Snakebite Treatment: Past, Present, and Future

The Antivenin Nearctic Crotalidae treated bites by crotalids such as cottonmouths (picture by Meg Jerrard on Unsplash)

Snakebites have challenged humans for centuries. Without a proper understanding of how snake venoms worked, physicians used the same ineffective treatments through much of history. These practices included manually sucking the venom out of a wound or serving Theriac, a concoction made of herbs, spices, opium, ground-up snakes, and even powdered mummies, to the victim. These remedies remained popular in western medicine into the seventeenth century.1

Antivenom, or antivenin, was developed in the 1890s as a new treatment for envenomation. Though who first created antivenom is heavily debated, most credit a French immunologist named Albert Calmette (1863-1933) who sought a treatment for cobra envenomations in Vietnam. Having witnessed a large number of monocle cobra bites after a heavy rainy season, he decided he had to act. He developed a new serum by injecting small, non-lethal doses of cobra venom into various animals; these animals went on to develop antibodies capable of neutralizing the venom. Calmette would then extract some blood from the animals and isolate the antibodies to purify into antivenom.2 This technique is still used in animals such as horses and goats to create antivenom today.3

Calmette’s discovery eventually led to commercial production of antivenoms. Three decades later, the HK Mulford Company of Philadelphia, overseen by the Antivenin Institute of America, began producing the first commercial antivenom in the United States. Their antivenom, called the Antivenin Nearctic Crotalidae, could treat the bites of various North American crotalids (copperheads, cottonmouths, and rattlesnakes). This versatility was possible because of the antivenom’s polyvalence–it contained antibodies effective against the venoms of numerous species.4

Antivenoms are now manufactured all over the world to treat all kinds of snakebites. However, the technology is far from perfect. Polyvalent antivenoms continue to be a work in progress today, and one of the main difficulties in creating a versatile and effective antivenom stems from the variation in venom across species. Elapids like cobras and taipans, for example, usually possess neurotoxic venom, while crotalids such as rattlesnakes and adders possess a completely different hemotoxic venom.

Due to significant diversity in venoms, drug companies must develop antivenoms specific to each snake species. Existing polyvalent antivenoms are limited and can only treat a few of the species most responsible for envenomations. For example, the main polyvalent antivenom produced in India only covers the “Big 4” snake species out of the 60 capable of envenoming humans. As a result, there is no antivenom treatment for people who have been bitten by many snakes not included in the “Big 4.” Without any other available treatment, doctors are forced to use this same antivenom on these patients, often leading to treatment failure. Furthermore, all Indian antivenom manufacturers source their venoms from one geographical population of each species, and because of variations within different populations of the same species, these antivenoms may not be very effective for patients of different locations.5 Similar issues exist with antivenoms produced around the world.

Current antivenom technology is limited due to the complexities of venom across and within species. However, scientists are creating new potential therapies with the goal of more effectively treating all snakebites. For example, the drug manufacturer Ophirex is conducting clinical trials for a PLA2 inhibitor, varespladib, which could treat snakebites from more species than any current treatment. Unlike traditional antivenom technology, the drug works by blocking PLA2 enzymes that play a major role in bleeding, tissue destruction, and paralysis. This class of enzymes are found in 95% of all snake venoms and may be the key to developing treatments that cover snakebites more broadly. Other small molecule therapeutics such as metalloproteinase inhibitors, aptamers, and chelators, among many others, are also currently being studied. As companies experiment with new therapies, antivenom technology will continue to grow and improve, hopefully resulting in better health outcomes for snakebite patients around the world.6

If you found this article informative, please consider donating to ASF today. Every donation is 100% tax deductible and goes directly to patient care in Africa.

1. https://www.nhm.ac.uk/discover/mastering-venom.html

2. https://www.nhm.ac.uk/discover/mastering-venom.htm

3. https://www.si.edu/spotlight/antibody-initiative/antivenom

4. https://www.si.edu/spotlight/antibody-initiative/antivenom

5. Casewell, N. R., Jackson, T., Laustsen, A. H., & Sunagar, K. (2020). Causes and Consequences of Snake Venom Variation. Trends in pharmacological sciences, 41(8), 570–581. https://doi.org/10.1016/j.tips.2020.05.006

6. https://www.ophirex.com/varespladib

What to Expect When You're Expecting... And Snakebitten

Pregnancy is a unique and life-changing journey, but it can also bring unexpected challenges and risks. One such risk, though rare, is the possibility of a snakebite. Snakebites during pregnancy require careful and prompt attention due to potential risks for both the mother and the unborn child. It is important for patients and their healthcare providers to understand the essential aspects of snakebite treatment in pregnancy, emphasizing safety measures for both the mother and her developing baby.

Understanding the Risks

Snakebites during pregnancy can be particularly concerning due to the potential complications they may cause. The severity of the snakebite and its subsequent effects on the mother and fetus depends on various factors, such as the snake species, the amount of venom injected, and the gestational stage of the pregnancy.

While snakebites can lead to serious consequences regardless of the victim's age or health, pregnant women face additional challenges due to the potential harm that venomous toxins can inflict on fetal development. It is crucial to address snakebite treatment promptly and efficiently to minimize risks.

Immediate Actions to Take

1. Seek Medical Attention: If a pregnant woman is bitten by a potentially venomous snake, immediate medical attention is crucial. She should call for emergency medical services or head to the nearest healthcare facility as soon as possible. It is essential to share her pregnancy status with healthcare providers so that they can make informed decisions about her treatment.

2. Immobilization: To slow down the spread of venom through the body, limit movement of the affected limb.

3. Stay Calm: Panic can accelerate the heart rate and spread venom more quickly throughout the body. It is essential for the pregnant woman, her partner, or any accompanying person to stay as calm as possible and reassure the mother.

Treatment Considerations

Snakebite treatment in pregnancy requires a careful balancing act between addressing the mother's health and ensuring the safety of the developing fetus. Here are some key considerations:

1. Antivenom Administration: The decision to administer antivenom should be made by healthcare professionals experienced in snakebite management. They will consider factors such as the snake species, the severity of the bite, and the mother's overall health, including her pregnancy status. Antivenom can be life-saving for both the mother and baby, but careful considerations need to be made.

2. Monitoring: Pregnant women who receive antivenom or other treatments for snakebites may require closer monitoring. Vital signs, fetal heart rate, and the progression of symptoms should be carefully observed.

3. Imaging and Laboratory Tests: Healthcare providers may use ultrasound or other imaging techniques to assess the fetus's well-being and development following a snakebite. Laboratory tests, such as complete blood count and coagulation profile, should be done to monitor for any abnormalities.

4. Preterm Labor Considerations: In severe snakebite cases, there may be a risk of inducing preterm labor. Healthcare providers will closely monitor the pregnancy and take necessary actions to prevent preterm delivery if possible.

Snakebites during pregnancy require immediate medical attention and careful consideration of treatment options. The health and safety of both the mother and the unborn child should be the top priority. Pregnant women, especially those in snake-prone areas, should take precautions, such as wearing protective clothing and being cautious when walking in tall grass or wooded areas.

In the unfortunate event of a snakebite, it is crucial to remember that prompt medical attention, appropriate antivenom use, and close monitoring are essential to improve the chances of a positive outcome for both the mother and her developing baby. Expert physicians are equipped to make informed decisions to ensure the best possible care and safety during this challenging time.

Breastfeeding

Breastfeeding is an intimate and often unique bonding time between mother and child.  Though rare, snakebites can occur to lactating mothers, and the question often arises whether breastfeeding should continue. While no good data exist on whether breastfeeding is safe, anecdotal evidence in areas where alternatives to breastfeeding are not readily available suggests it is safe to breastfeed both after a snakebite and after receiving antivenom.

If you found this article helpful, please consider donating to ASF today. Every donation is 100% tax deductible and goes directly to patient care in Africa.

Veterinary Experts Do Not Recommend The Rattlesnake Vaccine

Every spring, as the weather warms up, we want to shed our winter coats and get out with the dogs onto trails and into open spaces. Unfortunately, as our pooches explore the environment with their noses, they may encounter snakes coming out of brumation.

This can cause concerns for dog owners. Many will ask their vets, “What can I do?” Unfortunately, some vets will recommend the rattlesnake vaccine. Touted to “buy time” getting to an emergency clinic or even to ward off the envenomation, the rattlesnake vaccine is an often used but poorly supported treatment for dogs.

The rattlesnake vaccine uses inactivated western diamondback rattlesnake (Crotalus atrox) venom. The manufacturers claim it “is intended to help create an immunity to protect your dog against the effects of western diamondback rattlesnake venom.” However, there is no evidence to support the vaccine being effective, and some data suggest it could be harmful by causing an allergic reaction to snake venom.

The American Animal Hospital Association (AAHA) recently released a statement highlighting the lack of evidence of vaccine (toxoid) efficacy. Read It Here.

Key points from the AAHA’s statement:

1.      There is NO published data supporting the efficacy of the vaccine in dogs.

2.      In a study that was performed in mice, where mice were given 50-1,500 TIMES the dose of the toxoid given to dogs during routine vaccination, survival following exposure to snake venom was still not guaranteed, and some vaccinated mice actually died or required euthanasia earlier than unvaccinated mice exposed to the same amount of venom.

3.      Adverse reactions, including anaphylaxis, have been reported in vaccinated dogs.

4.      Though the manufacturers make claims of cross-protection (protection from envenomation by pit viper species other than the western diamondback rattlesnake, the species used in the production of the toxoid), there are no data to support this claim.

From the AAHA: “Veterinarians choosing to use this toxoid should be aware of the lack of peer-reviewed published data. Polyvalent antivenin therapy is an alternative to vaccination in suspect cases of rattlesnake bite.”

The vaccine did not prove effective in a retrospective study looking at 272 cases of rattlesnake envenomations in dogs. Read It Here.

Key findings from the study:

1.      There was no evidence that vaccination lessened morbidity or mortality.

2.      No measurable benefit could be identified associated with rattlesnake vaccination.

From this case series: “Vaccination for protection of the general canine population from rattlesnake envenomation cannot be recommended by these authors.”

Furthermore, the rattlesnake vaccine toxoid may predispose snakebitten dogs to anaphylaxis by providing the necessary sensitizing exposure to snake venom antigens. Read It Here.

Key findings from the study:

1.      There are no peer-reviewed publications providing evidence of clinical efficacy in snakebitten dogs.

2.      Anaphylaxis requires prior sensitization to an antigen; it is proposed that repeated vaccinations with the rattlesnake toxoid vaccine serve as a sensitization event to snake venom.

From the authors: “These dogs had previously been vaccinated with the C. atrox toxoid vaccine on more than one occasion, which may have served as the initial sensitization required for the development of anaphylaxis.”

Snakebites are medical emergencies for pets and humans alike. Effective antivenom is the only thing that can neutralize venom and improve outcomes.

If you would like to learn more about veterinary ativenoms, please see this post by Dr. Cory Woliver (A Primer on Antivenoms Used by Veterinarians).

If you found this article helpful, please consider donating to ASF today. Every donation is 100% tax deductible and goes directly to patient care in Africa.

How to Treat Snakebites For First Responders in the United States

Approximately 9,000 snakebite envenomations occur yearly in the United States.  Most of these envenomations are due to pit vipers, including rattlesnakes, cottonmouths, and copperheads.  Fortunately, due to rapid access to medical care, deaths are rare, with only 3 to 5 occurring nationwide each year.  Our emergency medical system is the first link in the chain of treating patients.  In comparison to many areas of the world, the U.S. has an advanced system of highly-trained EMTs and paramedics skilled in the prompt assessment, stabilization, and transport of critically ill patients.

We are often contacted to discuss the best way to treat patients in the prehospital setting.  The short of it is to consider a snakebite envenomation a medical emergency.  The mantra “time is tissue” applies to snakebites just the same as it does to STEMIs or strokes.  Getting to the hospital quickly (and safely) is a key part of EMS treatment for snakebites.  Antivenom is the only medication we have that will stop the progression of an envenomation.

Unfortunately, many outdated or even dangerous protocols persist. So for those looking for more guidance, here is a quick, evidenced-based guide for prehospital management of pit viper envenomations in the United States.

    1. As always, initially assess Airway, Breathing, and Circulation and treat any immediate life threats.

    2. If there are signs of an allergic reaction, treat them according to your local protocols.  Keep in mind that systemic toxicity from venom can look very similar to anaphylaxis.  Don’t worry about which is which in this scenario.  Treat both at the same time and figure out which one was the culprit later.

    3. Assess the affected limb.  Remove any jewelry, watches, rings, or other items that may cause constriction if swelling occurs or worsens.

    4. Establish IV access in an unaffected limb.

    5. Elevation of the extremity prehospital is controversial.  Some experts believe it increases systemic absorption, while others disagree.  Nonetheless, the general consensus is to keep it at least at the level of the heart or above.  Discussing which is better with a local snakebite expert may provide more clarity, as opinions typically vary by region.

    6. Provide pain control per your protocols. IV opioids are usually the first line, but other medications, including IV Tylenol or pain dose ketamine, may be viable options. Some experts use ketorolac or other NSAIDs in copperhead envenomations without adverse events occurring due to their very low rate of hematologic toxicity.

    7. Be judicious with IV fluids. If the patient is hypotensive, obviously treat with volume resuscitation.  But if they are comfortable and have normal or even high blood pressure, IV fluids may potentially worsen local edema and swelling.  This is theoretical but something to consider.  I would not flood them with a bunch of fluids if they look well.

    8. Transport the patient to the appropriate hospital per your local protocol.  Typically this would be your local hospital that stocks antivenom. However, some protocols may direct you to larger tertiary hospitals where a snakebite expert can see the patient at the bedside.

    9. When in doubt about a snakebite, contacting your base hospital or the poison center (1-800-222-1222) for further guidance is always a good option.

There are many misconceptions about snakebite first aid. You may encounter patients that have already done things that are not recommended, or you may have been taught some of these unsupported or potentially harmful practices. We DO NOT recommend the following.

    1.  DO NOT apply a tourniquet or compression bandage.

    2.  DO NOT use a suction device.

    3.  DO NOT cut near the wound or try to suck the venom out with your mouth.

    4.  DO NOT use a taser or other electrical shock devices.

    5.  DO NOT bring the snake to the hospital.  Taking a picture of the snake from a safe distance is ok, but identification isn’t necessary for proper treatment.

    6.  DO NOT apply ice or heat to the envenomation site.

If your protocols differ from the above recommendations, consider having your medical director contact a regional snakebite expert or our staff so your service can offer the best evidence-based care to patients.  We are always willing to help improve patient care locally and globally.

In summary, the best possible treatment is to manage the ABCs, provide good pain control, and get the patient to a hospital quickly so they can receive antivenom if necessary.

Nicklaus Brandehoff, MD

Asclepius Snakebite Foundation

If you found this article helpful, please consider donating to ASF today. Every donation is 100% tax deductible and goes directly to patient care in Africa.

Kindia, Guinea Clinic Update: July 2022

We recently wrapped up our June-July 2022 trip to Kindia, Guinea and overall it was a resounding success. One of the main purposes of this trip was to bring supplies for the new snakebite clinic and to be present for the opening of the clinic that everyone has been working towards for a few years now. The clinic has been the dream of Dr. Cellou Baldé and was made possible by a very generous donation from BTG Specialty Pharmaceuticals. Unfortunately, as often happens with coordinating construction projects such as this, the clinic was not quite ready to open when we were in Guinea. Most of the construction of the main clinic building is complete, and we hope that the transition and opening will be able to occur soon once a few final logistical issues are worked out. We were able to tour the clinic and the grounds for a morning and are excited to provide an update of its progress.

The clinic building has an office, a pharmacy, a triage room, a resuscitation room and then 4 rooms with beds for patients and/or family members. Each treatment room has 5 beds. There is also a conference room for educational teaching and meetings. Finally, there is another room for a future laboratory testing area.

The pharmacy with ample of storage.

One of the triage and resuscitation rooms, which are identical.

One of the 4 rooms with treatment beds for stable patients.

The conference and education room.

There is a bathroom area for the patients and families with 4 stalls containing toilets, sinks and showers.

The clinic sits on a 2 hectare (about 5 acres) piece of property that is quite beautiful. There are future plans to grow food on site to help feed the patients and surrounding community.

The group had a great time exploring the property!

There is another building nearby that will provide lodging for the people working at the clinic. There are 4 rooms completed, each with a bathroom. Connected to this building is a space that will be a kitchen/small restaurant for the local community.

While we were exploring the grounds, the group noticed a graceful chameleon Chameleo gracilis. Kate was in her element and showed it to some of the local children of the area.

While it’s unfortunate the clinic was not ready to open when we were in Guinea, it was wonderful to tour the grounds and really see everything coming together. It should be finished soon, and it is already clear it will save lives and serve as a key community resource for Kindia and the surrounding area.