Pseudonaja affinis
1. NAME
1.1 Scientific Name
(Cogger 1975, 1987; Cogger et al 1983; Mengden & Fitzgerald 1987)
Pseudonaja affinis
guttata
inframacula
ingrami
modesta
nuchalis
textilis
1.2 Family
Elapidae
Genus: Pseudonaja Gunther
1.3 Common Names
Scientific name Common name
Pseudonaja affinis affinis Dugite
affinis tanneri Dugite Tanner's brown snake
guttata Speckled brown snake,
downs tiger snake
inframacula Peninsula brown snake
ingrami Ingrams brown snake
modesta Five ringed snake,
ringed brown snake
nuchalis Gwardar western brown snake
textilis Common brown snake,
eastern brown snake
2. SUMMARY
2.1 Main risks and target organs
Brown snakes are probably the most common cause of significant
snakebites in Australia. Without appropriate antivenom
treatment, a significant number of cases may be fatal.
Main risks are: coagulopathy, acute renal failure, neurotoxic
paralysis.
Target organs: neuromuscular junction, coagulation system,
kidneys.
2.2 Summary of clinical effects
Locally: The bite is usually painless, without significant local
erythema, bruising or oedema. Bite marks may be difficult to see,
and vary from a single puncture to multiple punctures or multiple
scratches. Local secondary infection is unusual. Venom may spread
to draining lymph nodes with consequent pain and/or tenderness
and/or swelling.
Systemic: Headache, nausea, vomiting, abdominal pain, impaired
conscious state, occasionally loss of consciousness and
convulsions. Coagulopathy, rarely with overt bleeding
manifestations. Progressive neurotoxic paralysis can occur but is
unusual. Acute renal failure.
2.3 Diagnosis
Monitor coagulation to establish the presence and extent of
coagulopathy, and as an index of systemic envenomation. This
should be performed at presentation, on development of symptoms
or signs of systemic envenomation, regularly thereafter, and 1-2
hours after antivenom therapy until sufficient antivenom has been
given to reverse coagulopathy.
In the absence of a haematology laboratory, whole blood clotting
time in a glass test tube is useful. If a laboratory is
available, prothrombin ratio, activated partial thromboplastin
time, thrombin clotting time, fibrinogen level, and
fibrin(ogen) breakdown products are most useful.
Other useful tests are complete blood picture and platelet count,
serum electrolytes, creatinine, urea, serum enzymes, especially
creatine kinase, urine output and urine myoglobin, and venom
detection using CSL Venom Detection Kit. Best sample is swab from
bite site (sample swab stick in kit). If patient has systemic
envenomation urine may also be useful sample. Blood is not a
reliable sample.
2.4 First-aid measures and management principles
(a) If the patient develops evidence of respiratory or cardiac
failure, use standard cardiopulmonary resuscitation
techniques to maintain life.
(b) The patient should be encouraged to lie still, and
reassured to avoid panic.
(c) A broad compression bandage should be applied over the
bitten area, at about the same pressure as for a sprained
ankle. This bandage should then be extended distally, then
proximally, to cover as much of the bitten limb as
possible.
(d) The bandaged limb should be firmly immobilised using a
splint.
(e) The bite site wound should not be washed, cleaned, cut,
sucked, or treated with any substance.
(f) Tourniquets should not be used.
(g) The patient should be transported to appropriate medical
care.
(h) Nil orally unless the patient will not reach medical care
for a prolonged period of time in which case only water
should be given by mouth. No food should be consumed.
Alcohol should not be used.
(i) If the offending snake has been killed it should be brought
with the patient for identification.
(j) Remove any rings, bangles etc from the bitten limb.
Treatment principles
(a) Specific: If the patient has systemic envenomation, give
brown snake antivenom (CSL).
(b) General: Support of cardiac and respiratory functions;
treatment of shock; maintenance of adequate fluid load,
electrolyte balance, and renal output; tetanus prophylaxis;
treatment of local sepsis with antibiotics; treatment of
significant blood loss with blood transfusion.
(c) Local: Do not clean or touch local wound until appropriate
samples taken for venom detection. Thereafter ensure
antisepsis. Early surgical intervention is generally
contraindicated, and is only indicated theoretically in the
late stages, in the very rare event that significant local
necrosis has developed. Such cases have not been described
for brown snake bite.
2.5 Venom apparatus, poisonous parts or organs
Venom is produced in paired modified salivary glands,
superficially situated beneath the scales, posterior to the eye,
and surrounded by muscles, the contraction of which compress the
glands, expelling venom anteriorly via venom ducts to the fangs.
The paired fangs, situated at the anterior part of the upper jaw,
on the maxillary bones. They have an enclosed groove for venom
transport, with an exit point near the fang tip. Average fang
length in adult brown snakes is 2.8 mm (2.0 - 4.0 mm), and
average distance between fangs is 9 mm. Average venom yield is 2-
6 mg, maximum 167 mg (Pseudonaja textilis). Mean venom injected
at first bite (defensive strike) is 4.5 mg (0.03 to 9.10 mg),
mean venom left on skin is 0.22 mg.
2.6 Main toxins
Pseudonaja venom is a complex mixture of protein and non-protein
components, not all of which have been fully evaluated.
(a) Neurotoxins: both presynaptic (eg textilotoxin) and
postsynaptic (Pseudonajatoxin a and b).
(b) Procoagulants: principally prothrombin converters( factor
Xa analogues), converting prothrombin to thrombin
(meziothrombin).
(c) Nephrotoxins: Not conclusively demonstrated experimentally,
but strongly suspected on clinical evidence .
3. CHARACTERISTICS
3.1 Description of the animal
3.1.1 Special identification features
The brown snakes are oviparous, diurnal or crepuscular, and in
warm weather may be nocturnal. Food varies with species,
subspecies and locality and principally comprises small lizards
and small mammals. They do not possess discrete temperature-
sensing organs.
Brown snake dentition is proteroglyphous (maxilla), the paired
fangs being situated in the anterior portion of the upper jaw
("front fanged"), on partly mobile maxillae allowing limited
elevation for strike (10-15°). The fangs have venom transport
grooves, enclosed for most of their length. Average fang length
2.8 mm (2.0 - 4.0 mm), average distance between fangs 9 mm.
Pupils are circular. The head is not distinctly triangular.
(Cogger 1975)
Seven species are currently recognised, although some
taxonomists now believe some species actually comprise a
species complex, ie, P. nuchalis may comprise a complex of
5 species (Mengden & Fitzgerald 1987).
Genus Pseudonaja
Characterised by a large degree of individual and
population variation. Nasal and preocular scales in
contact, suboculars absent. Body scales generally smooth;
17-21 rows of scales at mid-body; ventral scales 145 to
235; anal scale divided, subcaudal scales divided; (Cogger
1975). The scalation posterior to the eye may assist in
differentiating Pseudonaja from similar brown coloured
snakes, eg, Pseudechis australis, Oxyuranus microlepidotus
(Figure ) (Mengden and Fitzgerald 1989). Virtually all
Pseudonaja have a distinctive pattern of paired orange
spots on each anterior ventral scale, forming a double row
ventrally, a feature not seen in other Australian elapid
snakes. However, it may not be distinct in P. affinis
tanneri & P. inframacula.
Pseudonaja affinis
Scalation: as for genus; mid-body scales 19 rows, ventrals
190-230, subcaudals 50-70.
Length: 1.5m (up to 2m)
Colour: grey, olive, or brown dorsally, head often paler
than rest of body, sometimes with darker speckling or
blotches particularly on the nape. Some specimens have
black scales randomly distributed.
Pseudonaja affinis taneri
Scalation: as above
Length: 1m
Colour: Darker (smaller) snake than P. affinis affinis as
above, it is usually very dark brown both dorsally and
ventrally.
Pseudonaja guttata
Scalation: as for genus; mid-body scales 19-21 rows,
ventrals 190-220, subcaudals 45-70.
Length: 0.5m (max. variously reported as 0.8m and 1.4m).
Colour: Variable, some specimens uniform pale fawn to
orange dorsally, but with a speckled appearance on
movement, or with 12-18 broad dark brown to black cross-
bands or blotches.
Pseudonaja inframacula
Scalation: As for genus; mid-body scales 17 rows, ventrals
185-235, subcaudals 45-75.
Length: 1.7m
Colour: Variable, from pale brown to almost black. Usually
has scattered black scales giving patchy speckled
appearance.
Pseudonaja ingrami
Scalation: As for genus; mid-body scales 17 rows, ventrals
190-220, subcaudals 55-70.
Length: 1.2m (max 1.7m)
Colour: Grey-brown to deep brown on dorsal head, and neck
black or speckled with dark grey. At least 5 colour morphs
noted. Buccal cavity dark, distinguishing it from closest
relative, P. textilis, which has pink buccal cavity.
Pseudonaja modesta
Scalation: As for genus; mid-body scales 17 rows, ventrals
145-175; subcaudals 35-55.
Length: 0.45m (max 0.6m)
Colour: Pale grey brown to brown dorsally, with a dark
brown to black head, pale nuchal band, followed by a dark
nuchal band, and a further 4-7 narrow dorsal bands evenly
spaced along the body and tail. Large specimens may
exhibit only very faint banding.
Pseudonaja nuchalis
Scalation: As for genus; mid-body scales 17-19 rows,
ventrals 180-230, subcaudals 50-70.
Length: 1.5m
Colour: Very variable, with at least 5 distinct colour
morphs probably representing distinct species. (Mengden &
Fitzgerald 1987). Mostly uniform colour for each specimen,
which may be light tan, or grey, orange, brown, dark brown,
russet, or almost black. Some specimens have a black head
and nape, sometimes with paler speckling on body, others
may have a series of dark brown or black bands on the body
and tail, others may have a series of dark brown or black
bands on the body and tail, others may lack any dark
markings. There may be randomly placed dark scales, or
vertebral blotches. Some forms may have a pale head.
Pseudonaja textilis
Scalation: As for genus; mid-body scales 17 rows, ventrals
185-235, subcaudals 45-75.
Length: 1.5m (max. over 2m)
Colour: Variable, mostly uniform for each specimen, ranging
from light tan, or grey, orange, russett, brown, to almost
black. There may be darker speckling, banding, blotches, or
purely uniform dorsal colour. The head may be uniform with
the body, or paler or dark. Juveniles variable but usually
with black head dorsally, then a pale orange nuchal band,
followed by a black band. The body may be unbanded or with
numerous narrow black bands or speckles.
3.1.2 Habitat
Brown snakes occupy a wide variety of habitats from arid
dessert, to scrubland, to moister areas. They are not
uncommon in association with man's activities, such as in
paddocks, around rubbish dumps and farm buildings, and
under elevated floors of country homesteads. Principally
diurnal, though active on warm nights.
3.1.3 Distribution
Brown snakes are restricted to continental Australia and a
few adjacent islands but not Tasmania (Longmore 1986). P.
textilis is also reported from Papua New Guinea. (Cogger
1975). Distribution for each species based on museum
records are shown in Figures .
3.2 Poisonous/Venomous Parts
Venom glands (paired) situated superficially in posterior part of
head, connected by ducts to forward placed (paired) fangs. Fangs
small, may leave classic single or double puncture in man, or a
more complicated array of scratches and other punctures, the
latter by non-fang teeth (White 1987a,c). Classic bite mark in
plaster is shown in Figure . Actual cases illustrated in
Figures .
3.3 The toxin(s)
3.3.1 Name: Pseudonaja venom; Brown snake venom; BSV
Components
Neurotoxins:Textilotoxin (= Textilon)
(Coulter et al 1979, Southcott and Coulter 1979, Coulter et
al 1983, SU et al 1983) Tyler et al 1987a)
Pseudonajatoxin a
(Parnett et al 1980)
Pseudonajatoxin b
(Tyler et al 1987b)
Coagulants:Prothrombin converter (unnamed) from P.
textilis.
(Coulter et al 1983, Masci et al 1987, White et al 1987).
3.3.2 Description
Whole venom production based on milking specimens, usually
in captivity. (White 1987b, Fairley & Splatt, 1929).
Average Maximum
Pseudonaja textilis 2 mg 67mg
Venom components
Neurotoxins
Textilotoxin (=Textilon). A presynaptic neurotoxin,
phopholipase A2 protein, with 5 subunits, 20% carbohydrate
content including sialic acid, MW approx. 74,000 D (or
88,000) LD50 0.001 mg/kg N (mouse) (an LD50 of 0.0006 mg/kg
IV mouse has been reported using dilution in BSA).
(Coulter et al 1979, Coulter et al 1983, SU et al 1983,
Tyler et al 1987).
Pseudonajatoxin a. A postsynaptic neurotoxin, protein, 117
amino acids, 7 disulphide bridges, MW 12280), LD50 0.3
mg/kg i.p. (mouse), binds strongly (perhaps irreversibly)
to acetylcholine receptors. (Barnett and Holden 1980).
Pseudonajatoxin b. A postsynaptic neurotoxin, protein, 71
amino acids, MW 7762 D, LD50 0.015 mg/kg i.p. (mouse),
binds to acetylcholine receptors on mammalian skeletal
muscle only weakly and reversibly, and may be similar to k-
bungarotoxin which blocks neuronal acetylcholine receptors
on sympathetic ganglia (Tyler et al 1987b).
Procoagulants
The prothrombin-converting activity of brown snake venoms
has been noted, and demonstrated for P. textilis, P.
nuchalis, P. affinis, and not found in P. modesta venom.
(Denson 1969, Chester and Crawford 1982, Marshall and
Hermann 1983, Sutherland et al 1981, White et al 1987).
The pro-coagulant is complete and independent of factor V.
From P. textilis it is a large glycoprotein, approx. MW
200,000, comprising approx. 40% of total venom protein, and
is lethal in rats at a dose of 0.023 mg/kg. (Masci et al
1987).
In a recent report, thrombocytopenia in association with
brown snake bite has been documented, with a suggestion
that this may be due to a platelet aggregating factor in
brown snake venom, apparently discovered by the same group
of researchers, from the venom of P. nuchalis and P.
affinis. (Morling et al 1989, Marshall and Hermann 1989).
However, there is some doubt about the validity and
clinical relevance of these conclusions (White 1990).
3.3.3 Other physico-chemical characteristics
No further data.
3.4 Other chemicals in the animal
No data.
4. CIRCUMSTANCES OF POISONING
4.1 Uses
Venom is used both in antivenom production and for laboratory
research. The neurotoxins in particular may prove valuable in
neuromuscular transmission research, and the procoagulants in
further elucidating the mechanism of normal human coagulation.
4.2 High risk circumstances
Children: when playing in areas were brown snakes are common,
either through accidental encounter (ie stepping on
snake) or while trying to emulate naturalists (ie
trying to catch snake).
Adults: when living in areas where brown snakes are common,
and moving around barefoot and without due care, or
while putting hands etc into non-reconnoitred
potential snake retreats (ie hollow logs etc).
Farm workers: when working in areas where brown snakes are
common.
Reptile keepers and snake handlers:
if due care is not exercised in catching and handling
snakes, including venom milking.
Recreation seekers:
camping or walking or playing sport in areas where brown
snakes are common.
Homes: around homes in brown snake prone areas where water is
seasonally scarce and free water is available in the
garden or home.
4.3 High risk geographical areas
Brown snakes are widely distributed in most habitats of mainland
Australia, but are absent form some southern islands and
Tasmania. While no high risk geographic regions have been
identified, it is evident that brown snakes may readily enter
metropolitan fringes, and country towns, and are frequently found
around country rubbish dumps and under the floors of elevated
country homesteads, and around farm buildings.
5. ROUTES OF ENTRY
5.1 Oral
No data, but unlikely to be hazardous unless there are open
wounds in the gastrointestinal tract.
5.2 Inhalation
Unknown.
5.3 Dermal
There is no evidence that venom can be absorbed through intact
skin. Current first-aid advice is to leave venom on skin for
later venom identification.
5.4 Eye
Unlikely, no cases reported.
5.5 Parenteral
5.5.1 Bites
In human envenomation, venom is always inoculated by the
snake biting. Owing to the size of the fangs, venom is
most likely to be inoculated cutaneously or subcutaneously.
5.5.2 Stings
Not possible.
5.6 Others
Experimentally, venom may be administered to test animals via
subcutaneous, intramuscular, intravenous, intraperitoneal, and
intraventricular (CNS) routes.
6. KINETICS
6.1 Absorption by route of exposure
The rate and amount of absorption will depend on the quantity of
venom injected, the depth of injection, site of injection
including vascularity, the activity of the victim, and the type,
efficiency of application and length of application of first aid.
Clinical evidence from human cases of envenomation suggests that
much initial venom movement is via the lymphatic pathways. This
is supported by work in monkeys. (Barnes & Trueta, 1941;
Sutherland et al 1975; Sutherland & Coulter, 1977; Sutherland et
al 1981a)
Direct intravenous injection, unrecorded in man, obviously allows
rapid systemic circulation of venom and may result in different
effects from normal routes of inoculation, particularly in regard
to coagulation.
6.2 Distribution by route of exposure
It appears that much venom is transported from the bite site via
the lymphatic system, then concentrating in draining lymph nodes,
before ultimately reaching the systemic circulation. However,
experience with numerous human cases of brown snake envenomation
shows that symptoms and signs of envenomation may occur within
15-30 minutes of the bite, especially in children. Such early
effects (eg headache, nausea, abdominal pain, collapse) may be
due to either rapidly systemically circulating venom toxins, or
systemically circulating autocoids released at the bite site by
the action of venom on local tissue.
Once in the systemic circulation, venom rapidly reaches high
concentrations in the kidneys and excreted in the urine. Such
venom must also exit the circulation, to enter the extravascular
space where it binds within the neuromuscular junction
(presynaptically and/or postsynaptically) and possibly other
nerve junction sites (eg autonomic system, perhaps causing
abdominal pain).
The kinetics of venom distribution, excretion, and detoxification
are incompletely understood. Neurotoxic paralysis usually takes
at least 2-4 hours to become clinically detectable. Coagulopathy
however may become well established within 30 minues of a bite.
6.3 Biological half-life by route of exposure
No data
6.4 Metabolism
Little information is available on the metabolism of venom
components in man, but most components are fully active in whole
venom, requiring no further modification for activity. Venom
reaches high concentrations in the kidneys and excreted in urine.
(Sutherland & Coulter, 1977 a,b). The fate of specific venom
components, particularly neurotoxins and procoagulants, is
unclear. It seems likely that these components are progressively
detoxified in situ.
6.5 Elimination by route of exposure
Most venom is eliminated via the kidneys in the urine.
7. TOXINOLOGY
7.1 Mode of action
Neurotoxic paralysis
Whole P. textilis venom contains a variable mixture of
presynaptic and postsynaptic neurotoxins. The composition of this
mixture is apparently not uniform across all populations of brown
snakes, and clinically neurotoxic paralysis is not commonly seen
with brown snake bite. Neurotoxins have not been described from
other species of Pseudonaja, but since research is scant this
does not preclude their existence.
The following is largely based on work with presynaptic
neurotoxins of some other Australian elapid venoms rather than
specific work with brown snake venom.The presynaptic neurotoxins
(eg Textilotoxin) appear to bind directly to the cell membrane
of the terminal axon, at the neuromuscular junction. After a
latent period of approximately 60-80 minutes, the neuromuscular
block becomes detectable (in isolated nerve-hemidiaphragm
preparations of mouse), and is rapidly established as essentially
complete paralysis. This is associated with a reduction in
cholinergic synaptic vesicle number, fusion of vesicles, and
damage of intracellular organelles such as mitochondria. There is
an increase in the level of free calcium in the nerve terminal.
Thus the neurotransmitter acetylcholine appears to be
progressively removed or made unavailable for release, causing
paralysis. (Dowdall et al 1977; Eaker 1978; Cull-Candy et al
1976; Datyner & Gage 1973).
The postsynaptic neurotoxins cause blockade of the acetylcholine
receptor on the muscle end-plate at the neuromuscular junction.
As this action is extracellular these toxins are more readily
reached by antivenom.
A newly described group of neurotoxins, the kappa-bungarotoxins,
appear to block the acetylcholine receptor on sympathetic
ganglia, and not on the muscle end-plate, and a postsynaptic
neurotoxin from brown snake venom may have a similar action
(Tyler et tal 1987b).
Procoagulants and coagulopathy
Procoagulants with similar characteristics have been described
from P. textilis, P. affinis, and P. nuchalis venom, and may also
be present in the venom of P. inframacula, P. ingrami and P.
guttata, but probably are not present in P. modesta venom. (White
et al 1987). They are proteins, but have not been fully
characterized. They cause conversion of prothrombin, through
intermediates, to thrombin. This product then converts
fibrinogen to fibrin clots in vitro.
In human envenomation there is widespread consumption of
fibrinogen resulting in defibrination and hypocoagulable blood.
Any injury to blood vessels then causes increased bleeding,
although spontaneous bleeding is not usually seen. Usually
platelets are not consumed, but factors V, VIII, Protein C and
plasminogen all show acute reductions in human envenomation
(White 1983c; White 1987c; White unpublished data).
While major clots are not seen in man, some fibrin cross linkage
and stabilisation does occur in vivo, as cross-linked fibrin
breakdown products (D-dimer) levels rise sharply in human
envenomation (White unpublished data).
In animal experiments IV bolus doses of venom cause intravascular
clotting, which may include intracardiac thrombosis, with lethal
effect. Thrombosis of the portal vein was also frequently
observed in these studies. Cerebral vascular thrombosis was not
noted (Kellaway 1929).
Rhabdomyolysis
Some presynaptic neurotoxins in other snake venoms are also
directly myolytic (eg notexin) and cause major destruction of
skeletal muscle, locally and systemically, both in experimental
animals and occasionally in human envenomation. However, this has
not been described for Textilotoxin, and experimental evidence
and clinical experience suggests that Pseudonaja venom does not
cause rhabdomyolysis (P. textilis), or only to a minor clinically
insignificant extent (P. nuchalis, P. affinis; in monkeys only,
not shown in man) (Sutherland et al 1981b).
Renal damage
No specific nephrotoxins have been detected in brown snake venom,
but several cases of renal function impairment have been
reported in humans envenomed by P. textilis, P. affinis and P.
nuchalis. Possible causes include breakdown products of fibrin
released secondary to the coagulopathy, and vascular impairment
in the early stages, eg secondary to "shock". There may also be
a direct nephrotoxin in the venom (Acott 1988). Acute tubular
necrosis appears to be the main renal pathology.
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
The human lethal dose for brown snake venom is
unknown. Without antivenom treatment, a few brown
snake bites may be fatal (Fairley 1929a), but even in
the early part of the 20th century, when neither
antivenom nor ICU facilities were available, only 8.6%
of reported brown snake bites were fatal. Despite
this, brown snakes are still thought to be the most
common cause of fatal snakebite in Australia. (Hilton
1989).
7.2.1.2 Children
No data available, but clearly the smaller body mass
of a child compared to available venom ensures that
children are more likely to receive a lethal dose
than adults.
7.2.2 Animal data
LD50 subcutaneous injection of dried venom in mice (Broad
et al 1979.
(mg/kg)
Pseudonaja textilis 0.053
Pseudonaja nuchalis 0.473
Pseudonaja affinis 0.660
7.2.3 Relevant in vitro data
No data available
7.3 Carcinogenicity
No data.
7.4 Teratogenicity
No data.
7.5 Mutagenicity
No data.
7.6 Interactions
No data of clinical significance.
8. TOXICOLOGICAL/TOXINOLOGICAL AND OTHER BIOMEDICAL
INVESTIGATIONS:
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
For venom detection swab from bite site moistened in
sterile saline. If systemic envenomation also collect
urine (5ml in sterile container).
For venom analysis (research only using
radioimmunoassay): 5ml blood; 5ml urine, frozen.
At autopsy collect vitreous humor, lymph nodes
draining bite area, excised bite site.
(For other laboratory tests see 10.2.1)
8.1.1.2 Biomedical analyses
For standard tests (eg. serum/plasma electrolytes, CK,
creatinine, urea) collect venous blood in a container
with appropriate anticoagulant as issued by the
laboratory (usually heparin).
8.1.1.3 Arterial blood gas analysis
Collect arterial blood by sterile arterial puncture
into a container as issued by the laboratory.
8.1.1.4 Haematological analyses
For whole blood clotting time as a "bedside" test
collect 5-10 ml of venous blood without anticoagulant
(either in the collection syringe or from a central
line or other venous access line that may have
anticoagulant ) and place in a glass test tube.
Carefully observe the time until a clot appears.
For standard tests (eg. coagulation studies, complete
blood picture) collect venous blood in appropriate
containers with anticoagulant as issued by the
laboratory ensuring that the right amount of blood is
used (for coagulation studies citrate will usually be
the anticoagulant, while EDTA will be used for
complete blood pictures).
8.1.1.5 Other (unspecified) analysis
No data
8.1.2 Storage oflaboratory samples and specimens
8.1.2.1 Toxicological analyses
For samples for standard venom detection:
Short term (less than 24 hrs) ordinary fridge is acceptable
(4°C), in sterile container.
Long term, store frozen (-20°C or lower).
For samples for venom analysis (research) store frozen
(-200°C or lower).
8.1.2.2 Biomedical analyses
For samples for standard tests refer to laboratory. In
general keep at 4°C, particularly for samples for
coagulation studies.
8.1.3 Transport of laboratory specimens
8.1.3.1 Toxicological analyses
Use insulated container.
8.2 Toxicological analyses and their interpretation:
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple qualitative test(s)
Simple qualitative test for presence of snake venom
and designation of species/genus group, corresponding
to the most appropriate monovalent anti-venom. This
test is a commercial test sold by antivenom
manufacturer as a kit (Snake Venom Detection Kit; CSL
Melbourne) (Coulter et al 1980; Chandler & Hurrell
1982; Hurrell & Chandler 1982).
(1) Principle of test
The kit uses an enzyme linked immunosorbent assay technique
with specific antibodies raised to each of the five main
venom types in Australia. If venom is present in the test
sample it will cause a colour change in the relevant well
of the kit, indicating the presence of venom for that
species.
(2) Sampling
See section 8.1. The best samples are a swab from the bite
site (swab stick etc. included in kit), or urine (only if
patient has systemic envenomation). Blood has not proved a
reliable sample (White 1987d).
(3) Chemicals and Reagents
All reagents needed for the test are included in the kit.
The kit should be kept at 4°C (standard fridge) and has a
shelf life of 6 months. A control is built into the kit.
If this fails the test results are invalid.
(4) Equipment
Virtually all equipment required for the test is provided
in the kit. The only item not provided is a timer, but an
ordinary watch is sufficient, each step taking
approximately 10 minutes. An empty specimen container in
which to discard waste fluid at each step is a useful
addition.
(5) Specimen preparation
Not applicable.
(6) Procedure
Refer to instructions in kit.
(7) Calibration procedure
Not applicable.
(8) Quality control
Included in kit.
(9) Specificity
Where testing for snake venom using a bite site swab or
urine no interference with a result is expected. If snake
venom is present it will react with specific antibody in
one of the wells, resulting finally in a colour change in
that well. After a further delay all wells will then change
colour. It is therefore important to carefully watch the
wells in the last stage and note which tube changes colour
first. A few snakes may cause simultaneous colour change in
two wells initially. Yellow faced whip snakes may cause
positive venom detection in either wells indicating brown
snake venom or tiger snake venom (Williams and White, 1990)
(10) Detection limit
The manufacturer states the kit will detect as low as 10ng
venom per ml.
(11) Analytical assessment
Not applicable.
(12) Medical interpretation
If the test is positive, it will indicate the presence of
snake venom and the species/genus of snake and therefore
the appropriate monovalent antivenom to neutralize the
effects of that venom.
If the test sample was a bite site swab, a positive result
does not indicate either the presence of systemic
envenomation, or the need to administer antivenom. Other
clinical criteria are required in this situation (see
sections 9 and 10).
If the test sample was urine a positive result indicates
present or past systemic envenomation and together with
other clinical and laboratory criteria may be used to
determine the need for antivenom therapy.
8.2.1.2 Advanced qualitative confirmation test(s)
As for 8.2.1.1
8.2.1.3 Simple quantitative method(s)
Not applicable.
8.2.1.4 Advanced quantitative method(s)
A radioimmune assay has been developed by staff at the
Commonwealth Serum Laboratories, Melbourne to detect
small quantities of many Australian snake venoms. It
is primarily a research tool, being too time consuming
to be practical in determining emergency treatment of
snakebite victims. It has proved useful in
demonstrating snake venom either at autopsy or after
patient recovery.
8.2.2 Tests for biological specimens
8.2.2.1 Simple qualitative test(s)
See 8.2.1.1.
8.2.2.2 Advanced qualitative confirmation test(s)
See 8.2.1.1.
8.2.2.3 Simple quantitative method(s)
Not applicable.
8.2.2.4 Advanced quantitative method(s)
See 8.2.1.4.
8.2.2.5 Other dedicated method(s)
No data.
8.2.3 Interpretation of toxicological analyses
For venom detection as for 8.1.1.1 subsection (12):
If the test is positive, it will indicate the presence of
snake venom and the species/genus of snake and therefore
the appropriate monovalent antivenom to neutralize the
effects of that venom.
If the test sample was a bite site swab, a positive result
does not indicate either the presence of systemic
envenomation, or the need to administer antivenom. Other
clinical criteria are required in this situation (see
sections 9 and 10).
If the test sample was urine a positive result indicates
present or past systemic envenomation and together with
other clinical and laboratory criteria may be used to
determine the need for antivenom therapy.
For venom analysis refer to the laboratory performing the
tests.
8.3 Biomedical investigations and their Interpretation:
8.3.1 Biomedical analyses
8.3.1.1 Blood, plasma or serum
Electrolytes: Look for imbalance, particularly
evidence of dehydration, hyponatraemia (inappropriate
ADH syndrome?), hyperkalaemia (renal damage,
rhabdomyolysis?).
Urea, creatinine: Look for evidence of renal function
impairment.
CK: If high may indicate rhabdomyolysis, usually
greater than 1000 u/l.
8.3.1.2 Urine
Output: Low output may indicate renal damage or poor
fluid input.
Myoglobin: If present indicates rhabdomyolysis, and
may be missed as the red colouration of urine may be
mistaken for haematuria (both may be positive on dip
stick testing).
Electrolytes if indicated (eg. inappropriate ADH
syndrome)
8.3.1.3 Other biomedical specimens
No data
8.3.2 Arterial blood gas analysis
Impaired respiratory function is usually secondary to
neurotoxic paralysis; look for evidence of poor oxygenation
and its sequelae.
8.3.3 Haematological analyses
Whole blood clotting time: If greater than 10 mins suspect
presence of coagulopathy and if no clot after 15 mins then
significant coagulopathy present. If no clot after 30 mins
then full defibrination is likely.
Coagulation studies: If possible these should be performed
as well as or instead of whole blood clotting time as they
will give a more comprehensive picture of any coagulopathy.
The principal defect likely is a defibrination-type
coagulopathy which will render the blood unclottable. This
will usually result in the following key results:
Prothrombin ratio /INR >12 (normal about 0.8-1.2).
APTT >150 secs (normal <38 secs).
Thrombin clotting time (TCT) > 150 secs
(normal <16 secs).
Fibrinogen <0.1 g/l (normal 1.5-4.0 g/l).
Fibrin(ogen) degradation products grossly elevated
(including D-Dimer).
Platelet count normal.
If the patient exhibits the above picture in the context of
a snakebite then they have a defibrination-type
coagulopathy.
This will require specific antivenom therapy (see section
10) and repeated tests of coagulation status to define
progress of the coagulopathy and titrate antivenom therapy
against resolution. The earliest sign of resolution will be
a rise in fibrinogen level and this may first be seen as a
reduction in the TCT from > 150 secs, often to 80 secs or
less. This may occur before there is a detectable rise in
fibrinogen titre. It indicates that the pathologic process
of venom induced defibrination has ceased implying that all
circulating venom has been neutralized, at which point
further antivenom therapy can be withheld until the trend
of improving results is confirmed, in which case no further
antivenom therapy for the coagulopathy is indicated (unless
there is a subsequent relapse).
In the patient seen late or treated initially elsewhere
there may be no abnormal clotting time, with an INR < 2.0,
but fibrinogen may be low associated with raised
degradation products. In this case the results may indicate
a minor or resolved coagulopathy not requiring antivenom
therapy.
Note that the platelet count (complete blood picture) will
usually be normal despite the intense defibrination.
In a few cases the platelet count may start to fall as or
after resolution of the defibrination occurs. This is
usually associated with renal damage and renal function
should be assessed. In this setting the thrombocytopenia
may well be secondary to the renal damage.
8.3.4 Other (unspecified) analyses
8.3.5 Interpretation of biomedical investigations
The interpretation of the above tests should be made in the
context of total patient assessment including clinical
evidence of pathology such as paralysis, myolysis,
coagulopathy and renal damage.
8.4 Other biomedical (diagnostic) investigations and their
interpretation
While other investigations are not usually required to make the
primary diagnosis of snakebite envenomation, they may be
indicated in response to secondary effects of envenomation. If
there is either renal failure or severe rhabdomyolysis (unlikely
with brown snake envenoming) there may be a hyperkalaemia, hence
an ECG may be appropriate. If the patient is unconscious,
especially in the presence of a severe coagulopathy, then a CT
head scan may be appropriate to determine if there is
intracranial pathology such as a haemorrhage.
8.5 Summary of most essential biomedical and toxicological analyses
in acute poisoning and their interpretation
Overall interpretation of the results of the above tests will
depend on the clinical setting. Results should never be
interpreted in isolation from an overall clinical assessment.
A patient with positive venom detection from either the bite site
or urine and a significant coagulopathy clearly is envenomed and
will usually require antivenom therapy.
A patient with positive venom detection from the bite site only
and with no clinical symptoms or signs of envenoming and all
other tests negative is not significantly envenomed at that point
in time and does not require antivenom therapy. However this
situation may change and so careful observation and repeat
testing would be indicated.
A patient presenting some hours after the bite with positive
venom detection from the urine but clinically well and with all
other tests either normal or showing a resolved coagulopathy,
probably had a minor degree of envenomation, now resolved and
will usually not require antivenom therapy. However they should
be observed carefully for evidence of relapse.
9. CLINICAL EFFECTS
9.1 Acute poisoning/envenomation
9.1.1 Ingestion
No data.
9.1.2 Inhalation
No data.
9.1.3 Skin exposure
Venom not absorbed through intact skin.
9.1.4 Eye contact
No data.
9.1.5 Parenteral exposure
In practical terms, the only likely route of entry, is by
s.c. or i.d. injection.
Early symptoms, usually in the first six hours.
Local: The wound is often painless, without local erythema,
oedema, or ecchymosis; persistent bleeding from wound,
variable; pain or swelling of draining lymph nodes (may
take 1-4 hours to develop).
Systemic: collapse, unconsciousness, convulsions may all
occur, especially in children, occasionally as rapidly as
15 minutes after the bite. Headache, nausea, vomiting,
abdominal pain, and visual disturbance may all occur. Early
signs of neurotoxic paralysis such as ptosis, diplopia,
dysarthria may develop within 1-3 hours of the bite, or be
delayed for 4-12 hours, or may not develop despite other
evidence of severe envenomation.
Coagulopathy may develop within 30 minutes of the bite.
Delayed symptoms
Local: Local bite site necrosis is not generally seen with
brown snake bites but possibly might occur, particularly if
first aid left in place more than 4 hours, or if a
tourniquet used (Sutherland 1981, 1983a; White 1987d).
Systemic:
Paralysis progressive up to complete paralysis.
Coagulopathy bleeding from all puncture wounds.
Renal impairment oliguria or anuria.
9.1.6 Other
No data.
9.2 Chronic poisoning
9.2.1 Ingestion
No data.
9.2.2 Inhalation
No data.
9.2.3 Skin contact
No data.
9.2.4 Eye contact
No data.
9.2.5 Parenteral exposure
No data.
9.2.6 Other
No data
9.3 Course, prognosis, cause of death
Course
Initially the patient is usually anxious. The subsequent course
will depend on (a) amount of venom injected, (b) size of patient
relative to venom load (ie children may be worse affected), (c)
degree of activity of patient after bite (physical activity
hastens venom absorption), (d) timing, type, effectiveness of
first aid, (e) speed and nature of specific medical treatment
given, if systemic envenomation ensues, (f) pre-existing health
factors for each patient (ie past renal problems, allergic
problems etc).
Minor envenoming: little or no venom injection, no development of
system envenomation, no need for antivenom treatment, no likely
sequelae or complications.
Moderate envenoming: bite may be painless or slightly painful,
with no or minor local reactions, subsequent development over
next few hours of some or all of the following: headache, nausea,
vomiting, abdominal pain, collapse, convulsions (especially in
children), occasionally early signs of paralysis, such as ptosis,
diplopia, and commonly laboratory evidence of coagulopathy.
Antivenom treatment at this stage will usually arrest or reverse
the various manifestations of systemic envenomation. Without
antivenom treatment, in most such cases the symptoms and signs
will show progressive worsening, with deepening coagulopathy and
an increased chance of secondary haemorrhage (beware intracranial
haemorrhage), in a few cases progressive paralysis which may
ultimately progress to complete respiratory paralysis, about 18-
24 hours post bite; secondary renal failure; secondary
complications of the above, particularly pneumonia; ultimate
outcome may be death, more than 24 hours post bite.
Severe envenoming: most likely if bite either multiple, or
associated with chewing bite and numerous teeth marks. Local
reactions still may be minimal. Rapid development of headache,
collapse, convulsions (especially children), sometimes within 30
minutes of bite. Subsequent symptoms may include headache,
nausea, vomiting, abdominal pain, and evidence of coagulopathy,
possibly progressive paralysis, and renal impairment.
Coagulopathy may be detectable within 30 minutes of bite; ptosis
and diplopia may be evident within 2 hours of bite. Renal damage
may occur early. Prompt antivenom treatment required as soon as
nature of envenomation evident. In some circumstances paralysis
may be sufficiently advanced at a cellular level that antivenom
cannot prevent severe paralysis. In this situation, intubation
and assisted ventilation may be required for a variable period
(up to several weeks). The coagulopathy may only reverse
following large amounts of antivenom. Renal damage is usually
reversible, after a period of haemodialysis.
Without antivenom treatment such cases will almost certainly die.
Special notes
Children are more likely to develop severe envenomation than
adults, and do so more rapidly.
Bites to the trunk or face may cause earlier development of
envenomation.
Secondary infection of the local bite wound may occur.
Physical activity after a snakebite increases the rate of
absorption of venom and so hastens the onset of envenomation.
This situation often occurs in bites to children.
Multiple bites nearly always are associated with potentially
lethal envenomation.
Prognosis
In the past up to 8.6% of all brown snake bites have proved fatal
when no antivenom treatment was used (this is based on statistics
pre-antivenom era, over 50 years ago: with the use of modern
intensive care facilities such figures may be over-pessimistic).
No data available on fatality rate with antivenom treatment, but
deaths do still occur, and it is thought that most snakebite
fatalities in Australia in recent years are due to brown snake
bites, at least in part reflecting the commonness of bites by
brown snakes compared to the incidence of bites by other species
of snakes.
Causes of death
Coagulopathy primary eg cerebral haemorrhage;
secondary eg renal failure.
Paralysis primary eg respiratory failure;
secondary eg pneumonia
Renal Failure includes secondary complications such as
infections.
Anaphylaxis acute allergic reaction to venom is
possible in a patient previously exposed
to brown snake venom (e.g. reptile keeper)
but there are no documented cases.
Cardiac complications likely to be secondary, and role in brown
snake bite fatalities uncertain.
9.4 Systemic description of clinical effects
9.4.1 Cardiovascular
Collapse, presumably due to hypotension, is common in the
early stages of systemic envenomation, especially in
children. The mechanism is uncertain but may be due to
release of vasoactive substances by or from the venom.
Specific cardiac abnormalities due to brown snake
envenomation in man are not described, although there has
been a suspicion that brown snake venom may cause cardiac
anomalies (Sutherland personal communication).
9.4.2 Respiratory
No primary effects of brown snake venom on the respiratory
system in man are reported, with the exception of
respiratory muscle paralysis (see below).
9.4.3 Neurological
9.4.3.1 CNS
While no direct CNS toxins have been reported for
brown snake venom, early collapse and convulsions do
occur, especially in children. Their aetiology
remains uncertain.
9.4.3.2 Peripheral nervous system
See 9.4.3.4
9.4.3.3 Autonomic
Abdominal pain.
9.4.3.4 Skeletal and smooth muscle
The effects of brown snake venom at the neuromuscular
junction, have been documented experimentally. Both
presynaptic and postsynaptic neurotoxins present,
causing progressive neuromuscular paralysis, up to
complete paralysis of all muscles of respiration.
9.4.4 Gastrointestinal
Nausea and vomiting may occur. In the presence of a venom-
induced coagulopathy, haematemesis and even melaena may
occur, though they appear to be rare even in severe
envenomation. Abdominal pain is sometimes described.
9.4.5 Hepatic
Direct hepatic effects of brown snake venom have not been
noted clinically, or experimentally.
9.4.6 Urinary
9.4.6.1 Renal
No direct nephrotoxin has been identified in brown
snake venom, but renal failure has been reported in a
number of cases, and is a very serious complication of
envenomation, with a significant mortality, despite
antivenom treatment. The nature of the renal injury
and its cause are poorly documented, but acute tubular
necrosis seems most likely. Renal cortical necrosis
has not been reported.
9.4.6.2 Other
No data.
9.4.7 Endocrine and reproductive systems
No data.
9.4.8 Dermatological
The local bite site is often painless or minimally painful
and swelling, and ecchymosis is not usually seen. Teeth
marks are variable, from single fang puncture to multiple
tooth punctures and scratches. Local necrosis has not been
described. Secondary infection may theoretically occur
(White 1983b).
9.4.9 Eye, ear, nose, throat: local effects
No data.
9.4.10 Haematological
Probably the major clinical effect of brown snake
envenomation in man is coagulopathy caused by potent
procoagulants in the venom, which cause prothrombin
activation and secondary fibrinogen consumption. The
resulting defibrination is associated with hypocoagulable
blood, and persistent bleeding from any vascular injury,
including venepuncture sites. Without antivenom treatment,
this may occasionally resolve.
However, as the venom is not apparently vasculotoxic, in
the absence of vascular injury bleeding does not occur,
thus in many patients the coagulopathy proves relatively
benign.
An early neutrophil leukocytosis may occur in some
patients. Significant depletion of circulating lymphocytes
may occur in the early stages of envenomation, with
resultant lymphopenia (White et al 1989).
9.4.11 Immunological
No data.
9.4.12 Metabolic
9.4.12.1 Acid base disturbances
No changes.
9.4.12.2 Fluid and electrolyte disturbances
Secondary fluid and electrolyte disturbances due to
renal failure if present.
The possibility of inappropriate ADH (anti-diuretic
hormone secretion) syndrome should be considered. In
this situation, otherwise acceptable intravenous fluid
loads may result in significant electrolyte imbalance
and other sequelae.
9.4.12.3 Others
Rise in serum levels of liver enzymes and CK (if
rhabdomyolysis). A rise in CK to below 1000 U/l is
not indicative of rhabdomyolysis. True venom-induced
rhabdomyolysis causes CK levels well above 1000 U/l.
This is not a usual feature of brown snake bites.
9.4.13 Allergic reactions
May occur due to allergy to venom or antivenom, and
resultant anaphylaxis may prove fatal.
Reptile keepers previously bitten by brown snakes are also
at potential risk of acute anaphylactic allergic reactions
on subsequent bites, which might cause collapse within
minutes of the bite. Fatalities have occurred due to this
mechanism, with bites by other species, but are not
documented for brown snakebites. (Sutherland 1983; White
1987 b,d).
9.4.14 Other clinical effects
Rhabdomyolysis has not been noted clinically.
9.4.15 Special risks
Pregnancy: no data
Breast feeding: no data
Enzyme deficiencies: no data
9.5 Others
No data
10. MANAGEMENT
10.1 General Principles
All patients suspected of having sustained a brown snake bite
should be admitted to hospital for observation over the first 24
hours. While all such cases should be treated as potentially
fatal not all cases will develop envenomation. Management of
cases with systemic envenomation may be divided into specific,
symptomatic, and general treatment.
The aims of treatment are:
(a) Maintain life through maintenance of vital bodily
functions.
(b) Neutralise inoculated venom.
(c) Correct venom-induced abnormalities.
(d) Prevent or correct secondary complications.
Specific treatment
If there is evidence of systemic envenomation, antivenom therapy
is the most important treatment. Once the snake has been
identified (eg by venom detection) give specific antivenom (CSL
Brown Snake Antivenom). (White 1981; 1987d; Sutherland 1983;
Trinca 1963)
Symptomatic and general treatment
Support of cardiorespiratory systems.
Treatment of shock.
Maintain adequate renal perfusion.
Replace major blood loss due to coagulopathy induced
haemorrhage (but use blood products only with great caution
until coagulopathy resolved ).
Tetanus prophylaxis.
Avoid intramuscular injection while there is a
coagulopathy.
Avoid respiratory depressant medications (eg morphine).
Avoid antiplatelet medications (eg aspirin).
10.2 Relevant laboratory analyses and other investigations
10.2.1 Sample collection
Venom for venom detection: use CSL Venom Detection Kit;
best sample is swab from bite site (swab stick etc in kit);
if systemic envenomation present then urine useful;
serum/plasma less reliable. If bandage applied over bite
site as first aid, keep bandage adjacent to wound, as this
may also have venom absorbed, and could be tested for venom
(after elution) if all other samples negative in presence
of significantly envenomed patient.
Blood: Initially collect for complete blood count (EDTA
sample), clotting studies (citrated sample), electrolytes
and enzymes (heparin and/or clotted sample) and possibly,
group (type) and screen serum (clotted sample). In
anticoagulated blood samples ensure correct ratio of blood
to anticoagulant (especially citrate samples) and proper
mixing. If laboratory facilities unavailable, collect for
whole blood clotting time (ie 5-10 ml in glass test tube,
and measure time to clot). Samples for clotting studies in
particular should be kept cold during transportation.
Urine: Measure urine output, visual check for
haemoglobinuria or myoglobinuria (dark red-brown urine); if
suspect myoglobinuria collect samples at intervals for
subsequent laboratory confirmation (5-10 ml).
10.2.2 Biomedical analysis
Venom detection: Venom at the bite site confirms only the
species of snake, but venom in the urine indicates systemic
envenomation.
Coagulation studies: In the absence of a haematology
laboratory, whole blood clotting time is a useful test, for
both the presence of a coagulopathy, and its progress and
resolution with adequate antivenom therapy.
If a laboratory is available, the most useful tests for
presence and extent of coagulopathy are: prothrombin
time/ratio; activated partial thromboplastin time; thrombin
clotting time; fibrinogen assay; fibrin(ogen) breakdown
products assay.
In addition, a complete blood count should always be
performed concurrently, particularly for a platelet count.
Other blood tests:
Electrolytes (eg Na, K etc);
Renal function (eg creatinine, urea);
Enzyme levels, especially CK;
Arterial blood gas, if appropriate (ie impaired
respiratory function).
Urine:For haemoglobinuria and myoglobinuria
10.2.3 Toxicological analysis.
Venom detection, see section 8.
10.2.4 Other investigations. As indicated medically.
10.3 Life supportive procedures and symptomatic treatment
Paralysis
In severe cases of systemic envenomation by brown snakes, where
antivenom treatment has been delayed, paralysis may occur and
progress to complete or near complete respiratory paralysis. In
this situation early intervention by endotracheal intubation and
artificial ventilation is lifesaving. Such respiratory support
may be needed for hours, days, or even weeks, until adequate
respiratory function returns.
Once established, such severe paralysis may not be reversed by
antivenom therapy.
Coagulopathy
The principal method of treatment of brown snake envenomation
coagulopathy is the neutralisation of all inoculated venom by
antivenom. Until this is achieved, use of clotting factor blood
products (eg fresh frozen plasma, cryoprecipitate, fibrinogen)
may only deepen the degree of coagulopathy, by providing more
substrate on which the venom may act. Once all venom is
neutralised normal homeostatic mechanisms quickly return
coagulation towards normal, without the need of replacement
therapy. The possible exception would be where there is major
bleeding as a result of the coagulopathy (eg cerebrovascular
accident), when replacement therapy should be considered once
adequate antivenom has been given. Heparin has no proven value
in this situation, and there is evidence it may be harmful.
In cases of severe envenomation a central venous pressure (CVP)
line may be highly desirable for patient management, but in the
presence of coagulopathy should be inserted with great caution,
due to the likelihood of significant haemorrhage from the
insertion site if insertion attempt is unsuccessful.
In such cases frequent testing of coagulation will be necessary
to titrate antivenom therapy. A CVP line will allow frequent
sampling without further breaches of veins, an important
consideration in severe coagulopathy where venepuncture may
result in bleeding for hours. For similar reasons, venepuncture
from major veins, such as the femoral, should be avoided, and
used only as a last resort.
Following resolution of the coagulopathy there may be rebound
hyperfibrinogenaemia at about 2-4 days post resolution. There is
a theoretical potential for hypercoagulability at this time,
particularly in the immobile paralysed ventilated patient, and
the possibility of thrombus formation and emboli, including
pulmonary emboli, should not be forgotten.
Renal failure
First priority is to avoid renal injury by ensuring adequate
renal perfusion. In all cases of significant systemic
envenomation, catheterisation of the bladder to monitor urine
output constantly is advisable. In severe cases of envenomation,
the use of a CVP line will assist in adjusting IV fluid load to
ensure adequate blood volume and renal perfusion.
Once renal injury is established, standard techniques of medical
management should apply. Haemodialysis may be required. Renal
biopsy should be avoided at least until the coagulopathy is
completely resolved.
Local bite site
The bite site should be cleaned only after adequate sampling for
venom. Local infection may occur, but is rare, and thus
prophylactic antibiotic therapy is not appropriate. Tetanus
prophylaxis should be ensured. In the rare event of minor local
necrosis, this could usually be successfully treated
conservatively. Local skin necrosis sufficient to warrant
debridement and grafting has not been reported.
General
Analgesia
May be necessary, though most cases will need no more than
paracetamol. Morphine should be avoided (CNS depressant effect).
Platelet-active drugs should be avoided (eg aspirin).
Steroids
May be useful in treatment or prophylaxis of serum sickness, but
their role in the general treatment of brown snake bite is
doubtful.
10.4 Decontamination
Not applicable.
10.5 Elimination
Not applicable.
10.6 Antidote treatment
10.6.1 Adults
Brown snake antivenom (CSL, Melbourne) is the specific treatment
of brown snake bite. It should only be used if there is definite
systemic envenomation. (Trinca 1963; Sutherland 1974, 1983b;
White 1981, 1987d)
The antivenom is a refined horse serum (Fab2 fragments), with all
the potential hazards of that product. One ampoule contains 1000
units of activity against brown snake venom. This is sufficient
to neutralise the "average" amount of venom produced by a single
milking of one snake (Pseudonaja textilis). In a severe bite, and
multiple bites, several ampoules of antivenom may be necessary.
The average volume of antivenom (horse serum) per ampoule is 4.5
ml, but the precise volume varies from batch to batch.
Brown snake antivenom must be given intravenously.
Since skin testing is unreliable and hazardous, there is no place
for pre-therapy sensitivity testing of antivenom. (Sutherland
1983b; White 1987d).
Acute allergic reactions up to and including potentially fatal
anaphylaxis may occur during antivenom therapy. Precautions
should be taken to reduce the risk to the patient. These
include:
Only give antivenom if staff, drugs and equipment to treat severe
anaphylaxis, including intubation facilities are available
(preferably in an intensive care unit), unless in extreme
emergency.
Always have adrenaline injection prepared and ready to use.
Always have a good reliable IV line inserted.
Always maintain adequate monitoring of patient during and after
antivenom therapy, especially blood pressure.
Dilute antivenom (1:5 to 1:10) in IV carrier solution (normal
saline; dextrose or Hartmann's).
Give antivenom initially very slowly, and increase rate if no
reaction, aiming to give whole dose over 15-20 minutes.
Premedication is proposed by some. (Sutherland 1983b) Suggested
premedications are subcutaneous adrenaline and intravenous
antihistamine. The author of this monograph does not routinely
use such premedication. (White 1987d) Antihistamine may make
the patient drowsy or irritable, and thus interfere with the
ongoing assessment of envenomation, especially in children.
Adrenaline is potentially hazardous, especially in older patients
or those with coagulopathy, and as acute severe allergic
reactions may be delayed up to an hour or more, such
premedication is of doubtful value. A patient with known or
likely allergy to horse serum presents a special case, where
premedication as above, possibly with the addition of steroids,
is worthy of active consideration. Similarly a sole country
medical practitioner managing a severe snakebite, where antivenom
must be given before an aeromedical evacuation team can arrive,
may well consider premedication with subcutaneous adrenaline a
worthwhile precaution.
In the presence of mild to moderate systemic envenomation
(ie no or minor paralysis, no active bleeding from
coagulopathy etc) initially give one ampoule of antivenom .
Follow up with further ampoule(s) if progression of
symptoms and signs, or if no resolution of coagulopathy.
Resolution of coagulopathy may be used to titrate antivenom
therapy. (White 1983c; 1987 c,d)
In the presence of severe envenomation, initially give 2
ampoules of antivenom, and be prepared to give more, as
above.
If using the resolution of coagulopathy to titrate
antivenom therapy, aim to retest coagulation (see section
10.2.1) about 1 to 1.5 hours after completion of antivenom
dose. First evidence of impending resolution may be a
reduction in the thrombin clotting time, often accompanied
by a slight rise in fibrinogen level. If there is no
significant improvement, give further antivenom. If there
is significant improvement, repeat test in a further 1-2
hours and reassess.
There is no mandatory upper limit on antivenom dosage, but
only rarely will more than 4-5 ampoules be required.
10.6.2 Children
The dosage of antivenom in children is identical to that in
adults. However, fluid volume considerations in small
children may force lower dilutions of antivenom. For any
given bite the degree of envenomation will be worse in
children due to lower body mass. Following antivenom
therapy there is a possibility that the patient may develop
serum sickness. This should be explained to the patient so
that if symptoms develop, they will seek appropriate
treatment.
If large volumes of antivenom are used (eg 50-100 ml or
more) then prophylaxis for serum sickness should be
considered (eg oral steroid therapy for 2 weeks). However,
most brown snake bites will be successfully treated with
between 1 and 4 ampoules of antivenom, less than 20 ml in
total volume.
10.7 Management discussion
Controversies in management exist in several areas:
First aid
Tourniquet versus pressure/immobilisation: the latter is now
well accepted as the method of choice. (Balmain & McClelland
1982, Fisher 1982, Murrell 1981, Sutherland 1983b; Sutherland et
al 1981 a,b; White 1987d)
Suction of wound: No proven value .
Cutting or excising wound: of no practical value and potentially
dangerous.
Antivenom
Use of premedication: not universally accepted. (Sutherland
1975, 1977a, 1977b, 1977c; 1983b; White 1987d)
Use of skin pretesting: not appropriate.
Coagulopathy
Use of fibrinogen, fresh frozen plasma etc as primary treatment:
No proven benefit and potentially very dangerous. (White 1987d)
Use of heparin: of no proven benefit and potentially dangerous.
Non-antivenom treatment
Based on the assumption that it is paralysis which kills the
patient and this can be managed adequately in an intensive care
unit by artificial ventilation, therefore antivenom is not
required, thus avoiding antivenom allergy problems. This ignores
the danger of coagulopathy, best managed by antivenom therapy,
and the fact that early antivenom therapy may avoid severe
paralysis and the hazards of artificial ventilation.
Research
There are many aspects of brown snake venom worthy of further
research, at a basic science level, as well as studies at a more
clinical level.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Case 1: (from Foxton 1914). A fatal snakebite in a man, age 29
years, bitten on the left hand by a brown snake. First aid was
scarification and local ligature. By one hour he had headache,
by 3 hours nausea, vomiting (blood stained) and this continued
overnight. He developed haemorrhage from the gums, and at 18
hours post-bite he collapsed, had convulsions, and was comatose.
He continued to have convulsions until his death, some 2 hours
later. Autopsy showed mid-brain and brain stem haemorrhages, and
small haemorrhagic areas in the stomach, intestines, kidneys, and
bladder. Death was attributed to the haemorrhages in the pons
and medulla and was clearly due to the coagulopathy.
Case 2: (from Fairley 1929). A fatal snakebite in a woman, age
29 years, bitten on the leg, through thick riding breeches, by a
brown snake which had been milked earlier the same day. First
aid was scarification and ligature. Initially well, she later
developed vomiting, severe abdominal pain, then signs of shock
with pallor, sweating, tachycardia and hypotension. She passed
bright blood per rectum. She also developed some paralysis, with
dysarthria, but died of "cardiovascular failure" 12 hours post-
bite. No autopsy. The cause of death may well have been due to
shock following blood loss associated with the coagulopathy.
Fairley comments that significant bleeding problems are common
after brown snake bite.
Case 3: (from Schapel et al 1971). A non-fatal case. A 19
year-old man was bitten on the left wrist by a captive brown
snake. At 15 minutes post-bite he was given a test dose of brown
snake antivenom I.V. (with adrenaline, antihistamine pre-
medication), which resulted in anaphylaxis, successfully treated
with adrenaline and steroids. He had received antivenom on 2
previous occasions. Three hours post-bite he developed extensive
generalized submucosal and subcutaneous bruising, oozing of blood
from skin puncture wounds, and haematemesis (500 ml).
Investigations showed a marked coagulopathy, and
thrombocytopenia. Further antivenom was clearly indicated and
given under cover of adrenaline and steroids, and in addition he
was heparinized. However, by 12 hours post-bite "bleeding was
controlled", although some evidence of coagulopathy was
apparently present for several days. There was a short-lived
rise in blood urea level, but urine output remained adequate.
There was no evidence of paralysis at any stage. An eventual
complete recovery was made.
Hermann et al 1972: Detailed report of three cases of brown
snake bite from Western Australia, with emphasis on haematologic
complications.
Case 4: Non-fatal bite to the hand of a 50 year-old man by P.
affinis. At 15 minutes post-bite he developed a severe frontal
headache. He was noted to have persistent oozing from the bite
site at two hours, and was given brown snake antivenom, and
subsequently made a full recovery. Platelet count remained
normal, despite a defibrination type coagulopathy, present for at
least 24 hours.
Case 5: Non-fatal bite to the leg of a 35 year-old woman by a
presumed P. affinis. At 30 minutes post-bite she developed
severe headache, nausea, visual difficulty, and "weakness", but
was not seen medically until 18 hours post-bite. Antivenom was
not given. Investigations showed a normal platelet count and
mild defibrination type coagulopathy.
Case 6: Non-fatal bite to the hand of a 45 year-old man by a P.
nuchalis. At 20 minutes post-bite he developed severe headache,
nausea, and vomiting. He was given polyvalent antivenom and
subsequently recovered. Investigations showed a normal platelet
count and a marked defibrination type coagulopathy.
The following discussion relates mostly to the therapy of the
coagulopathy, with the conclusion that antivenom is the most
effective treatment. Neurotoxicity was not noted in these cases.
Sutherland et al 1975: Three cases of snakebite where RIA venom
detection was used to prove the diagnosis. Two were due to brown
snakes.
Case 7: Non-fatal bite to the leg of a 42 year-old woman by P.
textilis. The patient did not believe she had been bitten. At 20
minutes post-bite she developed headache, then collapsed,
possibly had a convulsion or cardiac arrest, and was given brown
snake antivenom at 30 minutes post-bite. She promptly improved
clinically. She also developed persistent oozing of blood from
the bite site, and at 5 hours post-bite her blood was unclottable
(after three ampoules of antivenom). Fibrinogen was given but
the blood remained unclottable for at least several hours. She
subsequently made a full recovery. Blood taken prior to the
first dose of antivenom showed 20 ng/ml of brown snake venom.
Case 8: Non-fatal bite to the ankle of a 66 year-old woman by P.
textilis. She subsequently felt dizzy but this resolved, and no
further symptoms developed. She did not receive antivenom. A
level of 35 ng/ml of brown snake venom was detected in her serum.
No comment on tests for coagulopathy is made.
Harris et al 1976: Three cases of brown snake bite with renal
failure, from Western Australia.
Case 9: Non-fatal bite to the leg of a 35 year-old man by a
presumed P. nuchalis. Not treated with antivenom and early
history not noted. By 24 hours he developed abdominal pain,
vomiting, and oliguria. Investigation demonstrated acute renal
failure (requiring haemodialysis) and an associated micro-
angiopathic haemolytic anaemia with thrombocytopenia. He
subsequently recovered completely, though he was oliguric for 13
days.
Case 10: Non-fatal bite to the leg of a 60 year-old man by a
presumed P. affinis. At one hour post-bite he received brown and
tiger snake antivenoms. At 7 hours he became confused, commenced
vomiting, and was oliguric. This was managed conservatively for
five days, then he was transferred to a major hospital.
Investigations then showed acute renal failure and a micro-
angiopathic haemolytic anaemia with thrombocytopenia. There was
no evidence at this time of defibrination. He required
haemodialysis and was oliguric for 19 days, but made an almost
complete recovery (mild elevation of blood urea at 12 months).
Case 11: Non-fatal bite to the leg of a 53 year-old woman by a
presumed P. nuchalis. Initially she was hypertensive and
vomiting, but antivenom was not given. By the next day she was
oliguric, and also developed bleeding problems (epistaxes; per
vagina; multiple ecchymoses), and drowsiness. Investigations at
four days post-bite showed acute renal failure, a micro-
angiopathic haemolytic anaemia, and thrombocytopenia. There was
no evidence of defibrination. She required haemodialysis, and
was oliguric for 21 days. She subsequently made a full recovery.
These three cases show a consistent picture of reversible acute
renal failure associated haemolysis, but details of the early
findings are scant and thus possible association with an early
coagulopathy is not apparent.
Case 12: (from Crawford, 1980). A non-fatal bite to the foot of
a 57 year-old man by a juvenile P. nuchalis. Details of
symptomatology are scant, but no neurotoxicity was seen, and
bleeding problems were evident, with haemorrhage from
venepuncture sites. A defibrination type coagulopathy was
demonstrated, with normal platelet count. A haemolytic process
was also shown. Brown snake antivenom was given. The importance
of this case is principally that it clearly demonstrates juvenile
brown snakes are capable of inflicting potentially dangerous
bites.
Case 13: (from Pearn et al., 1981). A non-fatal bite to the
hand of an adult male by a P. textilis. A compression type
bandage was applied as first aid, without splint. During the two
hours this first aid was in place, the patient was symptom free,
but within five minutes of removal, headache and nausea
developed, then pallor, sweatiness, an ache of the face and neck,
and dyspnoea. Previously normal investigations now showed a
blood level of brown snake venom of 1.5 ng/ml (peaking at 5 ng/ml
at 45 minutes after release of first aid), and a defibrination
type coagulopathy. The latter persisted for at least 24 hours,
despite one ampoule of brown snake antivenom, which however
relieved the symptomatology. There was no evidence of
neurotoxicity. This case report is probably the most detailed
study of the effectiveness of the compression immobilization type
first aid (Sutherland et al 1979) in man.
Case 14: (from Sutherland et al 1982). A fatal bite to the foot
of a 39 year-old, 39-week pregnant woman, by a brown snake
(positive venom detection). The snake was small (approx 18cm?),
and the bite was initially thought to be trivial. By 30 minutes
post-bite she had developed a headache, then sudden collapse
while supine on a hospital couch. A cardiac arrest quickly
followed and resuscitation failed, the patient dying 1.5 hours
post-bite. Brown snake venom was found at the bite site, but not
in blood or urine, at autopsy, and no other abnormalities were
found. The ensuing discussion concludes that death was due to the
supine hypotensive syndrome of pregnancy rather than to
envenomation.
Case 15: (from Acott, 1988). An important case report,
demonstrating isolated renal failure after brown snake bite,
without evidence of significant coagulopathy or neurotoxicity.
A 51 year-old male was bitten on the right thumb by a small P.
textilis. About 2 hours post-bite he developed abdominal pain,
nausea, vomiting, and "felt terrible". Antivenom (one ampoule
polyvalent) was given at six hours post-bite. Investigations on
samples taken at that time showed normal renal function, a
platelet count of 110 X 109/l, and normal levels of fibrinogen
and FDP (XDP), and brown snake venom in the blood. There was no
evidence of neurotoxicity. He remained apparently stable and
well, but at 24 hours post-bite it was realized he was virtually
anuric, and retesting showed elevated urea and creatinine,
consistent with acute renal failure, a further drop in platelets
to 41 X 109/l, but normal coagulation tests. While otherwise well
his renal function deteriorated, requiring nine days of
haemodialysis. Renal biopsy showed acute tubular necrosis. he
subsequently had normal renal function.
Case 16: (from Milton, 1989). A fatal case of brown snake bite
in a girl aged 2 years 9 months, found comatose and apnoeic by
her parents. There was no history of snakebite. Resuscitation
failed. Autopsy revealed possible bite marks on the left leg,
from which tissue blocks were taken, and subsequently shown to
contain a high concentration of brown snake venom. There was
modest congestion and oedema of the lungs with petechial
haemorrhages. Further details not provided.
From Morling et al 1989: A paper detailing apparent
thrombocytopenia following brown snake bites in Western
Australia, presumably due to either P. affinis or P. nuchalis. 10
cases of such bites noted, all with evidence of a coagulopathy.
All those with sufficient clinical information had some evidence
of renal involvement. Four cases had platelet counts below the
normal range. It is suggested by the authors that this may be
evidence of a direct platelet aggregating effect of brown snake
venom, but some doubt has been cast on the validity of this
conclusion (White 1990).
11.2 Internally extracted case reports
Overall case analysis:
In Australia a significant number of cases of suspected snakebite
do not result in identification of the species of snake
responsible. However brown snakes are considered the leading
cause of snakebite. In the author's experience of over 200 cases
the snake species was identifiable in 118; 60 were due to brown
snakes.
Of the 60, 19 (32%) showed significant envenomation, however this
figure may be biased in favour of severe cases, as mild cases or
"dry bites" are less likely to result in identification of the
snake responsible.
Of the 19 cases with significant envenomation, 16 (+1) had
evidence of coagulopathy, 2 (+1) had evidence of neurotoxicity, 5
had evidence of renal damage, and none showed evidence of
myotoxicity.
Of the remaining 41 cases, 13 had evidence of possible mild
envenomation, and 28 had no evidence of envenomation.
Selected cases:
Case 1: (from White 1981). A two year-old boy was bitten
multiply on the left posterior upper thigh by a large brown
snake. Within 30 minutes the child had collapsed, had a possible
convulsion, and had developed a severe defibrination type
coagulopathy, with unclottable blood, no detectable fibrinogen,
gross elevation of FDP, and a normal platelet count. The first
dose of antivenom did not change these findings after 2.5 and 4
hours, but 2 hours after a second dose of antivenom there was
substantial improvement, which continued without need of further
antivenom. This child did not show evidence of neurotoxicity, or
renal damage. Evidence of recovery from the coagulopathy 2 hours
after the second dose of antivenom correlated with a clinical
improvement, the child ceasing to be irritable, and instead
happily playing with parents.
Case 2: (from White 1981). A seven year-old boy bitten once on
the thumb by a small (approx 0.6 m) brown snake, proven by venom
detection. By 30 minutes post-bite the child was irritable,
rousable but drowsy, with non-clottable blood, and a severe
defibrination type coagulopathy. A single dose of antivenom was
given and resolution of the coagulopathy was less prompt than in
the more aggressively treated case 1, despite case 1 being
overall less severely envenomed on clinical grounds. There was no
evidence of neurotoxicity or renal damage.
Case 3: (from White et al 1989). A 3.5 year-old boy was bitten
twice on the right ankle by an 86 cm P. textilis, and after an
early (inappropriate) removal of first aid, collapsed with grand-
mal convulsions. On arrival at hospital 30 minutes post-bite the
child was irritable, awake, with a rash on hands and leg, and
normotensive (almost hypertensive, BP 140/90). Unfortunately the
seriousness of the envenomation was not initially realized by the
treating staff. Over the next two hours the child became drowsy,
more irritable, vomited, complained of abdominal pain, and a
severe defibrination type coagulopathy was demonstrated. Expert
advice was sought, and antivenom therapy advised. Over the next
few hours five ampoules of brown snake antivenom were given. By
2.5 hours after the last dose of antivenom, there was substantial
improvement in the coagulopathy, which continued to resolve
thereafter, associated with a dramatic clinical improvement
within two hours, the child ceasing to be irritable, and instead
happily playing with parents. There was no evidence of
neurotoxicity or renal damage.
This case demonstrates clearly the method of titrating antivenom
dose against progress of the coagulopathy.
Case 4: (from White and Fassett 1983). A 26 year-old man was
bitten on the right thumb by a large P. nuchalis. He was
inebriated at the time and did not apply first aid or seek
treatment. The following day he was anuric, and developed a
severe DIC with platelet consumption and a micro-angiopathic
haemolytic anaemia. He required haemodialysis for 12 days, but
made an eventual complete recovery of renal function. Because of
his delay in seeking treatment, he did not receive antivenom
treatment until the renal and clotting problems were fully
established. Treatment with three ampoules of polyvalent
antivenom late on day one did not have a noticeable effect on the
coagulopathy. Seven ampoules of brown snake antivenom on days
five and six, were associated with resolution of the
coagulopathy, though this may have been coincidental. Heparin
therapy from day one to six did not appear effective in
controlling the coagulopathy.
Case 5: A 27 year-old male was bitten three times while handling
a juvenile P. textilis, and at the time was significantly
inebriated, with a blood alcohol of 280 mg/100ml. He presented
for treatment about 30 minutes post-bite, following a collapse at
home, from which he spontaneously recovered, and which was
preceded by headache, nausea, vomiting, and confusion. At
hospital he was severely agitated, requiring physical restraint
and relaxant medication, which delayed commencement of antivenom
therapy. By 45 minutes post-bite he had a severe defibrination
type coagulopathy. Antivenom therapy was commenced 2.5 hours
post-bite. Substantial resolution of the coagulopathy was not
apparent until five ampoules of brown snake antivenom had been
infused, some 12 hours post-bite, although a trend towards normal
was established two hours after the fourth ampoule. In this case
a mild thrombocytopenia was noted, and progressed despite
resolution of the coagulopathy. However, the renal function also
deteriorated reaching a peak creatinine level of 0.46 mmol/l on
day six, renal function remained impaired for several months,
although not sufficient to require dialysis.
This case demonstrates the unfortunate combination of alcohol and
snakebite, renal failure, and the association of renal failure
with thrombocytopenia.
Case 6: (from White 1987c). A 19 year-old man was bitten on his
arm while working under his house in a remote mining town. No
snake was seen. He ignored the "sting", but 45 minutes later
developed a headache, dizziness, and nausea. By two hours post-
bite this had worsened, and he had generalized muscle weakness,
blurred vision, and hyperaesthesia. A tentative diagnosis of
snakebite was made, and appropriate antivenom administered. One
hour post antivenom, while on an aeromedical retrieval flight to
Adelaide, he developed acute crushing chest pain, cyanosis, and
was clammy. This rapidly responded to s.c. adrenaline. On arrival
in Adelaide he was awake, but showed general muscle weakness,
though without obvious cranial nerve involvement other than
blurred vision. The possible bite site was tender, though not
swollen, and no bite marks were visible, but a swab for venom
detection was positive for brown snake venom. There was no
evidence of a coagulopathy, and renal function remained normal.
He gradually recovered full muscle power over the next three
days.
This case is important in that it represents a case of brown
snake bite with apparently significant envenomation, but without
the usual coagulopathy. P. nuchalis is found in the area this
patient was bitten, in two distinct colour morphs. The author
has seen one similar case with envenomation, generalized muscle
weakness, but no coagulopathy or renal damage, caused by what is
presumed to be a variant of P. nuchalis.
Case 7: (from White et al 1987). This represents the only case
report to date of envenomation by P. modesta. An 11 year-old girl
was bitten on her left foot by a 0.5 m specimen, which was killed
and identified. The only initial symptom was nausea, lasting six
hours, and then a headache, followed by abdominal pain, lasting
16 hours. There was no evidence of neurotoxicity, or a
coagulopathy. Renal function was normal. Brown snake venom was
detected in the urine confirming systemic envenomation. The
patient made a complete recovery without need of antivenom
therapy.
12. ADDITIONAL INFORMATION
12.1 Availability of antidotes and antitoxins
Specific brown snake antivenom and venom detection kits
available directly from the manufacture, Commonwealth Serum
Laboratories, 45 Poplar Road, Parkville, Victoria 3052,
Australia (telephone (03) 389 1911, telex AA 32789, Fax (03) 389
1434, international fax +61 3 389 1434).
12.2 Specific preventative measures
Avoid exposure to brown snakes. If working in areas where these
snakes exist, be alert, wear appropriate footwear and clothing,
do not place hands or other parts of body in places where snakes
may be present (eg down holes, in rubbish etc). If handling or
catching snakes use appropriate techniques and equipment,
regularly checked to ensure peak performance, carry first aid
equipment (eg bandages, splint), never work alone, and have an
emergency plan documented and tested. If allergy history or
known allergy to horse serum ensure this is documented
adequately.
12.3 Other
No data.
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White J (1987)d Elapid snakes: management of bites. In
Covacevich J, Davie P & Pearn J Eds. Toxic Plants & Animals: a
guide for Australia, Queensland Museum, 504 pp.
White J, Fassett R (1983) Acute renal failure and coagulopathy
after snakebite; Med. J. Aust., 2:142-143.
White J, Williams V, Passehl JH (1987). The five-ringed brown
snake, Pseudonaja modesta (Gunther): report of a bite and
comments on its venom; Med. J. Aust. 147:603-605.
White J, Williams V (1989) Severe envenomation with convulsion
following multiple bites by a common brown snake, Pseudonaja
textilis; Aust. Paediatr. J., 25:109-111.
White J (1990) Letter to editor; Med. J. Aust. , 152; 445-446.
Williams V and White J (1990) Variation in venom composition and
reactivity in two specimens of yellow-faced whip snake (Demansia
psammophis) from the same geographic area. Toxicon , 28, 1351-
1354.
13.2 Zoological
Cogger HG (1975) Reptiles and Amphibians of Australia, Sydney,
A.H. & A.W. Reed.
Cogger HG (1987) The venomous land snakes. In Covacevich,
J., Davie, P. & Pearn, J. Eds. Toxic Plants & Animals: a
guide for Australia, Brisbane, Queensland Museum, 504 pp.
Cogger HG, Cameron EE & Cogger HM (1983) Zoological catalogue of
Australia, Volume I, Amphibia and Reptilia, Canberra,
Australian Government Publishing Service.
Covacevich J (1988) Australia's dangerous snakes. In Pearn, J.
& Covacevich, J. Eds. Venoms and Victims, Brisbane, Queensland
Museum.
Longmore R (1986) Atlas of elapid snakes of Australia, Canberra,
Australian Government Publishing Service.
Schwaner TD, Baverstock PR, Dessauer HC & Mengden GA (1985)
Immunological evidence for the phylogenetic relationships of
Australian elapid snakes. In Grigg, G., Shine, R. & Ehmann, H.
Eds. Biology of Australasian Frogs and Reptiles, New South
Wales, Royal Zoological Society.
14. AUTHOR, ADDRESS
Dr Julian White
State Toxinology Services
Adelaide Children's Hospital
North Adelaide, South Australia, 5006
Australia
Phone: 61-8-2047000
Mobile phone: 61-18-832776
Fax: 61-8-2046049
July 1990
Reviewed by Working Group On Natural Toxins April 1991.
Revised April 1991, November 1991.