If possible, perform a parallel test on blood from a normal control (e.g. relative or staff member). If laboratory facilities are available, the key tests are prothrombin time (PT) or international normalised ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen titre, fibrin (ogen) degradation products (or d-dimer) titre, and platelet count.

Renal function tests are usually urea and creatinine levels. In the absence of a laboratory, monitoring renal output is all that is practical.

Muscle integrity relates to myolytic venoms, the best measure being creatine phosphokinase level (CK, CPK). In the absence of a laboratory, the presence of red, brown or black urine is suggestive of myolysis and myoglobinuria. However, red urine can also be caused by haematuria. If in doubt, spin down the urine and examine under a microscope, looking for evidence of red cell casts. Both haemoglobin and myoglobin test positive for blood with dipstix testing of urine.

If there is evidence of infection around the bitten area, culture and sensitivity should be performed on wound swabs.

In cases where there is clinical evidence of cardiovascular effects of envenoming, primary or secondary, or for bites by snakes known to be cardiotoxic, ECG monitoring is appropriate, but in other cases it may be unnecessary.

Chest X-ray (CXR) is only required if there are clinical grounds to suspect respiratory pathology. Similarly, arterial blood gas examination is not routinely required, but could be considered if there is respiratory impairment, particularly if there is respiratory paralysis developing. In the later stages, after extensive intravenous (IV) fluid therapy, secondary pulmonary oedema is a risk, especially in young children; if suspected, a CXR may be diagnostic.

Envenoming does not always manifest early. It is therefore appropriate to retest for coagulopathy, renal impairment and elevated CK, if the initial tests are normal. In general, a useful protocol is to retest 2–3 hours and 5–6 hours after the initial test, or earlier if symptoms or signs of envenoming develop and at 12 hours or later post bite, prior to any decision to discharge.

Differential diagnosis

A full discussion of all possible differential diagnoses for snakebite is beyond the scope of this chapter. It is important to include snakebite in the differential diagnosis for patients with unexplained collapse, convulsions, bleeding, coagulopathy, thrombosis (in Martinique, specifically), myolysis, flaccid paralysis, muscle fasciculation (mamba bites in Africa), renal failure or impairment, or local tissue injury.

Differential diagnosis can also be applied within snakebite, in determining the type of snake most likely to have caused the bite. Diagnostic algorithms have been developed for Australia (see Figs 22.1.5 and 22.1.6) and South-East Asia (Figure 22.1.14). These are based on cases with significant envenoming and will not function if the patient is not envenomed, though this hardly matters, as such a patient will not require antivenom therapy. In some regions, notably Australia, it is important to know the type of snake involved, because antivenom therapy can be targeted appropriately. A similar situation applies in some other regions, where specific antivenoms are available. In regions such as North America, this is less important, because there is only one polyvalent antivenom covering all venomous species, except coral snakes.

Fig. 22.1.14 Diagnostic algorithm for snakebite in southeast Asia.

After Warrell et al. Reproduced with permission of Dr Julian White.

Treatment

Snakebite treatment can be divided into several areas: first aid; diagnosis; and treatment, the latter further divided into specific (antivenom) and non-specific treatment.

First aid for snakebite is controversial. Many techniques have been advocated and are in use throughout the world. Almost none meet the critical criteria of safety and effectiveness. For snakes not likely to cause major tissue injury in the bitten area, the Australian-developed ‘pressure immobilisation’ method is appropriate. A broad bandage is applied over the bite site, then the rest of the bitten limb, at the same pressure as used for a sprain, that is firm but not occlusive. The limb is then immobilised using a splint. Correctly and promptly applied, this method is both safe and effective. However, for snakes likely to cause local tissue injury, even the pressure of this technique may cause further tissue damage, at least theoretically. For this reason, the pressure immobilisation method has not been recommended for all snakebites. The theoretical danger from this method has been challenged by recent research and it may be that extension of this research will show that the pressure immobilisation method is safe and effective for all snakebites.

Other popular first aid methods enjoy no such success and are either unsafe or ineffective, or both, and should never be used. Amongst these are tourniquets, ‘cut & suck’, patent venom extraction devices (suction), electric shock (‘stun guns‘ etc), application of chemicals to the bite, snake stones and ‘witch doctor’ treatments. The application of certain plant extracts is still undergoing evaluation.

Diagnosis of snakebite has been discussed earlier.

Definitive treatment for snakebite will vary depending on the type of snake, but some general principles apply.

First, not every bite will result in envenoming, but the extent of envenoming, if any, may not be immediately apparent, therefore all bites should be treated with caution.

Second, in many regions, the bulk of snake fauna is non-venomous, so many snake bites may be trivial. However, it is necessary to be sure of the snake’s identity as non-venomous, before dismissing the case and identification is rarely easy, especially in paediatric cases where history is scant. An exception is Australia, where almost all snakes causing bites are potentially lethal.

Third, if significant envenoming has occurred, with few exceptions, antivenom, if available, is the treatment of choice and should always be given IV. Choice of antivenom will be determined by the type of snake and the availability of methods to determine snake identity. Thus, in Australia, specific antivenoms are available, together with venom detection and diagnostic algorithms, so polyvalent antivenom is often not required. In contrast, in North America the only available snake antivenom is polyvalent, covering all endemic pit-viper species, so identifying the snake is less important. In general, antivenom will be more effective than any other therapeutic agent at reversing envenoming. Used appropriately it is life saving and the old ‘wisdom’ that ‘the antivenom is more dangerous than the venom’ is outdated, inappropriate and dangerous.

Fourth, antivenom is generally disappointing as therapy for local effects of envenoming, but is still better than other therapies in most cases. Equally, do not overlook adjunctive therapies, in particular adequate IV hydration if there is massive local or limb swelling following the bite, as untreated hypovolaemic shock secondary to such fluid shifts is potentially lethal, especially in children.

Fifth, for coagulopathy caused by venom, antivenom is the best treatment to reverse effects, and factor replacement therapy, including even whole blood, is best reserved for those cases with catastrophic bleeding, or no available antivenom, or where sufficient antivenom has already been given to neutralise all venom. Giving factor replacement therapy while active venom is still circulating is to invite worsening of the coagulopathy. Heparin is generally ineffective in these cases and should be avoided.

Finally, for cases with flaccid paralysis, consider anticholinesterase therapy as an adjunct to antivenom, if a Tensilon test has shown benefit (there is likely benefit for cobra bite causing paralysis, also death adders (but only some cases), possibly some kraits, sea snakes, possibly some coral snakes). Venoms with presynaptic neurotoxins will not show response to anticholinesterase therapy (most Australian snakes causing paralysis; exception is the death adder, which sometimes has only postsynaptic neurotoxins).

From the above it will be clear that antivenom is the key treatment for snakebite, when available. The latter is a real issue, because for many species and substantial areas of the rural tropics, antivenom is not available.