Anti-venom question..

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James1617
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Anti-venom question..

Post by James1617 »

I have heard that in some cases of venomous snake bites that the antivenom can actually make the situation worse. Is this true??

Lets say you are bitten by a copperhead. Not a serious bite. maybe small amount of venom injected.. Would you still need to administer antivenom?

Also I have heard that the more times you are bitten the more you are affected by the next bite.. If this is true then why do people say you can develop somewhat of an immunity?

-James
hellihooks
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Re: Anti-venom question..

Post by hellihooks »

the old species-specific antivenin's were 'horse serum' based, and many people (myself included) suffered allergic reactions to the horse serum, which could be more serious than the venom.
Not nearly as big a problem with the new polyvalent Crofab. jim
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Dan Krull
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Re: Anti-venom question..

Post by Dan Krull »

In this interview I discuss this topic with Daniel E. Keyler who is a Senior Clinical Toxicologist at SafetyCall International (SCI) and Pet Poison Helpline, and considered to be one of the world's leading experts on snake bite.

Take a listen. :)

http://www.herpnation.com/audio/the-dan ... gory=audio


Dan
SAW
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Re: Anti-venom question..

Post by SAW »

These are a couple of questions that do beg for specific answers. Here are some necessarily very truncated answers:

(1) As when treating any acute medical problem, treatment can be viewed as a ratio between risk to the patient and benefit of the considered therapy. Therefore, if a patient with a snakebite has a moderate-severe-envenoming (this is loosely defined in the US in some facilities by a snakebite severity score), the risk of adverse reactions to antivenom will be outweighed by the risk of an untreated envenoming. Therefore, antivenom will be provided. Please appreciate that this is a very general description as this is a voluminous topic. I will add that the clinical severity of a for example crotaline envenoming may be determined by an isolated, precipitous isolated systolic hypotension (sudden and profound fall in blood pressure) just as it may be assessed by a hemorrhagic coagulopathy with patently abnormal labs. Also, while the risks of antivenom are certainly present and occasionally increased in those with allergic tendencies, most of the adverse effects more often seen with antivenoms are related to the effects of providing large volumes and probable autopharmacological effects (e.g. the activation of some substances in the patient's blood such as complement; another long story). This is why provision of large amounts of polyvalent antivenoms is associated with a probable greater incidence of adverse reactions. Of course, those who have received antivenom previously can become sensitised to the source of the antibodies (whether it be ovine [sheep] or equine [horse]). It is correct that Fab2 ovine antivenom (CroFab) produces less adverse reactions, but there is still about a 3-5% rate (this is still, in clinical terms, significant), and this may be dependent on the amount used as well as the patient. The reasonably frequent recurrence phenomenon (e.g.simply, manifestation of coagulopathy days after initial antivenom treatment) that happens in some crotaline envenoming requires the provision of quite a bit of CroFab. Sean Bush and collaborators have just published their results of treating a small number of patients with continuous infusion of CroFab, and although this is subjectively promising, it does require quite a bit more study (again, this could go on for a while...).

(2) Local effects from a "borderline" moderate envenoming present a more difficult call because there are very few data that support the "reversal" of local effects with antivenom. I personally haven't seen this happen, although some other investigators have reported this (it has been an argumentative topic in the past), but I have seen the progression of expanding local effects blunted, but not fully stopped. Therefore, with a rapidly expanding local envenoming administration of antivenom is appropriate clinical practice.

(3) Anaphylaxis to venom antigens (immunogenic proteins) is well-established and can be rapidly fatal independent of the specific toxin effects. There is strong evidence that regular exposure to snake defecate, sheds, body fluids, and, of course, lyophilised venoms (possibly even defecated fangs which contain venom traces) will likely sensitise an individual to venoms. It is sensible to take careful precautions with captive husbandry (e.g. not to inhale aerosolised urates, when handling soiled substrate and moist fresh sheds, etc.) especially of captive venomous species. There is much more to this, but there just isn't the time to detail it further.

(4) Historically, immunity to snake venoms has proven to be transient. With the exception of a few early Australian subjects and, of course, the exceptional and unfortunately late Bill Haast, the natural exposure to venoms (e.g. being bitten, NOT solely with "self-immunization") doesn't seem to produce any lasting/long-term immunity. Some Ecuadorian (and others) tribal peoples have antibodies against venoms of several venomous snakes, but these do not seem to be neutralising populations of immunoglobulins, although this too merits further investigation. It is possible that some indigenous peoples have developed some immunity to repetitively encountered species. I can only say that as a physician, I am wholly against "self-immunization" as some foolishly do, because this is an inherently foolhardy and highly dangerous practice. Some who perform this claim that they are "investigating" the possible health benefits of venom, and of course that is, to be kind, poppycock. In those who are at risk of being bitten, the practice can more likely lead to potentially fatal sensitisation, rather than protection. If the person is involved in career-related risk of envenoming, meticulous care in handling specimens and stringent emergency protocols provide a far more reliable safety margin.

Hope that was of some help to you,
Scott
hellihooks
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Re: Anti-venom question..

Post by hellihooks »

Excellent reply Scott.
My understanding (as of 2010) is that there was a new anti venom/regimen in clinical trials... might that have been the continuous infusion you mentioned?
I had a rather mild Helleri envenomation in 010, which was not deemed severe enough (by Dr Bush) for the trials (I received 5 vials of Crofab, followed by 5 more, 6 hrs later... 24 hrs observation...went herping on the way home ;) )
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However, a month or so later, a lady I know got tagged in the heel by a big speck at her home, and was treated at a local hsp, as a 'dry bite' and she was sent home after like 12 hrs. later that evening she experienced the 'recurrence phenomenon' and was flown to Loma Linda, where she spent the next 6 days. 6 days treatment would certainly suggest (to me) a continuous infusion paradigm?
So... (in a nutshell).. the 'new treatment' was in methodology rather than a new anti venom formulation? thx... jim
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regalringneck
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Re: Anti-venom question..

Post by regalringneck »

... thankyou Dr. Scott for taking the time to type that very comprehensible synopsis, i suggest folks cut n paste it off & have a copy handy for any unexpected detours thru an ER, cuz this aint known everywhere!
We had a case not too long ago here in az-usa where a finger bite from a juvenile crote resulted in death in the ER from (reportedly) hasty infusion of equine based antiserum w/o pre-testing ...
The txt re indigenous people w/ antibodies is very interesting and new to me.
Jim, that looks like a friggn spider bite, get up & walk on outta there, you're make-en us geezers looks like wimps! Someday i must tell my own experience; rooting an iguana out of a ground squirrel hole ... in up to my armpit ... june 20 1975 & not 5 klicks from where we now live!

cheers / rxr
hellihooks
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Re: Anti-venom question..

Post by hellihooks »

Yeah rxr... never even admitted... 36 hrs in ER observation room, before they'd let me leave... :roll: Caught a fang through a bag, from one moment of complacency in the field... :roll: here's as bad as it got...
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What's really ironic is... the snake was only collected for the Crofab reformulation. I will/can confirm that the locale is one of the most 'neurotoxically' potent localities... hardly any pain... but almost instantly 'mind-bending' and almost instantaneously peripherally numbing... within 30 sec hands and feet were numb, and within 60 sec I was literally a 'numbskull'... :lol: :lol: jim
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Kent VanSooy
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Re: Anti-venom question..

Post by Kent VanSooy »

Can a "natural" exposure to venom mean anaphylaxis if the invidual is bitten again ??
SAW
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Re: Anti-venom question..

Post by SAW »

Some interesting comments and recounted experiences. Jim, I am glad that you came out reasonably intact from that significant C. o. helleri envenoming. From the wound and your description, I suspect that you my have had some arthropathy as sequelae, but as you well know, it could have been worse. I only have a few minutes to reply, so I will make this brief and, again, I regret necessarily limited in scope:

(1) Jim, you are correct that there is an additional Fab2 antivenom that is undergoing trials (antivipmyn produced by BioClon; see http://clinicaltrials.gov/show/NCT00639951). It is an equine-derived Fab2 and does show promise. However, as with CroFab, the cost of both products is exorbitant. There has been a long-standing discussion about the possible utility of continuous infusion, but remain cognizant that this does theoretically place the patient at risk. Therefore, one has to have a combination of reasonable safety factor protecting the patient; a willing envenomed patient consenting to try a new approach of therapy, as well as an envenoming that presents with features that would facilitate the assessment of such a new approach. The difficulty in procuring this combination of factors (not including other factors such as the possible need for institutional permission, etc.) is why this has taken some time and, to date, formally includes only 5 patients. The main advantages that this approach may offer, after further study and a larger number of treated cases of varying severity, are the probable need for smaller volumes of antivenom and the inherent management of recurrence.

(2) RXR, I think I am aware of the bite in AZ that you mentioned. One thing-pre-testing is always contraindicated. Very briefly, the reason why this is a useless screen is because, as I briefly mentioned, adverse reactions to antivenom are not commonly IgE-dependent. Meaning, adverse reactions to antivenom are not related to mechanisms of anaphylaxis which are a consequence of cross-linked IgE triggering the mast cell and basophil release of numerous vasoactive substances (e.g. SRSA, histamine, heparin, etc.) and a number of other complex autopharmacological events too extensive to outline here. Of course, as another aside, some bee venoms (e.g. that of Apis mellifera) also contain MDP (mast cell degranulating peptide) and these can trigger anaphylaxis without prior exposure to the antigen (there is a massive amount of mis-information on the Internet regarding this and the immunological implications to venoms, snakebite, etc.). The development of IgE is a result of mnemonic sensitization (development of immune memory cells, specifically a population of beta-plasmocytes), that produce the IgE against a given sensitizing antigen. The lack of relationship of this anaphylaxis mechanism with adverse reactions associated with antivenom is why skin testing has never been accurately predictive of those who might react to antivenom and those who might not. Of course, this may happen, as I alluded in my initial comments, because sensitization to foreign proteins can occur at any time. But, this is almost always the "outlier" case that occurs in those with multiple enevnomings and subsequent antivenom therapy. Thus, this is a special patient population, but this doesn't change the approach to management; it simply increases the scrutiny for adverse reactions. I always have anaphylaxis protocol in place prior to the administration of antivenom, but skin testing has no utility and should not be performed. In the case of an adverse reaction in the setting of a life threatening envenoming, the patient still requires the antivenom; therefore, the infusion is halted, anaphylaxis , if this is the adverse reaction, is treated, and after a time, the infusion is re-started at a slower rate and with careful monitoring.

(3) Kent, yes, one can develop venom sensitivity to "natural exposure", as several persons operating commercial venom extraction ventures have very unfortunately come to realize (I won't name them, but some are well know to all here). I began to develop a sensitivity in the late 1970's and early 1980's when I was less cautious during venom extractions for my venom research. But, I increased my attention to detail and haven't had a problem since. One can become sensitized at any time once exposed. Envenoming delivers venom antigens to the enormous populations of beta-plasmocytes and macrophages, thus antigen-presenting cells become activated and some MAY produce proanaphylactic IgE.
Again, hope this necessarily very brief description is helpful. I am happy to see thoughtful interest on the topic. If any of you are intrested in an overview of evidence-based envenoming mangement, I noticed that one of my papers was posted online: http://www.goodsamim.com/Articles/AHD/2 ... 436365.pdf
Scott
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regalringneck
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Re: Anti-venom question..

Post by regalringneck »

... well Dr Weinstein, im going to ruminate on that last response & your interesting link for a goodly period & then still not comment but again thankyou : }
... Jim thats a serious paw ... im thinkin ... dude otta put a glove on it ... :p
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