Snake envenomation Diagnosis and Management

Global and National Impact of Snake Envenomation

Snake envenomation is recognized by the World Health Organization (WHO) since $2017$ as a Category A neglected tropical disease. This classification has facilitated increased research and potential funding for the development of antivenoms.
Internationally, snakebites result in approximately $50,000$ deaths every year.
In the United States, snake envenomation is a rare but serious medical emergency. Approximately $7,000$ to $8,000$ bites occur annually, resulting in approximately $5$ deaths per year.
While mortality in the United States is low, morbidity remains very common.

Classification and Identification of Venomous Snakes in the United States

Crotalidae (Pit Vipers): Account for more than $95\%$ of venomous snakebites in the United States. This family includes rattlesnakes, water moccasins (cottonmouths), and copperheads.
- Physical Characteristics: Pit vipers possess a triangular head, elliptical eyes, and a heat-sensing pit located between each eye and nostril.
Elapidae: This family includes the coral snake. Unlike pit vipers, Elapidae bites are characterized by prominent neurotoxicity with minimal local reactions.
- Identification Mnemonic: "Red on yellow, kill a fellow; red on black, venom lack."
- Treatment: Requires species-specific antivenom.

Epidemiology and Risk Factors

Demographic Data: According to the North American Snakebite Registry (NASBR), snakebites are more frequent in men ( $69\%$ ) and involve children younger than $12$ years of age in nearly $30\%$ of cases.
Location of Incident: Most pediatric bites occur on the lower extremities, often associated with a lack of protective footwear. In one study, one-quarter of patients were barefoot, and more than $61\%$ were wearing sandals or flip-flops.
Preventive Measures:
- Wearing closed-toe shoes outdoors.
- Looking before stepping.
- Using extreme caution when reaching into holes or under logs/brush.
- Educating children not to provoke or pick up snakes.

Pathophysiology of Envenomation

Venom Purpose: Snakes produce venom primarily to target prey, but use it as a defense mechanism against perceived threats.
Clinical Effects: The severity of clinical effects is determined by the volume of toxin released and the potency of the specific venom.
Clinical Mechanisms: Identification and management are essential to mitigating tissue cytotoxicity, coagulopathy, and neurotoxicity.

Clinical Presentation and Symptoms

"Dry" Bites: Bites occurring without the injection of venom. These are difficult to differentiate clinically and require at least $8\,hours$ of observation for signs of systemic envenomation.
Crotalidae Envenomation Features:
- Rapidly progressive swelling and local ecchymosis or bullae.
- Hematologic toxicity: Coagulopathy (elevated prothrombin time, low fibrinogen) and thrombocytopenia (low platelets).
- Neurotoxicity: Paresthesia, fasciculations, or myokymia (eyelid twitching), typically developing within $12$ to $24\,hours$ .
Species-Specific Variations:
- Copperhead: Often causes local tissue injury and a metallic taste sensation.
- Mojave Rattlesnake: More likely to cause neurotoxicity.
- Rattlesnakes (General): Associated more closely with hematotoxicity and neurotoxicity.
Pediatric Signs: Young children may be unable to articulate symptoms. Systemic involvement may be signaled by unexplained vomiting, altered mental status, or swelling.

Prehospital and Initial Management

Scene Safety: The priority is moving to a safe location away from the snake and stabilizing the patient.
Limb Positioning: Remove jewelry or tight-fitting items. The bitten limb should be immobilized and kept at or slightly below heart level to minimize lymphatic absorption of venom.
Contraindicated Interventions: Strategies such as constriction bands, ice, suction, and wound incision are strongly discouraged as they are shown to cause increased tissue damage.
Timeframe for Care: Medical attention should be sought as soon as possible, preferably within $6\,hours$ of the bite.

Emergency Department (ED) Protocols

Assessment and Positioning: Once in the ED, the affected limb should be elevated to manage increasing edema. Joint flexion should be avoided.
Pain Management: Nonsteroidal anti-inflammatory drugs (NSAIDs) should be initially avoided due to potential venom interference with the coagulation cascade and increased bleeding risk.
Prophylaxis: Tetanus prophylaxis should be updated if indicated.
Monitoring:
- Serial measurements of the limb and swelling progression are critical.
- Labs: Complete blood count (CBC), prothrombin time (PT), partial thromboplastin time (PTT), and fibrinogen should be monitored every $6\,hours$ .
Observation: Patients with apparent dry bites or mild envenomation (no swelling progression or systemic symptoms) should be observed for a minimum of $8\,hours$ .

Antivenom Administration (CroFab and Anavip)

Indications: Antivenom is indicated for patients exhibiting:
1. Progressive swelling.
2. Hematologic abnormalities (low fibrinogen, low platelets, or elevated PT).
3. Systemic symptoms (hypotension, gastrointestinal distress, or neurotoxicity).
Pediatric Dosing: The pediatric dose is identical to the adult dose because the antivenom targets the total volume of venom injected ( $4$ to $6$ vials infused over $1\,hour$ ). For severe cases involving shock or uncontrolled bleeding, higher doses of $8$ to $12$ vials may be appropriate.
Adverse Reactions:
- Anaphylaxis: Requires immediate infusion cessation and treatment with epinephrine.
- Nonallergic Infusion-Related Reactions: Occur in up to $6\%$ of patients; symptoms include pruritus and urticaria.
Treatment Evaluation: Examine the patient and repeat labs within $1\,hour$ of administration to check response.
Initial Control: Defined by stable laboratory values, no progression of swelling, and improving systemic signs. Most patients require no more than $2$ doses for initial control.

Post-Treatment and Discharge Planning

Observation Period: After initial control, patients should be monitored for an additional $8$ to $24\,hours$ .
Bleeding Precautions: For rattlesnake bites or those with coagulopathy, patients must avoid contact sports, elective surgery, and dental work for $2\,weeks$ . Labs may need to be repeated post-discharge.
Serum Sickness: Occurs in $5\%$ to $10\%$ of patients $5$ to $14\,days$ after antivenom treatment. It presents as an influenza-like illness with a rash and is treated with antihistamines and steroids.
Prognosis: Favorable with early intervention. Rehospitalization occurs in $4\%$ of cases due to recurrence of swelling or hematologic issues. Long-term complications (tissue loss, chronic pain, or complex regional pain syndrome) are rare but possible if care is suboptimal.

Questions & Discussion

Interviewer/Editor Commentary (Janet Serwint, MD):

Question/Topic on Global Presence: Dr. Serwint finds it fascinating that snakes exist on every continent except Antarctica.
Question/Topic on Diagnosis Challenges: Diagnosing a bite can be difficult if there is only a single fang mark, if the puncture is obscured by edema, or in the case of simple abrasions from dry bites.
Question/Topic on Pediatric History: Challenges exist in obtaining an accurate history from children regarding the type of snake encountered and whether it was seen clearly.
Clinical Anecdote: Dr. Serwint treated a $10$ -year-old child bitten by a copperhead on the leg. The patient was a good historian and met criteria for antivenom due to marked swelling. The patient and parents exhibited significant fear following the body's dramatic reaction.
Additional Terminology: Neurotoxicity can manifest as myokymia, which is described specifically as eyelid twitching.
Consultation Recommendation: Because snakebites are rare for many clinicians, early consultation with Poison Control and medical toxicologists is categorized as an essential resource for geographic and species-specific guidance.