So You’ve Been Envenomated By a Snake. Now What?!
You’ve been bitten by a venomous snake. What are your treatment options?
It’s bad enough getting tagged by a venomous snake, but all too often, snakebite victims must deal with physicians who are inexperienced in the management of snakebite. It’s not that they are bad doctors; snakebite is just a relatively uncommon condition compared to other things emergency physicians learn about and treat.
There are some great articles that describe the prehospital management of snakebite. (I like this one best). The short version: don’t do any of the treatments that were historically recommended. They are useless at best and dangerous at worst. Just get to the closest appropriate facility ASAP.
You will be evaluated at the hospital, and any life-threatening conditions will be addressed.
It seems like most of the questions/concerns that arise (for both patients and physicians) are about antivenom. Specifically, what are the options and what are the indications?
For this article, I’m going to focus on pit viper, a.k.a. crotalid, envenomations. Pit vipers include rattlesnakes, copperheads, and cottonmouths. Collectively, they account for approximately 98% of all native snake envenomations in the US. Coralsnakes, which are elapids, account for the other 2% but are outside the scope of this story.
Pit viper envenomations are characterized by some combination of local tissue damage, hematologic toxicity, and systemic toxicity. Tissue damage is by far the most common manifestation; more than 95% of crotalid envenomations will have swelling, tenderness, and bruising. Necrosis, which may be superficial or full-thickness, is seen less frequently.
Historically, many patients have gone untreated with antivenom, even when their envenomations warranted it. Why, you may ask?
There are multiple reasons why a doctor may choose to not treat a patient with antivenom even when it is indicated. He or she:
- May think snakebites are not that serious.
2. May not believe antivenom is effective.
3. May not think antivenom is safe.
4. May think treatment with antivenom is not worth the cost.
5. May not want to bother with treatment because s/he is uncaring and/or lazy.
6. May face pressure from hospital leadership not to treat patients for various reasons, including financial.
7. May not be able to treat with antivenom because the hospital does not stock it.
Obviously, the first two reasons are totally bogus. We also know that CroFab has an excellent safety profile. More on that later.
There does need to be some discussion about the cost:benefit ratio when it comes to mild bites. Antivenom is not cheap, and it may be cost-prohibitive for someone without insurance. But there are also financial consequences of going untreated, because a significant percentage of people will end up with prolonged, or even permanent, disability. That’s why I almost always recommend treatment.
The fifth and sixth reasons are reprehensible, but I think they are more common than people want to acknowledge.
As for #7: it’s not necessarily essential for every single hospital to carry antivenom. If there’s a mechanism to get someone to another facility in a timely fashion, that’s acceptable. What’s not acceptable is to have someone languish, untreated, in a hospital that doesn’t carry antivenom. I think hospitals located in areas where snakebites are endemic should have sufficient antivenom to at least start the treatment process, and then rapidly ship them somewhere where they can receive definitive care.
But as I was saying… with rare exceptions, pit viper envenomations should be treated with antivenom.
In United States, there are two commercially available antivenoms, but they are not interchangeable.
CroFab is indicated for all North American pit viper envenomations. Anavip is only indicated for North American rattlesnake envenomations. That is not to say that Anavip would not work for Agkistrodon (moccasin) envenomations; there is simply not much evidence. In fact, that is the major issue with Anavip — there are many unknowns.
The only randomized clinical of Anavip trial did not look at everything that those of us who treat snakebites care about. The only conclusion from the RCT was that on days five and eight, there was less hematologic recurrence with Anavip than with CroFab. That said, all the lab work was pretty reassuring in all of the subjects. There may have been a statistically significant difference, but I’m not sure if it was clinically meaningful.
There’s no evidence that Anavip treats the local tissue injury, which is a much bigger concern for the vast majority of our snakebites. There’s no evidence it fails to treat. There’s just no evidence. On the other hand, both RCTs of CroFab demonstrated recovery from local, hematologic, and systemic effects.
There are no post-marketing studies looking at the safety of Anavip. CroFab has an excellent safety profile. The incidence of acute adverse reactions is estimated to be between 1.4% and 8%, depending on the study. The more recent studies estimate the incidence to be <2.7%.
Anavip is a Fab2, whereas CroFab is a Fab (these refer to what part(s) of the antibody are used to make the antivenom). The former is larger and has a longer elimination half-life. I think the longer half-life has both advantages and disadvantages. Its effect may last longer, but its persistence in the circulation theoretically increases the risk of sensitization.
Per vial, Anavip is cheaper than CroFab. However, it generally takes more vials of Anavip to do the job. In the package insert, the manufacturers recommend starting with 10 vials, but in the RCT comparing the two antivenoms, the mean number of vials needed was 14.2 (range 7–38) for Crofab and 27.2 (range 22–46) for Anavip.
I believe if someone uses Anavip for a bite from a species for which it’s not approved and there’s a bad outcome, it’s hard to defend in a court of law and/or the court of public opinion. I don’t think you can justify using Anavip for a copperhead or cottonmouth bite when CroFab, which is indicated for these envenomations, is available and has a 19+ year track record of success and excellent safety. Personally, I would also like to see some more formal safety data on Anavip.
For those of you with short attention spans:
1. Most crotalid envenomations should be treated with antivenom
2. CroFab is approved for all native pit viper envenomations, so exact species identification is not necessary. If a crotalid envenomation is diagnosed clinically, CroFab can be used.
3. Anavip is approved for all native rattlesnake, but not copperhead or cottonmouth, envenomations.
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