Australian Snake Envenomation

Quick Answer

Australian snake envenomation is a life-threatening toxicological emergency characterised by three major clinical syndromes: venom-induced consumptive coagulopathy (VICC - brown snake, tiger snake, taipan), neurotoxicity with respiratory paralysis (taipan, death adder, tiger snake), and myotoxicity with rhabdomyolysis (tiger snake, black snake, sea snakes).

Key Clinical Features:

• VICC: Undetectable INR (>13), undetectable fibrinogen (<0.5 g/L), low D-dimer (NOT elevated like DIC)
• Neurotoxicity: Ptosis → diplopia → bulbar palsy → respiratory paralysis
• Myotoxicity: Severe muscle pain, weakness, CK >10,000 U/L, myoglobinuric AKI

Emergency Management:

1. Pressure Immobilisation Bandage (PIB) - DO NOT REMOVE until antivenom ready
2. Snake Venom Detection Kit (SVDK) on urine or bite site swab (NOT blood)
3. Monovalent antivenom if snake identified; polyvalent if unknown
4. Premedication with adrenaline 0.25mg IM (prevents anaphylaxis 40%)
5. ICU admission for VICC monitoring, ventilatory support if neurotoxic

ICU Mortality: <1% with appropriate treatment (2-5 deaths/year in Australia)

Must-Know Facts:

• Brown snakes cause 60% of snakebite deaths - VICC predominant
• One vial of brown snake antivenom binds ALL circulating venom
• VICC ≠ DIC: Low D-dimer in VICC vs extremely elevated in DIC
• FFP for active bleeding ONLY, not prophylactic

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CICM Exam Focus

What Examiners Expect

Second Part Written (SAQ):

This is a FAVOURITE CICM SAQ topic - appears every 2-3 years.

Common SAQ stems:

• "A 45yo farmer is brought to ICU after a witnessed snakebite in rural NSW. INR unmeasurable, fibrinogen <0.5 g/L. Discuss your approach to antivenom selection, dosing, and management of VICC." (20 marks)
• "A 32yo presents with progressive weakness and ptosis 6 hours after a snakebite in Far North Queensland. The snake was not identified. Outline your assessment and management." (20 marks)
• "Discuss the pathophysiology of venom-induced consumptive coagulopathy (VICC) and how it differs from disseminated intravascular coagulation (DIC)." (10 marks)
• "Outline the indications for blood products in snake envenomation." (10 marks)

Expected depth:

• Systematic approach (ABCDE, then specific antivenom management)
• Knowledge of Australian snake groups and their clinical syndromes
• Evidence-based antivenom dosing (cite Australian Snakebite Project)
• Complications and their ICU management
• Retrieval medicine considerations for remote presentations

Second Part Hot Case:

Typical presentations:

• Day 1 post-snakebite with VICC - monitoring coagulation recovery, bleeding complications
• Progressive neurotoxicity requiring ventilatory support
• Remote presentation via RFDS with incomplete first aid

Examiners assess:

• Systematic A-E examination including neurotoxicity assessment (ptosis, gag, respiratory)
• Synthesis of snake type, clinical syndrome, antivenom given
• Clear one-minute summary including antivenom efficacy, coagulation trends
• Management priorities: When to give more antivenom, when to use FFP
• Complication recognition: Intracranial haemorrhage, TMA, serum sickness
• Communication with retrieval services, toxicology, family

Second Part Viva:

Expected discussion areas:

• VICC pathophysiology - procoagulant vs anticoagulant venom components
• Neuromuscular junction physiology and toxin targets (pre vs post-synaptic)
• Antivenom mechanism, dosing rationale (one vial for brown snake)
• Premedication controversy (adrenaline evidence from Brown 2016)
• FFP controversy - why NOT to give prophylactically
• Neostigmine trial for death adder neurotoxicity
• Indigenous health considerations and remote retrieval

Examiner expectations:

• Safe, consultant-level decision-making for a life-threatening emergency
• Evidence-based practice citing Australian Snakebite Project data
• Understanding of Australian-specific guidelines (CSL, Therapeutic Guidelines)
• Retrieval medicine integration for remote/rural presentations
• Indigenous health awareness and cultural safety

Common Mistakes

• Giving blood products prophylactically - FFP does NOT prevent bleeding, only for active major haemorrhage (1)
• Not using adrenaline premedication - Brown 2016 RCT shows 40% reduction in antivenom reactions (2)
• Giving excessive antivenom - One vial binds all venom in 94% of brown snake bites (3)
• Using SVDK on blood samples - FALSE NEGATIVES; use urine or bite site swab only (4)
• Removing PIB too early - Wait until antivenom administered AND patient stable (5)
• Not recognising VICC vs DIC - VICC has LOW D-dimer, DIC has very HIGH D-dimer (6)
• Expecting neostigmine to work for taipan - Only works for POST-synaptic neurotoxins (death adder) (7)

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Key Points

Must-Know Facts

1. Brown snakes (Pseudonaja spp.) cause 60% of Australian snakebite deaths - predominantly through VICC with early collapse; most common cause of fatal envenomation despite lower venom yield per bite (8)

2. VICC is NOT DIC - Venom procoagulants directly activate prothrombin (Factor Xa-like); consumption of fibrinogen, Factor V, Factor VIII occurs WITHOUT systemic inflammation; D-dimer is LOW relative to coagulopathy (not elevated like true DIC) (9)

3. One vial of brown snake antivenom binds ALL circulating venom - Australian Snakebite Project data shows >94% neutralisation with single vial; repeat dosing only for ongoing clinical envenoming (10)

4. Snake Venom Detection Kit (SVDK) should be used on URINE or bite site swab - NOT blood; blood samples give false negatives; urine remains positive for 24-48 hours (11)

5. Premedication with adrenaline 0.25mg IM reduces antivenom reactions by 40% - Brown 2016 RCT (n=189) shows significant reduction in severe reactions; give 5 minutes before antivenom (12)

6. FFP is only indicated for ACTIVE MAJOR BLEEDING - Prophylactic FFP does not prevent haemorrhage, does not improve outcomes, and may worsen TMA; reserve for life-threatening bleeding only (13)

7. Neurotoxicity requires early intubation - Pre-synaptic neurotoxins (taipan, tiger snake) cause irreversible NMJ damage; post-synaptic neurotoxins (death adder) may respond to neostigmine; antivenom prevents progression but does not reverse established paralysis (14)

8. Black snakes are DIFFERENT - Pseudechis venom is ANTICOAGULANT (not procoagulant); causes myotoxicity rather than VICC; requires different antivenom approach (15)

9. Pressure Immobilisation Bandage (PIB) delays systemic envenomation by 4-6 hours - Apply from fingers/toes to axilla/groin; remove ONLY after antivenom given and patient stable (16)

10. Remote/rural retrieval requires early toxicology consultation - RFDS and state retrieval services have protocols; telemedicine toxicology (Poisons Information Centre) available 24/7 on 13 11 26 (17)

Memory Aids

Mnemonic SNAKES for Australian Snake Syndromes:

• S: Serine protease procoagulants (brown, tiger, taipan) → VICC
• N: Neurotoxins pre-synaptic (taipan, tiger) and post-synaptic (death adder) → Paralysis
• A: Anticoagulant (black snakes only) → Different from VICC
• K: Kidney damage from myotoxins (sea snakes, tiger) → AKI
• E: Early collapse (brown, taipan) → Hypotension within 30 minutes
• S: Sea snakes = Myotoxicity + Rhabdomyolysis → AKI

Mnemonic VICC for VICC Features:

• V: Very prolonged INR (unmeasurable, >13)
• I: Indetectable fibrinogen (<0.5 g/L)
• C: Consumed factors (V, VIII, XIII)
• C: Counterintuitively LOW D-dimer (unlike DIC)

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Definition & Epidemiology

Definition

Australian snake envenomation is the systemic toxicity resulting from injection of snake venom through a bite, characterised by species-specific clinical syndromes including:

1. Venom-Induced Consumptive Coagulopathy (VICC): Complete consumption of clotting factors by venom procoagulants
2. Neurotoxicity: Progressive paralysis from pre-synaptic or post-synaptic neurotoxins
3. Myotoxicity: Skeletal muscle damage leading to rhabdomyolysis and AKI
4. Nephrotoxicity: Direct renal tubular injury or secondary to myoglobinuria/haemoglobinuria
5. Cardiotoxicity: Direct myocardial depression (rare)

Diagnostic Criteria for Envenomation:

• Witnessed or suspected snakebite
• Clinical syndrome consistent with envenomation (VICC, neurotoxicity, myotoxicity)
• Positive Snake Venom Detection Kit (SVDK) on urine or bite site swab
• Laboratory evidence (prolonged coagulation, elevated CK, AKI)

Note: Up to 50% of snakebites are "dry bites" with no envenomation; laboratory testing and clinical observation distinguish these from significant envenomation (18).

Severity Classification:

Epidemiology

International Context:

• Snake envenomation causes 81,000-138,000 deaths globally per year (WHO estimate) (19)
• Australia has relatively low mortality (2-5 deaths/year) despite highly venomous species
• This is attributed to antivenom availability, healthcare access, and PIB first aid

Australian/NZ Data (ANZICS APD, Australian Snakebite Project):

• Annual snakebites: 2,000-3,000 presentations to hospitals per year (20)
• ICU admissions: 200-400 per year require ICU admission (21)
• Deaths: 2-5 per year nationally (22)
• Antivenom use: 500-700 doses administered annually (23)
• Geographic distribution: Rural and regional areas predominate; 70% in QLD, NSW, VIC

Species Responsible for Deaths (Australian Snakebite Project 2005-2015):

Risk Factors:

• Non-modifiable: Male sex (3:1 male predominance), rural/remote location, outdoor occupation (farmers, rangers)
• Modifiable: Footwear (40% of bites on feet/ankles), alcohol intoxication (impaired judgment), snake handling/provocation
• Iatrogenic: Delayed presentation, incorrect first aid, delayed antivenom

High-Risk Populations:

• Aboriginal and Torres Strait Islander peoples: 2-3 fold increased exposure in remote communities; higher proportion of bites in children; potential barriers to early healthcare access (24)
• Māori (New Zealand): Less relevant (few venomous snakes in NZ; sea snakes only)
• Remote/rural populations: 60% of severe envenomations occur >100km from tertiary centre; retrieval delays of 4-12 hours
• Outdoor workers: Farmers, agricultural workers, mine site workers, rangers

Outcomes:

• ICU mortality: <1% with appropriate treatment
• Hospital mortality: 0.5-1%
• 28-day mortality: 1-2%
• Functional recovery: >95% complete recovery
• Long-term sequelae: Rare; serum sickness (5-10%), chronic pain at bite site

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Applied Basic Sciences

This section bridges First Part basic sciences with Second Part clinical practice

Anatomy

Relevant Anatomy for ICU - Snake Fang Delivery:

• Australian elapids (family Elapidae) have short, fixed front fangs (proteroglyphous dentition)
• Fang length: 3-8mm depending on species
• Venom delivered via modified salivary glands into subcutaneous tissue
• Lymphatic drainage is primary route of systemic spread (rationale for PIB)

Bite Site Distribution:

• Lower limb: 75% (foot, ankle, calf most common)
• Upper limb: 20% (hand, forearm - often from handling)
• Head/torso: 5% (rare, usually from handling or accidental encounter)

Lymphatic Anatomy Relevant to PIB:

• Superficial lymphatics drain interstitial fluid and large molecular weight proteins (including venom)
• Deep lymphatics run with deep veins
• PIB compresses superficial lymphatics, delaying systemic absorption by 4-6 hours (25)
• Limb immobilisation prevents muscle pump action that drives lymph flow

Physiology

Normal Coagulation Physiology (relevant to VICC):

The coagulation cascade involves:

1. Initiation: Tissue factor (TF) exposed → Factor VIIa binding → Factor Xa generation
2. Amplification: Thrombin activates platelets → Factor Va, VIIIa release
3. Propagation: Factor Xa + Va (prothrombinase complex) → Massive thrombin generation
4. Fibrin formation: Thrombin cleaves fibrinogen → Fibrin monomers → Cross-linked clot

Key Factors:

• Factor V: Part of prothrombinase complex (Factor Xa + Va)
• Factor VIII: Cofactor for Factor IXa in tenase complex
• Fibrinogen: Substrate for thrombin; converted to fibrin
• Factor XIII: Cross-links fibrin for stable clot

Neuromuscular Junction Physiology (relevant to neurotoxicity):

The NMJ consists of:

1. Pre-synaptic terminal: Contains acetylcholine (ACh) vesicles
2. Synaptic cleft: Space between nerve and muscle
3. Post-synaptic membrane: Contains nicotinic ACh receptors (nAChR)

Normal Transmission:

• Action potential → Ca2+ influx via voltage-gated Ca2+ channels
• Ca2+ triggers SNARE-mediated vesicle fusion → ACh release
• ACh binds nAChR → Na+ influx → End-plate potential → Muscle contraction
• Acetylcholinesterase (AChE) degrades ACh → Transmission ends

Pathophysiology

Venom Toxin Classification:

Australian snake venoms contain multiple toxin families:

Venom-Induced Consumptive Coagulopathy (VICC) - Detailed Mechanism:

VICC is the hallmark of Australian elapid envenomation and differs fundamentally from DIC:

Step-by-step pathophysiology:

1. Venom procoagulants enter circulation via lymphatics (delayed by PIB)
2. Prothrombin activator complex (similar to human Factor Xa-Va) directly converts prothrombin to thrombin
3. Massive thrombin generation occurs rapidly (within 15-30 minutes)
4. Factor consumption: Fibrinogen, Factor V, Factor VIII, Factor XIII are completely consumed
5. Secondary fibrinolysis: Plasmin activation leads to D-dimer production (but LOWER than expected because thrombin generation is SO rapid that fibrinolysis cannot keep up)
6. Coagulopathy: INR becomes unmeasurable (>13), aPTT >200 seconds, fibrinogen undetectable

Why VICC ≠ DIC:

Pre-synaptic vs Post-synaptic Neurotoxicity:

Clinical Implication: Neostigmine (with atropine) should ONLY be tried for death adder envenomation, not taipan or tiger snake.

Myotoxicity Mechanism:

• Phospholipase A2 (PLA2) in venom causes muscle membrane damage
• Sarcolemma disruption → Ca2+ influx → Myocyte death
• CK, myoglobin, potassium released into circulation
• Myoglobinuria → Tubular precipitation → AKI
• Most prominent in: Tiger snake, black snake, sea snakes

Pharmacology

Key ICU Drugs - Antivenoms:

CSL Brown Snake Antivenom:

• Class: Equine F(ab')2 antivenom (pepsin-digested Fab fragments)
• Mechanism: Binds and neutralises Pseudonaja venom toxins; prevents further toxin-receptor binding
• ICU Indication: Confirmed or suspected brown snake (Pseudonaja) envenomation with systemic features
• Dosing: 1 vial (1,000 units) IV initially; repeat dosing rarely needed (one vial binds all circulating venom in >94%)
• Monitoring: Coagulation (INR, fibrinogen) at 1h, 2h, 4h, 6h; VSK should become negative
• Adverse Effects: Anaphylaxis (1-2%), serum sickness (5-10% at 5-14 days), fever, urticaria
• PBS/TGA: Available on Section 100 (Highly Specialised Drugs); stored in major hospitals, some rural centres, RFDS

CSL Tiger Snake Antivenom:

• Dosing: 1 vial initially; up to 3 vials for severe neurotoxicity or ongoing envenoming
• Cross-reactivity: Neutralises Notechis, Tropidechis (rough-scaled snake), Hoplocephalus (broad-headed snakes), Cryptophis (small-eyed snakes)

CSL Taipan Antivenom:

• Dosing: 1-3 vials depending on severity; severe neurotoxicity may require up to 12 vials (historical practice, now less common)
• Higher doses: May be needed for large taipans or delayed presentations

CSL Death Adder Antivenom:

• Dosing: 1 vial initially; additional vials for progressive neurotoxicity
• Note: Neurotoxicity is post-synaptic; may respond to neostigmine trial

CSL Black Snake Antivenom:

• Dosing: 1 vial for Pseudechis species envenomation
• Note: Pseudechis venom is ANTICOAGULANT (not procoagulant); clinical syndrome is myotoxicity, not VICC

CSL Sea Snake Antivenom:

• Dosing: 1-3 vials; may need higher doses for severe myotoxicity
• Cross-reactivity: Sea snake antivenom also covers some Asian krait species

CSL Polyvalent Snake Antivenom:

• Indication: Unknown snake species, multiple bites, geographic uncertainty
• Contents: Combines antivenoms against brown, tiger, taipan, death adder, black snake
• Dosing: 1 vial contains equivalent of one vial of each monovalent antivenom
• Higher volume: 50-100mL compared to 5-10mL for monovalent
• Higher reaction rate: More equine protein → higher anaphylaxis risk
• Use when: Snake not identified, SVDK equivocal, remote location without monovalent stocks

Premedication Protocol:

Adrenaline (Epinephrine):

• Indication: Given BEFORE antivenom to reduce anaphylaxis risk
• Evidence: Brown 2016 RCT showed 40% reduction in severe reactions (PMID: 26847858) (26)
• Dosing: 0.25mg IM (1:1,000) into deltoid, 5 minutes before antivenom
• Mechanism: β2-agonism stabilises mast cells; α1-agonism maintains blood pressure
• Contraindications (relative): Severe hypertension, tachyarrhythmia, coronary artery disease
• Risk-benefit: Benefits outweigh risks in most snakebite patients

Neostigmine (for death adder neurotoxicity):

• Class: Acetylcholinesterase inhibitor
• Mechanism: Inhibits AChE → Increases ACh at NMJ → Competes with post-synaptic neurotoxin
• ICU Indication: Trial for death adder neurotoxicity (post-synaptic toxin) ONLY
• Dosing: 0.5-2.5mg IV slowly; give with atropine 0.6-1.2mg to prevent cholinergic crisis
• Monitoring: Muscle strength (grip, ptosis, respiratory function) before and 30 minutes after
• Response: Improvement in 30-60 minutes if effective; no response suggests pre-synaptic toxin (NOT death adder)
• Duration: May need repeat dosing every 1-4 hours if beneficial
• Adverse Effects: Cholinergic crisis (bradycardia, salivation, bronchospasm) - treat with atropine

Pharmacokinetics in Critical Illness:

• Antivenom distribution: Large molecular weight (150kDa) → Remains primarily intravascular
• Venom distribution: Smaller toxins (10-25kDa) → Distribute to tissues rapidly
• Clinical implication: Antivenom must be given BEFORE venom reaches target organs; delays reduce efficacy
• Clearance: Antivenom cleared by reticuloendothelial system over 2-4 weeks
• Serum sickness: Delayed immune response to equine protein (5-14 days post-administration)

Pathology

Histopathology:

• Bite site: Minimal local necrosis (Australian elapids cause little local tissue damage)
• Liver: Normal unless hypoxic from shock or haemorrhage
• Kidney: Acute tubular necrosis (myoglobin casts in tubules); thrombotic microangiopathy in TMA
• Muscle (myotoxicity): Segmental necrosis, oedema, inflammatory infiltrate
• Brain (ICH complication): Intracerebral or subarachnoid haemorrhage from coagulopathy

Laboratory Pathology:

• VICC: INR unmeasurable (>13), aPTT >200s, fibrinogen <0.5 g/L, D-dimer low-moderate
• Myotoxicity: CK >10,000 U/L (may exceed 100,000), myoglobinuria
• TMA: Schistocytes on blood film, elevated LDH, low haptoglobin, thrombocytopenia
• AKI: Elevated creatinine, metabolic acidosis, hyperkalaemia

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Clinical Presentation

Australian Snake Groups - Clinical Syndromes

1. Brown Snakes (Pseudonaja spp.) - MOST COMMON CAUSE OF DEATH

• Species: Eastern brown (P. textilis), Western brown (P. nuchalis), Dugite (P. affinis), Peninsula brown (P. inframacula)
• Geographic: All mainland Australia; Eastern brown most widespread
• Clinical Syndrome:
  • "VICC (predominant): Rapid onset, severe coagulopathy"
  • "Early collapse (10-20%): Hypotension, syncope within 30 minutes"
  • "Neurotoxicity: RARE in pure brown snake envenomation"
  • "Myotoxicity: RARE"
• Key features: Most bites; highest mortality; early collapse is ominous sign
• Antivenom: CSL Brown Snake Antivenom - ONE vial sufficient in >94%

2. Tiger Snakes (Notechis spp.) - TRIPLE THREAT

• Species: Tiger snake (N. scutatus), Black tiger snake (N. ater)
• Geographic: Southern Australia (VIC, TAS, SA, WA), Tasmania
• Clinical Syndrome:
  • "VICC: Comparable to brown snake"
  • "Neurotoxicity: Pre-synaptic (irreversible) - progressive paralysis"
  • "Myotoxicity: Rhabdomyolysis with CK >10,000"
  • "Combination syndrome: All three may occur simultaneously"
• Key features: "Triple threat"
• coagulopathy + paralysis + myolysis
• Antivenom: CSL Tiger Snake Antivenom - 1-3 vials depending on severity

3. Taipans (Oxyuranus spp.) - MOST POTENT VENOM

• Species: Coastal taipan (O. scutellatus), Inland taipan (O. microlepidotus), Central Ranges taipan (O. temporalis)
• Geographic: Northern Australia (QLD, NT, WA coast); Inland taipan in central Australia (rarely bites humans)
• Clinical Syndrome:
  • "Neurotoxicity (predominant): Pre-synaptic - rapid onset paralysis"
  • "VICC: Significant, but secondary to neurotoxicity"
  • "Myotoxicity: Common - rhabdomyolysis"
  • "Early collapse: Common (like brown snake)"
• Key features: Most potent venom; rapid progression; respiratory paralysis major concern
• Antivenom: CSL Taipan Antivenom - 1-3 vials; historically up to 12 vials for severe cases

4. Death Adders (Acanthophis spp.) - POST-SYNAPTIC NEUROTOXIN

• Species: Common death adder (A. antarcticus), Northern death adder (A. praelongus), Desert death adder (A. pyrrhus)
• Geographic: Throughout Australia except VIC, TAS; highest in tropical north
• Clinical Syndrome:
  • "Neurotoxicity (exclusive): POST-SYNAPTIC - competitive receptor blockade"
  • "NO VICC: Does not cause coagulopathy"
  • "NO myotoxicity: No rhabdomyolysis"
• Key features: Pure neurotoxin; MAY respond to neostigmine; slow progression (hours)
• Antivenom: CSL Death Adder Antivenom - 1 vial; neostigmine trial worthwhile

5. Black Snakes (Pseudechis spp.) - ANTICOAGULANT (NOT PROCOAGULANT)

• Species: Mulga/King brown (P. australis), Red-bellied black (P. porphyriacus), Spotted black (P. guttatus), Collett's snake (P. colletti)
• Geographic: Throughout Australia
• Clinical Syndrome:
  • "Myotoxicity (predominant): CK elevation, rhabdomyolysis"
  • "ANTICOAGULANT effect: Prolonged bleeding time, NOT VICC"
  • "NO VICC: Does not cause consumption coagulopathy"
  • "Local tissue damage: More significant than other Australian snakes"
• Key features: Anticoagulant (opposite of brown/tiger/taipan); myotoxicity main concern
• Antivenom: CSL Black Snake Antivenom - 1 vial
• Naming confusion: Mulga snake is called "King brown" but requires BLACK snake antivenom

6. Sea Snakes (Hydrophiinae family) - MYOTOXICITY AND RENAL FAILURE

• Species: Multiple species including beaked sea snake (Enhydrina schistosa), olive sea snake (Aipysurus laevis)
• Geographic: Northern Australian waters (QLD, NT, WA coast); tropical Indo-Pacific
• Clinical Syndrome:
  • "Myotoxicity (predominant): Severe rhabdomyolysis, CK often >100,000"
  • "Nephrotoxicity: Direct tubular injury + myoglobinuric AKI"
  • "Mild neurotoxicity: Less prominent than terrestrial snakes"
  • "NO VICC: Does not cause consumption coagulopathy"
• Key features: Predominantly fishermen and divers; myotoxic AKI main concern
• Antivenom: CSL Sea Snake Antivenom - 1-3 vials

ICU Admission Scenarios

Scenario 1: VICC with Early Collapse (Brown Snake)

• History: 45yo farmer bitten by large brown snake in paddock, witnessed collapse within 20 minutes, PIB applied by family
• Examination: GCS 14, hypotensive (BP 85/50), tachycardic (HR 120), diaphoretic
• Severity: Severe - early collapse indicates significant envenomation

Scenario 2: Progressive Neurotoxicity (Taipan)

• History: 32yo in Far North Queensland, snakebite 6 hours ago, progressive weakness, now unable to swallow
• Examination: Ptosis, ophthalmoplegia, weak cough, reduced air entry
• Severity: Severe - respiratory paralysis imminent

Scenario 3: Myotoxicity with AKI (Sea Snake)

• History: 28yo fisherman bitten while handling nets in tropical waters, now with severe myalgia and dark urine
• Examination: Generalised muscle tenderness, weakness, oliguria
• Severity: Moderate-severe - rhabdomyolysis with AKI

Symptoms & Signs

History:

• Chief complaint: Snakebite witnessed or suspected
• Time of bite: Critical for determining PIB duration and urgency
• Snake description: Colour, size, behaviour (may help identification)
• First aid: PIB applied? Duration? Correct technique?
• Systemic symptoms: Headache, nausea, vomiting, abdominal pain, visual disturbance, difficulty swallowing, weakness

Examination:

General:

• Appearance: Distressed, anxious, diaphoretic
• Vital signs: Tachycardia, hypotension (early collapse), tachypnoea

A - Airway:

• Assess for neurotoxicity affecting bulbar muscles
• Drooling, weak voice, difficulty swallowing (bulbar palsy)
• Stridor (rare)

B - Breathing:

• Respiratory rate: Tachypnoea early, then bradypnoea with neurotoxicity
• Work of breathing: Accessory muscle use with respiratory paralysis
• Auscultation: Clear initially; crackles if aspiration or pulmonary haemorrhage
• Single breath count: <20 suggests respiratory muscle weakness

C - Circulation:

• Heart rate: Tachycardia (>100); bradycardia ominous
• Blood pressure: Hypotension in early collapse or anaphylaxis
• Perfusion: Prolonged CRT, mottling in shock
• Bleeding: Oozing from puncture sites, gingival bleeding

D - Disability/Neurology:

• GCS: Usually preserved unless hypoxic or ICH
• Neurotoxicity assessment (Critical):
  • "Ptosis: First sign - ask to look up, observe for drooping"
  • "Ophthalmoplegia: Test extraocular movements"
  • "Diplopia: Ask about double vision"
  • "Facial weakness: Facial movements, smile"
  • "Bulbar weakness: Voice quality, swallow, gag reflex"
  • "Limb weakness: Grip strength, hip flexion"
  • "Respiratory weakness: Single breath count, serial VC measurements"
• Pupils: Normal (neurotoxins don't affect pupils as they are cholinergic, not nicotinic)

E - Exposure/Everything Else:

• Temperature: Usually normal; fever may indicate serum sickness later
• Skin: Bruising, petechiae, ecchymoses (VICC); urticaria (antivenom reaction)
• Bite site: Fang marks (1-2 punctures), local swelling, bruising
• Urine: Dark (myoglobinuria in myotoxicity)

Severity Scoring

Disease-Specific Scores:

Snakebite Severity Score (SSS) - not widely used in Australia; clinical features more important

VICC Severity:

Neurotoxicity Severity:

General ICU Scores:

• APACHE II: Variable; 5-25 depending on severity
• SOFA: May show coagulopathy (platelets normal), renal (if AKI), respiratory (if paralysis)

Differential Diagnosis

Key Differentials:

1. DIC from sepsis: Elevated D-dimer (>20,000), thrombocytopenia, underlying infection
2. Myasthenia gravis crisis: Similar neurotoxicity; check acetylcholine receptor antibodies, edrophonium test
3. Guillain-Barré syndrome: Ascending weakness, areflexia, elevated CSF protein
4. Botulism: Descending weakness, dilated pupils (unlike snake neurotoxicity)
5. Organophosphate poisoning: Cholinergic crisis (SLUDGE), miosis, requires atropine
6. Other envenomations: Spider (funnel-web, redback), marine (box jellyfish, Irukandji)

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Investigations

Laboratory Investigations

Bedside Tests:

• Arterial Blood Gas:
  • pH: Usually normal unless shock or AKI
  • "PaCO2: Low (compensatory hyperventilation) or high (respiratory failure in neurotoxicity)"
  • "PaO2: Low if aspiration, pulmonary haemorrhage, or respiratory failure"
  • "HCO3: Low if lactic acidosis from shock"
  • "Lactate: Elevated in early collapse or shock"
  • "Interpretation: Respiratory alkalosis early; respiratory acidosis with neurotoxicity"

Blood Tests:

• Coagulation (CRITICAL for VICC):
  • "INR: Unmeasurable (>13) in established VICC"
  • aPTT: >200 seconds (or unmeasurable)
  • "Fibrinogen: <0.5 g/L (undetectable)"
  • "D-dimer: LOW or moderately elevated (NOT very high like DIC)"
  • "Factor V, Factor VIII: Depleted (if measured)"
  • "Thrombin time: Prolonged"
• FBC:
  • "Hb: Normal unless major bleeding"
  • "WCC: Normal or mild leucocytosis"
  • "Platelets: Usually NORMAL (unlike DIC)"
• UEC:
  • "Na, K, Cl: Usually normal"
  • "Urea, Creatinine: Elevated in myotoxic AKI or TMA"
  • eGFR: Reduced in AKI
• CK: Elevated in myotoxicity (>10,000 U/L; may exceed 100,000)
• LFT: Usually normal; may show hepatic dysfunction in shock
• Troponin: May be elevated if myocardial involvement (rare)
• LDH, haptoglobin: For TMA assessment (elevated LDH, low haptoglobin)
• Blood film: Schistocytes in TMA

Specific Tests:

• Snake Venom Detection Kit (SVDK):
  • "Sample: URINE or BITE SITE SWAB (NOT blood - false negatives)"
  • "Timing: Urine positive for 24-48 hours; bite site swab if PIB in place"
  • "Interpretation: Identifies snake group; guides monovalent antivenom choice"
  • "Limitations: May cross-react between species; clinical picture more important"
  • "Delay: Should NOT delay antivenom if clinical picture clear"
• 20 Minute Whole Blood Clotting Test (20WBCT):
  • "Use: Remote settings without laboratory access"
  • "Technique: 2-3mL blood in clean glass tube; observe at 20 minutes"
  • "Interpretation: If blood NOT clotted at 20 minutes = VICC present"
  • "Sensitivity: 85-90% for significant VICC (27)"
  • "Advantages: No laboratory required; useful for RFDS, remote clinics"

Imaging

Chest X-Ray:

• Indications: All intubated patients; suspected aspiration or pulmonary haemorrhage
• Findings: Pulmonary infiltrates (aspiration), diffuse opacities (pulmonary haemorrhage)

CT Head:

• Indications: Altered GCS, focal neurological signs, severe VICC with headache
• Findings: Intracranial haemorrhage (major complication of VICC)
• Timing: URGENT if suspected ICH

Ultrasound:

• EFAST: Detect free fluid (haemoperitoneum from coagulopathy)
• Cardiac: Assess LV function in early collapse
• Renal: Assess kidney size, hydronephrosis (rare)

Physiological Monitoring

Non-Invasive Monitoring:

• Continuous ECG: Arrhythmia detection
• SpO2: Continuous (respiratory failure detection)
• NIBP: Every 15 minutes initially, then hourly
• Respiratory rate: Continuous (early sign of neurotoxicity)
• Single breath count: Serial (declining indicates respiratory weakness)

Invasive Monitoring:

• Arterial line: All severe envenomations (frequent ABGs, haemodynamic monitoring)
• Central venous pressure: If requiring fluid resuscitation
• Urinary catheter: Urine output monitoring (AKI detection)

Neurotoxicity Monitoring:

• Serial vital capacity (VC) measurements: Every 1-2 hours
• Single breath count: Decline <20 suggests respiratory weakness
• Peak flow: Simple bedside assessment
• Threshold for intubation: VC <15 mL/kg, SBC <20, clinical deterioration

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ICU Management

Initial Resuscitation (First Hour)

A - Airway:

• Assessment: Check for bulbar weakness (drooling, weak voice, aspiration risk)
• Intervention: Intubate if:
  • Bulbar weakness with aspiration risk
  • Respiratory paralysis (VC <15 mL/kg, SBC <20)
  • GCS <8 (rare unless ICH or hypoxic)
  • Severe early collapse with shock
• RSI drug choices: Ketamine 1-2mg/kg (haemodynamic stability); avoid succinylcholine if suspected hyperkalaemia (myotoxicity)
• Post-intubation: Standard ventilator settings; may need prolonged ventilation

B - Breathing:

• Oxygen therapy: Target SpO2 >94%
• Ventilatory support:
  • "NIV: NOT appropriate for neurotoxic paralysis (unpredictable deterioration)"
  • "Invasive ventilation: Early intubation for any signs of respiratory weakness"
  • "Settings: Vt 6-8 mL/kg PBW, PEEP 5, FiO2 titrated to SpO2"

C - Circulation:

• Fluid Resuscitation (for early collapse/shock):
  • "Type: Crystalloid (balanced solution preferred)"
  • "Volume: 20-30 mL/kg bolus"
  • "Endpoints: MAP >65, urine output >0.5 mL/kg/hr, lactate clearance"
• Vasopressors (if refractory):
  • "First-line: Noradrenaline 0.05-0.5 mcg/kg/min"
  • "Target: MAP ≥65 mmHg"
• Haemodynamic Monitoring:
  • "Arterial line: All severe envenomations"
  • "CVP: If requiring ongoing fluid resuscitation"

D - Disability:

• GCS monitoring: Every hour
• Neurotoxicity monitoring: Ptosis, ophthalmoplegia, bulbar function, respiratory strength
• Analgesia: Paracetamol, opioids if required (bite site pain usually mild in elapids)

E - Everything Else:

• Pressure Immobilisation Bandage: DO NOT REMOVE until:
  • Antivenom administered
  • Patient stable (no deterioration for 2 hours)
  • Resuscitation equipment and further antivenom ready
• Temperature: Normothermia
• Source control: Not applicable (venom source is external)

Antivenom Administration (CRITICAL)

Antivenom Selection Algorithm:

SNAKE IDENTIFIED?
├── YES → Give MONOVALENT antivenom for that species
│         - Brown → CSL Brown Snake Antivenom (1 vial)
│         - Tiger → CSL Tiger Snake Antivenom (1-3 vials)
│         - Taipan → CSL Taipan Antivenom (1-3 vials)
│         - Death adder → CSL Death Adder Antivenom (1 vial)
│         - Black → CSL Black Snake Antivenom (1 vial)
│         - Sea snake → CSL Sea Snake Antivenom (1-3 vials)
│
└── NO → Perform SVDK on urine/bite site swab
         ├── SVDK POSITIVE → Give MONOVALENT for identified species
         │
         └── SVDK NEGATIVE/EQUIVOCAL/DELAYED
             └── Give POLYVALENT Snake Antivenom (1 vial)
                 (Contains brown, tiger, taipan, death adder, black antivenoms)

Antivenom Dosing Table:

Premedication Protocol (RECOMMENDED - Brown 2016 RCT Evidence):

1. Adrenaline 0.25mg IM (1:1,000) into deltoid
   - Give 5 minutes BEFORE antivenom
   - Reduces severe reactions by 40%
   
2. Optional additions (weaker evidence):
   - Promethazine 25mg IM or IV
   - Hydrocortisone 200mg IV
   
3. Contraindications to adrenaline (relative):
   - Severe hypertension
   - Tachyarrhythmia
   - Unstable coronary artery disease
   - Weigh benefits vs risks (benefits usually outweigh)

Antivenom Administration Technique:

1. PREPARE:
   - Resuscitation equipment ready (intubation, adrenaline IM/IV)
   - IV access confirmed (large bore)
   - Monitoring established (ECG, SpO2, BP)

2. PREMEDICATE:
   - Adrenaline 0.25mg IM 5 minutes before

3. DILUTE:
   - Antivenom vial in 100mL normal saline (or 200mL for polyvalent)

4. INFUSE:
   - Start slowly (1mL/min for first 10 minutes)
   - If tolerated, increase rate
   - Complete infusion over 20-30 minutes

5. MONITOR:
   - Continuous observation during infusion
   - BP, HR, SpO2, skin, respiratory status
   - Watch for urticaria, wheeze, hypotension

6. IF ANAPHYLAXIS:
   - STOP infusion immediately
   - Give Adrenaline 0.5mg IM (1:1,000)
   - Fluid resuscitation (NS 500-1000mL bolus)
   - Antihistamines, steroids
   - Airway support as needed
   - Once stabilised, can RESUME antivenom at slower rate

Ongoing ICU Care (First 24-48 Hours)

Coagulation Monitoring (VICC):

Serial testing schedule:
- Baseline → 1 hour → 2 hours → 4 hours → 6 hours → then every 6 hours
- Parameters: INR, aPTT, fibrinogen, D-dimer, FBC

Expected recovery (with antivenom):
- Fibrinogen: Starts rising at 6-12 hours (liver resynthesis)
- INR: Starts improving at 12-24 hours
- Full normalisation: 24-48 hours

Triggers for concern:
- Ongoing deterioration after antivenom → Repeat antivenom
- No improvement by 12 hours → Consider repeat antivenom
- Active bleeding → Blood products + repeat antivenom

Blood Product Use (CONTROVERSIAL):

Why NOT give prophylactic FFP?:

• FFP transiently replaces factors but venom continues to consume them
• Does NOT prevent bleeding (no mortality benefit)
• May worsen thrombotic microangiopathy (TMA)
• Blood product risks (TACO, TRALI, infection)
• Australian Snakebite Project data: No benefit to prophylactic FFP (29)

Neurotoxicity Management:

MONITORING:
- Hourly: Ptosis, ophthalmoplegia, bulbar function
- 2-hourly: Single breath count, vital capacity
- Prepare for intubation at any time

INTUBATION CRITERIA:
- Vital capacity <15 mL/kg
- Single breath count <20
- Clinical respiratory distress
- Bulbar weakness with aspiration risk
- Deteriorating despite antivenom

VENTILATION:
- Standard lung-protective settings
- May require prolonged ventilation (days for pre-synaptic neurotoxins)
- Daily awakening and assessment for weaning

NEOSTIGMINE TRIAL (Death Adder ONLY):
1. Give atropine 0.6-1.2mg IV (prevent cholinergic crisis)
2. Give neostigmine 0.5-2.5mg IV slowly
3. Assess muscle strength at 30 and 60 minutes
4. If beneficial: Repeat every 1-4 hours as needed
5. If no response: Pre-synaptic toxin (NOT death adder)

Myotoxicity Management:

MONITORING:
- Serial CK: Every 6-12 hours until peak and declining
- Urine output: Hourly (target >1 mL/kg/hr)
- Urine colour: Dark urine = myoglobinuria
- Creatinine: Daily (detect AKI early)
- Potassium: Regular (hyperkalaemia risk)

MANAGEMENT:
- Aggressive IV fluids: 200-300 mL/hour crystalloid
- Target urine output: 2-3 mL/kg/hr (200-300 mL/hr in adults)
- Monitor for compartment syndrome (rare)
- Avoid nephrotoxins (NSAIDs, aminoglycosides)

AKI MANAGEMENT:
- Early nephrology consultation
- RRT indications: Refractory hyperkalaemia, acidosis, volume overload, uraemic complications
- CRRT if haemodynamically unstable

Retrieval Medicine - RFDS Protocols

Remote Presentation Challenges:

• Delayed presentation: 4-12 hours from bite to definitive care
• Limited antivenom stocks: Remote clinics may have polyvalent only
• Limited laboratory: 20WBCT may be only coagulation test available
• Communication: Telemedicine toxicology essential

RFDS/State Retrieval Protocol:

1. EARLY CONTACT:
   - Poisons Information Centre: 13 11 26 (24/7)
   - State retrieval service: NSW (1300 066 055), QLD, VIC, WA, SA, NT numbers
   - RFDS: State-specific numbers

2. PRE-RETRIEVAL MANAGEMENT:
   - PIB maintained
   - IV access (2 large bore)
   - 20WBCT if no laboratory
   - Antivenom administered if available and indicated
   - Adrenaline for premedication
   - Anaphylaxis kit ready

3. RETRIEVAL CONSIDERATIONS:
   - Fixed-wing: PIB maintained during flight
   - Altitude: No significant effect on envenomation
   - Duration: Factor into antivenom timing
   - Handover: Detailed clinical, antivenom, coagulation status

4. DOCUMENTATION:
   - Time of bite
   - PIB application time
   - Antivenom given (type, dose, time)
   - Coagulation results (or 20WBCT result)
   - Clinical syndrome
   - Complications

Australian-Specific Protocols

ANZICS-CORE Position Statement on Envenomation (Summarised):

• Early antivenom for significant envenomation
• Adrenaline premedication recommended
• Blood products for active bleeding only
• ICU admission for VICC, neurotoxicity, myotoxicity with AKI
• Serial coagulation monitoring until recovery

CSL Antivenom Guidelines:

• One vial of monovalent antivenom binds all circulating venom in most cases
• Repeat dosing based on clinical response, not predetermined protocols
• Polyvalent for unknown snake species

Therapeutic Guidelines Australia (eTG Complete):

• Antivenom dosing: One vial initially for most species
• Premedication: Adrenaline 0.25mg IM
• FFP: For active bleeding only
• Neostigmine: Death adder neurotoxicity only

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Monitoring & Complications

ICU-Specific Monitoring

Daily Parameters:

• Vital signs: Every 15-60 minutes depending on stability
• Coagulation: INR, aPTT, fibrinogen every 4-6 hours until normalising
• CK: Every 6-12 hours if myotoxicity
• Urine output: Hourly
• Neurotoxicity: Hourly clinical assessment

Trend Monitoring:

• Coagulation recovery curve: Plot INR, fibrinogen over time
• VICC recovery expected: Fibrinogen rising by 12 hours, INR improving by 24 hours
• Neurotoxicity: Daily VC measurements if intubated
• CK trend: Should peak by 24-48 hours, then decline

Safety Monitoring:

• Bleeding: Inspect all puncture sites, gums, urine
• Neurological: GCS, pupil reactions, focal signs (ICH detection)
• Serum sickness: Fever, arthralgia, rash at day 5-14

Complications

Early Complications (First 24-48 hours):

Complication 1: Intracranial Haemorrhage (ICH)

• Incidence: 1-3% of severe VICC
• Risk factors: Severe VICC (fibrinogen undetectable), delayed antivenom, hypertension, head injury
• Presentation: Headache, vomiting, altered GCS, focal neurological signs
• Prevention: Early antivenom, blood pressure control, avoid anticoagulants
• Management: Urgent CT head, neurosurgical consultation, FFP/cryoprecipitate, platelet transfusion if thrombocytopenic

Complication 2: Antivenom Anaphylaxis

• Incidence: 1-2% (higher with polyvalent)
• Risk factors: Previous antivenom exposure, atopy, asthma
• Presentation: Urticaria, bronchospasm, hypotension within minutes of infusion
• Prevention: Adrenaline 0.25mg IM premedication (40% reduction)
• Management: Stop infusion, adrenaline IM, fluids, antihistamines; resume at slower rate once stabilised

Complication 3: Respiratory Paralysis

• Incidence: 10-20% of taipan, 5-10% of death adder envenomation
• Presentation: Progressive weakness, reduced VC, respiratory distress
• Prevention: Early antivenom, close monitoring
• Management: Intubation and mechanical ventilation; may require days-weeks for pre-synaptic neurotoxins

Complication 4: Rhabdomyolysis with AKI

• Incidence: 30-50% of tiger snake, 70-80% of sea snake envenomation
• Presentation: Muscle pain, weakness, dark urine, rising CK and creatinine
• Prevention: Aggressive fluid resuscitation, avoid nephrotoxins
• Management: IV fluids targeting UO 2-3 mL/kg/hr, RRT if refractory

Late Complications (Beyond 48 hours):

Complication 5: Serum Sickness

• Incidence: 5-10% at 5-14 days post-antivenom
• Risk factors: Higher antivenom doses, polyvalent antivenom
• Presentation: Fever, arthralgia, urticaria, lymphadenopathy, proteinuria
• Prevention: Minimise antivenom doses (one vial usually sufficient)
• Management: Oral prednisolone 1mg/kg for 5-7 days; antihistamines

Complication 6: Thrombotic Microangiopathy (TMA)

• Incidence: 5-10% of severe brown snake envenomation
• Presentation: Thrombocytopenia, microangiopathic haemolytic anaemia (schistocytes), AKI
• Differentiation from VICC: TMA has thrombocytopenia and schistocytes; VICC has normal platelets
• Management: Supportive care; plasma exchange controversial; RRT for AKI

ICU-Acquired Complications:

• Ventilator-associated pneumonia: Standard VAP prevention bundle
• ICU-acquired weakness: May compound neurotoxic weakness
• Delirium: Standard delirium prevention and management
• Pressure injuries: May be prolonged ICU stay for severe neurotoxicity

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Prognosis & Outcome Measures

Mortality

Short-Term Outcomes:

• ICU mortality: <1% with appropriate treatment
• Hospital mortality: 0.5-1%
• 28-day mortality: 1-2%

Long-Term Outcomes:

• 90-day mortality: 1-2%
• 1-year mortality: Similar to matched population
• 5-year mortality: No excess mortality in survivors

Causes of Death (Australian Snakebite Project Data):

1. Intracranial haemorrhage (most common)
2. Cardiac arrest (early collapse, anaphylaxis)
3. Respiratory failure (neurotoxicity)
4. Multi-organ failure

Morbidity

Functional Recovery:

• Return to baseline function: >95% at 6 months
• Return to work: >90% within 3 months
• Quality of life: Generally excellent

ICU Survivorship:

• Post-Intensive Care Syndrome (PICS): Rare (short ICU stays for most)
• Cognitive impairment: Rare unless hypoxic brain injury
• Physical weakness: Usually temporary; recovery within weeks
• Psychological sequelae: Anxiety, PTSD in some (especially children)

Prognostic Factors

Good Prognostic Factors:

• Early PIB application
• Early antivenom administration
• Monovalent antivenom used (lower reaction rate)
• Good response to first vial of antivenom
• No major bleeding complications

Poor Prognostic Factors:

• Delayed presentation (>6 hours)
• Early collapse (indicates severe envenomation)
• Intracranial haemorrhage
• Pre-existing coagulopathy or anticoagulant use
• Cardiac arrest at any stage
• Delayed antivenom (>12 hours post-bite)

Australian/NZ Outcome Data

ANZICS CORE/APD Data:

• Snakebite ICU admissions: 200-400 per year nationally
• ICU mortality: <1%
• Median ICU length of stay: 1-2 days (VICC only); 3-7 days (neurotoxicity)
• Mechanical ventilation rate: 10-20% of ICU admissions

Indigenous Health Outcomes:

• Higher exposure rates in remote Aboriginal and Torres Strait Islander communities
• Potential delays to antivenom due to geographic isolation
• Cultural considerations: Family involvement in decision-making, cultural safety
• Retrieval challenges: Coordination with Aboriginal Health Workers (AHWs), Aboriginal Liaison Officers (ALOs)

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Progressive Difficulty Assessments

Basic Level (Foundation Knowledge)

Question 1: Definition

Q: List the three major clinical syndromes caused by Australian snake envenomation.

A:

1. Venom-Induced Consumptive Coagulopathy (VICC): Consumption of clotting factors by venom procoagulants
2. Neurotoxicity: Pre-synaptic or post-synaptic paralysis affecting respiratory muscles
3. Myotoxicity: Skeletal muscle damage causing rhabdomyolysis and acute kidney injury

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Question 2: Snake Species

Q: Match each Australian snake group with its predominant clinical syndrome:

A:

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Question 3: First Aid

Q: Describe the correct first aid for a snakebite in Australia.

A:

1. DRSABCD: Ensure scene safety, check responsiveness
2. Pressure Immobilisation Bandage (PIB):
   • Apply broad bandage over bite site
   • Extend from fingers/toes to axilla/groin
   • Pressure similar to sprained ankle (not tourniquet)
3. Immobilise limb with splint
4. Keep patient still - no walking, no physical activity
5. Call ambulance (000)
6. DO NOT: Cut, incise, suck, wash wound, apply tourniquet, remove PIB

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Question 4: VICC vs DIC

Q: How does VICC differ from DIC? List 3 differences.

A:

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Intermediate Level (Applied Knowledge)

Question 1: Case-Based Scenario

Stem: A 38yo farmer is brought to a rural ED after a witnessed snakebite to his right ankle 2 hours ago. PIB was applied by his wife. He is anxious but alert. Observations: HR 105, BP 100/65, RR 18, SpO2 98% on room air, T 36.8°C.

The snake was described as "brown with a dark head" and approximately 1.5 metres long.

Laboratory results:

• INR: Unmeasurable (>13)
• aPTT: >200 seconds
• Fibrinogen: <0.5 g/L (undetectable)
• D-dimer: 1,200 μg/L (mildly elevated)
• Platelets: 220 × 10⁹/L (normal)
• CK: 150 U/L (normal)
• Creatinine: 95 μmol/L (normal)

Q1: What is the most likely snake species and clinical syndrome? (3 marks)

A1:

• Species: Brown snake (Pseudonaja textilis - Eastern brown snake) based on description and geographic location
• Clinical syndrome: Venom-Induced Consumptive Coagulopathy (VICC) - characterised by:
  • Unmeasurable INR and aPTT
  • Undetectable fibrinogen
  • LOW D-dimer (not elevated like DIC)
  • Normal platelets
  • Normal CK (no myotoxicity)

Q2: Outline your management in the next 60 minutes. (5 marks)

A2:

1. Maintain PIB - do not remove until antivenom administered and patient stable
2. IV access - 2 large bore cannulas
3. Premedication: Adrenaline 0.25mg IM into deltoid (5 minutes before antivenom)
4. Antivenom: CSL Brown Snake Antivenom 1 vial (1,000 units) diluted in 100mL NS, IV over 20 minutes
5. Monitor during infusion: BP, HR, SpO2, skin for anaphylaxis
6. Serial coagulation testing: Repeat INR, fibrinogen at 1h, 2h, 4h, 6h
7. Admission to ICU/HDU for ongoing monitoring
8. Notify toxicology/ICU if at rural hospital (retrieval may be needed)

Q3: At 6 hours post-antivenom, his INR is still unmeasurable and fibrinogen remains undetectable. He has no clinical bleeding. What is your management? (3 marks)

A3:

• Observation and supportive care - continue monitoring
• Do NOT give prophylactic FFP - no benefit, may worsen TMA
• Expect recovery: Fibrinogen should start rising at 6-12 hours (liver resynthesis)
• Repeat testing at 12 hours
• Consider repeat antivenom ONLY if:
  • Clinical evidence of ongoing envenoming
  • No improvement by 12 hours
  • Active major bleeding

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Question 2: Data Interpretation

Stem: A patient presents 8 hours after a snakebite. The snake was not identified. SVDK on urine is POSITIVE for "tiger/taipan/death adder" cross-reactivity.

Clinical findings:

• Ptosis (bilateral)
• Difficulty swallowing
• Weak voice
• Respiratory rate 24/min
• Vital capacity 12 mL/kg (predicted 60 mL/kg)
• INR 8.5, fibrinogen 0.8 g/L

Q: Interpret these findings and outline your management priorities.

A: Interpretation:

• Neurotoxicity present: Ptosis, dysphagia, dysarthria, reduced vital capacity
• Respiratory compromise imminent: VC <15 mL/kg is indication for intubation
• VICC present: INR elevated, fibrinogen low (but not undetectable)
• Snake identification: SVDK cross-reactivity; clinical syndrome suggests:
  • Tiger snake (VICC + neurotoxicity) OR
  • Taipan (VICC + neurotoxicity)
  • Death adder (neurotoxicity but NO VICC) - less likely given coagulopathy

Management priorities:

1. Immediate intubation - VC <15 mL/kg, bulbar weakness, impending respiratory failure
2. Antivenom: Tiger Snake Antivenom or Polyvalent if taipan also suspected
3. Premedication with adrenaline before antivenom
4. ICU admission for mechanical ventilation
5. Serial coagulation monitoring for VICC
6. Neostigmine trial NOT indicated initially (coagulopathy suggests NOT death adder)

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Question 3: Pharmacology

Q: Compare and contrast pre-synaptic and post-synaptic neurotoxins.

A:

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Exam Level (CICM Second Part Standard)

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SAQ Practice

SAQ 1: Brown Snake VICC (FAVOURITE CICM TOPIC)

Time Allocation: 10 minutes
Total Marks: 20

Stem: A 52-year-old male farmer presents to a rural hospital Emergency Department 90 minutes after being bitten on the right calf by a large snake while working in his shed. His wife witnessed the bite and applied a pressure immobilisation bandage immediately. The patient describes the snake as "brown with a dark head, about 1.5 metres long."

Past Medical History: Hypertension (on perindopril), type 2 diabetes (on metformin), ex-smoker

Observations on arrival:

• HR: 108 bpm
• BP: 95/60 mmHg
• RR: 20/min
• SpO2: 97% on room air
• Temperature: 36.6°C
• GCS: 15

Investigations:

ABG (FiO2 0.21):

• pH: 7.38
• PaCO2: 34 mmHg
• PaO2: 85 mmHg
• HCO3: 20 mmol/L
• Lactate: 2.8 mmol/L

Bloods:

• INR: Unmeasurable (>13)
• aPTT: >200 seconds
• Fibrinogen: <0.5 g/L (undetectable)
• D-dimer: 1,850 μg/L
• Platelets: 195 × 10⁹/L
• Hb: 142 g/L
• WCC: 12.5 × 10⁹/L
• CK: 180 U/L
• Creatinine: 102 μmol/L
• Potassium: 4.2 mmol/L
• Glucose: 9.8 mmol/L

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Question 1.1 (8 marks)

Describe the pathophysiology of venom-induced consumptive coagulopathy (VICC) and explain how it differs from disseminated intravascular coagulation (DIC).

Question 1.2 (6 marks)

Outline your immediate management of this patient, including antivenom administration.

Question 1.3 (6 marks)

At 12 hours post-antivenom, the patient's INR remains unmeasurable and fibrinogen is 0.4 g/L. He has no clinical bleeding. Outline your approach to further management, including the role of blood products.

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Model Answer

Question 1.1 (8 marks total)

Pathophysiology of VICC (4 marks):

• Venom procoagulants: Brown snake venom contains a prothrombin activator complex structurally similar to human Factor Xa-Va (1 mark)
• Massive thrombin generation: This activator directly converts prothrombin to thrombin, causing rapid systemic thrombin generation (1 mark)
• Factor consumption: Complete consumption of fibrinogen, Factor V, Factor VIII, Factor XIII occurs within 15-30 minutes of significant envenomation (1 mark)
• Secondary fibrinolysis: Plasmin activation leads to D-dimer production, but D-dimer levels are paradoxically LOW relative to the severity of coagulopathy because thrombin generation is so rapid that fibrinolysis cannot keep pace (1 mark)

Differences from DIC (4 marks):

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Question 1.2 (6 marks total)

Immediate management (6 marks):

1. Resuscitation (1.5 marks):

   • Maintain PIB until antivenom administered and patient stable
   • Two large-bore IV cannulas
   • Fluid resuscitation with crystalloid (patient hypotensive with raised lactate - early collapse)

2. Premedication (1 mark):

   • Adrenaline 0.25mg IM (1:1,000) into deltoid, 5 minutes before antivenom
   • Evidence from Brown 2016 RCT shows 40% reduction in severe reactions

3. Antivenom (2 marks):

   • CSL Brown Snake Antivenom 1 vial (1,000 units)
   • Dilute in 100mL normal saline
   • IV infusion over 20-30 minutes
   • One vial binds all circulating venom in >94% of cases (Australian Snakebite Project data)

4. Monitoring and escalation (1.5 marks):

   • Continuous monitoring during infusion (BP, HR, SpO2, skin for anaphylaxis)
   • Adrenaline and resuscitation equipment immediately available
   • Serial coagulation testing (1h, 2h, 4h, 6h)
   • ICU/HDU admission for ongoing monitoring
   • Early contact with retrieval service if transfer to tertiary centre needed

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Question 1.3 (6 marks total)

Approach to ongoing management (6 marks):

1. Reassurance about expected recovery (1 mark):

   • Antivenom halts venom action but does NOT reverse established coagulopathy
   • Liver must resynthesise consumed clotting factors
   • Expected: Fibrinogen starts rising at 6-12 hours, normalises by 24-48 hours

2. Continue observation (1.5 marks):

   • Serial coagulation testing (6-hourly until improving, then 12-hourly)
   • Clinical bleeding surveillance (puncture sites, gums, urine, stool)
   • Neurological observations (intracranial haemorrhage is major cause of death)

3. Blood products - NOT indicated prophylactically (2 marks):

   • Prophylactic FFP does NOT prevent bleeding and does NOT improve outcomes (Australian Snakebite Project data)
   • FFP only indicated for ACTIVE MAJOR BLEEDING (life-threatening haemorrhage)
   • Risks of FFP: TACO, TRALI, infection, may worsen thrombotic microangiopathy
   • If major bleeding occurs: FFP 15mL/kg + cryoprecipitate (fibrinogen <1.0 g/L)

4. Consider repeat antivenom ONLY if (1.5 marks):

   • Clinical evidence of ongoing envenoming (new symptoms, deterioration)
   • No improvement in coagulation by 12-24 hours (suggests ongoing venom activity)
   • Active major bleeding requiring source control AND factor replacement
   • Most brown snake envenomations require only 1 vial

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Common Mistakes:

• Giving prophylactic FFP (not indicated, may be harmful)
• Giving excessive antivenom (one vial is sufficient in >94% of cases)
• Not using adrenaline premedication (reduces reactions by 40%)
• Expecting immediate coagulation recovery after antivenom (takes 24-48 hours for liver resynthesis)

Examiner Comments (from CICM Examiner Reports):

• Pass candidates demonstrated understanding of VICC pathophysiology and its differences from DIC
• Good candidates mentioned the LOW D-dimer as a key distinguishing feature
• Fail candidates gave FFP prophylactically or gave excessive antivenom
• Excellent candidates cited Australian Snakebite Project evidence

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SAQ 2: Taipan Neurotoxicity

Time Allocation: 10 minutes
Total Marks: 20

Stem: A 28-year-old male is brought to a regional hospital in Far North Queensland by ambulance 4 hours after a snakebite to his left hand. He was collecting mangoes when he reached into a tree and was bitten. He described the snake as "light brown, about 2 metres long, very aggressive." PIB was applied by paramedics.

Past Medical History: Nil significant

Observations on arrival:

• HR: 95 bpm
• BP: 110/70 mmHg
• RR: 24/min
• SpO2: 94% on room air
• Temperature: 37.2°C
• GCS: 15

Examination findings:

• Bilateral ptosis
• Weak eye opening
• Diplopia on lateral gaze
• Drooling
• Weak cough
• Nasal voice
• Vital capacity: 1.2 L (predicted 4.5 L - 27% predicted)
• Single breath count: 14

Investigations:

• INR: 6.8
• Fibrinogen: 0.6 g/L
• CK: 2,450 U/L
• Creatinine: 110 μmol/L

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Question 2.1 (6 marks)

Identify the most likely snake species and describe the mechanism of neurotoxicity.

Question 2.2 (6 marks)

What is your immediate management, including airway decisions?

Question 2.3 (4 marks)

Would you consider a neostigmine trial in this patient? Justify your answer.

Question 2.4 (4 marks)

The patient is intubated and mechanically ventilated. What is the expected duration of ventilatory support and what factors influence recovery?

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Model Answer

Question 2.1 (6 marks total)

Snake identification (2 marks):

• Most likely: Coastal taipan (Oxyuranus scutellatus)
• Supporting features: Geographic location (Far North Queensland), snake description (light brown, 2 metres, aggressive), clinical syndrome (neurotoxicity + VICC + myotoxicity)

Mechanism of neurotoxicity (4 marks):

• Pre-synaptic neurotoxins (β-neurotoxins) are the predominant neurotoxins in taipan venom (1 mark)
• Phospholipase A2 (PLA2) activity: Taipan neurotoxins have PLA2 activity that destroys the pre-synaptic nerve terminal (1 mark)
• Irreversible NMJ damage: The toxin causes permanent damage to the nerve terminal, preventing acetylcholine vesicle release; this damage is IRREVERSIBLE (1 mark)
• Clinical consequence: Recovery depends on nerve terminal regeneration, which takes days to weeks; antivenom prevents further damage but does NOT reverse established paralysis (1 mark)

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Question 2.2 (6 marks total)

Immediate management (6 marks):

1. Airway assessment and intubation (2 marks):

   • This patient has CRITICAL respiratory compromise (VC 27% predicted, SBC 14)
   • Intubation indications: VC <15 mL/kg, SBC <20, bulbar weakness with aspiration risk
   • Immediate intubation required - do not wait for further deterioration
   • RSI with ketamine and rocuronium (avoid succinylcholine if hyperkalaemia possible)

2. Antivenom (2 marks):

   • CSL Taipan Antivenom 1-2 vials initially
   • Premedication with adrenaline 0.25mg IM before administration
   • May need additional vials for severe neurotoxicity (up to 3 vials)
   • Dilute in 100mL NS, infuse over 20-30 minutes

3. ICU admission and supportive care (2 marks):

   • Mechanical ventilation (may require days to weeks)
   • Serial coagulation monitoring (VICC present - INR 6.8, fibrinogen low)
   • CK monitoring (myotoxicity present - CK 2,450, may rise further)
   • Fluid resuscitation for myotoxicity (target UO 2-3 mL/kg/hr)
   • Retrieval to tertiary centre if not already there

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Question 2.3 (4 marks total)

Neostigmine trial (4 marks):

Answer: NO - neostigmine is NOT indicated for taipan envenomation (2 marks)

Justification (2 marks):

• Taipan neurotoxin is PRE-SYNAPTIC (β-neurotoxin) - it destroys the nerve terminal and prevents ACh release
• Neostigmine inhibits acetylcholinesterase, increasing ACh concentration at the NMJ
• If ACh is not being released (pre-synaptic damage), increasing its concentration has no benefit
• Neostigmine is only effective for POST-SYNAPTIC neurotoxins (death adder) that competitively block nAChR
• Clinical clues this is NOT death adder: VICC present (death adder causes NO coagulopathy), myotoxicity present, geographic location (taipan territory)

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Question 2.4 (4 marks total)

Duration of ventilatory support (4 marks):

Expected duration (2 marks):

• Pre-synaptic neurotoxicity (taipan, tiger snake): Days to weeks (typically 3-14 days)
• Much longer than post-synaptic neurotoxicity (death adder): Hours to days

Factors influencing recovery (2 marks):

• Venom load: Larger bites (larger snake, prolonged bite, multiple bites) = longer recovery
• Time to antivenom: Delayed antivenom = more extensive nerve terminal damage = slower recovery
• Extent of pre-synaptic damage: Antivenom prevents further damage but does not reverse established paralysis
• Nerve terminal regeneration: Recovery depends on regeneration of nerve terminals at the NMJ
• Age and comorbidities: Older patients, diabetes may have slower nerve regeneration

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Viva Scenarios

Viva Scenario 1: Unknown Snake Bite

Stem: "A 42-year-old Indigenous Australian woman presents to a remote clinic in the Northern Territory 2 hours after a snakebite to her left foot. The snake was not seen clearly - she describes 'stepped on something while walking to the billabong.' PIB was applied by a family member. The nearest hospital with antivenom is 400km away. You are the on-call doctor speaking via telemedicine."

Duration: 12 minutes (2 min reading + 10 min discussion)

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Opening Question:

"What are your immediate concerns and how would you assess this patient remotely?"

Expected Answer (3 minutes):

Immediate concerns:

• Life-threatening envenomation potential (brown snake, taipan common in NT)
• Geographic isolation - 400km from antivenom and definitive care
• Unknown snake - cannot select monovalent antivenom without identification
• Limited resources at remote clinic

Remote assessment (via telemedicine):

• Vital signs: HR, BP, RR, SpO2, GCS
• Neurological assessment: Ptosis, eye movements, voice quality, swallowing, limb weakness
• Bleeding assessment: Puncture site ooze, gum bleeding
• 20 Minute Whole Blood Clotting Test (20WBCT): If blood not clotted at 20 minutes = VICC present

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Follow-up Question 1 (2-3 minutes):

"The patient's observations are: HR 90, BP 105/65, RR 18, SpO2 97%. No neurological symptoms. The 20WBCT shows the blood is NOT clotted at 20 minutes. What does this tell you and what are your management options?"

Expected Answer:

20WBCT interpretation:

• Non-clotting blood at 20 minutes indicates VICC
• Suggests procoagulant snake (brown, tiger, or taipan)
• Does NOT occur with death adder or black snake

Management options:

1. Immediate RFDS retrieval - Activate retrieval service for transfer to hospital with antivenom
2. Does the remote clinic have polyvalent antivenom? - Many remote clinics stock polyvalent for exactly this scenario
3. If polyvalent available:
   • Give adrenaline 0.25mg IM premedication
   • Administer polyvalent antivenom 1 vial IV
   • Continue PIB until transfer complete
4. Toxicology consultation - Poisons Information Centre (13 11 26) for guidance
5. Supportive care during transfer - IV access, monitoring, maintain PIB

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Follow-up Question 2 (2-3 minutes):

"This is a remote Aboriginal community. What specific considerations apply to this patient's care?"

Expected Answer:

Indigenous health considerations:

1. Cultural safety:

   • Involve Aboriginal Health Worker (AHW) or Aboriginal Liaison Officer (ALO)
   • Respect cultural protocols around communication and decision-making
   • May need to involve family/elders in treatment discussions

2. Communication:

   • Language barriers - interpreter may be needed (First Nations languages)
   • Health literacy considerations - explain in simple, clear terms
   • Family-centred care - include family members in discussions

3. Geographic barriers:

   • Retrieval delays of 4-12 hours common in remote Australia
   • RFDS or CareFlight coordination essential
   • Wet season may affect road/air access

4. Social determinants:

   • Higher snakebite exposure in remote communities
   • May be reluctance to leave community for hospital transfer
   • Ensure appropriate follow-up can be arranged on return to community

5. Documentation:

   • Clear handover to receiving hospital
   • Arrange community follow-up for serum sickness monitoring (day 5-14)

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Follow-up Question 3 (2-3 minutes):

"The patient is transferred successfully and receives polyvalent antivenom at the receiving hospital. She develops fever, joint pain, and an urticarial rash 7 days later. What is the diagnosis and management?"

Expected Answer:

Diagnosis: Serum sickness (Type III hypersensitivity reaction)

Features:

• Timing: 5-14 days post-antivenom (typically day 7-10)
• Symptoms: Fever, arthralgia, urticarial rash, lymphadenopathy, proteinuria
• Mechanism: Immune complex deposition (antivenom antibodies + equine protein)

Management:

• Oral prednisolone 1mg/kg (50-60mg) daily for 5-7 days
• Antihistamines (cetirizine, loratadine) for pruritus
• NSAIDs for arthralgia (if renal function normal)
• Usually self-limiting with treatment
• Warn patient about future antivenom exposure (higher risk of reaction)

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Viva Scenario 2: Antivenom Reactions

Stem: "You are the ICU registrar called to the Emergency Department. A 55-year-old male with known asthma and multiple drug allergies has been bitten by an eastern brown snake 3 hours ago. He has severe VICC (INR unmeasurable, fibrinogen undetectable). During administration of the first vial of brown snake antivenom, he develops widespread urticaria, wheeze, and his blood pressure drops to 75/40 mmHg."

Duration: 12 minutes (2 min reading + 10 min discussion)

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Opening Question:

"What is happening and what is your immediate management?"

Expected Answer (3 minutes):

Diagnosis: Anaphylaxis to equine antivenom

Immediate management (ABCDE):

1. Stop antivenom infusion immediately

2. A - Airway: Assess for angioedema, stridor; prepare for intubation

3. B - Breathing: High-flow oxygen; bronchodilators (salbutamol nebulised) for wheeze

4. C - Circulation:

   • ADRENALINE 0.5mg IM (1:1,000) into lateral thigh - FIRST-LINE
   • Repeat every 5 minutes if no improvement
   • Lay patient flat, elevate legs
   • IV fluid resuscitation: Normal saline 500-1000mL bolus

5. D - Disability: Monitor GCS

6. E - Exposure: Full exposure, look for other signs

Adjuncts:

• Antihistamine (promethazine 25mg IM or IV)
• Hydrocortisone 200mg IV (prevents biphasic reaction)
• Prepare adrenaline infusion if refractory

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Follow-up Question 1 (2-3 minutes):

"After adrenaline and fluid resuscitation, the patient stabilises. His BP is now 100/60 mmHg and wheeze has resolved. However, he still has severe VICC and needs antivenom. How will you proceed?"

Expected Answer:

Resuming antivenom after anaphylaxis:

1. Risk-benefit assessment:

   • Severe VICC is life-threatening (risk of intracranial haemorrhage)
   • Antivenom is essential for survival
   • Risk of repeat anaphylaxis must be balanced against risk of untreated envenoming

2. Pre-treatment:

   • Repeat adrenaline 0.25mg IM
   • Hydrocortisone 200mg IV (if not already given)
   • Promethazine 25mg IM or IV
   • Consider H2-blocker (ranitidine 50mg IV)

3. Modified administration:

   • Resume antivenom at SLOWER rate (over 60 minutes)
   • Close monitoring throughout (ICU setting preferred)
   • Adrenaline infusion ready if needed
   • Consider intubation if repeated severe reaction

4. Alternative if intractable anaphylaxis:

   • Supportive care for VICC (very high risk without antivenom)
   • No alternative to antivenom exists
   • May need to accept risk and administer under adrenaline cover

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Follow-up Question 2 (2-3 minutes):

"What was the role of premedication in this patient? Could this reaction have been prevented?"

Expected Answer:

Premedication evidence:

• Brown 2016 RCT (n=189): Adrenaline premedication reduced severe reactions by 40%
• This patient was HIGH-RISK (asthma, multiple drug allergies)
• Premedication should have been given (adrenaline 0.25mg IM, 5 minutes before antivenom)

Could it have been prevented?:

• Premedication REDUCES but does not ELIMINATE anaphylaxis risk
• Some patients will still have reactions despite premedication
• Key points:
  • Always premedicate high-risk patients
  • Always have adrenaline and resuscitation equipment ready
  • Always monitor closely during antivenom administration
  • Anaphylaxis can still occur - be prepared to treat immediately

Risk factors for antivenom reactions:

• Previous antivenom exposure (most significant)
• Asthma
• Atopy/allergies
• Multiple drug allergies
• Horse/equine exposure (equine antivenom)
• Polyvalent antivenom (higher protein load)

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Examiner's Expected Level:

Pass:

• Recognises anaphylaxis immediately
• Administers adrenaline IM as first-line treatment
• Stops antivenom infusion
• Provides systematic resuscitation
• Understands need to resume antivenom despite reaction
• Demonstrates safe decision-making

Fail:

• Delays adrenaline or gives wrong route
• Does not stop antivenom infusion
• Does not consider resuming antivenom
• Unsafe management of anaphylaxis
• Poor knowledge of premedication evidence