Snake Envenomation

By Schon Roberts, MD
Emergency Medicine Resident

28 yo F presents to ED s/p snake bite at 2200. States that she was trying to catch a rattlesnake in Nelson, NV. She states that it is a sidewinder (this knowledge due to the fact that she is an avid snake hobbyist). While attempting to catch the snake the pt was bit by 1 fang at her L 3rd DIP joint of her UE. She did not present for 4 hours as she thought that this bite was unsubstantial. When the swelling increased she called to multiple hospitals and presented to the only hospital with antivenom. Other than swelling pt had no other substantial symptoms. Vital signs are Temp: 98.0 HR: 80 RR: 16 BP: 140/85 SpO2 98% RA. Pt’s labs are remarkable for WBC of 15.2, platelets of 90, Potassium of 3.3, PT of 14.4, and INR of 1.3. The first treatment should be:


A. Fresh Frozen Plasma
B. Weight based antivenom
C. KCL IV 80 mg STAT
D. 4-6 vials of antivenom regardless of weight
E. Intubation

Answer
A.  4-6 vials of antivenom regardless of weight

Clinical Pearls

• Snake envenomation should be considered in any individual who presents with reported bite or suspected bite with a constitution of neurological symptoms and/or coagulopathy.
• Snake envenomations that warrant antivenom include the Western Diamondback Rattlesnake, Eastern Diamondback Rattlesnake, Mojave Rattlesnake, and Water Moccasin (Cottonmouth).
• Crofab dosage is severity based as opposed to weight based and reverses neurotoxicity and most venom induced coagulopathies.

 
Pathophysiology

• Locally Acting Toxins
  • Consist of enzymes that cause tissue destruction.
                -phospholipase A2                                 -peptidases,
                -phosphodiesterases                        -metalloproteinases
                -hyaluronidases 
• Neurotoxins
  • Presynaptic- based on PLA2 and damage terminal axon. Non-reversible (days-weeks recovery)
  • Postsynaptic- long/short chain peptides that antagonizes Acetylcholine receptors on the muscle endplate. Sometimes reversed with antivenom and/or anticholinesterases.​

​(Source: Tropical Medicine. Image by Van den Enden MD)

• Myotoxins
  • Local Muscle Necrosis
    • ​Rhabdomyolysis
• • Systemic Myotoxins
• Systemic Hemostasis Toxins
  • Anticoagulation- primarily through targeting Factors V, IX, and X. Others target include Fibrinogenolysis and inhibition of VWF. Reversed by antivenom
  • Pro thrombotic less common, but may result in DVT, PE, and/or CVA. Targets include Factor II activation and/or activation of VWF.
  • Blood Vessel Damage
• Cardiotoxins
  • ACE-Inhibition and Naturetic Peptide induced hypotension

• Kidney
  • Direct action of some venoms
  • AKI from rhabdomyolysis/hypotension
• Misc. Toxins

            -Histamine                        -5-HT                     -L-amino Oxidase
 
Symptoms/Exam Findings

• Local/systemic pain
• Local/systemic paresthesias
• Tachycardia
• Hypotension
• Compartment Syndrome
• Ptosis
• Mydriasis
• Poor Facial Tone
• Limited Mouth opening/tongue extrusion
• Drooling
• Decreased DTRs
• Gait Disturbances
• Cranial Nerve Dysfunction
• Edema
• Skin necrosis/ecchymosis
• DIC
• Respiratory Depression
• Nausea and vomiting
• Erythema
• Urticaria
• Sweating

(Source: Uptodate. Figure by Cheng)
​

Crofab
Indications (US):

• C Atrox (Western Diamondback Rattlesnake),
• C Adamanteus (Eastern Diamondback Rattlesnake),
• C Scutulatus (Mojave Rattlesnake),
• A Piscivous (Cottonmouth/Water Moccasin)

(Source: Wikipedia. Images by Robertson)
​

MOA: Purified Fab fragments of Sheep IgG against the C Atrox, C Adamanteus,, C Scutulatus, and A Piscivous, which bind venom and are renally excreted.
              Pros:

• Since development snakebite mortality has dropped from 36% in the 1950s to 0.06% in 2009.
• Neutralizes neurotoxins
• Halts progression of coagulopathy in most pts 
  Cons:

• Hypersensitivity (Immediate in 6% and Delayed in 8%)
• Shorter half life than actual venom
• Expensive (around $20,000 per vial)

(Source: Uptodate. Figure by Cheng)
​

References
 
1. White MD,  Julian. “Snakebites worldwide: Clinical manifestations and diagnosis." Uptodate. 3 Jun. 2014. Web. 30 Sept. 2015. <http://www.uptodate.com/contents/snakebites-worldwide-clinical-manifestations-and-diagnosis?source=machineLearning&search=snake+bite&selectedTitle=3~39&sectionRank=3&anchor=H61373588#H61373588>
 
2. Van den Enden MD, Erwin. "Illustrated Lecture Notes on Tropical Medicine-Snakes-Clinic." Illustrated Lecture notes on Tropical Medicine. Health and Medical Publishing Group. Web. 30 Sept. 2015. < http://itg.author-e.eu/Generated/pubx/173/snakes/clinic.htm>.
 
3. Warrell DA. Envenoming and injuries by venomous and nonvenomous reptiles worldwide. In: Wilderness Medicine, 6th Edition, Auerbach PS. (Ed), Elsevier Mosby, Philadelphia 2012. p.1040. 

4. ​White J. Overview of venomous snakes of the world. In: Medical Toxicology, 3rd edition, Dart RC. (Ed), Lippincott, Williams, & Wilkins, Philadelphia 2004. p.1543. 

5. ​Maduwage K, Buckley NA, de Silva HJ, et al. Snake antivenom for snake venom induced consumption coagulopathy. Cochrane Database Syst Rev 2015; 6:CD011428.
 
6. ​Isbister GK. Antivenom efficacy or effectiveness: the Australian experience. Toxicology 2010; 268:148
 
7. ​Seifert SA, Boyer LV, Benson BE, Rogers JJ. AAPCC database characterization of native U.S. venomous snake exposures, 2001-2005. Clin Toxicol (Phila) 2009; 47:327.
 
8. ​Cheng, Allen C. “Management of Crotalinae (rattlesnake, water moccasin [cottonmouth], or copperhead) bites in the United States." Uptodate. 3 Jun. 2014. Web. 30 Sept. 2015. < http://www.uptodate.com/contents/management-of-crotalinae-rattlesnake-water-moccasin-cottonmouth-or-copperhead-bites-in-the-united-states?source=see_link&sectionName=Indications&anchor=H18#H18>

9. Robertson, Clinton. Western Diamondback Rattlesnake (Cortalus Atrox). Digital image. Wikipedia. Wikimedia Foundation Org, 6 May 2007. Web. 2 Oct. 2015. <https://en.wikipedia.org/wiki/Western_diamondback_rattlesnake#/media/File:Western_Diamondback_Rattlesnake.jpg>.
 
​10. Eastern Diamondback Rattle Snake Crotalus adamanteus. Digital image. Wikipedia. Wikimedia Foundation Org, 6 May 2007. Web. 2 Oct. 2015. <http://www.neoperceptions.com/snakesandfrogs.com/scra/snakes/ediabks.htm>. 

11. Northern Mohave Rattlesnake - Crotalus scutulatus scutulatus Digital image. Wikipedia. Wikimedia Foundation Org, 6 May 2007. Web. 2 Oct. 2015. < http://www.californiaherps.com/snakes/pages/c.s.scutulatus.html>. 

12. ​Water Moccasin Agkistrodon piscivorus Digital image. Wikipedia. Wikimedia Foundation Org, 6 May 2007. Web. 2 Oct. 2015. < https://en.wikipedia.org/wiki/Agkistrodon_piscivorus#/media/File:Florida_Water_Moccasin_056.jpg>.