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Introduction   

The Centers for Disease Control and Prevention (CDC) reports almost 8,000 snakebite incidents per year in the United States [1]. Across the globe, snakebite envenoming (exposure to a poison or toxin), affects between 1.8 to 2.7 million people per year, causing more than 100,000 deaths [2]. The toxins in snake venom can lead to serious medical conditions and long-term physical complications including amputation, contractures, chronic ulcers, paralysis, disability, and psychological impacts [3]. Conditions persisting more than six weeks after snakebite envenoming define long-term or delayed effects of envenoming [3].  

The World Health Organization (WHO) has classified venomous snakes into two categories to inform antivenom production based on their medical significance: Category 1, for snakes of the highest medical importance that lead to snakebites, causing significant morbidity, disability, and mortality; and Category 2, for snakes of secondary medical importance, which can also cause morbidity, disability, or death but are encountered less or lack comprehensive epidemiological and clinical data [4]. The WHO has recognized snakebite envenoming as a critical neglected tropical disease (NTD) and initiated the snakebite envenoming roadmap, aiming to reduce the global snakebite burden by half by the year 2030 [5].  

There are over 600 known species of venomous snakes classified under the families Viperidae and Elapidae [6][7]. Long, retractable fangs, distinctive triangular head shapes, elliptical pupils, scaled tails characterize the Viperidae family, which includes vipers, pit vipers, and adders [6]. Pit vipers possess an additional feature, a heat-sensing organ near their nostrils, enabling them to detect infrared radiation [6]. In contrast, the Elapids encompass cobras, coral snakes, mambas, and copperheads, features snakes with fixed, shorter fangs, less pronounced triangular head shapes, round (circular) pupils, and broader scales on their tails [7]. Venomous snakes from the remaining species fall into the Atractaspididae, Colubridae, and Hydrophidae families [7].  

For medical professionals, it is essential to understand bites from snakes considered non-venomous can lead to infections or allergic reactions in certain individuals [8]. It is advisable for patient safety to treat every snakebite as venomous and seek emergency medical care until the identification of the snake species. Prompt medical snakebite treatment, including the administration of antivenom can mitigate the risks of severe health complications or death [8]. Antivenom, also known as antivenin, is a form of antibody snakebite treatment designed to neutralize the toxins present in particular venoms when administered following a bite [9]. Albert Calmette, a French scientist and doctor, developed of the first snake antivenom in 1894 [10]. 

Mitigation of Risk  

For individuals venturing into natural environments or residing in regions known for elevated snake populations, awareness and preparedness are key to mitigating the dangers posed by venomous snakes [8]. The incidence of snakebites peaks during the wetter months, a period that coincides with intensified farming activities and the breeding season for snakes [8]. Essential precautions include the ability to recognize venomous snakes, accessibility to medical assistance in emergencies, and recognition of increased snake activity in warmer temperatures. The most prevalent venomous snakebites in the U.S. include Pit vipers, rattlesnakes, copperheads, and cottonmouths (water moccasins) and Coral snakes [11][18].  

Snakes from this Crotalinae subfamily account for 98% of the almost 8,000 venomous snakebites that occur per year in the United States [18]. Among these, rattlesnake bites are the predominant cause of venomous incidents, with coral snakes and exotic species contributing to a lesser extent [11].  

Symptomatic snakebite treatment includes airway management, breathing, circulation, bleeding control, and wound care as needed [14]. In cases where antivenom is unavailable, expeditious referral to a supplied medical facility is critical and advised for patients displaying systemic symptoms [15].  

While antivenom is an essential snakebite treatment option for snake envenomation, adverse reactions (EARs) restrict its broad application [15]. Initial management of a snakebite included keeping the affected limb immobilized during transport to a healthcare facility, and the use of pressure immobilization and tourniquets, which are debated and discouraged today [12]. 

Case Study: Management of a Copperhead Snakebite  

A 35-year-old male, an avid hiker, received a bite on his right lower leg by a Copperhead (Agkistrodon contortrix) snake while walking through a wooded trail in the outskirts of Asheville, North Carolina.  

Initial Response 

The patient remained calm, immobilized the affected limb, and called for emergency services. Upon arrival, the paramedics noted two puncture wounds with minimal bleeding, increased swelling, and pain. After limb immobilization, emergency medical services (EMS) transported the patient to the nearest hospital with capabilities to manage snakebites. 

In the field, differentiating between snake bites with or without venom injection is challenging due to the absence of clear, immediate symptoms [16].  

Snakebite treatment emphasis has evolved from on-site treatments to prioritizing rapid transport to the nearest healthcare facility. Employing a tourniquet to prevent venom from returning to the central circulation can obstruct necessary blood flow to the site and delay systemic toxic reactions [17]. In addition, a tourniquet may concentrate the venom within the affected limb, which can escalate local tissue destruction exacerbating swelling and the venom’s local impact [17].  

Moreover, the removal of the tourniquet may result in a surge of venom into the bloodstream, leading to severe complications such as shock, pulmonary embolism, and death [17]. Due to these risks and the questionable advantages, several clinical protocols and recommendations advise against the use of tourniquets, highlighting the possibility of increased local tissue damage [17]. 

Hospital Admission and Treatment 

• Emergency Department Assessment: Vital signs BP 103/75 lying down, right arm; P 89; RR 16; T 99.1°F; Wt. 108kg. Localized swelling, redness, and pain in the bite area was noted. The patient reported a tingling sensation in the affected leg. 

• Laboratory Tests and Imaging: Blood tests assessed coagulation status and organ function. An ultrasound evaluated tissue damage. 

• Identification and Antivenom Administration: A herpetologist confirmed the snake as a Copperhead based on the patient’s description and photographs of the area. Supportive care can manage most Copperhead bites. The decision to administer antivenom is based on the signs of systemic envenoming or significant local tissue involvement [18]. 

• Supportive Care: The patient received tetanus prophylaxis, pain management with analgesics, and wound care. Elevation of the affected limb can reduce swelling. 

• Observation: 24-hour observation followed with the nurse observing for signs of systemic involvement, including changes in blood pressure, breathing difficulties, and signs of coagulopathy. 

Outcome and Follow-Up 

The patient’s symptoms remained localized without systemic complications. The swelling and pain began to subside within 48 hours. Discharge instructions included wound care, observing for signs of infection, and a follow-up appointment scheduled with a healthcare provider in one week. At the follow-up visit, the patient showed no signs of complications and reported feeling well. The wound had healed without signs of infection or necrosis. 

Assessment 

The manifestation of symptoms following a snakebite can differ based on the species of the snake involved [7][8]. Victims may notice puncture marks at the site of the wound, accompanied by redness, swelling, bruising, bleeding, or blistering. The patient often experiences severe pain and tenderness to the bite area. Additional symptoms may include nausea, vomiting, or diarrhea, and in more severe cases, difficulty breathing, which can escalate to a cessation of breathing [7][8]. 

Other signs include a rapid heart rate (tachycardia), weak pulse, and low blood pressure (hypotension), along with blurred vision [7][8]. Some individuals report experiencing unusual tastes (such as metallic, mint, or rubber) along with increased salivation and sweating [1][7][8]. Numbness or tingling may occur around the face and/or limbs, and muscle twitching is also common among the array of symptoms [1][7][8]. 

A comprehensive history is critical for patients suspected of suffering from a snakebite as it helps outline the appropriate course of treatment. Key assessment data includes the time and place of the bite, symptoms experienced by the patient, and first aid measures taken. 

Physical examinations may reveal fang marks, alongside signs of local tissue damage, such as bruising, blistering, or necrosis.  

Elapid bites result in minimal local damage but significant systemic neurotoxic effects, while Viperid bites cause extensive local damage and systemic hemotoxic symptoms [7][19]. Neurotoxic symptoms like generalized weakness, drooping eyelids, and eye movement paralysis may appear, progressing to facial muscle paralysis and respiratory failure due to diaphragm obstruction or paralysis [7][19].  

Hemotoxic effects may be evident from significant bleeding at the bite site, nosebleeds, or spontaneous bleeding signs [7][19]. Shock symptoms due to venom-induced vasodilation, low blood volume, or anaphylactic reactions may also occur [7][19].  

Pathophysiology 

Clinical symptoms following a snake bite can occur several hours after the initial insult. Estimates project that 20% of pit viper bites do not result in envenomation (dry bites), with an additional 25% categorized as mild envenomations [16]. The variability of symptoms resulting from snake envenomations stems from the venom’s toxic elements.  

The composition of snake venom varies between species, resulting in a spectrum of outcomes from local tissue damage to significant coagulation abnormalities. The effect on humans is determined by both the potency of the venom and the quantity delivered through the bite [7][20]. 

Clinical Signs and Symptoms 

The clinical effects of snakebites manifest in local and systemic tissue. Local reactions can include swelling, blistering, and bruising [8]. Acute compartment syndrome may develop following a deep bite into a limb, characterized by intense pain, abnormal sensations, or the presentation of a cold, pulseless, and immobile limb [8][22]. Venom ophthalmia occurs when venom droplets or spray enter the eyes, causing intense pain, redness, blepharitis, blepharospasm, and corneal erosions [23].  

The primary endocrine complication arising from a snakebite is hypopituitarism (HP), a condition that can stay suppressed for years [21]. Early indicators of corticotroph axis involvement in acute scenarios are often unexplained incluce recurrent hypoglycemia, and hypotension that does not respond to treatment [21]. Acute kidney injury, capillary leak syndrome, and disseminated intravascular coagulation are also key signs pointing towards HP [24][27][31].  

Systemic snake venom can cause substantial vascular damage, common in the viperid and Australopapuan elapids species and some non-front-fanged colubroids, leading to clotting failure, platelet abnormalities, and vessel wall damage [8][25]. These effects can range from abnormalities in clotting tests to mild bleeding at the bite site or mucosal areas to severe spontaneous systemic or intracranial hemorrhage [8][25]. The 20-minute whole blood clotting test (20WBCT) demonstrates high specificity and satisfactory sensitivity in identifying and monitoring coagulopathy in settings with limited resources [13].  

The accuracy of the 20WBCT as a diagnostic tool increases when detecting severe coagulopathy [13]. Shock (resulting result from bleeding or plasma leakage into the swollen limb), myocardial dysfunction, pituitary hemorrhages, vasodilation, sepsis, and anaphylaxis may occur [7][19]. Neuromuscular effects observed with elapid and some viperid venoms can cause paralysis through actions at the neuromuscular junction either pre- or post-synaptic [21][26]. Initial symptoms may include weakness of the eye muscles presenting as ptosis, diplopia, and blurred vision, leading to sequential weakness of bulbar, neck, respiratory, and limb muscles [8][25][26]. 

Management/Treatment 

Effective first-aid includes calming the victim, applying pressure over the bite, immobilizing the affected limb, and facilitating immediate transport for medical attention. Pressure immobilization (PBI) is the sole first aid method supported by evidence that can hinder the spread of venom following a snakebite [1]. Identifying the snake species can aid in appropriate treatment, achievable through expert identification, photos, or clinical symptoms. 

Treatment involves antivenom, a life-saving medicine recognized by the WHO, as the primary antidote for envenoming [1]. Administration should occur when the benefits outweigh the risks. Skin tests for antivenom sensitivity are unreliable and not recommended [28]. Prophylactic adrenaline can reduce antivenom reaction risks unless the antivenom’s reaction risk is minimal [8]. Antivenom administration occurs via intravenous injection or infusion, with adrenaline available for potential allergic reactions [29].  

In cases where specific antivenom is unavailable, conservative treatment may be sufficient. For certain venom-induced kidney injuries, conservative management or dialysis may be effective [31]. A provider may perform a fasciotomy under specific conditions, including corrected coagulopathies, and confirmed acute compartment syndrome [30].  

Upon discharge, patients should receive advice on bite prevention and follow-up care for any late reactions or sequelae.  

Venom / Research Findings 

Antivenoms consist of a polyclonal blend of immunoglobulins or their fragments. Snake antivenom, known as antivenin, antivenene, or anti-snakebite serum, is a purified mixture of immunoglobulins obtained from hyperimmunized animals (horses or sheep) [9]. Antivenom stands as the sole remedy accessible for treating snakebite envenoming, demonstrating efficacy in neutralizing the harmful and fatal effects of various venoms [9]. An example of antivenom is Crotalidae Immune F(ab’)2 equine [32]. This specific antivenom counteracts the effects of venom from American pit vipers, including species such as cottonmouths, rattlesnakes, and copperheads [32].  

Researchers at Scripps Research have developed an antibody that can neutralize the toxins found in snake venoms from various continents including Africa, Asia, and Australia [35] [36]. The research demonstrated the use of lab-created toxin variants to search through billions of human antibodies, leading to the discovery of one that can block the venom’s harmful effects [34][36].  

When addressing a snakebite, the critical clinical judgement involves determining the necessity of administering antivenom [33]. This decision is crucial due to the potential for severe adverse reactions in some patients, prohibitive cost, limited availability of antivenom, and the fact that not all individuals bitten by snakes require it [33]. 

Conclusion

The comprehensive examination of snakebite incidents, their medical implications, and the advancement in snakebite treatment options, as depicted through numerous studies and real-life scenarios, underscores the critical nature of understanding and addressing snakebites. The statistics presented by the CDC and WHO illustrate the significant health burden posed by snake envenomation – affecting millions worldwide and resulting in substantial morbidity and mortality [2]. The classification of venomous snakes into categories based on their medical significance aids in prioritizing antivenom production and research efforts [4]. 

The importance of effective first-aid techniques (such as pressure immobilization), and the critical role of antivenom in the management of envenomed patients emphasize the key components within the snakebite treatment paradigm [1]. 

Furthermore, the ongoing research and development of new antivenom products, including the groundbreaking work by researchers at Scripps Research, represent significant strides towards improving the outcomes for snakebite victims [35]. The creation of an antibody capable of neutralizing toxins across various snake species marks a promising advancement in the quest for a universal antivenom solution [36]. 

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