COMMENTARY

From Cow Manure to Sucking Venom: Snakebite Treatment Myths

Robert D. Glatter, MD; Benjamin N. Abo, DO

Disclosures

October 30, 2019

This transcript has been edited for clarity.

Robert D. Glatter, MD: Hi. I'm Dr Robert Glatter, editorial advisor for Medscape Emergency Medicine. Managing snakebites has traditionally relied on antivenoms that treat specific types of snake envenomations. But advances in immunology and the emerging field known as toxinology—the study of specific components of venoms—are now opening up the possibility for a universal vaccine or antivenom to treat all types of snakebite or other envenomations.

Joining us to discuss this topic is Dr Ben Abo, an emergency medicine and EMS physician, paramedic, and clinical assistant professor of emergency medicine at the University of Florida.

To begin, can you explain the main principles of treating snakebite and the myths that you'd like to dispel?

Benjamin N. Abo, DO: Venom is basically a toxin that's injected. Our medical books describe that there are heme toxins (you bleed to death) or neurotoxins (you're paralyzed).

The fact of the matter is that venoms—no matter if its hymenoptera (bees, wasps, ants), marine life, snakes, scorpion—are so diverse, and I like to think of it as a cocktail. You might think that you're ordering a mojito, but the ingredients that are actually being used are completely different. The cocktail venom is a whole slew of various toxins, and there are hundreds of different identified toxins so far that are within each of these venoms.

Each venom is so diverse, based on geography and species, based on what is needed for protection or for eating and capturing prey. Really, it comes down to these proteins. You find the protein and need to neutralize it from doing other things to the body. That's what care is about.

I don't know which would have been worse: dying from venom or dying from the suffocation of cow manure.

Glatter: In terms of the myths regarding care of snakebites, obviously all of us have heard about the very unusual things that people would do for a snakebite, such as cutting it, trying to suck any kind of poison out, or using electricity. These things abound in the literature, and I want to get it from you—the expert—about what works and what doesn't work.

Abo: The main thing that works is antivenom. There have been many things over the years that have proven or disproven some of the stories. There was an article recently about a traditional healer in India who put a woman in a pile of cow manure following a cobra bite, and she suffocated to death. I don't know which would have been worse: dying from the venom or dying from the suffocation of cow manure, but these are the things that occur.

We should not use tourniquets or put ice on a snakebite. There are all of these myths, but really, the treatment for venom is the antivenom. We need to fight those proteins. We need to neutralize them and get them out of the body.

Glatter: Right. You've written about this in that it's a toxin emergency, especially in the setting of where people try to do fasciotomies on swollen limbs, and you obviously advocate not to do that. Could you expand upon that a little bit?

Abo: Back in the day, before we had antivenoms, snakebite envenomation was a surgical emergency. The fact of the matter is that we've been developing antivenoms since the late 1800s and they've gotten better and better. There was even, here in North America, a polyvalent antivenom made by Wyeth that was famous until the late '90s. It would neutralize venom, but it had all of these horrible side effects.

We used to have to do many fasciotomies, wound debridement, and things like that. But if you get quality care and quality antivenom upfront—and there are many quality antivenoms out there—you do not need a fasciotomy.

You do not need debridement as long as you do the proper thing. If you don't use electricity, don't put a tourniquet on (especially for a pit viper), or don't delay getting proper antivenom, you don't need to have surgical intervention. In fact, I tongue-in-cheek say that one of the roles of the emergency physician or toxicologist is to keep the surgeon out of the room.

It might get to the point where we need some wound care, but if they're thinking that there's compartment syndrome, you better measure that compartment first and really prove it to me. That's only going to happen if you have a real failure to treat. It really should not happen.

Glatter: According to what you've written, pain and tenderness guide treatment, rather than the number of vials or any other factor. I imagine that's something you stick to?

Abo: Correct. When it comes to North American envenomation, we have two basic types of venoms that we have to deal with for indigenous snakebites: We have the pit vipers, which are rattlesnakes and other pit vipers that don't have rattles to warn you (including the cottonmouth and the copperhead or the water moccasin); and we have an elapid, the coral snake.

When it comes to pit viper envenomation, we have a recognized, unified, set algorithm to help guide treatment, because snakes don't come with meters. You can't look at a snake and determine that it only injected 50%.

We have set guidelines that are proven by evidence- and experience-based medicine. There are three things that we look at. There are local effects—so, lymphatically, the swelling, redness, or even blood blisters; local tissue effects can be spreading. We'll mark and observe the rate of how quickly and how much it's progressing. That's one of my vital signs with envenomation.

Second, other than local effects, are lab values, including certain coagulation studies, CBC, platelets, CK, which are relevant to the lab.

Third are the systemic effects. If someone was bitten on the hand or the foot and is showing systemic effects like syncope, near syncope, shortness of breath, cardiac dysrhythmias, renal failure, retching, or vomiting, it's a very serious envenomation.

I have to treat to get control of all three of those effects before I can say that the situation is under control. A big thing about that and what you were starting to refer to is that in terms of the local effects, we need to monitor the swelling, the pain, and the tenderness.

If you look at the algorithm, it says swelling and tenderness. Well, people just mark that it's red to here, and that's really not enough. That cocktail of what was injected into the victim really necessitates things.

I had a patient who was bitten by a canebrake, which is often known as a timber rattlesnake. The person almost went into cardiac arrest. He was bleeding out from everywhere; he had gross blood in his urine. He was on three pressors and his blood pressure was 50/30 mm Hg. He was tachycardic in the 160s. You had to look very closely to see the bite mark; the swelling didn't show up until the next day. That's why we have to use the pain and the tenderness also, and that really gives us a great idea of how quickly things are spreading out.

Glatter: Absolutely. In terms of the coagulation profile, fibrinogen, platelets, and these other factors, is that the most sensitive way to monitor from a lab standpoint?

Abo: For our lab studies, that's the best thing that we can do in terms of time, sensitivity, and cost. There are some other specific things that a tertiary or an academic center can get, but clinically, it just doesn't really help.

When I'm in the middle of a foreign country, if I'm in Guinea, where I'm actually going to next week, and there's a pit viper envenomation, I don't even have some of those lab studies. My coagulation study is filling a syringe with blood and timing how long it takes to coagulate.

How Close Are We to Developing a Universal Antivenom?

Glatter: I was wondering if you could describe the role of the phospholipase inhibitors as a contributor and a mechanism toward developing a universal antivenom or vaccine.

Abo: What it all comes down to, as I have mentioned, is that there are so many toxins that we're trying to specifically identify and hit. It would be great, and there have been some recent articles that identify possible keys to targeting things.

However, it's all in how you look at it and how you spin it, because there are probably 50-100 phospholipases A2 (PLA2s). So, how do you target that and mix all of those things? It's just one of the many specific enzymes or proteins that we need antivenoms to target.

Glatter: Are there any other types of proteins within the snake venom that are also good candidates to attack in that sense? Also, do you believe that nanoparticles have a role in helping to treat envenomations?

Abo: First, regarding the nanoparticles. I remember hearing about this in some of the talks from UC Davis that initially suggested that this might be a possibility. However, I haven't heard anything since. Theoretically, it would be great if it worked. I have not seen any actual science or any development of that. To me, it's no different from seeing the movie GI Joe and then talking about nanoparticles.

The proteins are so different geographically. If you have the same species in a different location or the food is a little bit different, the proteins change. I like that we're continuing to catalog and figure out similarities between them.

That's exactly what our antivenoms do. They target specific proteins and toxins within the venom, such as PLA2, necrotoxins, myotoxins, cardiotoxins, the wasp kinins, and all these different things. There are many out there, but none have proven to be a universal catch to say that something works for a whole region.

Some articles that came out about PLA2 say that it is a key. Well, we have many PLA2 receptors and a large amount of venom within snakes like the Micrurus fulvius, an Eastern coral snake, where 33% of its venom is a PLA2, but it's a different PLA2 from certain pit vipers, where it could be anywhere from 30% to 70%. So, it's not 100% and it's very varied. That's exactly how antivenom works. We just have to hit all the right targets.

Glatter: I have another question about using recombinant technology and avoiding animal models to produce antibodies against snake venom, ie, using cell culture and producing it using human recombinant antibodies. There has been work on this, and certainly that's moving forward. Do you see this as a possible alternative going forward?

Abo: It's possibly an alternative moving forward, but I think we're still very far away from it. It definitely would be great if we can just have it and clone it and kind of go from there once we have that safe product. But it's so expensive. It's labor-, money-, and research-intensive, and we need to look at it. We need to also make sure that we're concentrating on a proven methodology that we know works and that is safe.

When you have these small products, the F(ab')2 products, you're cleaving things that cause most of the reactions. It's safe and it works. It only takes a couple of weeks for a horse to develop antibodies, and we can do it in a large volume. They get 7 pints each time from a horse and they separate all of the antibodies, and they can keep using it and doing it without hurting the horse. Again, in short, it depends. It's a possibility and it would be nice, but it's so labor- and money-intensive that I don't see it anytime soon.

Snakebites on a Global Scale

Glatter: I'm going to switch gears and talk about the World Health Organization's (WHO's) recently published guidelines, which include a first-ever global strategy to tackle the problem of snakebites. Their goal has been stated as to cut in half the number of people who are either killed or disabled by snakes by 2030. Maybe you can provide some insight on these guidelines. Are they realistic, and how do you see them being deployed?

Abo: I am very excited to see it finally recognized as a major issue. With the proper approach that the WHO and my foundation (the Asclepius Snakebite Foundation) are talking about, and which many other experts have been pushing for a number of years, I think it can be even better than cutting it to 50%.

Some of the numbers in our experience have shown that getting proper antivenom out to where most of these snakebites occur can decrease it to 10%. If you provide training and education for both the public and practitioners on how to use it and when to use it, that's even better. We can probably get it down to 1%-3%. You need to have a multifaceted approach because it's a multifaceted problem.

Glatter: Some people say we're putting too much emphasis on snakebites, whereas other types of infectious diseases, like Ebola, kill many more people. When you look at the WHO numbers, for example, they talk about 5.4 million people bitten each year, with up to 2.7 million envenomations; globally, maybe 180,000 people dying from snakebites is what has been reported. Can you put this in context? In other words, there's been this thought of whether we really need to devote this much time and resources to snakebite.

Abo: People say to me all the time that people don't really die from snakebites. There are only five to six people in the United States who die per year, and most of those had major delays in care or something similar. The fact of the matter is that not as many people die as get envenomed, but if you have an envenomation, especially in many of these other places, you are permanently disabled, permanently disfigured, or permanently in pain.

Let's say that I have a family and I'm just doing my normal farm work or I'm a firefighter in Guyana, and I get bitten by a snake. I can't afford the medical care, and even if I don't get the medical care and I survive, how am I going to be able to provide for my family? How am I going to be able to provide education for my children?

Medicine and global health, public health, really needs to be a combination of high-hanging and low-hanging fruit. Envenomation care is both a top-notch problem and a low-hanging fruit. It's something that we can really make a big difference on so that, ultimately, we have more money and more resources for other problems.

Glatter: So, the concept of an EpiPen for a snakebite, just like how we treat anaphylaxis, is something that you really don't see happening soon?

Abo: For a universal, global antivenom, no, I don't see it coming anytime soon. I honestly don't even see it regionally because of the cost and everything involved. Part of that also comes down to the technicalities, including how much venom a snake injects into you and how toxic it is. There are all of these factors in trying to decide. I don't want to give everyone 20 vials when you might only need two vials and the next person needs 30.

Glatter: Right. I think that's an important point. It's such a variation. Some people have talked about just simple prevention measures—being careful when you're walking in high grasses and wearing plastic-type boots to prevent snakebites.

Abo: When I was a resident trauma surgeon, a friend was a fellow attending. He and I had a band together, the Navy's cover band. We called it The Prevention so we could say we were better than The Cure. That just always comes to mind because it's true. It's the same with mosquito abatement and malaria. If you can prevent it, then you're doing so much better. So, watching where you're walking and watching where you're picking up are helpful.

In a certain part of Florida, there are a ton of envenomations because farmworkers are picking up ferns at a nursery, they aren't looking, and they get envenomed by a pigmy rattlesnake that loves to be in that area. If they would use a stick to move the foliage a little bit or look before they grab, some of these envenomations could be avoided.

Wear proper footwear. I get plenty of people who are jumping around in flip-flops in high-cut grass. There are many things, such as wearing proper footwear, that could really make a difference and we wouldn't be in that predicament.

There's always going to be that percentage that will get bitten. It happens, but we can really reduce the numbers and be able to concentrate on that treatment.

Glatter: I want to wrap up with your involvement, as you're the director of the Asclepius Foundation. Please tell us a little more about the goals of the organization and your work with it.

Abo: The Asclepius Snakebite Foundation was founded, in particular, by Jordan Benjamin, who's a herpetologist, a snake venom expert, and a paramedic. I'm co-medical director with Nick Brandehoff, who's a toxicologist in Fresno, moving to Denver. The three of us, along with a lot of other experts and huge names in the field, including Ray Morgan, Leslie Boyer, and some others, are taking that multifaceted approach, and that's what it's all about.

It's a multifaceted approach to snakebite care by delivering quality education to the public; quality education to practitioners, nurses, and doctors; delivering and assuring that there's quality antivenom getting out there. We're doing research on all of the aspects.

One of the projects that we recently did that we're publishing right now is, we had a certain snakebite of a certain type of cobra for which, theoretically, the African polyvalent antivenom should have worked. This wasn't actually a cobra, so I said that it was not going to work, but it was tried, and in fact, it did not work. We were able to prove it because it worked in the lab. So we want to tease those things out.

Three Key Takeaways

Glatter: Can you give our audience three takeaways?

Abo: My big takeaway would be that if you don't know something, know someone who knows it. Feel free to consult specialists like myself or Dr Bernstein down in Miami, Florida, or Nick Brandehoff in Fresno, California. We know what we're talking about, and just because you were taught something in medical school, in residency, or something like that, it doesn't mean that that's the way it is, because the science has changed. There are many simple things that can really make a difference; and many things that we were taught in the past can really be harmful, believe it or not.

With that, in the US, if you have an envenomation, please, as soon as possible, do not use ice, don't cut or suck, but elevate it as high as possible—not just as high as a sprained ankle. I like to walk in the room and ask, "Oh, does your foot have a question?" Give them pain control, and don't be afraid if you need to use the antivenom, because the side-effect profile is so much better than it used to be.

In fact, there was recently a death here in the US from a local snakebite envenomation, and they did not give antivenom because there was the fear of an allergy. By golly, I'm an emergency doctor. When I was a 16-year-old kid as an EMT in South Jersey, I could treat an allergic reaction. In an emergency department, I can treat an allergic reaction if you have it, but those instances are rare.

Don't feel afraid to reach out to specialists. We're all available 24/7 globally. Know what makes a big difference and that things actually change, and don't be afraid to use the antivenom.

Glatter: Thank you. This has been such valuable information that you've provided to our audience. Have a great day.

Robert D. Glatter, MD, is an attending physician at Lenox Hill Hospital in New York City and assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. Glatter is an editorial advisor and hosts the Hot Topics in EM series on Medscape. He is also a medical contributor for Forbes.

Benjamin N. Abo, DO, is an EMT-P and the medical director for the elite Venom One and Venom Two response teams of Miami-Dade Fire Rescue and Lake County Rescue, and has extensive experience treating and consulting on snakebites around the country, as well as internationally. Abo was the 2014 recipient of the EMS Provider of the Year Award from the National Collegiate EMS Foundation after saving the life of an unconscious man who fell onto the PATH train tracks as a train was approaching the station in Greenwich Village in New York City.

Follow Medscape on Facebook, Twitter, Instagram, and YouTube

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....