1.   NAME


     1.1  Scientific Name

          Pseudechis australis
                     butleri
                     colletti 
                     guttatus
                     papuanus
                     porphyriacus

          (Cogger 1975, 1987; Cogger et al 1983; Covacevich 1988; 
          Schwaner,1985) 


     1.2  Family

          Elapidae

          Genus: Pseudechis

     1.3  Common Names

          Scientific Name           Common Name

          Pseudechis australis      mulga snake, king brown
                     butleri        Butler's snake
                     colletti       Collett's snake
                     guttatus       spotted black snake,
                                    blue bellied black snake
                     papuanus       Papuan black snake
                     porphyriacus   red bellied black snake

    2.   SUMMARY

     2.1  Main risks and target organs

          Black snakes are only a moderately common cause of significant 
          snakebites in Australia. Severity depends on species, with P. 
          australis often causing significant envenomation while some other 
          species, notably P. porphyriacus, only rarely causing severe 
          envenomation. In the past P. papuanus has been thought to be a 
          significant cause of snakebites in Papua New Guinea, but there is 
          some doubt that this is still so. 
          
          Main risks are:  rhabdomyolysis, acute renal failure, and 
          possibly coagulopathy and neurotoxic paralysis in some species. 
          
          Target organs:  skeletal muscle, coagulation system, and possibly 
          the neuromuscular junction for some species. 

     2.2  Summary of clinical effects

          Locally: usually immediately painful, with subsequent development 

          of mild to marked local oedema, and sometimes ecchymosis. Bite 
          marks vary from single puncture, through multiple punctures, to 
          multiple scratches. Local secondary infection unusual. Venom may 
          spread to draining lymph nodes with consequent pain, tenderness 
          or swelling.
          
          Systemic: headache, nausea, vomiting, abdominal pain, impaired 
          consciousness, occasionally loss of consciousness  and possibly 
          convulsions. Coagulopathy with overt bleeding manifestations is 
          rare. Neurotoxic paralysis is not well documented clinically. 
          Muscle movement is painful. Acute renal failure. Rhabdomyolysis 
          may dominate the clinical picture for P. australis bites and 
          possibly for P. butleri bites. 

     2.3  Diagnosis

          Monitor coagulation to establish the presence and extent of 
          coagulopathy. This should be performed at presentation, on 
          development of symptoms or signs of systemic envenomation, and 1-
          2 hours after antivenom therapy. However, coagulopathy due to 
          Pseudechis bites is poorly documented and defibrination has not 
          been reported.
          
          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 for venom 
          detection is a swab from the 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 
                specific snake antivenom (CSL). 
                
                Snake                    Antivenom  
          
                Pseudechis australis     black snake antivenom
                           butleri       black snake antivenom
                           colletti      tiger snake antivenom 
                           guttatus      tiger snake antivenom
                           porphyriacus  tiger snake antivenom
                           papuanus      black snake antivenom
          
          (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 the local wound until 
                appropriate samples taken for  venom detection. Thereafter 
                ensure antisepsis. Early surgical intervention is generally 
                contraindicated, and is only rarely indicated in the late 
                stages if significant local necrosis has developed. 

     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 fangs are likewise paired, 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.




     2.6  Main toxins

          Pseudechis  venom  is  a  complex  mixture  of  protein and non-
          protein components, not all of which have been fully evaluated. 
          
          (a)   Neurotoxins:  both presynaptic  and postsynaptic may be 
                present, though neither appear to be clinically important 
                in human envenomation. 
          
          (b)   Procoagulants:  principally  anticoagulants.
          
          (c)   Myotoxins:   second  action  of  presynaptic  neurotoxins  
                which is a phospholipase A2, and also a separate action of 
                distinct phospholipase toxins without significant 
                neurotoxic action. 

    3.   CHARACTERISTICS

     3.1  Description of the animal

          3.1.1 Special identification features

          The black snakes belong to the Class Reptilia; Order Squamata; 
          Suborder Serpentes: Family Elapidae.  They are oviparous (except 
          P. porphyriacus which is ovoviviparous),  diurnal or crepuscular, 
          and in warm weather may be nocturnal.  Food varies with species, 
          subspecies and locality, and includes frogs, small lizards, and 
          small mammals. 
          
          Black 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 .  The  fangs have venom transport  
          grooves, enclosed for most of their length. For fang details see 
          section 3.3.2. 
          
          
          
          Six species are currently recognized.
          
                Scientific Name           Common Name
          
                Pseudechisaustralis       mulga snake, king brown
                          butleri         Butler's snake
                          colletti        Collett's snake
                          guttatus        spotted black snake, 
                                          blue bellied black snake
                          papuanus        Papuan black snake
                          porphyriacus    red bellied black snake 
         
                Genus Pseudechis:  Characterized by smooth scales, mid-body 
                scales in 17-19 rows, anal and subcaudal scales variable, 
                anal usually divided, but anterior subcaudals usually 
                single, suboculars absent, head usually broad to triangular 
                in outline with some vertical compression. 
          

          
                P. australis
          
                Scalation:  smooth, 17 rows in mid body, ventrals 185-225, 
                anal divided (occasionally single), subcaudals 50-75, 
                usually single anteriorly. 
         
                Length:   2 metres (max over 2.7 m)
         
                Colour:  Colour usually uniform dorsally, ranging from pale 
                brown, through russet brown, to dark brown depending on 
                specimen and location. Scales usually lighter in colour 
                proximally becoming darker near their tips giving an 
                overall reticulated pattern on close inspection. Ventrally 
                cream to pink often with darker blotches. 
          
                P. butleri
            
                Scalation:  smooth, 17 rows in mid body, ventrals 204-216, 
                anal usually divided, subcaudals 55-65, usually single 
                anteriorly. 
          
                Length:   1.6 metres
           
                Colour:  Sides and front of head brown or reddish brown, 
                rest of head dorsally black or brown black, extending to 
                nape of neck, body with reticulated appearance as each 
                scale has a base colour of dark brown to black with a large 
                central area of pale yellow. Ventrally yellow with black 
                blotches. 
          
                P. colletti
          
                Scalation:  smooth, 19 rows in mid body, ventrals 215-235, 
                anal usually divided, subcaudals 50-70, single anteriorly. 
          
                Length:  1.5 metres (maximum about 2 m).
          
                Colour:  Distinctive, with deep brown to black dorsally 
                with numerous irregular cross bands of pink, or cream 
                scales, tending to dominance laterally, more vivid in 
                juveniles where the colour may be deeper  and even orange 
                or red orange, ventrally cream to yellow or orange. 
          
                P. guttatus
          
                Scalation:  smooth, 19 rows in mid body, ventrals 175-205, 
                anal usually divided, subcaudals 45-65, single anteriorly. 
          
                Length:  1.5 metres (maximum about 2 m).
          
                Colour:  Variable. Two basic forms, one black to blue black 
                dorsally with grey to black ventrally (blue bellied black 
                snake), the other black with brown blotches dorsally and 
                laterally, grey ventrally (spotted black snake), and in 
                some specimens the dominant dorsal scale colour may be 

                cream with black tips. 
          
                P. papuanus
          
                Scalation:  smooth, 19-21 rows in mid body, ventrals 215-
                230, anal usually divided, subcaudals 45-65, mostly single 
                but divided posteriorly. 
          
                Length:  2.1 metres.
          
                Colour:  Dorsally black (occasionally brown), ventrally 
                grey or bluish grey. 
          
                P. porphyriacus
          
                Scalation:  smooth, 17 rows in mid body, ventrals 170-215, 
                anal usually divided, subcaudals 40-70, single anteriorly. 
          
                Length:  1.25 metres (maximum about 2.5 m).
          
                Colour:  Dorsally black, ventrally usually red, 
                occasionally pink, or pale cream to white, or black. 
          
                (Cogger 1971, Cogger 1975, Mirtschin & Davis 1983, Smith 
                1982) 

          3.1.2 Habitat

                Habitat varies with species ranging from arid lands to 
                wetlands 
                
                
                Pseudechis australis (mulga snake, king brown)
                
                Found in a diverse range of habitats from arid areas across 
                central Australia, through to sub-tropical and tropical 
                regions. Principally diurnal, it is however active on warm 
                nights. 
                
                P.butleri (Butler's snake)
                
                Essentially similar to P. australis but with a more limited 
                range, not encompassing tropical areas. 
                
                P. colletti (Collett's snake)
                
                Relatively little known about the ecology of this snake, 
                but it is found principally in arid and semi-arid areas. 
                
                P. guttatus (Spotted black snake, blue bellied black snake)
                
                
                This species favours wetland areas including riverine and 
                floodplain habitats. 
                 
                P. papuanus (Papuan black snake)

                
                The papuan black snake is confined to Papua New Guinea 
                chiefly in southern and coastal regions. It has been 
                recorded in savanna woodland, adjacent forrest, and in 
                swampland. The true distribution and ecology and habitat 
                preferences of this snake have yet to be defined. 
                
                P. porphyriacus (Red bellied black snake)
                
                Essentially a wetlands species favouring swamps, riverine, 
                and similar habitats. 

          3.1.3 Distribution

                The distribution for each species based on museum records 
                and published accounts is 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).  The classic bite mark 
          in plaster is shown in Figure. 

     3.3 The toxin(s)

          3.3.1 Name  

                P. australis   Mulga snake venom
                               Mulgatoxin a (specific myotoxin)
                               Pa 10a, Pa 11, Pa 13 (PLA2 [=phospholipase 
                               A2] toxins)
                
                P. porhyriacus Black snake venom
                               Pseudexin A,B,C (PLA2 toxins)
                
                P. colletti    Colletts snake venom
                
                P. guttatus    Spotted black snake venom
                
                P. papuanus    Papuan black snake venom

          3.3.2 Description

         Whole venom production based on milking specimens, usually 
            in captivity.  (White 1987b, Fairley & SPLATT, 1929) 
    
                Venom yield and fang length, where known, are listed below 
    
                (Fairley 1929b, Kellaway 1929, Kellaway and Thompson 1930, 
                Martin and Smith 1892, Sutherland 1983, White 1987a, 
                Worrell 1970, Morrison et al 1982) 
    
    

    Snake:         P.aus   P.but   P.col   P.gut   P.por   P.pap 
    
    Average adult
    fang length
    (mm)               6.5      -       -      3.5     4.0      -
    
    Average distance
    between fangs
    (mm)                -       -       -       -      12       -
    
    Average venom
    yield (mg)         180      -       30      -      40       -
    
    Maximum venom
    yield (mg)         600      -       50      -      94       -
    
    Mean venom injected
    (defensive strike)
    (mg)               61.6     -        -      -      1.3      -
    
    Mean venom left
    on skin
    (mg)               0.07     -        -      -      0.9      -
    
    
     
                Venom components
    
                Myotoxins:
    
                Mulgatoxin a
    
                From P. australis venom: (also as Pa VIIIa,), Basic PLA2 
                single chain protein, 122 AA, 7 disulphide bridges, MW 
                13484 D, LD50 200 mg/kg ip mice, a specific myotoxin in 
                mice causing myoglobinuria, affecting skeletal muscle, and 
                with death due to probable paralysis at high doses, without 
                histological evidence of damage to heart or smooth muscle 
                (Leonardi et al 1979, Mebs & Samejima 1980) 
    
                P. a.Frac.5
    
                From P. australis venom: Lethal, causes myoglobinuria in 
                mice, LD50 0.25 mg/kg ip mice. (Leonardi et al 1979) 
    
                Pseudexin
    
                From P. porphyriacus venom: Initially described as a PLA 
                single chain polypeptide, MW 16500 D, LD50 0.48 mg/kg ip 
                mice. Later shown to be a dimer, then a mixture of 3 
                isomers, A,B,& C,with respective LD50s and MWs of; A= LD50 
                1.3 mg/kg ip mice, 117 AA, MW 13096D; B= LD50 0.75 mg/kg, 
                117 AA, MW 13002D; C= non-toxic in mice, not further 
                elaborated. It was further noted that monoclonal antibody 
                to Pseudexin neutralized the presynaptic neurotoxin from 
                tiger snake venom (notexin, Notechis scutatus). Although 

                principally described as a lethal myotoxin, it is therefore 
                possible that pseudexin also functions as a neurotoxin. 
                (Vaughan et al 1981, Moon & Rys 1984, Schmidt & Middlebrook 
                1989) 
    
                P. porph.Ib
    
                From P. porphyriacus venom: A lethal myotoxin, basic PLA2 
                protein, 120 AA, MW 13400D, LD50 6.4 mg/kg sc mice, minimum 
                dose for myoglobinuria 1.4 mg/kg sc mice. (Mebs & Samejima 
                1980) 
    
                P. coll/gut.
    
                From a mixture of P.  colletti and P. guttatus venom. Two 
                lethal myotoxins , both PLA2 basic proteins, II = 127 AA, 
                MW 14170D, LD50 4.5 mg/kg sc mice; IV = 129 AA , MW 14100D, 
                LD50 4.3 mg/kg sc mice. For all toxins described in this 
                study (including Ib and VIIIa above) death occurred in 
                hours due to respiratory paralysis at high doses, but in 
                days due to myolysis and renal failure at lower doses. 
                (Mebs & Samejima 1980) 
    
                P. coll.
    
                From P. colletti venom: Lethal PLB protein, dimer, MW 
                33000D in two chains of 16500D, LD50 approx. 2 mg/g ip 
                mice. Causes death due to myolysis and also associated 
                ataxia, respiratory difficulty, possibly neurotoxic, and 
                also strongly haemolytic. (Bernheimer et al 1987) 
    
                Neurotoxins
    
                Pa 10a
    
                From P. australis venom: Lethal single chain PLA2 protein, 
                LD50 0.1 mg/g iv mice. Produces paralysis by reducing 
                acetylcholine release from the terminal axon at the 
                neuromuscular junction, and by direct blockade of muscle 
                fibre contractility. (Rowan et al 1989) 
    
                Pa 11
    
                From P. australis venom: Lethal single chain PLA2 protein, 
                LD50 0.23 mg/g iv mice, MW 14000D, 118 AA. Action similar 
                to Pa10a. (Nishida et al 1985, Rowan et al 1989) 
    
                Pa13
    
                From P. australis venom: Single chain PLA2 protein, MW 
                13500, 118 AA, initially described as non-lethal, later as 
                lethal at higher doses with an LD50 6.8 mg/g iv mice. 
                Action similar to PA10a. (Nishida et al 1985, Rowan et al 
                1989) 
    
                Pa a

    
                From P. australis venom: Single chain protein, 62 AA, MW 
                7100D, LD50 76 mg/kg iv mice. Described as a short chain 
                neurotoxin with considerable homology to similar sea snake 
                neurotoxins, presumably post-synaptic in action. (Takasaki 
                & Tamiya 1985) 
    
                Pa 1D
    
                From P. australis venom: Single chain protein, 68 AA, non-
                lethal to mice, considered a long chain neurotoxin 
                homologue. (Takasaki 1989) 
    
                Procoagulants
    
                None isolated. Pseudechis venoms appear to be anticoagulant 
                in vitro rather than procoagulant. (Sutherland et al 1981, 
                Marshall & Herrmann 1983, Campbell 1967, Campbell & 
                Chesterman 1972, Trethewie 1971). They are not noted to 
                have significant platelet activity. (Marshall & Herrmann 
                1989) 
    
                Haemolysins
    
                In vitro haemolytic activity of Pseudechis venoms has long 
                been recognized but few haemolysins have been characterized 
                specifically. Significant activity has been noted for P. 
                australis, P. porphyriacus, P. papuanus, P. colletti. 
                Phospholipase B has been characterized as a haemolytic 
                fraction of P. colletti venom. (Doery & Pearson 1961, 
                Bernheimer et al 1986,1987) 

     3.4  Other chemical contents

          There are few data on most of these components, which include L-
          amino acid oxidase.
          
          (Trethewie 1971, Takasaki & Tamiya 1982)

          


    4.   CIRCUMSTANCES OF POISONING

     4.1  Uses

          Venom is used both in antivenom production and for laboratory 
          research. 
 


     4.2  High risk circumstances

          Children:  when playing in areas where black snakes are common, 
          either through accidental encounter (ie stepping on snake) or 
          while trying to emulate noted naturalists (ie trying to catch 

          snake). 
          
          Adults:  when living in areas where black 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 black snakes are 
          common. 
          
          Reptile keepers & snake handlers:  if due care is not exercised 
          in catching and handling snakes, including venom milking. 
          
          Recreation seekers:  camping or walking or playing sport (ie 
          water sports, water skiing) in areas where black snakes are 
          common. 
          
          Homes:  around homes in black snake prone areas where water is 
          seasonally scarce and free water is available in the garden or 
          home. 

     4.3  High risk geographical areas

          No specific high risk areas for black snake bites have been 
          documented. P. porphyriacus most likely to be encountered in 
          wetlands areas and along creeks. P. australis most common in arid 
          central and north Australia where it may be a major cause of 
          snakebite. P. papuanus is common in parts of Papua New Guinea. 

    5.   ROUTES OF ENTRY

     5.1  Oral

          Not applicable.

     5.2  Inhalation

          Unknown.

     5.3  Dermal

          Venom cannot be absorbed through intact skin.

     5.4  Eye

          Not applicable.

     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. 
          
          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, ultimately reaching the systemic 
          circulation.  Experience with human cases of black snake 
          envenomation shows that symptoms and signs of envenomation may 
          occur within 60 minutes of the bite, especially in children, 
          particularly for P. australis bites.  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, whence it is excreted in the 
          urine.  Venom must also exit the circulation and enter the 
          extravascular space, where it binds within target organs.
          
          The kinetics of venom distribution, excretion, and detoxification 
          are incompletely understood. Coagulopathy potentially may become 
          well established within 30 minutes of a bite, although this is 
          poorly documented for most Pseudechis spp. (P. papuanus is an 
          exception which may cause significant coagulopathy, but there is 
          doubt over the validity of the clinical data on which this is 
          based (Campbell 1967, Campbell & Chesterman 1972). 


     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 and require no  further  modification  for activity.  Venom 
          reaches  high concentrations in the kidneys, where it is excreted 
          in urine.  (Sutherland & Coulter, 1977 a,b). The fate of specific 
          venom components, particularly neurotoxins and procoagulants, is  
          unclear. 
 
     6.5  Elimination by route of exposure

          Most venom appears to be eliminated via the kidneys in the urine.

    7.   TOXINOLOGY

     7.1  Mode of action

          Neurotoxic paralysis
          
          Whole venom of at least some species of Pseudechis contains a  
          variable mixture of presynaptic and postsynaptic neurotoxins.  
          Composition of this mixture may not be uniform  across  all  
          populations  of black snakes. However current clinical case data 
          and some animal experimental work indicates that neurotoxic 
          envenomation by these snakes is either not seen or is of minor 
          extent. It should be noted that relatively few case reports are 
          available for most species thus the issue of paralysis due to 
          Pseudechis bites remains unresolved. 
          
          Procoagulants and coagulopathy
          
          No procoagulants have been isolated from Pseudechis venoms, which 
          distinguishes these venoms from those of other major Australian 
          snakes (Notechis, Oxyuranus, Pseudonaja, Tropidechis) which 
          contain potent procoagulants. Early research suggested that 
          Pseudechis venoms have a procoagulant action in vitro but it now 
          appears that its action is anticoagulant. 
          
          Anticoagulants
          
          Early clinical work in Papua New Guinea suggested P. papuanus 
          caused a defibrination-type coagulopathy in man (Campbell 1967), 
          but subsequent reviews have indicated that this was probably 
          false due to misidentification of the snake. Experimental 
          evidence clearly supports the anticoagulant action of these 
          venoms (Campbell & Chesterman 1972, Marshall & Herrmann 1983). 
          
          P. papuanus has a potent anticoagulant action in vitro with 
          inhibition of thromboplastin generation, and inhibition of 
          conversion of prothrombin to thrombin (Campbell & Chesterman 
          1972). Anticoagulant action and lack of procoagulant action was 
          shown with in vitro experiments using P. papuanus and P. 
          australis venom (Marshall & Herrmann 1983). This latter work 
          showed a slight coagulant effect without apparent anticoagulant 

          effect for P. porphyriacus venom. In vivo experiments using 
          monkeys demonstrated an apparent "coagulopathy" using P. 
          australis venom, with prolongation of partial thromboplastin time 
          and prothrombin time, but no comment on fibrinogen levels and FDP 
          were made, thus these results are equally consistent with an 
          anticoagulant action (Sutherland et al 1981). 
          
          Rhabdomyolysis
          
          While some presynaptic  neurotoxins  are  also   directly 
          myolytic (eg notexin) and cause major destruction of skeletal 
          muscle, locally and systemically (Harris et al 1975), both in 
          experimental animals and occasionally in human envenomation, some 
          Pseudechis venoms contain direct myotoxins which do not appear to 
          exert significant neurotoxic activity. However these myotoxins, 
          which have been found in all Pseudechis venoms searched (eg. P. 
          australis, P. porphyriacus, P. colletti, P. guttatus), do appear 
          to be mostly PLA2 toxins closely related to the myotoxic 
          presynaptic neurotoxins. Based on extensive work with these 
          latter toxins the mode of action of Pseudechis myotoxins may be 
          inferred. The phospholipase  A2  activity  of  these toxins may 
          hydrolyse muscle cell membrane phospholipids (Mebs & Samejima 
          1980).  Not all muscle cells are equally  affected,  skeletal  
          muscle  being  most susceptible,  and immature muscle cells 
          appear resistant.  In experimental animals muscle cell 
          destruction may occur in only a  few hours; within 3 days  the 
          process is complete and cell regeneration commences, with 
          complete regeneration taking 3-4 weeks (Harris et al 1975).  
          Following acute muscle  damage there is a progressive rise  in 
          serum  levels of  creatine kinase (CK) peaking  at 10 - 20 hours  
          post-bite.  Myoglobin levels  also rise  and are excreted in  the 
          urine, causing the typical dark brown discolouration (Sutherland 
          et al 1981b). 
          
          In humans, the  peak CK may be extraordinarily high (up to 
          300,000 U/l or more), and myoglobinuria may  continue for many 
          days (for example, the maximum is 11 days for N. ater niger bite) 
          (White, unpublished data; Hood and Johnson, 1975). Data on human 
          cases of Pseudechis envenomation with myolysis is scant, but the 
          author's experience is that P. australis bites often cause severe 
          myolysis but  bites by P. porphyriacus and P. guttatus do not. 
          
          Renal damage
          
          No specific  nephrotoxins have  been detected in Pseudechis snake 
          venom, and no clear cases of renal function impairment have been 
          reported in humans envenomed by Pseudechis. However, a fatal case 
          of P. australis envenomation did show evidence of renal damage at 
          autopsy, possibly secondary to extensive myolysis (Rowlands et al 
          1969). 

     7.2  Toxicity

          7.2.1 Human data

                7.2.1.1   Adults

                     The  human lethal dose for Pseudechis venoms is 
                     unknown. However,  without antivenom treatment, a 
                     significant number of  P. australis bites will prove 
                     fatal. The same may apply for P. papuanus and possibly 
                     P. butleri (for which there are no human case 
                     reports), but for P. porphyriacus, and possibly P. 
                     colletti and P. guttatus human fatalities are very 
                     rare, and envenomation by these species is very 
                     unlikely to be life threatening, except perhaps in a 
                     small child. 

                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 Relevant animal data

                Snake                  LD50 mg/kg sc mice
                
                P. australis              2.38
                P. butleri                no data
                P. colletti               2.38
                P. guttatus               2.13
                P. papuanus               1.09
                P. porphyriacus           2.52

          7.2.3 Relevant in vitro data

                No data available.

     7.3  Carcinogenicity

          No data available. 

     7.4  Teratogenicity

          No data available. 

     7.5  Mutagenicity

          No data available. 

     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 there is 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 till 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, and EDTA will be used for complete 
                     blood pictures). 

          8.1.2 Storage of laboratory 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). 
                
                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 samples and 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 materials

                8.2.1.1   Simple qualitative test(s)

                     A simple qualitative test for presence of snake venom 
                     and designation of species/genus  group, corresponding 
                     to the most appropriate monovalent anti-venom 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. This is particularly true for P. 
                     porphyriacus, P. colletti and P. guttatus which may 
                     cause simultaneous colour change in wells for both 
                     mulga snake venom and tiger snake venom. 
                     
                     (10) Detection limit
                     
                     The manufacturer states the kit will detect 
                     concentrations of venom as low as 10 ng/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. Note however 
                     that for some species of Pseudechis there may be a 
                     colour change in two tubes simultaneously which may 
                     cause confusion. This most often is manifest by change 

                     in the tubes for both mulga snake and tiger snake 
                     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  radioimmunoassay  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 biologicals 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 methods(s)

                     see 8.2.1.4

                8.2.2.5   Other dedicated methods(s)

                     No data available.

          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 Biochemical 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 be due to 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 biological specimens


                     No data

          8.3.2 Arterial blood gas analysis

                Performed in the setting of impaired respiratory function, 
                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 is likely to be 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. This implies that all circulating venom has been 
                neutralized, at which point further antivenom therapy can 
                be withheld until the trend of improving results is 
                confirmed. No further antivenom therapy for the 
                coagulopathy is indicated (unless there is a subsequent 
                relapse). 
                  
                In the patient seen late or initially treated elsewhere 
                there may be no abnormal clotting time (INR < 2.0) but 
                fibrinogen may be low and 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 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 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. These 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 which is 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 available.

          9.1.2 Inhalation

                No data available.

          9.1.3 Skin exposure

                If skin surface intact, no effects.

          9.1.4 Eye contact

                No data available.

          9.1.5 Parenteral exposure

                In practical terms, subcutaneous or intradermal injection 
                is the only likely route of entry. 
                 
                Early symptoms (usually in the first six hours).
                
                Local:  pain, mild to  severe; oedema,  mild; ecchymosis, 
                variable, mild;  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. 
                
                Delayed symptoms
                
                Local:  rarely a small area of superficial necrosis may 
                develop, particularly if first aid is left in place more 
                than 4 hours, or if a tourniquet is used (Sutherland 1981, 
                1983a; White 1987d; Frost, 1981). 
                
                Systemic:
                
                Myolysis - muscle weakness and movement pain.   Dark urine. 
                Renal impairment - oliguria or anuria. Paralysis and 
                coagulopathy not convincingly reported.

          9.1.6 Other

                No data

     9.2  Chronic poisoning by: 

          9.2.1 Ingestion

                No data available.

          9.2.2 Inhalation

                No data available.

          9.2.3 Skin exposure

               No data available.

          9.2.4 Eye contact

                No data available.

          9.2.5 Parenteral exposure

                No data available.

          9.2.6 Other

                No data available.

     9.3  Course, prognosis, cause of death

          Course
          
          Initially the patient will usually be anxious, knowing they have 
          sustained a snakebite.  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). 
           
          Bites will vary in severity with the species of black snake 
          involved in addition to the factors mentioned above. 
          
          P. australis:    Potentially moderate to severe bite, 
                           potentially lethal.
          P. butleri:      As above (no human case data).
          P. papuanus:     As above.
          P. porphyriacus: Generally mild bites, not lethal in adults 
                           in general.
          P. colletti:     As for P. porphyriacus (little human case data)
          P. guttatus:     As for P. porphyriacus (little human case data).
          
          Minor envenoming:  little or no venom injection, no development 
          of systemic envenomation, no need for antivenom treatment, no 
          likely sequelae or complications. 
          
          Moderate envenoming:  bite usually at least slightly painful, 
          with some local reactions usually including local swelling and 
          sometimes ecchymosis, subsequent development over the next few 

          hours of some or all of the following:  headache, nausea, 
          vomiting, abdominal pain, collapse, and possibly convulsions 
          (more likely in children). 
           
          On the evidence of current human case data, paralysis is unlikely 
          to occur following Pseudechis envenomation but caution dictates 
          that it should at least be sought; early signs include ptosis and 
          diplopia. The same applies to coagulopathy which, if present, is 
          most likely due to true anticoagulation rather than 
          defibrination; however, laboratory evidence of coagulopathy 
          should be sought.  
          
          Antivenom treatment at this stage may arrest or reverse the 
          various manifestations of systemic envenomation.  Without 
          antivenom treatment, in most  cases of P. australis, P. papuanus, 
          and probably P. butleri envenomation, the symptoms and signs will 
          show progressive worsening. Progressive myolysis and muscle 
          movement pain; and secondary renal failure are particular risks; 
          secondary complications of the above, particularly pneumonia, 
          should be considered. The ultimate outcome may be death, more 
          than 24 hours post-bite. 
          
          For bites by P. porphyriacus, and probably P. colletti and P. 
          guttatus, the clinical picture is in general less severe. There 
          may be quite significant local symptoms (especially swelling and 
          pain) and some systemic symptoms (headache, nausea, vomiting, and 
          abdominal pain). It is rare for other problems to occur. 
          Specifically it appears that significant myolysis and renal 
          damage are not seen, and most bites with envenomation are not 
          life-threatening and, at least in healthy adults, may not require 
          antivenom therapy. 
          
          Severe envenoming:  most likely if the bite is either multiple, 
          or associated with a chewing bite and numerous teeth marks. P. 
          porphyriacus, P. colletti, P. guttatus bites are not likely to be 
          lethal. Severe envenoming is only likely after bites by P. 
          australis, P. butleri, P. papuanus. Note that, as with any form 
          of envenomation, atypical cases may occur which are more severe 
          than might be expected for that species. 
          
          The following applies to bites by P. australis, P. butleri, P. 
          papuanus. Local reactions such as ecchymosis, oedema and pain 
          likely.  Rapid development of headache, and possibly collapse, 
          and convulsions (especially children), sometimes within 30 
          minutes of bite.  Subsequent symptoms may include headache, 
          nausea, vomiting, abdominal pain, and evidence of progressive  
          myolysis and renal impairment. Paralysis and defibrination-type 
          coagulopathy are not likely on the evidence of current case data 
          (although research data suggest that paralysis may be possible). 
          However, myolysis may mimic some features of paralysis due to 
          muscle movement pain and intrinsic weakness. Features of 
          paralysis should be looked for such as ptosis and diplopia. 
          Myolysis may take several hours to develop.  Renal damage may 
          occur early.  Prompt antivenom treatment is required as soon as 
          nature of envenomation evident.  The myolysis may not be 
          preventable, and may result in widespread muscle damage, which 

          will eventually resolve.  Renal damage is probably reversible, 
          after a period of dialysis. 
          
          Without antivenom treatment  patients with severe envenoming may 
          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 more 
                severe envenomation. 
          
          Prognosis
          
                In the past, perhaps as many as 30% of all P. australis 
                snake bites have proved fatal when no antivenom treatment 
                was used. No data are available on the fatality rate 
                associated with antivenom treatment, but deaths do still 
                occur.The situation with P. papuanus and P. butleri is 
                probably similar or less severe. For P. porphyriacus it is 
                clear that very few deaths have occurred, and probably none 
                in normal healthy adults, but children and the elderly may 
                be at more risk. This should be born in mind when deciding 
                on the merits of antivenom therapy as the subjective 
                symptomatology for the patient may be worse than the degree 
                of envenomation actually present. Bites by P. colletti and 
                P. guttatus are probably similar in severity to those of P. 
                porphyriacus, although case data are lacking, and there are 
                no known fatalities. 
          
          Causes of death
          
                Myolysis            This appears to be the major clinical
                                    problem. Fatal cases poorly
                                    documented.
          
                Renal Failure       Includes secondary complications such
                                    as infections.
          
                Anaphylaxis         Acute allergic reaction to venom in a
                                    patient previously exposed to
                                    Pseudechis  snake venom (eg reptile
                                    keeper).
         

                Cardiac complications likely to be secondary, and their 
                                    role in Pseudechis snake bite 
                                    fatalities uncertain.

     9.4  Systematic description of clinical effects

          9.4.1 Cardiovascular

                Collapse, presumably due to hypotension, is seen in the 
                early stages of systemic envenomation at least by P. 
                australis, especially in children. The mechanism is 
                uncertain but may be due to release of vasoactive 
                substances.
                
                Specific cardiac abnormalities due to Pseudechis 
                envenomation in man are not described. 

          9.4.2 Respiratory

                No primary effects of Pseudechis venom on the respiratory 
                system in man are reported. 

          9.4.3 Neurological

                9.4.3.1   CNS

                     No direct CNS toxins have been reported for Pseudechis 
                     venom, early collapse and convulsions may occur, 
                     especially in children.  Their aetiology remains 
                     uncertain. 

                9.4.3.2   Peripheral nervous system

                     Effect of venom uncertain and of little clinical 
                     significance. 

                9.4.3.3   Autonomic

                     Abdominal pain.

                9.4.3.4   Skeletal and smooth muscle

                     Pseudechis venom has been shown to act at the 
                     neuromuscular junction experimentally but not 
                     clinically. Presynaptic  neurotoxins are present but 
                     their clinical significance is uncertain. 
                     Theoretically, they may cause progressive 
                     neuromuscular paralysis, up to complete paralysis of 
                     all muscles of respiration. No documented cases. 

          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 rare, even in severe 
                envenomation.  Abdominal pain is sometimes described. 

          9.4.5 Hepatic

                Direct hepatic effects of Pseudechis venom have not been 
                noted clinically or experimentally. 

          9.4.6 Urinary

                9.4.6.1   Renal

                     No direct nephrotoxin has been reported from 
                     Pseudechis venom, nor has renal failure  been reported 
                     but in one fatal case there was evidence of renal 
                     damage, and it is potentially a very serious 
                     complication of envenomation.  The nature of the renal 
                     injury and its cause are poorly documented, but acute 
                     tubular necrosis seems most likely. 
  
                9.4.6.2   Other

                     No data available.

          9.4.7 Endocrine and reproductive systems

                No data available.

          9.4.8 Dermatological

                The local bite site is often painful, with significant 
                swelling, and ecchymosis is sometimes seen.  Teeth marks 
                are variable, from single fang puncture to multiple tooth 
                punctures and scratches. Local necrosis may occur, but is 
                usually minor if present, unless a tourniquet is used as 
                first aid.  Secondary infection may occur (White 1983b). 

          9.4.9 Eye, ear, nose, throat: local effects

                No data available.

          9.4.10 Haematological

                A major clinical effect of most Australian  snake 
                envenomation in man is coagulopathy caused by potent 
                procoagulants in the venom, which cause prothrombin 
                activation and secondary fibrinogen consumption. Initially, 
                this was also thought to be true of Pseudechis bites, 
                especially P. papuanus and P. australis. It now appears 
                this is not so and therefore major bleeding is not likely. 
                However, minor bleeding problems associated with the 
                anticoagulant effect of the venom may occur.
                
                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. 

          9.4.11 Immunological

                No data available.

          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), or myolysis may occur. 
                     Beware particularly of hyperkalaemia.
                      
                     The possibility of inappropriate ADH (antidiuretic 
                     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 occurs).  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. 

          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 black snakes are also 
                at risk of acute anaphylactic allergic reactions on 
                subsequent bites, which may cause collapse within minutes 
                of the bite.  Fatalities have occurred due to this 
                mechanism with other species (Notechis), and the author is 
                aware of severe non-fatal acute allergic type reactions 
                following bites by P. porphyriacus (Sutherland 1983; White 
                1987 b,d, White unpublished observations). 



          9.4.14 Other clinical effects

                Rhabdomyolysis

                Due to direct action of myotoxins on muscle cells, causing 
                widespread muscle damage. This causes muscle weakness, 
                muscle tenderness, muscle movement pain, diminished deep 
                tendon reflexes, rise in serum CK, and myoglobinuria (dark 
                brown urine). If muscle damage is severe, recovery may take 

                weeks, although full functional recovery is possible.  
                Severe muscle wasting may be apparent, and intensive 
                physiotherapy is required to prevent contractures in the 
                early stages, and to promote rapid muscle regeneration in 
                the later stages. 

          9.4.15 Special risks

                No data available. 

     9.5  Others

          No data available.

    10.  MANAGEMENT

     10.1 General Principles

          All patients suspected of having sustained a Pseudechis 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 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 by supporting 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) consider  giving specific 
          antivenom depending on the clinical situation and the species of 
          snake involved (see section 9). Bites by P. australis, P. 
          papuanus, and probably P. butleri will require antivenom therapy 
          (CSL Black Snake Antivenom). 
           
          Bites by P. porphyriacus, and probably P. colletti and P. 
          guttatus often may not require antivenom therapy despite systemic 
          envenomation (especially in adults, see section 9), and if 
          antivenom is required then CSL Tiger Snake Antivenom is preferred 
          (cheaper and of lower volume) (White 1981; 1987d; Sutherland 
          1983; Trinca 1963). 
          
          Symptomatic and general treatment
           
                Support of cardiorespiratory systems.
                Treatment of shock.
                Maintain adequate renal perfusion.
                Tetanus prophylaxis.
                Avoid respiratory depressant medications (eg morphine).

                Avoid antiplatelet medications (eg aspirin).

     10.2 Relevant laboratory analysis 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 is useful but 
                serum or plasma are 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).  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. 
                
                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 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

          Myolysis
          
          Antivenom therapy, maintenance of adequate renal diuresis and, in 
          the latter stages during recovery, appropriate diet (high 
          protein) and physiotherapy. Carefully monitor for hyperkalaemia, 
          both directly, and by ECG changes. 
          
          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.  Dialysis may be required. 
          
          Local bite site
          
          The bite site should be cleaned only after adequate sampling for 
          venom. Local infection may occur, but is not usual, and thus 
          prophylactic antibiotic therapy is not appropriate.  Tetanus 
          prophylaxis should be ensured.  If there is minor local necrosis, 
          this can usually be successfully treated conservatively.  Only 
          rarely will local skin necrosis be sufficient to warrant 
          debridement and grafting, and this is best left until the acute 
          phase of envenomation is over, and the area of injury clearly 
          delineated. Pseudechis  bites do not apparently cause sufficient 
          local reaction to justify surgical decompression, although local 
          swelling can be quite severe, and extend to involve most or even 
          all of the bitten limb, and occasionally the adjacent trunk 
          (especially bites by P. australis).  If compartment syndrome is 
          suspected, then it should be confirmed by intracompartmental 
          pressure measurement prior to any surgical intervention. 
          
          Coagulopathy
          
          The principal method of treatment of defibrination-type 
          coagulopathy is the neutralisation of all inoculated venom by 
          antivenom. However, it is unclear whether this applies to the