Transcript Evaluation and Current Treatment Options for North American

Evaluation & Current Treatment
Options for North American
Poisonous Snake Envenomations
Matthew T. Hamonko MD, MPH,
FACEP, FAWM, FAAEM
Identification
• Coral Snake
“Red on yellow, kill a fellow;
red on black, venom lack.”
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Identification
• Coral Snake
“Red on yellow, kill a fellow; red on black, venom lack.”
ONLY WORKS IN NORTH AMERICA, NORTH OF
MEXICO CITY!
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Identification: Pit Vipers
• Pit Viper
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• Non-venomous snake
Triangular head
Elliptical eyes
Fangs
Pit
Single row of subcaudal
plates
*Pits
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Rounded head
Round eyes
No fangs
No pits
Double row of subcaudal
plates
are the only 100% consistent finding
*subcaudal plates only useful in North America
Marx, et. al. Rosen’s Emergency Medicine: Concepts and Clinical Practice 5th ed. Mosby, 2002.
Identification
• Corbett, S.W., et. al., “Most lay People can Correctly identify
Indigenous Venomous Snakes.” Amer Journal Emerg
Med.,2005;23:759-762.
– N=265 (169 adults, 72 children)
– 4 non-venomous snakes, 2 venomous snakes
• Gopher snake, moutain king snake, common king snake,
rosy boa, mojave rattlesnake, southern pacific
rattlesnake
– Southern California street fair
– Random members of the public were able to
differentiate venomous from non-venomous 81%
of the time
Pit Vipers
• Present in all 48 contiguous states except
Maine
• Distribution
– Rattlesnakes- all of North America
– Copperheads- central and southeastern U.S.
– Water moccasins- southeastern U.S. in to Texas
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Pit Vipers
• Eastern Diamondback Rattlesnake can exceed 6.5 ft in
length
• Maximum pit viper speed = 3 mph
• “Crotaline snakes do not chase people”
• Can voluntarily decide how much venom to inject
– Envenomation in 75%-80% of bites
– 35% mild, 25% moderate, 10-15% severe
• Most elaborate venom delivery system of all snakes
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Pit Vipers
• Hollow fangs
• Individually foldable
• Up to 20mm in
length
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Pit Vipers
• Venom
– Roughly 100
chemical components
– Protein (90%-95%)
and non-protein
based (5%-10%)
– Phospholipase A2
neurotoxins
– Metalloproteinases
– Other
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Pit Vipers
• Venom
– Phospholipase A2 neurotoxins
• Noncompetitively binds presynaptic calcium channels
– Inhibits acetylcholine release at NMJ
– Muscle inactivation
– Respiratory paralysis
• Damages muscle cell membranes
– Calcium influx
– CK release
– Myonecrosis, rhabdomyolysis
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Pit Vipers
• Venom
– Metalloproteinase
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Primary cause of local tissue destruction
Activation of TNF-α
Activates endogenous metalloproteinases
Causes RBC leakage from vasculature causing ecchymosis
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Pit Vipers
• Venom
– Thrombin like enzymes
• Consumptive coagulopathy
– Disintegrins
• Inhibit platelet interaction with fibrinogen
– Bradykinins
– Hyaluronidase
• Decreased connective tissue viscosity
– Lysolecithin
• Damage mast cell membranes causing histamine release
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Pit Vipers
• Signs and symptoms after Rattlesnake envenomation
– Local: severe burning, swelling, bleeding, ecchymosis, fang
marks, vesicles, bullae
– Systemic: nausea, vomit, generalized weakness, odd taste,
tachypnea, tachycardia, pulmonary edema, hypo- or
hypertension, shock, muscle fasciculations, parasthesias,
numbness, focal muscle weakness, bleeding (Neuro, GI/GU,
pulm, gingival)
– Estimated mortality for untreated bites: 2.6%
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Elapids
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Found in the Arizona, Texas and the Southeastern U.S.
Bites uncommon
Less aggressive, unable to strike like crotalines
Simple venom delivery apparatus
– fixed fangs, about 2mm in length
– Must chew on the victim to inject sufficient venom
– Envenomation in 40% of bites
• Venom
– Minimum proteolytic activity
– Contains some hyaluronidase, myotoxins and phospholipases
Primary component: Neurotoxin
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Norris, R.L, et al, “Apparent Coral Snake Envenomation in a Patient Without Visible Fang
Marks.” Amer Journ Emerg Med, 1989;7:402-405.
Elapids
• Venom
– Neurotoxin
• Low molecular weight protein
• Non-depolarizing neuromuscular blocker
• Postsynaptic competitive binding of acetylcholine receptors at NMJ
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Norris, R.L, et al, “Apparent Coral Snake Envenomation in a Patient Without Visible
Fang Marks.” Amer Journ Emerg Med, 1989;7:402-405.
Elapids
• Signs and Symptoms
– Local: early, mild, transient pain, +/- fang marks
(85%)
– Systemic (4-10 hours later sometimes delayed up
to 13 hours): nausea, vomit, headache, abdominal
pain, diaphoresis, pallor, parasthesias, numbness,
altered mental status, cranial nerve dysfunction,
focal motor weakness, respiratory paralysis
– Estimated mortality for untreated bite: 10%
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Norris, R.L, et al, “Apparent Coral Snake Envenomation in a Patient Without Visible Fang Marks.”
Amer Journ Emerg Med, 1989;7:402-405.
Elapids
• Norris, R.L, et al, “Apparent Coral Snake Envenomation in a Patient
Without Visible Fang Marks.” Amer Journ Emerg Med, 1989;7:402405.
– 27 year old male
– Bitten on finger by coral snake
– Complains of finger parasthesias at bite site and blurred
vision
– No evidence of trauma on examination of the finger under
magnification
– Normal vital signs, normal exam
– Given antivenin based on history and symptoms
– Total resolution of symptoms after antivenin infusion
completed (4 hours after bite)
Evaluation
• Rapid detailed history
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Time of the bite
General description of the snake
First aid measures used
Coexisting medical conditions
Drug and food allergies
Allergies to horse or sheep products
History of previous snake bites and subsequent therapy
History of tetanus immunization (update if necessary)
Gold, B.S., et. al., “Bites of Venomous Snakes.” NEJM, 2002;347:347-356.
Evaluation
• Physical exam
– ABC’s
– Special attention to cardiovascular, pulmonary and
neurologic systems
– Bite exam:
• Fang or tooth marks (snakes have regular teeth too),
scratches, edema, erythema, ecchymoses
• Baseline circumferential measurement with repeat every
15-20 minutes
• Evaluate for compartment syndrome
Gold, B.S., et. al., “Bites of Venomous Snakes.” NEJM, 2002;347:347-356.
Marx, et. al. Rosen’s Emergency Medicine: Concepts and Clinical Practice 5th ed. Mosby,
2002.
Evaluation
• Laboratory studies
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CBC
PT, PTT, INR, fibrinogen, fibrin degradation products
Chem
UA
CK
Type and cross for 4 units
CXR
EKG
ABG (respiratory compromise)
Gold, B.S., et. al., “Bites of Venomous Snakes.” NEJM, 2002;347:347-356.
Marx, et. al. Rosen’s Emergency Medicine: Concepts and Clinical Practice 5th ed. Mosby, 2002.
Evaluation
• Laboratory results
– Coral Snakes
• No likely laboratory abnormalities
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Evaluation
• Laboratory results
– Pit Vipers
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WBC elevation (neutrophil leukocytosis)
Thrombocytopenia
Hyperglycemia
Elevated CK
Elevated BUN and Crt
Elevated LFT’s
Elevated PT, PTT and INR
Low fibrinogen, elevated fibrin degradation products, (+)DDimer
• UA:hematuria, proteinuria
• EKG: ischemia
• CXR: pulmonary vascular congestion, pulmonary edema
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Treatment
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General management
Refractory thrombocytopenia
Anaphylaxis
Antibiotic prophylaxis and empiric treatment
Antivenom administration
Pressure dressings
Surgical techniques
Suctioning
Treatment
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Between 1000 and 600 BC
Hindu physician: Sushruta
Medical book: Ayurveda
Treatment of snake bites: tourniquet, incision,
suction, wound cautery
Wingert, W.A., “Rattlesnake Bites in Southern California and Rationale for
Recommended Treatment.” The Western Journal of Medicine, 1988;148:37-44.
Treatment
• Early American method: Whiskey
• 1908, Archives of Internal Medicine article
reported a significant number of deaths more likely
to be caused by forced alcohol intake than the bite
itself, often in children
Dart, R.C., et al., “Efficacy, Safety, and Use of Snake Antivenoms in the United States.” Ann of Emerg Med,
2001;37:181-188.
Burch, J.M., et al, “The Treatment of Crotalid Envenomation without Antivenin.” Journal of Trauma, 1988;28:35-43.
General Management
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Early intubation for pit viper bites to the face or neck
2 large bore IV lines
Pulse ox and cardiac monitor
IV crystalloid
Albumin trial if refractory to 2 liters of crystalloid (or 40ml/kg
in a child)
Vasopressors if hypotension refractory to fluid resuscitation
and antivenom infusion has been started
Opioid analgesia (no NSAIDS, may exacerbate coagulopathy)
Tetanus prophylaxis if indicated
Wound cleaning
Splinting of involved extremity
Elevation of the extremity above the heart (if antivenom is
indicated, start before elevating the limb)
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Refractory Thrombocytopenia
• Gold, B.S., et al., “Refractory Thrombocytopenia Despite Treatment
for Rattlesnake Envenomation.” N Engl J Med, 2004;350:1912-1913.
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38 year old male bitten on left hand by timber rattlesnake
Swelling, ecchymosis, tenderness
Normal vital signs
Platelet count on admission: 157,000
Platelet count five hours later: 28,300
Received 46 vials of Crofab
Platelet count 10 days later prior to discharge: 26,300
No incidence of spontaneous bleeding during his 10 day
hospital stay
– Platelet count 3 weeks after envenomation: 245,000
Refractory Thrombocytopenia
• Recommendation:
– Administer antivenom prior to administration of
blood products (FFP, platelets, PRBC’s, cryo)
• Regardless of bleeding, platelet transfusion for levels
below 20,000
– Consumptive coagulopathy refractory to
replacement of coagulation factors or other blood
components while un-neutralized venom
components are present
– Coagulopathy may resolve after antivenom alone
Gold, B.S., et. al., “Bites of Venomous Snakes.” NEJM, 2002;347:347-356.
Brooks, D.E., et. al. “Airway Compromise After First Rattlesnake Envenomation.” Wilderness and Environmental
Medicine, 2004; 15:188-193.
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Anaphylaxis
• Brooks, D.E., et. al. “Airway Compromise After First Rattlesnake
Envenomation.” Wilderness and Environmental Medicine, 2004;
15:188-193.
– 26 year old male, bitten on the hand by a sidewinder
rattlesnake (Crotalus cerastes)
– History of handling and eating rattlesnakes but no previous
envenomations
– Initial BP 68/28, no rash or edema at wound site
– Severe Airway edema developed within 45 minutes of ED
presentation
– Swelling of the entire right arm at 72 hours post
envenomation
– Subsequent hematuria, renal failure, large bowel
enterocutaneous fistulas, sepsis and malnutrition
Anaphylaxis
•
Ryan, K.C., et. al. “Life-threatening Anaphylaxis Following Envenomation by
two Different Species of Crotalidae.” Journal of Wilderness Medicine,
1994;5:263-268.
– 42 year old male bitten on the hand by a rattlesnake
– Previous history of envenomation by another species of
rattlesnake
– 5 minutes post bite he present with dyspnea, nausea, vomiting,
abdominal pain, intensely pruritic, erythematous rash covering
his upper extremities, anterior chest and abdomen
– 3 years later, bitten on the hand by another species of rattlesnake
– Once again presents with vomiting, dyspnea, diffuse
erythematous rash as well as expiratory wheezing
– Symptoms responded well to SQ epinephrine and IV solumedrol
– Discharged the following day with no antivenin administered on
either occasion
Anaphylaxis
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Primarily case reports
Uncommon entity
Type I IgE mediated
Type III immune complex mediated
IgE and IgG shown to be produced after sensitization
to venom
• One type of venom may cause sensitization to another
• Airborne, GI and cutaneous exposures may be
involved
• Treat like any other anaphylactic reaction
Brooks, D.E., et. al. “Airway Compromise After First Rattlesnake Envenomation.” Wilderness and Environmental
Medicine, 2004; 15:188-193.
Ryan, K.C., et. al. “Life-threatening Anaphylaxis Following Envenomation by two Different Species of Crotalidae.”
Journal of Wilderness Medicine, 1994;5:263-268.
Antibiotics?
•
LoVecchio, F., et. al., “Antibiotics After Rattlesnake Envenomation.” Journ of
Emerg Med, 2002;23:327-328.
• Prospective observational study
• N=56
• Inclusion criteria: presentation to hospital within 24 hours,
completion of follow up at 7-10 day
• Exclusion criteria: antibiotics initiated before evaluation at research
institution
• (+) infection defined as: report of infection by a physician, use of
antibiotics within 10 days, report of purulent discharge by patient,
positive wound culture
• 61% bites to upper extremity, 39% bites to lower extremity
• 70% had tender proximal lymph nodes
• No cases of documented infection
• Antibiotics given to 3 patients by their primary doctor
– Reasoning: prophylaxis, presumed standard of care, ecchymosis
Antibiotics?
• Gold, B.S., et. al., “Bites of Venomous Snakes.” NEJM, 2002;347:347356.
• Recommendation:
– “Wound infections are rare after pit viper bites;
therefore, the prophylactic use of antibiotics is not
recommended. Antibiotics should be administered
if there is clinical and microbiologic evidence of
wound infection.”
Antibiotics?
• Secondary infection pending cultures
– Ciprofloxacin 500 mg PO BID
– +/- metronidazole or clindamycin (anaerobic)
– Pregnant woman and children
• Ceftriaxone 50mg/kg up to1 gram IV or IM then
amoxicillin/clavulanate 40mg/kg PO divided TID
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Antivenom
• To give or not to give?
– Coral snakes:
• If a coral snake is identified: give it
• If There is evidence by history or exam that the snake
delivered an effective bite: give it
• If there are systemic findings: give it
• If there are no systemic findings after a confirmed coral
snake envenomation: give it
• If there are no local findings after a confirmed coral
snake envenomation: give it
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Antivenom
• To give or not to give?
– Pit vipers
• Grading systems
• Decision rules
Antivenom
Gold, B.S., et. al., “Bites of Venomous Snakes.” NEJM, 2002;347:347-356.
Antivenom
 Crofab
 Mild 4-6 vials
 Moderate 4-6 vials
 Severe 6 vials
 ACP
 Mild 0 or 5 vials
 Moderate 10 vials
 Severe 15-20 vials
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Antivenom
• Wyeth’s (manufacturer) scale
– 0- no evidence of envenomation, fang wound may
be present, minimal pain, <1 inch surrounding
edema/erythema, no systemic manifestations
during the 1st 12 hours, no lab changes
– I- minimal envenomation, fang wound usually
present, moderate pain at wound site, 1-5 inch of
surrounding erythema, no systemic involvement
after 12 hours of observation, no lab changes
Marx, et. al. Rosen’s Emergency Medicine: Concepts and Clinical Practice 5th ed. Mosby, 2002.
Antivenom
• Wyeth’s (manufacturers) scale
– II- moderate envenomation, more severe and
widely distributed pain, edema spreading toward
trunk, petechiae and ecchymosis limited to area of
edema. Nausea, vomit, giddiness and mild temp
elevation usually present
– III- severe envenomation, rapidly progressive,
within 12 hours edema spreads up extremity and
may involve trunk, petechiae and ecchymoses may
be generalized. Systemic manifestations may
include tachycardia, hypotension, subnormal temp
Marx, et. al. Rosen’s Emergency Medicine: Concepts and Clinical Practice 5th ed. Mosby, 2002.
Antivenom
• Wyeth’s (manufacturers) scale
– IV- very severe envenomation, sudden pain,
rapidly progressing swelling that may reach the
trunk within a few hours, ecchymoses, bleb
formation, necrosis. Systemic manifestations
(often within 15 minutes) of weakness, nausea,
vomiting, vertigo, numbness and tingling of the
lips and face, muscle fasciculations, muscle
cramps, pallor, sweating, cold/clammy skin,
rapid/weak pulse, incontinence, convulsions,
coma, death
Marx, et. al. Rosen’s Emergency Medicine: Concepts and Clinical Practice 5th ed. Mosby, 2002.
Antivenom
Grade
Preferred route
O
Amount
administered
(ACP)
None
I
None
None
II
5 vials
IV 1:10 dilution
III
5-10 vials
IV 1:10 dilution
IV
10-20 vials
IV 1:10 dilution
None
Marx, et. al. Rosen’s Emergency Medicine: Concepts and Clinical Practice 5th ed. Mosby, 2002.
Antivenom
• Copperhead snakes
– Rosen’s: “Bites by copperheads usually cause a
moderate amount of edema but do not usually
require antivenin”
– Gold, et. al, “Bites of Venomous Snakes” NEJM :
“Envenomations by copperheads are not
considered to be as toxic as rattlesnake or
cottonmouth bites and rarely require treatment;
however, severe envenomations left untreated in
children or elderly persons may result in death”
Antivenom
• Preparation
– Informed consent ( all U.S. antivenoms are class C
in pregnancy)
– No skin test (ineffective, may cause allergic
reaction)
– Expand intravascular volume with crystalloid
– Pretreat with H1 and H2 antihistamines
– Consider prophylactic dose of SQ epinephrine in
high risk patients
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Antivenom
Antivenom
manufacturer venom
composition
cost
Crofab (all
north
american pit
vipers)
Savage
Laboratories
eastern/
western
diamondback,
mojave,
cottonmouth
Fab fragment
(ovine)
$2000 per 2
vial box
Antivenom
Wyeth-Ayerst
crotalidae
Laboratories
polyvalent (all
north
american pit
vipers)
Eastern/
western
diamondback,
tropical, ferde-lance
IgG (equine)
$900 per vial
Coral snake
(eastern and
texas coral
snakes)
Eastern coral
snake
IgG (equine)
$1300 per vial
Wyeth-Ayerst
Laboratories
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Brubacher, J.R., et al, “Efficacy of Wyeth Polyvalent Antivenin use in the Pretreatment of Copperhead
Envenomation in mice.” Wilderness and Environ Med, 1999;10:142-145.
Antivenom
Antivenom
Serum sickness
Acute reaction
Crofab
3%
14.3%
ACP
18-86%
23-56%
Coral Snake
10%
35%
*Atleast 3 anaphylaxis related deaths reported after ACP
administration
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Dart, R.C., et al., “Efficacy, Safety, and Use of Snake Antivenoms in the United States.” Ann of Emerg
Med, 2001;37:181-188.
• Crofab vs. ACP
Antivenom
– Crofab less likely to cause acute reaction or serum sickness
– Recent data suggests Crofab may be more effective
especially against mojave rattlesnake venom
– Crofab has a shorter half life and faster clearance rate
leading to recurrence phenomena
– *less long term data on Crofab (Crofab introduced in 2000,
ACP introduced in 1954)
– ACP IgG may maintain binding ability better than Crofab
fragments
– Time for reconstitution: Crofab 40 minutes, ACP 90
minutes
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Dart, R.C., et al., “Efficacy, Safety, and Use of Snake Antivenoms in the United States.” Ann of Emerg Med,
2001;37:181-188.
Seifert, S.A., et. al., “Recurrence Phenomena After Immunoglobulin Therapy for Snake Envenomations: Part 1.
Pharmacokinetics and Pharmacodynamics of Immunoglobulin Antivenoms and Related Antibodies.” Ann Emerg Med.,
2001;37:189-195.
Boyer, L.V., et al, “Recurrence Phenomena After Immunoglobulin Therapy for Snake Envenomation: Part 2.
Guidelines for Clinical Management with Crotaline Fab Antivenom.” Ann of Emerg Med,2001;37:196-201.
Antivenom
• Administration
– Coral snake antivenom
• Initial dose: 3-6 vials diluted in 500-1000 ml crystalloid
in adults and or 20-40 ml/kg in peds (same dose)
• IV infusion at slow rate (1 ml/min) to be completed over
2 hours with gradual increase in rate if no signs of
allergic reaction occur
• Redosing: 3-5 more vials as needed (rarely more than
10 needed)
• *Questionable role for anticholinesterase administration
(i.e. neostigmine)
• No reported deaths since antivenom went in to use
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Antivenom
• Administration
– Crofab (recommended within first 6 hours but case reports
have documented efficacy after 9 hours)
• Initial dose: 4-6 reconstituted vials diluted in 250 ml of normal
saline for adults or 20-40 ml/kg for peds up to 250 ml (same dose)
• IV infusion at slow rate (1ml/min) to be completed over 1 hour
with gradual increase in rate if no signs of allergic reaction occur
• Redosing: repeat initial dose if signs, symptoms or laboratory
abnormalities do not improve or worsen
• Post stabilization: 2 vials Q6H times 3 (shown to prevent
recurrence phenomena)
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Bebarta, V., et al, “Effectiveness of Delayed Use of Crotalidae Polyvalent Immune Fab (ovine) Antivenom.” Journ of
Toxicology, 2004;42:321-324.
Boyer, L.V., et al, “Recurrence Phenomena After Immunoglobulin Therapy for Snake Envenomation: Part 2. Guidelines
for Clinical Management with Crotaline Fab Antivenom.” Ann of Emerg Med,2001;37:196-201.
Antivenom
• Administration
– ACP
• Intial dose: 5-20 vials based on severity diluted in 1 liter of
crystalloid for adults and 20-40 ml/kg in peds (same dose)
• IV infusion at slow rate (1ml/min) to be completed over 1-2 hours
with gradual increase in rate if no signs of allergic reaction occur
• Redosing: 5-10 vials every 30 minutes to 2 hours if signs,
symptoms or laboratory abnormalities do not improve or worsen
(typical total dose 20-40 vials)
• Mortality rate reduced from 5-25% to 0.28% after antivenom went
in to use
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Antivenom
• Administration in adults
•
Dart, R.C., et al., “A Randomized Multicenter Trial of Crotaline Polyvalent
Immune Fab (ovine) Antivenom for the Treatment for Crotaline Snakebite in the
United States.” Arch Intern Med, 2001;161:2030-2036.
– 1st Randomized , controlled trial of Crofab in the U.S.
– Inclusion criteria: minimal or moderate envenomation, envenomation
within past 6 hours, age 10 or older, worsening symptoms before
Crofab administration
– Exclusion criteria: lack of symptoms progression, severe
envenomation, copperhead bite, infusion of >1 vial ACP, h/o sheep
product allergy, use of steroids or experimental meds within 4 weeks,
pregnancy or lactation, previous enrollment, inability to provide
consent, any disease interfering with examination
– N = 31
– Randomized to receive either an initial dose then PRN treatments or an
initial dose then scheduled treatments
Antivenom
• Administration in adults
• Dart, R.C., et al., “A Randomized Multicenter Trial of Crotaline Polyvalent
Immune Fab (ovine) Antivenom for the Treatment for Crotaline Snakebite
in the United States.” Arch Intern Med, 2001;161:2030-2036.
– Results: mean severity scored decreased from 4.35
to 2.39 (p<0.001), schedule group required no
PRN doses, 50% of PRN group required PRN
doses, acute reactions in 6% of patients
– Conclusion: “Fab AV effectively terminated venom
effects”
Antivenom
• Administration in adults
• Lavonas, E.J, et al, “Initial Experience With Crotalidae
Polyvalent Immune Fab (ovine) Antivenom in the Treatment
of Copperhead Snakebite.” Ann of Emerg Med;43:200-206.
– Retrospective chart review
– N = 32
– Outcome measures: progression of limb swelling,
coagulopathy, hemodynamic status, adverse effects of Fab
therapy, recurrence phenomena
– Results: 88% of patients had cessation of progression of
tissue injury within 4 hour, recurrent swelling in 19%, one
minor allergic reaction
Antivenom
• Administration in children
• Pizon, A.F., et al, “Safety and Efficacy of Crotalidae
Polyvalent Immune Fab in Pedatric Crotaline
Envenomation.” Acad Emerg Med, 2007;14:373376.
– Retrospective analysis
– Children 13 years or younger treated with Crofab between
2000-2005
– N=24, mean age 7.3
– 5 had resolution of swelling, 4.2% had a possible acute
allergic reaction, no deaths, no improvements in
thrombocytopenia
– No patients required blood products, debridement or
fasciotomy
Antivenom
• Administration in children
• Offerman, S.R., et al., “Crotaline Fab Antivenom for
the Treatment of Children with Rattlesnake
Envenomation.” Pediatrics, 2002;110:968-971.
– Prospective and retrospective analysis of pediatric patients,
13 years old or younger treated with Crofab during 2001
– N=12, mean age 6.9 years
– Severity scores stabilized or improvement in all patients
within 24 hours
– No surgical intervention required, no permanent sequelae,
no immediate or delayed hypersensitivity reactions
occurred
Antivenom
• Administration in Children
• LoVecchio, F., et. al., “Antibiotics After
Rattlesnake Envenomation.” Journ of Emerg
Med, 2002;23:327-328.
– 10 year retrospective chart review of chilren
receiving ACP
– N = 50, children <13 years old
– 19 with immediate hypersensitivity reaction, no
deaths
Antivenom
• Allergic Reactions
– Treatment:
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•
Stop antivenom infusion
Treat with antihistamines, steroids, epinephrine
Consider restarting antivenom after reaction subsides
Consider dilution (twofold)
Consider slower rate
Consider epinephrine drip (0.1µg/kg/min and titrated)
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Pressure Dressings
• 1st study published in Lancet by Sutherland in Australia in 1979
• Pressure dressings were applied after Elapid bites
• Theory: pressure dressings will impede lymphatic return to the
central circulation and delay systemic toxicity
• Based on monkey trials and case reports, the method is
considered to be effective after Elapid envenomation in Australia
• Studies have documented the ability of the pressure dressing to
retard venom spread through tissue
• Due to its primarily local effect causing skin necrosis, the use of
this technique after pit viper envenomation is questionable
• Currently recommendations are to keep the patient immobilized
after placement of the dressing and to avoid removal of the
dressing until definitive care and antivenom is available
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Norris, R.L., “Physicians and Lay People are Unable to Apply Pressure Immobilization Properly in a Simulated
Snakebite Scenario.” Wilderness and Environmental Medicine, 2005;16:16-21.
Bush, S.P., et al, “Pressure Immobilization Delays Mortality and Increased Intracompartmental Pressure After Artificial
Intramuscular Rattlesnake Envenomation in a Porcine Model.” Ann Emerg Med, 2004;44:599-604.
German, B.T., et al, “Pressure Immobilization Bandages Delay Toxicity in a Porcine Model of Eastern Coral Snake
(Micrurus fulvius fulvius) Envenomation.” Ann Emerg Med,2005;45:603-608.
Pressure Dressings
• German, B.T., et al, “Pressure Immobilization Bandages Delay
Toxicity in a Porcine Model of Eastern Coral Snake (Micrurus
fulvius fulvius) Envenomation.” Ann Emerg
Med,2005;45:603-608.
– Randomized unblinded controlled trial
– N = 10
– Leg Injected with 10 mg of eastern coral snake
venom (lethal dose in humans 4-5 mg)
– Randomized to no treatment or compressive
dressing
– Vital signs and quality of respiration measured
– Outcome measures: respiratory failure or survival
to 8 hours, histologic change at envenomation site
Pressure Dressings
• German, B.T., et al, “Pressure Immobilization Bandages Delay
Toxicity in a Porcine Model of Eastern Coral Snake (Micrurus
fulvius fulvius) Envenomation.” Ann Emerg
Med,2005;45:603-608.
– Results: no histologic changes seen at any
envenomation sites, 4/5 pigs in treatment group
survived to 8 hours as opposed to 0/5 pigs in the
control group, mean time of survival in control
group was 170±33 minutes, time of death of one
treatment subject was 310 minutes
– Conclusion: Pressure immobilization should be
considered after coral snake envenomation
Pressure Dressings
German, B.T., et al, “Pressure Immobilization Bandages Delay Toxicity in a Porcine Model of Eastern Coral
Snake (Micrurus fulvius fulvius) Envenomation.” Ann Emerg Med,2005;45:603-608.
Pressure Dressings
• Bush, S.P., et al, “Pressure Immobilization Delays Mortality and Increased
Intracompartmental Pressure After Artificial Intramuscular Rattlesnake
Envenomation in a Porcine Model.” Ann Emerg Med, 2004;44:599-604.
– Prospective randomized controlled study
– N = 20 ( 10 control, 10 treatment)
– Pigs injected in the leg with 20mg/kg of
rattlesnake venom
– Outcome measures: time to death, leg
circumference postmortem,
intracompartmental pressure (before
injection and after 2 hours)
Pressure Dressing
• Bush, S.P., et al, “Pressure Immobilization Delays Mortality and Increased
Intracompartmental Pressure After Artificial Intramuscular Rattlesnake
Envenomation in a Porcine Model.” Ann Emerg Med, 2004;44:599-604.
– Results: 100% mortality, median survival time greater
in treatment group (36 minutes, 23% delay, P=0.0122),
mean intracompartmental pressure was greater in the
treatment group (43 mmHg, 95% CI 32 to 53)
compared to the control group (24±5 mm Hg), mean
circumference was greater in the control group (-4.8
cm, 95% CI -5.7 to -3.9)
– Conclusion: pressure immobilization cannot be
recommended widely at this time for pit viper
envenomation due to the increased risk of local tissue
damage and significantly elevated compartmental
pressures, therefore the risks and benefits of this
treatment must be considered on a case by case bases
Pressure Dressings
• Australian pressure immobilization technique
• Apply a broad pressure bandage over the bite site (now
application at the most distal point of the bitten extremity
recommended)
• Apply bandage as tightly as you would wrap a sprained ankle
• Extend the bandage as high as possible
• Apply a splint
• Bind splint as firmly to as much of the leg as possible
Norris, R.L., “Physicians and Lay People are Unable to Apply Pressure Immobilization Properly in a Simulated
Snakebite Scenario.” Wilderness and Environmental Medicine, 2005;16:16-21.
Pressure Dressings
• Parameters for application based on a human
radio-labeled mock venom model published in
Australia in 1994
– Achieve pressure under the wrap between 40 to 70
mmHg in the upper extremities and 55 to 70 mm
Hg in the lower extremities
– Pressures outside these ranges enhanced venom
spread
Norris, R.L., “Physicians and Lay People are Unable to Apply Pressure Immobilization Properly
in a Simulated Snakebite Scenario.” Wilderness and Environmental Medicine, 2005;16:16-21.
Pressure Dressings
• Norris, R.L., “Physicians and Lay People are Unable to Apply Pressure
Immobilization Properly in a Simulated Snakebite Scenario.” Wilderness
and Environmental Medicine, 2005;16:16-21.
–
–
–
–
–
–
–
–
20 lay volunteers and 20 EM physicians
Instructed in proper placement of Pressure Dressing
Applied dressing five times
Criteria for correct application: wrap beginning at bite site,
entire extremity wrapped, splint or sling applied, pressures
in appropriate range
Pressures determined using pressure measuring device at
simulated bite site
EM physician: 13/100 applications were correct (17 at
correct pressure)
Lay Person: 5/100 applications were correct (14 at correct
pressure)
Conclusion: Appropriate pressure is the issue
Surgical Managment
•
•
•
•
Incision/excision of bite site
Fasciotomy
Digit dermotomy
“There is no randomized controlled clinical
study of surgical procedures versus appropriate
use of antivenom for the treatment of
snakebites in the United States”
Hall, E.L. “Role of Surgical Intervention in the Management of Crotaline Snake Envenomation.”
Ann Emerg Med.,2001;37:175-180.
Surgical Management
• Incision of the bite site
– No longer recommended
– Initial recommendations based on animal studies
– Lacerated tendons, nerves, arteries and increased
infection rates reported after incision attempts
– 20-30% dry bite rate, making incision unnecessary
in roughly ¼ of cases
Hall, E.L. “Role of Surgical Intervention in the Management of Crotaline Snake Envenomation.” Ann Emerg
Med.,2001;37:175-180.
Surgical Managment
• Excision of bite site
– No longer recommended
– Initial recommendations based on animal studies (dogs
injected with radiolabeled venom)
– Human study: 54 patients who underwent “conservative”
excision (“plug” of subcutaneous tissue excised down to
the fascia + removal of all ecchymotic discolored tissue)
had a 16% complication rate (i.e. osteomyelitis, loss of
digit)
• Twice the complication rate of larger antivenom only trials
– Studies indicate difficulty in differentiating necrotic muscle
fibers from viable fibers by visualization alone
Hall, E.L. “Role of Surgical Intervention in the Management of Crotaline Snake Envenomation.” Ann Emerg
Med.,2001;37:175-180.
Surgical Managment
• Fasciotomy
– Recommended in the case of compartment syndrome
refractory to antivenom with pressures consistently
above 30-40 mmHg
– The symptoms of the venom may mimic the symptoms
of compartment syndrome
– The pressure MUST be measured
– High permanent functional loss after 12 hours at high
pressure
Hall, E.L. “Role of Surgical Intervention in the Management of Crotaline Snake Envenomation.” Ann Emerg
Med.,2001;37:175-180.
Surgical Management
• Digit Dermotomy
– Recommended in the case of an envenomated,
tense, pale or cyanotic digit
– Procedure: longitudinal skin incision over the
medial or lateral aspect of the digit extending from
the web to the mid, distal phalanx
• Shallow incision
• Hemostat used to spread incision and avoid the
neuromuscular bundle
– Healing by secondary intention
Hall, E.L. “Role of Surgical Intervention in the Management of Crotaline Snake Envenomation.” Ann Emerg
Med.,2001;37:175-180.
Venom Extraction
• First studies performed in Texas on dogs,
published in 1927
• Initial recommendations for incision and
suction
• Later modified to include only suction
• Recent studies refute any form of suctioning
Hall, E.L. “Role of Surgical Intervention in the Management of Crotaline Snake Envenomation.”
Ann Emerg Med.,2001;37:175-180.
Bush, S.P, et al, “Snakebite Suction Devices Don’t Remove Venom: They Just Suck.” Ann Emerg
Med, 2004;43:187-188.
Venom Extraction
• Bush, S.P., et. al., “Effects of a Negative Pressure Venom Extraction Device
(Extractor) on Local Tissue Injury after Artificial Rattlesnake
Envenomation in a Porcine Model.” Wilderness and Environmental
Medicine, 2000;11:180-188.
– Prospective, randomized, controlled trial
– 10 pigs
– Injected with the same rattlesnake venom
– Leg circumference measured at 1,2,3,4,5,6,24,48,72 and 96 hours
– Extractor applied 3 minutes after injection and left in place for 30
minutes
– No significant difference in limb swelling when the suction was used
when compared to controls
– 2 subjects had necrosis at the extractor site leading to tissue loss
Venom Extraction
• Alberts, M.B., et. al., “Suction for Venomous Snakebite: A
study of Mock Venom Extraction in a Human Model.” Ann.
Emerg Med., 2004;43:181-186.
– Prospective human trial
– Mock venom injected 1cm into the legs of 8 male volunteers using a 16
gauge, curved needle
– Sawyer Extractor applied after 3 minutes, left in place for 5 minutes,
then repeated immediately for 10 minutes
– Radioactive counts measured and compared between the leg and the
extracted blood
– Mean radioactivity found in the blood extracted was 0.04% of the
envenomation load
– Post-extraction leg radioactivity count decreased by 2.0%
– A larger amount of radioactivity was measured in spontaneously oozing
fluid than in the extracted fluid
– Conclusion: the extractor removed virtually no mock venom
Venom Extraction
• Rosen’s 5th ed. (2002)
– “If the patient is seen within 15 minutes of the time of the bite, suction
should be performed. The Sawyer Extractor is a suction device
developed for snakebites”
• Tintinalli 6th ed. (2004)
– “First aid treatments such as suction and incision are dangerous and
should not be used.”
– “The Sawyer Extractor (Sawyer Products) suction pump purportedly
removes venom without incision; however, serious questions regarding
its safety and efficacy have been raised.”
• Auerbach 5th ed. (2007)
– “At least three studies, done independently of each other and using
different methodologies, arrived at the same conclusion-that the
Extractor does not work for venomous snakebites and could make
things worse”
Venom Extraction
7 year old male, 20 minutes after placement of a suction device
for a copperhead bite
Holstege, C.P., “Images in Emergency Medicine.” Ann Emerg Med., 2006;48:105.-1618.
Observation and Disposition
• No envenomation evident & the snake was either
nonvenomous or a pit viper
– 4-6 hour observation, follow up in 1-2 days
• Local pain & minimal edema & the snake was either
nonvenomous or a pit viper
– 12 hour observation, discharge if pain and swelling
improve and no systemic symptoms develop
• Moderate to severe envenomation by a pit viper
– ICU admission
• Coral snake, Mojave rattlesnake bite +/- symptoms
– ICU admission
Marx, et. al. Rosen’s Emergency Medicine: Concepts and Clinical Practice 5th
ed. Mosby, 2002.
Observation and Disposition
•
Swindle, G.M, et. al. “The Six Hour observation rule for Grade I Crotalid
Envenomation: Is it Sufficient? Case Reports of Delayed Envenomation.” Journal
of Wilderness Medicine, 1992; 3:168-172
– Case Report
– 16 year old male bitten on left leg by a rattlesnake with initial pain at
bite site
– Exam: two small wounds and a small contusion with tenderness but
otherwise normal
– Observed for 6 hours
– No complaints or objective criteria at time of discharge to indicate
envenomation (i.e. no swelling, normal labs, no systemic complaints)
– Returned 36 hours later with significant pain and swelling at bite site
– Patient states that his symptoms started <4 hours after discharge
– Successfully treated with antivenom
Observation and Disposition
• Kitchens, C.S, et al, “Envenomation by the Eastern Coral Snake.”
JAMA, 1987;258:1615
– Case series of 39 victims of coral snake bites over a 12 year
period
– No deaths reported
– Local swelling (40%), parasthesias (35%), nausea (30%)
and vomiting (25%) were the most common findings
– Weakness in only 15% of cases and dyspnea in only 10%
of cases
– Mean time to symptoms onset was 1 hour and 20 minutes
with a range of 30 minutes to 13 hours
Observation and Disposition
• Apparent dry bite by a pit viper
– Admit or observe for at least 8 hours
• Mild to moderate degree of envenomation by a pit
viper
– Admission to regular hospital floor with close observation
• Severe envenomation by a pit viper with progressive
findings despite antivenom, any degree of
envenomation by a coral snake, anyone bitten in the
head, neck or trunk by a pit viper
– ICU Admission
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Summary
• There are various rules established to
differentiate between venomous and
nonvenomous snakes but the best rule is to
avoid any questionable snake
• Pit vipers and coral snakes are the primary
indigenous snakes in North America
• Coral snakes produce primarily nerve toxin
whereas pit vipers produce both nerve and
tissue toxins
Summary
• The patient history should include the events
surrounding the envenomation, any history of
allergies to horse or sheep products and any
previous history of snake bites
• Exam should always include evaluation for
compartment syndrome and frequent reevaluation of the progression of swelling
• Laboratory evaluation should always include a
coagulation profile
Summary
• Tetanus booster should be given if indicated
• Post envenomation thrombocytopenia is often
described and may not correct with blood product
administration unless addition antivenom is given
• Anaphylaxis can occur secondary to the venom or the
antivenom and should be treated accordingly
• Wound infections are uncommon and antibiotics
should only be given if signs of infection are present
Summary
• Antivenoms are available for most coral snakes and
all pit vipers indigenous to North America and all
have documented effectiveness
• There are decision rules to aid the ED physician in
determining severity of envenomation and amount of
antivenom required
• The Pressure dressing method maybe effective in
coral snake envenomation but may worsen outcomes
in pit viper envenomations
• Fasciotomy and dermotomy are still acceptable
surgical options for the treatment of snake
envenomation
Summary
• Venom extraction is no longer recommended
• All patients bitten by a coral snake or a mojave
rattle snake require ICU admission
• Patients bitten by other pit vipers may either be
admitted or observed for several hours
dependent upon their clinical presentation
References
•
•
•
•
•
•
•
•
•
•
•
•
•
Alberts, M.B., et. al., “Suction for Venomous Snakebite: A study of Mock Venom Extraction in a Human
Model.” Ann. Emerg Med., 2004;43:181-186.
Auerbach, P.S. Wilderness Medicine. Mosby, 2007.
Bebarta, V., et al, “Effectiveness of Delayed Use of Crotalidae Polyvalent Immune Fab (ovine)
Antivenom.” Journ of Toxicology, 2004;42:321-324.
Boyer, L.V., et al, “Recurrence Phenomena After Immunoglobulin Therapy for Snake Envenomation: Part
2. Guidelines for Clinical Management with Crotaline Fab Antivenom.” Ann of Emerg Med,2001;37:196201.
Burch, J.M., et al, “The Treatment of Crotalid Envenomation without Antivenin.” Journal of Trauma,
1988;28:35-43.
Bush, S.P., et. al., “Effects of a Negative Pressure Venom Extraction Device (Extractor) on Local Tissue
Injury after Artificial Rattlesnake Envenomation in a Porcine Model.” Wilderness and Environmental
Medicine, 2000;11:180-188.
Bush, S.P., et al, “Pressure Immobilization Delays Mortality and Increased Intracompartmental Pressure
After Artificial Intramuscular Rattlesnake Envenomation in a Porcine Model.” Ann Emerg Med,
2004;44:599-604.
Bush, S.P, et al, “Snakebite Suction Devies Don’t Remove Venom: They Just Suck.” Ann Emerg Med,
2004;43:187-188.
Brooks, D.E., et. al. “Airway Compromise After First Rattlesnake Envenomation.” Wilderness and
Environmental Medicine, 2004; 15:188-193.
Brubacher, J.R., et al, “Efficacy of Wyeth Polyvalent Antivenin use in the Pretreatment of Copperhead
Envenomation in mice.” Wilderness and Environ Med, 1999;10:142-145.
Corbett, S.W., et. al., “Most lay People can Correctly identify Indigenous Venomous Snakes.” Amer Journal
Emerg Med.,2005;23:759-762.
Dart, R.C., et al., “A Randomized Multicenter Trial of Crotaline Polyvalent Immune Fab (ovine) Antivenom
for the Treatment for Crotaline Snakebite in the United States.” Arch Intern Med, 2001;161:2030-2036.
Dart, R.C., et al., “Efficacy, Safety, and Use of Snake Antivenoms in the United States.” Ann of Emerg
Med, 2001;37:181-188.
References
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Dart, R.C, Et al., “Validation of a severity Score for the Assessment of Crotalid Snakebite.” Ann Emerg
Med, 1996;27:321326.
Davidson, T.M., “Sam Splint for Wrap and Immobilzation of Snakebite.” Wilderness and Environmental
Medicine, 2001;12:206-207.
Gold, B.S., et. al., “Bites of Venomous Snakes.” NEJM, 2002;347:347-356.
Gold, B.S., et al., “Refractory Thrombocytopenia Despite Treatment for Rattlesnake Envenomation.” N
Engl J Med, 2004;350:1912-1913.
German, B.T., et al, “Pressure Immobilization Bandages Delay Toxicity in a Porcine Model of Eastern
Coral Snake (Micrurus fulvius fulvius) Envenomation.” Ann Emerg Med,2005;45:603-608.
Hall, E.L. “Role of Surgical Intervention in the Management of Crotaline Snake Envenomation.” Ann
Emerg Med.,2001;37:175-180.
Holstege, C.P., “Images in Emergency Medicine.” Ann Emerg Med., 2006;48:105.-1618.
Kitchens, C.S, et al, “Envenomation by the Eastern Coral Snake.” JAMA, 1987;258:1615
Lavonas, E.J, et al, “Initial Experience With Crotalidae Polyvalent Immune Fab (ovine) Antivenom in the
Treatment of Copperhead Snakebite.” Ann of Emerg Med;43:200-206.
LoVecchio, F., et. al., “Antibiotics After Rattlesnake Envenomation.” Journ of Emerg Med, 2002;23:327328.
LoVecchio, F., et. al. “Snakebite Envenomation in Children: a 10 year Retrospective Review.” Wilderness
and Environmental Medicine, 2001;12:184-189
Marx, et. al. Rosen’s Emergency Medicine: Concepts and Clinical Practice 5 th ed. Mosby, 2002.
Norris, R.L, et al, “Apparent Coral Snake Envenomation in a Patient Without Visible Fang Marks.” Amer
Journ Emerg Med, 1989;7:402-405.
Norris, R.L., “Physicians and Lay People are Unable to Apply Pressure Immobilization Properly in a
Simulated Snakebite Scenario.” Wilderness and Environmental Medicine, 2005;16:16-21.
References
•
•
•
•
•
•
•
•
•
Offerman, S.R., et al., “Crotaline Fab Antivenom for the Treatment of Children with
Rattlesnake Envenomation.” Pediatrics, 2002;110:968-971.
Pizon, A.F., et al, “Safety and Efficacy of Crotalidae Polyvalent Immune Fab in Pedatric
Crotaline Envenomation.” Acad Emerg Med, 2007;14:373-376.
Ruha, A. et al, “Initial Post marketing Experience With Crotalidae Polyvalent Immune Fab for
Treatment of Rattlesnake Envenomation.” Ann Emerg Med, 2002;39:609-615
Ryan, K.C., et. al. “Life-threatening Anaphylaxis Following Envenomation by two Different
Species of Crotalidae.” Journal of Wilderness Medicine, 1994;5:263-268.
Seifert, S.A., et. al., “Recurrence Phenomena After Immunoglobulin Therapy for Snake
Envenomations: Part 1. Pharmacokinetics and Pharmacodynamics of Immunoglobulin
Antivenoms and Related Antibodies.” Ann Emerg Med., 2001;37:189-195.
Stewart, M.E., et al., “First Aid Treatment of Poisonous Snakebite: Are Currently
Recommended Procedurs Justified.” Ann Emerg Med, 1981;10:331-335.
Swindle, G.M, et. al. “The Six Hour observation rule for Grade I Crotalid Envenomation: Is it
Sufficient? Case Reports of Delayed Envenomation.” Journal of Wilderness Medicine, 1992;
3:168-172
Tintinalli. Emergency Medicine: A Comprehensive Study Guide. McGraw-Hill, 2004.
Wingert, W.A., “Rattlesnake Bites in Southern California and Rationale for Recommended
Treatment.” The Western Journal of Medicine, 1988;148:37-44.