SNAKE VENOM POISONING IN THE UNITED STATES:

A MEDICAL EMERGENCY!

Robert Norris, MD, FACEP

Associate Professor, Surgery

Chief, Division of Emergency Medicine

Stanford University

“Their supreme arrogance, developed over millions of years as masters of their environment, commands respect out of all proportion to their size.”

- Chris Mattison, author of Snakes of the World

I. OBJECTIVES:

Following this presentation, participants will be able to:

- identify the venomous snakes indigenous to the U.S.

- discuss appropriate first aid measures for venomous snakebite.

- outline the appropriate hospital management of venomous snakebites.

II. INTRODUCTION:

- Approximately 3000 snake species in the world (approximately 375 are venomous);

approximately 120 species in the U.S. (20 venomous)

- U.S. venomous snakes can be divided into two groups:

- Pitvipers (98% of bites): rattlesnakes, water moccasins and copperheads

- Elapids: coral snakes (related to cobras, mambas, etc.)

- All 48 contiguous states (except Maine) have at least one species of venomous snake; none in Hawaii or Alaska

- Approximately 8,000 venomous snakebites reported in the U.S. each year with 10-20 deaths

- An individual has a 1:10 million chance of dying of a snakebite in the U.S.

III. IDENTIFICATION OF U.S. SNAKES:

Nonvenomous Pitvipers Coral Snakes

Head: round or triangular triangular round

Pupils: round elliptical round

Facial Pits: absent present absent

Fangs: none (regular teeth) anterior, elongated, anterior, short,

retractable fixed

Subcaudal Scales: double row single row double row

Rattles: absent usually present in rattlesnakes absent

Color: variable variable, little help in ID red/yellow/black

IV. ANATOMY:

A. Pitvipers:

1. Venom Apparatus: Venom Gland; Compressor Glandulae Muscle; Primary Duct; Accessory Gland;

Secondary Duct; Fang Sheath; Fangs

2. Facial Pit Organs (Foveal Organs): highly sensitive, paired receptors of infrared radiation that can detect

temperature changes of < 0.2 degrees C; used to detect warm blooded prey/predators and aim strike

and may have a role in determining volume of venom injected

3. Rattles: interlocking keratin rings at tip of tail in rattlesnakes; a new rattle is added with each shed of the skin

(every 50-400 days); some are lost due to trauma

4. The Strike: aimed primarily by facial pits; rarely strike farther than 1/2 their body length;

speed = approximately 8 feet/second

- rattlesnakes generally inject 25-75% of their venom volume when they bite humans

- can bite without injecting any venom (“dry bite”)

- overall: 20% no envenomation, 30% mild, 50% moderate to severe

B. Coral Snakes:

- 2 enlarged, hollow, anterior maxillary fangs that are fixed in erect position (smaller than pitvipers’)

- hang-on and chew (do not “strike”); can bite any location with relatively loose skin

- less than 40% of bites result in envenomation

- approximately 20 bites in U.S. per year

V. VENOM:

- old classification of “neurotoxic”,“hemotoxic”,“cytotoxic”,“myotoxic” is too simplified for crude venoms and

apt to result in inappropriate management; virtually every organ system can be effected by any one venom

- treat the envenomed patient as a multiple poisoning

- venom composition varies:

- species to species

- snake to snake within the same species

- time of year/environmental conditions

- age, size, health of snake

- most venoms contain 10-20 distinct, biologically active components:

- 5-15 enzymes

- 3-12 nonenzymatic, low molecular weight polypeptides

- probably account for most lethal fractions of venoms

- some are 5-20 X more lethal than crude venom

- > 6 other unidentified substances

- elapid venoms are less complex than viperid venoms

- the effects of all venom components are compounded by the release of vasoactive autopharmacologic compounds

such as histamine, bradykinin, and serotonin in the victim

VI. SIGNS AND SYMPTOMS OF SNAKE VENOM POISONING:

A. Pitvipers:

1. Local:

a. Puncture Wounds/Scratches:

- pattern can be misleading (venomous vs. nonvenomous)

- must differentiate from other animal/insect bites or plant puncture wounds

- usually venomous snakebite wounds are larger, with more bleeding

- may be one or many fang marks present; range few mm to >4 cm apart

b. Pain, Edema, Erythema:

- usually present within 30 minutes if envenomation occurs

- more severe envenomation generally yields more rapid progression and more severe pain

i) Pain:

- usually burning & immediate in onset

- usually confined to bite site

ii) Edema:

- usually limited to SQ tissues (with no increase in intracompartmental pressures)

- usually starts within 5 minutes (if none in 10 minutes probably no significant envenomation

unless dealing with Mojave rattlesnake [Crotalus scutulatus)

- gradually spreads up extremity for > 36 hours

(severe envenomation may have total involvement of extremity in 1 hour)

- danger of airway obstruction in bites to face or neck

c. Ecchymosis:

- starts within several hours

- may involve entire extremity (especially common in areas of skin-skin contact - fingers, axilla)

d. Lymphangitis: venom absorbed rapidly through lymphatics

(which are highly susceptible to destructive effects)

e. Petechiae, Vesicles, Hemorrhagic Bullae:

- will occur in most untreated rattlesnake envenomations

- rarely see when treated early with adequate antivenom

- usually occur at 6-36 hr after bite (vesicles may appear within 3 hr)

f. Necrosis, Tissue Destruction:

- due to direct venom effects (not increased tissue pressures, even if venom injected IM)

- probably can totally prevent if adequate antivenom is given within 2 hours of bite

2. Systemic:

a. Nausea, Vomiting: common (early onset may indicate severe envenomation)

b. Weakness, Diaphoresis, Chills, Dizziness/Vertigo, Syncope: common with all pit vipers

- proportional to severity

c. Change in Taste: may complain of minty, rubbery, metallic taste

d. Increased Salivation

e. Fever

f. Tingling, Numbness in Scalp/Face/Fingers/Toes: can occur within 10 min and indicates moderate

- severe envenomation

g. Fasciculations in Face/Neck/Back/Involved Extremity: can occur early (within 10 min)

and indicate severe envenomation

h. Visual Disturbances: blurred vision, yellow vision, blindness (due to retinal hemorrhages)

i. Tachycardia, Bradycardia

j. Hemorrhage, Hemolysis:

- bleeding from wounds, gingival bleeding, epistaxis, hematuria, hematemesis, melena,

lower GI bleeding, pulmonary bleeding, peritoneal hemorrhage, cerebral hemorrhage

- can occur as early as 6 hr (and fatal hemorrhage has been reported 1 hr after rattlesnake bite);

more commonly 12-72 hr after bite

- systemic bleeding only occurs in moderate to severe envenomation (not seen in copperhead bites)

- most coagulopathic effects secondary to proteinases acting at various sites in the coagulation cascade

k. Hypotension, Shock:

- can occur rapidly in severe envenomation

- early, due to pooling of blood (extremities, pulmonary bed, splanchnic bed)

- later, may be due to loss of volume (bleeding and third spacing of plasma) and hemolysis

(this form usually presents 6-26 hr after envenomation)

- generally little effect from decreased cardiac contractility

l. Pulmonary Edema:

- common in severe envenomation

- secondary to injury to intimal linings of pulmonary vasculature and pooling of blood

in major vessels & capillary beds of lungs

- compounded by direct cardiodepressant factor in some venoms

m. Oliguria, Anuria: multifactorial

- hypotension with resultant decreased GFR (#1)

- hemoglobinuria and myoglobinuria with renal tubular obstruction

- ATN secondary to arteritis and fibrin deposition in capillary lumina of kidneys

n. Paresis, Paralysis:

- seen with eastern diamondback (Crotalus adamanteus) and Mojave rattlesnakes

- uncommon with other rattlesnakes

o. Respiratory Failure:

- uncommon with pitviper bites (except Mojave)

- complicated by CV failure

p. Seizures: probably due to hypotension and hypoxia

q. Coma: usually sensorium is clear

- when coma occurs, it is secondary to cerebral anoxia or intracranial bleed

r. Death:

- generally occurs at 6-48 hr in untreated severe envenomations

(can occur sooner with IV envenomation)

- 68% in 6-48 hr; 17% < 6 hr; 4% < 1 hr

B. Coral Snakes:

- fang marks may be hard to see (range 2-8 mm apart)

- frequent delay in onset of Sx’s (up to 10 hr), followed by extremely rapid progression

- little or no pain at bite site; occasional numbness

- no local necrosis

- earliest evidence may be drowsiness or euphoria

- N/V, increased salivation, paresthesias at bite site

- bulbar paralysis (may occur within 90 min) progressing to peripheral paralysis (curare-like effects)

- paresthesias, fasciculations

- occasional seizures (especially in children)

- mild hypotension

- death is due to respiratory and cardiovascular failure (can occur 8-12 hr after onset of Sx’s)

VII. FACTORS EFFECTING SEVERITY OF ENVENOMATION:

A. Age, Size, General Health of Victim

B. Nature, Location, Depth of Bite

C. Amount of Venom Injected

D. Species, Age, Size, Sex, General Health of Snake

E. Time of the Year, Environmental Conditions

F. Victim’s Sensitivity to the Venom

G. Pathogens Present in Snake’s Mouth

H. Degree of Activity of Victim After Bite

I. Type of First Aid Measures and Subsequent Medical Care Rendered

VIII. GRADING SEVERITY OF ENVENOMATION:

- Problems with Grading Scales:

- based largely on local findings and their progression over the first 12 hours

- these local findings may be absent with deep, potentially fatal envenomations

- should never use this type of scale in cases of Mojave rattlesnake or coral snake bites

(due to relative lack of local Sx’s) or in cases of exotic venomous snakebites

- USE GOOD CLINICAL JUDGEMENT - DO NOT OVERLY RELY ON ANY GRADING SCALE!

- SINCE SNAKE VENOM POISONING IS A DYNAMIC PROCESS, THE PATIENT REQUIRES

FREQUENT REASSESSMENT & UPGRADING OF SEVERITY AS APPROPRIATE

SEVERITY GRADING:

Severity: nonenvenomation mild moderate severe

Fang Marks: +/- + + +

Pain: none moderate severe severe

Edema: none minimal moderate severe

(0-15cm) (15-30cm) (>30cm)¹

Erythema: none + + +

Ecchymosis: none +/- + +

Systemic Sx’s: none none mild early, severe

Labs: NL NL mildly abnormal very abnormal

¹ may be minimal swelling if IM or IV envenomation

IX. LABORATORY ANALYSIS:

Important in pitviper envenomations (no major changes noted with coral snake bites):

- CBC; Platelet Count

- Type & Cross-Match (Get ASAP)

- PT/PTT/TT; Fibrinogen Levels; FSP’s/d-dimer; Bleeding/Clotting Times; Clot Retrax Time

- Electrolytes/BUN/Cr; Liver Fxn Tests; CPK

- Cardiac Markers

- Urinalysis

- Arterial Blood Gases, ECG & CXR if moderate or severe or significant co-morbidity

X. MANAGEMENT OF SNAKE VENOM POISONING:

A. First Aid Measures in Pitviper Envenomation:

1. ?? Kill the Snake and Bring it in for Identification:

- only vital to identify the snake when Mojave rattlesnake or coral snake bites are a possibility as management is altered

- risk of a second bite to the victim or rescuer (decapitated snake heads can “bite” up to 1 hr after killed - reflex)

- should never delay transportation of the victim

2. Remove any Jewelry that could become a Tourniquet

3. Calm, Reassure: to decrease heart rate and circulation of venom

4. Constriction Band (CB):

- controversial (not a tourniquet; avoid total occlusion of vascular supply to the extremity)

- does decrease venom spread, BUT potential risk of increased local complications

- might consider if > 60 min. to medical care and bitten by a potentially lethal snake (e.g. large rattlesnake)

- should be > 1/2 inch wide

- apply 5-10 cm proximal to swelling (or above proximal joint)

and step-wise advancement periodically to keep ahead of progressing edema

- apply only tight enough to occlude lymphatic & superficial venous return

- no benefit when applied > 30 after bite

- maintain CB until antivenom is started (when indicated)

5. Incision and Suction (I&S):

- NO incisions - increased risk of infection/necrosis; damage to vital structures; hemorrhage

- suction controversial:

- no proof of significant venom return

- might increase tissue loss at the bite site

- if used, best applied by mechanical means (e.g., “Extractor” in the Sawyer First Aid Kit [Long Beach, CA]

- approximately $15.00)

- should be started immediately and continued for 30-60 min

- do not use mouth suction

- contamination of wound with oral flora

- potential risk of envenoming rescuer if open lesions of mouth or stomach

6. Rest and Immobilization:

- put victim at rest and splint extremity in position of function, at or just below heart level

- allow room for swelling in splint

7. Ice:

- avoid any method of cooling

- may drive certain venom components deeper into tissues and cause further ischemia

8. Watch for Adverse Reactions:

- rare documented cases of anaphylaxis (IgE-mediated) caused by snake venom in patients previously bitten

or otherwise exposed to snake venom

- some evidence that venom can activate the alternate complement system directly and cause a similar reaction

9. Rapid Transportation to a Medical Facility:

- the most important measure in first aid

- no other measures should delay this since antivenom is the only proven efficacious therapy

B. Hospital Management of Pitviper Envenomation:

- a medical emergency that requires immediate attention and the use of considerable clinical judgment

1. General:

- ABC’s; 0₂; monitor; 2 large-bore IV’s (NS or RL)

- rapid H&P

- measure circumference of extremity at bite site and 2 sites more proximal (mark positions) and follow q 15 min

2. Antivenom – Currently two for use in North American pitviper bites:

a) Antivenin [Crotalidae] Polyvalent (ACP) (Wyeth Labs) – used since 1954

- a polyvalent, equine serum good for all N. American pitvipers, most C.&S. American pitvipers, and some Asian species

- made by immunizing horses with eastern diamondback rattlesnake (Crotalus adamanteus),

western diamondback rattlesnake (C. atrox), tropical rattlesnake (C. durissus terrificus)

and fer-de-lance venom (Bothrops atrox)

- contains whole immunoglobulin molecules and other contaminants (such as albumin)

that can cause adverse reactions (see below)

b) CroFab (Protherics) – released by the FDA in 10/00

- a monclonal polyvalent bovine antivenom good for all U.S. pitvipers and probably all New World pitvipers

- made by immunizing sheep with a single venom

- eastern diamondback rattlesnake (Crotalus adamanteus), western diamondback rattlesnake (C. atrox),

Mojave rattlesnake (C. scutulatus) or cottonmouth water moccasin (Agkistrodon piscivorus) venom.

- antibodies are collected and papain digested to Fab & Fc fragments

- immunogenic Fc fragments are discarded and the Fab fragments are purified

- equal amounts of the four components are mixed to yield the polyspecific product

- In general, all antivenoms:

- contain specific antibodies against various venom fractions (confer passive immunity to patient);

but variable purity depending on the product

- should only be given IV

- are effective in reversing systemic effects (including coagulopathy)

and possibly some benefit in reducing local destruction if given very early

- are most effective if given within 2 hr (once venom is bound to tissue receptor sites, antivenom is of little benefit),

but probably efficacious up to 24 hr after the bite (though not for limiting necrosis)

- after 24 hr, use only if significant coagulopathies or other severe systemic manifestations are present

- if the victim applied a CB, should begin antivenom, if indicated, a few minutes before releasing

METHOD OF ANTIVENOM ADMINISTRATION

- obtain written, informed consent if possible before giving

- draw up epinephrine in a syringe at bedside, ready for administration in the event of an anaphylactic/-oid reaction

- skin testing: no clinical benefit (but is recommended by Wyeth for ACP; not recommended for CroFab)

- a “medicolegal procedure”; wastes 20-30 min of time

- test is not 100% accurate:

- a negative test to ACP does not r/o possibility of a hypersensitivity rxn (occurs in approx. 1-10%)

- not all patients who have a positive skin test demonstrate a reaction if given ACP

(does not contraindicate giving antivenom to a patient with a life-threatening envenomation)

- always be prepared for an anaphylactic reaction in any patient given AV (ACP or CroFab)

- expand intravascular volume with crystalloid if no contraindication (to limit severity of any anaphylactoid reaction)

- if giving ACP, administer an IV dose of H1 & H2 blockers (e.g. diphenhydramine & cimetidine) prior to beginning infusion

- dilute antivenom to be given in NS or RL (for CroFab: 250 ml; for ACP: 50-100 ml for each vial to be given; e.g. 5 vials in 250-500 ml)

- begin the infusion slowly (approx. 15 drops/min) through an IV in an uninjured extremity

- if no reaction over several minutes, increase rate to complete dose in 1 hour

- if a reaction occurs (see below), temporarily stop the antivenom and treat with epi, diphenhydramine, cimetidine and steroids as needed

SUGGESTED STARTING DOSES

# of Vials (ml)

Severity: CroFab ACP

nonenvenomation 0 0

mild 4-6 0 or 5 (50) - controversial

moderate 4-6 10 (100)

severe/very severe 6 15 (150)

- Monitoring Therapy:

- after the initial dose is given, reassess clinical response…

- for CroFab: watch over the next hour… if progression of Sx/Lab abnormalities, give another 4-6 vials (and continue

in this fashion until stable); then give 2 more vials q6h x 3 additional doses

(these dosage recommendations may change as more experience is gained with this product)

- for ACP: if swelling or systemic Sx progress or recur, give 1-5 more vials q 30 min - 2 hr prn

(very severe envenomations may require 20-30 vials); keep ACP levels high for first 4 hr

- with adequate antivenom:

- swelling/erythema will quickly begin to reverse

- patient subjectively improves (decreased pain)

- systemic Sx’s improve (e.g. bleeding, GI sx’s)

- normalization of vital signs and urine output

- fasciculations may disappear

- better to err on side of overtreatment than undertreatment

- children require at least an adult starting dose (due to decreased resistance to venom); adjust volume of diluent as needed

- benefits generally outweigh risks in pregnancy (pitviper venom poisoning known to cause fetal demise)

MANAGEMENT OF THE PATIENT WITH AN ALLERGY TO ANTIVENOM AND A SEVERE ENVENOMATION:

- if starting with ACP, switch to CroFab if available

- can still usually give ACP if no patient is severely envenomed and no CroFab available

- consult a specialist (allergist or expert in snake envenomations)

- Complications of Antivenom Therapy:

i) Anaphylaxis/Anaphylactoid Reactions:

- 3-54% of patients develop some early rxn to whole immunoglobulin equine antivenoms

- the incidence & severity of reactions to CroFab appears to be significantly reduced

(7 of first 42 patients treated had an early reaction – 5 urticaria, 1 cough, 1 urticaria/dyspnea and wheezing)

- due to a type I hypersensitivity reaction (IgE-mediated) or direct complement activation (more likely)

- most reactions are mild (urticaria, N/V, diarrhea, headache, fever); 40% severe; very few deaths reported

ii) Serum Sickness:

- occurrence not predicted by results of skin testing

- a type III hypersensitivity reaction (IgG, IgM production in response to an injected antigen - i.e. antivenom)

- occurs in 30-75% receiving ACP, depending on total dose given (occurs in approx. 100% if given > 7 vials)

- again, less common with CroFab

(5 of first 42 patients – 2 rash, 1 pruritus, 1 urticaria, 1 severe rash & puritus)

- usually occurs 1-2 weeks after ACP therapy

- serious rxns are rare

- treatment:

- steroids: e.g. Prednisone 40-100mg qd until Sx’s resolve & taper over 7-10 days

- diphenhydramine for symptomatic relief

3. Surgical Modalities: Source of major controversy in some regions

i) Excision of Bite Site:

- venom spreads too rapidly to be significantly removed by this method

- many complications

ii) Exploration and Debridement (E&D)/Fasciotomy:

- does nothing to mitigate systemic venom effects

- may worsen outcome by adding unnecessary surgical trauma & hemorrhage

- prolongs hospitalization

- fasciotomy will decrease any rise in intracompartmental pressure (ICP) if such a rise occurs

- if concerned, follow ICP:

- if pressures < 30mm Hg, no surgery; antivenom alone

- if pressures > 30-40, proceed with fasciotomy in addition to antivenom

4. Crystalloids/Colloids:

- volume expansion is the treatment of choice for shock secondary to snake venom poisoning

(not reversed by antivenom alone)

- 5% albumin appears to be more efficacious than saline, Ringer’s lactate, or dextran

(stays in vascular space longer; does not bind or inactivate venom);

use if patient fails to respond to crystalloids

- pressors can be tried in refractory cases

5. Blood Products:

- PRBC’s, cryoprecipitate, FFP, platelets, etc.: use as needed to treat coagulopathies

(with evidence of clinically significant bleeding) and anemia

- must begin antivenom therapy first

- otherwise any blood components given will add further fuel to the ongoing consumptive coagulopathy

6. Analgesics:

- frequently required (acetaminophen, hydrocodone, meperidine, MS, etc.)

7. Wound Care:

- r/o retained fangs/teeth in wounds (examine wounds closely; x-rays)

- update tetanus status prn

- clean wounds with germicidal solution

- leave wounds open & cover with light, sterile dressing

- splint in position of function (well padded) with cotton between fingers/toes

- elevate after antivenom, if indicated, has been started

- can use 1:20 Burow’s solution soaks several times/day (15 min per treatment);

daily sterile whirlpool baths

- paint wounds with triple dye (Brilliant Green 1:400; Gentian Violet 1:400; Acriflavine 1:1000) 4 times/wk

- apply antimicrobial ointment qhs

- hyperbaric oxygen therapy may be useful in cases with severe necros