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Disorders Caused by Venomous Snakebites and Marine Animal Exposures¶

Chapter 471 | Part 14: Poisoning, Drug Overdose, and Envenomation · Part 14 – Poisoning, Overdose & Environmental · Chapter 471

Key Clinical Points¶

Snake envenomation is the deadliest neglected tropical disease globally; deaths are projected to increase to 68,799 by 2030 despite WHO goals.
Dry bites (no venom release) occur in 20–25% of pit viper bites and up to 75% of sea snake bites.
Antivenom is the mainstay of treatment for significant envenomation; it must be specific to the offending snake species.
Pressure-immobilization is recommended for neurotoxic elapid bites but contraindicated for viperid bites.
Compartment syndrome is rare in North American crotalid envenomations; fasciotomy is not routinely recommended.
Serum sickness typically develops 1–2 weeks after antivenom administration and is treated with systemic glucocorticoids.
Acetylcholinesterase inhibitors (edrophonium, neostigmine) may be used as a trial for neurotoxicity before intubation.
Avoid salicylates and NSAIDs for pain management due to bleeding risks; use acetaminophen or opioids.
Early identification of envenomation is critical; antivenom is most effective in reversing active venom toxicity rather than established damage (e.g., renal failure).
Marine animal stings (e.g., jellyfish) require immediate decontamination with sea water or vinegar.

DEFINITION & OVERVIEW¶

• General Principles: Poisoning is a preventable illness. Management of envenomation focuses on supportive care and specific antivenoms. • Dry Bite: → Definition: A bite where no venom is released. → Incidence: ◦ Pit vipers: 20–25% ◦ Sea snakes: up to 75%

EPIDEMIOLOGY¶

• Global Impact: Snake envenomation is the deadliest neglected tropical disease globally. • Statistics (2019): → Total deaths: 63,415 (95% UI, 38,930–78,633) → Projected deaths by 2030: 68,799 (95% UI, 41,372–97,613) • Risk Factors: → Geography: Higher in tropical/temperate regions with agriculture and fishing. → Emerging factors: Climate change, travel, and internet-sourced products affecting exposure patterns.

ETIOLOGY & PATHOPHYSIOLOGY¶

• Snake Families: → Viperidae (Viperinae: Old World vipers; Crotalinae: New World/Asian pit vipers) → Elapidae (Cobras, coral snakes, sea snakes, kraits, and all Australian venomous snakes) → Lamprophiidae (e.g., burrowing asps) → Colubridae (mostly nonvenomous; some have Duvernoy's glands) • Venom Mechanisms: → Local: Tissue necrosis, swelling, ecchymosis. → Systemic: Coagulation pathway disruption, organ dysfunction, neuromuscular junction interference.

Snake Anatomy & Identification¶

• Viperids: Triangular heads, elongated/mobile fangs; some have loreal pits (pit vipers). → Note: Identifying by color is unreliable as nonvenomous snakes often mimic venomous ones. • Elapids: Fixed, smaller fangs; include cobras and sea snakes.

Venoms & Clinical Manifestations¶

• Viperid/Some Elapid Venoms: Cause progressive local pain, swelling, ecchymosis, and potential tissue loss. • Neurotoxic Elapids (e.g., Kraits, some Cobras, Sea Snakes): → Early: Nausea, headache, paresthesias, altered mental status. → Late: Cranial nerve abnormalities (ptosis, dysphagia), peripheral motor weakness, diaphragmatic paralysis → respiratory failure. • Sea Snake Venoms: Local pain, myalgias, trismus, rhabdomyolysis, and delayed flaccid paralysis.

CLINICAL FEATURES¶

• Local Findings: Pain, swelling, ecchymosis, blistering, and necrosis (e.g., Russell's viper). • Systemic Findings: Fatigue, nausea/vomiting, taste changes, tachycardia/bradycardia, hypotension, pulmonary edema, renal dysfunction, and hemorrhage. • Neurological Findings: Cranial nerve abnormalities (ptosis, diplopia, dysphagia) and peripheral motor weakness.

Complications¶

• Compartment Syndrome: Rare in North American crotalid envenomations; risk higher with deep bites. • Rhabdomyolysis: Common with sea snake envenomation or deep bites. • Renal Failure: Usually due to acute tubular necrosis (ATN); often reversible. → Note: Bilateral cortical necrosis carries a less favorable prognosis. • Serum Sickness: Develops 1–2 weeks post-antivenom → treat with systemic glucocorticoids.

DIFFERENTIAL DIAGNOSIS¶

• Dry Bite vs. Envenomation: Difficult to distinguish without lab evidence; antivenoms are useless and potentially harmful in dry bites. • Mimics: Cellulitis, insect bites, and other traumatic injuries.

INVESTIGATIONS & DIAGNOSIS¶

Laboratory Studies: • CBC (hemorrhage/hemolysis/thrombocytopenia) • Blood type & cross-match • Metabolic panel, PT/INR/PTT, Fibrinogen, FDP • CK (rhabdomyolysis) and Urinalysis (myoglobin/blood)
Monitoring Frequency: • If labs are normal: Repeat CBC and coagulation studies every 4 h until no systemic envenomation is evident. • If labs are abnormal: Repeat every 6 h after antivenom administration until swelling has stabilized.
Resource-Limited Settings (20-min whole-blood clotting test): • Procedure: 1–2 mL venous blood in a clean, dry glass receptacle → leave undisturbed for 20 min → invert. • Result: If blood remains liquid/no clot forms → coagulopathy present.
Imaging: • ECG and Chest X-ray (severe cases or comorbidities). • Ultrasound (to assess compartment pressures).

MANAGEMENT & TREATMENT¶

Prehospital Management: • Rapid transport to facility with antivenom. • Remove jewelry/tight clothing → prevent constriction from swelling. • Wound care: Clean with soap/water; cover with sterile dressing. • Splinting: Apply splint to limit movement; maintain at heart level. • Prohibited Actions: Do not incise, suck, or use tourniquets (venom sequestration devices). • Pressure-Immobilization: → Indicated for: Neurotoxic elapid bites. → Contraindicated for: Viperid envenomations.
Hospital Management: • ABC stabilization and monitoring (vitals, cardiac rhythm, O_2 saturation). • Establish two large-bore IV lines in unaffected extremities. • Fluid Resuscitation: Isotonic crystalloid (saline or Lactated Ringer's) → 20–40 mL/kg if hemodynamically unstable. • Monitoring: Mark edges of swelling/ecchymosis; measure circumference at 3 points every 15 min until stable, then every 1 h.
Antivenom Administration: • General Rule: Must be specific to the offending snake species. • Pit Viper Antivenom (Table 1): → CroFab® (Crotalidae polyvalent immune Fab):
Moderate: 4–6 vials
Severe: 6 vials → Anavip® (Crotalidae immune F(ab’)):
Moderate: 10 vials
Severe: 10 vials → Administration: Dilute in 250 mL NS; infuse over 1 h. Start at 25–50 mL/h for first 10 min → if no reaction, increase to 250 mL/h. • Coral Snake Antivenom: → Antivenin (Micrurus fulvius) (Equine). → Dilute 3–5 vials in 250–500 mL NS; infuse over 1 h. Max 10 vials total.
Specialized Interventions: • Acetylcholinesterase Inhibitors (Table 2): → Indicated for: Clear evidence of neurotoxicity (e.g., ptosis, inability to maintain upward gaze). → Pretreatment: Atropine 0.6 mg IV (Child: 0.02 mg/kg min 0.1 mg). → Test Dose: Edrophonium 10 mg IV (Child: 0.25 mg/kg) OR Neostigmine 0.02 mg/kg IV or IM (Child: 0.04 mg/kg). → If improved after 30 min:
Neostigmine: 0.5 mg every 1 h as needed.
Atropine: 0.6 mg continuous infusion over 8 h (Child: 0.02 mg/kg over 8 h). • Pain Management: Use acetaminophen and/or opioids; avoid salicylates and NSAIDs due to bleeding risk.

Table 1: Pit Viper & Coral Snake Management¶

• Pit Viper (Rattlesnake, Cottonmouth, Copperhead): → Assessment: Determine severity (None/Dry; Mild; Moderate; Severe). → Antivenom: CroFab® or Anavip®. → Follow-up: Monitor for 8–12 h before discharge if no envenomation. If envenomated, provide additional antivenom (CroFab® 2 vials every 6 h; Anavip® 4 vials for coagulopathy).

Table 2: Acetylcholinesterase Inhibitors¶

• Indication: Clear evidence of neurotoxicity. → Step 1: Atropine (0.6 mg IV) → Edrophonium (10 mg IV) or Neostigmine (0.02 mg/kg IV/IM). → Step 2: If improved, Neostigmine (0.5 mg every 1 h) and Atropine (0.6 mg continuous infusion over 8 h).

Table 3: Ciguatera Poisoning¶

• Gastrointestinal: Abdominal pain, nausea, vomiting, diarrhea. → Dermatologic: Conjunctivitis, maculopapular rash, skin vesiculations, dermographism. → Other: Chills, dysuria, dyspnea, fatigue, headache, arthralgias, myalgias.

PROGNOSIS & COMPLICATIONS¶

• Renal Failure: Usually due to acute tubular necrosis (ATN); often reversible. → Note: Bilateral cortical necrosis carries a less favorable prognosis. • Compartment Syndrome: Risk of tissue loss and loss of function; monitor for rising intracompartmental pressures. • Serum Sickness: Develops 1–2 weeks post-antivenom → treat with systemic glucocorticoids.

SPECIAL CONSIDERATIONS¶

• Pediatric Patients: → Neostigmine dose: 0.02 mg/kg IV or IM (Child: 0.04 mg/kg) for initial test; 0.01 mg/kg every 1 h for maintenance. → Atropine dose: 0.02 mg/kg over 8 h. • Resource-Limited Settings: → Use 20-min whole-blood clotting test to identify coagulopathy when labs are unavailable.

KEY PEARLS & CLINICAL TRAPS¶

• Antivenom Timing: Antivenom is the mainstay of treatment for significant envenomation; it must be specific to the offending snake species. • Drug Selection: Avoid salicylates/NSAIDs due to bleeding risk. Use acetaminophen/opioids. • Dry Bite Identification: Difficult to distinguish without lab evidence; antivenoms are useless and potentially harmful in dry bites. • Referral: Contact regional poison control for assistance.

Reference Tables¶

TABLE 471-1 Management of Venomous Snakebites in the United States and Canada a Pit Viper Bites: Rattlesnakes (…¶

Harrison's 22e, p.3720

Pit Viper Bites: Rattlesnakes (Crotalus and Sistrurus spp.), Cottonmouth Water Moccasins (Agkistrodon piscivorus), and Copperheads
(Agkistrodon contortrix)
• Stabilize airway, breathing, and circulation.
• Institute monitoring (vital signs, cardiac rhythm, and oxygen saturation).
• Establish two large-bore IV lines.
• If patient is hypotensive, administer isotonic crystalloid bolus (20–40 mL/kg IV).
• Take thorough history and perform complete physical examination.
• Identify offending snake (if possible).
• Measure and record circumference of bitten extremity every 15 min until swelling has stabilized. Can take measurements every 1 h once stabilized.
• Order laboratory studies (CBC, blood type and cross-matching, metabolic panel, PT/INR/PTT, fibrinogen level, FDP, CK, urinalysis).
• If normal, repeat CBC and coagulation studies every 4 h until it is clear that no systemic envenomation has occurred.
• If abnormal, repeat every 6 h after antivenom administration until swelling has stabilized (see below).
• Determine severity of envenomation.
• None: fang marks only (“dry” bite)
• Mild: local findings only (e.g., pain, ecchymosis, nonprogressive swelling)
• Moderate: swelling that is clearly progressing, systemic symptoms or signs, and/or laboratory abnormalities
• Severe: neurologic dysfunction, respiratory distress, and/or cardiovascular instability/shock
• Contact regional poison control center.
• Locate and administer antivenom as indicated: Crotalidae polyvalent immune Fab (Ovine) (CroFab®) (BTG International Inc., West Conshohocken, PA) or Crotalidae
immune F(ab’) (Equine) (Anavip®) (Instituto Bioclon S.A de C.V., Tlalpan CDMX, Mexico).
2
• Starting dose:
• Based on severity of envenomation
• None or mild: none
• Moderate: CroFab® (4–6 vials), Anavip® (10 vials)
• Severe: CroFab® (6 vials), Anavip® (10 vials)
• Dilute reconstituted vials in 250 mL of normal saline.
• Infuse IV over 1 h (with medical provider in close attendance).
• Start at rate of 25–50 mL/h for first 10 min.
• If there is no allergic reaction, increase rate to 250 mL/h.
• If there is an acute reaction to antivenom:
• Stop infusion.
• Treat with standard doses of epinephrine (IM or IV; latter route only in setting of severe hypotension), antihistamines (IV), and glucocorticoids (IV).
• When reaction is controlled, restart antivenom as soon as possible (at rate of 5–10 mL/h; titrate up as tolerated).
• Monitor clinical status over 1 h.
• Stabilized or improved: Admit to hospital.
• Progressing or unimproved: Repeat starting dose. Continue this pattern until patient’s condition is stabilized or improved. Admit to ICU if possible.
• Blood products are rarely needed; if required, they should be given only after antivenom administration.
• Provide tetanus immunization as needed.
• Prophylactic antibiotics are unnecessary unless prehospital care included incision or mouth suction.
• Pain management: Administer acetaminophen and/or opioids as needed; avoid salicylates and nonsteroidal anti-inflammatory agents.
• Admit patient to hospital. (If there is no evidence of envenomation, monitor for 8–12 h before discharge.)
• Give additional antivenom: CroFab® (2 vials every 6 h for 3 additional doses), Anavip® (4 vials for recurrent coagulopathy).
• Monitor for evidence of rising intracompartmental pressures (see text).
• Provide wound care (see text).
• Start physical therapy (see text).
• At discharge, warn patient of possible recurrent coagulopathy and symptoms/signs of serum sickness. Schedule repeat laboratory testing to monitor for recurrent
coagulopathy.
Coral Snake Bites: Eastern coral snake (Micrurus fulvius), Texas coral snake (Micrurus tener), and Sonoran coral snake (Micruroides euryxanthus)
• Stabilize airway, breathing, and circulation.
• Institute monitoring (vital signs, cardiac rhythm, and oxygen saturation).
• Establish two large-bore IV lines and initiate normal saline infusion.
• Take thorough history and perform complete physical examination.
• Identify offending snake (if possible).
• Laboratory studies are unlikely to be helpful.
• Contact regional poison control center.
• Locate and administer antivenom as indicated: Antivenin (Micrurus fulvius) (Equine) (commonly referred to as North American Coral Snake Antivenin; Pfizer Inc.,
Philadelphia, PA).b
• Refer to antivenom package insert.
• Dilute 3–5 reconstituted vials in 250–500 mL of normal saline.
• Infuse IV over 1 h (with medical provider in close attendance).
• If signs of envenomation progress despite initial dosing, repeat starting dose; up to 10 vials total may be required.

TABLE 471-2 Use of Acetylcholinesterase Inhibitors in Envenomations by Neurotoxic Snakes and Cone Snails 1. Patients…¶

Harrison's 22e, p.3721

1. Patients with clear, objective evidence of neurotoxicity (e.g., ptosis or
  inability to maintain upward gaze) should receive a test dose of edrophonium
  (if available) or neostigmine.
  a. Pretreat with atropine: 0.6 mg IV (children, 0.02 mg/kg with a minimum of
  0.1 mg)
  b. Treat with:
  Edrophonium: 10 mg IV (children, 0.25 mg/kg)
  or
  Neostigmine: 0.02 mg/kg IV or IM (children, 0.04 mg/kg)
  2. If objective improvement is evident after 30 min, treat with:
  a. Neostigmine: 0.5 mg IV, IM, or SC (children, 0.01 mg/kg) every 1 h as
  needed
  b. Atropine: 0.6 mg as IV continuous infusion over 8 h (children, 0.02 mg/kg
  over 8 h)
  3. Closely monitor airway and perform endotracheal intubation if needed.

TABLE 471-3 Representative Symptoms and Signs of Ciguatera Poisoning SYSTEM Gastrointestinal Neurologic¶

Harrison's 22e, p.3727

SYSTEM	SYMPTOMS/SIGNS
Gastrointestinal	Abdominal pain, nausea, vomiting, diarrhea
Dermatologic	Conjunctivitis, maculopapular rash, skin vesiculations, dermographism
Other	Chills, dysuria, dyspnea, dyspareunia, fatigue, nasal congestion and dryness, insomnia, hypersalivation, diaphoresis, headache, arthralgias, myalgias