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EUROPEAN SNAKES

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Europe has comparatively few species of snakes, possibly due to the cool climate, scarcity of suitable habitats and history of glaciation which eliminated most snakes around 10,000 to 20,000 years ago.
    B) Venomous snakes in Europe seem to be limited in distribution, especially in the northern regions. In Scandinavia and Finland, the European Viper ranges slightly above the Arctic Circle. The Mediterranean region has the greatest number of venomous snake species and the most dangerous of the snake species in Europe.
    C) Envenomations usually result from bites by snakes of the following families: Viperidae, Colubridae, and Crotalidae.

Specific Substances

    1) SNAKE BITE (EUROPEAN)
    2) SNAKE VENOM POISONING, EUROPE
    3) SNAKES OF EUROPE

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) BACKGROUND: There are relatively few poisonous snakes in Europe, and the species present are relatively less dangerous than other species around the world. Venomous snakes that may be encountered include the asp viper (Vipera aspis), common adder or common viper (Vipera berus), long-nosed adder or sand viper (Vipera ammodytes), Pallas' viper (Agkistrodon halys), Lataste's viper (Vipera lastastei) and Ursini's viper (Vipera ursinii).
    B) TOXICOLOGY: The venoms of European snakes are complex mixtures containing proteins with enzymatic and toxic properties, hyaluronidase, phospholipases and phosphodiesterases.
    C) EPIDEMIOLOGY: A study showed that the annual number of snake bites in Europe's population of approximately 730 million people is about 25,000. Approximately 8000 bites result in envenomation, with 90% of those patients requiring hospitalization. Approximately 30 deaths could be attributed to snake bites. No deaths due to snake bites have occurred in Great Britain since 1975. Bites are more likely to occur in rural areas of southern Europe including Spain and Italy, where rates can be as high as 5 in 100,000 people.
    D) WITH POISONING/EXPOSURE
    1) ENVENOMATION
    a) SUMMARY: While there are several different species of viper native to Europe, the manifestations caused by envenomation are similar among species.
    b) LOCAL EFFECTS: Initial pain is generally mild, but it may become quite severe as local injury progresses. Edema is common. In severe cases, edema can progress for 48 to 72 hours and may involve the entire bitten extremity and the trunk. After approximately 24 hours, edema becomes hemorrhagic. Blisters may develop along with ecchymosis and regional lymphadenopathy. Necrosis and gangrene are uncommon but have been reported. Edema generally resolves over 1 to 2 weeks.
    c) SYSTEMIC EFFECTS: The following events can develop and are listed based on the frequency of occurrence:
    1) GASTROINTESTINAL: Nausea, vomiting, diarrhea and abdominal pain are the most common systemic effects. GI effects generally develop within minutes to a few hours in patients with moderate to severe envenomation. GI bleeding is uncommon.
    2) CARDIOVASCULAR: Tachycardia is a common early finding. Hypotension may develop with severe envenomation secondary to both vasodilation and intravascular volume loss. ECG changes (T wave flattening or inversion) have been reported. Dysrhythmias are uncommon, but atrial fibrillation, second degree heart block, bradycardia and tachycardia have been described. Myocardial infarction is a rare complication.
    3) NEUROLOGIC: Dizziness, vertigo, anxiety fatigue and somnolence may occur. Coma may occur with severe envenomation, and seizures have been reported, but are rare. Cranial nerve palsies (ophthalmoplegia, ptosis, difficulty swallowing or speaking), and paralysis of the bitten limb have been reported after V. Ipera aspis, V. latasti and V. ursinii envenomation, but are not common. Paresthesia has been reported after V. berus envenomations.
    4) RENAL: Proteinuria and hematuria are well described. Acute renal insufficiency and oliguria are rare, but may develop secondary to shock and/or hemolysis.
    5) RESPIRATORY: Angioneurotic edema occurs in a significant minority of patients after V berus envenomation. Bronchospasm occurs rarely. Acute lung injury may develop several days after severe envenomation, particularly in children.
    6) HEMATOLOGIC: Early hemoconcentration and leukocytosis are common, often followed by mild anemia. Thrombocytopenia is common in severe envenomation and prolongation of INR and PTT may also develop. Systemic bleeding is unusual but may occur.
    2) SEQUELAE
    a) Mild swelling, joint stiffness and restricted mobility, pain, sensory disturbances, and lymphedema may persist for months after envenomation, particularly in adults.
    3) DRY BITES
    a) Approximately 10% to 20% of bites are "dry" and do not result in envenomation.
    0.2.3) VITAL SIGNS
    A) WITH POISONING/EXPOSURE
    1) Tachycardia and hypotension may develop.
    0.2.4) HEENT
    A) WITH POISONING/EXPOSURE
    1) Ptosis and swelling of the face and lips or tongue develops in 10% to 30% of patients with V. berus envenomation, more commonly after moderate or severe envenomation.
    0.2.5) CARDIOVASCULAR
    A) WITH POISONING/EXPOSURE
    1) Circulatory collapse, hemorrhage, and ECG changes may occur in severe envenomations.
    0.2.6) RESPIRATORY
    A) WITH POISONING/EXPOSURE
    1) Bronchospasm and respiratory distress may occur. Angioedema develops in about 10% to 20% of patients with V. berus envenomation, and may cause respiratory compromise if severe. Acute lung injury may develop with severe envenomation.
    0.2.7) NEUROLOGIC
    A) WITH POISONING/EXPOSURE
    1) CNS depression, weakness, and paresthesias are fairly common. Seizures and bulbar palsy are rare complications. Dysphonia has been reported in two patients following V aspis envenomation.
    0.2.8) GASTROINTESTINAL
    A) WITH POISONING/EXPOSURE
    1) Nausea, vomiting, and diarrhea are commonly seen in severe envenomations. Rare reports of intestinal infarction have occurred with V aspis envenomation.
    0.2.10) GENITOURINARY
    A) WITH POISONING/EXPOSURE
    1) Proteinuria and hematuria may occur. Renal failure may also occur secondary to rhabdomyolysis.
    0.2.13) HEMATOLOGIC
    A) WITH POISONING/EXPOSURE
    1) Leukocytosis and anemia are common. Thrombocytopenia, hemorrhage and coagulopathy may develop with severe envenomation. Hemolysis has been reported after V. berus envenomation.
    0.2.14) DERMATOLOGIC
    A) WITH POISONING/EXPOSURE
    1) Severe local reactions may be seen with marked swelling, vesicle formation, ecchymoses, and rarely necrosis.
    0.2.15) MUSCULOSKELETAL
    A) WITH POISONING/EXPOSURE
    1) There may be rhabdomyolysis and tissue damage from the proteolytic enzymes in the venom. Compartment syndrome is rare.
    0.2.19) IMMUNOLOGIC
    A) WITH POISONING/EXPOSURE
    1) Anaphylactic (IgE mediated) and anaphylactoid reactions have occurred to the venom of Vipera species.
    0.2.20) REPRODUCTIVE
    A) There are three published cases where severe envenomation in pregnant women resulted in fetal demise. Normal pregnancy outcomes have been reported after moderate envenomation treated with antivenom.

Laboratory Monitoring

    A) Monitor vital signs and mental status. Monitor for development and progression of local swelling.
    B) Monitor CBC with platelet count and urinalysis.
    C) In patients with progression of swelling or evidence of systemic envenomation, monitor serum electrolytes, renal function, CK, coagulation studies (INR, aPTT, fibrinogen, fibrin degradation products) and tests for hemolysis (free hemoglobin and LDH).
    D) Monitor ECG in patients with evidence of systemic envenomation.

Treatment Overview

    0.4.7) BITES/STINGS
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Patients should be observed for signs of progression of local symptoms, or any clinical or laboratory evidence of envenomation for at least 8 hours. Management is mainly supportive.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Severe toxicity is manifested as disseminated intravascular coagulopathy (DIC) causing severe bleeding and end-organ ischemia. These patients should receive antivenom, if available, for the identified species. The administration of clotting factors (FFP) and platelets are not supported by evidence, but should be considered in patients with severe bleeding. A species specific or partially specific antivenom should be administered. Regional poison centers will be able to access information on the most appropriate antivenom, guidelines and availability. MAVIN, the Munich Antivenom Index, provides a list of venomous European snakes, the corresponding antivenom as well as the name and location of centers holding the antivenom.
    C) AIRWAY MANAGEMENT
    1) Airway management is unlikely to be necessary unless the patient develops severe DIC causing central nervous system ischemia and loss of airway reflexes or if the patient has an anaphylactoid type reaction.
    D) ANTIVENOM
    1) Antivenom is indicated in patients with hypotension or shock, intense or prolonged gastrointestinal symptoms, rapidly progressing or extensive edema, coagulation disturbances, or neurologic disturbances. It should also be considered in patients with less severe circulatory effects and any of the following: metabolic acidosis, increased CK, hemolysis, ECG changes or coagulopathy. Several monovalent and polyvalent antivenoms are available. Any antivenom may cause an acute allergic reaction, administer in a setting with careful monitoring and be prepared to treat anaphylaxis.
    E) PATIENT DISPOSITION
    1) HOME CRITERIA: Any patient with a European snake bite should be sent to the hospital. Most species are minimally dangerous to humans, but the species may be unclear at presentation.
    2) OBSERVATION CRITERIA: Patients with a clear nonvenomous species envenomation can be discharged after wound care. If the snake is not definitively identified, the most conservative approach is to observe the patient for local symptoms and evaluate for coagulopathy for at least 8 hours. Patients who do not develop any clinical or laboratory evidence of envenomation during that time may be discharged.
    3) ADMISSION CRITERIA: All patients who develop clinical or laboratory evidence of envenomation should be admitted.
    4) CONSULT CRITERIA: Consult a medical toxicologist, toxinologist or poison center for any patient with significant envenomation or in whom the diagnosis is unclear. The local poison control center can help locate appropriate antivenom.
    F) PITFALLS
    1) Coagulopathy can be delayed.
    G) DIFFERENTIAL DIAGNOSIS
    1) Elapid envenomations, a nonvenomous snake bite, DIC due to infection or malignancy.

Range Of Toxicity

    A) TOXIC DOSE: About 10% to 20% of bites are "dry" and no envenomation develops. A single bite can cause severe envenomation and can be lethal, but death is unusual with modern medical care.

Clinical Effects

Summary Of Exposure

    A) BACKGROUND: There are relatively few poisonous snakes in Europe, and the species present are relatively less dangerous than other species around the world. Venomous snakes that may be encountered include the asp viper (Vipera aspis), common adder or common viper (Vipera berus), long-nosed adder or sand viper (Vipera ammodytes), Pallas' viper (Agkistrodon halys), Lataste's viper (Vipera lastastei) and Ursini's viper (Vipera ursinii).
    B) TOXICOLOGY: The venoms of European snakes are complex mixtures containing proteins with enzymatic and toxic properties, hyaluronidase, phospholipases and phosphodiesterases.
    C) EPIDEMIOLOGY: A study showed that the annual number of snake bites in Europe's population of approximately 730 million people is about 25,000. Approximately 8000 bites result in envenomation, with 90% of those patients requiring hospitalization. Approximately 30 deaths could be attributed to snake bites. No deaths due to snake bites have occurred in Great Britain since 1975. Bites are more likely to occur in rural areas of southern Europe including Spain and Italy, where rates can be as high as 5 in 100,000 people.
    D) WITH POISONING/EXPOSURE
    1) ENVENOMATION
    a) SUMMARY: While there are several different species of viper native to Europe, the manifestations caused by envenomation are similar among species.
    b) LOCAL EFFECTS: Initial pain is generally mild, but it may become quite severe as local injury progresses. Edema is common. In severe cases, edema can progress for 48 to 72 hours and may involve the entire bitten extremity and the trunk. After approximately 24 hours, edema becomes hemorrhagic. Blisters may develop along with ecchymosis and regional lymphadenopathy. Necrosis and gangrene are uncommon but have been reported. Edema generally resolves over 1 to 2 weeks.
    c) SYSTEMIC EFFECTS: The following events can develop and are listed based on the frequency of occurrence:
    1) GASTROINTESTINAL: Nausea, vomiting, diarrhea and abdominal pain are the most common systemic effects. GI effects generally develop within minutes to a few hours in patients with moderate to severe envenomation. GI bleeding is uncommon.
    2) CARDIOVASCULAR: Tachycardia is a common early finding. Hypotension may develop with severe envenomation secondary to both vasodilation and intravascular volume loss. ECG changes (T wave flattening or inversion) have been reported. Dysrhythmias are uncommon, but atrial fibrillation, second degree heart block, bradycardia and tachycardia have been described. Myocardial infarction is a rare complication.
    3) NEUROLOGIC: Dizziness, vertigo, anxiety fatigue and somnolence may occur. Coma may occur with severe envenomation, and seizures have been reported, but are rare. Cranial nerve palsies (ophthalmoplegia, ptosis, difficulty swallowing or speaking), and paralysis of the bitten limb have been reported after V. Ipera aspis, V. latasti and V. ursinii envenomation, but are not common. Paresthesia has been reported after V. berus envenomations.
    4) RENAL: Proteinuria and hematuria are well described. Acute renal insufficiency and oliguria are rare, but may develop secondary to shock and/or hemolysis.
    5) RESPIRATORY: Angioneurotic edema occurs in a significant minority of patients after V berus envenomation. Bronchospasm occurs rarely. Acute lung injury may develop several days after severe envenomation, particularly in children.
    6) HEMATOLOGIC: Early hemoconcentration and leukocytosis are common, often followed by mild anemia. Thrombocytopenia is common in severe envenomation and prolongation of INR and PTT may also develop. Systemic bleeding is unusual but may occur.
    2) SEQUELAE
    a) Mild swelling, joint stiffness and restricted mobility, pain, sensory disturbances, and lymphedema may persist for months after envenomation, particularly in adults.
    3) DRY BITES
    a) Approximately 10% to 20% of bites are "dry" and do not result in envenomation.

Vital Signs

    3.3.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Tachycardia and hypotension may develop.
    3.3.2) RESPIRATIONS
    A) WITH POISONING/EXPOSURE
    1) Respirations may be increased.
    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) Fever develops in some patients following envenomation (Al et al, 2010).
    2) A prospective analysis regarding the clinical presentation of venomous snakebites in the Herzegovina region from 1997 to 2002, reported the occurrence of fever in approximately 8% of patients (n=71) who were admitted to the hospital following the snakebites. Snake identification was not presented within this analysis (Bubalo et al, 2004).
    3) In a series of 147 patients with viper bites (mostly V ammodytes) treated in a hospital in Greece, 34 (23%) had fever (Frangides et al, 2006).
    4) In a series of 79 patients with Vipera ammodytes envenomation from southeast Turkey, fever was reported in 15 (19%) patients (Al et al, 2010).

Heent

    3.4.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Ptosis and swelling of the face and lips or tongue develops in 10% to 30% of patients with V. berus envenomation, more commonly after moderate or severe envenomation.
    3.4.2) HEAD
    A) WITH POISONING/EXPOSURE
    1) CASE SERIES: In 12 of 29 cases of severe V berus envenomation, swelling of the face and lips and/or tongue developed, sometimes immediately post-bite, and lasted for up to 2 days (Reid, 1976).
    2) CASE SERIES: In a series of 46 patients with V. berus envenomation, 10 (22%) developed angioedema within 6 hours of the bite (Karlson-Stiber & Persson, 1994).
    3) CASE SERIES: Swelling of the lips and tongue developed in 10 of 68 patients (15%) of patients with V berus bites in a series from Finland (Gronlund et al, 2003).
    4) CASE SERIES: Angioedema was reported in 9% of 204 patients with V berus envenomation in one Swedish series(Karlson-Stiber et al, 2006), and 10 out of 30 patients (33%) in another (Karlson-Stiber & Persson, 1994a). It appears to be more common in patients with moderate or severe envenomation (Karlson-Stiber et al, 2006).
    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) PTOSIS
    a) Paresis of the third cranial nerve producing ptosis, ophthalmoplegia, diplopia and reduced visual acuity occurred in patients envenomated by Vipera berus bosniensis (Balkan adder). Ptosis was the most common sign of neurotoxicity in these victims. Symptoms gradually resolved. These neurotoxic events were relatively common compared to Central or Eastern European V berus berus bites (Malina et al, 2011).
    2) DIPLOPIA
    a) Diplopia was reported in an adult following a bite by a V berus with some strabismus about 90 minutes after the bite. Nystagmus was absent. The patient refused antivenom therapy due to concerns about a reaction. Diplopia last about 11 hours and resolved spontaneously (Malina et al, 2008a).

Cardiovascular

    3.5.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Circulatory collapse, hemorrhage, and ECG changes may occur in severe envenomations.
    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) SUMMARY: Hypotension is a relatively common systemic adverse event following a Vipera (V aspis and V bera) envenomation (Magdalan et al, 2010; Moser & Roeggla, 2009; Gronlund et al, 2003; Audebert et al, 1992; Persson & Irestedt, 1981). Shock has been observed in some envenomations by V berus species (Magdalan et al, 2010; Luksic et al, 2010). Transient hypotension has occurred following Vipera Acridophaga ursinii (Meadow viper) envenomation in a number of cases (Krecsak et al, 2011)
    b) CASE SERIES: Hypotension, nausea, vomiting and dizziness were the most common systemic events observed following V berus and V ursinii envenomations (Malina et al, 2008).
    c) CASE REPORT: A 12-year-old boy was bitten on the finger by a V bera and within 10 minutes developed hypotension (BP 75/55 mmHg) and tachycardia (heart rate: 145 beats/min). Prehospital care included IV fluids, epinephrine and oxygen. Upon arrival to the hospital, BP was 90/60 mmHg. The patient made a complete recovery following supportive care; no further episodes of hypotension occurred (Moser & Roeggla, 2009).
    d) INCIDENCE OF HYPOTENSION
    1) In most large series of patients with envenomation by European vipers, hypotension develops in about 10% to 25% of patients (Krecsak et al, 2011; Al et al, 2010; Magdalan et al, 2010). In some reports a majority of patients (60% to 83%) had hypotension (Karlson-Stiber & Persson, 1994; Gonzalez, 1982).
    2) CASE SERIES: In a series of 228 patients with viper envenomation (125 V latasti, 80 V aspis, and 23 V seoanei), 60% of patients developed hypotension and tachycardia (Gonzalez, 1982).
    3) CASE SERIES: In a study of 136 cases of envenomation in Sweden, shock occurred in 27 patients, 8 of whom had symptoms of circulatory failure for more than 2 hours (Persson & Irestedt, 1981). The patients in shock exhibited symptoms including: weakness, sweating, peripheral coolness, pallor, thirst, tachycardia, and hypotension. Shock occurred in all cases within the first 2 hours, but has been reported to be delayed by several hours after the bite.
    4) CASE SERIES: In a series of 102 patients with envenomations by Vipera berus or Vipera aspis, 12 patients developed mild to moderate hypotension, 3 developed severe hypotension and 2 developed shock (Audebert et al, 1992).
    5) CASE SERIES: In a series of 46 patients with Vipera berus envenomation 38 (83%) developed hypotension (Karlson-Stiber & Persson, 1994).
    6) CASE SERIES: In a retrospective study of 68 patients with Vipera berus presenting to a hospital in Finland, 12 patients (18%) developed hypotension. In 6 patients hypotension was mild, in 4 patients it was severe, and 2 patients were classified as having shock (Gronlund et al, 2003).
    B) HYPERTENSIVE DISORDER
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: An adult was bitten by a V berus and within 90 minutes developed hypertension (BP 18/120 mmHg) and slight tachycardia (heart rate: 103 beats/min). Captopril 12.5 mg was given; two hours later the blood pressure was 150/90 mmHg. Slightly elevated blood pressure was reported for about 24 hours (Malina et al, 2008a).
    C) TACHYCARDIA
    1) WITH POISONING/EXPOSURE
    a) SUMMARY: Tachycardia can develop as a systemic sign of Vipera envenomation (Al et al, 2010). In an infant, tachycardia was an early significant finding of a V ammoydtes ammoydtes envenomation. The infant's course was complicated by shock, coma and eventual multiorgan failure (Luksic et al, 2010). Transient tachycardia has occurred following Vipera Acridophaga ursinii (Meadow viper) envenomation in a number of cases (Krecsak et al, 2011).
    b) INCIDENCE OF TACHYCARDIA
    1) In most large case series or patients envenomated by European vipers, tachycardia develops in a significant minority of patients, in the range of 10% to 40% (Krecsak et al, 2011; Al et al, 2010; Bubalo et al, 2004).
    2) CASE SERIES: A retrospective analysis regarding the clinical presentation of venomous snakebites in the Herzegovina region from 1997 to 2002, reported the occurrence of tachycardia in approximately 39% of patients (n=71) who were admitted to the hospital following the snakebites. Snake identification was not presented within this analysis (Bubalo et al, 2004).
    D) CONDUCTION DISORDER OF THE HEART
    1) WITH POISONING/EXPOSURE
    a) Supraventricular arrhythmias have been reported following Vipera (V berus) envenomation (Magdalan, 2009).
    b) CASE SERIES: In a series of 46 patients with Vipera berus envenomation one developed transient atrial fibrillation and another transient tachy- and bradydysrhythmias (Karlson-Stiber & Persson, 1994).
    E) ELECTROCARDIOGRAM ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: In a series of 46 patients with Vipera berus envenomation, 2 (4%) developed transient ST elevation (Karlson-Stiber & Persson, 1994).
    b) T-wave flattening or inversion is the most commonly reported ECG abnormality (Persson, 1995).
    F) MYOCARDIAL INFARCTION
    1) WITH POISONING/EXPOSURE
    a) Myocardial infarction is a rare complication of severe envenomation (Karlson-Stiber et al, 2002; Persson, 1995).
    3.5.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) CARDIAC ARREST
    a) IN VITRO STUDIES: V ammodytes venom produces parenchymal degeneration when applied to the myocardium of isolated rat hearts. After fractionating the venom, the authors found that only two of the eleven fractions caused degeneration and resultant cardiac arrest (Unkovic-Cvetkovic et al, 1983).

Respiratory

    3.6.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Bronchospasm and respiratory distress may occur. Angioedema develops in about 10% to 20% of patients with V. berus envenomation, and may cause respiratory compromise if severe. Acute lung injury may develop with severe envenomation.
    3.6.2) CLINICAL EFFECTS
    A) DYSPNEA
    1) WITH POISONING/EXPOSURE
    a) SUMMARY: Dyspnea has been observed in some patients following envenomation (Al et al, 2010; Karlson-Stiber & Persson, 1994).
    b) CASE SERIES: In a series of 46 patients with V berus envenomation, 9 (20%) developed respiratory distress (severity not specified) within 6 hours of the bite (Karlson-Stiber & Persson, 1994).
    c) CASE SERIES: Respiratory distress (severity not specified) developed in 2% of 204 patients with V berus envenomation in a Swedish series (Karlson-Stiber et al, 2006), and 8 of 68 (12%) in a Finnish series (Gronlund et al, 2003).
    d) CASE REPORT/PEDIATRIC: Respiratory insufficiency, requiring mechanical ventilation, occurred in a 6-year-old boy 24 hours after a V berus bite (Schroth et al, 2003).
    B) ACUTE LUNG INJURY
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: Pulmonary edema developed in 2 patients with oliguric renal failure following asp viper bites (Sainty et al, 1987).
    b) CASE REPORT/PEDIATRIC: A 15-month-old boy developed recurrent pulmonary edema 5 days after V berus envenomation (Cederholm & Lennmarken, 1987).
    C) BRONCHOSPASM
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A snake biologist sustained two V aspis envenomations in 4 years (Kopp et al, 1993). With the second bite he developed an urticarial rash, angioedema and wheezing, which were postulated to result from an allergic reaction to the venom.
    b) CASE REPORT/PEDIATRIC: A 15-month-old boy developed slight bronchial obstruction after V berus envenomation (Cederholm & Lennmarken, 1987).
    D) ANGIOEDEMA
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: In 12 of 29 cases of severe V berus envenomation, swelling of the face and lips and/or tongue developed, sometimes immediately post-bite, and lasted for up to 2 days (Reid, 1976).
    b) CASE SERIES: In a series of 46 patients with V berus envenomation, 10 (22%) developed angioedema within 6 hours of the bite (Karlson-Stiber & Persson, 1994).
    c) CASE SERIES: Swelling of the lips and tongue developed in 10 of 68 patients (15%) of patients with V berus bites in a series from Finland (Gronlund et al, 2003).
    d) CASE SERIES: Angioedema was reported in 9% of 204 patients with V berus envenomation in one Swedish series(Karlson-Stiber et al, 2006), and 10 out of 30 patients (33%) in another (Karlson-Stiber & Persson, 1994a). It appears to be more common in patients with moderate or severe envenomation (Karlson-Stiber et al, 2006).
    E) AIRWAY EDEMA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 24-year-old man developed severe oral, pharyngeal and facial edema causing airway obstruction, severe hypoxemia and hypotension after a tongue envenomation by a Vipera berus while under the influence of alcohol. Upon presentation. Airway control via oral or fiberoptic intubation was not possible and an emergency tracheotomy was preformed. The patient was given 2 doses of antivenom, the first approximately 2 hours after envenomation, the second given 16 hours after envenomation, along with supportive care for hypoxia and cardiac decompensation. The patient continued to improve and was discharged from the hospital 11 days after envenomation (Hoegberg et al, 2009).

Neurologic

    3.7.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) CNS depression, weakness, and paresthesias are fairly common. Seizures and bulbar palsy are rare complications. Dysphonia has been reported in two patients following V aspis envenomation.
    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM DEFICIT
    1) WITH POISONING/EXPOSURE
    a) Two cases of envenomation by V aspis produced a neurotoxic syndrome that included ptosis, dysphagia, dysphasia and paralysis of the bitten limb (Gonzalez, 1982).
    b) CASE SERIES: Dizziness, hypotension, nausea, vomiting and dizziness were the most common systemic events observed following V berus and V ursinii envenomations (Malina et al, 2008).
    c) CASE SERIES: In a study of 136 patients, slight CNS disturbances with confusion and somnolence were observed in 11 cases, and unconsciousness in 4 patients. Except for incontinence in one case, other neurological signs were absent (Persson & Irestedt, 1981).
    d) CASE SERIES: In a series of 46 patients with V berus envenomation, 16 (35%) developed mild CNS depression and 8 (17%) became comatose within 6 hours of the bite (Karlson-Stiber & Persson, 1994).
    e) CASE SERIES: In a retrospective study of 68 patients with Vipera berus bites presenting to a hospital in Finland, 10 (15%) developed mild CNS disturbances such as somnolence or confusion (Gronlund et al, 2003).
    f) CASE SERIES: In a series of 204 patients with V berus envenomation, 7 were unconscious on admission (Karlson-Stiber et al, 2006).
    g) CASE REPORT: An adult was bitten by a V berus and developed diplopia and dizziness and vertigo within approximately 2 hours of envenomation. Nystagmus was absent. Significant hypertension (BP 180/120 mmHg) was also noted and treated with captopril. The patient refused antivenom therapy due to concerns about an adverse event. Dizziness gradually resolved over 2 days; no permanent sequelae occurred (Malina et al, 2008a).
    B) PARESTHESIA
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: In a series of 102 viper envenomations in France (V berus of V aspis), 5 patients developed paresthesias (Audebert et al, 1992).
    b) A retrospective analysis regarding the clinical presentation of venomous snakebites in the Herzegovina region from 1997 to 2002, reported the occurrence of paresthesias in approximately 11% of patients (n=71) who were admitted to the hospital following the snakebites. Snake identification was not presented within this analysis (Bubalo et al, 2004).
    c) In a series of 147 patients with viper (predominantly V ammodytes) envenomation presenting to a hospital in Greece, 10 (7%) developed paresthesias (Frangides et al, 2006).
    C) MUSCLE WEAKNESS
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: In a series of 102 viper envenomations in France (V berus of V aspis), 6 patients developed subjective weakness (Audebert et al, 1992).
    D) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT/PEDIATRIC: A 15-month-old boy developed recurrent seizures (possibly secondary to cerebral edema) 40 hours after V berus envenomation (Cederholm & Lennmarken, 1987).
    b) In a series of 147 patients with viper (predominantly V ammodytes) envenomation presenting to a hospital in Greece, 1 patient developed seizures (Frangides et al, 2006).
    c) In a series of 79 patients with Vipera ammodytes envenomation from southeast Turkey, seizures were reported in 2 (3%) patients (Al et al, 2010).
    E) GUILLAIN-BARRé SYNDROME
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 37-year-old herpetologist was bitten on the hand by a V aspis aspis and initially developed localized swelling; antivenom was not given and he was treated. Approximately 10 days after being bitten, the patient developed paresthesia in all extremities and ataxia which progressed to motor deficiency in all extremities. Upon readmission, studies showed slowing of motor conduction. A lumbar puncture was positive for albumino-cytological dissociation. A demyelinating Guillan-Barre syndrome was diagnosed (Neil et al, 2012)
    F) PARALYSIS
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 20-year-old man bitten by V aspis developed bilateral facial palsies, bilateral ptosis and external ophthalmoplegia, pharyngolaryngeal paralysis, and ocular immobility (Antonini et al, 1991). Strength of the skeletal and respiratory muscles, sensation, and deep tendon reflexes were intact. Bulbar paralysis improved by day 5 and resolved by day 10.
    G) DIFFICULTY SPEAKING
    1) WITH POISONING/EXPOSURE
    a) CASE REPORTS: Two patients experienced dysphonia (lowering of the voice's pitch without hoarseness) after V aspis envenomation (Beer & Putorti, 1998).
    H) CRANIAL NERVE DISORDER
    1) WITH POISONING/EXPOSURE
    a) Ptosis, ophthalmoplegia, difficulty swallowing or speaking, facial paresthesias, difficulty with accommodation and ageusia have been reported occasionally after evenomation by V aspis (de Haro et al, 2002).

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Nausea, vomiting, and diarrhea are commonly seen in severe envenomations. Rare reports of intestinal infarction have occurred with V aspis envenomation.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) SUMMARY: Nausea and/or vomiting are often early finding(s) of Vipera (V. aspis, V ammoydtes, V berus, V ursinii) envenomation (Bubalo et al, 2004; Malina et al, 2008; Karlson-Stiber et al, 2002; Cederholm & Lennmarken, 1987).
    b) CASE SERIES: Nausea, vomiting, dizziness and hypotension were the most common systemic events observed following V berus and V ursinii envenomations (Malina et al, 2008).
    c) CASE SERIES: Vomiting developed in 23% of cases in one United Kingdom study of V. berus bites (Alldridge et al, 1993).
    d) CASE SERIES: In two other large series vomiting and/or diarrhea developed in 22% and 85% of patients with V. berus or V. aspis envenomation (Audebert et al, 1992; Karlson-Stiber & Persson, 1994).
    e) CASE SERIES: Vomiting, diarrhea, and abdominal pain occurred in 18 of 68 patients (26.5%) who received adder bites (Gronlund et al, 2003).
    f) In a series of 79 patients with Vipera ammodytes envenomation from southeast Turkey, nausea was reported in 56 (71%) and vomiting in 29 (37%) patients (Al et al, 2010).
    B) DIARRHEA
    1) WITH POISONING/EXPOSURE
    a) Diarrhea may an early finding of a Vipera envenomation (Magdalan et al, 2010).
    C) VASCULAR INSUFFICIENCY OF INTESTINE
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: One case of intestinal infarction associated with V. aspis envenomation has been reported (Beer & Putorti, 1998).

Genitourinary

    3.10.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Proteinuria and hematuria may occur. Renal failure may also occur secondary to rhabdomyolysis.
    3.10.2) CLINICAL EFFECTS
    A) ACUTE RENAL FAILURE SYNDROME
    1) WITH POISONING/EXPOSURE
    a) Acute renal failure and anuria may occur from severe envenomations (Sainty et al, 1987) and anuria for a period of 3 days has occurred after adder bites (Reid, 1976).
    B) BLOOD IN URINE
    1) WITH POISONING/EXPOSURE
    a) Hematuria has been reported after V. berus envenomation (Cederholm & Lennmarken, 1987).
    b) CASE SERIES: In a series of 46 patients with V. berus envenomation, 14 (30%) developed hematuria within 6 hours of the bite (Karlson-Stiber & Persson, 1994).
    c) CASE SERIES: In a series of 204 patients with V. berus envenomation, 9% developed hematuria (Karlson-Stiber et al, 2006). Hematuria was more common in patients with severe envenomation.
    d) CASE SERIES: In a series of 147 viper bites (predominantly V. ammodytes) presenting to a hospital in Greece, 32 (22%) had hematuria and/or proteinuria (Frangides et al, 2006).
    C) RENAL FUNCTION TESTS ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) Laboratory data, presented in a retrospective analysis regarding the clinical presentation of venomous snakebites in the Herzegovina region from 1997 to 2002, reported an elevation of BUN and serum creatinine levels and hyperbilirubinemia in approximately 10% and 11% of patients (n=71), respectively, who were admitted to the hospital following the snakebites. Snake identification was not available (Bubalo et al, 2004).
    b) CASE SERIES: In a series of 147 viper bites (predominantly V. ammodytes) presenting to a hospital in Greece, 22 (15%) had an elevated serum creatinine (Frangides et al, 2006).
    c) In a series of 79 patients with Vipera ammodytes envenomation from southeast Turkey, elevated creatinine was reported in 10 (13%) patients (Al et al, 2010).

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) ACIDOSIS
    1) WITH POISONING/EXPOSURE
    a) Metabolic acidosis has developed in patients with severe envenomation (Cederholm & Lennmarken, 1987).
    b) Lactic acidosis developed in a 24-year-old man who experienced life threatening airway compromise, severe hypoxemia and hypotension after envenomation by a V berus on the tongue. Upon presentation, the serum pH was 7.26 with a lactate level of 4.6 mmol/L. The patient was eventually put on mechanical ventilation and treated with antivenom and supportive care. He was released from the hospital 11 days after envenomation (Hoegberg et al, 2010).

Hematologic

    3.13.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Leukocytosis and anemia are common. Thrombocytopenia, hemorrhage and coagulopathy may develop with severe envenomation. Hemolysis has been reported after V. berus envenomation.
    3.13.2) CLINICAL EFFECTS
    A) ANEMIA
    1) WITH POISONING/EXPOSURE
    a) Anemia may develop late (6 hours to several days) after V. berus envenomation (Karlson-Stiber & Persson, 1994).
    b) CASE SERIES: In a series of 46 patients with V. berus envenomation, 30 of whom received antivenom, the incidence of anemia was lower in the antivenom treated group (10% vs 44%) (Karlson-Stiber & Persson, 1994).
    c) A retrospective analysis regarding the clinical presentation of venomous snakebites in the Herzegovina region from 1997 to 2002, reported the rare occurrence of anemia in approximately 3% of patients (n=71) who were admitted to the hospital following the snakebites. Snake identification was not presented within this analysis (Bubalo et al, 2004).
    B) LEUKOCYTOSIS
    1) WITH POISONING/EXPOSURE
    a) Leukocytosis is common within 6 hours after V. berus envenomation, occurring in 57% of patients in one series of 46 patients (Karlson-Stiber & Persson, 1994).
    b) Early and pronounced leukocytosis is considered to indicate severe poisoning, especially if over 20 x 10(9)/L (Persson & Irestedt, 1981).
    c) The white cell count was monitored in 59 of 68 cases of V. berus envenomation. The average leukocyte count was 20.4 x 10(9)/L, 15.2 x 10(9)/L, 10.5 x 10(9)/L, and 8.6 x 10(9)/L in severe (n=7), moderate (n=12), mild (n=23), and minor (n=17) poisonings, respectively. The correlation coefficient between the severity of poisoning and an early leukocyte count was 0.65 (Gronlund et al, 2003).
    d) A retrospective analysis regarding the clinical presentation of venomous snakebites in the Herzegovina region from 1997 to 2002, reported the occurrence of leukocytosis in approximately 11% of patients (n=71) who were admitted to the hospital following the snakebites. Snake identification was not presented within this analysis (Bubalo et al, 2004).
    e) In a series of 45 snakebites, leukocytosis was demonstrated in 38 (84%) of the cases. The mean white blood cell count (WBC) was 14,077.33 +/- 4933.76 (6000 to 27,000) mm(3). The authors found a statistically significant relationship between WBC and severity of the snakebite (p < 0.05) (Acikalin et al, 2008).
    C) BLOOD COAGULATION PATHWAY FINDING
    1) WITH POISONING/EXPOSURE
    a) Thrombocytopenia, decreased fibrinogen levels, elevated fibrin degradation products and increased PT or INR have been reported after Viper envenomation (Acikalin et al, 2008; Karlson-Stiber & Persson, 1994) .
    b) Viper venom in France was found to be proteolytic and coagulant in small doses and procoagulant and hemolytic at higher doses (Gonzalez, 1982).
    c) Thrombocytopenia and shortened thrombin and prothrombin times were reported in approximately 3% and 8% of patients (n=71), respectively, who were involved in a retrospective analysis regarding the clinical presentation of venomous snake bites occurring in the Herzegovina region from 1997 to 2002 (Bubalo et al, 2004). Snake identification was not presented within this analysis.
    d) CASE REPORT: A 56-year-old man envenomated by a Vipera ammodytes ammodytes developed severe coagulopathy including acute thrombocytopenia (platelet 10 x 10(9)/L) and disseminated intravascular coagulation syndrome. Symptoms lasted almost 2 weeks and required antivenom therapy, platelet therapy, and fresh frozen plasma. Ecchymosis was present on the envenomated extremity as well as the back. By day 18, laboratory studies showed resolution of the coagulopathy and the patient was discharged with no permanent sequelae (Marinov et al, 2010).
    e) CASE SERIES: In a series of 147 viper bites (predominantly V. ammodytes) presenting to a hospital in Greece, 34 (23%) had prolonged PT and/or PTT and 12 (8%) had thrombocytopenia (Frangides et al, 2006).
    f) CASE SERIES: In a series of 204 patients with V. berus envenomation, 5% developed thrombocytopenia (Karlson-Stiber et al, 2006).
    g) CASE SERIES/PEDIATRIC: In a series of 77 children admitted to an ICU in Turkey after viper envenomation (species not specified), 7 (9%) developed disseminated intravascular coagulation (Ozay et al, 2005). Three of these patients died.
    D) HEMOLYSIS
    1) WITH POISONING/EXPOSURE
    a) Hemolysis has been reported after V. berus envenomation (Cederholm & Lennmarken, 1987).
    E) BLOOD COAGULATION DISORDER
    1) WITH POISONING/EXPOSURE
    a) In a series of 45 snakebites, bleeding complications were seen in only 7 (15.6%) of the cases. Bleeding complications included nose bleeds, gingival bleeds, and petechia (Acikalin et al, 2008).

Dermatologic

    3.14.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Severe local reactions may be seen with marked swelling, vesicle formation, ecchymoses, and rarely necrosis.
    3.14.2) CLINICAL EFFECTS
    A) EDEMA
    1) WITH POISONING/EXPOSURE
    a) SUMMARY
    1) The most common local finding of envenomation following a V berus bite is edema (Al et al, 2010; Magdalan et al, 2010; Audebert et al, 1992; Gronlund et al, 2003; Bubalo et al, 2004). Localized swelling with and without erythema was frequently reported following Vipera Acridophaga ursinii (Meadow viper) envenomation (Krecsak et al, 2011).
    2) CASE REPORT/PEDIATRIC: A 6-year-old child was bitten by V. berus and, within hours, developed swelling of the bitten right forearm that progressively worsened. Twenty-four hours after envenomation, the patient developed respiratory insufficiency requiring mechanical ventilation. Despite administration of V. berus antivenom 24 hours post envenomation, the patient's right arm, chest, and neck region became hemorrhagic. A fasciotomy was performed and the patient gradually recovered with physical therapy. It is believed that delayed administration of the antivenom may have resulted in its ineffectiveness in this patient (Schroth et al, 2003).
    b) INCIDENCE OF EDEMA
    1) In most large series of patients with envenomation by European vipers, local swelling occurs in 80% to 100% of patients (Krecsak et al, 2011; Al et al, 2010; Magdalan et al, 2010).
    2) CASE SERIES: In a series of 46 patients with V. berus envenomation, 30 of whom received antivenom, the incidence of edema involving the trunk was lower in the antivenom treated group (23% vs 88%) (Karlson-Stiber & Persson, 1994).
    3) A retrospective analysis regarding the clinical presentation of venomous snakebites in the Herzegovina region from 1997 to 2002, reported that swelling and erythema, at the bite site, were common occurrences in approximately 87% and 68% of patients (n=71), respectively, who were admitted to the hospital following the snakebites. Snake identification was not presented within this analysis (Bubalo et al, 2004).
    c) SEVERITY
    1) CASE SERIES: In a series of 102 patients with V. berus or V. aspis envenomation, 48 developed local edema, 29 regional edema and 5 developed extensive edema (Audebert et al, 1992). The remaining 20 patients had "dry" bites.
    2) CASE SERIES: Edema was reported in 62 of 68 cases of V. berus envenomation (92.1%). In 14 cases (20.6%), the edema was extensive, involving the entire affected extremity and extending to the trunk (Gronlund et al, 2003).
    d) DURATION
    1) Local edema was the most common effect seen after bites of Viper berus in one United Kingdom study. Edema persisted a median of 7 days, but in 20% of the cases swelling existed for 1 month (Alldridge et al, 1993).
    2) In a series of 26 patients with Vipera berus envenomation in Southwest Poland, edema resolved in less than a week in 10 (38%) patients, in 1 to 2 weeks in 12 (46%) patients, and in 2 to 2 weeks in 2 (8%) patients (Magdalan et al, 2010).
    B) ECCHYMOSIS
    1) WITH POISONING/EXPOSURE
    a) Ecchymosis has been observed following envenomation of Vipera (V ammodytes) (Al et al, 2010).
    C) BLISTER
    1) WITH POISONING/EXPOSURE
    a) Vesicles or blisters develop at the site of the bite in a significant number of patients.
    b) CASE SERIES: In a series of 147 viper bites (predominantly V. ammodytes) presenting to a hospital in Greece, 9 (6%) developed hemorrhagic blisters at the bite site (Frangides et al, 2006).
    c) In a series of 79 patients with Vipera ammodytes envenomation in southeast Turkey, 26 (33%) patients developed local hemorrhagic bullae (Al et al, 2010).
    D) ECCHYMOSIS
    1) WITH POISONING/EXPOSURE
    a) Ecchymosis at the bite site is common, and may spread to involve much of the affected limb in patients with severe envenomation.
    b) CASE SERIES: In a series of 102 patients with V. berus or V. aspis envenomation, 16 developed ecchymosis at the bite site (Audebert et al, 1992).
    c) CASE SERIES: Bruising was reported in 35 of 68 patients (51.5%) with V. berus envenomation (Gronlund et al, 2003).
    d) In a series of 79 patients with Vipera ammodytes envenomation from southeast Turkey, ecchymosis developed in 73 (92%) patients (Al et al, 2010).
    E) LOCAL INFECTION OF WOUND
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: In a series of 147 viper bites (predominantly V. ammodytes) presenting to a hospital in Greece, 20 (14%) developed a wound infection (Frangides et al, 2006).
    b) In a series of 79 patients with Vipera ammodytes envenomation from southeast Turkey, wound infection developed in 31 (39%) patients (Al et al, 2010).
    F) BLEEDING
    1) WITH POISONING/EXPOSURE
    a) Bleeding may develop from the bite site.
    b) CASE SERIES: In a series of 147 viper bites (predominantly V ammodytes) presenting to a hospital in Greece, 9 (6%) developed bleeding from the bite site (Frangides et al, 2006).
    c) CASE SERIES/PEDIATRIC: In a series of 77 children admitted to an ICU in Turkey after viper envenomation (species not specified), 3 developed bleeding at the bite site (Ozay et al, 2005).
    G) TISSUE NECROSIS
    1) WITH POISONING/EXPOSURE
    a) Tissue necrosis rarely develops (Ozay et al, 2005; Frangides et al, 2006); superficial tissue necrosis has occurred in a child after a V berus bite (Moser & Roeggla, 2009).
    b) CASE SERIES: In a series of 147 viper bites (predominantly V ammodytes) presenting to a hospital in Greece, 4 (3%) developed local necrosis with tissue loss and one required amputation of a digit (Frangides et al, 2006).
    c) CASE SERIES/PEDIATRIC: In a series of 77 children admitted to an ICU in Turkey after viper envenomation (species not specified), 10 (13%) developed tissue necrosis (Ozay et al, 2005).
    d) In a series of 79 patients with Vipera ammodytes envenomation from southeast Turkey, local necrosis with tissue loss developed in 7 (9%) patients (Al et al, 2010).

Musculoskeletal

    3.15.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) There may be rhabdomyolysis and tissue damage from the proteolytic enzymes in the venom. Compartment syndrome is rare.
    3.15.2) CLINICAL EFFECTS
    A) RHABDOMYOLYSIS
    1) WITH POISONING/EXPOSURE
    a) There may be rhabdomyolysis and tissue destruction from the proteolytic enzymes in the venom.
    b) CASE SERIES: In a series of 147 viper bites (predominantly V ammodytes) presenting to a hospital in Greece, 38 (26%) developed an increased CK, 8 (5%) developed myoglobinemia, and 7 (5%) developed myoglobinuria (Frangides et al, 2006).
    c) In a series of 79 patients with Vipera ammodytes envenomation from southeast Turkey, elevated CK was reported in 35 (44%) patients (Al et al, 2010).
    B) COMPARTMENT SYNDROME
    1) WITH POISONING/EXPOSURE
    a) In a series of 79 patients with Vipera ammodytes envenomation from southeast Turkey, compartment syndrome developed in 6 (8%) patients (Al et al, 2010).
    b) CASE SERIES/PEDIATRIC: In a series of 77 children admitted to an ICU in Turkey after viper envenomation (species not specified), 7 (9%) developed compartment syndrome (Ozay et al, 2005).
    c) CASE SERIES: In a series of 147 viper bites (predominantly V ammodytes) presenting to a hospital in Greece, 2 developed compartment syndrome (Frangides et al, 2006).
    d) CASE REPORT: A 44-year-old man was bitten by an adder on the hand and received supportive care and was transferred the following day to a University Hospital due to persistent swelling and lymphangitis of the extremity. Upon admission, the patient had significant swelling of the hand, forearm and upper arm and lymphangitis extending to the axilla along with significant pain (7 out of 10 on a visual analogue). The patient underwent local incision of the hand and forearm; necrotic muscle tissue and some bleeding were noted. Clinically, the site was improving and secondary wound closure occurred on day 4. The patient continued to improve and at 1-year follow-up he reported normal function of his hand and arm (Evers et al, 2010).

Immunologic

    3.19.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Anaphylactic (IgE mediated) and anaphylactoid reactions have occurred to the venom of Vipera species.
    3.19.2) CLINICAL EFFECTS
    A) ANAPHYLACTOID REACTION
    1) WITH POISONING/EXPOSURE
    a) An anaphylactic reaction to a viper bite has been reported.
    b) One patient bitten by an asp viper developed an immediate generalized anaphylactic reaction (Sainty et al, 1987).
    c) A Vipera aspis bite produced an anaphylactic reaction (confirmed by venom specific IgE radioimmunologic assay) which caused abdominal pain, urticaria, dyspnea, cyanosis, laryngeal edema, hypotension, and shock (Hosemann et al, 1992).
    d) CASE REPORT: A snake biologist sustained two V aspis envenomations in 4 years (Kopp et al, 1993). With the second bite he developed an urticarial rash, angioedema and wheezing. IgE against V aspis venom was found in the patient's serum, and a skin test with V. aspis venom produced a wheal.
    e) CASE SERIES: In a series of 103 V aspis or V berus bites, 7 developed anaphylactoid reactions (Audebert et al, 1992).
    f) CASE SERIES: In a series of 147 viper bites (predominantly V ammodytes) presenting to a hospital in Greece, 4 developed allergic reactions after the bite (Frangides et al, 2006).
    g) CASE SERIES: In one series, 5 out of 125 patients (4%) with V lasasti envenomation developed anaphylactoid reactions (Gonzalez, 1982).

Reproductive

    3.20.1) SUMMARY
    A) There are three published cases where severe envenomation in pregnant women resulted in fetal demise. Normal pregnancy outcomes have been reported after moderate envenomation treated with antivenom.
    3.20.3) EFFECTS IN PREGNANCY
    A) FETAL DEMISE
    1) There are three published cases where severe envenomation in pregnant women resulted in fetal demise (Persson, 1995).
    B) NO EFFECT
    1) In another report, three pregnant women were bitten by european vipers at 32, 18, and 27 weeks gestation (Sebe et al, 2005). All three developed moderate regional swelling as the only manifestation of envenomation, and were treated with antivenom. There was no evidence of fetal distress at the time of envenomation. All three went on to deliver healthy infants at term.
    2) In a series of 45 snakebites, 1 case was a female at 20 weeks gestation. She presented with moderate envenomation symptoms and was treated with 4 vials of antivenom. Her hospital stay was uncomplicated, and she went on to deliver a healthy baby (Acikalin et al, 2008).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs and mental status. Monitor for development and progression of local swelling.
    B) Monitor CBC with platelet count and urinalysis.
    C) In patients with progression of swelling or evidence of systemic envenomation, monitor serum electrolytes, renal function, CK, coagulation studies (INR, aPTT, fibrinogen, fibrin degradation products) and tests for hemolysis (free hemoglobin and LDH).
    D) Monitor ECG in patients with evidence of systemic envenomation.
    4.1.2) SERUM/BLOOD
    A) HEMATOLOGIC
    1) Monitor serial complete blood count with platelets (Persson, 1995).
    B) COAGULATION STUDIES
    1) Monitor coagulation profile (INR, PTT, fibrinogen, fibrin split products) and tests for hemolysis (free hemoglobin, LDH) in patients with systemic symptoms or progressive edema (Persson, 1995)
    C) OTHER
    1) Type and hold for cross match, if moderate or severe envenomation.
    D) BLOOD/SERUM CHEMISTRY
    1) Monitor serum electrolytes, BUN, creatinine, CK, in patients with systemic envenomation or progressive edema (Persson, 1995).
    4.1.3) URINE
    A) URINALYSIS
    1) Monitor urine for evidence of hematuria or hemolysis.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) Measure circumference of involved extremity just above the bite and 10 and 20 centimeters above this point. Repeat and record these readings every 15 minutes during antivenin administration and every 1 to 2 hours thereafter to document progression or resolution of edema. Measurement of the of bitten extremity may also be compared to that of the contralateral extremity.
    b) Mark the skin at the leading edges of edema with a pen every 15 to 30 minutes as well as following circumferential measurements.

Methods

    A) IMMUNOASSAY
    1) An ELISA has been developed for measuring V. ammodytes venom antigens in whole blood (Labrousse et al, 1988). It is not currently used clinically.
    2) An ELISA has been developed for measuring V. aspis venom antigens in urine and blood (Audebert et al, 1992).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.6) DISPOSITION/BITE-STING EXPOSURE
    6.3.6.1) ADMISSION CRITERIA/BITE-STING
    A) All patients who develop clinical or laboratory evidence of envenomation should be admitted.
    B) Any patient who has been bitten by a proven or suspected venomous snake should be admitted to a hospital for a 6 to 8 hour observation period. Patients who develop systemic effects or progression of edema during this period should be admitted to the hospital for a minimum of 24 hours (Persson, 1995).
    6.3.6.2) HOME CRITERIA/BITE-STING
    A) Any patient with a European snake bite should be sent to the hospital. Most species are minimally dangerous to humans, but the species may be unclear at presentation.
    6.3.6.3) CONSULT CRITERIA/BITE-STING
    A) Consult a medical toxicologist, toxinologist or poison center for any patient with significant envenomation or in whom the diagnosis is unclear. The local poison control center can help locate appropriate antivenom.
    6.3.6.5) OBSERVATION CRITERIA/BITE-STING
    A) Any patient who has been bitten by a proven or suspected venomous snake should be admitted to a hospital for a 6 to 8 hour observation period. If these is no evidence of systemic envenomation and no progression of edema during this time period the patient may be discharged home (Persson, 1995).

Monitoring

    A) Monitor vital signs and mental status. Monitor for development and progression of local swelling.
    B) Monitor CBC with platelet count and urinalysis.
    C) In patients with progression of swelling or evidence of systemic envenomation, monitor serum electrolytes, renal function, CK, coagulation studies (INR, aPTT, fibrinogen, fibrin degradation products) and tests for hemolysis (free hemoglobin and LDH).
    D) Monitor ECG in patients with evidence of systemic envenomation.

Range Of Toxicity

Summary

    A) TOXIC DOSE: About 10% to 20% of bites are "dry" and no envenomation develops. A single bite can cause severe envenomation and can be lethal, but death is unusual with modern medical care.

Minimum Lethal Exposure

    A) SUMMARY
    1) Death has been known to occur in individuals from a single snake envenomation, but is unusual with modern medical care.
    B) CASE REPORT
    1) INFANT: A 45-day-old infant was bitten on the neck by a V ammodytes ammodytes while outside in a carriage with his family in a town in southern Croatia. Neck swelling and profuse sweating were observed soon after the bite. Upon admission, the infant was in shock. Due to the location of the bite an endotracheal tube was placed along with a central line. Two doses of Zagreb antivenom were given shortly after admission. Mechanical ventilation was required about 3 hours after the bite. Despite aggressive care, the infant died 6 hours after the bite due to severe hyperkalemia (peak potassium 9.0 mmol/L), hemodynamic dysfunction (ie, massive intravascular hemolysis, severe coagulopathy) and persistent cardiac dysfunction (bradycardia and hypotension) (Luksic et al, 2010).
    2) ADULT: A single death has been reported following the envenomation by Vipera berus bosniensis (Balkan adder). Its typical habitat is southwestern Hungary and northern Croatia (Malina et al, 2011).
    C) CASE SERIES
    1) In a series of 77 children admitted to an intensive care unit in Turkey, 3 children died, all of whom developed severe coagulopathy (Ozay et al, 2005).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) V. aspis
    1) LD50- (SUBCUTANEOUS)MOUSE:
    a) 3 to 6 mg/kg (Brown, 1973)
    B) V. berus
    1) LD50- (SUBCUTANEOUS)MOUSE:
    a) 3-8 mg/kg (Brown, 1973)
    C) V. lebetina
    1) LD50- (SUBCUTANEOUS)MOUSE:
    a) 5 to 6 mg/kg (Brown, 1973)

Pharmacology Toxicology

Toxicologic Mechanism

    A) IN VITRO STUDIES - V. ammodytes venom produces parenchymal degeneration when applied to the myocardium of isolated rat hearts. After fractioning the venom, the authors found that only two of the eleven fractions caused degeneration and resultant cardiac arrest (Unkovic-Cvetkovic et al, 1983).
    B) Venom from Agkistrodon blomhoffi brevicaudus, a pit viper, contains a phospholipase A2 neurotoxin that cross-reacts immunologically with crotoxin from Crotalus durissus terrificus venom (Choumet et al, 1991).

Pharmacologic Mechanism

    A) Snake venoms are made up of multiple components of biological chemicals which may cause changes in multiple organs and systems in the body.

Animal Toxicology

Clinical Effects

    11.1.13) OTHER
    A) OTHER
    1) Clinical effects in small or large animals are similar to those effects seen in human victims.
    2) Acute renal failure and severe coagulopathy has been described in a German shepard dog following V. aspis envenomation. Post-mortem histopathologic evaluation of the kidneys showed a discrete glomerular hypercellularity, messangial lysis and renal tubule filled with hyaline casts and necrotic cells (Puig et al, 1995).

Treatment

    11.2.1) SUMMARY
    A) GENERAL TREATMENT
    1) Treatment is the same as for human victims.

Continuing Care

    11.4.1) SUMMARY
    11.4.1.2) DECONTAMINATION/TREATMENT
    A) GENERAL TREATMENT
    1) Treatment is the same as for human victims.

References

General Bibliography

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