Bites by Crotalinae snakes (rattlesnakes, water moccasins [cottonmouths], or copperheads) in the United States: Clinical manifestations, evaluation, and diagnosis

INTRODUCTION — The clinical manifestations, evaluation, and diagnosis of venomous Crotalinae (rattlesnake, water moccasin [cottonmouth], or copperhead) snakebites are reviewed here. The principles of management of Crotalinae snakebites, coral snakebites, and snakebites outside the United States are discussed separately. (See "Bites by Crotalinae snakes (rattlesnakes, water moccasins [cottonmouths], or copperheads) in the United States: Management" and "Evaluation and management of coral snakebites" and "Snakebites worldwide: Clinical manifestations and diagnosis".)

TERMINOLOGY — Rattlesnakes (Crotalus and Sistrurus species), water moccasins (cottonmouths, Agkistrodon piscivorus), and copperheads (Agkistrodon contortrix) are members of the family Viperidae, subfamily Crotalinae, and constitute the most common medically important snakes in North America (table 1). These snakes are also commonly called "pit vipers," a name that refers to the heat-sensing pit located behind the nostrils.

EPIDEMIOLOGY — Approximately 5000 venomous snakebites are reported to the American Association of Poison Control Centers annually [1]. Among venomous snakes, copperheads, rattlesnakes, and water moccasins (cottonmouths) account for the most snakebites in the United States; copperhead snakes are responsible for nearly half of all venomous snakebites in the United States [2-4]. These snakes are also found in southern Canada and northern Mexico. Elapids (coral snakes) and imported exotic snakes cause a much smaller number of envenomations (approximately 100 snakebites annually) [3,5].

Snakebites occur more frequently in the summer months when snakes are most active [5]. Copperhead and rattlesnake bites are more frequent than cottonmouth bites. Copperhead bites happen more commonly in the southeastern United States and rattlesnake bites in the west. Southern and western states with warmer climates, including Texas, Oklahoma, Florida, California, Arizona, Louisiana, Georgia, and North Carolina, report the greatest number of venomous snakebites [5].

Among all patients, snakebites to the lower extremity are most common [2,3]. However, among men, bites to the upper extremity predominate. Clinical effects after Crotalinae envenomation are generally more severe in patients with rattlesnake envenomation than from copperhead and cottonmouth species. However, fatalities are rare for any snakebite in the United States [5].

APPEARANCE AND GEOGRAPHICAL DISTRIBUTION — Crotalinae snakes (rattlesnakes, water moccasins [cottonmouths], and copperheads) are members of the Viperidae family and are commonly referred to as "pit vipers" [6]. They have folding, long fangs; triangular heads with an abrupt transition to the body; and numerous smaller scales on the head. Pit vipers also have heat-sensing pits towards the front of the head (for infrared "vision") and elliptical pupils. Many nonvenomous snakes are effective mimics.

Crotalinae snakes are widely distributed in the United States:

●Rattlesnake (Crotalus and Sistrurus species) – Rattlesnakes (picture 1) live throughout the continental United States; they are native to all states except Alaska, Hawaii, and Maine.

●Water moccasin (Agkistrodon piscivorus) – Water moccasins (cottonmouths) (picture 2) are found in the southeastern and southern United States, from Virginia to Florida and west to Texas.

●Copperhead (Agkistrodon contortrix) – Copperheads (picture 3) are common in the eastern half of the continental United States, extending as far west as eastern Missouri, Arkansas, and Oklahoma and extending north to south from Massachusetts to Texas.

Climate change has resulted in observable geographic and seasonal changes in United States snakebite incidence patterns in some regions [7]. For maps of geographic distributions for snake species or specific snakes by genus, species, and subspecies, refer to the Toxinology snake search.

VENOM PROPERTIES — Crotalinae venom is a complex mixture of over 50 types of toxic compounds including phospholipase A₂ (PLA₂), serine proteases, and metalloproteinases [8]. Venom composition varies across and within snake species and appears to be strongly impacted by geography, environmental conditions, including seasonal variation and prey preferences related to environment as well as snake size and location [9].

Crotalinae venom toxins produce a variety of effects after envenomation:

●Local tissue and muscle damage – Local toxic effects are seen in 90 to 100 percent of Crotalinae envenomations [3,10]. Within one hour of envenomation, enzymatic action on the extracellular matrix, the vascular endothelium, and the basement membrane causes tissue swelling, redness, and pain. Progressive swelling involving the entire extremity and/or tissue necrosis indicates a severe envenomation with potential for significant tissue loss and, for bites to the fingers or toes, autoamputation [4].

Myotoxic compounds have been identified in some rattlesnake species [5]. However, rhabdomyolysis occurs in <10 percent of Crotalinae snake envenomations. It has been most commonly described after bites by the canebrake rattlesnake (Crotalus horridus atricaudatus [no longer recognized as a subspecies of the Timber rattlesnake, Crotalus horridus]) and the Mohave rattlesnake (Crotalus scutulatus) [11-13].

●Hemotoxicity – Hemotoxicity occurs in up to 40 percent of rattlesnake envenomations and up to 15 percent of copperhead envenomations and is characterized by prolonged prothrombin time (PT), hypofibrinogenemia, and thrombocytopenia [3,14]. Frank bleeding occurs in a minority of patients, and life-threatening hemorrhage is rare [15]. Hypofibrinogenemia and thrombocytopenia occur as a result of the actions of multiple venom components, including thrombin-like enzymes, metalloproteinases, PLA₂, disintegrins and C-type lectin-like proteins [16]. This pathophysiology is in contrast to true disseminated intravascular coagulation (DIC), where fibrinolysis is activated by increased levels of endogenous thrombin.

●Cardiovascular – Hypotension may arise from a variety of venom effects such as increased capillary permeability, vasodilation, and bleeding [4].

Angioedema, hypotension, and cardiovascular collapse may arise from anaphylactic or anaphylactoid reactions but are uncommon (<1 percent of envenomations). Factors that may increase the risk of anaphylaxis to venom include previous snakebites by similar species, ingestion of rattlesnake meat, or snake handling [4,10,17,18]. Several components of venom, including bradykinin potentiating peptides and phospholipases A2, may lead to hypotension [19,20].

●Neurotoxicity – Acute neurotoxicity is uncommon after most North American snakebites [4]. Neurotoxic effects include perioral and extremity paresthesias, bulbar abnormalities (eg, dysarthria, dysphagia), and myokymia (rippling muscle movement often seen in the face and proximal extremity muscle groups; frequently characterized as fasciculations in snakebite literature). Antivenom is indicated for neurotoxicity, but both success and failure have been reported [21-23].

It is not clear why myokymia occurs, but interaction of venom components with calcium binding sites on peripheral nerves has been hypothesized [24]. Myokymia or fasciculations are most often reported after bites by the Timber rattlesnake (Crotalus horridus], but also occur after envenomation by many western rattlesnake species, including the Mohave (Crotalus scutulatus), Grand Canyon (Crotalus lutosus abyssus), Southern Pacific (Crotalus helleri), Midget Faded (Crotalus concolor), and Western diamondback (Crotalus atrox) rattlesnakes [23-27]. Myokymia may interfere with swallowing and cause upper airway obstruction or ataxia such that victims describe difficulty walking.

Severe weakness, bulbar abnormalities, and paralysis after rattlesnake bites are very uncommon but may result from envenomation by some populations of the Mohave rattlesnake (Crotalus scutulatus) and the Southern Pacific rattlesnake (Crotalus helleri) [23]. In certain locales, the venom of these snakes may possess Mojave toxin, a PLA₂ that acts presynaptically to inhibit release of acetylcholine [4,22,28,29].

●Other systemic effects – Crotalinae envenomation may also lead to nausea, vomiting, diarrhea, and metallic taste [3,4].

CLINICAL MANIFESTATIONS — Clinical findings of Crotalinae envenomation (which by definition excludes so-called "dry bites") vary by geography, the specific snake species, degree, and depth of envenomation. Envenomation tends to evolve clinically over time and more dramatically the longer treatment is delayed. Estimated frequencies include [3,4]:

●Local swelling, erythema, and pain: 90 to 100 percent.

●Thrombocytopenia and/or coagulopathy: Up to 40 percent.

●Vomiting: Up to 20 percent.

●Bleeding (typically not life-threatening): Up to 8 percent.

●Neurotoxicity: Up to 8 percent (primarily after rattlesnake bites, includes myokymia [rippling muscle movement, often seen in the face]).

●Tachycardia and/or hypotension: Up to 6 percent (primarily after rattlesnake bites).

●Rhabdomyolysis: <5 percent.

●Angioedema (allergic or anaphylactoid reaction): 1 to 2 percent.

●Weakness, paralysis: Rare for Crotalinae snakebites overall, but described in 50 percent of Mojave rattlesnake bites in one 1997 report from southern California [30].

Presenting features can also be organized as local versus systemic signs and symptoms:

●Local – The bite wound is characterized by two puncture wounds (fang marks) (picture 4 and picture 5); the distance between the wounds varies according to the size of the snake [31]. One puncture wound may also be seen and should not be dismissed as a sting or assumed to be a nonvenomous bite (picture 6).

Crotalinae envenomation produces pain, swelling (picture 7 and picture 8), ecchymoses (picture 9), and erythema at the bite site. These findings typically develop within an hour of the bite but can be slower in onset, occasionally taking eight hours or more to become apparent. Proximal spread of swelling as well as tenderness along lymphatic pathways suggests progressive toxicity [3,10]. When an extremity is elevated, swelling may move proximally due to gravity, and continued swelling distal to the bite will aid in determining progression of envenomation.

Hemorrhagic bullae (picture 10) develop at the bite site in up to 40 percent of patients with bites to upper extremities (picture 11) [32].

"Dry bites" (in which no venom was injected) occur in approximately 25 percent of Crotalinae snakebites in the United States and show only minimal local irritation [1,6,10].

●Systemic – Nausea, vomiting, tachycardia, paresthesias, hypotension, and dizziness suggest more severe envenomation [1,3,4,10]. Bleeding, hypotension, fasciculations, weakness, and altered mental status signal a potentially life-threatening envenomation.

EVALUATION — Identifying signs of envenomation and indications for antivenom will guide further management (algorithm 1). Clinical findings are likely to progress over time and may progress slowly; even very minor findings at presentation may develop into significant ones over time. Thus, any patient with a possible Crotalinae snakebite warrants emergency evaluation and observation for at least 8 to 12 hours, even in the absence of symptoms [10]. (See "Bites by Crotalinae snakes (rattlesnakes, water moccasins [cottonmouths], or copperheads) in the United States: Management".)

Stabilization — Prior to evaluation, emergency stabilization of airway, breathing, and circulation should occur as needed.

Emergency management of shock followed by timely antivenom administration to patients with moderate or severe envenomation comprise the most common actions needed when stabilizing patients with Crotalinae snakebites. Patients with myokymia, muscle weakness, angioedema, or bites to the face or neck warrant close airway assessment and may require emergency endotracheal intubation. (See "Bites by Crotalinae snakes (rattlesnakes, water moccasins [cottonmouths], or copperheads) in the United States: Management".)

History — When a snakebite is reported or suspected, key information to determine includes:

●Where and when the bite occurred

●A description of the snake, whenever possible

●How the bite occurred and whether there was more than one bite

●Any signs or symptoms and the timing of onset

●Initial treatment and first aid that was provided, including timing of first aid (see "Bites by Crotalinae snakes (rattlesnakes, water moccasins [cottonmouths], or copperheads) in the United States: Management", section on 'First aid')

●Any recent ethanol or recreational drug use that may modify the patient's presentation

●Pertinent past medical history, such as current medications (especially anticoagulants or beta blockers), any prior snakebites for which antivenom was given, or allergy to animals used in antivenom production (eg, horses or sheep)

In most cases, the Crotalinae snakebite is immediately felt. However, children may occasionally present with irritability, shock, or sudden collapse without any reported snakebite.

Although Crotalinae envenomations most frequently present with local tissue effects, the signs and symptoms of a snakebite can be nonspecific and frequently may be difficult to differentiate from manifestations of anxiety and emotional disturbance caused by the bite. Findings such as nausea, vomiting, abdominal pain, and diarrhea may be the first symptoms of systemic envenomation and warrant close assessment for onset of angioedema, hypotension, or shock.

Symptoms also vary according to the venom characteristics of the biting snake. In general, rattlesnake envenomations cause more severe signs and symptoms than water moccasins (cottonmouths) or copperheads [5]. Copperheads usually cause only limited local tissue swelling and pain with no systemic symptoms [14,33]. However, the identity of the offending snake is often unknown. In addition, bites from any of the Crotalinae snakes (rattlesnake, water moccasin [cottonmouth], or copperhead) may cause clinically significant findings. (See 'Clinical manifestations' above.)

Weakness after a snakebite in the appropriate region suggests a bite by the Mohave rattlesnake (Crotalus scutulatus), or, less commonly, the Southern Pacific rattlesnake (Crotalus helleri) [28,30]. (See 'Venom properties' above.)

Physical examination — Findings on physical examination vary based on many factors related to both the snake and the patient and may evolve over time:

●Vital signs

•In the calm patient, envenomation without systemic toxicity typically presents with normal or near-normal vital signs.

•Mild tachycardia or tachypnea may reflect anxiety or pain, or represent early findings of systemic envenomation.

•Marked tachycardia, tachypnea, or hypotension often indicates systemic toxicity.

●Systemic findings

•Cardiovascular – Tachycardia and findings of shock, including hypotension and/or poor tissue perfusion (eg, prolonged capillary refill time, altered mental status, and decreased urine output) signify severe Crotalinae envenomation. Causes include venom-induced vasodilation and/or hypovolemia from bleeding or "third spacing" of fluids into the bitten limb. These patients warrant emergency stabilization. (See "Bites by Crotalinae snakes (rattlesnakes, water moccasins [cottonmouths], or copperheads) in the United States: Management", section on 'Initial stabilization'.)

Angioedema, hypotension, and cardiovascular collapse may arise from anaphylactic or anaphylactoid reactions. Individuals with any one of the following may be at increased risk for anaphylaxis to venom: snakebites by similar species, ingestion of rattlesnake meat, or snake handling [4,10,17,18].

•Hemotoxicity – Signs of overt bleeding should be sought and usually present as low-grade bleeding from gums, oozing from needle puncture sites, epistaxis, or petechiae. Bleeding is most common when severe venom-induced thrombocytopenia and coagulopathy coexist, but risk is also increased in patients using anticoagulant or antiplatelet medications [15].

•Tissue and muscle toxicity – Most patients with Crotalinae envenomation have local tissue swelling surrounding the bite site, as described below.

Less commonly, muscle pain on palpation or with muscle use, muscle weakness, and dark urine may indicate the presence of rhabdomyolysis. Early findings of rhabdomyolysis may be subtle and frequently require measurement of serum creatine kinase and urine studies for confirmation. (See 'Ancillary studies' below.)

Although rare after a Crotalinae snakebite, compartment syndrome may occur if marked extremity swelling or direct envenomation of a muscle compartment occurs. (See "Bites by Crotalinae snakes (rattlesnakes, water moccasins [cottonmouths], or copperheads) in the United States: Management", section on 'Elevated tissue pressures'.)

Findings of compartment syndrome can significantly overlap with local and systemic effects of envenomation and include (see "Acute compartment syndrome of the extremities", section on 'Clinical features'):

-Pain upon passive stretching of the muscle (although this can also be caused by venom-induced myolysis)

-Marked burning or aching pain that is not controlled despite parenteral opioid analgesia (eg, morphine)

-Paresthesias and/or diminished sensation

-Muscle weakness (although this can also be caused by venom-induced myolysis or neurotoxicity)

-Tense compartment with a wooden feeling to palpation (late sign)

-Pallor and/or pulselessness (late sign)

Direct measurement of compartment pressures are essential to verify the clinical impression. (See "Acute compartment syndrome of the extremities", section on 'Measurement of compartment pressures'.)

•Neurotoxicity – Weakness may occur after bites by some populations of the Mohave rattlesnake (Crotalus scutulatus) or Southern Pacific rattlesnake (Crotalus helleri). Myokymia (rippling muscle movement often seen in the face) is a more common neurologic manifestation that has been associated with bites by several species of rattlesnakes, including the Timber rattlesnake (Crotalus horridus), the Mohave rattlesnake (Crotalus scutulatus), the Grand Canyon rattlesnake (Crotalus lutosus abyssus), the Southern Pacific rattlesnake (Crotalus helleri), the Midget Faded rattlesnake (Crotalus concolor), and the Western diamondback rattlesnake (Crotalus atrox) [24-27].

●Wound site – The clinician should examine the bite site and surrounding region for the following:

•Presence of fang marks (eg, single or multiple punctures or scratches; fang marks may be difficult to visualize in some species) (picture 4 and picture 5 and picture 6 and picture 12).

•Local evidence of envenomation including redness, swelling, blistering, ecchymosis, persistent blood ooze, or tissue necrosis (picture 7 and picture 8 and picture 9 and picture 10 and picture 11).

•Degree of swelling, using demarcation of the extent of swelling from the bite site for reference during repeated examinations (picture 7). If a leading edge of swelling is not evident, repeated measurement of extremity circumference both proximal and distal to the bite site may be used to determine if swelling is progressing over time.

Swelling that progresses only proximally after elevation of the extremity does not alone represent progression of envenomation.

•Swelling or tenderness of regional lymph nodes indicating venom spread.

Ancillary studies — Evaluation for suspected Crotalinae envenomation (rattlesnake, water moccasin [cottonmouth], or copperhead bite) should include the following studies to assess for evidence of hematologic and muscle toxicity:

●Complete blood count

●Fibrinogen level

●Prothrombin time (PT)

●International normalized ratio (INR)

Patients with evidence of systemic toxicity should also have the following studies obtained:

●Serum creatine kinase (CK)

●Serum electrolytes, creatinine and blood urea nitrogen

●Chest radiograph

●Electrocardiogram (ECG)

Concern for compartment syndrome or neurotoxicity:

●Serum CK

If fibrinogen testing is not immediately available, a D-dimer or fibrin degradation products (fibrin split products [FSPs]) can be obtained, ideally at least four hours post-envenomation, to determine if fibrinogenolytic effects are occurring. Some experts routinely obtain D-dimer at four or more hours after a Crotalinae snakebite to identify patients whose initial labs do not show significant abnormalities, but who remain at risk for delayed hemotoxicity.

Presence of venom-induced thrombocytopenia or hypofibrinogenemia indicates an increased risk of postdischarge hematologic recurrence, although late hemotoxicity may also occur in patients without early platelet or fibrinogen abnormalities. (See "Bites by Crotalinae snakes (rattlesnakes, water moccasins [cottonmouths], or copperheads) in the United States: Management", section on 'Prevention of early recurrent toxicity'.)

Hematologic toxicity (prolonged PT, thrombocytopenia, or hypofibrinogenemia) may not be apparent at presentation but can develop over several hours after the snakebite. Platelet count and fibrinogen levels should be repeated at regular intervals. If antivenom is given, they should be repeated one hour following administration to assess for control of hematological effects. Additional monitoring of hematologic toxicity depends upon patient response and specific antivenom given. The frequency of repeated measurements varies depending on the severity of the envenomation. (See "Bites by Crotalinae snakes (rattlesnakes, water moccasins [cottonmouths], or copperheads) in the United States: Management", section on 'Identification and treatment of late hemotoxicity'.)

Reassessment — Frequent, repeated examinations are important to ensure detection of all signs of Crotalinae snake envenomation and to identify serious and progressive local or systemic effects. All patients with a potentially toxic snakebite warrant frequent measurement of blood pressure and continuous cardiorespiratory and pulse oximetry monitoring.

Hematologic studies should also be repeated:

●Potential dry bite or minimal local findings – Repeat at least four hours after initial studies and at least eight hours after the bite occurred. If any decrease in platelets or fibrinogen occurs, even if the values remain within normal range, repeat again after at least another four hours.

●Envenomation – Repeat one hour after each administration of antivenom. Recommendations for monitoring of late hematotoxicity after administration of Crotalidae polyvalent-immune Fab (ovine), brand name CroFab (FabAV), and Anavip are discussed separately. (See "Bites by Crotalinae snakes (rattlesnakes, water moccasins [cottonmouths], or copperheads) in the United States: Management", section on 'Prevention of early recurrent toxicity'.)

DIAGNOSIS — The diagnosis of bites by Crotalinae snakes (rattlesnakes, water moccasins [cottonmouths], or copperheads) is usually straightforward because the bite is immediately felt and a snake is seen. The presence of fang marks (picture 4 and picture 5 and picture 6 and picture 12), pain, and local effects of swelling, ecchymosis, and blistering (picture 7 and picture 8 and picture 9 and picture 10 and picture 11), or evidence of systemic envenomation provide confirmation. (See 'Clinical manifestations' above.)

Snakebites may go unrecognized if they occur in young or unsupervised children or cause sudden collapse with unconsciousness in older children and adults. Thus, the clinician should maintain a high index of suspicion for a Crotalinae snakebite when evaluating presentations of abrupt onset of irritability (young children), unilateral extremity swelling, cardiovascular collapse, and/or neurologic impairment, especially in regions where venomous snakes are common (eg, southern and western United States and Mexico) [34].

Treatment of any suspected Crotalinae snakebite should proceed based on signs and symptoms irrespective of the snake species [10]. Thus, definitive identification of the biting snake is not required to establish a diagnosis of envenomation.

DIFFERENTIAL DIAGNOSIS — In many patients, the diagnosis of a snakebite is obvious based upon clinical findings. For these patients, the key differential diagnosis is between bites by venomous (eg, Crotalinae) and nonvenomous snakes. Serious envenomation is established by the development of characteristic local or systemic effects after the bite. (See 'Clinical manifestations' above.)

When a snakebite is not obvious from the clinical presentation, sudden collapse, syncope, unexplained hematologic abnormalities (eg, thrombocytopenia, hypofibrinogenemia, and/or coagulopathy), developing descending flaccid paralysis (rare), or rhabdomyolysis (rare) should raise the possibility of Crotalinae snakebite within a wider set of differential diagnoses. In addition, a patient stating that they have suffered a snakebite may potentially present with clinical features that could have other etiologies that might become apparent after further evaluation:

●Other hematologic disease with coagulopathy or bleeding – Sepsis, multiple trauma, obstetrical complications, or malignancy may present with similar hematologic features to snake envenomation, but are readily distinguished by clinical findings (eg, the presence of fever and signs of infection [eg, pneumonia, urinary tract infection, and/or petechiae] in patients with sepsis, evidence of multiple trauma, or known or suspected malignancy). (See "Evaluation and management of disseminated intravascular coagulation (DIC) in adults".)

Bleeding may also be caused by a wide array of other disease states, including hereditary abnormalities of the hemostasis system (eg, hemophilia or von Willebrand disease). Of note, mild variants of such congenital abnormalities are an important underlying cause for unexplained, minor changes in coagulation tests in a snakebite patient who otherwise shows no evidence of significant envenomation. In many instances, a careful history and physical examination and more rigorous laboratory testing can define the underlying cause. (See "Approach to the child with bleeding symptoms" and "Approach to the adult with a suspected bleeding disorder".)

●Rhabdomyolysis – Rhabdomyolysis may be caused by other disease states. The causes of rhabdomyolysis can be broadly divided into three categories:

•Traumatic or muscle compression (eg, crush syndrome or prolonged immobilization)

•Nontraumatic exertional (eg, marked exercise, hyperthermia, or metabolic myopathies)

•Nontraumatic nonexertional (eg, drugs or toxins such as snake venoms, infections, or electrolyte disorders)

In most instances, rhabdomyolysis caused by snakebite is associated with pain and local swelling and thus is readily distinguished from other causes. The causes of rhabdomyolysis and its diagnosis are discussed in detail separately. (See "Rhabdomyolysis: Epidemiology and etiology" and "Rhabdomyolysis: Clinical manifestations and diagnosis".)

●Acute weakness and paralysis (Mohave or Southern Pacific rattlesnake bite) – Toxic encounters in addition to snakebites that may cause flaccid paralysis include paralytic tick envenomation, paralytic shellfish poisoning, nicotine poisoning (ingestion or dermal exposure), or botulism. In most instances, history of a snakebite and fang marks will rapidly distinguish these rattlesnake bites from other toxic conditions.

Additional differentiating features include the following:

•Tick paralysis typically has a slower onset of weakness and may present with ataxia or localized facial or extremity paralysis. Tick paralysis is diagnosed by finding an attached argasid or ixodid tick. (See "Tick paralysis", section on 'Clinical manifestations'.)

•Food history including ingestion of shellfish (especially noncommercially harvested bivalve mollusks) or home-canned foods helps to identify paralytic shellfish poisoning or foodborne botulism, respectively. (See "Overview of shellfish, pufferfish, and other marine toxin poisoning", section on 'Paralytic shellfish poisoning' and "Botulism", section on 'Clinical manifestations'.)

•Secondary muscarinic symptoms (eg, salivation, lacrimation, vomiting, diarrhea, wheezing, diaphoresis, small pupils) and primary nicotinic signs (eg, tachycardia, hypertension, and seizures) suggest nicotine poisoning. (See "Potentially toxic plant ingestions in children: Clinical manifestations and evaluation", section on 'Nicotinic poisoning'.)

The approach to acquired muscle weakness caused by other medical illness (eg, myasthenia gravis or demyelinating disease) is described separately. (See "Approach to the patient with muscle weakness" and "Etiology and evaluation of the child with weakness" and "Evaluation of the adult with acute weakness in the emergency department".)

ADDITIONAL RESOURCES

Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Envenomation by snakes, arthropods (spiders and scorpions), and marine animals".)

SUMMARY AND RECOMMENDATIONS

●Medically important snakes – Rattlesnakes (Crotalus and Sistrurus species) (picture 1), water moccasins (cottonmouths; Agkistrodon piscivorus) (picture 2), and copperheads (Agkistrodon contortrix) (picture 3) are members of the family Viperidae, subfamily Crotalinae (formerly Crotalidae) and represent the most common medically important snakes found in North America (table 1). They are also commonly called pit vipers, a name that refers to the heat-sensing pits located behind their nostrils. (See 'Terminology' above.)

Among venomous snakes, copperheads, rattlesnakes, and water moccasins (cottonmouths) account for the most snakebites in the United States. These snakes are also found in southern Canada and Mexico. (See 'Epidemiology' above and 'Appearance and geographical distribution' above.)

●Clinical manifestations – Symptomatic Crotalinae (rattlesnake, water moccasin [cottonmouth], or copperhead) envenomation typically causes swelling, local tissue damage with ecchymosis, and hematologic toxicity. Other potential sequelae include vomiting, diarrhea, oral paresthesias, an unusual metallic taste, shock, bleeding, rhabdomyolysis, angioedema with cardiovascular collapse, myokymia, or neuromuscular weakness (typically after bites by the Mohave or Southern Pacific rattlesnake). (See 'Clinical manifestations' above and 'Venom properties' above.)

●Evaluation – Clinical evaluation of Crotalinae snakebites begins with emergency stabilization of any systemic effects (eg, hypotension, bleeding, altered mental status, or, for bites to the face or neck, upper airway obstruction) followed by an assessment of the wound site and local adjacent tissues. Determining presence of envenomation is essential to guide further management (algorithm 1). (See 'Evaluation' above.)

Signs of envenomation include (see 'Physical examination' above):

•Presence of fang marks (picture 4 and picture 5 and picture 6 and picture 12).

•Redness, swelling, blistering, ecchymosis, persistent blood ooze, or tissue necrosis at the bite site (picture 7 and picture 8 and picture 9 and picture 10 and picture 11).

•Progression of swelling, using demarcation of the extent of swelling from the bite site for reference during repeated examinations (picture 7) or, if a leading edge of swelling is not evident, repeated measurement of extremity circumference both proximal and distal to the bite site. Proximal redistribution of edema resulting from limb elevation alone does not constitute progression of swelling.

•Bleeding other than at the bite site (eg, epistaxis, bleeding from gums, or oozing at needle puncture sites), hypotension, anaphylaxis, myokymia (rippling muscle movement often seen in the face), or, rarely, weakness.

●Ancillary studies – Initial laboratory studies after a suspected Crotalinae snakebite include (see 'Ancillary studies' above):

All patients:

•Complete blood count

•Fibrinogen level

•Prothrombin time (PT)

•International normalized ratio (INR)

Patients with evidence of systemic toxicity should also have the following studies obtained:

•Serum electrolytes, creatinine and blood urea nitrogen

•Serum creatine kinase (CK)

•Chest radiograph

•Electrocardiogram (ECG)

Concern for compartment syndrome or neurotoxicity:

•Serum CK

Hemotoxicity (prolonged PT, thrombocytopenia, or hypofibrinogenemia) may not be apparent at presentation but can develop over several hours after the snakebite.

●Reassessment – Frequent, repeated examinations are important to ensure detection of all signs of Crotalinae snake envenomation and to identify serious and progressive local or systemic effects. All patients with a potentially toxic snakebite warrant frequent measurement of blood pressure and continuous cardiorespiratory and pulse oximetry monitoring. (See 'Reassessment' above.)

Hematologic studies and blood chemistries should be repeated according to the severity of the envenomation. (See "Bites by Crotalinae snakes (rattlesnakes, water moccasins [cottonmouths], or copperheads) in the United States: Management", section on 'Initial stabilization'.)

●Diagnosis – The diagnosis of bites by Crotalinae snakes (rattlesnakes, water moccasins [cottonmouths], or copperheads) is usually straightforward because the bite is immediately felt and a snake is seen. The presence of fang marks, pain, and local effects of swelling, ecchymosis, and blistering, or evidence of systemic envenomation provide confirmation. Definitive identification of the biting snake is not required to establish a diagnosis of a Crotalinae snakebite. (See 'Diagnosis' above.)

The clinician should also maintain a high index of suspicion for a Crotalinae snakebite when evaluating presentations of abrupt onset of irritability (young children), unilateral extremity swelling, cardiovascular collapse, and/or neurologic impairment, especially in regions where venomous snakebites are common (eg, southern and western United States and northern and central Mexico). (See 'Diagnosis' above.)

ACKNOWLEDGMENT — We are saddened by the death of Steven A Seifert, MD, FAACT, FACMT, who passed away in May 2022. UpToDate gratefully acknowledges Dr. Seifert's outstanding work as an author for this topic.