Venom

• Venom


  Complex mixture of many substances – toxins, enzymes, growth factor activators, and inhibitors
• Venom


  • Interacts in the body with a large number of proteins and receptors
  • Activation of the inflammatory response
  • Release and activate pro-inflammatory cytokines and other mediator (such as nitric oxide)
• Cytokines


  Initiate a cascade of events that lead to illness behaviors (fever, anorexia, vasodilation, hypotension etc)
• Venom and immune responses

  Trigger the release of cytokines leading to a cascade that results in illness
• Venoms


  • Crude
  • Purified
• Endogenous mediators


  • Platelet Activating Factor
  • Pro-inflammatory (IL-1, IL-6, TNF-ɑ)
  • Humoral defenses systems
  • Nitrite Oxides
  • Arachidonic acid metabolites
  • Cytokines (IFN-ɣ, IL-2, IL-4, IL-6, IL-8, IL-10)
• Endogenous mediators


  • ↑ vascular permeability, vasodilatation, fever, pain
  • Vasoconstriction, platelet aggregation
• Endogenous mediators


  • Leukotrienes
  • Prostaglandins
  • Thromboxane
• Endogenous mediators


  • Loss of balance
  • Systemic spillover
  • Organ dysfunction
  • Circulatory failure
  • Shock
• Endogenous mediators


  • Recovery
  • Death
• Venomous snakes


  • Viperidae (subfamily Viperinae: Old World vipers; subfamily Crotalinae: New World and Asian pit vipers)
  • Elapidae (including cobras, coral snakes, sea snakes, kraits, and all Australian venomous snakes)
  • Lamprophiidae (subfamily Atractaspidinae: burrowing asps)
  • Colubridae (a large family in which most species are nonvenomous)

  
• Most snakebites occur in developing countries with temperate and tropical climates in which populations subsist on agriculture and fishing

  
• Recent estimates indicate that somewhere between 1.2 million and 5.5 million snakebites occur worldwide each year, with 421,000–1,200,000 envenomations and 81,000–138,000 deaths

  
• Challenges of collecting accurate data - many victims in these areas either do not seek medical attention or have insufficient access to antivenom, and reporting and record-keeping are generally poor
• Venomous snake anatomy


  • The typical snake venom delivery apparatus consists of bilateral venom glands situated behind the eyes and hollow anterior maxillary fangs
  • Approximately 20–25% of pit viper bites and higher percentages of other snakebites (up to 75% for sea snakes) are "dry" bites, in which no venom is released
  • Differentiating between venomous and nonvenomous snake species can be challenging

  
• Venomous snakes


  • Long rectangular head shape
  • Two large canines on the upper jaw
  • Two major bite wounds from canines

  
• Non-venomous snakes


  • Small canines
  • Bite marks: smooth wound in the form of an arch
  • Triangle-shaped head

  
• Snake venom


  • Proteolytic
  • Hemotoxin - slower onset, painful
  • Neurotoxin - the deadliest

  
• Pathophysiology of snake venoms

  • Swelling and bruising - increased vascular permeability
  • Local tissue necrosis - direct action of myotoxins and cytotoxins
  • Ischemia - by thrombosis; compression of blood vessels by first-aid methods such as tight tourniquets; or by swollen muscle within a tight fascial compartment
  • Hypotension and shock - plasma leakage, blood loss, vasodilatation
  • Coagulopathy - procoagulant enzyme
  • Thrombocytopenia - platelet activation/inhibition, sequestration
  • Spontaneous bleeding - N-metalloprotease haemorrhagins enzyme
  • AKI - acute tubular necrosis, proliferative glomerulonephritis, interstitial nephritis, etc.

  
• Local clinical manifestations


  • Swelling, hemorrhagic blebs within hours
  • Rapid extension within a few hours
  • Enlarged tender lymphnode draining the affected area
  • Hemostatic abnormality
• Systemic clinical manifestations


  • Neurotoxic signs (ptosis, ophthalmoplegia, paralysis, etc)
  • Cardiovascular abnormalities
  • Acute kidney injury
  • Myoglobinuria/generalized rhabdomyolysis/hemolysis
  • Supporting lab evidence of systemic envenoming (DIC, rhabdomyolysis, etc)
  • ARDS - more common in coral snakes

  
• Field management


  1. Rapid transport to a medical facility equipped to provide supportive management and antivenom therapy

  2. Remove any jewelry or tight-fitting clothing near the bite to avoid constriction

  3. Clean the wound with soap and running water then cover with a sterile dressing

  4. Apply a splint to the bitten extremity to limit movement and assist with positioning

  5. Attempting to capture and transport the offending snake is not advised; instead, take digital photographs from a safe distance

  
• Most of the first-aid measures recommended in the past are of little benefit and may worsen outcomes
• Incising and/or applying suction to the bite site should be avoided, as these measures exacerbate local tissue damage, increase the risk of infection, and have not been shown to be effective
• Venom sequestration devices (e.g., lympho-occlusive bandages or tourniquets) are not advised, as they may intensify local tissue damage by restricting the spread of potentially necrotizing venom

  
• Tourniquet use can result in loss of function, ischemia, and limb amputation, even in the absence of envenomation
• Hospital management


  1. Focus on the victim's airway, breathing, and circulation

  2. Patients with bites to the face or neck may require early endotracheal intubation to prevent loss of airway patency caused by rapid soft-tissue swelling

  3. Establish two large-bore IV lines in unaffected extremities

  4. Fluid resuscitation with isotonic saline (20–40 mL/kg IV) should be initiated if there is any evidence of hemodynamic instability

  5. Vasopressors (e.g., norepinephrine, epinephrine) should be considered if venom-induced shock persists after aggressive volume resuscitation and antivenom administration
• Work up


  1. Anamnesis (the time of the bite + any symptoms of envenomation) and a complete physical examination - focus on the neurovascular status

  2. Limb: palpate axillary/inguinal lymph nodes (lymphatic spread)

  3. Evaluate the progression of local envenomation: the leading edge of swelling/ecchymosis should be marked and limb circumference should be measured at three points (e.g., at the bite site, the joint proximal, and the joint distal) every 15 min until the local-tissue effects have stabilized; or using RPP (rapid progressive proximal) method

  4. Victims of neurotoxic envenomation should be monitored closely for evidence of cranial nerve dysfunction - impending airway compromise necessitating intubation and mechanical ventilation
• RPP


  If there is a 2x or more increase in 2 hours, antivenom should be administered immediately
• Work up


  1. 20 minutes whole blood clotting time

  2. Complete blood count - to determine the degree of hemorrhage or hemolysis and to detect thrombocytopenia; blood type and cross-matching

  3. Assessment of renal and hepatic function

  4. Coagulation studies

  5. Measurement of creatine kinase for suspected rhabdomyolysis

  6. Testing of urine for blood or myoglobin

  7. ECG

  8. Chest x-ray
• After antivenom therapy, laboratory values should be rechecked every 6 h until clinical stability is achieved
• Antivenom


  • The mainstay of treatment is prompt administration of specific antivenom
  • Antivenoms are produced by injecting animals (generally horses or sheep) with venoms from medically important snakes - develop antibodies - harvest the serum & isolate the antibodies
  • The goal of antivenom administration is to allow antibodies (or antibody fragments) to bind and deactivate circulating venom components before they can attach to target tissues
  • Antivenoms may be monospecific (directed against a particular snake species) or polyspecific (covering several species in a geographic region)
  • Antivenom selection must be specific for the offending snake - provide no benefit and may lead to unnecessary complications
• Antivenom administration


  1. Indications (for viperids or cytotoxic elapids bites): significant progressive local findings (e.g., soft-tissue swelling that crosses a joint, involves more than half the bitten limb, or is rapidly spreading; extensive blistering or bruising; severe pain) and any evidence of systemic envenomation (e.g., systemic symptoms or signs, laboratory abnormalities)

  2. 2 vials SABU + 100 ml NS drip 60 – 80 per minutes

  3. Repeated every 6 – 8 hours
• Adjunct treatments


  • Anticholinesterase - for neurotoxin envenoming
  • Antibiotics - for secondary infection
  • Analgetic - morphine, acetaminophen
• Salicylates and nonsteroidal anti-inflammatory agents should be avoided because of their potential effects on blood clotting
• Morbidity and mortality


  • The overall mortality rates for victims of venomous snakebites are low in regions with rapid access to medical care and appropriate antivenoms
  • The incidence of morbidity—defined as permanent functional loss in a bitten extremity—is difficult to estimate but is substantial
  • Morbidity may be due to muscle, nerve, or vascular injury or to scar contracture

  
• Snakes responsible for a large number of deaths

  • Cobras (Naja species)
  • Carpet and sawscaled vipers (Echis species)
  • Russell's vipers (D. russelii)
  • Large African vipers (Bitis species)
  • Lancehead pit vipers (Bothrops species)
  • Tropical rattlesnakes (C. durissus)

  
• The global incidence of marine envenomations is likely underestimated, as the majority of cases are mild
• Cnidarians


  • Possess thousands of specialized stinging organelles called cnidocysts distributed along their tentacles
  • Nematocysts contain a coiled hollow thread bathed in venom that is discharged when provoked by mechanical stimuli, osmotic changes, or other chemical stimuli

  
• Cnidarians


  • Possess thousands of specialized stinging organelles called cnidocysts distributed along their tentacles
  • Nematocysts contain a coiled hollow thread bathed in venom that is discharged when provoked by mechanical stimuli, osmotic changes, or other chemical stimuli
  • The venom contains enzymes (phospholipases, metalloproteases), pore-forming toxins, neurotoxins, and nonprotein bioactive substances, such as tetramine, 5-hydroxytryptamine, histamine, and serotonin
  • Venom flows through the hollow thread into the victim's skin
  • Cnidocysts that possess barbs on the ends of their threads can penetrate human skin; only a subset of cnidarians are toxic to humans