Another Bloody Snakebite

aka Toxicology Conundrum 052

A 30 year-old man was walking alone in rural New South Wales, Australia.

He was startled by a brown-coloured snake and stepped backwards into a nearby bush. He didn’t see the snake bite him, but as it slithered away he noticed blood oozing from a scratch on his leg.

He anxiously walked to his car, and drove to the nearest hospital, arriving 45 minutes later.

Questions

Q1. Would you apply a pressure immobilization bandage (PIB) on arrival at the hospital?

Yes – there is little to lose.

This patient has been moving around for 45 minutes after a possible snakebite. Chances are that applying a PIB at this point won’t do much in terms of decreasing systemic absorption of snake venom – probably a case of shutting the gate after the horse has bolted.

Exactly how long after a bite a PIB will be effective is debatable, and probably depends on how mobile the patient was in the interim. Some snakebite experts have suggested that PIB may be ineffective if applied after 30-45 minutes in most settings.

However there is an argument that any potential snakebite, whatever the time of presentation (within reason) should have PIB applied. This helps to:

  • (perhaps) limit ongoing systemic absorption of venom from the bite site and the nearby lymphatics.
  • maintain skills in PIB application among staff
  • reinforce its importance to staff, the patient and the general public that PIB is a useful first aid measure

The patient is anxious and feels nauseated. A small amount of blood is oozing from the scratch mark near his right ankle. His right inguinal lymph nodes are mildly tender. There is no evidence of bleeding from other sites and his cranial nerve exam is normal.

His blood tests show the following:

Q2. Describe and interpret these blood results. Given the clinical context, what Australian snakes, if any, are these results consistent with?

There is evidence of venom-induced consumptive coagulopathy (VICC):

  • Immeasurably high INR and aPTT with an unmeasurable fibrinogen and positive D-dimer.
  • This cannot be anticoagulation due to a black snake, because fibrinogen would be normal.

The presence of VICC limits the possible snake envenoming syndromes to those of brown snakes, tiger snakes and taipans. The latter can be supposedly excluded based on geography (there may be areas of NSW where the Inland Taipan is present – bites by this, the snake with the most lethal venom of any in the world, are extremely rare). An inland taipan bite in NSW featured in the news recently.

The full blood count is suggestive of thrombotic microangiopathy resulting in microangiopathic hemolytic anemia (Hb 95) and thrombocytopenia (plt 60). Further tests are needed to confirm hemolysis (e.g. blood film, LDH, Hb in urine, haptoglobin). Leucocytosis (WBC 12.3) is a non-specific finding in possible snakebite.

Any of the snakes that cause VICC can cause MAHA. It is rare, but when present is usually in the context of delayed presentations (unlike this scenario!).

The UEC, with an elevated creatinine (Cr 190) is consistent with . This could be due to direct nephrotoxicity (thought to occur in brown snake envenoming, and possibly Tigers and Taipans), due to myotoxicity resulting in rhabdomyolysis (this would exclude brown snake envenoming), or due to MAHA.

MAHA is the most likely cause of renal impairment in this setting. Most patients will require renal replacement therapy but most will recover after a few weeks.

The combination of VICC with thrombotic microangiopathy mimics disseminated intravascular coagulation (DIC).

Conclusion

Based on geography and the available clinical and laboratory data the patient has evidence of systemic envenoming by a Brown Snake or a Tiger snake.

Q3. What is the role of the snake venom detection kit (VDK) in the assessment and management of the possible snakebite patient?

The VDK does NOT indicate that a patient is envenomed.

Envenoming is determined by the presence of characteristic clinical and laboratory features, that are clearly present in this case (see Q2).

The VDK result can help decide which antivenom to give, IF the patient is envenomed.

Antivenom selection is based on:

  • Geography (different snakes have different geographic distributions)
  • Clinical and laboratory features (consistent with the specific envenoming syndromes of different types of snake)
  • VDK result

In my opinion, the VDK is the LEAST important of the three.

Except in rare circumstances (e.g. when a recognized snake expert is available), snake identification plays no role in antivenom selection. Brown snakes can have stripes and Tiger snakes can be brown…

There is no clinical or laboratory evidence of rhabdomyolysis due to myotoxicity (which may or may not occur in Tiger snake envenoming).

A VDK is performed using a bite site swab. Well 2 turns rapidly turns strongly blue, and is soon followed by Well 7, then after a couple of minutes, Well 1.

CSL VDK (image from CSL packaging)

Q4. What antivenom would you give, and how much?

Brown snake antivenom — the brown snake well is strongly positive and is consistent with the geography, clinical and laboratory features.

It is not unusual for other wells to change colour as well. For this reason it is important that the VDK is observed closely. It is best performed by a laboratory technician rather than a doctor in a busy ED!

If the VDK result doesn’t match the geography, clinical and laboratory data – don’t believe the VDK. Remember Osler, who told us to listen to the patient as he will tell us the diagnosis!

Give brown snake antivenom as follows:

  • Administer 1 ampoule in 500 mL normal saline over 20 minutes in a resuscitation area.
  • Ensure that the patient has 2 working IV lines and that adrenaline is immediately available in case of antivenom anaphylaxis.

Finally, I recommend discussing Australian snake bite cases with a toxicologists via the Poisons Information Center and enrolling patients in the Australian Snakebite Project (ASP). The dose of snake antivenom remains controversial, be guided by a toxicologist.

References

Lifeinthefastlane.com

Journals and Textbooks

  • Canale E, Isbister GK, Currie BJ. Investigating pressure bandaging for snakebite in a simulated setting: bandage type, training and the effect of transport. Emerg Med Australas. 2009 Jun;21(3):184-90. PubMed PMID: 19527277.
  • Isbister GK, Little M, Cull G, McCoubrie D, Lawton P, Szabo F, Kennedy J, Trethewy C, Luxton G, Brown SG, Currie BJ. Thrombotic microangiopathy from Australian brown snake (Pseudonaja) envenoming. Intern Med J. 2007 Aug;37(8):523-8. PubMed PMID: 17640187.
  • Isbister GK. Snakebite doesn’t cause disseminated intravascular coagulation: coagulopathy and thrombotic microangiopathy in snake envenoming. Semin Thromb Hemost. 2010 Jun;36(4):444-51. Epub 2010 Jul 7. Review. PubMed PMID: 20614396.
  • Murray L, Daly FFS, Little M, and Cadogan M. Toxicology Handbook (2nd edition), Elsevier Australia 2011. [Google Books Preview]
  • Sutherland SK, Coulter AR, Harris RD. Rationalisation of first-aid measures for elapid snakebite. Lancet. 1979 Jan 27;1(8109):183-5. PubMed PMID: 84206.
  • Sutherland SK, Harris RD, Coulter AR, Lovering KE. Simple method to delay the movement from the site of injection of low molecular weight substances. Med J Aust. 1980 Jan 26;1(2):81. PubMed PMID: 6767176.
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Comments

  1. says

    Really useful

    For those of us in isolated rural areas, the issue is often whether we are dealing with a ‘stick’ bite or a ‘snake’ bite

    We don;t have access to bloods -- or at least not for 24 hr turnaround

    I still use whole blood clotting time with glass test-tube…and an INR

    Locally only snakes on Kangaroo Island, SA are copperhead and tiger snake -- both respond to tiger snake antivenom, which makes VDK academic…harder is decision to retrieve or not, hence importance of determining snake vs stick bite in absence of APTT/PT

    Thoughts?

    • says

      Tim, stick bites are really a huge problem. Mass hysteria ensues after a confirmed bite in small towns -- every scratch could become a ” bite”.
      I want to see a study into e historical features of the bite. The variables to include: how drunk was the victim, did they actually see a snake, and Parker’s Quotient in snake bites = IQ of the victim is proportional to the distance of the bite from the individual’ s nose divided by the number of bites ( per incident)
      Once I treated a drunk guy who tried to catch ( for ID purposes) the snake that innocently slithered past his foot, it then bit him on the hand and the nose resulting in renal replacement therapy. Calculate that IQ!
      Casey

    • says

      Hi Tim

      Great point about WBCT in places without full laboratory facilities. Probably should put GLASS in capital letters -- as you’ve implied, don’t use plastic tubes as they’re unreliable. In a remote setting WBCT and a careful cranial nerve exam (focusing on the early detection of ptosis) are key in assessing snakebite.

      You mentioned INR -- last I checked point-of-care INR were inaccurate in snake bite envenoming. One of my colleagues was validating such a device for general ED use, it was good except in one case -- a Tiger snake envenoming. I think it gave an INR in the low single digits when it was in fact unmeasurable. I don’t know why.

      As you say VDK adds nothing in Kangaroo Is (unless someone has an unusual pet).

      The requirements for managing snake bite are:

      1. skilled and willing doctor
      2. adequate antivenom stocks
      3. access to appropriate lab test facilities.

      I can’t remember if you have stocks of antivenom on Kangaroo Is. If you do then serial WBCT and serial clinical examination for 12 hours in an asymptomatic patient sounds reasonable. If no antivenom, then discretion is the better part of valour. In all cases I’d phone a friend and determine the plan in conjunction with the toxicologist on call.

      Chris

  2. says

    Yeah, I am with you on INR…but local policy has been to use this….and to take away our glass tubes (deemed too dangerous in case we cut ourselves…hell, am allowed to play with scalpels and mindaltering drugs…but not glass testtubes!)

    Luckily I have a secret stash kept away from hospital administrators…and Julian White as friendlynlocal toxicologist.

    Casey…that snake vs stick bite study could be a goer…

  3. Michael Toolis says

    Nice. Thanks.

    Went to a grand rounds in regional WA two years ago by some FACEMs on snake bites. Some comments were made that the mono-valent and poly-valent antivenoms were actually identical. Any thoughts on this?

    • says

      Hi Michael

      They are not identical but with the exception of sea snake antivenom, which appears to be truly monovalent, it seems that all other monovalent snake antivenoms are actually polyvalent. This is apparently due to the antivenom being harvested from horses that have been exposed to multiple snake venoms. It is still best to treat with the correct specific monovalent antivenom as it guaranteed to have the specified amount amount of the antivenom required. This polyvalency has been found for antivenoms with expiry dates over a 15 year period, however there is no guarantee that it will be the same for future antivenoms. Some have called for a rationalisation of Australian antivenoms -- perhaps just two different antivenoms could be developed that would be sufficient in Australia. Although the monovalent antivenoms have polyvalency they still have a lower protein load than the official polyvalent antivenom, and thus side-effects are less frequent.

      What does this mean practically? Where possible use the correct monovalent antivenom. Use polyvalent if you need to cover 3 or more snakes and do not have time or means of refining the possibilities further. If two different snakes are possible it is probably still best practice to use two monovalent antivenoms -- although brown and tiger snake monovalent antivenoms appear to cross-neutralise due to their actual polyvalency.

      If there are two possible snakes as a cause, the patient is envenomed, and only a single type of monovalent antivenom available and no other -- then it is reasonable to give the monovalent antivenom rather than delay. Similarly if there is only one possible snake as the cause, but only a different monovalent antivenom is available and the patient is envenomed. These situations are unusual however.

      Reference
      O’Leary MA, Isbister GK. Commercial monovalent antivenoms in Australia arepolyvalent. Toxicon. 2009 Aug;54(2):192-5. Epub 2009 Apr 16. Review. PubMed PMID: 19375442.
      http://www.ncbi.nlm.nih.gov/pubmed/19375442

  4. Kerry says

    Thanks Chris for great discussion. As one of those WA FACEM toxicologists Michael has aluded to there a couple of new things to add.

    1. VDK is unreliable and may confuse clinical management. As stated above, positive VDK (even urine VDK) does not indicate envenoming and should not be “treated”. Antivenom selection is based on clinical syndrome and geographical location, VDK is only helpful if it confirms your choice. To make things worse, in a recent series of tiger snake envenoming where venom was detected in serum by radioimmunoassay and compared with VDK results, the VDK was incorrect in 5/44 cases giving a positive result for brown snake venom and resulting in the wrong antivenom being administered (1). Brown and early tiger snake envenoming syndromes can look identical clinically (isolated VICC) so if there is any doubt one vial of each antivenom is recommended. We recommend VDK only be performed after envenoming is confirmed clinically. Negative predictive value has been quoted as 80% (2) so a negative result doesn’t exclude envenoming, and a positive result may be more confusing than helpful. We’ve recently started removing VDK from most hospitals in WA.

    2. Antivenom: While it is true that all monovalent antivenoms are partially polyvalent, we still recommend using the specific antivenom where possible to ensure adequate cover. Polyvalent AV should not be required except in small areas of Australia where browns, tigers and taipans coexist (mostly Qld and NSW) but if that is all you have, go for it (higher risk of anaphylaxis and serum sickness due to the large protein load). Antivenom does not reverse established toxicity (with the exception of post-synaptic neurotoxicity from death adder envenoming) but appears to halt further progression of neurotoxicity, myotoxicity and probably anosmia (black snake group).

    3. Lab tests: Point of care INR and D-dimer machines are not reliable in envenoming. Most POC INR machines are only accurate for INR less than 8.0. Unfortunately, results outside this range tend to default to normal, hence our (now frequent) anecdotal experience of patients returning normal results from POC tests despite complete defibrination. They were designed for monitoring warfarin, so it is perhaps not surprising that they don’t work well for the complex coagulopathy seen from envenoming. Similarly WBCT, while supposedly easy to perform at the bedside is (in my experience) fraught with danger and operator dependant -- assuming you can even find a glass tube. Once again, treat the patient, not the test. Our WA practice is to transfer all patients to a centre where the 3 criteria above (lab, antivenom, willing doctor) are available. RFDS usually discuss cases with us and take appropriate antivenom out with them. While this means we transfer a lot of stick bites around a huge state, we are willing to accept that risk rather than manage a case in an inappropriate area (after all, 5-10 years ago all potential bites came to Perth for a compulsory ICU admission while they had their bloods done and until resolution of their envenoming syndrome, now we manage them all in regional centres or in the emergency observation unit, so it’s still cheaper!).

    4. Stick bites: unfortunately most Aussie snakes don’t leave much of a calling card. The classic VICC patient has incoagulable blood but has no external bite mark and feels completely well (until just before they bleed out and die!). Historical features are often hazy (I’ve seen sober people present with bleeding complications and NO known history of snake contact) and alcohol is usually involved. As a result we take stick bites seriously and any suggestion of snakebite mandates work up +/- transfer, again, a risk we have to wear as it is better than the alternative. We all know the T’s of snake bite: Testosterone, Tequila, Tshirt, Tattoos, Toothless, Teasing, Trailer park, Truck with a gun rack…

    In all seriousness, snake envenoming is one of the fastest changing areas in medicine at present, with new (significantly different) recommendations every season; most of us cannot hope to keep up with the changes and the literature lags behind. It takes 12 hours or more to exclude envenoming (3) and there are anecdotal cases of delayed onset neurotoxicity, so we recommend a minimum 12 hour stay and not discharging patients at night. Please call the poisons centre (131126) or your local toxicology service 24/7 for the most up to date information and management advice (there’s nothing better than a 2am wake up call, as Chris can attest!).

    REFERENCES:

    (1) Isbister GK , O’Leary MA, Elliot M, Brown SGA. Tiger snake (Notechis spp) envenoming: Australian Snakebite Project (ASP-13). MJA 2012; 197: 173–177. http://www.ncbi.nlm.nih.gov/pubmed/22860796

    (2) Sutherland, S. Antivenom use in Australia. Premedication, adverse reactions and the use of venom detection kits. Medical Journal of Australia, 1992;157:734-739. http://www.ncbi.nlm.nih.gov/pubmed/1360618

    (3) Ireland, G. et al. Changes in serial laboratory test results in snakebite patients: when can we safely exclude envenoming? Medical Journal of Australia, 2010;193(5):285-290. http://www.ncbi.nlm.nih.gov/pubmed/20819048

    Kerry

    • Kerry says

      PS. Please consider enrolling all patients in the Australian snakebite project (ASP), where all these changes are originating, as it is only through Australia wide data collection that we can achieve the best outcome for patients. Info through the PIC.
      K

  5. says

    Where to start? First question should be where in NSW as that limits the snakes under consideration. Inland taipan bites to non-keepers are very rare because the snake is hard to locate even within it’s habitat, which is largely in very sparsely populated areas. Tiger snakes (with rare and specific exceptions) are largely limited to wetter areas or near watercourses. Brown snakes range widely and across most habitats, probably why they cause the most bites.

    First aid 45 min post-bite in a person who has been active will have little benefit, but if the patient has arrived at a hospital unable to give antivenom, it should be applied anyway, just in case it might help, given there is no definitive treatment available until retrieval.

    Yes, the labs show classic defibrination coagulopathy, in this case complete defibrination (a much better and established term, in my view, than the new “VICC”). At this early stage this could be any of the snakes you suggested (brown, tiger, taipan). The Hb & platelet levels are suspicious for developing MAHA -- what did the blood film look like? In Australian snakebite (and many snakebites elsewhere) asking for a blood film, not just a Coulter count, is useful, especially looking for spherocytes & schistocytes as evidence of active haemolysis. MAHA is most common after brown snake bites and usually only becomes obvious many hours post-bite, often after the coagulopathy is largely reversed. The etiology is uncertain. We mostly see it in cases treated with antivenom, so there was a suspicion it was associated with antivenom treatment, but I have now seen cases with envenoming, who refused antivenom, who also developed MAHA. In my experience the renal injury in most cases is mild and so many cases do not require haemodialysis. The creatinine & urea climb for several days before trending back towards normal, without a problem of renal output. It is clearly important to watch renal output with a strict fluid balance chart. Again, in my experience, running a snakebite patient on the dry side in the first 12+ hours is a risk for MAHA and concomitant use of alcohol around the time of the bite is a warning flag for MAHA.

    Venom detection is best used when the patient is clearly envenomed and then has a useful role. In deciding which antivenom to use it is always best to have dual routes to your answer. Route 1 is use of a diagnostic algorithm, which basically uses the combination of local & systemic effects to predict the most likely snake(s) involved, which can then be correlated with snakes known from that geographic area. Route 2 is the SVDK. If both routes give the same answer, you can be reasonably confident you know what type of snake and so the best choice of antivenom. If the two routes disagree, you have a problem, so ask an expert (a clinical toxinologist -- via the toxinology dept at the Women’s & Children’s Hospital in Adelaide, or via CSL).

    In this particular case everything fits brown snake and I recommend giving 2 vials (not 1 vial) of CSL Brown Snake Antivenom, or if not available, 1 vial of their polyvalent AV. I strongly disagree with the recommendation from some key members of ASP (and I helped start ASP and remain listed as an ASP member) that 1 vial is enough for all brown snake bites. It may be enough for some cases, but I am very unconvinced by the ASP data that it is enough for all cases, after 35+ years treating snakebites. When considering an AV dose we should consider not the average case, but the most severe case because often we can’t be sure at the outset how severe the case may be. The average moderate envenoming, historically, will usually have a good outcome anyway. What we should be aiming for is ensuring the rarer really severe envenoming will get a good outcome as well. ASP data suggested that brown snakes don’t cause paralysis. Sorry, but they do, albeit rarely, and I speak from experience with cases and knowing the older historic data.

    Why dilute the antivenom to nearly 1:100? I have long recommended about a 1:10 dilution. Sure, for low volume AV like brown snake, it does no harm to have a higher dilution, but that much is unnecessary in my view. Of course if this was also a way of giving an IV fluid load, maybe OK, but wouldn’t it be better to give the IV fluid load separately, through another IV? That way, if you have to temporarily cease the AV infusion because of an adverse reaction, you can still maintain your fluid loading (if a hypotensive reaction then IV fluid push will be needed anyway).

    To the issue of what each antivenom neutralises. When I informed the assembled toxicologists at a PIC meeting in Sydney, some years ago, that due to manufacturing changes CSL antivenoms were no longer mostly true monovalents, there was “shock and horror”. The reality was/is that CSL continually strive for more efficient ways to produce antivenom, to try and control the costs as far as possible, without compromising neutralising ability. They discovered that they could change procedures to reduce volume (a good thing) and that by using polyvalent-immunised horses, they could produce a more reliable supply (a good thing -- horses immunised with only 1 venom were frequently poor responders, so harder to make enough antibody to supply AV needs). Thus, progressively over several years, production switched from monovalent-immunisation to polyvalent-immunisation. The situation now is as follows; brown snake AV comes from horses either polyvalent-immunised or tiger-brown immunised; tiger snake AV comes from either of these same groups of horses, or rarely (not sure if at all now) from tiger snake & sea snake immunised horses (the latter used principally for sea snake antivenom); all other “monovalent AVs (death adder, black, taipan) come from polyvalent-immunised horses. However, and this is an important caveat, for any monovalent AV, the only guaranteed neutralising minimum dose is for the snake group indicated, so you cannot be sure and should not assume that the monovalent AV will have effective neutralising capacity against non-listed snakes. Only polyvalent AV has guaranteed minimum neutralising capacity for all 5 snake venom groups.

    Yes, point-of-care INR etc tests are not reliable in snakebite. We have at least 2 cases from WA and plenty from Qld that show this. This is a major problem in managing snakebite in smaller country hospitals without a lab. WBCT20 may help, but in my experience is not reliable, even using glass tubes. Unfortunately this means retrieving all suspected snakebites from smaller hospitals back to base hospitals with 24hr labs. Why does POC INR not work? Most (maybe all) POC INR systems use a substrate to mimic normal clotting and this does not respond to venom in the same way as normal haemostasis so that it can “see a clot” where none exists, because the venom can directly convert the substrate. Remember that Australian snake venom group C & D procoagulants are very powerful.

    As to sources of information, both SA & NSW have state health dept guidelines on managing snakebite and spiderbite (though now several years old) and CSL are about to release the new edition of the antivenom handbook (it has a new title), which has been expanded from 69 to 326 pages, with much new material and (hopefully) will be the definitive guide for managing envenoming in Australia. Don’t forget the http://www.toxinology.com website as another useful resource.

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