Current management for Australian snakebite


The treatment of snakebite and snake envenoming has changed over the last 5 years which is based mainly on evidence from the Australian snakebite project. This has been summarised in a review of the management of snakebite - "Snakebite in Australia: a practical approach to diagnosis and treatment." which can be downloaded.
One of the important changes is the dosing of antivenom with small doses being recommended and no requirement for repeat doses. The following includes a flow chart and clinical pathway that can be downloaded, summary tables of the clinical effects and treatment of snake bite and references from the Australian snakebite project.

Antivenom Dose
For all snake types only one vial of the appropriate snake monovalent antivenom is recommended for treatment of snake envenoming in adults and children. The indications for antivenom are listed below. Larger doses are not required and repeat dosing is also not required based on in vitro and clinical evidence from the Australian snakebite project. Snake envenoming takes time to recover and antivenom will only prevent the clinical effects (neurotoxicity, myotoxicity and VICC) and will not speed their recovery.

Snakebite Flowchart and Suspected bite clinical pathway


Summary of the approach to snakebite in Australia including envenomed and non-envenomed patients. The second sheet is a clinical pathway for suspected snakebites and aims at ruling out envenoming.

1. Clinical syndromes from Australian snake envenoming
Clinical Syndrome
Characteristics
Venom-induced consumption coagulopathy (VICC)
Activation of the clotting pathway by prothrombin activator toxins and consumption of fibrinogen, factor V and factor VIII leading to a consumptive coagulopathy.
  • INR and aPTT are prolonged or unrecordable
  • Fibrinogen is low or undetectable
  • D-Dimer is very high (at least 10x and up to 1000x normal)
Complete or severe VICC is defined as:
  • Undetectable fibrinogen, unrecordable INR and aPTT, and very high d-Dimer (10-1000 times the assay cut-off).
Partial VICC (less severe changes) is defined as:
  • Low but detectable fibrinogen, and an abnormal INR <3.0
Neurotoxicity


Descending flaccid paralysis which first involves the eye muscles (ptosis; diplopia and blurred vision due to external ophthalmoplegia), followed by bulbar muscles, respiratory muscle paralysis and limb paralysis.
Myotoxicity






Local or generalised myalgia and/or muscle tenderness:
  • The CK is usually normal on admission and then rapidly increases over 24 to 48 hours. The CK ranges from >1000 U/L in mild cases to >100,000 U/L in severe cases and may take days to resolve.
  • Renal impairment and an elevated potassium may develop in severe cases
Sudden collapse
Collapse or syncope that occurs within 1 hour of the bite:
  • Collapse is associated with hypotension and loss of consciousness.
  • Spontaneous recovery usually occurs within 5 to 15 minutes
  • A minority of patients will have a cardiac arrest or seizure.
Systemic symptoms
Non-specific systemic symptoms include nausea, vomiting, headache, abdominal pain and diarrhoea.
Anticoagulant coagulopathy
The aPTT is elevated although some aPTT assays may be insensitive to this coagulopathy. There may be a mild elevation of the INR, but normal fibrinogen. This coagulopathy is not clinically important but does provide a good marker of envenoming by black snakes, including mulga snakes.
Thrombotic microangiopathy (TMA)
Presence of fragmented red blood cells on blood film (microangipathic haemolytic anaemia), thrombocytopenia and an abnormal creatinine, which may lead to acute kidney injury requiring dialysis.
INR – international normalized ratio; aPTT – activated partial thromboplastin time; CK – creatine kinase.

2. Summary of the features of clinically important venomous Australian snakes.
Snake
Coagulopathy
Neurotoxicity
Myotoxicity
Systemic symptoms
Thrombotic microangiopathy
Cardiovascular effects
Antivenom
Brown Snake
VICC1
Rare and mild
-
<50%
10%
Collapse (33%); Cardiac arrest (5%)
Brown snake
Tiger Snake Group
Tiger snake
Rough-scale snake

VICC1
VICC1

Uncommon
Uncommon

Uncommon
Uncommon

Common
Common

5%
<5%

Rare
Rare

Tiger snake
Tiger snake
Hoplocephalus sp.2
VICC1
-
-
< 50%
<5%
Rare
Tiger or Brown snake
Death Adder
-
Common
-
Common
-
-
Death Adder3
Taipan
VICC1
Common
Rare
Common
5%
Uncommon
Taipan3
Black snakes
Mulga snake
Red-bellied black snake

Anti-coagulant
Anti-coagulant

-
-

Common
Common

Common
Common

-
-

-
-

Black snake3
Tiger snake
Sea Snakes
-
Uncommon
Common
Common
-
-
Sea snake4
1 Partial venom induced consumption coagulopathy (VICC) occurs in 20 to 30% of cases for all snakes that cause VICC, except taipan envenoming where partial VICC occurs in almost 50% of cases 2 The Hoplocephalus genus/group includes Stephen’s banded snake (H. stephensi), the broad headed snake (H. bungaroides) and the pale-headed snake (H. bitorquatus); 3 Polyvalent antivenom can be substituted for these large volume monovalent antivenom with no increase in risk or cost.; 4 Polyvalent or tiger snake antivenom cannot be used for sea snake envenoming.

3. Absolute and relative indications for antivenom.
Absolute indications:
  • History of sudden collapse, seizure or cardiac arrest
  • Abnormal INR
  • Any evidence of paralysis with ptosis and/or ophthalmoplegia being the earliest signs
Relative Indications:
  • Systemic symptoms (vomiting, headache, abdominal pain, diarrhoea)
  • Leukocytosis (may be associated with lymphopenia)
  • Abnormal aPTT1
  • CK > 1000U/L2
INR – international normalized ratio (Normal range: 0.9 to 1.3); aPTT – activated partial thromboplastin time; CK – creatine kinase; 1 Although an abnormal aPTT may not be clinically significant it is often an early marker of envenoming; 2 The CK may be abnormal on admission, usually between 250 and 1000U/L which is unlikely to be associated with myotoxicity. An increasing CK or abnormal CK rises more than 6 hours post-bite are more likely to be due to myotoxicity

4. Management of systemic hypersensitivity reactions to antivenom.

1.
Stop antivenom infusion
Many reactions resolve with stopping antivenom. It can then be restarted at a slower rate
2.
Lie patient flat, start high flow O2, support airway/ventilation if required
3.
For hypotension, give rapid infusion of 1L normal saline (20ml/kg in children)
Severe antivenom reactions with hypotension will have reduced venous return, so a supine posture and fluid resuscitation are essential.
4.
For hypotension, hypoxaemia, wheeze or upper airway obstruction, give adrenaline intramuscularly, 0.01 mg/kg to a maximum of 0.5 mg.
Alternatively, those experienced with IV infusions of adrenaline may go straight to step 5
5.
Consider cautious IV infusion of adrenaline – avoid BP surges
- Envenomed patients may be severely coagulopathic and high BP may cause or worsen intracerebral haemorrhage. Some patients can have exaggerated hypertensive responses to IM adrenaline, especially to second doses.
- If no response to steps 1-4, consider starting a cautious and closely monitored IV infusion of adrenaline, which can be reduced as soon as BP starts to recover, preventing BP surges.
- Use 1mg in 100mL by infusion pump: Start at 0.5 mL/kg/hour and titrate according to response; monitor BP every 3-5 minutes (using the arm opposite to the infusion); beware that as the reaction resolves adrenaline requirements will fall, the BP will rise and the infusion rate will need to be rapidly reduced.
6.
For persistent hypotension, repeat normal saline bolus
7.
For bronchospasm, consider nebulized salbutamol
8.
For upper airway obstruction, consider nebulized adrenaline
9.
Seek further advice from a clinical toxicologist or Poison Centre
A modification of standard anaphylaxis guidelines is recommended due to the risk of coagulopathy.

See ee also NSW Health Snake Guidelines

References

  1. Isbister GK, O'leary MA, Schneider JJ, Brown SG, Currie BJ; on behalf of the ASP Investigators. Efficacy of antivenom against the procoagulant effect of Australian brown snake (Pseudonaja sp.) venom: In vivo and in vitro studies. Toxicon 2007 Jan;49(1):57-67.
  2. Isbister GK, Williams V, Brown SGA, White J, Currie BJ. Clinically applicable laboratory end-points for treating snakebite coagulopathy. Pathology 2006;38(6):568–572
  3. Isbister GK, Little M, Cull G, McCoubrie D, Lawton P, Ferenc SF, Kennedy J, Trethewy C, Luxton G, Brown SGA, Currie BJ. Thrombotic microangiopathy from Australian Brown Snake (Pseudonaja) Envenoming Intern Med J. 2007 Aug;37(8):523-8.
  4. Isbister GK, Brown SGA, MacDonald E, White J, Currie BJ for the ASP Investigators. Current use of Australian snake antivenoms and frequency of immediate-type hypersensitivity reactions and anaphylaxis. Med J Aust 2008; 188(8):473-6 IF:2.582
  5. Brown SGA, Caruso N, Borland ML, McCoubrie DL, Celenza A, Isbister GK. Clotting factor replacement and recovery from snake venom induced consumption coagulopathy. Intensive Care Med. 2009 Sep;35(9):1532-8.
  6. Isbister GK, Brown SGA, Duffull SB. Failure of antivenom to improve recovery in Australian snakebite coagulopathy. QJM. 2009 Aug;102(8):563-8
  7. Gan M, O’Leary MA, Brown SGA, Jacoby T, Spain D, Tankel A, Gavaghan C, Garret P, Isbister GK. Rough scale snake (Tropidechis carinatus) envenoming: a series of confirmed cases. Med J Aust. 2009 Aug 3;191(3):183-6
  8. Kulawickrama S, O’Leary MA, Hodgson,WC, Brown SGA, Jacoby T , Davern,K, Isbister GK. Development of a sensitive enzyme immunoassay for measuring taipan venom in serum. Toxicon. 2010 Jul;55(8):1510-8.
  9. Ireland G, Brown SGA, Buckley NA, Stormer J, Currie BJ, White J, Spain D, Isbister GK. Changes in serial laboratory test results in snakebite patients: when can we safely exclude envenoming? Med J Aust 2010 Sep 6;193(5):285-90
  10. Isbister GK, Scorgie FE, O'Leary MA, Seldon M, Brown SG, Lincz LF; for the ASP Investigators. Factor deficiencies in venom induced consumption coagulopathy resulting from Australian elapid envenomation: Australian Snakebite Project (ASP-10). J Thromb Haemost. 2010 Nov;8:2504-2513
  11. Churchman A, O’Leary MA, Buckley NA, Page CP, Tankel A, Gavaghan C, Holdgate A, Brown SGA, Isbister GK Clinical effects of red-bellied black snake (Pseudechis porphyriacus) envenoming and correlation with venom concentrations: Australian snakebite project (ASP-11). Med J Aust. 2010 Dec 6;193(11-12):696-700
  12. Isbister GK, White J, Currie BJ, O'Leary MA, Brown SG; for the ASP Investigators. Clinical effects and treatment of envenoming by Hoplocephalus spp. snakes in Australia: Australian Snakebite Project (ASP-12). Toxicon. 2011 Dec 1;58(8):634-40.
  13. Isbister GK, O’Leary MA, Elliott M, Brown SGA. Tiger Snake (Notechis spp) Envenoming: Australian snakebite project (ASP-13). Med J Aust. 2013 Mar 4;198(4):194-5.
  14. Allen GE, O’Leary MA, Brown SGA, Buckley NA, Currie BJ, White J, Isbister GK. Brown snake (Pseudonaja spp.) envenoming: clinical effects and antivenom dosing - Australian snakebite project (ASP-14). PLoS One. 2012;7(12):e53188.
  15. Isbister GK, Brown SGA. Bites in Australian snake handlers - Australian snakebite project (ASP-15). QJM. 2012 Nov;105(11):1089-95.
  16. Johnston CI, O'Leary MA, Brown SGA, Currie BJ, Isbister GK for the ASP investigators. Death adder envenoming causes neurotoxicity not reversed by antivenom - Australian Snakebite Project (ASP-16). PLoS Negl Trop Dis. 2012;6(9):e1841.
  17. Gulati A, Isbister GK, Duffull SB. Effect of Australian elapid venoms on blood coagulation: Australian Snakebite Project (ASP-17). Toxicon. 2013 Jan;61:94-104.
  18. Isbister GK, Buckley NA, Page CB, Scorgie FE, Lincz LF, Seldon M, Brown SGA for the ASP Investigators. A randomised controlled trial of fresh frozen plasma for treating venom induced consumption coagulopathy in Australian snakebite (ASP-18). J Thromb Haemost. 2013 Jul;11(7):1310-8.
  19. Johnston CI, Brown SGA, O'Leary MA, Currie BJ, Greenberg R, Taylor M, Barnes C, White J, Isbister GK for the ASP investigators. Mulga snake (Pseudechis australis) envenoming: a spectrum of myotoxicity, anticoagulant coagulopathy, haemolysis and the role of early antivenom therapy - Australian Snakebite Project (ASP-19). Clin Toxicol (Phila). 2013 Jun;51(5):417-24

Other publications


  1. O'Rourke KM, Correlje E, Martin CL, Robertson JD, Isbister GK. Point-of-care derived INR does not reliably detect significant coagulopathy following Australian snakebite. Thromb Res. 2013 Sep 10. doi:pii: S0049-3848(13)00404-0. 10.1016/j.thromres.2013.09.004. [Epub ahead of print]
  2. Cubitt M, Armstrong J, McCoubrie D, White J, Williams V, Isbister GK. Point-of-care testing in snakebite: an envenomed case with false negative coagulation studies. Emerg Med Australas. 2013 Aug;25(4):372-3. doi: 10.1111/1742-6723.
  3. Isbister GK, Maduwage K, Shahmy S, Mohamed F, Abeysinghe C, Karunathilake H, Ariaratnam CA, Buckley NA. Diagnostic 20-min whole blood clotting test in Russell's viper envenoming delays antivenom administration. QJM. 2013 Oct;106(10):925-32. doi: 10.1093/qjmed/hct102. Epub 2013 May 14.
  4. Chaisakul J, Isbister GK, Konstantakopoulos N, Tare M, Parkington HC, Hodgson WC. In vivo and in vitro cardiovascular effects of Papuan taipan (Oxyuranus scutellatus) venom: Exploring "sudden collapse". Toxicol Lett. 2012 Sep 3;213(2):243-8. doi: 10.1016/j.toxlet.2012.06.015. Epub 2012 Jul 3.
  5. Barber CM, Isbister GK, Hodgson WC. Solving the 'Brown snake paradox': in vitro characterisation of Australasian snake presynaptic neurotoxin activity. Toxicol Lett. 2012 May 5;210(3):318-23. doi: 10.1016/j.toxlet.2012.02.001. Epub 2012 Feb 10.
  6. Casamento AJ, Isbister GK. Thrombotic microangiopathy in two tiger snake envenomations. Anaesth Intensive Care. 2011 Nov;39(6):1124-7


1. Isbister GK, O'leary MA, Schneider JJ, Brown SG, Currie BJ; on behalf of the ASP Investigators. Efficacy of antivenom against the procoagulant effect of Australian brown snake (Pseudonaja sp.) venom: In vivo and in vitro studies. Toxicon 2007 Jan;49(1):57-67.
2. Isbister GK, Williams V, Brown SGA, White J, Currie BJ. Clinically applicable laboratory end-points for treating snakebite coagulopathy. Pathology 2006;38(6):568–572
3. Isbister GK, Little M, Cull G, McCoubrie D, Lawton P, Ferenc SF, Kennedy J, Trethewy C, Luxton G, Brown SGA, Currie BJ. Thrombotic microangiopathy from Australian Brown Snake (Pseudonaja) Envenoming
Intern Med J. 2007 Aug;37(8):523-8.
4. Isbister GK, Brown SGA, MacDonald E, White J, Currie BJ for the ASP Investigators. Current use of Australian snake antivenoms and frequency of immediate-type hypersensitivity reactions and anaphylaxis. Med J Aust 2008; 188(8):473-6 IF:2.582
5.
Brown SGA, Caruso N, Borland ML, McCoubrie DL, Celenza A, Isbister GK. Clotting factor replacement and recovery from snake venom induced consumption coagulopathy. Intensive Care Med. 2009 Sep;35(9):1532-8.
6. Isbister GK, Brown SGA, Duffull SB. Failure of antivenom to improve recovery in Australian snakebite coagulopathy. QJM. 2009 Aug;102(8):563-8
7. Gan M, O’Leary MA, Brown SGA, Jacoby T, Spain D, Tankel A, Gavaghan C, Garret P, Isbister GK. Rough scale snake (Tropidechis carinatus) envenoming: a series of confirmed cases. Med J Aust. 2009 Aug 3;191(3):183-6
8. Kulawickrama S, O’Leary MA, Hodgson,WC, Brown SGA, Jacoby T , Davern,K, Isbister GK. Development of a sensitive enzyme immunoassay for measuring taipan venom in serum. Toxicon. 2010 Jul;55(8):1510-8.
9. Ireland G, Brown SGA, Buckley NA, Stormer J, Currie BJ, White J, Spain D, Isbister GK. Changes in serial laboratory test results in snakebite patients: when can we safely exclude envenoming? Med J Aust 2010 Sep 6;193(5):285-90
10. Isbister GK, Scorgie FE, O'Leary MA, Seldon M, Brown SG, Lincz LF; for the ASP Investigators. Factor deficiencies in venom induced consumption coagulopathy resulting from Australian elapid envenomation: Australian Snakebite Project (ASP-10). J Thromb Haemost. 2010 Nov;8:2504-2513
11. Churchman A, O’Leary MA, Buckley NA, Page CP, Tankel A, Gavaghan C, Holdgate A, Brown SGA, Isbister GK Clinical effects of red-bellied black snake (Pseudechis porphyriacus) envenoming and correlation with venom concentrations: Australian snakebite project (ASP-11). Med J Aust. 2010 Dec 6;193(11-12):696-700
12. Isbister GK, White J, Currie BJ, O'Leary MA, Brown SG; for the ASP Investigators. Clinical effects and treatment of envenoming by Hoplocephalus spp. snakes in Australia: Australian Snakebite Project (ASP-12). Toxicon.
2011 Dec 1;58(8):634-40.

13. Isbister GK, O’Leary MA, Elliott M, Brown SGA. Tiger Snake (Notechis spp) Envenoming: Australian snakebite project (ASP-13). Med J Aust. 2013 Mar 4;198(4):194-5.
14. Allen GE, O’Leary MA, Brown SGA, Buckley NA, Currie BJ, White J, Isbister GK. Brown snake (Pseudonaja spp.) envenoming: clinical effects and antivenom dosing - Australian snakebite project (ASP-14). PLoS One. 2012;7(12):e53188.
15. Isbister GK, Brown SGA. Bites in Australian snake handlers - Australian snakebite project (ASP-15). QJM. 2012 Nov;105(11):1089-95.
16.
Johnston CI, O'Leary MA, Brown SGA, Currie BJ, Isbister GK for the ASP investigators. Death adder envenoming causes neurotoxicity not reversed by antivenom - Australian Snakebite Project (ASP-16). PLoS Negl Trop Dis. 2012;6(9):e1841.
17. Gulati A, Isbister GK, Duffull SB. Effect of Australian elapid venoms on blood coagulation: Australian Snakebite Project (ASP-17). Toxicon. 2013 Jan;61:94-104.
18.
Isbister GK, Buckley NA, Page CB, Scorgie FE, Lincz LF, Seldon M, Brown SGA for the ASP Investigators. A randomised controlled trial of fresh frozen plasma for treating venom induced consumption coagulopathy in Australian snakebite (ASP-18). J Thromb Haemost. 2013 Jul;11(7):1310-8.
19. Johnston CI, Brown SGA, O'Leary MA, Currie BJ, Greenberg R, Taylor M, Barnes C, White J, Isbister GK for the ASP investigators. Mulga snake (Pseudechis australis) envenoming: a spectrum of myotoxicity, anticoagulant coagulopathy, haemolysis and the role of early antivenom therapy - Australian Snakebite Project (ASP-19). Clin Toxicol (Phila). 2013 Jun;51(5):417-24