bites and stings poisonous animals valuable source

8/14/2019 Bites and Stings Poisonous Animals Valuable Source

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Bites and stings from animals, venomous and non-venomous, cause an unknown number of injuries per year, but

statistics from a few key groups of venomous animals indicate that there are millions of cases annually, with at least

125,000 deaths. While in most cases of venomous animal injury, the primary problem is direct venom toxicity effects,

there may also be significant local tissue injury and non-venomous animals will principally cause direct trauma.

Because of the global magnitude of human injury, morbidity and mortality from venomous animal bites and stings, this

area will be dealt with in some detail, even though it encompasses more than just primary physical trauma.

Venomous animals

Venomous animals are found in most groups or classes of the Animal Kingdom and in most habitats, both terrestrial

and marine, reflecting the selective advantage venom may bestow, in both acquiring prey and deterring predators. In

this section of the chapter, the types of animals, the types of venoms, clinical effects and general comments on

management will be covered. This is followed by a more detailed look at individual types of animals and their effects

on humans.

Overview of venomous animals

Of the approximately 26 Phyla of animals, at least 6 contain species that use venom or internal poison, as either pure

defense, or both for offence and defense (Figure 1). A few groups, however, account for the vast majority of cases of

human envenoming or poisoning by animals:

Venomous snakes >125,000 deaths/year.

Scorpions approximately 5,000 deaths/year.

Stinging insects hundreds of deaths/year due to anaphylactic reactions to venom.

Puffer fish several hundred deaths/year.

Jellyfish possibly scores of deaths/year.

Spiders perhaps 10-50 deaths/year.

Stinging fish perhaps 1-10 deaths/year.

Venomous molluscs perhaps 1-10 deaths/year.

Taxonomy considerations

Fundamental to the understanding of trauma from venomous animals is a knowledge of the taxonomy of these

animals, for without a reliable way of identifying an animal, it will not be possible to accurately record cause and

effect, essential in elucidating epidemiology, etiology, pathophysiology, and clinical management. It is beyond the

scope of this chapter to detail the taxonomy of all venomous animals. A simplified scheme is outlined in Figure 1.

Overview of venoms

Venoms are nearly always complex mixtures of varied biologically active substances (toxins) which may work

independently or synergystically and each of which may have one or more quite distinct target sites and actions. In

many venoms a single component or group of closely related components may be responsible for most or all major

effects in envenomed humans, but in other venoms, particularly snake venoms, a multitude of diverse components

may each cause distinct major effects, resulting in a complex, multisystem disease process.


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Venoms have evolved principally because they benefit the venomous animal, giving it some competitive advantage

over related non-venomous species. In many species the venom has evolved from digestive juices, especially

enzymes, the venom gland being a highly evolved digestive gland. It is not surprising therefore that many venomous

animals use their venom principally to aid digestion, explaining many of the rather unpleasant effects on envenomed

humans. At some point in evolution some venomous animals have evolved venom with rather different effects,

designed to assist acquiring prey or as a defense against predators. It is this latter group of venom toxins that often

cause the major systemic effects of envenoming in humans. Often these toxins may have evolved from digestive

enzymes, but their principal action is not related to enzymic activity. Indeed, there may be no significant residual

enzymic activity, despite considerable sequence homology with the original enzyme. Classic examples of this are the

phospholipase A2 (PLA2) toxins that are so prominent in snake venoms and have evolved into potent toxins such as

neurotoxins, myotoxins, procoagulants, anticoagulants, platelet-active toxins and necrotoxins.

There are many methods of classifying venom components and types of toxins. The method used herein is based on

clinical effect. A single toxin may be active within several categories.

Neurotoxins

Neurotoxins are classic venom components causing potentially lethal envenoming in humans. There are many types,

widely distributed amongst venomous animals. Some cause flaccid paralysis, others cause hyperstimulation of

portions of the nervous system.

Paralysing neurotoxins

Presynaptic neuromuscular junction neurotoxins

These toxins act at the neuromuscular junction (NMJ) in humans, damaging the terminal axon, resulting in a brief

period of neurotransmitter release, followed by cessation of all neurotransmitter release, resulting in irreversible

paralysis. This manifests clinically as progressive flaccid paralysis. Antivenom therapy cannot reverse such paralysis,

which may persist for days, weeks or occasionally months, but if given at the earliest sign of paralysis, may prevent

progression to widespread severe paralysis. As these toxins affect the skeletal NMJ, they affect skeletal muscle only,

including respiration, but not cardiac or smooth muscle. They have evolved from PLA2 toxins, but some are complex

multicomponent molecules without residual enzymatic activity. These toxins are particularly found in some snake

venoms.

Postsynaptic neuromuscular junction neurotoxins

Like the presynaptic neurotoxins, these toxins act principally at the skeletal muscle NMJ, causing progressive flaccid

paralysis, but act extracellularly by reversibly binding to the acetylcholine receptor on the muscle end plate. Their

effect is therefore reversible with sufficient antivenom therapy and may also be at least partially overcome by the use

of anticholinesterases, such as neostigmine, though this often requires ongoing dosing. These toxins are also

particularly found in some snake venoms.


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Presynaptic and postsynaptic synergystic neuromuscular junction neurotoxins

These toxins are found in African mamba snake venoms. The dendrotoxins act presynaptically to increase release of

the neurotransmitter, acetylcholine, flooding the NMJ and causing overstimulation of the muscle. This action is

synergystically compounded by the second set of toxins in mamba venoms, the fasciculins, which act as

anticholinesterases, preventing removal of the acetylcholine, thus increasing the neurotransmitter concentration andadding to the flooding effect, resulting in muscle fasciculation and effective paralysis of skeletal muscle.

Sodium channel neurotoxins

There are a variety of these toxins, the best known of which is tetrodotoxin (TTX), found in such diverse animals as

the Australian blue ringed octopus (in its saliva) and the flesh of puffer fish (fugu). A small molecule, TTX causes

rapid, reversible short-lived flaccid paralysis of skeletal muscle principally by blocking nerve transmission, through

action on the sodium channels of axons.

Potassium channel neurotoxins

A variety of channel blocking toxins exist in venoms, most notably in some scorpion venoms and cone shell venoms.

A variety of potassium channels may be affected, the usual clinical effect being flaccid paralysis, though hypertonic

paralysis may also occur.

Excitatory neurotoxins

A number of excitatory neurotoxins have been reported from venoms, especially arthropod venoms such as from

spiders and scorpions. These toxins may target diverse parts of the human nervous system, often as an unfortunate

biproduct of toxicity designed to immobilise prey species, mostly other arthropods. A good example is the Australianfunnel web spider, the principal toxin of which will affect arthropod prey, but not most mammals, an unfortunate

exception being humans, who are exquisitely susceptible to this venom. Some of these toxins affect neuronal ion

channels, though mechanisms of action are still uncertain in many cases.

Autonomic neurotoxins

A number of neurotoxins from venoms may affect part or all of the autonomic system, either primarily or secondarily.

This includes neurotoxins from the previously mentioned classes, especially the excitatory and ion channel toxins.

Myotoxins

There are two principal types of myotoxic action in venoms; local, at the bite/sting area and systemic. The latter is of

most clinical significance. Systemic myolysins are particularly important in some snake venoms, which in humans

may result in potentially lethal myolysis of skeletal muscle. These latter myotoxins are PLA2 toxins and in some

cases are the same toxin as presynaptic neurotoxins (an example is notexin from Australian tiger snake venom),

mediating myotoxicity through a part of the molecule distinct from the neurotoxic active site. Myotoxins cause


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extensive membrane and intracellular damage to individual muscle cells, commencing within 60 minutes of reaching

their target site and by 24 hours (in experimental models) cell destruction is complete. However, the basal lamina

remains intact, so that after about 3 days cellular reconstruction commences, completing around 28 days. There is

some evidence that only slow fibres regenerate, not fast fibres. In the process of muscle cell degeneration there is

release of cell contents into the circulation, most notably myoglobin, creatine kinase (CK) and potassium. The former

may cause secondary renal damage or failure; the latter cardiac arrhythmia or arrest. Cardiac and smooth muscle

appear largely unaffected by venom myolysins.

Cardiotoxins

There are a number of PLA2 cardiotoxins described from some snake venoms, but these are mostly just general

cellular toxins which cause cell damage and tissue necrosis. There are, however, a variety of toxins which can

directly or indirectly affect the myocardium. These are found in a variety of venoms, notably snake venoms, but

indirect cardiac effects are prominent in envenoming by some arthropods (especially scorpions) and marine animals

(some jellyfish and cone shells). The mechanisms of action and structural identity of such toxins are diverse and

beyond the scope of this chapter.

Coagulopathic Toxins

Many snake venoms have actions on the human haemostatic system. A broad outline of modes of action is given in

Table 1 and Figure 3.

Procoagulants

While the name procoagulant accurately depicts the primary action of these venom toxins, the clinical effects in

humans are more complex and subtle. In normal haemostasis the formation of a blood clot by crosslinking fibrin

occurs in a protective platelet plug at the site of haemorrhage. It is therefore protected from dissolution by the

fibrinolytic system until vessel wall repair has occurred. Venom procoagulants act outside this structured environment.

Fibrinogen is rapidly converted to fibrin, which starts to crosslink, but fibrinolysis is also rapidly activated, so that

within minutes of the venom causing microclotting, there is hyperfibrinolysis, causing fibrin to be destroyed as rapidly

as it is formed. So powerful is this reaction with some venom procoagulants, notably the prothrombin convertors of

some Australian Elapid snake venoms, that all circulating fibrinogen can be consumed within 5-15 minutes, rendering

the patient profoundly anticoagulated and at risk of haemorrhage. If envenoming is severe, there may be a brief

period at the outset of procoagulant action, before fibrinolysis is established, where substantial thrombi will form and

potentially embolise. These may cause diverse and potentially catastrophic effects, notably coronary occlusionleading to cardiac arrhythmia or arrest. Subsequent fibrinolysis will quickly remove such thrombi, so that they will not

be evident at autopsy in fatal cases. This mechanism is postulated as a cause of the rapid collapse and cardiac

problems seen particularly with envenoming by the Australian brown snake. Venom procoagulants are usually

multicomponent molecules, sometimes quite large, as seen in some prothrombin convertors, and generally their

structure mimics normal components of human haemostasis, particularly part or all of the prothrombinase complex

(factor Xa, Va, phospholipid, Ca). The specific types of procoagulants are listed in Table 1.


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SERPIN inactivators

SERPIN (plasma SERine Protease Inhibitors) inactivators are found in some viperid and colubrid snake venoms.

SERPINs are important controlling enzymes for haemostasis, making up 10% of all plasma proteins (eg antithrombin

1-proteinase inhibitor) and their inactivation removes checks onIII, thrombosis, clearly synergistic with other

haemostatically active venom components.

Nephrotoxins

Renal damage from envenoming is not a rare event and may follow envenoming by a wide range of venomous

animals, as a secondary effect of venom induced hypotension, causing renal hypoxic damage, or by deposition of

byproducts of venom induced coagulopathy or myolysis. However, at least a few snakes appear to possess primary

nephrotoxins in their venom, which can induce severe renal failure. There are also instances, following snakebite, of

permanent major renal injury, notably renal cortical necrosis, the etiology of which is uncertain and probably

multifactorial.

Necrotoxins

A variety of venomous animals can cause local tissue necrosis at the bite/sting site, through a variety of mechanisms.

Some snakes (eg many vipers, pit vipers, some cobras) commonly cause major local tissue injury, as a result of a

variety of different venom effects, including the effects of cytolytic phospholipase A2 toxins. A few spiders cause local

necrosis as the most prominent feature of envenoming (eg recluse spiders; Loxosceles spp.). A few jellyfish may also

cause local necrosis along the tracks of stings (eg box jellyfish).

Other venom components

There are many other components found in venoms, most of which may have little clear clinical effect, but some,

such as hyaluronidase, may enhance other venom actions, while others, such as histamine, serotonin and 5HT, may

have potent, if short lived actions. These latter components are particularly prominent in arthropod venoms, notably

those of stinging hymenoptera, which also contain specialised small peptides such as apamin and melitin (eg honey

bee venom), which have potent cardiovascular actions. In addition these peptides may also be highly allergenic,

resulting in anaphylaxis on subsequent exposure in sensitive individuals. This is a common problem with honey bee

venom, but also with a variety of other bee and wasp venoms and is particularly common with some of the Australian

primitive stinging ant venoms (eg hopper and inch ants, Myrmecia spp.).

Pharmacodynamics of envenoming

The way venoms are introduced by a bite or sting, the depth of injection, quantity involved, the size and action of

venom components, size, age, pre-existing disease and post envenoming activity of the victim will all influence the

rate of absorption, clinical effectiveness and elimination of venom. With a range of quite different venom components

all working at once, in different ways, understanding the pharmacodynamics of envenoming can be difficult. In

general terms, however, the speed of onset of action of a particular component will be determined by its size and

target tissue location. Thus necrotoxins and other locally active toxins may commence clinical effects almost


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immediately after the bite or sting, as they are already at their target site, while systemically active toxins must first

reach the bloodstream (Figure 4). Toxins active within the bloodstream will rapidly exert their effect, but toxins with

extravascular targets, such as neurotoxins and myotoxins, will generally have a more delayed onset. The rapidity of

effect will also be influenced by any latency period, between time of binding to the target tissue, and onset of

detectable action. As an example, presynaptic neurotoxins may have a latency period of 60 minutes, while

postsynaptic neurotoxins may have almost no latency period; these differences are relected in the speed of onset of

neurotoxic symptoms and signs. However, in real clinical circumstances, assessment is rarely so simple, for a single

venom will contain a diverse array of toxins. Again, using the neurotoxins as an example, the venom may well contain

both pre- and postsynaptic neurotoxins, so there will be a continuous onset and development of paralysis, as each

type of neurotoxin exerts its effect. Many venoms are eliminated by the kidneys, explaining why testing urine for

venom can be rewarding and this renal excretion may commence as soon as venom reaches the circulation. Thus

blood levels of venom reflect not just the quantity of venom absorbed, but the rate of absorption and of excretion. In

most cases, when venom is injected by a sting or bite, it will be deposited subcutaneously or intradermally. Some

snakes such as large vipers, with long fangs, may occasionally inject deeper, even into muscle. While direct injection

into blood vessels can occur, it seems a rare event, except for some jellyfish, notably species such as the lethal boxjellyfish. The precise mechanism of venom introduction will be discussed later, but these jellyfish may inject a major

part of their venom directly into subdermal capillaries, resulting in very rapid, devastating and sometimes lethal

envenoming.

Clinical effects of venoms

With such a wide array of venomous animals and venom components, the range of clinical effects might be

considered immense. However, a few major themes of venom action dominate, so that there just a few major classes

of clinical effect, with classic symptoms, signs and laboratory findings. It must be remembered that venomous

animals are not evolutionarily frozen; their venoms may still be evolving, so that effects may also evolve and change.

This is clearly true for venomous snakes. Both the nature of venom components and the snakes abundance,

geographical range and even diet are the subject of rapid change. It follows that whatever may presently be stated as

the effects, range, habits etc for a given species of venomous animal must be continuously reinterpreted as the

animals change, and the unexpected should always be looked for.

Neurotoxic paralysis

Neurotoxic paralysis is usually a result of neuromuscular junction pre- and/or postsynaptic neurotoxins which act

systemically rather than locally, affecting voluntary and respiratory muscle. It is a classic effect of many snake

venoms, but is also seen with envenoming by other animals such as paralysis ticks and a few marine animals,

notably cone shells and blue ringed octopuses. These latter marine animals may rapidly induce paralysis, withclinically apparent effects in 10-30 minutes, but neurotoxic snakes usually cause a more delayed onset paralysis,

which may take 1 to 12 or more hours to become evident, while for ticks it may take days to become apparent. In all

cases, however, it is a progressive flaccid paralysis, often first seen in the cranial nerves, where it is easily missed if

not sought by careful examination. Ptosis, partial, then complete ophthalmoplegia, loss of facial tone, dysarthria and

dysphagia are all common early signs of paralysis (Figures 5, 6). The pupils may become dilated and unresponsive to

light. Progressive weakness of limbs and bulbar function may follow, the latter often mandating intubation and


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ventilation to protect the airway. Accessory muscles of respiration may become prominent and the patient more

agitated or drowsy as hypoxia develops. The diaphragm is often the last muscle to be paralysed and may not be fully

affected for up to 24 hours after a neurotic snakebite. If the neurotoxin is extracellular, such as snake postsynaptic

neurotoxins, tetrodotoxin, conotoxins, then the paralytic effect may last only a few hours or may be reversible with

treatment, such as antivenom or anticholinesterase, but presynaptic paralysis usually involves damage to the terminal

axon, so reversal must await regeneration, which may take days, weeks or months.

Exicitatory neurotoxin effects

Excitatory neurotoxins, as found in some arachnid (spider) and related arthropod (scorpion) venoms, usually cause

very rapid onset of clinical effects, with potentially catastrophic effects possible within 10 to 30 minutes of a sting or

bite. So rapidly are these toxins absorbed, transported and bound to target tissues, that antivenom therapy is

frequently administered too late to have optimal effect. The clinical effect will vary with species, but commonly

includes local pain, rapid onset of anxiety, hypertension, tachycardia, and in some species, dyspnoea and pulmonary

oedema (eg Australian funnel web spiders) or cardiac arrhythmias (eg some scorpions) or muscle fasciculation (some

scorpions, spiders). There is often evidence of autonomic excitation, such as piloerection, priapism (banana spider),

sweating, lachrymation, hypersalivation, in addition to the cardiovascular manifestations.

Cardiotoxin effects

In many cases, cardiovascular effects are secondary to other venom actions, but direct cardiovascular effects, such

as hyper- or hypotension, brady- or tachycardia, cardiac arrhythmias can occur, particularly in scorpion venoms and a

few jellyfish venoms (eg box jellyfish), as well as a few snake venoms (eg gabboon viper).

Myotoxin effects

Local myotoxins will cause local tissue damage, resulting in local effects such as pain and swelling and secondary

effects, such as compartment syndrome and hypovolaemic shock. Systemic myotoxins, such as those in some snake

venoms, will cause progressive myolysis of skeletal muscle, resulting in muscle pain, tenderness, weakness, that

may mimic paralysis, and secondary effects, notably myoglobinaemia, myoglobinuria (with potential secondary renal

failure) (Figure 7), hyperkalaemia (with potential secondary cardiac arrhythmia) and rise in serum enzymes,

especially creatine kinase (CK), which may reach extraordinary levels. Myoglobinuria gives the classic red to black

urine that is dipstix positive for blood.

Haemostasis effects

The wide variety of haemostatically active venom components, particularly present in many snake venoms, may give

rise to a variety of clinical disorders of haemostasis, distinguishable by detailed coagulation and platelet function

studies. However, just three basic syndromes are generally evident; incoagulable blood with bleeding tendency,

poorly coagulable or incoagulable blood without clinically apparent bleeding tendency, and thrombotic tendency. The

latter is unusual, but is clearly present in envenoming by a few Central American vipers, where DVT is a common

sequelae of envenoming. Those with bleeding tendency may exhibit no clinical signs other than persistent bleeding


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from the bite site (Figure 8), but more commonly there is also bleeding from the gums, and GIT bleeding (manifest as

haematemesis or malaena) and haematuria may also occur. Bleeding into a major organ or space (eg intracranial)

will produce classic signs, but more localised bleeding, such as into the pituitary (Sheehans syndrome following

Burmese Russells viper bite) may produce more subtle or delayed signs. Any artificial breach of vascular integrity,

such as insertion of canulae, may result in prolonged and significant bleeding. This has obvious management

implications.

Haemorrhagin effects

The effects of haemorrhagins are similar to the more severe effect of haemostatically active toxins, in that they will

produce clinically apparent bleeding. As the two groups of toxins are usually present together and are synergistic,

bleeding can be major. There may be marked bleeding in the bitten area (Figures 9, 10), as other venom components

assist tissue breakdown and allow extravasation of blood from vessels damaged by haemorrhagins.

Nephrotoxin effects

Nephrotoxins, primary or secondary, will exert their effect somewhat silently at first, the first indication of problems

often being a rapidly falling urine output, accompanied by rising creatinine and urea. In an case of envenoming where

renal failure is possible, such as many snakebites, it is therefore advisable to carefully monitor fluid input and output

and give an initial IV fluid load.

Other systemic effects

A variety of specific systemic effects may be induced by envenoming by certain species. Of particular note is

haemolysis, seen with some snakebites and with severe envenoming by recluse spiders. Liver damage may also

occur, following bites or stings by many animals, but is rarely of major significance. Pancreatitis can be induced by

some scorpion stings.

Necrotoxin effects

These may be rapidly evident, as is seen with some snakebites (eg many vipers, pit vipers, some cobras), as

progressive swelling, blistering, ecchymosis and darkening of skin, or liquefaction of skin (Figure 10). Over 24 to 48

hours this may progress to clear skin necrosis, resulting in deep ulceration, sometimes involving muscle and other

deeper tissues. Pain is present in most cases. Spider necrotoxins may cause more insidious effects, particularly

recluse spiders. The bite may go unnoticed, frequently occurring at night while the victim is asleep. This is followed by

local redness, sometimes, but not always associated with local pain. Blisters may form after 12 to 48 hours, or areas

of ecchymosis (Figure 11), becoming darker and more clearly necrotic over the next 1 to 7 days, eventually

developing a full thickness skin ulcer or ulcers, which may occupy an area far greater than the original bite region.

Jellyfish necrotoxins, such as those in box jellyfish venom, are associated with major envenoming. The sting is

intensely painful, with wheal formation, with necrosis taking several days to become evident.


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Other local effects

The local effects of envenoming, dependent on both species and dose, may include pain, swelling, blistering,

ecchymosis, necrosis, persistent bleeding, blanching, wheal formation, or almost no visible effect at all, even in the

presence of life threatening systemic envenoming. Some elapid snakes and a variety of other animals can envenom

sufficient to cause major systemic effects, yet leave little evidence locally, not even significant pain.

General systemic effects

The range of general systemic effects of envenoming is considerable and variable. Snakebite often is associated with

headache, nausea, vomiting and abdominal pain. Diarrhoea may also occur. Collapse and even convulsions may

occur as early manifestations of major envenoming, especially in children.

First aid for envenoming

First aid for envenoming is often controversial and frequently based on inadequate experimental or clinical research.

The first principle should always be do no harm. As a general rule immobilisation of the bitten limb is a useful

technique to reduce venom transport, as many venom components are of moderate to large molecular weight and

lymphatic flow is important in their transport. The use of compression bandaging (Figure 12) is more controversial,

but is apparently beneficial for certain types of snake and spider bite and a few major marine toxins (box jellyfish,

cone shells, blue ringed octopus). Application of a cold pack to the wound area is a useful technique for many types

of envenoming by marine invertebrates, especially jellyfish, and some terrestrial invertebrates, but is not applicable

for envenoming by vertebrates (snakes, fish). For fish with venomous spines and for stingrays, immersion of the

stung limb in hot water is effective in reducing local pain (be sure the water is not so hot it may cause thermal injury).

There are some first aid methods which are known to be either of no value or potentially harmful and so should not be

used. These include tourniquets, cutting and suction of the wound, application of chemicals such as condys crystals,

use of cryotherapy and electric shock to the bite site. All these methods are still used in various regions of the world,

most commonly for snakebite, despite the evidence that they frequently cause harm, without conferring benefit. Of

these techniques, the use of medically supervised tourniquets has merit in certain circumstances, where the bite is

from a lethal species and transport time to a hospital with appropriate antivenom is less than 30 minutes. The use of

proprietory suction devices to remove venom is advocated by their manufacturers, but studies of efficacy do not

inspire confidence in the technique, as even in optimal circumstances, at least 70% of the venom will be left in the

victim. Cryotherapy has been clearly shown to be harmful. Electric shock for snakebite, though still promoted by

manufacturers of these devices, has been shown to offer no benefit and its use may delay more appropriate first aid.

Medical management of envenoming

Most doctors will see few cases of significant envenoming, thus acquiring and maintaining skills in management is

problematic. It is therefore advisable, when faced with a case of major envenoming, to seek expert advice at the

earliest opportunity, either from a regional expert or from a regional poisons information centre, the staff of which may

facilitate referral to an appropriate expert.


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Diagnosis

Diagnosis is no less crucial in effective management, than in other areas of medicine, yet is often far from simple.

Patients may present with a clear history of a bite or sting and either a good description of their assailant or the

assailant itself. The latter may introduce further problems if it is still alive (such as an angry venomous snake!). In this

situation, while the diagnosis may be clear, some expertise may be required to determine the true identity of theassailant, sometimes crucial in determining which type of antivenom to consider. Equally, the extent of envenoming

may not be immediately apparent, and some major types of envenoming, such as paralysis, myolysis, coagulopathy

and renal damage may not be initially evident from examination, or require appropriate laboratory investigation. Given

these obstacles to early accurate diagnosis, where the assailant is clearly known, the situation becomes far more

complex when the assailant is most uncertain, as is frequently the case. Children may be unable to give a history of a

bite or sting and may present with advanced envenoming, manifest as symptoms and signs that could point to a

miriad of diagnoses. Beware the child with unexplained collapse and convulsions, which might be indicative of major

envenoming by a snake, scorpion or spider. Adults may also be unaware of being bitten, as some bites (eg by certain

snakes, blue ringed octopuses, ticks) may be painless. They will later present with symptoms that might indicate a

wide range of diagnoses and the lack of a noted bite may erroneously point the diagnostic process away fromenvenoming. Envenoming should be considered in otherwise unexplained collapse, convulsions, flaccid paralysis,

autonomic stimulation, myolysis, coagulopathy, thrombosis (DVT), haemorrhage, renal failure, chest pain, abdominal

pain, regional pain, muscle fasciculation, excessive sweating, nausea and vomiting, headache, local swelling,

ecchymosis, blistering, ulceration, cardiac arrhythmias and pulmonary oedema. This list covers only some of the

more common effects of envenoming.

History

The mix of the following points in history taking will be determined by the circumstances and the nature of the

assailant.

Precise date and time of the incident that might have involved a bite or sting.

Geographic location at the time of the incident (to narrow down potential assailant fauna).

A description of the assailant, if possible.

A detailed description of how the bite or sting occurred, including how many bites or stings

(multiple bites or stings are generally more severe), or the patients activity at the time an un-

noticed bite or sting might have occurred.

What first aid, if any, was used, its timing after the bite or sting, and patient physical activity

both before and after first aid applied (physical activity may decrease first aid effectiveness).

A list of symptoms observed by the patient and their time of onset and cessation. Specifically

ask for symptoms indicative of envenoming by likely assailant species.

A list of any signs noted by those with the patient, including timing of onset and cessation.


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Relevant past medical history, including allergy, particularly to animals used to produce

antivenom (eg horses, sheep, rabbits) and any medications used by the patient. Also inquire

about recent use of alcohol or recreational drugs that might affect symptoms or signs.

Examination

It is easy to detect many signs of envenoming if looked for, but even easier to miss them if not considered during

examination. Envenoming frequently evolves over time, so repeated examination may be vital in detecting important

signs. This is particularly true for systemic effects of envenoming (see Figures 5 11).

Check bite or sting site for evidence of bite/sting marks (is there a sting left behind consider

honey bee), distance between bite marks (may indicate mouth size for snakebite), multiple

bites or stings, local effects such as erythema, oedema, blistering, ecchymosis, necrosis,

physical trauma (eg lacerations following sting ray injury).

Check regional lymph nodes for evidence of venom spread (swelling or tenderness).

Check general systemic function (BP, pulse, respiration).

Look for specific venom effects:

Flaccid paralysis ptosis, ophthalmoplegia (partial or complete), pupil dilation, loss of facial

tone, limited mouth opening or tongue extrusion, palatal paresis, drooling, limb weakness, gait

disturbance, accessory respiratory muscle use, depressed or absent deep tendon reflexes,

depressed or absent response to painful stimuli (note the patient still feels the pain, but cannot

withdraw due to paralysis, so consideration for patient distress is important), cyanosis, signs of

hypoxia, including confusion.

Excitatory neurotoxic effects anxiety, restlessness, hyperreflexia, piloerection, increased

sweating, salivation, lacchrymation, muscle fasciculation, confusion, hypoxia, pulmonary

oedema, uncontrolled random limb movements (some scorpion stings).

Myotoxicity muscle tenderness, pain on contraction against resistance, weakness (may

mimic paralysis), muscle spasm, rarely compartment syndrome signs due to massive muscle

swelling. Also check ECG for evidence of hyperkalaemic effects.

Cardiotoxicity cardiac arrhythmias, arrest, ECG abnormalities (various).

Coagulopathy and haemorrhagins persistent ooze of blood from bite site, venepuncture sites,

bleeding gums, bruising, occasionally signs consistent with a bleed into an internal

organ/space (eg intracranial etc).

Nephrotoxicity usually little to find, check for oliguria or anuria.

Laboratory tests

The extent and nature of laboratory tests will be determined by the likely type and extent of envenoming and the

availability of laboratory resources.


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Basic health facility:

Urine output check for haematuria or myoglobinuria (red or black urine; dipstix test positive

for blood; simple microscopy for red cells).

Coagulopathy 20 minute whole blood clotting test (if poor or absent clot, indicates

coagulopathy; requires only needle, syringe and glass tube or container).

Venom detection (Australia only) simple commercial ELISA based test for Australian snake

venoms (Figure 13). Best sample is the bite site. If there is systemic envenoming, then urine

could be tested, but blood is unreliable as a sample. A positive result indicates both that a

snakebite has occurred and the most appropriate antivenom, but is not an indication to give

antivenom, as venom can be on the skin, without significant systemic envenoming. A negative

result does not exclude snakebite, so is of little diagnostic help.

Fully resourced hospital

Urine output - check for haematuria or myoglobinuria (red or black urine; dipstix test positive for

blood; simple microscopy for red cells).

Blood tests:

Extended coagulation studies - (prothrombin time/INR; aPTT; fibrinogen level; fibrin(ogen)

degradation products).

Complete blood picture raised WCC suggestive of envenoming or infection; absolute

lymphopenia suggestive of certain types of snake envenoming; Hb level (look for evidence of

haemolysis); thrombocytopenia may indicate direct or indirect effect of some snake venoms orsecondary DIC.

Electrolytes and renal function look for hyperkalaemia if there is myolysis or renal failure.

Creatine kinase (CK) elevated, sometimes to extreme levels, in presence of myolysis.

Liver function tests enzyme levels may be elevated if there is myolysis.

Arterial blood gas relevant only if advanced respiratory failure due to neurotoxic paralysis or

pulmonary oedema.

Venom detection (Australia only) simple commercial ELISA based test for Australian snake

venoms (Figure 13). Best sample is the bite site. If there is systemic envenoming, then urinecould be tested, but blood is unreliable as a sample. A positive result indicates both that a

snakebite has occurred and the most appropriate antivenom, but is not an indication to give

antivenom, as venom can be on the skin, without significant systemic envenoming. A negative

result does not exclude snakebite, so is of little diagnostic help.

Critical Care


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Major envenoming is often optimally managed in an intensive care setting. The major requirement for intensive care

will be respiratory support for cases with advanced neurotoxic flaccid paralysis or severe pulmonary oedema.

Respiratory support, including intubation and ventilation, may be needed only for a few hours, but for some snake

species, may be required for days, weeks or months, until the neuromuscular junction regenerates. Intubation and

ventilation is often required to maintain airway safety, long before there is full respiratory paralysis. Tracheostomy

should be avoided until there is complete resolution of any coagulopathy or haemorrhagic tendency (some snakebite

cases); all invasive procedures with the potential to cause bleeding should be avoided for similar reasons.

In cases of cardiac arrest or severe dysfunction following envenoming by cardiotoxic species, notably the Australian

box jellyfish, prolonged cardiac support may be required.

Antivenoms

Antivenoms are the treatment of choice, where available, for most forms of major envenoming, particularly systemic

envenoming. Old aphorisms suggesting antivenom is more dangerous than envenoming are generally ill-founded and

inappropriate. Nevertheless, antivenom therapy carries certain risks and should only be used when clearly indicated.However, for many venomous animals and in many less developed regions, antivenom is either unavailable or

economically impractical.

Antivenoms are specific antidotes to venoms. Virtually all are whole or fractionated animal IgG raised against a target

whole venom, not specific venom components. Antivenoms are polyclonal and may contain far more neutralising

activity against some venom components than others. To produce antivenoms, a source of venom for immunising

must be determined. The choice of venoms may strongly influence the clinical efficacy of an antivenom; if only a

narrow range of species or species from a small part of a geographic range is used, then the antivenom may lack

efficacy against bites from a wider range of species or against bites from the target species from other parts of its

geographic range. Antivenoms may be truly monovalent (raised against the venom of a single species of animal),

monovalent to genus level (cover all or several species within a genus, or ocasionally closely related genera) or

polyvalent (raised against a venoms from a variety of species, usually unrelated apart from a common geographic

range). Most commonly, the animal used for immunising is the horse, but sheep, goats, rabbits and even chicken egg

yolk have been used. Horse based antivenoms, in particular, have a generally high incidence of adverse reactions,

but the rate of reactions will also be determined by the degree and quality of refining, particularly removal of non-IgG

components such as albumin and where IgG has been fractionated, removal of FC fragment contaminents. The three

major types of antivenom, based on the degree of fractionation are; whole IgG, F(ab)2 and Fab (Figure 14). Their

individual characteristics are listed in Table 2.

Principles of antivenom therapy

The first principle of antivenom therapy is to tailor the dose to the individual situation. From this it follows that just as

the degree of envenoming varies from nil (dry bite) to severe systemic, so the amount of antivenom required will

vary from none to potentially large quantities. The quantity required will therefore be determined by the assailant

venomous animal and not the size of the patient; there are no paediatric doses of antivenom; children require the

same amount as adults. Determining how much antivenom to administer requires considerable clinical judgement.

For some regions there are guidelines covering common species of venomous animal, notably snakes. This

information is not always available in product literature. It is beyond the scope of this chapter to detail how much of


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each antivenom to give in any possible clinical case. Consultation with regional, national or international experts is

advised if the dose required is unclear. In the past, most failures of antivenom therapy can be attributed to inadequate

dosage, or wrong choice of antivenom.

The second principle of antivenom therapy is to give as soon as possible, once it is indicated. From this it follows that

in most situations of acute envenoming, the IV route is preferred, but there are exceptions, which will be noted forparticular animals as they apply.

The third principle is to monitor carefully for the effect of antivenom therapy. This includes monitoring both

effectiveness in counteracting envenoming and observing for adverse effects of therapy. It is frequently the case that

an initial dose of antivenom may be insufficient and that follow up doses may be required. Some venom may be

sequestrated at the bite site, being released over a period of hours or days, necessitating ongoing antivenom therapy.

Equally, the type of antivenom will influence clearance as well as compartmental distribution. Fab antivenoms are

more rapidly cleared than F(ab)2 or whole IgG antivenoms, so are more likely to require continuous infusion or

regular repeated doses.

Complications of antivenom therapy

The principle complications of antivenom therapy are:

Acute adverse reactions.

Anaphylaxis and related early reactions.

Rash.

Febrile reactions (usually related to toxin contamination).

Delayed adverse reactions.

Serum sickness.

Failure of efficacy.

Incorrect antivenom.

Inadequate dose.

Inappropriate route of administration (IM or local when IV was required).

Therapy commenced too late.

Out of date antivenom or poorly stored antivenom (ie refrigerated antivenom that has been

exposed to prolonged heat).

Poor quality antivenom.

Several methods have been employed to minimise the chance of adverse effects from antivenom therapy.

Skin sensitivity testing prior to administration. This method is flawed in both theory and

practice. Such sensitivity testing will delay treatment, fail to reliably predict major adverse


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reactions (eg anaphylaxis), potentially sensitise the patient to antivenom should it be required

in the future and may precipitate an anaphylactic reaction. For these reasons skin sensitivity

testing is not recommended, even though it is advised by a number of antivenom producers

and is routinely used in some countries (eg USA).

Premedication prior to antivenom therapy. This is controversial and is not widely accepted orused. Antihistamines and steroids have been shown to have no real benefit in preventing acute

antivenom reactions. In addition, antihistamines may induce drowsiness or occasionally,

hyperexcitability, both potentially dangerous in major envenoming. Epinephrine (adrenaline)

has been shown to reduce the likelihood of adverse reactions for certain high risk antivenoms

(those that are poorly refined, with a high rate of adverse reactions) in a single trial, but its

benefit for other antivenoms is uncertain and it carries clear risks that may outweigh any

potential benefits. This is particularly true if the envenoming causes increased bleeding, as

seen with many snakebites. Premedication is not currently recommended by antivenom

producers. Future studies may better define its role, if any.

Use of diluted antivenom infusions. Most antivenoms should be given IV. Many experts

recommend dilution of the antivenom up to 1:10 in a suitable diluent for IV use, such as normal

saline or Hartmans solution. The degree of dilution will be limited by the volume of antivenom

and the size of the patient. While this technique may be useful, it is not strictly necessary, as

studies have shown that IV push neat antivenom does not carry a higher incidence of acute

adverse effects. In addition, the latter technique requires the doctor to stay with the patient

throughout the antivenom infusion, which increases the chances of rapidly and effectively

responding to acute adverse events.

Antivenom should always be given in the expectation that anaphylaxis may occur, even though this complication is

rare with good quality antivenoms. Thus epinephrine (adrenaline) should always be ready in a syringe or set up as an

infusion, prior to commencing antivenom therapy and both staff and equipment for resuscitation should be on hand.

Sourcing antivenoms

For antivenoms required for local species there will usually be a common source, often a regional or national

antivenom producer. There are significant areas of the world with moderate to high rates of envenoming where

antivenom is either in short supply, very expensive, or completely unavailable. There are many venomous animals for

which there is either no specific antivenom or no useable antivenom. For exotic venomous animals, such as

venomous snakes in zoos or private collections, appropriate exotic antivenoms may be unavailable or difficult to

source in reasonable time and quantity. A number of major zoos with reptile houses in both North America and

Europe stock a range of exotic antivenoms. Poisons information centres may also have lists of institutions stocking

exotic antivenoms, as well as experts in clinical toxinology who may be consulted on the management of envenoming

by exotic animals. There are several published lists of antivenoms and antivenom producers globally and similar lists

may be available on the internet.


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Non-antivenom treatments

While antivenom is often the preferred treatment of significant envenoming, it is not available for all animals, nor in all

areas of the world. Non-antivenom treatments may be effective as adjuncts to antivenom or as alternatives in some

situations.

Pharmaceutical

Apart from the standard range of pharmaceuticals used in a wide array of diseases, a few agents have specific roles

in certain forms of envenoming.

Anticholinesterases: Useful for flaccid neurotoxic paralysis due to post-synaptic snake

neurotoxins. They may be used as an adjunct to antivenom or as sole therapy where

antivenom is unavailable. First perform a tensilon test to determine efficacy.

Dapsone: Potentially useful for reducing necrosis in known recluse spider bites, if used early,

but toxic and controversial.

Fresh frozen plasma: Of value in replacing depleted clotting factors after snakebite

coagulopathy, but potentially hazardous if given prior to neutralisation of all circulating

antivenom.

Surgical

Surgical intervention is rarely appropriate in acute envenoming, with the exception of injuries causing acute significant

local trauma, such as some stingray injuries or where a portion of the biting or stinging apparatus remains in the

wound and requires urgent removal. Some surgical manouvres are worthy of particular comment.

Fasciotomy: This technique for releasing local tissue pressure is generally only warranted to

relieve proven (by intracompartmental pressure manometry or by doppler) intracompartmental

syndrome, where failure to do so would be likely to result in significant long term ischaemic

injury. Even in this latter, uncommon situation, most likely encountered with some forms of

snakebite, any coagulopathy should first be under control. Unwarranted fasciotomy in

snakebite, used mearly because of extensive tissue swelling, frequently results in long term

cosmetic and functional deformity and is to be avoided.

Bite or sting site wound excision: There is no substantial evidence to suggest that excising the

area of immediate envenoming is likely to be a useful procedure and it may often result in short

and long term complications. For necrotic arachnidism it is clear that early debridement of thenecrotic region (within the first 4-5 weeks) may actually extend the area of necrosis.

Other

Hyperbaric oxygen therapy: This has been used for necrotic arachnidism to both reduce the

associated pain and to accelerate healing. There is limited clinical evidence in support and the


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therapy is controversial, but may be useful in at least some patients. Guidelines for use in

envenoming are not yet established.

Complications of envenoming

Of the many potential complications of envenoming that may occur, a few particularly common or important varietiesare discussed here, most pertaining to snakebite.

Paralysis

Flaccid neurotoxic paralysis is a potentially lethal complication of major envenoming by a variety of venomous

animals (see Table 3). It may develop very rapidly (eg envenoming by the blue ringed octopus) or be more gradual

and insidious in onset. The latter may result in missing early signs, so that diagnosis is not made until paralysis is

advanced. The three principle manouvers available to manage significant paralysis are:

Intubation and ventilation.

Antivenom. Only effective for postsynaptic type paralysis.

Anticholinesterases. Only effective for postsynaptic type paralysis.

A fully paralysed snakebite patient may appear severely cerebrally injured, with fixed dilated pupils, absent reflexes,

flaccid tone and no response to painful stimuli, yet throughout an examination to establish these signs, may be

awake, terrified and well able to feel painful stimuli. Great care and consideration is required in managing such

patients. By manually opening their eyes and moving their head around, they will be able to see their environment

and those caring for them. Often it is possible to find at least some residual muscle movement which can be used to

establish communication, even if just indicating yes and no. Aspiration pneumonia and secondary infections are

also significant risks in these patients. If the paralysis is presynaptic, then assisted ventilation may be required for

weeks or months, necessitating consideration of tracheostomy after 1-2 weeks.

Myolysis

Major myolysis is particularly a feature of snakebite by some species (see Table 4). Myolysis is most problematic

when systemic. Even late administration of antivenom may sometimes speed resolution. Early and maintained good

renal throughput, by ensuring adequate hydration, may reduce the chance of secondary renal damage.

Hyperkalaemia is always a risk in these cases and should be actively sought and vigorously treated if present. At

least in the early stages, over the first 1-10 days, when muscle breakdown is peaking, it is advisable to avoid

procedures that might increase muscle damage, such as active physiotherapy.

Coagulopathy

While coagulopathy can be a secondary result of cardiovascular collapse after envenoming by a wide range of

animals, by far the most common cause is snakebite (see Table 5). Antivenom is the preferred treatment, giving

enough to neutralise expected venom load. In general, replacement therapy (FFP, cryoprecipitate) is unnecessary.


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Great care is required in avoiding iatrogenic bleeding, through injudicious insertion of canulae. Beware femoral

punctures, and subclavian and jugular line insertions and arterial blood gas sampling. For established coagulopathy,

where repeat venous sampling is required to titrate antivenom therapy against response, an indwelling line, such as a

long line through the cubital vein, may be advantageous.

Necrosis

The single most important aspect of care for necrotic bite wounds is good wound care; keeping the wound clean,

elevated and avoiding early surgical debridement (if a recluse spider bite). Particularly with necrotic arachnidism,

ulcers may be indolent, slow healing, suggestive of vascular impairment. A number of unfortunate patients have had

limb amputations for intractable bite ulcers whose impaired healing is falsely ascribed to peripheral vascular disease.

Early debridement and grafting most often fails and should generally be avoided. Infection should be treated with

antibiotics targeted to the causative organism, thus culture and sensitivity testing should be routine.

Infection

Infection is always possible after any penetrating injury, such as a bite or sting. Though uncommon, tetanus does

occasionally occur in venomous bites and stings, so tetanus prophylaxis should be routine. Avoid injections in

snakebite, however, until any coagulopathy is resolved. In most cases, prophylactic antibiotics are unnecessary. If

secondary infection occurs, endeavor to culture the organism and so target antibiotic therapy. If this is impractical,

assume a wide possibility of organisms and use an antibiotic combination appropriate to provide wide coverage.

Follow up

While mild envenoming without complications may not warrant follow up, major envenoming usually does. In

particular, patients who have received antivenom should be informed of the symptoms of serum sickness, so that

they will report for early assessment should this complication arise. Both major physical and emotional sequelae of

envenoming may occur and require extensive follow up.

Venomous snakes

Venomous snakes are the single most important cause of envenoming globally, because of the high rate of major

morbidity and mortality. Most snakes are non-venomous, with the exception of Australia, where venomous species

predominate. Many people may have difficulty distinguishing venomous from non venomous species and anxiety may

cause symptoms that mimic those of true envenoming. There are four Families of venomous snakes.

Colubrids

Most colubrid snakes lack either fangs or venom glands. A few species have fangs towards the back of the mouth(see Figure 15), associated with well developed venom glands and potent venom. A number of other colubrids may

have enlarged teeth and salivary glands producing toxic secretions, thus may cause envenoming. Venomous

colubrids account for only a small fraction of major snakebites. The most important species are listed in Table 6. The

approximate global distribution of colubrids (all species, not just venomous species) is shown in Figure 16.

Elapids


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Elapids, or cobra type snakes, are a diverse Family, all of whose members are venomous, with both developed

venom glands and fangs (see Figure 17). Major groups of elapids include cobras, kraits, mambas, coral snakes, sea

snakes and Australian and New Guinea species (Figures 18-20). Historically, elapid envenoming has been

considered as primarily neurotoxic, with minimal local effects; this is almost entirely incorrect. While many elapids can

cause paralysis, some may also cause coagulopathy, myolysis, primary or secondary renal failure and many African

and Asian cobras cause severe local necrosis. A few cobras actually spit their necrotic venom towards the eyes of

victims. The major species groups are listed in Table 7. The approximate global distribution of elapids is shown in

Figure 21.

Atractaspids

Atractaspid snakes were, until recently, included with vipers. They are restricted to Africa and the Middle East. They

are predominantly burrowing snakes and the dangerous species (from Genus Atractaspis) have sideways striking

fangs and unusual venom, that contains endothelin like toxins, the sarafotoxins. The approximate global distribution

of atractaspids is shown in Figure 22.

Vipers

Vipers probably cause the highest percentage of global snakebite mortality. They are widely represented, found even

up to nearctic regions, but are absent from New Guinea and Australia. They have highly evolved envenoming

structures, with a mobile fang that folds against the roof of the mouth when not in use. This enables long fang lengths

compared to other types of venomous snakes (see Figure 23). There are two subfamilies. Viperinae includes the old

world vipers, such as European adders, African vipers such as puff adders and Gaboon vipers, Russells vipers and

the saw scaled or carpet vipers (Figures 24-27). These latter two groups are undoubtedly the cause of many deaths

in Africa and Asia. Crotalinae covers the pit vipers, those species with infrared sensing pit organs on the head,

enabling the snake to detect and strike warm blooded prey in pitch darkness. Species groups include rattlesnakes,

moccasins, bushmasters and other South American vipers, and the Asian terrestrial and arboreal pit vipers (Figures

28-31). Traditionally, viper envenoming has been characterised as coagulopathic and locally necrotic; as with elapids,

this simplistic overview is quite inaccurate. Many viper species will cause local swelling and even bruising or necrosis

at the bite site, but a minority may cause minimal local effects. Coagulopathy is a feature of some viper bites, but not

all. A few cause primary renal failure. Several species cause predominantly paralysis, while a few others cause

myolysis. The major species are listed in Table 8. The approximate global distribution of viperids is shown in Figure

32.

Venomous lizards

There are only two species of venomous lizards, both closely related, in the Family Helodermatidae. They are found

only in parts or arid northern Mexico and adjacent parts of south western USA. They have primitive venom glands in

the lower jaw. Venom is innoculated through injuries inflicted by the teeth during a bite; there are no true fangs. The

venom is multicomponent. Clinically it causes intense local pain, assisted by the mechanical injury of the bite. The

jaws are strong and it may be difficult to prise the lizard off. The pain may last several hours and there is often local


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swelling. The wounds do not develop necrosis. Uncommonly there may be systemic effects, notably hypotension,

which may be severe and appears to be a direct venom effect, resulting in shock. Paralysis, myolysis, coagulopathy

and renal damage do not occur, although the latter two might develop as secondary complications in severe shock.

There is no antivenom available. Treatment is directed to pain relief and symptomatic therapy and treatment of shock

and its complications, if these arise.

Venomous arthropods

There are a vast number of arthropod species, inhabiting almost all parts of the globe. A considerable number are

venomous, but relatively few can cause significant envenoming of humans. Morbidity and secondary allergy is a far

bigger problem than mortality from arthropod envenoming.

Spiders

There are many thousands of species of spiders, nearly all of which are venomous, but only a few are capable of

envenoming humans significantly. Spiders may be present in high concentrations; numbers exceeding 2 million perhectare have been reported in the UK. Spiderbite is probably very common. Where incidences have been studied, as

in Australia, the number of cases is 5 to 10 times higher than snakebite, but most of the bites are of minor medical

significance. Of the relatively few species that can inflict significant injury to humans, most fall into just four groups;

the widow spiders (Genus Latrodectus); the recluse spiders (Genus Loxosceles); the banana spiders (Genus

Phoneutria); and the Australian funnel web spiders (Genera Atrax and Hadronyche). There is a fifth group, those

spiders, other than recluse spiders, causing local necrosis (necrotising arachnidism), but the species responsible are

generally poorly documented and vary with geographic region. Those spiders known to have caused injury to humans

are listed in Table 10.

The management of spiderbite varies with the type of spider involved. Antivenom is available for envenoming by

spiders known to cause problems, as listed earlier. A Discussion of all types of spiderbite is beyond the scope of this

chapter. A summary of features and management for important species is given below.

Widow spiders (latrodectism)

Widow spiders are globally distributed and probably the most common cause of medically significant spider bites.

They are sexually dimorphic, the female being far larger than the male (Figure 33). Only the female is likely to cause

significant envenoming. The venom contains a mixture of related complex -latrotoxin, appearsprotein neurotoxins,

the latrotoxins, only one of which, to be active in humans, in whom it causes widespread neurotransmitter release.

Most widow spider bites are minor, with 20% or less resulting in significant envenoming. In this latter group, the bite is

most often felt, but is usually not severely painful. A variable time later, from 10 minutes to several hours, but usually

within 60 minutes, the bite site becomes progressively painful, sometimes associated with local sweating or

erythema. The pain becomes severe and gravitates proximally to involve regional lymph nodes and produce a severe

regional pain syndrome. The rate of progression is quite variable, from less than one hour, to more than 24 hours.

Untreated the pain may spread further, giving rise to severe chest pain (mimicing myocardial ischaemia) or abdominal

pain (mimicing acute abdomen), often associated with marked localised or generalised sweating, mild to severe

hypertension, nausea, occasionally vomiting and general malaise. Rarely pulmonary oedema may ensue. Where pain


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involves the face and head, particularly with bites in or near to these regions, the severity of the pain may result in

marked facial grimacing; facies latrodectisma. Localised or generalised muscle spasms occur in some cases. True

flaccid muscle paralysis does not occur, but some patients complain of muscle weakness. There are few laboratory

abnormalities in latrodectism, but a raised white cell count is common and rarely a mild rise in CK is seen. Without

treatment, latrodectism can cause distressing symptoms for days, weeks or even months. While a few deaths have

been reported, these are most likely due to secondary complicatiuons rather than primary venom toxicity and given

the high number of cases of loxoscelism, fatality is quite rare. Latrodectism is not associated with local tissue injury or

necrosis at the bite site.

In those cases with significant regional or systemic envenoming, antivenom is the best treatment option. Several

antivenoms are available, depending on the geographic region. All are equine. Australian CSL Red Back Spider

Antivenom (RBSAV)has been tested with a variety of major widow spider venoms, including those from Australia,

North America and Europe, and found to be effective for all (this testing remains unpublished at time of writing this

chapter and was not conducted by CSL). It is possible some other widow spider antivenoms may also have a wide

spectrum of use, but this is untested. Experience in Australia with the CSL RBSAV, which has been used in tens of

thousands of patients, has shown this product to be safe and effective, in contrast to some similar widow spiderantivenoms in other regions. The following advice on antivenom administration is therefore based on the CSL RBSAV.

Antivenom should be used in all cases with significant systemic envenoming and if there is severe regional

envenoming, notably severe pain, as this is usually unresponsive to standard analgesia. In contrast to most other

antivenoms, this antivenom appears effective if given IM. Give a single ampoule IM, with epinephrine (adrenaline)

and resuscitation facilities ready, in case of anaphylaxis (rare with this antivenom). Wait two hours; if there has been

minimal response or a relapse, give a second ampoule. Repeat the procedure, up to three ampoules. Occasionally,

particularly where treatment has been delayed or the patient is large, higher doses are required. Five ampoules is

the usual maximum, but higher doses have occasionally been used. If envenoming is severe, consider the IV route.The antivenom appears effective even when commenced late, even days, occasionally weeks after the bite. While

the theoretical basis for this is obscure, the finding is established by clinical experience with numerous cases. Non-

antivenom treatments are generally far less effective; IV calcium gluconate or chloride and pharmaceuticals such as

diazepam have been used with mixed success; they should not be considered in preference to antivenom.

Recluse spiders (loxoscelism) and necrotic arachnidism

Recluse spiders, also known as brown recluse, fiddleback or violin spiders, genus Loxosceles, are globally

distributed, but most cases of significant envenoming are reported from the Americas, southern Europe and southern

Africa. The spiders are small, delicate, usually with a characteristic violin shaped marking on the dorsal cephalothorax(Figure 34). These spiders may be present in houses, yet rarely seen, because of their cryptic habits. They are most

active at night, when most bites occur, often while the victim is asleep in bed. Their venom is complex and

incompletely understood, but can cause direct tissue injury at the bite site, with marked necrosis, occasionally

extending well beyond the bite area. Microvascular damage, thrombosis and occlusion, chemotaxis of neutrophils,

releasing cytotoxic components and direct cellular injury are all postulated as mechanisms involved in the local

necrosis. The percentage of bites resulting in necrosis is unknown, but certainly less than 100%. The bite is usually


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not felt and often the spider is not seen, thus diagnosis of loxoscelism is often presumptive. A variable time later, often

many hours, the bite area will become painful, red, then progressively discolour, often with a violaceous colour, or

suggestion of bruising. Blisters may form, containing clear fluid or blood tinged fluid. The central area may become

increasingly dark, dry, suggesting a dry gangrene eschar. This progression may take from 2 to 7 days. The eschar, on

separation, will reveal underlying necrosis. In the early stages of the illness, the patient often suffers non-specific

systemic symptoms, such as fever, sweats, nausea, malaise, usually resolving after about 48 hours. The area of

necrosis may extend over days to weeks and is usually very slow to heal. It is often painful, but not always so and

there are cases where the whole process of necrosis and ulceration is pain free, at least in the first week or so.

Secondary infection is a significant problem once ulceration has become established. Venom has been detected in

the ulcerated area for at least 28 days post bite, possibly explaining why early debridement often results in extending

the lesion. This syndrome of local and non-specific systemic effects is classified as cutaneous loxoscelism. More

rarely, there may be a specific systemic syndrome associated, classified as viscerocutaneous loxoscelism,

characterised by all the features of the cutaneous form, plus a major and potentially lethal systemic illness, with

intravascular haemolysis, haemorrhage into major organs, DIC and renal failure. This form has been associated with

30% mortality, even with antivenom treatment. It is rare in North American cases of loxoscelism, but more common inSouth America.

Necrotic arachnidism is more common and widespread than loxoscelism, though loxoscelism is undoubtedly the most

common cause of necrotic arachnidism globally. A few other species of spiders are suspected of causing necrosis

(see Table 10). Their venoms are generally not characterised. The pattern of non-loxosceles necrotic arachnidism is

generally similar to loxoscelism, but without the viscerocutaneous form. For all forms of necrotic arachnidism,

including loxoscelism, it is apparent that overdiagnosis occurs; a variety of other conditions, including infections,

allergy, drug reactions, other venomous bites, vascular disease, secondary effects of systemic diseases such as

diabetes mellitus, may cause a clinical picture similar to necrotic arachnidism. The patient is not well served by

mislabelling such problems as necrotic arachnidism, as the opportunity for appropriate and effective treatment may

be missed. Equally, these and similar diseases may be invoked as a diagnosis, when necrotic arachnidism is the real

cause, resulting in detrimental early surgical intervention and later unnecessary amputation of viable limbs, presumed

non-viable due to vascular disease. In Australia there is a common belief in the community and amongst members

of the medical profession that a common house spider, the white tailed spider, Lampona cylindrata, is a frequent

cause of necrotic arachnidism. This belief is not supported by evidence; reported bites by this spider do not result in

extensive necrosis, indeed there are only 5 cases where even minor ulceration has occurred and in at least 3 of these

the identity of the spider is suspect. In all other confirmed cases, no tissue injury has occurred. Further, venom

research has failed to demonstrate any necrotic activity in this venom. It is therefore inappropriate to label cases of

suspected necrotic arachnidism in Australia as white tailed spider bites.

Treatment of loxoscelism and necrotic arachnidism is contoversial. Antivenom (for loxoscelism) is only available inparts of South America, notably Brazil (IV Instituto Butantan Polyvalent Spider Antivenom; Soro anti-aracndico

polivalente), where it is reported as effective at reducing the extent of tissue injury, but studies elsewhere have not

reproduced this effectiveness in animal models. Pharmaceutical reduction in chemotaxis, using dapsone, has been

advocated and if used early may reduce tissue injury, but adverse drug toxicity has cast doubt on this treatment.

Steroids have not been shown beneficial. As mentioned earlier, surgical debridement within the first 3-5 weeks of the

bite may extend and worsen the necrotic lesion and skin grafting is usually unsuccessful within the first 1-3 months.


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Hyperbaric oxygen therapy (HBO) is advocated by some physicians, with limited research giving equivocal and

contadictory results on its benefit. Experience in Australia with HBO in necrotic arachnidism has been more positive,

but not yet confirmed by clinical trials. HBO appears to be effective at reducing or abolishing local pain associated

with the necrosis and probably reduces the extend and hastens recovery of the necrotic area, but does not show

benefit in all patients. Overall, the most effective treatment for loxoscelism and necrotic arachnidism, is good wound

care, targeted antibiotic therapy if secondary infection occurs, and avoidance of early surgical debridement or

grafting.

Banana spiders

Banana spiders, of the genus Phoneutria, are found principally in South America, particularly Brazil. They are large

robust looking spiders (see Figure 35) and are common in some Brazilian urban areas, where they dominate as a

cause of significant spiderbite. Their venom contains excitatory neurotoxins (Na+ channel activators), resulting in a

syndrome of systemic envenoming characterised by local and generalised pain, local swelling, sweating, hyper

lachrymation and salivation, piolerection, hypertension, muscle spasm, priapism, nausea, vomiting and rarely, cardiac

arrhythmias and pulmonary oedema. Death is very rare and local wound necrosis is not a problem.

The most effective treatment is IV Instituto Butantan Polyvalent Spider Antivenom (Soro anti-aracndico polivalente),

but is generally reserved for those with moderate to severe envenoming, characterised by clear systemic effects such

as hypertension (or hypotension), vomiting, salivation, priapism, marked sweating, cardiac arrhythmia, or pulmonary

oedema. Dosage is 2-5 ampoules, depending on severity of envenoming. For local pain in all cases, a regional

anaesthetic block is effective, though infiltration of 2% lignocaine or similar SC is also effective in many cases.

Australian funnel web spiders

Australian funnel web spiders are primitive mygalomorph spiders of the Family Hexathelidae, genera Atrax (3

species) and Hadronyche (30+ species), restricted to wetter areas of eastern and southern Australia (Figures 36-38).They are generally large spiders with long fangs, found in burrows with typical silk funnel-like entrances, most often

on the ground, though a few species are arboreal. Mature male spiders leave their burrows to mate and are therefore

more commonly encountered by humans. Bites may occur by stepping on the spider, or by close contact with a spider

which has entered shoes or clothing left on the ground, indoors or out. They can survive prolonged periods in

swimming pools. Unfortunately, several major urban centres, notably parts of Sydney and surrounds, are built on

major habitat for funnel web spiders. Worse still, at least for the Sydney funnel web spider, Atrax robustus, it is the

more frequently encountered male spider which is most toxic. In the past most reported funnel web spider bites and

fatalities occurred in the Sydney region, but there are now confirmed cases and fatalities from a wider geographic

range (most of eastern New South Wales and SE Queensland) and a wide range of species, including several

Hadronyche species. This clinical experience and venom research now suggests that possibly all species of funnel

web spiders may cause severe envenoming in humans. This greatly extends the area and population at risk.

Mitigating this is the rarity with which these spiders are encountered outside the range of recorded major bites, as

listed above. For those species examined, the venom appears similar, containing polypeptide excitatory neurotoxins

that result in widespread neurotransmitter release and a catecholamine storm.

Most funnel web spider bites are minor, but cause local pain, partly due to mechanical trauma from the large fangs.

The venom is acidic, also causing pain. In cases developing systemic envenoming, there is rapid progression to


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systemic effects, with potentially lethal envenoming occurring within 60 minutes of the bite in some cases. Fatalities

have occurred as soon as 15 minutes post bite. First seen is perioral tingling, then tongue spasms, nausea, vomiting,

abdominal pain, profuse sweating, salivation and lachrymation, tachycardia, hypertension and severe dyspnoea

secondary to pulmonary oedema. Cerebral hypoxia may lead to confusion or coma. Generalised fits have been

reported, in one case being status epilepticus, resulting in ultimately fatal cerebral injury. The pulmonary oedema

can be extreme and was a common cause of death. Those surviving this stage sometimes developed generalised

muscle spasms, progressing to insidious hypotension and death due to cardiac arrest.

First aid for suspected funnel web spider bite is important as it may both delay onset of envenoming and allow local

inactivation of venom. The approved method is the pressure immobilisation bandage, as used for Australian

snakebite (see First Aid section). All cases should be admitted for observation, as late envenoming can occur. If there

is any evidence of systemic envenoming, then CSL Funnel Web Spider Antivenom should be given IV without delay.

The starting dose is 2 ampoules, or 4 if severe envenoming and further doses may be needed in severe cases,

titrated against response. Apparent recovery, then relapse with pulmonary oedema suggests re-envenoming,

requiring further antivenom, but beware overhydration as an alternate cause of late pulmonary oedema. Anaphylaxis

is unlikely with this antivenom, because of the catecholamine storm, but serum sickness has been reported in asingle case. The antivenom is rabbit IgG. In the absence of antivenom, severe envenoming may prove lethal despite

full intensive care treatment. Intubation and positive pressure mechanical ventilation may help control pulmonary

oedema. Pharmaceutical manipulation has generally proved unhelpful, with the exception of atropine and

occasionally isoprenaline, while beta blockers are considered contraindicated.

Scorpions

Of the numerous scorpion species, only those in the Family Buthidae cause significant envenoming in humans.

Several buthid scorpions are potentially lethal and their stings result in hundreds of thousands of cases of

envenoming and thousands of deaths each year. They are therefore far more dangerous than spiders overall, though

none would be considered as more dangerous than Australian funnel web spiders. The medically important types ofscorpion are listed in Table 11. Scorpions envenom by using a sting in their tail. Their venom contains mixtures of

potent toxins, particularly proteins, notably excitatory neurotoxins targeting neuronal ion channels (Na+, K+, Ca++).

The clinical effects of scorpion envenoming vary between species, but in general stings cause immediate marked

pain, sometimes associated with local erythema, pruritis or hyperaesthesia. When systemic envenoming ensues, it

usually does so rapidly, often within an hour. Systemic features may include hyperexcitability, tachy- or bradycardia,

hyperthermia, restlessness or uncoordinated movements of limbs or eyes, profuse sweating, lachrymation and

salivation, nausea, vomiting or diarrhoea, abdominal pain or distension, dyspnoea, pulmonary oedema, cough, hypo-

or hypertension, cardiac arrhythmias, shock, convulsions, ataxic gait, muscle fasciculation or coma. Local sting site

necrosis is not usually a problem, with the occasional exception of stings by Hadrurus species. Most stings occur at

night, often when the person stands, sits or lies upon a scorpion. Children are most likely to develop severe or fatalenvenoming.

The treatment of scorpion envenoming is controversial and varies both with species and country. In most regions

where potentially lethal species exist, specific antivenom is available and there appears ample evidence to support its

effectiveness, but in some countries, notably Israel, there are physicians who decry its use. Antivenom choice will

depend on the species and country, as will initial and subsequent dosage, but in all cases it is most effective if given

early and IV, with the usual precautions against anaphylaxis. There is continuing unresolved argument about the


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relative merits of Fab versus F(ab)2 versus whole IgG antivenoms for scorpion envenoming. In the absence of

antivenom, or as adjunctive therapy, IV hydration (especially in shock), inotropes etc for control of blood pressure,

diazepam and related drugs for muscle spasm or involuntary muscle movement, and airway maintenance may all be

useful. Prazosin, in particular, is favoured by some clinicians and is reported as effective in controlling systemic

envenoming by Indian scorpions, without use -blockers are likely to worsen envenoming and are of antivenom.

contraindicated. Atropine may potentiate the pulmonary oedema, so is not generally recommended, but may be

required if there is severe bradycardia. Neostigmine, steroids, barbiturates and narcotics are either of no proven

value or are potentially hazardous.

Insects

There are a vast array of insect species whose bite or sting can harm humans, often through transmission of disease.

Hymenopteran insects (bees, wasps, ants) include many species with stings and venom glands. Their venom mostly

contains peptides, components such as melittin, apamin, histamine, serotonin and dopamine. While these may

induce both local and systemic effects in sufficient quantity, most stings inject too little to induce major toxicity.

Multiple stings, particularly from honey bee species (eg. Africanised bees) and some large wasps (European wasps,

hornets etc), can cause systemic toxicity, often causing haemolysis, with secondary renal failure, DIC and secondary

organ failure and shock. Particularly in children, this can be rapidly fatal. In most fatal cases the number of stings

exceeds 1,000, though significant toxicity is possible with fewer stings.

The other major effect of hymenopteran stings is acute allergy, specifically anaphylaxis in individuals previously

stung, who have developed IgE to venom components. Far more humans die from anaphylactic reactions to

hymenopteran venom than sucumb to toxicity from multiple stings. In North Carolina (1972-89) 42.4% of all animal

injury deaths were caused by insect stings, almost entirely due to anaphylactic reaction to a hymenopteran sting

(17.4% honey bees; 8.7% wasps; 7.6% yellow jackets; 2.2% hornets). The common honey bee, Apis mellifera, is a

prime cause of such sting allergy, but it may occur with stings from other species, notably native bees, common

wasps (European wasps, hornets etc) and a few species of primitive stinging ants (eg. Inch and jumping ants in

Australia; Myrmeciinae, genus Myrmecia). These latter ants have particularly potent and allergenic venom and are a

significant cause of major hymenopteran allergy in SE Australia. Desensitisation is appropriate for individuals with a

history of major systemic reactions to stings, but venom for such therapy is generally only available for honey bee

sting allergy.

Some ants lack stings, but can bite, their saliva causing local pain or irritation, or spray venom from the abdomen. For

most species this is minor, but for some, such as fire ants genus Solenopsis, an introduced pest species in North

America, the effects may be significant, their sting causing local burning, pruritis and blistering due to

dialkylpiperidines and other venom alkaloids.

A number of beetles (coleopterans) may cause local tissue injury as a result of their bite, spraying saliva or abdominal

or prothoracic gland contents. The latter is most important in toxic reactions. Most prominent of these are the blister

beetles (Meloidae), the principal toxin being cantharidin (Spanish fly), which causes blistering of the skin and local

dermatitis, for which there is no specific treatment. Contr

bites and stings poisonous animals valuable source

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