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Snakebite…
Now what?
A Talk by Chris Nickson
No $
“Julius Caesar and the Crossing of the Rubicon,” Francesco Granacci, 1494
Assessment
Is the patient
      envenomed?

If so, what antivenom &
  treatment is needed?




                      Photo by Iguana Joe
Snake bite


         Lymphatics


Non-specific Systemic Features


Specific Envenoming Syndromes
Specific Envenoming Syndromes

     Venom-induced
     Consumptive Coagulopathy
     Anticoagulation
     Neurotoxicity
     Myotoxicity
     Others
Does he look sick?




Photo by JD Hancock
Life Threats

  Hypotension
Respiratory failure
     Seizure
  Haemorrhage
Assessment
         Geographic area
      Anatomic site of bite
        Number of strikes
            Use of PIB
Pre-hospital course and treatment
       Previous snakebites
        Systemic features
          Investigations
Brown snake      Taipan
Pseudonaja spp   Oxyuranus spp




Tiger snake
Notechis spp
Death Adder                   Sea Snakes
Acanthophis spp               Hydrophiidae




Black snake       Photo by
Pseudechis spp    Gnangarra
Investigations
   Whole blood clotting test
Coagulation profile (INR, APTT)
  Fibrinogen, D-Dimer, FDPs
       Full blood count
       Creatine kinase
 Renal function and urinalysis
   Lactate Dehydrogenase
  Venom Detection Kit (VDK)
VDK does NOT tell
you if a patient is
   envenomed
If envenomed…
  VDK is an aid to
     monovalent
antivenom selection
First
 Aid
Pressure Immobilisation Bandage


          PIB
Warrell DA. Treatment of bites by adders and exotic venomous snakes. BMJ. 2005 Nov
26;331(7527):1244-7.
Management
Not envenomed

      Remove PIB
   Serial examination
 Serial laboratory tests
  Observe for 12 hours
Envenomed

    Address life threats
        Replace PIB
      Give Antivenom
     Serial assessment
Seek and treat complications
Antivenom
  Indications
      Collapse
    Coagulopathy
      Paralysis
   Rhabdomyolysis
Protracted GI distress
Which Antivenom to give?

          1. Geography
       2. Clinical features
     3. Laboratory findings
http://www.kingsnake.com/aho/species/extras/budden.html
What about the
   snake?
How to give
    Antivenom
    Resuscitation area

        2 x IV lines

Give in 500 mL normal saline
         over 20 min
Give
Monovalent
if Possible
Severe
Anaphylaxis
1%         Monovalent


5%           Polyvalent
 Isbister et al. MJA 2008; 188: 437-476
Polyvalent
   Antivenom
Appropriate monovalent AV
      not available


 Need >2 monovalent AV
          and
No SVDK or no time to wait
Premedication?   Photo by Gaptone
Does
Antivenom
  Work?
Efficacy
            Inefficacious antivenom?
            Irreversible venom effect?
            Rapid onset venom effect?




Effectiveness
Isbister GK. Antivenom efficacy or effectiveness: the Australian experience.
Toxicology. 2010 Feb 9;268(3):148-54.
Yeung JM, Little M, Murray LM, Jelinek GA, Daly FF. Antivenom dosing in
35 patients with severe brown snake (Pseudonaja) envenoming in Western
Australia over 10 years. Med J Aust. 2004 Dec 6-20;181(11-12):703-5.
Expect >8 hours until
 fibrinogen returns




   Isbister et al. Pathology (2006) 38(6) 568-572
FFP: Fuel for the Fire?
Don’t forget
  ASP
THE
      END
http://lifeinthefastlane.
com/education/toxicolo
           gy/



                            Photo by Peter Firminger

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Snakebite... Now what?

  • 1. Snakebite… Now what? A Talk by Chris Nickson
  • 3. “Julius Caesar and the Crossing of the Rubicon,” Francesco Granacci, 1494
  • 5. Is the patient envenomed? If so, what antivenom & treatment is needed? Photo by Iguana Joe
  • 6. Snake bite Lymphatics Non-specific Systemic Features Specific Envenoming Syndromes
  • 7. Specific Envenoming Syndromes Venom-induced Consumptive Coagulopathy Anticoagulation Neurotoxicity Myotoxicity Others
  • 8. Does he look sick? Photo by JD Hancock
  • 9. Life Threats Hypotension Respiratory failure Seizure Haemorrhage
  • 10. Assessment Geographic area Anatomic site of bite Number of strikes Use of PIB Pre-hospital course and treatment Previous snakebites Systemic features Investigations
  • 11. Brown snake Taipan Pseudonaja spp Oxyuranus spp Tiger snake Notechis spp
  • 12. Death Adder Sea Snakes Acanthophis spp Hydrophiidae Black snake Photo by Pseudechis spp Gnangarra
  • 13. Investigations Whole blood clotting test Coagulation profile (INR, APTT) Fibrinogen, D-Dimer, FDPs Full blood count Creatine kinase Renal function and urinalysis Lactate Dehydrogenase Venom Detection Kit (VDK)
  • 14. VDK does NOT tell you if a patient is envenomed
  • 15. If envenomed… VDK is an aid to monovalent antivenom selection
  • 18. Warrell DA. Treatment of bites by adders and exotic venomous snakes. BMJ. 2005 Nov 26;331(7527):1244-7.
  • 20. Not envenomed Remove PIB Serial examination Serial laboratory tests Observe for 12 hours
  • 21. Envenomed Address life threats Replace PIB Give Antivenom Serial assessment Seek and treat complications
  • 22. Antivenom Indications Collapse Coagulopathy Paralysis Rhabdomyolysis Protracted GI distress
  • 23. Which Antivenom to give? 1. Geography 2. Clinical features 3. Laboratory findings http://www.kingsnake.com/aho/species/extras/budden.html
  • 24. What about the snake?
  • 25. How to give Antivenom Resuscitation area 2 x IV lines Give in 500 mL normal saline over 20 min
  • 27. Severe Anaphylaxis 1% Monovalent 5% Polyvalent Isbister et al. MJA 2008; 188: 437-476
  • 28. Polyvalent Antivenom Appropriate monovalent AV not available Need >2 monovalent AV and No SVDK or no time to wait
  • 29. Premedication? Photo by Gaptone
  • 31. Efficacy Inefficacious antivenom? Irreversible venom effect? Rapid onset venom effect? Effectiveness Isbister GK. Antivenom efficacy or effectiveness: the Australian experience. Toxicology. 2010 Feb 9;268(3):148-54.
  • 32. Yeung JM, Little M, Murray LM, Jelinek GA, Daly FF. Antivenom dosing in 35 patients with severe brown snake (Pseudonaja) envenoming in Western Australia over 10 years. Med J Aust. 2004 Dec 6-20;181(11-12):703-5.
  • 33. Expect >8 hours until fibrinogen returns Isbister et al. Pathology (2006) 38(6) 568-572
  • 34. FFP: Fuel for the Fire?
  • 36. THE END http://lifeinthefastlane. com/education/toxicolo gy/ Photo by Peter Firminger

Notas do Editor

  1. 5% to 10% of snakebite patients develop severe envenoming
  2. Emerg Med Australas. 2009 Jun;21(3):184-90.Investigating pressure bandaging for snakebite in a simulated setting: bandage type, training and the effect of transport.Canale E, Isbister GK, Currie BJ.SourceTropical Toxinology Program, Menzies School of Health Research, Charles Darwin University, and Northern Territory Clinical School, Royal Darwin Hospital, Darwin, Northern Territory, Australia.AbstractBACKGROUND: The clinical evidence base for the use of pressure bandaging in snakebite is limited. We aimed to investigate if pressure bandages (PB) generated and maintained presumptive optimal pressures in a simulated setting.METHODS: A total of 96 subjects were recruited, 78 health professionals and 18 from the general public. Participants were asked to apply PB with crepe and with an elasticized bandage without instruction. A paediatric blood pressure cuff attached to a pressure transducer was used to measure the pressure generated. PB application with elasticized bandages was repeated by 36 participants (18 general public and 18 health professionals) with feedback on pressures attained, and reassessment on the sixth subsequent attempt. Pressure was also measured under correctly applied bandages during an ambulance ride.RESULTS: The median pressure generated under crepe bandages was 28 mmHg (interquartile range [IQR]: 17-42 mmHg) compared with 47 mmHg (IQR 26-83 mmHg) with elasticized bandages, with most subgroups applying the elasticized bandage closer to the estimated optimal pressure (55-70 mmHg). Following training, the median pressure for the 36 participants was 65 mmHg (IQR 56-71 mmHg), closer to the optimal range than initial attempts. On initial bandaging, 5/36 (14%) participants achieved optimal pressure range with elasticized bandages, compared with 18/36 (50%) after training (P = 0.002). Crepe bandages initially correctly applied did not maintain desired pressure during ambulance transport on urban roads over 30 min. Elasticized bandages maintained pressure.CONCLUSIONS: PB was poorly done by the general public and health professionals. Crepe bandages rarely generated optimal pressures compared with elasticized bandages, but training did improve participants' ability to apply elasticized bandages. PB recommendations should be modified to specify appropriate bandage types.Emerg Med Australas. 2008 Jun;20(3):267-70.Effectiveness of pressure-immobilization first aid for snakebite requires further study.Currie BJ, Canale E, Isbister GK.SourceTropical Toxinology Program, Menzies School of Health Research, Charles Darwin University, Northern Territory, Australia. bart@menzies.edu.auAbstractIn the prospective Royal Darwin Hospital snakebite study, pressure-immobilization first aid (PI) was used more often than in previous studies. However, bandages were not uncommonly too loose or not applied to the whole limb and immobilization was often neglected. While PI should continue to be promoted as the standard for Australia for the present, prospective multicentre studies of snakebite with quantitative assays for blood venom concentration will hopefully better elucidate the real effectiveness of PI and define the limitations of timing of application and determine the optimum types of bandage materials to use and the pressure required to be maintained.
  3. Photo by Iguana Joe
  4. Snake biteLymphaticsNon-specfic featuresVICC or anticoagulationNeurotoxicityMyotoxicityNephrotoxicity
  5. Snake biteLymphaticsNon-specfic featuresVICC or anticoagulationNeurotoxicityMyotoxicityNephrotoxicity
  6. Is the patient sick?Photo by JD Hancock
  7. ff
  8. ff
  9. ff
  10. Emerg Med Australas. 2009 Jun;21(3):184-90.Investigating pressure bandaging for snakebite in a simulated setting: bandage type, training and the effect of transport.Canale E, Isbister GK, Currie BJ.SourceTropical Toxinology Program, Menzies School of Health Research, Charles Darwin University, and Northern Territory Clinical School, Royal Darwin Hospital, Darwin, Northern Territory, Australia.AbstractBACKGROUND: The clinical evidence base for the use of pressure bandaging in snakebite is limited. We aimed to investigate if pressure bandages (PB) generated and maintained presumptive optimal pressures in a simulated setting.METHODS: A total of 96 subjects were recruited, 78 health professionals and 18 from the general public. Participants were asked to apply PB with crepe and with an elasticized bandage without instruction. A paediatric blood pressure cuff attached to a pressure transducer was used to measure the pressure generated. PB application with elasticized bandages was repeated by 36 participants (18 general public and 18 health professionals) with feedback on pressures attained, and reassessment on the sixth subsequent attempt. Pressure was also measured under correctly applied bandages during an ambulance ride.RESULTS: The median pressure generated under crepe bandages was 28 mmHg (interquartile range [IQR]: 17-42 mmHg) compared with 47 mmHg (IQR 26-83 mmHg) with elasticized bandages, with most subgroups applying the elasticized bandage closer to the estimated optimal pressure (55-70 mmHg). Following training, the median pressure for the 36 participants was 65 mmHg (IQR 56-71 mmHg), closer to the optimal range than initial attempts. On initial bandaging, 5/36 (14%) participants achieved optimal pressure range with elasticized bandages, compared with 18/36 (50%) after training (P = 0.002). Crepe bandages initially correctly applied did not maintain desired pressure during ambulance transport on urban roads over 30 min. Elasticized bandages maintained pressure.CONCLUSIONS: PB was poorly done by the general public and health professionals. Crepe bandages rarely generated optimal pressures compared with elasticized bandages, but training did improve participants' ability to apply elasticized bandages. PB recommendations should be modified to specify appropriate bandage types.Emerg Med Australas. 2008 Jun;20(3):267-70.Effectiveness of pressure-immobilization first aid for snakebite requires further study.Currie BJ, Canale E, Isbister GK.SourceTropical Toxinology Program, Menzies School of Health Research, Charles Darwin University, Northern Territory, Australia. bart@menzies.edu.auAbstractIn the prospective Royal Darwin Hospital snakebite study, pressure-immobilization first aid (PI) was used more often than in previous studies. However, bandages were not uncommonly too loose or not applied to the whole limb and immobilization was often neglected. While PI should continue to be promoted as the standard for Australia for the present, prospective multicentre studies of snakebite with quantitative assays for blood venom concentration will hopefully better elucidate the real effectiveness of PI and define the limitations of timing of application and determine the optimum types of bandage materials to use and the pressure required to be maintained.
  11. Emerg Med Australas. 2009 Jun;21(3):184-90.Investigating pressure bandaging for snakebite in a simulated setting: bandage type, training and the effect of transport.Canale E, Isbister GK, Currie BJ.SourceTropical Toxinology Program, Menzies School of Health Research, Charles Darwin University, and Northern Territory Clinical School, Royal Darwin Hospital, Darwin, Northern Territory, Australia.AbstractBACKGROUND: The clinical evidence base for the use of pressure bandaging in snakebite is limited. We aimed to investigate if pressure bandages (PB) generated and maintained presumptive optimal pressures in a simulated setting.METHODS: A total of 96 subjects were recruited, 78 health professionals and 18 from the general public. Participants were asked to apply PB with crepe and with an elasticized bandage without instruction. A paediatric blood pressure cuff attached to a pressure transducer was used to measure the pressure generated. PB application with elasticized bandages was repeated by 36 participants (18 general public and 18 health professionals) with feedback on pressures attained, and reassessment on the sixth subsequent attempt. Pressure was also measured under correctly applied bandages during an ambulance ride.RESULTS: The median pressure generated under crepe bandages was 28 mmHg (interquartile range [IQR]: 17-42 mmHg) compared with 47 mmHg (IQR 26-83 mmHg) with elasticized bandages, with most subgroups applying the elasticized bandage closer to the estimated optimal pressure (55-70 mmHg). Following training, the median pressure for the 36 participants was 65 mmHg (IQR 56-71 mmHg), closer to the optimal range than initial attempts. On initial bandaging, 5/36 (14%) participants achieved optimal pressure range with elasticized bandages, compared with 18/36 (50%) after training (P = 0.002). Crepe bandages initially correctly applied did not maintain desired pressure during ambulance transport on urban roads over 30 min. Elasticized bandages maintained pressure.CONCLUSIONS: PB was poorly done by the general public and health professionals. Crepe bandages rarely generated optimal pressures compared with elasticized bandages, but training did improve participants' ability to apply elasticized bandages. PB recommendations should be modified to specify appropriate bandage types.Emerg Med Australas. 2008 Jun;20(3):267-70.Effectiveness of pressure-immobilization first aid for snakebite requires further study.Currie BJ, Canale E, Isbister GK.SourceTropical Toxinology Program, Menzies School of Health Research, Charles Darwin University, Northern Territory, Australia. bart@menzies.edu.auAbstractIn the prospective Royal Darwin Hospital snakebite study, pressure-immobilization first aid (PI) was used more often than in previous studies. However, bandages were not uncommonly too loose or not applied to the whole limb and immobilization was often neglected. While PI should continue to be promoted as the standard for Australia for the present, prospective multicentre studies of snakebite with quantitative assays for blood venom concentration will hopefully better elucidate the real effectiveness of PI and define the limitations of timing of application and determine the optimum types of bandage materials to use and the pressure required to be maintained.
  12. Prospective multi-centre study of snakebite in Australia with over 60 hospitals involved Aims:To investigate appropriate use and safety of snake AVsTo investigate efficacy and safety of FFP for treatment of severe VICCAny patient >2 years of age with definite or suspected snakebiteTake extra blue and red tube with any bloodsCall ASP investigatorConsent patient or NOK ASAP and faxStart datasheetsHistory, management, clinical features, adverse reactions, VDKIf INR/ PT/ aPTT twice normal and high D-dimerthen extra bloods, 2 vials AV, randomise to FFP or notComplete datasheets and fax
  13. Warrell DA. Treatment of bites by adders and exotic venomous snakes. BMJ. 2005 Nov 26;331(7527):1244-7.No patient who received early and appropriate PIB has subsequently diedKeep patient calm and stillDo no harmTourniquets, ice, cutting, sucking, electric shocksPressure immobilisation bandaging (PIB)Entire limbImmobilise limb and rest of patient!Trunk bitesLocal pressure, adrenaline sc (0.5 mL 1:10,000)Don’t wash wound!Transport to appropriate hospital:Skilled and willing Doctor24-hour lab facilitiesAntivenom available
  14. Emerg Med Australas. 2009 Jun;21(3):184-90.Investigating pressure bandaging for snakebite in a simulated setting: bandage type, training and the effect of transport.Canale E, Isbister GK, Currie BJ.SourceTropical Toxinology Program, Menzies School of Health Research, Charles Darwin University, and Northern Territory Clinical School, Royal Darwin Hospital, Darwin, Northern Territory, Australia.AbstractBACKGROUND: The clinical evidence base for the use of pressure bandaging in snakebite is limited. We aimed to investigate if pressure bandages (PB) generated and maintained presumptive optimal pressures in a simulated setting.METHODS: A total of 96 subjects were recruited, 78 health professionals and 18 from the general public. Participants were asked to apply PB with crepe and with an elasticized bandage without instruction. A paediatric blood pressure cuff attached to a pressure transducer was used to measure the pressure generated. PB application with elasticized bandages was repeated by 36 participants (18 general public and 18 health professionals) with feedback on pressures attained, and reassessment on the sixth subsequent attempt. Pressure was also measured under correctly applied bandages during an ambulance ride.RESULTS: The median pressure generated under crepe bandages was 28 mmHg (interquartile range [IQR]: 17-42 mmHg) compared with 47 mmHg (IQR 26-83 mmHg) with elasticized bandages, with most subgroups applying the elasticized bandage closer to the estimated optimal pressure (55-70 mmHg). Following training, the median pressure for the 36 participants was 65 mmHg (IQR 56-71 mmHg), closer to the optimal range than initial attempts. On initial bandaging, 5/36 (14%) participants achieved optimal pressure range with elasticized bandages, compared with 18/36 (50%) after training (P = 0.002). Crepe bandages initially correctly applied did not maintain desired pressure during ambulance transport on urban roads over 30 min. Elasticized bandages maintained pressure.CONCLUSIONS: PB was poorly done by the general public and health professionals. Crepe bandages rarely generated optimal pressures compared with elasticized bandages, but training did improve participants' ability to apply elasticized bandages. PB recommendations should be modified to specify appropriate bandage types.Emerg Med Australas. 2008 Jun;20(3):267-70.Effectiveness of pressure-immobilization first aid for snakebite requires further study.Currie BJ, Canale E, Isbister GK.SourceTropical Toxinology Program, Menzies School of Health Research, Charles Darwin University, Northern Territory, Australia. bart@menzies.edu.auAbstractIn the prospective Royal Darwin Hospital snakebite study, pressure-immobilization first aid (PI) was used more often than in previous studies. However, bandages were not uncommonly too loose or not applied to the whole limb and immobilization was often neglected. While PI should continue to be promoted as the standard for Australia for the present, prospective multicentre studies of snakebite with quantitative assays for blood venom concentration will hopefully better elucidate the real effectiveness of PI and define the limitations of timing of application and determine the optimum types of bandage materials to use and the pressure required to be maintained.
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  17. AV for: colapse, coagulopathy, neurotoxicityAnd rhabdomyolysis (: CK >5000)Also refractory GI symptoms from Black Snake
  18. http://www.kingsnake.com/aho/species/extras/budden.html
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  20. Antivenom inefficacyIrreversible venom-mediated effects Inability of antivenom to reach venom target Rapid venom onsetMismatch of venom and antivenom pharmacokinetics The inability of the antibodies in the antivenom to bind the toxins in the venom. This appears to be rare. Toxin injury that is irreversible such as pre-synaptic neurotoxicity (nerve terminal destruction) (Kuruppu et al., 2008), myotoxicity or renal injury (Isbister et al., 2007a). This can occur with venom-mediated injury at the bite site or when toxin molecules are much smaller than antivenom molecules (e.g. short chain neurotoxins compared to IgG molecules) (Chippaux and Goyffon, 1998). Rapid onset of envenoming such that antivenom is unable to prevent or reverse severe or life-threatening effects, such as in cardiac toxicity from box jellyfish (Winter et al., 2009). This will manifest as “recurrence” and is thought to occur when there is ongoing venom absorption after antivenom has been eliminated. This is usually only a problem with the rapidly eliminated Fab type antivenoms (Boyer et al., 2001). Brown snake AV is highly efficaciousSpirulivis et al 1996 found that antivenom couldn’t neutralise venom in vitro – this lead to concerns that 10 to 25 amps of brown snake antiveno might be required to neutraliseantivenom but subsequently shown they were using way to much antivenom
  21. Antivenom inefficacyIrreversible venom-mediated effects Inability of antivenom to reach venom target Rapid venom onsetMismatch of venom and antivenom pharmacokinetics The inability of the antibodies in the antivenom to bind the toxins in the venom. This appears to be rare. Toxin injury that is irreversible such as pre-synaptic neurotoxicity (nerve terminal destruction) (Kuruppu et al., 2008), myotoxicity or renal injury (Isbister et al., 2007a). This can occur with venom-mediated injury at the bite site or when toxin molecules are much smaller than antivenom molecules (e.g. short chain neurotoxins compared to IgG molecules) (Chippaux and Goyffon, 1998). Rapid onset of envenoming such that antivenom is unable to prevent or reverse severe or life-threatening effects, such as in cardiac toxicity from box jellyfish (Winter et al., 2009). This will manifest as “recurrence” and is thought to occur when there is ongoing venom absorption after antivenom has been eliminated. This is usually only a problem with the rapidly eliminated Fab type antivenoms (Boyer et al., 2001). Brown snake AV is highly efficaciousSpirulivis et al 1996 found that antivenom couldn’t neutralise venom in vitro – this lead to concerns that 10 to 25 amps of brown snake antiveno might be required to neutraliseantivenom but subsequently shown they were using way to much antivenom
  22. Contains 1 amp of each monovalent, expensive, high protein load, less specific
  23. Given the low prevalence of severe anaphylactic and anaphylactoid reactions to CSL antivenoms (1% for monovalent; 5% for polyvalent), premedication to prevent allergic reactions is not routinely indicatedPatients who receive snake antivenom are counselled about the possibility of serum sickness 4-21 days after antivenom administration. Prednisolone 1 mg/kg/day (up to 50 mg/day) for five days may attenuate the severity of serum sickness. Photo by Gaptone
  24. Antivenom inefficacyIrreversible venom-mediated effects Inability of antivenom to reach venom target Rapid venom onsetMismatch of venom and antivenom pharmacokinetics The inability of the antibodies in the antivenom to bind the toxins in the venom. This appears to be rare. Toxin injury that is irreversible such as pre-synaptic neurotoxicity (nerve terminal destruction) (Kuruppu et al., 2008), myotoxicity or renal injury (Isbister et al., 2007a). This can occur with venom-mediated injury at the bite site or when toxin molecules are much smaller than antivenom molecules (e.g. short chain neurotoxins compared to IgG molecules) (Chippaux and Goyffon, 1998). Rapid onset of envenoming such that antivenom is unable to prevent or reverse severe or life-threatening effects, such as in cardiac toxicity from box jellyfish (Winter et al., 2009). This will manifest as “recurrence” and is thought to occur when there is ongoing venom absorption after antivenom has been eliminated. This is usually only a problem with the rapidly eliminated Fab type antivenoms (Boyer et al., 2001). Brown snake AV is highly efficaciousSpirulivis et al 1996 found that antivenom couldn’t neutralise venom in vitro – this lead to concerns that 10 to 25 amps of brown snake antiveno might be required to neutraliseantivenom but subsequently shown they were using way to much antivenom
  25. Antivenom inefficacyIrreversible venom-mediated effects Inability of antivenom to reach venom target Rapid venom onsetMismatch of venom and antivenom pharmacokinetics The inability of the antibodies in the antivenom to bind the toxins in the venom. This appears to be rare. Toxin injury that is irreversible such as pre-synaptic neurotoxicity (nerve terminal destruction) (Kuruppu et al., 2008), myotoxicity or renal injury (Isbister et al., 2007a). This can occur with venom-mediated injury at the bite site or when toxin molecules are much smaller than antivenom molecules (e.g. short chain neurotoxins compared to IgG molecules) (Chippaux and Goyffon, 1998). Rapid onset of envenoming such that antivenom is unable to prevent or reverse severe or life-threatening effects, such as in cardiac toxicity from box jellyfish (Winter et al., 2009). This will manifest as “recurrence” and is thought to occur when there is ongoing venom absorption after antivenom has been eliminated. This is usually only a problem with the rapidly eliminated Fab type antivenoms (Boyer et al., 2001). Brown snake AV is highly efficaciousSpirulivis et al 1996 found that antivenom couldn’t neutralise venom in vitro – this lead to concerns that 10 to 25 amps of brown snake antiveno might be required to neutralise antivenom but subsequently shown they were using way to much antivenom
  26. Yeung JM, Little M, Murray LM, Jelinek GA, Daly FF. Antivenom dosing in 35 patients with severe brown snake (Pseudonaja) envenoming in Western Australia over 10 years. Med J Aust. 2004 Dec 6-20;181(11-12):703-5.This lead to large amounts of antivenom being used. This observational study by Yeung et al led to the conclusion that an initial dose of 10 amps is appropriateIn clinical practice, this seemed valid because serial measurements of coags should recovery was delayed, necessitating repeat doses.However, there were flaws in the logic leading to this situation:Spirulivis 1996 and Tibballs and Sutherland 1991 used excessive concentrations of venom – probably 10-100 times ! - This has been confirmed by measuring venom levels in envenomed patients.It is reassuring that Tibballs and Sutheralnd found some effect with 10-25 amps – suggesting that 1 amp is OK.The other issue is that we now know that recovery from VICC can take up 12-18h – coagulopathy will still be present regardless of antivenomadminsitration before this time.Subsequent in vitro studies by Isbister suggest that 1 amp is sufficient to neutraliseprocoagulant levels typically found in envenomed humansSimilar concerns – due to the same fallacies – have been held about tiger snake venom. It seems that one amp is enough.
  27. Photo by Vermin IncFFP arm of ASP – seems reasonable now that evidence suggests procoagulant venom is rapidly dactivatedTraditionally withheld until all circulating venom is neutralised by AVASP may change this…Traditionally 4-8 hour recovery time for coagulation factorsWhat is the endpoint for venom neutralisation?
  28. Prospective multi-centre study of snakebite in Australia with over 60 hospitals involved Aims:To investigate appropriate use and safety of snake AVsTo investigate efficacy and safety of FFP for treatment of severe VICCAny patient >2 years of age with definite or suspected snakebiteTake extra blue and red tube with any bloodsCall ASP investigatorConsent patient or NOK ASAP and faxStart datasheetsHistory, management, clinical features, adverse reactions, VDKIf INR/ PT/ aPTT twice normal and high D-dimerthen extra bloods, 2 vials AV, randomise to FFP or notComplete datasheets and fax