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MIDDLE EASTERN SNAKES-VIPERIDAE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Several of the world's most lethal snakes are found in the Middle East. There are 51 species of snakes in the Middle East, and venomous varieties are divided into 5 families: the Colubridae, Elapidae, Aractaspididae, Hydrophidae and Viperidae. This management is limited to the discussion of VIPERS and ATRACTASPIDIDAE.
    B) Elapids are discussed in MIDDLE EAST SNAKES-ELAPIDAE management.
    C) Colubrids are discussed in SNAKES, COLUBRID, OLD WORLD management.

Specific Substances

    1) ARACTASPIDIDAE
    a) Atractaspis microlepidota (small scaled burrowing asp)
    2) VIPERIDAE
    a) Atractaspis microlepidota
    1) Small-scaled burrowing asp
    b) Bitis arietans
    1) Puff Adder
    c) Cerastes cerastes
    1) Horned Sand viper
    2) Desert viper
    d) Cerastes vipera
    1) Pygmy Sand viper
    e) Echis carinatus
    1) Saw-scaled viper
    f) Echis coloratus
    1) Carpet viper
    g) Echis pyramidum
    1) Egyptian Saw-scaled viper
    h) Eristocohis mcmahoni
    1) Leaf-nosed viper
    i) Pseudocerastes persicus
    1) False-horned viper
    j) Vipera berus
    1) European adder or viper
    k) Vipera lebetina
    1) Blunt-nosed viper
    l) Vipera palaestinae
    1) Palestine viper
    m) Vipera ursinii
    1) Meadow viper
    2) Orsini's viper
    n) Vipera xanthina
    1) Coastal viper
    2) Near East viper
    3) Ottoman viper
    3) Middle eastern snakes
    4) SAUDI ARABIAN SNAKES
    5) SNAKE BITE (MIDDLE EASTERN)
    6) SNAKE BITE (SAUDI ARABIAN)
    7) SNAKES, SAUDI ARABIAN

Available Forms Sources

    A) FORMS
    1) VIPERS OF THE MIDDLE EAST
    a) VIPERIDAE: Saudi Arabia hosts 4 genera and 6 species of the family Viperidae. Their venom is, in the main, vasculotoxic and the snakes have a highly sophisticated system with which to deliver it. Hollow fangs are situated in the front of the mouth and function like hypodermic needles, capable of penetrating deep into subcutaneous and muscular tissues. The fangs fold into the roof of the mouth, but are erectile and become almost perpendicular in the biting mode.
    1) CERASTES CERASTES, the Horned Sand Viper is the commonest venomous snake found in Saudi Arabia, up to an elevation of about 1500 meters. Its color matches the sand of the region. Spurs or "horns" are present above the eyes, and it attains a length of 75 cm.
    2) PSEUDOCERASTES is a little longer, but difficult to differentiate from it. Pseudocerastes fieldi may be seen in Saudi Arabia (Russell, 1991) and has been found in Iran (Dehghani et al, 2012).
    3) The genus ECHIS is represented by 2 species occurring near the mountains adjoining the Red Sea.
    a) ECHIS CARINATUS has a predilection for agricultural areas. It is reddish-brown with pretty white patterns, accounting for its common name of the Carpet Viper. It has rather a short tail and carinate lateral scales which make a rasping sound as the snake's coils rub together when disturbed (Corkill, 1956).
    b) ECHIS COLORATUS prefers rocky outcrops as high as 1500 meters. Its coloring is in shades of gray or silver with a dappled pattern. Both E CARINATUS and E COLORATUS are nocturnal and may move with great speed and agility, although neither species attains a length of more than about 50 cm. They can inflict the most catastrophic of bites (Reid, 1984).
    4) BITIS ARIETANS is a Puff-adder, inhabits southern Morocco, western Algeria, West Sahara, Mauritania, coastal southwest Arabia (above 1500 meters) and Dhofar in Oman. It is a fat snake with long fangs and can attain a length of 1.5 meters. It is nocturnal and slow-moving, hissing when aroused. It is easily trodden upon. When such an accident occurs, it strikes rapidly, inflicting a most dangerous bite.
    5) ARACTASPIDIDAE: ATRACTASPIS MICROLEPIDOTA, the Burrowing Adder or Mole Viper, is occasionally reported in the southern half of Saudi Arabia. It is, as its common name implies, mainly subterranean, venturing to the surface at night and also during the day after the rains (Warrell et al, 1976). Also it is not common and bites are very rare. It is, however, extremely hazardous to handle as it is something of a contortionist and can bite both backwards and sideways.

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: This management is limited to vipers of the Middle East region of most medical importance. Some geographic overlap may occur in this management with venomous snakes of Africa. Please refer to the AFRICAN SNAKES-VIPERIDAE management as appropriate.
    B) TOXICOLOGY: Snake venom varies in composition and quantity dependent on the species and size of the snake and the mechanical efficiency in which the bite always result in envenomation. Viper venom is delivered via a pair of fangs, which are long, curved, cannulated and fully erectile, held from the upper jaw in a sheath of mucous membrane. Clinically important components of viper venom include proteolytic/procoagulant enzymes, cytolytic/necrotic toxins, hemolytic/myolytic phospholipase A2, neurotoxins (limited species in this region; eg, V palaestinae), vasodilators (ie, bradykinin) and hemorrhagins.
    C) EPIDEMIOLOGY: Several of the world's most lethal snakes are found in the Middle East. True epidemiologic data on snakebites are difficult to ascertain. Because of the inaccuracies of reporting systems, the estimate of the annual incidence from snakes of the Middle East region is as high as 20,000 bites with 15,000 envenomations and 100 deaths. In Iran, venomous viperidae of most medical importance are Vipera lebetina, Echis carinatus, Psedocerastes persicus, and Vipera albicornuta.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: The primary clinical events with a viper envenomation in this region includes local tissue injury, coagulopathy and hypotension. LOCAL TISSUE INJURY: The bite site may show evidence of one or more fang marks along with pain, edema, erythema, sometimes local bleeding, ecchymosis, and lymphangitis, bleb formation, tissue necrosis and sloughing. Local effects are common and swelling may be observed within 15 minutes of a viper bite. Swelling can progress to include the entire limb and the regional lymph nodes. Local tissue injury can progress to tissue necrosis following envenomation and may require surgical debridement and amputation in some cases. True compartment syndrome is not common. PAIN: Usually develops immediately following a bite, and can be out of proportion to that produced by a simple traumatic puncture. Without therapy, it generally increases during the first several hours, and is accentuated by swelling.
    2) SEVERE TOXICITY: Severe cases may include hypotension and shock, bleeding/hemorrhage, hypovolemia, cardiovascular events (abnormal ECG, cardiac dysrhythmias by Bitis or Echis species), pulmonary edema, dyspnea, renal failure, CNS depression and possible anaphylactic reactions (venoms can release of histamine, bradykinins to trigger an anaphylactic response). Less severe systemic effects include fever, anemia, light-headedness, nausea and vomiting, and elevated liver enzymes. Less commonly reported features with Vipera berus and possibly other vipera are pulmonary edema, generalized plasma leakage, seizures, deep venous thrombosis, compartment syndrome, and myocardial infarction. COAGULOPATHY: Persistent bleeding or oozing at the puncture site or veinpuncture sites is a sign of incoagulable blood. Thrombocytopenia, prolongation of PT or PTT, decreased fibrinogen and/or elevated fibrin split products, may develop usually without evidence of hemolysis. Bleeding complications can also include bleeding gums, hemoptysis, hematemesis, rectal bleeding, melena, hematuria, vaginal bleeding, and rarely intracranial hemorrhage. Both ischemic and hemorrhagic strokes have been reported with Cerastes cerastes envenomations infrequently. Coagulation abnormalities associated with envenomation are usually reversed by antivenin therapy, and generally do not require blood products or factors unless there is active bleeding. HYPOTENSION: Envenomations can produce hypotension which is mainly associated with hypovolemia but can occur from direct cardiotoxicity (B. arietans) or release of vasodilators (ie, bradykinins; V palaestinae). COMPARTMENT SYNDROME: Cases of compartment syndrome have been described after envenomation by B. arietans. INFREQUENT: Neurotoxicity (E pyramidum) has been reported infrequently. Circulatory failure has been reported infrequently due to a neurotoxic polypeptide (acting on medullary center) found in V palaestinae venom. Deaths have been reported from snakes originating in this region.
    0.2.3) VITAL SIGNS
    A) WITH POISONING/EXPOSURE
    1) A low grade fever is common after envenomation. Hypotension may be profound in severe envenomation. Tachycardia or bradycardia may occur; bradycardia may at times be severe.

Laboratory Monitoring

    A) Monitor vital signs and mental status.
    B) Monitor for progression of edema, pain and lymphadenopathy.
    C) Mark leading edge of soft tissue swelling and measure circumference at the area of the bite, reassess for progression every 15 to 30 minutes.
    D) The following tests should be obtained upon admission and repeated every 6 hours to assess worsening envenomation and/or efficacy of antivenom:
    1) Obtain complete blood count with differential. Monitor coagulation studies including INR, PTT, fibrinogen, fibrin degradation products, and whole blood clotting time over 20 minutes if other tests are not available.
    2) Obtain serum electrolytes, renal function tests and urinalysis and repeated as needed.
    3) Culture wound if evidence of secondary infection is present.
    E) Caution should be used in all venipuncture studies due to the risk of bleeding and/or oozing that may occur at the site. Arterial punctures should be avoided when possible, particularly in incompressible sites.

Treatment Overview

    0.4.7) BITES/STINGS
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Mild to moderate envenomations can be observed for at least 24 hours in a healthcare facility. Antivenom may be warranted if clinical or laboratory markers worsen. Mild hypotension can be managed by intravenous fluid administration. Wounds should be gently cleaned and monitored closely for signs of progression (ie, swelling, pain). Antiemetics and analgesia may be administered for mild systemic symptoms. Patients should be continually monitored (physical and laboratory exams) for changes or progression of symptoms.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Close attention to airway, breathing and circulation is warranted in all cases of severe envenomation. Systemic effects or severe local tissue injury should be treated with antivenom. Hypotension or shock that is unresponsive to fluids may require vasopressor agents (eg, dopamine, norepinephrine, or epinephrine) if antivenom is not available. Epinephrine and steroids may be needed for signs and symptoms of anaphylaxis. Coagulation abnormalities and hemorrhage can be treated with clotting factors and platelets (eg, fresh frozen plasma and cryoprecipitate with platelet concentrates), if antivenom is not available. Patients who develop rhabdomyolysis need aggressive hydration. Acute renal failure will need adequate hydration and may need dialysis. For suspected compartment syndrome, surgical consult may be indicated after a viper envenomation in the presence of severe swelling to rule out compartment syndrome. Early antivenom administration remains an effective measure to prevent or minimize irreversible muscle damage. Surgical procedures should probably be based on documented compartment pressures that are consistent with compartment syndrome and do not improve with antivenom.
    C) DECONTAMINATION
    1) PREHOSPITAL: Remove the snake if still attached to the victim. Do NOT attempt to capture or manipulate the snake with bare hands, and be cautious because a dead snake may still be able to envenomate. Remove constricting clothing, and jewelry from the bitten limb. Immobilize the limb at heart level and transport the patient to a medical facility as soon as possible. Pressure immobilization is not recommended in viper bites as it can increase local tissue injury. Do NOT use a tourniquet or use cautery, incision, suction, vacuum pumps, instillation of chemical compounds, application of ice, or electric shock. Rapidly transport the patient to the nearest emergency department; ideally a facility with experience in treating snake bites.
    D) WOUND CARE
    1) CLINICAL ASSESSMENT: Early and thorough clinical assessment for local and systemic symptoms are of the utmost importance. Determine location and time course of bite. Assess for signs of local envenomation. WOUND ASSESSMENT: Early debridement and prophylactic antibiotics for local tissue injuries are not recommended without clear evidence of necrosis. Wounds should be gently cleaned and monitored closely for signs of progression. Blisters and bullae should be left intact. Update tetanus immunization if necessary. Monitor circumference measurements in the bite area and marking the leading edge of the pain or edema.
    E) CONTRAINDICATED TREATMENT
    1) Arterial or venous tourniquets are very dangerous. Other measures to avoid include aspirin, which increases bleeding. Steroids are only indicated for serum sickness or allergic reaction. Cryotherapy increases necrosis. Local incisions or wound excision and suction devices are not effective and only add additional trauma and delay treatment.
    F) ANTIDOTE
    1) Antivenom is indicated after a viper snake bite if the following effects are present: severe local envenomation (eg, local swelling involving more than half the limb or lymph node involvement, swelling of digits), coagulation abnormalities (eg, spontaneous bleeding, laboratory evidence of coagulopathy), and generalized rhabdomyolysis. Administration of antivenom can reverse systemic envenomation effects even after several days, but cannot reverse established tissue necrosis and may be less effective on effects of local envenomation unless given within several hours after the bite. Antivenoms are available from several countries in the region with claimed efficacy to various species of Viperidae in this region (See detailed treatment section for specific antivenoms). If the snake species is positively identified, administer a species-specific antivenom when available. Regional polyspecific antivenoms are appropriate when the snakes species cannot be reliably identified or a species-specific antivenom is not available. A regional poison center can provide information on and help locate antivenoms for exotic species. Antivenoms can produce acute allergic reactions. Begin administration slowly with careful monitoring for allergic reactions and resuscitation equipment at the bedside. Gradually increase the rate of administration as tolerated. Consultation with a medical toxicologist or toxinologist is strongly recommended. The dosage of the antivenom should be guided by symptoms, signs, and laboratory findings. To prevent local tissue necrosis, antivenom should be given as soon as possible.
    G) ENHANCED ELIMINATION
    1) Hemodialysis may be indicated in the presence of acute renal injury (ie, fluid overload, oliguria, symptomatic hyperkalemia).
    H) PATIENT DISPOSITION
    1) HOME CRITERIA: There should be NO home treatment for bites from proven or suspected venomous snakes. The goal of prehospital care is rapid transport to a healthcare facility.
    2) OBSERVATION CRITERIA: Any patient suspected of having been bitten by an Middle East viper should be referred to healthcare facility and closely observed for a period of 24 hours. Patients who present with fang marks only should be observed for at least 8 to 12 hours, then discharged if no signs or symptoms. During this time the bitten limb should be elevated and the tourniquet or constricting bands are removed. Patients with a suspected envenomation with no clinical effects can also be discharged after 3 normal consecutive WBCT (whole blood clotting times) tests.
    3) ADMISSION CRITERIA: Any patient who has been bitten by a proven or suspected venomous viper should be admitted to a hospital for a 24 hour observation period. During the observation period the patient should be followed for progression of local signs every 15 to 30 minutes, coagulation abnormalities and systemic effects. If symptoms progress, airway compromise occurs or the patient requires antivenom administration, admit the patient to an intensive care setting. DISCHARGE CRITERIA: Patients can be discharged once they complete their antivenom if needed, their symptoms are improving, no paralysis or respiratory failure, their lab values are normal or a definite trend towards normal, and there is no evidence of recurrence. Early post-discharge physiotherapy referral and 2 to 4 days after discharge outpatient follow-up (for lab re-evaluation and assessing for serum sickness symptoms) should be arranged.
    4) CONSULT CRITERIA: Consult a local herpetologist for proper identification of the snake if it is available. Consultation with a medical toxicologist or a toxinologist is strongly recommended with administration of antivenom. A local poison center can provide information on the appropriate antivenom and how to obtain it for bites by exotic species.
    I) PITFALLS
    1) The use of tourniquets is NOT recommended; blockage of circulation from any constrictive ligature could result in worsening tissue damage. A potential delay in presenting symptoms can mimic a "dry bite" early on. Patients with a suspected envenomation warrant close observation for at least 24 hours. Early antivenom treatment is necessary to prevent progression of local tissue destruction, but systemic symptoms and coagulation abnormalities may respond to antivenom even in delayed administration.
    J) TOXICOKINETICS
    1) Onset of symptoms from viper envenomation is usually immediate with subsequent severe pain, erythema and swelling after a bite. Swelling usually develops within 15 minutes of a viper envenomation. Venom can be rapidly absorbed and evidence of bruising, blistering and necrosis can be present with 24 hours. In general, the later the onset of systemic symptoms, the better the prognosis (ie, less venom absorbed).
    K) DIFFERENTIAL DIAGNOSIS
    1) Early sign and symptoms may mimic envenomation from other creatures (eg, scorpions, hymenoptera and spiders). Local tissue injury can resemble or be concurrently present with cellulitis or other soft tissue infections (eg, necrotizing fascitis). Systemic findings warrant evaluation for trauma, sepsis, metabolic derangements or other exposed toxic substances.

Range Of Toxicity

    A) Not all snakes are venomous, and not all venomous snakes inject the same amount of venom if any (ie, dry bites) with each strike. Treatment therefore has to be based on symptoms rather than number of strikes.

Clinical Effects

Summary Of Exposure

    A) BACKGROUND: This management is limited to vipers of the Middle East region of most medical importance. Some geographic overlap may occur in this management with venomous snakes of Africa. Please refer to the AFRICAN SNAKES-VIPERIDAE management as appropriate.
    B) TOXICOLOGY: Snake venom varies in composition and quantity dependent on the species and size of the snake and the mechanical efficiency in which the bite always result in envenomation. Viper venom is delivered via a pair of fangs, which are long, curved, cannulated and fully erectile, held from the upper jaw in a sheath of mucous membrane. Clinically important components of viper venom include proteolytic/procoagulant enzymes, cytolytic/necrotic toxins, hemolytic/myolytic phospholipase A2, neurotoxins (limited species in this region; eg, V palaestinae), vasodilators (ie, bradykinin) and hemorrhagins.
    C) EPIDEMIOLOGY: Several of the world's most lethal snakes are found in the Middle East. True epidemiologic data on snakebites are difficult to ascertain. Because of the inaccuracies of reporting systems, the estimate of the annual incidence from snakes of the Middle East region is as high as 20,000 bites with 15,000 envenomations and 100 deaths. In Iran, venomous viperidae of most medical importance are Vipera lebetina, Echis carinatus, Psedocerastes persicus, and Vipera albicornuta.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: The primary clinical events with a viper envenomation in this region includes local tissue injury, coagulopathy and hypotension. LOCAL TISSUE INJURY: The bite site may show evidence of one or more fang marks along with pain, edema, erythema, sometimes local bleeding, ecchymosis, and lymphangitis, bleb formation, tissue necrosis and sloughing. Local effects are common and swelling may be observed within 15 minutes of a viper bite. Swelling can progress to include the entire limb and the regional lymph nodes. Local tissue injury can progress to tissue necrosis following envenomation and may require surgical debridement and amputation in some cases. True compartment syndrome is not common. PAIN: Usually develops immediately following a bite, and can be out of proportion to that produced by a simple traumatic puncture. Without therapy, it generally increases during the first several hours, and is accentuated by swelling.
    2) SEVERE TOXICITY: Severe cases may include hypotension and shock, bleeding/hemorrhage, hypovolemia, cardiovascular events (abnormal ECG, cardiac dysrhythmias by Bitis or Echis species), pulmonary edema, dyspnea, renal failure, CNS depression and possible anaphylactic reactions (venoms can release of histamine, bradykinins to trigger an anaphylactic response). Less severe systemic effects include fever, anemia, light-headedness, nausea and vomiting, and elevated liver enzymes. Less commonly reported features with Vipera berus and possibly other vipera are pulmonary edema, generalized plasma leakage, seizures, deep venous thrombosis, compartment syndrome, and myocardial infarction. COAGULOPATHY: Persistent bleeding or oozing at the puncture site or veinpuncture sites is a sign of incoagulable blood. Thrombocytopenia, prolongation of PT or PTT, decreased fibrinogen and/or elevated fibrin split products, may develop usually without evidence of hemolysis. Bleeding complications can also include bleeding gums, hemoptysis, hematemesis, rectal bleeding, melena, hematuria, vaginal bleeding, and rarely intracranial hemorrhage. Both ischemic and hemorrhagic strokes have been reported with Cerastes cerastes envenomations infrequently. Coagulation abnormalities associated with envenomation are usually reversed by antivenin therapy, and generally do not require blood products or factors unless there is active bleeding. HYPOTENSION: Envenomations can produce hypotension which is mainly associated with hypovolemia but can occur from direct cardiotoxicity (B. arietans) or release of vasodilators (ie, bradykinins; V palaestinae). COMPARTMENT SYNDROME: Cases of compartment syndrome have been described after envenomation by B. arietans. INFREQUENT: Neurotoxicity (E pyramidum) has been reported infrequently. Circulatory failure has been reported infrequently due to a neurotoxic polypeptide (acting on medullary center) found in V palaestinae venom. Deaths have been reported from snakes originating in this region.

Vital Signs

    3.3.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) A low grade fever is common after envenomation. Hypotension may be profound in severe envenomation. Tachycardia or bradycardia may occur; bradycardia may at times be severe.
    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) FEVER: A low grade fever can occur after envenomation and is significantly higher in those patients who develop a neutrophil leukocytosis (Warrell et al, 1975).
    3.3.4) BLOOD PRESSURE
    A) WITH POISONING/EXPOSURE
    1) Hypotension may be profound in severe envenomation due to fluid or blood loss, direct cardiotoxicity, or anaphylactoid reaction.
    3.3.5) PULSE
    A) WITH POISONING/EXPOSURE
    1) Tachycardia or bradycardia may occur; bradycardia may at times be severe.

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) SYSTEMIC EYE EFFECTS
    a) Eye disturbances may occur as a result of systemic absorption of venom from cobra (Elapidae family) or viper (Viperidae family) bites (Grant, 1986).
    1) Reversible paralysis of the extraocular muscles and transient loss of vision are the most common effects. Antivenom generally resolves the paralytic effects.
    2) Retinal hemorrhage, optic atrophy, and permanently impaired vision are rare effects. Optic atrophy and permanent vision defects may be related to retinal hemorrhage, rather than being direct effects of venom.
    b) CASE REPORTS
    1) ERISTICOPHIS MACMAHONII: A 31-year-old man developed bilateral ptosis with angioedema of the eyelids after E macmahonii envenomation. No loss of vision was reported. Following supportive care which included antihistamines, oxygen and IV steroids, symptoms improved within 12 hours (denEndenErwin & Emmanuel, 2005).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) BITIS ARIETANS: Circulatory collapse occurs and may be delayed. Previously, this was attributed to hemorrhage into the bitten limb, gut and/or pelvis. More recently, it has been considered a direct action of the venom on the myocardium or autonomic nervous system (Warrell et al, 1974).
    b) ECHIS COLORATUS: Envenomation by this snake causes a transient hemostatic failure, including hypotension and abnormal bleeding (Gilon et al, 1989; Schulchynska-Castel et al, 1986).
    c) ERISTICOPHIS MACMAHONII: Syncope was reported shortly after envenomation in an adult. At the time of hospital admission, that patient was normotensive (BP 120/80) and no further episodes were reported (denEndenErwin & Emmanuel, 2005).
    d) VIPERA XANTHINA PALAESTINAE: Hypotension has been reported after significant envenomation (Ben Abraham et al, 2001; Bentur et al, 1997).
    e) VIPERA BERUS: In a series of 231 patients bitten by V. berus, 25 (11%) had "dry" bites. Swelling localized to the bite site developed in 40% of envenomated patients, in 25% swelling involved half the extremity, in 28% it involved the whole extremity, and in 5% it spread into the trunk. Vomiting, diarrhea and abdominal pain were the most common systemic manifestations, and developed in 38% of patients. Angioedema developed in 9%. Hypotension developed in 21%. Other manifestations of severe envenomation included CNS depression (mild in 75%, coma in 3%), respiratory distress (9%) thrombocytopenia (5%), and anemia (5%) (Karlson-Stiber et al, 2006).
    B) SHOCK
    1) WITH POISONING/EXPOSURE
    a) Circulatory failure has been reported infrequently due to a neurotoxic polypeptide (acting on medullary center) found in V palaestinae venom.(Warrell, 1995).
    C) BRADYCARDIA
    1) WITH POISONING/EXPOSURE
    a) VIPERA PALAESTINAE/CASE REPORT: A 62-year-old woman was bitten on the hand by a Vipera palaestinae and treated with antivenom on admission. On day 2, she was noted to have an asymptomatic bradycardia at 30 bpm while sleeping. There were no other ECG changes. Bradycardia continued for 2 days and resolved spontaneously and she was discharged in normal sinus rhythm (Blum et al, 2004).
    D) MYOCARDIAL INFARCTION
    1) WITH POISONING/EXPOSURE
    a) VIPERA PALAESTINAE/CASE REPORT: A 40-year-old man was bitten on the ankle by a snake (probably Viperae palaestinae) and developed progressive swelling of the leg to the groin with associated ecchymosis despite repeated antivenom infusion. Approximately 7 hours after envenomation, he developed retrosternal chest pain, nausea and vomiting and ECG changes consistent with an acute inferior myocardial infarction. CK was 831 U/L with a positive MB fraction, but cardiac troponin T was normal. One month later, cardiac catheterization revealed normal coronary arteries (Saadeh, 2001).
    b) VIPERA BERUS/CASE REPORT: An elderly woman, with extensive arteriosclerosis, had a myocardial infarction 8 days following envenomation by a Vipera berus, presumably related to anemia and underlying cardiac disease. Myocardial infarction has also been reported in a young girl immediately following envenomation by a European viper, which raises the possibility of a cardiotoxin in the venom (Karlson-Stiber et al, 2006).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) ACUTE LUNG INJURY
    1) WITH POISONING/EXPOSURE
    a) VIPERS: Pulmonary edema has been reported with severe fatal envenomation by Russell's viper and after envenomation by Vipera xanthina palaestinae and Vipera berus (Karlson-Stiber et al, 2006; Warrell et al, 1976; Bentur et al, 1997).
    B) DYSPNEA
    1) WITH POISONING/EXPOSURE
    a) ERISTICOPHIS MACMAHONII: Dyspnea without bronchospasm was reported in an adult following envenomation by an Eristicophis macmahonii. Symptoms resolved within 12 hours following supportive care including oxygen, antihistamines, and IV steroids. Recovery was uneventful (denEndenErwin & Emmanuel, 2005).
    b) VIPERA BERUS: In a series of 231 patients bitten by V. berus, 25 (11%) had "dry" bites. Swelling localized to the bite site developed in 40% of envenomated patients, in 25% swelling involved half the extremity, in 28% it involved the whole extremity, and in 5% it spread into the trunk. Vomiting, diarrhea and abdominal pain were the most common systemic manifestations, and developed in 38% of patients. Angioedema developed in 9%. Hypotension developed in 21%. Other manifestations of severe envenomation included CNS depression (mild in 75%, coma in 3%), respiratory distress (9%) thrombocytopenia (5%), and anemia (5%) (Karlson-Stiber et al, 2006).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) PARALYSIS
    1) WITH POISONING/EXPOSURE
    a) Neurotoxicity is most common following elapid and sea snake envenomation. However, mild neurotoxic (early ptosis, ophthalmoplegia) symptoms have developed in patients envenomed by E pyramidum (Warrell, 1995; Warrell, 1993). Symptoms can progress to respiratory muscle weakness and flaccid paralysis with E pyramidum envenomation (Warrell, 1995).
    b) ATRACTASPIS MICROLEPIDOTA: The venom of ATRACTASPIS MICROLEPIDOTA is said to be both vasculotoxic and neurotoxic.
    B) CENTRAL NERVOUS SYSTEM DEFICIT
    1) WITH POISONING/EXPOSURE
    a) SUMMARY: CNS depression may develop with severe envenomation (Warrell et al, 1976).
    b) VIPERA BERUS/CASE SERIES: Seven of 231 patients with Vipera berus envenomation were unconscious on admission and seizures occurred in one case (Karlson-Stiber et al, 2006).
    c) Systemic absorption of venom following the bite of some snakes in the Elapidae (cobra) and Viperidae (viper) families can result in transient paralysis of the extraocular muscles and temporary visual impairment. Antivenom generally resolves the paralytic effects (Grant, 1986).
    C) PARESTHESIA
    1) WITH POISONING/EXPOSURE
    a) ERISTICOPHIS MACMAHONII/CASE REPORT: A 31-year-old man bitten on the finger by an E macmahonii developed pronounced paresthesia in the contralateral arm and fingers without perioral tingling, muscular weakness, dyspnea, and bilateral ptosis. Following supportive care including oxygen antihistamines and IV steroids, symptoms improved within 12 hours and patient developed no permanent sequelae (denEndenErwin & Emmanuel, 2005).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) GASTROINTESTINAL HEMORRHAGE
    1) WITH POISONING/EXPOSURE
    a) Gastrointestinal bleeding may develop in patients with significant coagulopathy (Warrell, 1995; Warrell, 1993; Schulchynska-Castel et al, 1986; Benbassat & Shalev, 1993).
    B) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) Nausea and vomiting may develop (Warrell, 1995; denEndenErwin & Emmanuel, 2005; Ben Abraham et al, 2001; Warrell et al, 1976; Britt & Burkhart, 1997).
    b) VIPERA BERUS: In a series of 231 patients bitten by V. berus, 25 (11%) had "dry" bites. Swelling localized to the bite site developed in 40% of envenomated patients, in 25% swelling involved half the extremity, in 28% it involved the whole extremity, and in 5% it spread into the trunk. Vomiting, diarrhea and abdominal pain were the most common systemic manifestations, and developed in 38% of patients. Angioedema developed in 9%. Hypotension developed in 21%. Other manifestations of severe envenomation included CNS depression (mild in 75%, coma in 3%), respiratory distress (9%) thrombocytopenia (5%), and anemia (5%) (Karlson-Stiber et al, 2006).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) VIPERA XANTHINA PALAESTINAE: Transient increases in hepatic enzyme concentrations have been reported after envenomation by Vipera xanthina palaestinae (Gold & Pyle, 1998) .

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) BLOOD IN URINE
    1) WITH POISONING/EXPOSURE
    a) Gross hematuria may develop in patients with significant coagulopathy (Warrell, 1995; Warrell, 1993).
    B) ACUTE RENAL FAILURE SYNDROME
    1) WITH POISONING/EXPOSURE
    a) CERASTES CERASTES: Two men bitten while handling captive Saharan horned vipers (Cerastes cerastes) developed extensive local swelling, coagulopathy, fibrinolysis, thrombocytopenia, micro-angiopathic hemolytic anemia and acute renal failure (Schneemann et al, 2004).
    C) GLOMERULONEPHRITIS
    1) WITH POISONING/EXPOSURE
    a) NECROTIZING GLOMERULONEPHRITIS
    1) CASE REPORT: A 38-year-old man living in Saudi Arabia was bitten on his right hand by an unknown snake. Upon admission approximately 5 hours later, he had moderate swelling of his hand, anxiety, and appeared jaundice. He had laboratory evidence of disseminated intravascular coagulation (DIC) and renal failure (creatinine, 770 mg/dL). A renal biopsy was performed and the pathology findings were consistent with acute thrombotic microangiopathy with segmental glomerular scarring and concurrent acute renal injury. Treatment consisted of IV fluids, multiple doses of polyvalent antivenom, packed red blood cells and fresh frozen plasma. His coagulopathy was corrected but he had ongoing renal dysfunction. On day 3, hemodialysis was started and 3 weeks later he was clinically stable but required outpatient hemodialysis 3 times per week for 2 months with renal improvement (Al Qahtani et al, 2014). Of note, renal injury has been associated with a bite by members of the following families found in the Middle East: puff adder (Bitis arietans), stiletto snakes (Atractaspis microlepidoka andersoni and A. engaddensis), and saw scaled viper (Echis carinatus and E. coloratus).

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) ACIDOSIS
    1) WITH POISONING/EXPOSURE
    a) If massive necrosis, shock or renal failure occur there will be a metabolic acidosis, otherwise acid-base status is usually normal.

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) CEREBRAL HEMORRHAGE
    1) WITH POISONING/EXPOSURE
    a) ECHIS CARINATUS: A hallmark of poisoning by Echis carniatus spontaneous bleeding, cerebral or subarachnoid hemorrhage being the most common cause of death (Benbassat & Shalev, 1993).
    b) MECHANISM: The victim's blood fails to coagulate due to a consumptive coagulopathy initiated by a postcoagulants direct action on prothrombin (Kornalick & Blomback, 1975). Fibrinogen is severely depleted while fibrin degradation products (FDP) are increased. Factors II, V, VIII, X and XIII are also depleted (Warrell, 1995; Warrell et al, 1975).
    c) ECHIS SPECIES: In the presence of incoagulable blood, antivenom should be administered even if the patient is not seen until days after the bite, because deaths from cerebral hemorrhage have been described up to 12 days after envenomation. Recurrence of coagulopathy may occur in patients with E carinatus envenomation within 12 to 24 hours after initial correction with antivenom or as long as 42 hours after correction (Vijeth et al, 2000).
    d) CASE SERIES: In one study of 115 patients bitten by E CARINATUS in Nigeria, spontaneous bleeding occurred in 57% (Bhat, 1974).
    B) HEMORRHAGE
    1) WITH POISONING/EXPOSURE
    a) BITIS ARIETANS: Rarely produces spontaneous hemorrhage. Circulatory collapse, previously thought to be due to hemorrhage into the bitten limb, gut, or pelvis, is now thought to be due to direct action of the venom on the myocardium or autonomic nervous system (Warrell, 1995a; Warrell et al, 1974).
    C) BLOOD COAGULATION DISORDER
    1) WITH POISONING/EXPOSURE
    a) ECHIS COLORATUS: Markedly prolonged prothrombin time and partial thromboplastin time and decreased fibrinogen often occur with severe envenomation (Schulchynska-Castel et al, 1986). Spontaneous bleeding (from the gastrointestinal and genitourinary tracts, mucus membranes, and at puncture sites) may develop, but is not as common as with E carinatus bites (Benbassat & Shalev, 1993). Thrombocytopenia may develop but is less common (Schulchynska-Castel et al, 1986).
    b) ECHIS CARINATUS: Severe coagulopathy (incoagulable blood, frank bleeding, fibrinolysis and DIC) may develop (Vijeth et al, 2000). The hallmark of envenomation by E CARINATUS is spontaneous bleeding (Coppols & Hogan, 1992).
    1) In one study of 115 patients bitten by E CARINATUS in Nigeria it was found that local pain and swelling were virtually always present (Warrell et al, 1975). In addition, there was blistering (13%), necrosis (11%), incoagulable blood (93%), spontaneous bleeding (57%) and pain in the regional lymph nodes (77%). There was no evidence of neurotoxicity. Renal failure occurred in one case.
    2) In another study of 42 patients with Echis carinatus envenomation, 22 had severe coagulation abnormalities (incoagulable blood), 20 had mild coagulation defects (bleeding time more than 11 minutes but blood not incoagulable), 8 had evidence of DIC, and 24 had spontaneous bleeding. Two patients died secondary to renal failure (Vijeth et al, 2000).
    c) CERASTES CERASTES: Two men bitten while handling captive Saharan horned vipers (Cerastes cerastes) developed extensive local swelling, coagulopathy, fibrinolysis, thrombocytopenia, micro-angiopathic hemolytic anemia and acute renal failure (Schneemann et al, 2004).
    d) CERASTES VIPERA: CASE REPORT: A 3-year-old developed significant coagulopathy with thrombocytopenia, hypofibrinogenemia, prolonged PT and aPTT, and clinical bleeding (Lifshitz et al, 2000)
    e) Slightly prolonged prothrombin time/INR has been reported after envenomation with Cerastes vipera and king cobra envenomation (Ben-Baruch et al, 1986; Gold & Pyle, 1998).
    D) THROMBOCYTOPENIC DISORDER
    1) WITH POISONING/EXPOSURE
    a) VIPERA XANTHINA PALAESTINAE: Thrombocytopenia was reported in 5 of 16 patients treated with delayed administration of antivenom, 2 of 16 patients developed anemia (Bentur et al, 1997).
    E) ANEMIA
    1) WITH POISONING/EXPOSURE
    a) Anemia may accompany snake envenomation because of blood loss into injured tissues, bleeding secondary to coagulation abnormalities, hemolysis, or excessive crystalloid infusion.
    F) THROMBOEMBOLIC DISORDER
    1) WITH POISONING/EXPOSURE
    a) Deep venous thrombosis (DVT) is often suspected and rarely confirmed, but can occur.
    b) VIPERA BERUS: In one case series, DVT was suspected in 8 of 231 patients envenomated by Vipera berus. Six received venography and one had a confirmed DVT (Karlson-Stiber et al, 2006).
    c) Other workers have occasionally reported arterial thrombosis at a site remote from the bite (Bhat, 1974).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) BITE - WOUND
    1) WITH POISONING/EXPOSURE
    a) BITIS ARIETANS exhibits severe local reaction with very marked swelling, blistering, bruising, necrosis and the potential for the development of a compartment syndrome and arterial thrombosis.
    b) CERASTES CERASTES: Two men bitten while handling captive Saharan horned vipers (Cerastes cerastes) developed extensive local swelling, coagulopathy, fibrinolysis, thrombocytopenia, micro-angiopathic hemolytic anemia and acute renal failure (Schneemann et al, 2004).
    c) ECHIS COLORATA: Pain, swelling and local bleeding are common (Schulchynska-Castel et al, 1986; Benbassat & Shalev, 1993). Tissue necrosis may develop (Benbassat & Shalev, 1993).
    d) ECHIS CARINATUS: In one study of 115 patients bitten by E CARINATUS in Nigeria it was found that local pain and swelling were virtually always present (Warrell et al, 1975). In addition, there was blistering (13%), necrosis (11%), incoagulable blood (93%), spontaneous bleeding (57%) and pain in the regional lymph nodes (77%). There was no evidence of neurotoxicity. Renal failure occurred in one case.
    e) ERISTICOPHIS MACMAHONII: Tenderness of the extremity, generalized pain and swelling of lymph nodes in the region, and an extensive, burning skin rash developed in one adult following envenomation. Most symptoms resolved within 24 hours following supportive care. Necrosis of the tip of the finger was evident one day after the bite with only a small scar remaining at 6 months (denEndenErwin & Emmanuel, 2005).
    f) VIPERA PALAESTINAE: Pain, swelling, edema, blisters and hematomas may develop in the area of the bite (Ben Abraham et al, 2001).
    1) CASE REPORTS: In Vipera palaestinae envenomations, swelling may continue to progress for up to 4 days, with regression of swelling beginning after a week. Three cases of V palaestina bites involving the distal limbs developed tense swelling progressing to the trunk over 24 to 36 hours. Swelling involved the neck in 2 patients, causing dysphagia and impending upper airway obstruction. In the third, swelling resulted in urinary retention requiring urinary catheterization (Bentur & Cahana, 2003).
    2) CASE REPORT: A 5-year-old boy was bitten on the foot and developed generalized plasma leakage with swelling of the face (Karlson-Stiber et al, 2006).
    g) VIPERA BERUS: In a series of 231 patients bitten by V. berus, 25 (11%) had "dry" bites. Swelling localized to the bite site developed in 40% of envenomated patients, in 25% swelling involved half the extremity, in 28% it involved the whole extremity, and in 5% it spread into the trunk. Vomiting, diarrhea and abdominal pain were the most common systemic manifestations, and developed in 38% of patients. Angioedema developed in 9%. Hypotension developed in 21%. Other manifestations of severe envenomation included CNS depression (mild in 75%, coma in 3%), respiratory distress (9%) thrombocytopenia (5%), and anemia (5%) (Karlson-Stiber et al, 2006).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) DISORDER OF IMMUNE FUNCTION
    1) WITH POISONING/EXPOSURE
    a) COMPLEMENT: There is activation of complement by the classical, as well as the alternative pathway (Warrell et al, 1975). Venom antibodies are present in the victim's serum within 24 hours of being bitten.
    B) ANAPHYLACTOID REACTION
    1) WITH POISONING/EXPOSURE
    a) Some venoms have enzymes which cause the release of histamine, bradykinin and serotonin, which may trigger a serious anaphylactic reaction. Symptoms associated with anaphylaxis can include vomiting, colic, diarrhea, angio-edema and wheezing (Warrell, 1995).
    b) Patients with previous sensitization to venom may collapse within minutes of a bite and remain unconscious for upwards of 30 minutes due to an anaphylactic reaction (Warrell, 1995).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs and mental status.
    B) Monitor for progression of edema, pain and lymphadenopathy.
    C) Mark leading edge of soft tissue swelling and measure circumference at the area of the bite, reassess for progression every 15 to 30 minutes.
    D) The following tests should be obtained upon admission and repeated every 6 hours to assess worsening envenomation and/or efficacy of antivenom:
    1) Obtain complete blood count with differential. Monitor coagulation studies including INR, PTT, fibrinogen, fibrin degradation products, and whole blood clotting time over 20 minutes if other tests are not available.
    2) Obtain serum electrolytes, renal function tests and urinalysis and repeated as needed.
    3) Culture wound if evidence of secondary infection is present.
    E) Caution should be used in all venipuncture studies due to the risk of bleeding and/or oozing that may occur at the site. Arterial punctures should be avoided when possible, particularly in incompressible sites.
    4.1.2) SERUM/BLOOD
    A) HEMATOLOGIC
    1) Obtain a complete blood count with differential. A coagulation profile which includes INR/PT and PTT, platelet count, fibrinogen level, and fibrin degradation products should be obtained after a viper envenomation. Repeat every 6 hours, or as indicated to assess for progression of envenomation or response to antivenom.
    B) BLOOD/SERUM CHEMISTRY
    1) Monitor blood urea nitrogen and creatinine as indicated.
    2) Obtain creatine kinase in patients with severe swelling or evidence of compartment syndrome.
    4.1.3) URINE
    A) URINALYSIS
    1) Obtain urinalysis. Monitor for evidence of bleeding (hematuria) or acute renal failure (proteinuria).
    4.1.4) OTHER
    A) OTHER
    1) CULTURES
    a) Obtain wound culture in necrotic wounds with suspected infection.

Methods

    A) SAMPLING
    1) WHOLE BLOOD CLOTTING TEST-If PT/INR and PT cannot be performed readily, a method to determine whole blood clotting can be done at the bedside with a few millimeters of venous blood placed in a new, clean, dry, glass tube (or bottle), if the patient has no history of coagulopathies. The steps are as follows and may be useful if the species is unknown or difficult to identify (Anon, 1999):
    1) Place a few millimeters of venous blood in a GLASS tube
    2) Leave undisturbed for 20 minutes at room temperature
    3) Tip the vessel once:
    a) If blood is still liquid and runs out it is indicative of a venom-induced coagulopathy.
    b) Inaccurate results may occur if the vessel had been cleaned previously with detergent. Incoagulable blood is more frequently associated with viper envenomations.
    a) FALSE NEGATIVE results could occur if clot identification is read beyond 20 minutes (Stone et al, 2006).
    b) FALSE POSITIVE results could occur if polypropylene or polyethylene tubes are used instead of glass (Stone et al, 2006).
    1) A blinded methodological study was conducted to determine the potential effectiveness of various plastic containers as compared to glass in performing the whole blood clotting time (WBCT) (for 20 minutes) in envenomed patients. An initial pilot study demonstrated that WBCT without venom was significantly different between glass and various plastic containers (ie, polypropylene, polyethylene and polycarbonate). Polypropylene and plain polyethylene were considered unsuitable for further testing because of their prolonged clotting times of greater than 60 minutes in the presence of venom. The findings further suggested that various venom concentrations (0 ng/mL to 100,000 ng/ml were initially tested) could significantly alter the clotting time. No clotting was observed in either the glass or polycarbonate tube for venom concentrations above 100 ng/mL. Samples of 0 ng/mL and 10 ng/mL were used in the study because they clotted in 20 minutes. Polycarbonate (mean time of 29.5 minutes in the presence of venom) was considered a suitable alternative to glass if the threshold for clot identification was increased to 35 minutes. However, the authors concluded that differentiating between various plastic materials may be difficult and polycarbonate tubes may not be readily available in all healthcare facilities; therefore, the authors recommended the continued use of glass tubes (Stone et al, 2006).
    a) LIMITATIONS - Although glass tubes have been found to be sensitive and specific indicators of severe coagulopathy, false negative results could occur if the test results are read beyond the 20 minute threshold time. Other potential limitations could include: measurement bias of clot size, container volumes were not standardized, and use of one venom type (Pseudechis australis) may influence extrapolation of findings to other venom types.
    c) If there is any doubt, repeat the test and include a "control" (blood from an unexposed individual) (Anon, 1999).
    B) IMMUNOASSAY
    1) The ELISA method has been used to identify specific venom and in blood, serum, urine, saliva, sputum, CSF and aspirates from a bite site, blisters and wounds (Pugh & Theakston, 1987).

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) Any patient who has been bitten by a proven or suspected venomous viper should be admitted to a hospital for a 24 hour observation period. During the observation period the patient should be followed for progression of local signs every 15 to 30 minutes, coagulation abnormalities and systemic effects. If symptoms progress, airway compromise occurs or the patient requires antivenom administration, admit the patient to an intensive care setting.
    B) DISCHARGE CRITERIA: Patients can be discharged once they complete their antivenom if needed, their symptoms are improving, no paralysis or respiratory failure, their lab values are normal or a definite trend towards normal, and there is no evidence of recurrence. Early post-discharge physiotherapy referral and 2 to 4 days after discharge outpatient follow-up (for lab re-evaluation and assessing for serum sickness symptoms) should be arranged.
    6.3.6.2) HOME CRITERIA/BITE-STING
    A) There should be NO home treatment for bites from proven or suspected venomous snakes. The goal of prehospital care is rapid transport to a healthcare facility.
    6.3.6.3) CONSULT CRITERIA/BITE-STING
    A) CONSULT CRITERIA: Consult a local herpetologist for proper identification of the snake if it is available. Consultation with a medical toxicologist or a toxinologist is strongly recommended with administration of antivenom. A local poison center can provide information on the appropriate antivenom and how to obtain it for bites by exotic species.
    6.3.6.4) PATIENT TRANSFER/BITE-STING
    A) All patients should be taken to the nearest hospital or clinic stocking antivenom. If in a non-native geographic area and antivenom is not immediately available or routinely stocked, it will have to be obtained from the nearest zoo source, which may be at a distance and require some time. Thus, the patient should be taken to the nearest hospital capable of managing the patient's existing medical condition. Splint bitten extremity or area. Turn on side to prevent aspiration of vomitus.
    6.3.6.5) OBSERVATION CRITERIA/BITE-STING
    A) Any patient suspected of having been bitten by an Middle East viper should be referred to healthcare facility and closely observed for a period of 24 hours.
    B) Patients who present with fang marks only should be observed for at least 8 to 12 hours, then discharged if no signs or symptoms. During this time the bitten limb should be elevated and the tourniquet or constricting bands are removed. Patients with a suspected envenomation with no clinical effects can also be discharged after 3 normal consecutive WBCT (whole blood clotting times) tests (Monzavi et al, 2014).

Monitoring

    A) Monitor vital signs and mental status.
    B) Monitor for progression of edema, pain and lymphadenopathy.
    C) Mark leading edge of soft tissue swelling and measure circumference at the area of the bite, reassess for progression every 15 to 30 minutes.
    D) The following tests should be obtained upon admission and repeated every 6 hours to assess worsening envenomation and/or efficacy of antivenom:
    1) Obtain complete blood count with differential. Monitor coagulation studies including INR, PTT, fibrinogen, fibrin degradation products, and whole blood clotting time over 20 minutes if other tests are not available.
    2) Obtain serum electrolytes, renal function tests and urinalysis and repeated as needed.
    3) Culture wound if evidence of secondary infection is present.
    E) Caution should be used in all venipuncture studies due to the risk of bleeding and/or oozing that may occur at the site. Arterial punctures should be avoided when possible, particularly in incompressible sites.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) FIRST AID
    1) FIELD OR FIRST AID TREATMENT
    a) Put victim at rest and keep warm.
    b) Remove rings and constrictive items. Apply dressing if bleeding.
    c) Immobilize injured part in functional position and keep just below heart level.
    d) Give reassurance.
    e) Rapidly transport the patient to the nearest emergency department; ideally a facility with experience in treating snake bites.
    f) If constriction bands or pressure wraps are placed on the wound at the scene and without vascular compromise, they should be left in place until arrival at a health care facility. Consider placement of a constriction band or pressure wrap (to delay systemic absorption of venom) for prolonged transport times or for patients whose conditions are rapidly deteriorating (McKinney, 2001).
    1) The pressure bandage (ie, Sutherland's compression method) is suggested after bites by neurotoxic species such as mambas (Dendroaspis) and cobras (N. haje, N. melanoleuca, N. nivea) which may be found in this region (Warrell, 1995).
    2) Pressure immobilization is not recommended in patients bitten by Middle Eastern viper and spitting cobras because it is likely to produce an intensification of locally necrotic effects by the venom produced by these snakes. Secondary ischemic effects may result from increased pressure in tight fascial compartments, in particular the anterior tibial compartment (Warrell, 1995).
    g) The following first aid measures are contraindicated: ice, tourniquets, incision of any type, and any type of suction. Electric shock treatment for snakebite is ineffective and is potentially quite dangerous (Russell, 1987; Howe & Meisenheimer, 1988; Dart et al, 1988; Bucknall, 1991; Dart & Gustafson, 1991; McKinney, 2001).

Eye Exposure

    6.8.2) TREATMENT
    A) IRRIGATION
    1) Recovery typically occurs in 2 or 3 days, but may be require 1 or 2 weeks if severe corneal edema initially occurred (Grant, 1986). Permanent blindness and other effects have been reported (Warrell & Ormerod, 1976), and may be due in part to delayed treatment or infection.
    2) EYE EFFECTS FROM SYSTEMIC ABSORPTION OF VENOM: Extraocular muscle paralysis generally resolves within 2 to 5 days. Antivenom may reduce paralysis. Vision loss generally resolves within about 2 hours with Elapidae (cobra) venoms (Grant, 1986).

Abstracts

Case Reports

    A) ANIMAL DATA
    1) VIPERA PALESTINAE: In a retrospective review of hospital records, 327 cases of V palestinae envenomations in dogs was confirmed. The most frequent clinical signs included local swelling and edema (99.6%), viper teeth marks (51%), tachypnea (50%), panting (44%), increased body temperature (19.2%), tachycardia (19%), salivation (18%), and lameness (15.6%). Common hematologic findings included increased hematocrit (47%), increased hemoglobin concentration (45%), leucocytosis (39%), and thrombocytopenia (30%). The prothrombin time and activated partial thromboplastin times were prolonged in 68% and 21% of the cases, respectively. Other laboratory findings included increased muscle enzymes, hyperglycemia, hyperbilirubinemia, hyperglobulinemia and hypocholesterolemia (Segev et al, 2004).
    a) Mortality rate was 4%. Factors associated with an increased risk of mortality included body weight below 15 kg, limb envenomation, envenomation at night, severe lethargy, hypothermia, systemic bleeding, shock, dyspnea, tachycardia, thrombocytopenia, and glucocorticosteroid therapy. Dogs younger than 4 years had a lower risk of death. Specific antivenom therapy at 10 mL/dog was not associated with a higher survival rate.
    2) VIPERA XANTHINA PALESTINAE/CASE SERIES: In another retrospective review of 16 fatal dog envenomations, the most frequent clinical signs were soft tissue swelling and edema, local pain, depression, bleeding, lameness, dyspnea, and 6 dogs were in shock. Thrombocytopenia was seen in 14 cases, and hemoconcentration was present in the majority. Creatine kinase was markedly elevated in 2 cases. Severe complications included DIC, acute renal failure, seizures, cardiac dysrhythmias, necrotizing pancreatitis and laryngeal edema, requiring intensive care. Specific antivenom, 10 mL given to 8 dogs did not prevent death, although the dose given was considerably less than that used in humans. Steroid use was associated with a variety of complications. Two dogs in apparent recovery died within 1 to 2 days of discharged of indeterminate causes (Aroch et al, 2004).
    B) PEDIATRIC
    1) VIPERA PALAESTINAE
    a) In a retrospective study of 37 children ranging in age from 2 to 18 years (mean 8.9 years) bitten by V palaestinae and treated in 2 medical centers over a 9 year period, 15 (40.5%), 15 (40.5%) and 7 (19%) developed mild, moderate and severe envenomation, respectively. Major complications of envenomation included compartment syndrome (n=2) and respiratory dysfunction (n=2). Species-specific monovalent antivenom was given to 16 children (43%) of whom, 4 patients were in the severe group, 7 in the moderate group and 5 in the mild group. No patient suffered a significant infection, tissue loss, permanent disability or death (Paret et al, 1997).

Range Of Toxicity

Summary

    A) Not all snakes are venomous, and not all venomous snakes inject the same amount of venom if any (ie, dry bites) with each strike. Treatment therefore has to be based on symptoms rather than number of strikes.

Minimum Lethal Exposure

    A) Not all snakes are venomous, and not all venomous snakes inject the same amount of venom if any (ie, dry bites) with each strike. Treatment therefore has to be based on symptoms rather than number of strikes.
    B) Limited data. Deaths have been reported from snakes (B arietans) originating in this region (Warrell, 1995).

Maximum Tolerated Exposure

    A) VIPERA BERUS
    1) CASE SERIES: In a series of 231 patients bitten by V. berus, 25 (11%) had "dry" bites. Swelling localized to the bite site developed in 40% of envenomated patients, in 25% swelling involved half the extremity, in 28% it involved the whole extremity, and in 5% it spread into the trunk. Vomiting, diarrhea and abdominal pain were the most common systemic manifestations, and developed in 38% of patients. Angioedema developed in 9%. Hypotension developed in 21%. Other manifestations of severe envenomation included CNS depression (mild in 75, coma in 3%), respiratory distress (9%) thrombocytopenia (5%), and anemia (5%) (Karlson-Stiber et al, 2006).
    2) CASE REPORT: An elderly woman, with extensive arteriosclerosis, had a myocardial infarction 8 days following envenomation by a Vipera berus, presumably related to anemia and underlying cardiac disease. Myocardial infarction has also been reported in a young girl immediately following envenomation by a European viper, which raises the possibility of a cardiotoxin in the venom (Karlson-Stiber et al, 2006).
    B) VIPERA PALAESTINAE
    1) PEDIATRIC: In a retrospective study of 37 children ranging in age from 2 to 18 years (mean 8.9 years) bitten by V palaestinae and treated in 2 medical centers over a 9 year period, 15 (40.5%), 15 (40.5%) and 7 (19%) developed mild, moderate and severe envenomation, respectively. Major complications of envenomation included compartment syndrome (n=2) and respiratory dysfunction (n=2). Species-specific monovalent antivenom was given to 16 children (43%) of whom, 4 patients were in the severe group, 7 in the moderate group and 5 in the mild group. No patient suffered a significant infection, tissue loss, permanent disability or death (Paret et al, 1997).
    2) ADULT/CASE REPORT: A 62-year-old woman was bitten on the hand by a Vipera palaestinae and treated with antivenom on admission. On day 2, she was noted to have an asymptomatic bradycardia at 30 bpm while sleeping. There were no other ECG changes. Bradycardia continued for 2 days and resolved spontaneously and she was discharged in normal sinus rhythm (Blum et al, 2004).
    3) ADULT/CASE REPORT: A 40-year-old man was bitten on the ankle by a snake (probably Viperae palaestinae) and developed progressive swelling of the leg to the groin with associated ecchymosis despite repeated antivenom infusion. Approximately 7 hours after envenomation, he developed retrosternal chest pain, nausea and vomiting and ECG changes consistent with an acute inferior myocardial infarction. CK was 831 U/L with a positive MB fraction, but cardiac troponin T was normal. One month later, cardiac catheterization revealed normal coronary arteries (Saadeh, 2001).
    C) ECHIS CARINATUS
    1) CASE SERIES: In one study of 115 patients bitten by E CARINATUS in Nigeria it was found that local pain and swelling were virtually always present. In addition, there was blistering (13%), necrosis (11%), incoagulable blood (93%), spontaneous bleeding (57%) and pain in the regional lymph nodes (77%). There was no evidence of neurotoxicity. Renal failure occurred in one case (Warrell et al, 1975).
    D) ERISTICOPHIS MACMAHONII
    1) CASE REPORT: A 31-year-old man bitten on the finger by an E macmahonii developed pronounced paresthesia in the contralateral arm and fingers without perioral tingling, muscular weakness, dyspnea, and bilateral ptosis. Following supportive care including oxygen antihistamines and IV steroids, symptoms improved within 12 hours and patient developed no permanent sequelae (denEndenErwin & Emmanuel, 2005).

Pharmacology Toxicology

Toxicologic Mechanism

    A) TISSUE NECROSIS is attributable to abundant proteolytic enzymes and phospholipases A2 that are present in viper venom (Warrell, 1995b).
    B) CARDIOVASCULAR EFFECTS: Viper venom can produce a decline in blood pressure by increasing vascular permeability leading to hypovolemia; some species (i.e., B gabonica, B arietans) can have a direct effect on the heart and other species (i.e., B arietans) can produce splanchnic vasodilatation, and autopharmacological release of vasodilators such as bradykinin can occur in some species (e.g., V palaestinae) (Warrell, 1995b).
    C) NEUROTOXICITY may occur in some species and has been associated with the berg adder (B atropos) and E. pyramidum species. PLA2 neurotoxins have been found in the B caudalis (horned adder) and the B atropos (puff adder). The V Palestine (Palestine viper) has a neurotoxic polypeptide "vipertoxin" which can cause circulatory failure by acting on the medullary center (Warrell, 1995b).
    D) HEMOSTATIC TOXICITY: Several species are responsible for producing hematological disturbances (Warrell, 1995b):
    1) B. arietans (puff adder) has botrocetin-like activity which can cause platelet aggregation and hemorrhagin activity;
    2) B. gabonica (gaboon viper) has fibrinogen clotting activity which can split off fibrinopeptides A and B from fibrinogen, has direct fibrinogenolytic activity, and hemorrhagin activity;
    3) Cerastes Cerastes (horned or desert viper) activates Factor X and has direct fibrinogenolytic activity;
    4) C. rhombeatus - procoagulant activity, also contains a serine protease which inactivates antithrombin III and hemorrhagin activity;
    5) Echis carinatus (carpet viper) activates prothrombin and Factor X, direct fibrinogenolytic activity, inhibits platelet activation, contains a fibrinogenolysin and contains hemorrhagins (i.e., zinc metalloproteinase) that can damage vascular endothelium;
    6) E. coloratus (white-bellied carpet viper) activates Factor X and hemorrhagin activity;
    7) E. sochureki (Sochurek's saw-scaled viper) activates protein C;
    8) Psuedocerastes persicus (false-horned viper) - procoagulant activity.

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