Pit Viper Snakebite Assessment and Treatment

Course #94111 - $60 -


Self-Assessment Questions

    1 . All of the following snakes are considered pit vipers, EXCEPT:
    A) Cottonmouth
    B) Western massasauga
    C) Eastern garter snake
    D) Eastern diamondback rattlesnake

    PIT VIPERS

    The North American pit vipers include [9,13,15,18,21,47]:

    • Eastern diamondback rattlesnake (Crotalus adamanteus)

    • Western diamondback rattlesnake (Crotalus atrox)

    • Timber rattlesnake (Crotalus horridus)

    • Canebrake rattlesnake (Crotalus horridus atricaudatus)

    • Prairie rattlesnake (Crotalus viridis viridis)

    • Great Basin rattlesnake (Crotalus viridis lutosus)

    • Southern Pacific rattlesnake (Crotalus viridis helleri)

    • Northern Pacific rattlesnake (Crotalus viridis oreganus)

    • Mojave rattlesnake (Crotalus scutulatus)

    • Sidewinder rattlesnake (Crotalus cerastes)

    • Red diamond rattlesnake (Crotalus ruber ruber)

    • Northern black-tailed rattlesnake (Crotalus molossus)

    • Pygmy rattlesnake (Sistrurus miliarius)

    • Eastern massasauga (Sistrurus catenatus catenatus)

    • Western massasauga (Sistrurus catenatus tergemin)

    • Cottonmouth or water moccasin (Agkistrodon piscivorus)

    • Copperhead (Agkistrodon contortrix)

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    2 . In North America, most snakebites occur in the
    A) nighttime.
    B) early morning.
    C) fall and winter.
    D) spring and summer.

    THE SNAKEBITE

    By far, most bites to humans occur in the spring and summer. Snakes are cold-blooded, so they seek warmth underground or among rocks in cold weather. In the spring they are quite active, so one may see relatively many bites as the ground warms. More bites occur in the evenings, as people are more active outside and as the snakes become more active in seeking food during the time of day that better meets their temperature requirements. Wingert notes that [37]:

    Although snakes prefer nocturnal activity, a major proportion of the bites (approximately 45%) occur between 3 p.m. and 9 p.m. Males are bitten in a ratio of 4:1 over females. [Male humans suffer from a prefrontal cortex that matures later than that of the female, and many of this subset when bitten have recently consumed alcohol and/or other mind-altering drugs.] Fifty percent of bites occur in children or young adults younger than 20 years of age, with the highest proportion in the 16 to 24 year age group. Of all bites, 65% occur in the upper extremities (usually the hands or fingers) and 34% in the lower extremities. Approximately one-third of all bites are non-accidental; that is, the patient was purposefully handling or playing with a venomous snake.

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    3 . Approximately what percentage of rattlesnake bites are "dry" (no venom injected)?
    A) Less than 1%
    B) 25%
    C) 50%
    D) 80%

    THE SNAKEBITE

    Exposure to snakes occurs in a variety of places—gopher holes, open air conditioning ducting under buildings, on the roadside, commercial nurseries after the snakes are transported in potted plants, garages, gutter downspouts, corn fields, tall grass, woodpiles, and flowerbeds. According to experts at the Arizona Poison and Drug Information Center, 25% of rattlesnake bites are dry bites—no venom is injected. In another 25%, so little is injected that antivenom is not required [3]. Of an estimated 8,000 bites reported in the United States each year, only 8 to 15 result in death. Most of these deaths can be attributed to complications of the injury, errors in management, or other factors not directly related to snake venom [24].

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    4 . The majority of deaths from snakebite in the United States are by the
    A) copperhead.
    B) water moccasin.
    C) Mojave rattlesnake.
    D) eastern diamondback rattlesnake.

    VENOM: ITS EFFECTS AND IMPLICATIONS FOR MANAGEMENT

    The venom of rattlesnakes is responsible for more deaths, more hospitalizations, and more injuries than the venom of any other animal in North America [24]. The eastern diamondback rattlesnake accounts for the majority of deaths from snakebite in the United States [51]. Unlike the less complex neurotoxic venom of elapids, pit viper venoms, particularly those of the rattlesnakes (crotalids), are composed of as many as 20 different components.

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    5 . In general, envenomation by the massasauga is associated with
    A) extensive and irreversible necrosis.
    B) less severe edema than crotalid bites.
    C) a predomination of neurotoxic symptoms.
    D) fasciculations, particularly across the muscles of the back.

    VENOM: ITS EFFECTS AND IMPLICATIONS FOR MANAGEMENT

    Envenomation by the massasauga (Sistrurus catenatus) in general causes edema that is far less severe than with crotalid bites, although it may sometimes be marked in an untreated case. Ecchymosis is not unusual, and blebs may form. Necrosis is minimal. Patients do not complain of paresthesia, nor is fasciculation seen. In most cases, there is some immediate pain [11]. Nausea and vomiting may occur. Lethal toxicity is significant [13].

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    6 . The bite from a pit viper usually causes some degree of swelling around the bite area within
    A) 5 seconds.
    B) 60 seconds.
    C) 2 to 4 minutes.
    D) 5 to 10 minutes.

    VENOM: ITS EFFECTS AND IMPLICATIONS FOR MANAGEMENT

    The bite from a pit viper usually causes some degree of swelling around the bite area within 5 to 10 minutes. Nearly all bites cause pain, and pain that is initially mild usually increases in severity as edema progresses. The bite of a non-venomous snake may also be painful, but the pain results simply from the trauma of the bite and is of limited severity and duration, in contrast to the dull, constant pain and tenderness caused by envenomation. As local tissue damage increases, there is progressive swelling and ecchymosis.

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    7 . Which of the following statements regarding local signs and symptoms of pit viper envenomation is TRUE?
    A) Bites rarely penetrate subcutaneous tissue.
    B) The early spread of venom is by venous flow.
    C) Swelling and tenderness of regional lymph nodes is rare.
    D) Deeper bites are more likely to result in rapid clinical deterioration.

    VENOM: ITS EFFECTS AND IMPLICATIONS FOR MANAGEMENT

    Local swelling resulting from a deposit of venom may be immediate, greatly delayed, or absent, depending on the venom load and the depth of the bite. Deeper bites that penetrate muscle are more likely than subcutaneous bites to swell less, especially early on, but the venom is likely to make a more rapid entry into the systemic circulation due to the greater vasculature of muscle. This increases the likelihood of rapid clinical deterioration and more severe clotting abnormalities.

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    8 . When fasciculations are noted following a bite by an unidentified snake, which of the following snakes is more likely to be the offending reptile?
    A) Copperhead
    B) Water moccasin
    C) Southern Pacific rattlesnake
    D) Northern black-tailed rattlesnake

    VENOM: ITS EFFECTS AND IMPLICATIONS FOR MANAGEMENT

    Pit viper envenomation can rise to the level of a complex poisoning, affecting every organ system, resulting in coagulopathy and hemoconcentration (early) followed by a decrease in erythrocytes (anemia), thrombocytopenia, hematuria, proteinuria, hematemesis, melena, hemoptysis, epistaxis, and hypotension [19]. Hypofibrinogenemia and thrombocytopenia are common findings. Physiologic responses to envenomation, such as release of bradykinin, contribute to the severity of pain and, short of a shock state, may cause significant but transient hypotension [15]. Difficulty swallowing (dysphagia), blurred vision, and marked thirst may occur, and the patient may experience significant weakness after eastern and western diamondback envenomation [12]. The patient may feel faint, nauseated, and/or numb or tingly around the mouth, tongue, scalp, fingers, toes, or site of the bite [19]. Such paresthesias indicate that a significant envenomation exists. Fasciculations are very common in human victims, and when present after a bite by an unidentified snake should suggest the eastern diamondback, the Mojave, or the southern Pacific rattlesnake as the offending reptile. Fasciculations in severe cases may become generalized, especially with eastern diamondback rattlesnake bites [15]. Transient myosis is said to be a symptom of severe envenomation due to the bite of the eastern diamondback rattlesnake [15]. Convulsions are particularly common in children [12]. Prolongation of bleeding and clotting times may occur [19]. In addition to visible tissue destruction (including blebs, sloughing, and gangrene), changes in capillary permeability may occur, leading to great fluid loss and hypovolemic shock as well as pulmonary edema (both of which are frequent causes of death) and swelling of entire limbs. Anaphylaxis and Kounis syndrome are unlikely but possible results of snakebite and should be considered in the overall assessment of the patient.

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    9 . The greatest threat to the victim of a pit viper snakebite is
    A) severe and extensive edema.
    B) severe pain that does not respond to strong analgesics.
    C) activation of the coagulation cascade coupled with hypovolemic shock.
    D) None of the above

    VENOM: ITS EFFECTS AND IMPLICATIONS FOR MANAGEMENT

    While local swelling in the region of the snakebite may be the most visible sign used to identify progression or lack of progression of envenomation, it is important to bear in mind that an occasional patient will have scant or even no swelling and yet a severe coagulopathy demonstrated by a plummeting fibrinogen level and likely plummeting platelet count as well. The impact of the venom on the blood coagulation cascade, coupled with the possibility of hypovolemic shock resulting from leakage of intravascular fluid into the tissues, constitutes the greatest threat to the victim. Incipient coagulopathy following envenomation is, in a sense, a "stealth attack," because coagulopathy cannot be felt by the patient or seen by the clinician unless overt bleeding is present. This, along with the fact that an occasional coagulopathy develops only after a surprising number of hours, is the reason that all pit viper snakebite victims who have and continue to have no swelling or other signs or symptoms should be evaluated for coagulopathy and monitored clinically by an informed staff in an urgent care setting with the ability to perform all required laboratory studies for 8 to 12 hours before being discharged home. Typical urgent care units are unlikely to be able to perform timely fibrinogen or FDP testing and thus would be an inappropriate setting for pit viper snakebite evaluation. As such, patients typically initially present to a hospital-connected emergency center, and those who begin to demonstrate any signs or symptoms of envenomation should be admitted to an ICU for a minimum of 24 hours.

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    10 . CroFab and Anavip work by
    A) interrupting venom cell wall synthesis.
    B) binding with and neutralizing venom toxins.
    C) facilitating concentration of the venom in the target tissues.
    D) inhibiting coagulation cascade activation and causing cell death.

    THE ANTIVENOMS

    Antivenoms currently in use (CroFab and Anavip) that target pit viper venom are suspensions of venom-neutralizing antibodies prepared from the serum of animals hyperimmunized against specific venoms [33]. Protherics Inc., the manufacturer, describes Crotalidae Polyvalent Immune fragment antigen binding (Fab) (Ovine) (CroFab) as [9]:

    …a sterile, nonpyrogenic, purified, lyophilized preparation of ovine Fab (monovalent) immunoglobulin fragments obtained from the blood of healthy sheep flocks immunized with one of the following North American snake venoms: Crotalus atrox (western diamondback rattlesnake), Crotalus adamanteus (eastern diamondback rattlesnake), Crotalus scutulatus (Mojave rattlesnake), and Agkistrodon piscivorus (cottonmouth or water moccasin). To obtain the final antivenin product, the four different monospecific antivenins are mixed. CroFab is a venom-specific "Fab" fragment of immunoglobulin G (IgG) that works by binding and neutralizing venom toxins, facilitating their redistribution away from target tissues and their elimination from the body.

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    11 . Which of the following is a fundamental and critical point about the assessment of the snakebite victim?
    A) The early clinical course does not necessarily indicate a benign outcome.
    B) It is important to observe patients who present with snakebite for at least eight hours.
    C) An unremarkable physical exam and laboratory profile at presentation does not reliably indicate that the degree of envenomation is insignificant.
    D) All of the above

    ASSESSMENT

    Because of the variable composition of pit viper venoms, the systemic manifestations of poisoning are variable in onset and progression; optimal management requires careful, frequently repeated clinical assessment over an extended period while anticipating the serious complications that may be associated with snake envenomation [39]. Hurlbut et al. make three fundamental and critical points about assessment of the snakebite victim [50]:

    • An unremarkable physical exam and laboratory profile at presentation does not reliably indicate that the degree of envenomation is insignificant.

    • The early clinical course does not necessarily indicate a benign outcome.

    • It is important that physicians observe patients who present with snakebite for more than eight hours.

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    12 . An emotional or anxiety reaction is suggested by nonspecific symptoms (e.g., weakness, dizziness, nausea) that occur
    A) almost immediately after the bite.
    B) 30 to 60 minutes after the bite.
    C) 2 hours after the bite.
    D) more than 4 hours after the bite.

    ASSESSMENT

    Weakness, dizziness, cold and clammy skin, tachycardia, nausea, vomiting, and diarrhea are all nonspecific symptoms and may be manifestations of an emotional or anxiety reaction (Table 1), in which case they appear almost immediately after the bite. Such symptoms may also reflect systemic envenomation, in which case they generally occur after 30 to 60 minutes, or longer[15]. Importantly, "nausea and diaphoresis accompanied by dizziness and weakness are probably not primary neurologic signs but indications of early hypotension due to intravascular volume depletion," in which case treatment with antivenom and a normal saline bolus would be indicated [25].

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    13 . A "trivial" envenomation is indicated when
    A) the patient has moderate swelling and ecchymoses.
    B) the patient has a positive fibrin/FDP test result but only mild symptoms.
    C) swelling is localized 30 to 60 minutes after the bite and there are no other symptoms, including no coagulopathy after 8 to 12 hours of observation.
    D) the patient is only experiencing mild parasthesias and swelling is limited to the affected extremity.

    ASSESSMENT

    "Trivial" envenomation exists when swelling is localized 30 to 60 minutes after a bite and the patient ultimately exhibits no paresthesias, fasciculations, or ecchymoses; no symptoms other than minor pain; and no abnormal serial laboratory findings [12]. Antivenom is not indicated for apparent trivial envenomation. Instead, the affected part should be cleaned and immobilized and the patient should be immunized against tetanus and studied for at least 12 hours or overnight to ensure that delayed progression does not develop [12].

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    14 . All of the following are possible causes of mental status changes in the patient with snakebite, EXCEPT:
    A) A comorbidity
    B) Direct effect of venom on the brain
    C) Cerebral bleed due to coagulopathy
    D) Hypoxia related to pulmonary failure

    ASSESSMENT

    Pit viper venom does not cross the blood brain barrier and thus does not affect the brain directly. The presence of mental status changes suggests a comorbidity, prescription or recreational drug use, or the possibility of a cerebral bleed as a result of coagulopathy. Other complications of envenomation that may lead to mental status change include hypoxia secondary to pulmonary edema, cardiac failure, or hypovolemic shock. Aberrant behavior and seizure point to hypoxia, the etiology of which should be immediately explored.

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    15 . Which of the following is usually adequate for the treatment of hypotension in patients with snakebite envenomation?
    A) Blood transfusions
    B) Dopamine agonists
    C) IV fluid resuscitation
    D) Sympathomimetic amines with vasoconstrictor (alpha-adrenergic) activity

    TREATMENT OVERVIEW

    As noted, IV fluid resuscitation with normal saline (at least 20 mL/kg in both children and adults) is usually adequate for the treatment of hypotension in patients with snakebite envenomation. It is advisable to give IV fluids cautiously, monitoring cardiac function and pulmonary signs so as not to exacerbate peripheral edema or precipitate pulmonary edema, especially in the treatment of severe envenomation. Vasopressors should be used only as short-term agents for the treatment of shock and only after hypovolemia as the likely cause of shock has been considered and addressed [12].

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    16 . All of the following are benefits of urinary catheterization in patients with snakebite, EXCEPT:
    A) No risk of bleeding
    B) Continuous monitoring of fluid balance
    C) Early laboratory analysis, early detection, and early treatment of hematuria
    D) Facilitation of fluid management of myoglobinuria and prevention of renal failure

    TREATMENT OVERVIEW

    Risk of significant bleeding as a result of urinary catheter insertion is not of great concern in patients envenomed by pit vipers. Hematuria due to coagulopathy does not preclude urinary catheter insertion. Some risk of bleeding obviously exists; however, for patients with severe envenomation and those who are unable to void every one to two hours, the benefits of catheterization include:

    • Continuous monitoring of fluid balance, which is required to maintain vital signs and to prevent fluid overload

    • Facilitation of fluid management of myoglobinuria and prevention of renal failure, by real-time monitoring of urinary output and color and the presence of blood and/or myoglobin

    • Early laboratory analysis and detection of hematuria and/or myoglobinuria lead to early treatment with antivenom, a core component of proper management of pit viper envenomation

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    17 . In the prehospital setting, patients with suspected snakebite envenomation should
    A) be transported with lights and sirens.
    B) have any band or tourniquet removed immediately.
    C) not receive pain medication in order to avoid obfuscating symptoms.
    D) have the leading edge of swelling or tenderness marked, with time documented.

    THE STANDARD

    In the prehospital setting, emergency responders should remain calm and reassure the patient continually. Death from snakebite is very rare. If the patient is stable and the hospital is close, avoid lights and sirens, as less excitement keeps capillary pressure (and thus the pressure gradient) lower, resulting in slower absorption of the venom. The patient should be instructed to avoid any unnecessary activity and movement.

    If possible, the snake should be photographed and identified, but the animal should only be transported if its identity is in question and if it is safe to do so. Reflexes persist even after beheading, so all snakes should be treated as if alive.

    Jewelry should be removed, but any constricting band or tourniquet should remain until removal is instructed by a physician's order. The extremity should be lightly splinted/immobilized after marking and timing the leading edge of swelling or tenderness. The extremity should be positioned slightly below heart level. If a suction pump device (e.g., the Sawyer Venom Extractor) is used, it should be limited to one minute to prevent further tissue damage.

    If pain is severe, morphine sulfate should be administered (slowly, to avoid nausea), unless the patient has a history of allergy. One large-bore IV should be started away from the bitten extremity with warmed normal saline (as cold fluids can contribute to shock) administered and titrated to keep the patient's blood pressure within normal limits and pulse less than about 110–120 beats per minute in an adult; loss of vascular fluid volume should be considered. If circumstances allow for perfect sterile technique, start an IV lock away from the bitten extremity. Blood should be drawn using a large clot tube first, followed by tubes of all colors. All tubes should be fully labeled and signed, and a blood bank form (with phlebotomist signature) should be completed on arrival at the hospital.

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    18 . Asymptomatic patients with known or suspected snakebite should be studied for a minimum of
    A) 1 to 2 hours.
    B) 4 to 6 hours.
    C) 8 to 12 hours.
    D) 24 to 48 hours.

    THE STANDARD

    For all patients with known or suspected snakebite, assessment is based on laboratory values and progression, if any, of signs and symptoms. It is important to remember that even asymptomatic patients should be studied for 8 to 12 hours from the time of the bite [13].

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    19 . For suspected or known snakebite victims, all of the following laboratory studies should be performed immediately and every six hours thereafter, EXCEPT:
    A) Fibrinogen
    B) Lipid panel
    C) Urine myoglobin
    D) Hemoglobin and hematocrit

    THE STANDARD

    A blood band should be applied, and the blood requisition is labeled "Snakebite: hold clot tube only." The signed blood sample and requisition are sent to the blood bank, but type and screen or crossmatch should be performed only if it becomes necessary. Differential, creatine kinase (CK), and ethanol (if indicated) tests should also be included in the initial laboratory assessment. The following tests should be performed immediately and every six hours thereafter:

    • Hemoglobin and hematocrit

    • Platelets

    • Fibrinogen

    • FDPs (Once positive, do not repeat unless ordered by physician.)

    • PT/international normalized ratio (INR)

    • PTT

    • Chemistry panel

    • Urinalysis

    • Urine myoglobin (Must be a fresh specimen. Once positive, do not repeat unless ordered by physician.)

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    20 . Which of the following should be avoided in patients with signs and/or symptoms of envenomation?
    A) Strict bed rest
    B) Morphine sulfate
    C) Withholding food and liquids
    D) Automated blood pressure measurements

    THE STANDARD

    All patients with any signs/symptoms of envenomation should be admitted to an ICU. These patients are kept NPO and on strict bed rest initially, with vital signs taken every 15 minutes (including pulse oximetry); automated blood pressure measurements should be avoided. Morphine sulfate may be administered as needed for pain if the patient has no history of allergy. Infection is rarely an issue in the early management of snakebite, and prophylactic antimicrobials are not indicated. If there is uncertainty about the diagnosis or if objective signs (e.g., purulent discharge, fever) develop as a late complication of tissue breakdown, antimicrobial therapy may be indicated, guided by cultures [12].

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    21 . If coagulation values are normal, blebs, vesicles, and superficial necrotic tissue at the site of a snakebite should be aseptically debrided
    A) immediately.
    B) within 24 hours.
    C) on the fourth or fifth day.
    D) after resolution of all symptoms, usually after 10 to 14 days.

    THE STANDARD

    Blebs, vesicles, and superficial necrotic tissue should be aseptically debrided on the fourth or fifth day, per local protocol, if coagulation values are normal. Active and passive rehabilitation therapy should be initiated as soon as the patient is able to tolerate it to prevent contractures, and the patient with significant injury should be referred to rehabilitation therapy at discharge.

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    22 . In patients with snakebite, antivenom treatment should be initiated in the presence of
    A) frank bleeding.
    B) multicomponent coagulopathy.
    C) rapid swelling beyond the area of the bite.
    D) Any of the above

    THE STANDARD

    Antivenom treatment should be initiated in the presence of any of the following signs or symptoms [86]:

    • Frank bleeding

    • Shock

    • Rapid swelling beyond the area of the bite

    • Significant swelling (i.e., progresses at a rate of 1 cm per hour, whether linearly or circumferentially) that fails to localize within 30 to 60 minutes from the time of the bite

    • Ecchymosis progressing beyond the bite site

    • Any degree of true neurotoxicity, including localized fasciculations or myokymia (with the possible exception of bites by the south-ern Pacific rattlesnake unless in combination with other significant signs or symptoms)

    • Single-component coagulopathy (one of the following):

      • Low fibrinogen (less than 50 mg/dL)

      • Fibrinogen trending significantly downward (consider history of familial afibrinogenemia)

      • Low platelets (less than 25,000/mcL)

      • Platelets trending significantly downward (consider history of taking anticoagulants or thrombocytopenia), INR greater than 3.0, or PTT greater than 50 seconds

      • PTT or INR trending significantly upward

      • Low hemoglobin/hematocrit or hemoglobin/hematocrit trending significantly downward (consider history of anemia)

    • Multicomponent coagulopathy (same as single-component coagulopathy except fibrinogen less than 75 mg/dL and platelet count less than 50,000/mcL)

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    23 . Regardless of the site of the bite, progression of circumferential or linear swelling is considered significant if it measures
    A) 0.2 cm/hour.
    B) 1 cm/hour.
    C) 1 cm/day.
    D) 3 cm/day.

    THE STANDARD

    Progression of circumferential or linear (leading edge) swelling measuring 1 cm/hour is considered to be significant, regardless of the site of the bite. Without early and adequate treatment, swelling and healing can take weeks to return to a level of maximum improvement. With early and adequate treatment, swelling can be expected to subside in approximately 10 days [4]. It is therefore important to not wait hours to see how far swelling progresses before beginning antivenom administration, because further and perhaps irreversible tissue destruction may well be occurring during that time. Swelling can occur haltingly as the venom dissolves different types and layers of tissue and can be thought to have stopped, only to become obvious again. One should not wait for multiple episodes of such a pattern to pass before beginning treatment.

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    24 . When reconstituting CroFab,
    A) the materials should be mixed by gentle swirling.
    B) the reconstituted materials should never be returned to the IV bag.
    C) the materials should be mixed by continuous gentle manual inversion.
    D) it is important not to release pressure from the vial after the diluent is added.

    THE STANDARD

    Each vial of CroFab should be reconstituted with 18 mL of 0.9% saline drawn from an IV bag of normal saline containing the volume of fluid the patient is to receive over the next hour (minimum: 250 mL) [4]. The diluent should be instilled gently along the wall of each vial to avoid foaming. To hasten mixing, release pressure after all diluent is added. Each vial of CroFab should be mixed by continuous, gentle manual inversion at a rate no faster than two complete inversions per second, until no solid material is visible in the vial; to prevent foaming, it should not be shaken. The reconstituted antivenom is then returned to the IV bag.

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    25 . For severe envenomations, regardless of patient age, CroFab is initially administered in increments of
    A) 2 vials.
    B) 6 vials.
    C) 10 vials.
    D) 20 vials.

    THE STANDARD

    Regardless of patient age, in severe envenomation CroFab is initially administered approximately each hour in increments of 10 vial doses to gain control (rather than the routine 6 vial doses discussed later) until initial control is achieved. Consultation should be sought early with severe envenomation, particularly if initial control is not achieved by the administration of two 10-vial doses of CroFab.

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    26 . The onset of recurrent or delayed hematologic venom effects typically occurs
    A) within 24 hours after initial control.
    B) 2 to 7 days after initial control.
    C) 10 to 12 days after initial control.
    D) more than two weeks after initial control.

    THE STANDARD

    After swelling appears to have ceased and coagulation studies have normalized or are trending substantially toward normal, one should continue to measure and mark the zone of local swelling every 30 minutes to 2 hours for the next 48 hours. Importantly, recurrence or delayed-onset of one or more venom effects occurs in up to approximately half of patients treated with CroFab antivenom [87]. Recurrence can also occur after treatment with Anavip. Local tissue recurrence typically develops within 6 to 36 hours of initial control. The onset of recurrent or delayed-onset hematologic venom effects typically occurs 2 to 7 days after initial control, with some cases up to 10 days after initial control [88].

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    27 . The first-line therapy for management of anaphylaxis is
    A) cimetidine.
    B) epinephrine.
    C) methylprednisone.
    D) diphenhydramine.

    THE STANDARD

    Epinephrine is the drug of choice for anaphylaxis and should be administered as first-line therapy. Epinephrine may rarely be used prophylactically in patients known to be acutely sensitive to antivenom or its components and who have a life-threatening envenomation.

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    28 . Any patient with signs of anaphylaxis who does not respond promptly and completely to epinephrine should be assumed to have
    A) shock.
    B) intravascular volume depletion.
    C) a common delayed response to epinephrine.
    D) another cause of symptoms—not anaphylaxis.

    THE STANDARD

    Massive fluid shifts can occur rapidly in anaphylaxis due to increased vascular permeability, with transfer of up to 35% of the intravascular volume into the extravascular space within minutes [82]. Any patient who does not respond promptly and completely to injected epinephrine should be assumed to have intravascular volume depletion causing persistent hypotension despite maximum vasoconstriction. Large-volume warmed fluid resuscitation should be initiated immediately in patients who present with orthostasis, hypotension, or incomplete response to IM epinephrine [81]. Adults may require 1–2 L normal saline administered at a rate of 5–10 mL/kg in the first five minutes. Children should receive up to 30 mL/kg in the first hour [98].

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    29 . Snakebite patients at risk for local or coagulopathy recurrence (i.e., with abnormal coagulation during the first 36 hours) should be reassessed
    A) once prior to discharge.
    B) every 48 hours after the last antivenom dose.
    C) until the antivenom dose is fully administered.
    D) for 24 hours after the antivenom dose is fully administered.

    THE STANDARD

    Boyer et al. recommend that patients who have received antivenom should be re-evaluated at least once within five days after treatment [5]. If the results of laboratory testing remain normal, recurrence is unlikely. However, patients at risk for recurrence (i.e., with abnormal coagulation during the first 36 hours) should be reassessed every 48 hours after the last antivenom dose, until coagulation values are clearly stable or improving for several days [5].

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    30 . Antivenom re-treatment should be considered in patients with
    A) a low-risk comorbid condition.
    B) platelet count greater than 80,000/mcL.
    C) fibrinogen concentration less than 50 mg/dL.
    D) a clear improvement trend after mild early coagulopathy.

    THE STANDARD

    If coagulation values become significantly abnormal on follow-up, or if there is a definite downward trend, then laboratory test results should be monitored daily and consideration should be given to re-treatment with antivenom. Until more data are available, re-treatment with FabAV should be considered in patients with any of the following [5]:

    • Fibrinogen concentration less than 50 mg/dL

    • Platelet count less than 25,000/mcL

    • INR greater than 3.0

    • PTT greater than 50 seconds

    • Multicomponent coagulopathy with abnormal laboratory values of a lesser degree

    • A clear worsening trend at follow-up in patients who had a severe early coagulopathy

    • High-risk behavior or comorbid conditions

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