Organophosphate Poisoning

Quick Answer

Organophosphate (OP) poisoning is a medical emergency requiring immediate antidotal therapy with atropine and pralidoxime. OPs cause irreversible inhibition of acetylcholinesterase (AChE), leading to accumulation of acetylcholine at muscarinic, nicotinic, and CNS receptors. Present with SLUDGE (Salivation, Lacrimation, Urination, Defecation, Gastrointestinal distress, Emesis) and the "Killer Bs" (Bronchorrhoea, Bronchospasm, Bradycardia). Atropine (1.2-2.4mg IV bolus, double every 5 min) treats muscarinic effects; Pralidoxime/2-PAM (30mg/kg loading, then 8-10mg/kg/h infusion) reactivates AChE if given before aging occurs. Respiratory failure from bronchorrhoea and muscle weakness is the primary cause of death. Key: Titrate atropine to dry airway and HR greater than 80 bpm, not pupil size.

ACEM Exam Focus

Primary Written: Focus on pharmacology of AChE inhibition, mechanism of atropine and oximes, SLUDGE mnemonic, and the concept of enzyme "aging."

Primary Viva: Applied physiology of cholinergic transmission, pharmacodynamics of muscarinic vs nicotinic receptors, and dose-response relationships for antidotes.

Fellowship Written: Clinical management priorities, antidote dosing regimens, recognition of intermediate syndrome, and complications of prolonged atropine therapy.

Fellowship OSCE:

• Resuscitation station: Managing airway in cholinergic crisis
• Communication: Discussing prognosis with family in intentional overdose
• Toxicology station: Calculating atropine infusion rates and interpreting cholinesterase levels

Key Points

1. Mechanism: OPs cause irreversible phosphorylation of AChE → acetylcholine accumulation → cholinergic crisis
2. "Killer Bs": Bronchorrhoea, Bronchospasm, Bradycardia are primary causes of mortality
3. Atropine: Titrate to dry lungs and HR greater than 80; do NOT use pupil size as endpoint
4. Pralidoxime: Must be given before "aging" (1-2 hours for dimethyl, 24-48 hours for diethyl OPs)
5. Intermediate Syndrome: Delayed proximal muscle weakness occurring 24-96 hours post-exposure
6. Seizures: Require benzodiazepines; may precipitate rhabdomyolysis and hyperthermia
7. Staff Safety: OPs are absorbed transdermally - wear PPE during decontamination

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Pathophysiology

Acetylcholinesterase Inhibition

Acetylcholinesterase (AChE) is the enzyme responsible for hydrolysing acetylcholine (ACh) at cholinergic synapses. Organophosphates are irreversible inhibitors of AChE through a two-step process:

Step 1: Phosphorylation

AChE + Organophosphate → AChE-OP Complex (inactive)

The OP molecule covalently binds to the serine hydroxyl group at the active site of AChE, preventing ACh hydrolysis.

Step 2: Aging

AChE-OP Complex → AChE-Aged Complex (permanently inactive)

Over time, the phosphorylated complex undergoes dealkylation (aging), becoming resistant to oxime therapy. The rate of aging varies between OP compounds:

• Dimethyl OPs: Rapid aging (1-2 hours) - e.g., dichlorvos, malathion
• Diethyl OPs: Slower aging (24-48 hours) - e.g., chlorpyrifos, diazinon, parathion

Receptor Overstimulation

Accumulation of ACh causes excessive stimulation at three receptor types:

Differential Effects

Muscarinic Effects (parasympathomimetic):

• Salivation (excessive drooling)
• Lacrimation (tearing)
• Urination (incontinence)
• Defecation (diarrhoea)
• Gastrointestinal cramps
• Emesis (vomiting)
• Miosis (pinpoint pupils)
• Bradycardia
• Bronchorrhoea (excessive secretions)
• Bronchospasm

Nicotinic Effects:

• Muscle fasciculations
• Weakness (proximal > distal)
• Tachycardia
• Hypertension
• Palpitations
• Diaphoresis

CNS Effects:

• Anxiety, agitation, restlessness
• Confusion, delirium
• Seizures (status epilepticus)
• Coma
• Respiratory centre depression

Clinical Syndrome Progression

Phase I: Acute Cholinergic Crisis (minutes to hours)
   → Muscarinic + Nicotinic + CNS symptoms
   → Peak at 6-12 hours post-ingestion

Phase II: Intermediate Syndrome (24-96 hours)
   → Proximal muscle weakness, cranial nerve palsies
   → Respiratory muscle weakness requiring ventilation
   → May occur despite adequate atropinisation

Phase III: Delayed Polyneuropathy (1-3 weeks)
   → Sensorimotor peripheral neuropathy
   → "Ginger jake" paralysis (historical)
   → Distal limb weakness, stocking-glove sensory loss

Metabolism and Elimination

OPs are metabolised primarily in the liver by cytochrome P450 enzymes, which can:

1. Activate some OPs to more toxic oxons (e.g., parathion → paraoxon)
2. Detoxify OPs to less toxic metabolites (e.g., malathion to monocarboxylic acids)

Elimination is primarily renal, with elimination half-lives ranging from 2-4 hours for water-soluble compounds to 24-48 hours for lipid-soluble compounds.

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Clinical Features

Presentation Timeline

Onset of Symptoms:

• Inhalation: Seconds to minutes
• Ingestion: 30 minutes to 6 hours
• Dermal absorption: 2-6 hours (up to 24 hours with clothing contamination)

Muscarinic Manifestations (SLUDGE + BBB)

Nicotinic Manifestations

CNS Manifestations

• Anxiety, restlessness, agitation
• Confusion, delirium, psychosis
• Seizures (can be prolonged or refractory)
• Coma
• Central respiratory depression

Specific Findings

Garlic-like odour: Many OP compounds have a characteristic smell on breath and clothing

Pinpoint pupils (Miosis): Classic but NOT always present; can be absent due to nicotinic stimulation causing mydriasis

Hypersecretions: Profuse salivation, lacrimation, bronchorrhoea

Muscle fasciculations: Often seen in face, tongue, neck, shoulders

Respiratory failure: Combination of bronchorrhoea, bronchospasm, respiratory muscle weakness, and CNS depression

Complications

Immediate (0-24 hours):

• Respiratory failure (primary cause of death)
• Cardiac arrhythmias (QTc prolongation, torsades de pointes)
• Aspiration pneumonia
• Seizures and status epilepticus
• Rhabdomyolysis
• Hyperthermia

Intermediate Syndrome (24-96 hours):

• Proximal muscle weakness (neck flexors, shoulder girdle)
• Cranial nerve palsies (ptosis, diplopia, dysphagia)
• Respiratory muscle weakness requiring reintubation
• Occurs in 10-20% of severe poisonings

Delayed Polyneuropathy (1-3 weeks):

• Distal sensorimotor peripheral neuropathy
• "Ginger jake" paralysis
• Ataxia, spasticity
• May be permanent

Chronic Sequelae:

• Cognitive impairment
• Peripheral neuropathy
• Psychiatric disorders (depression, PTSD)
• Extrapyramidal syndromes (parkinsonism)

Clinical Severity Grading

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Diagnosis

Clinical Diagnosis

Diagnosis is primarily clinical, based on:

1. History of exposure (occupational, accidental, intentional)
2. Characteristic toxidrome (SLUDGE + bronchorrhoea + miosis)
3. Garlic-like odour
4. Pupillary findings (miosis, though not always present)

Diagnostic Challenge: In cases of uncertain exposure or atypical presentations (e.g., isolated miosis, respiratory failure without clear exposure), consider the atropine challenge test.

Atropine Challenge Test

Indication: Uncertain diagnosis, consider alternative diagnoses (e.g., opioid poisoning)

Protocol:

1. Administer atropine 0.5-1 mg IV
2. Observe for 5-10 minutes

Interpretation:

• OP Poisoning: No change in HR or pupils (massive ACh excess overcomes atropine)
• Non-OP: Expected response (HR increase, pupillary dilation, dry mouth)

Caution: May precipitate anticholinergic toxicity in non-OP patients

Laboratory Investigations

Confirmatory Tests:

Timing:

• PChE decreases within 4-6 hours of exposure
• RBC AChE decreases within 12-24 hours
• Recovery of RBC AChE correlates with clinical recovery (half-life 30-50 days)

Utility: Confirmatory, but do not delay treatment while awaiting results

ED Availability: Usually not available in most hospitals; send to reference laboratory

Alternative Tests:

• Direct measurement of OP compounds in blood, urine, or gastric lavage fluid (research only)
• Butyrylcholinesterase activity (rapid bedside test in some centres)

Bedside Assessment Tools

Poison Severity Score (PSS):

Predictors of Mortality:

• Delay in atropine administration
• Delayed presentation (greater than 12 hours)
• Intentional ingestion (larger doses)
• Presence of intermediate syndrome
• Lack of ICU facilities

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Management

Immediate Priorities (Platinum Ten Minutes)

1. SCENE SAFETY - Wear PPE (chemical resistant gloves, gown, eye protection)
2. Remove patient from contaminated area
3. Remove all contaminated clothing
4. Decontaminate skin with soap and water
5. ABC assessment with aggressive airway protection
6. Administer atropine (do NOT wait for labs)
7. Secure IV access
8. Call toxicology/POISONS (13 11 26)

Decontamination

Dermal Decontamination:

• Remove ALL clothing (place in sealed biohazard bag)
• Wash skin and hair thoroughly with soap and water
• Pay attention to hair, axillae, groin, and fingernails
• Avoid hot water (increases absorption and vasodilation)
• Repeat until odour resolves
• Staff must wear appropriate PPE

Gastric Decontamination:

• Activated Charcoal: 50-100 g PO/NG if:
  • Within 1 hour of ingestion
  • Airway is protected (intubated)
  • No signs of bowel obstruction
• Gastric Lavage: Consider only if:
  • Within 1 hour of ingestion
  • Large, life-threatening ingestion
  • Airway protected (intubated)
  • Experienced operator available

Contraindications to Gastric Decontamination:

• Unprotected airway
• Late presentation (greater than 1-2 hours)
• Corrosive co-ingestants
• Patient comatose without airway protection

Airway and Breathing

Airway Management:

• Early intubation is critical for severe poisoning
• Indications:
  • GCS below 8
  • Uncontrollable bronchorrhoea
  • Respiratory failure (RR below 10, SpO2 below 90% on oxygen)
  • Seizures requiring sedation

Intubation Considerations:

• Use RSI (Rapid Sequence Intubation)
• Cautious use of succinylcholine: Prolonged paralysis due to reduced pseudocholinesterase activity
• Prefer rocuronium or vecuronium
• Staff must wear PPE during procedure (bronchorrhoea contains OP compounds)
• Suction aggressively before and after intubation

Ventilation Strategy:

• High PEEP may be needed for bronchorrhoea
• Monitor for auto-PEEP due to bronchospasm
• Consider inhaled bronchodilators (salbutamol, ipratropium)

Circulation

Fluid Resuscitation:

• Isotonic crystalloids (e.g., 0.9% NaCl, Hartmann's)
• Target MAP ≥65 mmHg
• Avoid hypotension (exacerbates CNS depression)

Cardiac Monitoring:

• Continuous ECG monitoring
• Watch for arrhythmias:
  • Bradycardia (muscarinic)
  • Tachycardia (nicotinic)
  • QTc prolongation
  • Torsades de pointes
• Treat arrhythmias per ACLS algorithms
• Correct electrolyte abnormalities (K+, Mg2+)

Antidotal Therapy

Atropine

Mechanism: Competitive antagonist at muscarinic ACh receptors; does NOT reverse nicotinic effects

Indications: All patients with signs of muscarinic toxicity

Dosing:

Atropinisation Endpoints (STOP atropine when achieved):

• Dry lung fields on auscultation (primary endpoint)
• Heart rate greater than 80 bpm
• Systolic BP greater than 90 mmHg
• Clear secretions

Important:

• Do NOT use pupil size as endpoint (may remain miotic due to nicotinic effects)
• Total doses can reach 50-100 mg in severe poisoning
• Continue atropine infusion for 24-48 hours or longer if ongoing exposure

Side Effects:

• Tachycardia (expected, not harmful)
• Fever (hyperthermia)
• Urinary retention
• Constipation
• Delirium (atropine psychosis) with prolonged high-dose therapy

Contraindications:

• Relative: Tachyarrhythmias, narrow-angle glaucoma

Pralidoxime (2-PAM, P2S, Protopam)

Mechanism: Oxime that reactivates phosphorylated AChE by dephosphorylation; must be given before "aging" occurs

Indications:

• Severe poisoning (respiratory failure, seizures, coma)
• Evidence of nicotinic toxicity (muscle weakness, fasciculations)
• Within 12-24 hours of exposure (before aging)

Dosing:

Duration:

• Continue for 24-48 hours in dimethyl OP poisoning (rapid aging)
• Continue for 48-72 hours in diethyl OP poisoning (slower aging)
• Continue until clinical improvement and no further atropine requirement

Evidence:

• Eddleston et al. (Lancet 2009): WHO-recommended dose (2g loading) showed NO benefit over placebo
• Pawar et al. (Lancet 2006): High-dose continuous infusion (2g load + 500 mg/h) reduced mortality and need for ventilation

Adverse Effects:

• Hypertension
• Nausea, vomiting
• Dizziness
• Laryngospasm (rare, with rapid bolus)
• Hepatotoxicity (prolonged use)

Contraindications:

• Carbamate poisoning (carbamates spontaneously reactivate; oximes unnecessary)
• Known hypersensitivity

Adjunctive Therapies

Benzodiazepines

Indications:

• Seizures (initial or status epilepticus)
• Severe agitation
• Muscle fasciculations (nicotinic effects)

Dosing:

• Adult: Lorazepam 2-4 mg IV q5-10 min OR diazepam 5-10 mg IV q5-10 min
• Child: Lorazepam 0.05-0.1 mg/kg IV (max 4 mg) OR diazepam 0.2-0.3 mg/kg IV

Maintenance:

• Diazepam infusion 0.1-0.2 mg/kg/h
• Consider continuous EEG for refractory seizures

Inhaled Bronchodilators

• Salbutamol: 2.5-5 mg nebulised q20 min PRN for bronchospasm
• Ipratropium: 0.5 mg nebulised q6h PRN
• Combination: Duolin (salbutamol + ipratropium) q4h PRN

Magnesium Sulfate

• Indication: Persistent bronchospasm despite bronchodilators
• Dose: 2 g IV over 20 min, then 1-2 g/h infusion
• Monitor: Deep tendon reflexes, respiratory rate, serum Mg2+ (target 2-4 mmol/L)

Anticonvulsants

• Phenytoin: 15-20 mg/kg IV load (max 1 g), then 5-7 mg/kg/d IV
• Levetiracetam: 20 mg/kg IV load, then 10-20 mg/kg q12h
• Consider prophylactic phenytoin/levetiracetam in severe poisoning

Monitoring

Clinical Monitoring:

• Hourly vital signs (HR, BP, RR, SpO2, temp)
• Neurological observations (GCS, pupils)
• Lung auscultation (hourly)
• Fluid balance (strict I/O)
• Bowel function (constipation is common)

Laboratory Monitoring:

Pharmacological Monitoring:

• Atropine infusion rate titrated to clinical response
• Pralidoxime infusion rate continued until weaning
• Monitor for atropine toxicity (fever, delirium, urinary retention)

Disposition

Admission Criteria (admit ALL patients with):

• Symptomatic poisoning (any muscarinic or nicotinic signs)
• History of significant exposure (greater than 30 min dermal, any ingestion)
• Abnormal cholinesterase levels
• Need for atropine therapy

ICU Admission:

• Severe poisoning (GCS below 12, respiratory failure, seizures)
• Intermediate syndrome (proximal muscle weakness)
• Need for mechanical ventilation
• High-dose atropine requirement (greater than 50 mg total)

Ward Admission:

• Mild to moderate poisoning
• Stable on maintenance atropine
• No respiratory compromise

Safe Discharge (rare):

• Asymptomatic greater than 24 hours post-exposure
• Normal examination
• Normal cholinesterase level (if available)
• Reliable observation at home
• Clear decontamination completed

Follow-up:

• Review in 1-2 weeks
• Monitor for intermediate syndrome (24-96 hours)
• Monitor for delayed polyneuropathy (1-3 weeks)
• Psychiatric evaluation if intentional ingestion

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Special Considerations

Paediatric Population

Age-Specific Considerations:

• Higher metabolic rate → faster onset
• Lower body fat → different distribution
• Immature blood-brain barrier → increased CNS toxicity
• Immature liver → slower metabolism

Dosing Adjustments:

• Atropine: 0.02-0.05 mg/kg IV bolus (max 2 mg)
• Pralidoxime: 30 mg/kg IV load (max 1 g)
• Benzodiazepines: Dose by weight

Unique Challenges:

• Accidental exposure (household pesticides, agricultural exposure)
• Smaller airways → more prone to respiratory failure
• Dehydration from vomiting → hypotension
• Developmental impact of prolonged hospitalisation

Pregnancy

Fetal Considerations:

• OPs cross placenta → fetal AChE inhibition
• Risk of fetal bradycardia, meconium aspiration, stillbirth
• Atropine crosses placenta → fetal tachycardia

Management:

• Aggressive maternal resuscitation is fetal resuscitation
• Atropine: Use standard dosing (benefit > risk)
• Pralidoxime: Category B (limited data, use if indicated)
• Obstetrics consultation
• Continuous fetal monitoring if viable gestation

Elderly

Age-Related Factors:

• Reduced renal clearance → prolonged OP effect
• Polypharmacy → drug interactions
• Comorbidities (CAD, COPD, CKD) complicate management
• Altered autonomic response

Dosing:

• Start low, go slow (especially with atropine)
• Monitor for anticholinergic toxicity (delirium, urinary retention)
• Adjust for renal/hepatic impairment

Chronic Exposure

Occupational Exposure:

• Agricultural workers, pesticide applicators, greenhouse workers
• Low-level dermal and inhalational exposure
• Non-acute, cumulative toxicity

Clinical Features:

• Headache, fatigue, dizziness
• Mood changes, irritability
• Memory impairment
• Peripheral neuropathy (distal sensorimotor)
• Visual disturbances

Diagnosis:

• Serial cholinesterase monitoring
• Environmental exposure assessment
• Workplace evaluation

Management:

• Remove from exposure
• Supportive care
• Monitor for neuropathy
• Neurological rehabilitation

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Australian Context

Epidemiology in Australia

Incidence:

• 400-500 cases/year requiring hospitalisation (Australian Institute of Health and Welfare)
• Lower than global rates due to strict pesticide regulations
• Peak in agricultural regions (Queensland, New South Wales, Victoria)

Seasonal Variation:

• Peak during planting/harvest seasons (Spring/Summer)
• Higher in rural areas with intensive agriculture

Common Organophosphates in Australia:

• Chlorpyrifos (widely used insecticide)
• Diazinon (agricultural, domestic)
• Parathion (agricultural, restricted)
• Malathion (agricultural, less toxic)
• Dichlorvos (domestic, slow-release strips)

Regulatory Framework

Australian Pesticides and Veterinary Medicines Authority (APVMA):

• Regulates pesticide registration and use
• Phasing out high-risk OP compounds (e.g., parathion, methyl parathion)
• Mandates safety labelling and handling instructions

Work Health and Safety (WHS) Regulations:

• Mandatory PPE for pesticide handlers
• Safe storage requirements
• Restricted sale to licensed applicators
• Worker safety training requirements

Indigenous Health Considerations

Higher Risk:

• Higher proportion working in agriculture
• Remote/rural location with limited healthcare access
• Cultural factors around pesticide use and storage
• Language barriers in understanding safety instructions

Cultural Safety:

• Involve Aboriginal Health Practitioners and Elders
• Use plain language and visual aids
• Respect cultural beliefs about illness and treatment
• Consider cultural obligations when arranging retrieval

Communication:

• Use Aboriginal Health Practitioners (AHPs) as cultural brokers
• Provide interpreter services if needed
• Explain the "whys" of intensive treatment (ICU, intubation)
• Involve family in decision-making

Environmental Health:

• If accidental exposure, involve environmental health officers
• Assist with home decontamination
• Prevent secondary exposure to family members
• Community education on pesticide safety

Remote and Rural Considerations

Challenges:

• Limited antidote stocks (atropine, pralidoxime)
• Delayed access to ICU/mechanical ventilation
• Limited laboratory support (no cholinesterase testing)
• Retrieval logistics (distance, weather, aircraft availability)
• Staff exposure risk (limited PPE, small EDs)

Management in Remote Settings:

Antidote Availability:

• Remote clinics must stock atropine (50-100 ampoules minimum)
• Pralidoxime availability varies; check local protocols
• Activate early retrieval if pralidoxime needed

Airway Management:

• Early intubation recommended if bronchorrhoea present
• Have skilled intubator available
• Stock RSI medications
• Ensure backup airway equipment (LMA, surgical airway)

Retrieval Coordination:

Communication:

• Early contact with state toxicology service
• Poisons Information Centre: 13 11 26 (24/7 nationwide)
• Consult with retrieval physician early
• Provide detailed handover to receiving facility

Staff Safety:

• Minimal staff in decontamination area
• Full PPE for all staff in patient area
• Adequate ventilation (off-gassing concerns)
• Remove contaminated clothing before patient transfer

Local Resources:

• Consult Primary Clinical Care Manual (PCCM) (QLD/NT)
• Use Toxicology Handbook (Murray et al.) as bedside reference
• Follow local health service protocols

Retrieval Medicine Considerations

Flight Considerations:

• Hypobaric hypoxia: Maintain SpO2 94-98% (higher altitude)
• Gas expansion: Ensure gastric tube is on free drainage
• Motion sickness: Antiemetic prophylaxis
• Noise: Communicate via headphones or written notes

Patient Stability:

• Must be atropinised before transport (dry lungs, HR greater than 80)
• Secure airway if any respiratory compromise
• Continuous atropine infusion during transport
• Bring sufficient antidotes (atropine, pralidoxime) for journey
• Have suction equipment ready (bronchorrhoea persists)

Receiving Facility:

• Ensure ICU bed available
• Confirm availability of ventilator
• Notify toxicology and ICU teams
• Provide patient details and treatment summary

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Complications

Respiratory Complications

Respiratory Failure:

• Incidence: 20-30% of severe poisonings
• Mechanism: Bronchorrhoea, bronchospasm, respiratory muscle weakness, CNS depression
• Management: Early intubation, mechanical ventilation, high PEEP, bronchodilators

Aspiration Pneumonitis:

• Risk: Vomiting + depressed airway reflexes
• Prophylaxis: Early intubation, NG tube drainage, H2 blockers
• Treatment: Antibiotics if infection suspected, supportive care

Pulmonary Oedema:

• Mechanism: Hydrostatic (fluid overload) + permeability (direct OP toxicity)
• Treatment: Diuretics, ventilatory support, consider inotropes

Cardiovascular Complications

Arrhythmias:

• Bradycardia: Muscarinic effect (treat with atropine)
• Tachycardia: Nicotinic effect (beta-blockers contraindicated)
• QTc Prolongation: Monitor for torsades (treat with magnesium)
• Ventricular arrhythmias: Rare, treat per ACLS

Myocardial Injury:

• Elevated troponin in 10-20% of severe cases
• Mechanism: Catecholamine surge, hypoxia, direct toxicity
• Treatment: Supportive, monitor for cardiac dysfunction

Neurological Complications

Seizures:

• Incidence: 10-20% of severe poisonings
• Treatment: Benzodiazepines, phenytoin/levetiracetam, monitor EEG
• Complications: Rhabdomyolysis, hyperthermia, neuronal injury

Intermediate Syndrome:

• Onset: 24-96 hours post-exposure
• Features: Proximal muscle weakness, cranial nerve palsies, respiratory failure
• Risk Factors: Severe initial poisoning, delayed atropine therapy, specific OP compounds
• Treatment: Mechanical ventilation, supportive care, physiotherapy

Delayed Polyneuropathy:

• Onset: 1-3 weeks post-exposure
• Features: Distal sensorimotor neuropathy, ataxia, spasticity
• Treatment: Supportive, rehabilitation, may be permanent
• Mechanism: OP-induced inhibition of neuropathy target esterase (NTE)

Metabolic Complications

Rhabdomyolysis:

• Incidence: 5-10% with seizures or prolonged immobilisation
• Treatment: Aggressive fluids, monitor CK, urine output, renal function

Hyperthermia:

• Mechanism: Seizures, muscle activity, anticholinergic effect
• Treatment: Cooling, benzodiazepines for muscle rigidity

Electrolyte Abnormalities:

• Hypokalaemia: From GI losses, beta-agonists
• Hypomagnesaemia: From renal losses, arrhythmia risk
• Hypernatraemia: From dehydration, free water deficit

Infectious Complications

Aspiration Pneumonia:

• Common in comatose patients
• Treatment: Broad-spectrum antibiotics (cover anaerobes)

Healthcare-Associated Infections:

• Ventilator-associated pneumonia
• Central line-associated bloodstream infection
• Prevention: Hand hygiene, early weaning, line bundles

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Prognosis

Mortality

Global:

• Untreated severe poisoning: 10-20% mortality
• With optimal treatment: below 2% mortality in high-resource settings
• Higher mortality in low-resource settings (limited ICU access)

Australian:

• Overall mortality: 1-2%
• Higher mortality in:
  • Intentional ingestion (larger doses)
  • Delayed presentation (greater than 12 hours)
  • Severe poisoning requiring mechanical ventilation
  • Age greater than 60 years
  • Underlying comorbidities

Predictors of Poor Outcome

Worse Prognosis:

• GCS below 8 on presentation
• Delayed atropine administration (greater than 2 hours)
• Need for mechanical ventilation
• Presence of intermediate syndrome
• Specific OP compounds (dimethyl compounds, parathion)
• Age greater than 60 years
• Co-ingestants (e.g., alcohol, other pesticides)

Better Prognosis:

• Early presentation (below 1 hour)
• Mild to moderate poisoning (no respiratory involvement)
• Prompt atropine therapy
• Access to ICU care
• Younger age (below 40 years)

Long-Term Outcomes

Neurological Sequelae:

• Peripheral neuropathy (10-20%): Usually mild, may improve over 6-12 months
• Cognitive impairment (5-10%): Memory, attention, executive function
• Psychiatric disorders (15-20%): Depression, PTSD, anxiety

Quality of Life:

• Most survivors return to baseline function
• Severe poisoning may have lasting cognitive/psychological effects
• Rehabilitation important for intermediate syndrome recovery

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Pitfalls and Pearls

Common Pitfalls

1. Relying on pupil size as atropine endpoint

• Pitfall: Stopping atropine when pupils dilate
• Correct: Titrate to dry lungs and HR greater than 80 bpm
• Reason: Nicotinic effects can maintain miosis despite adequate atropine

2. Inadequate atropine dosing

• Pitfall: Fixed dose (e.g., 1 mg bolus) for all patients
• Correct: Weight-based dosing, double every 5 min until atropinised
• Reason: Severe poisoning may require 50-100+ mg

3. Delaying pralidoxime for lab confirmation

• Pitfall: Waiting for cholinesterase results
• Correct: Give pralidoxime early (before aging) in severe poisoning
• Reason: Once aging occurs, pralidoxime ineffective

4. Using succinylcholine for RSI

• Pitfall: Prolonged paralysis (hours instead of minutes)
• Correct: Use rocuronium or vecuronium
• Reason: Pseudocholinesterase inhibited by OPs

5. Neglecting staff safety

• Pitfall: Staff exposure during decontamination
• Correct: Full PPE for all staff, adequate ventilation
• Reason: OPs absorbed transdermally and inhaled

6. Overlooking intermediate syndrome

• Pitfall: Premature extubation or discharge
• Correct: Observe for 24-96 hours for delayed muscle weakness
• Reason: Respiratory failure can occur days after initial presentation

7. Missing delayed polyneuropathy

• Pitfall: No follow-up after discharge
• Correct: Arrange 1-2 week review
• Reason: Neuropathy develops 1-3 weeks post-exposure

Clinical Pearls

1. "Dry lungs, not dry eyes"

• Atropine's primary goal is clearing bronchorrhoea
• Pupils may remain miotic due to nicotinic effects
• Focus on auscultation, not pupillary examination

2. Double until dry

• Atropine dosing is an incremental doubling protocol
• 1.2 → 2.4 → 4.8 → 9.6 mg every 5 min until atropinised
• Continue maintenance infusion (10-20% of load/hour)

3. Pralidoxime window

• Dimethyl OPs: Give within 1-2 hours (rapid aging)
• Diethyl OPs: Give within 12-24 hours (slower aging)
• If greater than 24 hours since exposure, limited benefit

4. Benzodiazepines early

• Seizures are common and dangerous
• Give benzodiazepines proactively in severe poisoning
• Monitor for prolonged sedation

5. Suction aggressively

• Bronchorrophoea is torrential
• Suction before and after intubation
• Have suction ready continuously in resuscitation bay

6. ICU for all severe cases

• Respiratory failure can be abrupt
• Intermediate syndrome requires ventilation
• Close monitoring essential

7. Call Poisons early

• Poisons Information Centre (13 11 26) 24/7
• They provide dosing guidance, confirm diagnosis
• Access to toxicology registrar for complex cases

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Viva Practice

Viva Scenario 1: Basic Science - Cholinergic Transmission

Stem: A 45-year-old agricultural worker presents after accidental dermal exposure to chlorpyrifos insecticide. He has profuse salivation, lacrimation, and bronchorrhoea.

Q1: Describe the normal physiology of cholinergic neurotransmission at the neuromuscular junction.

Model Answer:

1. Presynaptic terminal: Voltage-gated calcium channels open on depolarisation
2. Calcium influx: Triggers vesicle fusion with presynaptic membrane
3. Acetylcholine release: Quantum release into synaptic cleft
4. Acetylcholine diffusion: Crosses synaptic cleft to postsynaptic membrane
5. Nicotinic receptor binding: ACh binds to α-subunits of nicotinic receptors
6. Receptor activation: Ligand-gated sodium channel opens → depolarisation
7. Action potential: If threshold reached, muscle fibre contracts
8. Acetylcholinesterase: Hydrolyses ACh to choline and acetate within 1 ms
9. Choline reuptake: Choline recycled to presynaptic terminal
10. Signal termination: Rapid signal termination allows fine motor control

Q2: Explain how organophosphates inhibit acetylcholinesterase, including the concept of "aging."

Model Answer:

1. Phosphorylation: OP covalently binds to serine hydroxyl group at AChE active site
2. Irreversible inhibition: Phosphorylated complex (AChE-OP) is inactive
3. ACh accumulation: No hydrolysis of ACh → excessive stimulation
4. Aging: Over time, phosphorylated complex undergoes dealkylation
5. Permanently inactive: Aged complex cannot be reactivated by oximes
6. Time-dependent:
   • Dimethyl OPs: Aging 1-2 hours (e.g., dichlorvos, malathion)
   • Diethyl OPs: Aging 24-48 hours (e.g., chlorpyrifos, diazinon, parathion)
7. Clinical implication: Pralidoxime must be given before aging occurs
8. Spontaneous regeneration: New AChE synthesised over 30-50 days (RBC half-life)

Q3: Describe the muscarinic receptor subtypes (M1-M5) and their clinical effects.

Model Answer:

Q4: Explain the mechanism of atropine's therapeutic effect and its limitations.

Model Answer:

Mechanism:

1. Competitive antagonist: Binds to muscarinic receptors, prevents ACh binding
2. Reversible blockade: Displaces ACh but does not displace OP from AChE
3. Dose-dependent: Higher doses overcome excessive ACh stimulation

Effects (positive):

1. Dries bronchial secretions (bronchorrhoea)
2. Relieves bronchospasm
3. Increases heart rate (bradycardia)
4. Reduces GI secretions and motility
5. Decreases sweating, salivation, lacrimation

Limitations:

1. Does NOT reverse nicotinic effects: Muscle weakness, fasciculations persist
2. Does NOT reverse CNS effects: Seizures, confusion require benzodiazepines
3. Does NOT reactivate AChE: Pralidoxime required for enzyme reactivation
4. Does NOT prevent aging: Irreversible enzyme damage continues
5. Pupillary response unreliable: Miosis may persist due to nicotinic effects
6. Toxicity with high doses: Fever, delirium, urinary retention (atropine psychosis)

---

Viva Scenario 2: Clinical Management - Severe Poisoning

Stem: A 28-year-old woman presents 2 hours after intentional ingestion of an unknown amount of chlorpyrifos insecticide. On arrival, she is comatose (GCS 6), has pinpoint pupils, profuse bronchorrhoea, and oxygen saturation 88% on 15 L/min.

Q1: Outline your immediate management priorities.

Model Answer:

Immediate Actions (First 10 minutes):

1. Scene safety: Staff wear full PPE (gloves, gown, eye protection)

2. Remove clothing: Seal in biohazard bag

3. ABCDE assessment:

   • Airway: Immediate intubation for GCS 6, bronchorrhoea, respiratory failure
   • Breathing: 100% oxygen, suction aggressively
   • Circulation: 2 large-bore IVs, fluid bolus, ECG monitoring
   • Disability: GCS assessment, pupils
   • Exposure: Full secondary survey

4. Atropine administration:

   • Bolus 2.4 mg IV (adult)
   • Double every 5 minutes until atropinised (dry lungs, HR greater than 80)
   • Anticipate large total dose (potentially 50-100 mg)

5. Call for help:

   • ICU activation
   • Poisons Information Centre (13 11 26)
   • Retrieval service (if non-tertiary hospital)
   • Toxicology registrar

6. Monitor: Continuous ECG, SpO2, capnography

Q2: Discuss your airway management strategy, including RSI medication choices.

Model Answer:

Pre-oxygenation:

• 100% oxygen for 3-5 minutes
• Suction aggressively before intubation

RSI Medication:

• Induction agent: Ketamine 1-2 mg/kg IV (maintains haemodynamic stability)
  • "Alternative: Propofol 1-2 mg/kg (if normotensive)"
• Neuromuscular blocker: Rocuronium 1.2 mg/kg IV (sugammadex available)
  • "Contraindicated: Succinylcholine (prolonged paralysis due to pseudocholinesterase inhibition)"
  • "Alternative: Vecuronium 0.1 mg/kg IV"

Intubation considerations:

• Staff wear full PPE (bronchorrhoea contains OP compounds)
• Have suction ready (torrential secretions)
• Rapid sequence intubation with cricoid pressure
• Confirm placement with ETCO2 waveform and chest auscultation
• Secure tube (coughing and movement can displace)

Post-intubation:

• Suction regularly
• Continue atropine (bronchorrhoea continues despite intubation)
• Start pralidoxime infusion (30 mg/kg load, then 8-10 mg/kg/h)
• Sedation: Propofol infusion ± fentanyl or ketamine infusion
• Ventilation: Lung-protective strategy, high PEEP for bronchorrhoea

Q3: How will you manage the atropine therapy?

Model Answer:

Loading Phase:

• Start: 2.4 mg IV bolus
• Double every 5 minutes if no response: 4.8 mg → 9.6 mg → 19.2 mg
• Continue until atropinisation achieved:
  • "Primary endpoint: Dry lung fields on auscultation"
  • "Secondary endpoints: HR greater than 80 bpm, SBP greater than 90 mmHg"
  • "Not: Pupillary dilation (may remain miotic)"

Maintenance Phase:

• Calculate total loading dose required
• Start infusion at 10-20% of loading dose per hour
  • "Example: If 50 mg total load, start 5-10 mg/h infusion"
• Titrate to maintain dry lungs and HR 80-100 bpm

Duration:

• Continue for 24-48 hours (minimum)
• May need longer if ongoing re-absorption from skin/GI tract
• Continue until all clinical signs resolved

Monitoring:

• Hourly lung auscultation
• Hourly vital signs
• Watch for atropine toxicity:
  • Fever greater than 38.5°C
  • Delirium, hallucinations (atropine psychosis)
  • Urinary retention
  • Paralytic ileus
• Treat toxicity with physostigmine (rare, severe cases only)

Q4: What are the indications for pralidoxime, and how will you dose it?

Model Answer:

Indications:

1. Severe poisoning: Coma, respiratory failure, seizures
2. Nicotinic signs: Muscle fasciculations, weakness
3. Within therapeutic window:
   • Dimethyl OPs: below 1-2 hours (rapid aging)
   • Diethyl OPs: below 12-24 hours (slower aging)
   • This patient is 2 hours post-ingestion of chlorpyrifos (diethyl OP) → Still within window

Contraindications:

• Carbamate poisoning (carbamates spontaneously reactivate)
• Known hypersensitivity

Dosing (Adult):

• Loading dose: 30 mg/kg IV over 30 minutes (max 1 g)
• Maintenance infusion: 8-10 mg/kg/h continuous infusion
• Duration: 48-72 hours for diethyl OPs (chlorpyrifos)
  • Continue until clinical improvement and no further atropine requirement

Evidence:

• Eddleston et al. (Lancet 2009): WHO-recommended 2 g bolus showed NO benefit
• Pawar et al. (Lancet 2006): High-dose continuous infusion (2 g load + 500 mg/h) reduced mortality
• I will use the high-dose continuous infusion protocol

Monitoring:

• Monitor blood pressure (pralidoxime can cause hypertension)
• Observe for adverse effects: Nausea, vomiting, dizziness, laryngospasm
• Continue until nicotinic signs resolve and atropine requirement minimal

---

Viva Scenario 3: Intermediate Syndrome

Stem: A 35-year-old man was admitted 48 hours ago after chlorpyrifos ingestion. He was initially intubated, successfully atropinised, and extubated after 24 hours. 12 hours post-extubation, he develops progressive proximal muscle weakness and difficulty breathing.

Q1: What is intermediate syndrome, and what are its clinical features?

Model Answer:

Definition:

• Delayed onset of proximal muscle weakness and cranial nerve palsies
• Occurs 24-96 hours after acute organophosphate poisoning
• Can occur despite adequate atropinisation
• Also called Type II paralysis or organophosphate-induced delayed neuropathy (different from delayed polyneuropathy)

Clinical Features:

Proximal muscle weakness:

• Neck flexor weakness (unable to lift head off pillow)
• Shoulder girdle weakness (difficulty lifting arms)
• Hip flexor weakness (difficulty raising legs)
• Key sign: Patient cannot sit up from supine position

Cranial nerve palsies:

• Ptosis (drooping eyelids)
• Diplopia (double vision) - CN III, IV, VI
• Facial weakness - CN VII
• Dysphagia, dysphonia (difficulty swallowing, hoarse voice) - CN IX, X
• Difficulty protecting airway

Respiratory involvement:

• Weak respiratory muscles (diaphragm, intercostals)
• Ineffective cough
• CO2 retention
• May require reintubation and mechanical ventilation

Other features:

• Absence of muscarinic signs (already atropinised)
• Absence of seizures
• Conscious and alert
• Sensory examination normal

Q2: What are the risk factors for developing intermediate syndrome?

Model Answer:

Patient factors:

• Severe initial poisoning (coma, respiratory failure)
• Delayed atropine administration
• Large dose of organophosphate ingested
• Specific organophosphate compounds (more common with dimethoate, fenthion)

Treatment factors:

• Inadequate atropine therapy
• Delayed pralidoxime administration
• Prolonged initial mechanical ventilation

Other factors:

• Age greater than 40 years
• Chronic exposure history
• Co-ingestants (alcohol, other pesticides)

Epidemiology:

• Occurs in 10-20% of severe poisonings
• More common with dimethyl OPs
• Variable incidence between different organophosphate compounds

Q3: How will you manage this patient?

Model Answer:

Immediate Actions:

1. Airway assessment:

   • Check respiratory rate, oxygen saturation, work of breathing
   • Assess gag reflex and cough strength
   • Measure negative inspiratory force (NIF) if available
   • Consider early reintubation if any respiratory compromise

2. Blood gas:

   • ABG or VBG
   • Look for hypercapnia (PaCO2 greater than 50 mmHg)
   • Assess for hypoxaemia

3. Examination:

   • Full neurological examination
   • Assess cranial nerves (ptosis, eye movements, facial symmetry, gag reflex)
   • Assess motor strength (proximal vs distal)
   • Sensory examination (usually normal)

4. Supportive care:

   • If respiratory compromise: Immediate reintubation and mechanical ventilation
   • High-dose atropine (if any bronchorrhoea recurs)
   • Continue pralidoxime infusion (may benefit from continued oxime therapy)
   • Aggressive physiotherapy and chest physiotherapy
   • Nutritional support (NG feeding if intubated)

Specific Interventions:

Ventilation strategy:

• Lung-protective ventilation (TV 6-8 mL/kg, PEEP 5-10 cmH2O)
• Permissive hypercapnia if needed
• Daily spontaneous breathing trials
• Plan for prolonged ventilation (days to weeks)

Pralidoxime:

• Continue infusion (evidence for benefit in intermediate syndrome)
• Some experts recommend higher doses (up to 20 mg/kg/h)
• Continue until muscle strength improves

Physiotherapy:

• Passive range of motion exercises
• Regular turning and position changes
• Chest physiotherapy to prevent atelectasis/pneumonia
• Gradual mobilisation as weakness improves

Monitoring:

• Daily neurological assessment
• Serial blood gases if ventilated
• Monitor for complications:
  • Ventilator-associated pneumonia
  • Pressure injuries
  • DVT prophylaxis (unfractionated heparin or LMWH)
  • Stress ulcer prophylaxis

Prognosis:

• Recovery usually occurs over 3-15 days
• Most patients fully recover
• Some may have residual weakness for weeks to months
• Rarely permanent weakness

Q4: How will you counsel the patient and family about expected recovery?

Model Answer:

Explanation of condition:

• "This is called intermediate syndrome, a known complication of severe organophosphate poisoning"
• "It's not the initial poisoning returning, but a separate phase of weakness"
• "The muscles, especially those that help breathing, are temporarily weak"

Expected course:

• "Most people recover fully over 3-15 days"
• "The weakness will gradually improve day by day"
• "Some people need help with breathing for a week or more"
• "Physical therapy will help speed up recovery"

Rehabilitation plan:

• "Once breathing improves, we'll start physical therapy"
• "You'll work on strengthening exercises"
• "Most people return to their normal activities"
• "We'll arrange follow-up with rehabilitation specialist"

Long-term outlook:

• "Most patients make a complete recovery"
• "Some people have mild weakness that can last several weeks"
• "Very rarely, there can be long-term weakness or numbness (delayed polyneuropathy)"
• "We'll monitor for this with follow-up appointments"

Psychological support:

• "This is a stressful experience; it's normal to feel anxious or depressed"
• "We have counsellors and social workers available to support you"
• "If this was an intentional overdose, we'll arrange psychiatric follow-up"

---

Viva Scenario 4: Rural and Indigenous Health

Stem: You are working in a remote community health clinic in rural Queensland. A 22-year-old Aboriginal man presents after accidentally inhaling pesticide while spraying crops. He has salivation, lacrimation, vomiting, and wheeze. The clinic is 4 hours by road from the nearest hospital, with no helicopter available due to weather.

Q1: What are your immediate management priorities in this remote setting?

Model Answer:

Immediate Actions:

1. Scene safety and decontamination:

   • Full PPE for all staff (chemical resistant gloves, gown, eye protection)
   • Remove all contaminated clothing
   • Wash skin and hair thoroughly with soap and water
   • Place contaminated clothing in sealed bag

2. ABCDE assessment:

   • Airway: Assess for airway compromise (bronchorrhoea, secretions)
   • Breathing: RR, SpO2, auscultation for wheeze/crackles
   • Circulation: HR, BP, capillary refill, ECG
   • Disability: GCS, pupils
   • Exposure: Full examination, look for further contamination

3. Atropine administration:

   • Check clinic stock (should have 50-100 ampoules)
   • Give 1.2-2.4 mg IV bolus (adult)
   • Double every 5 minutes until atropinised (dry lungs, HR greater than 80)
   • Document doses carefully

4. Secure IV access:

   • 2 large-bore IVs
   • Start fluid resuscitation (0.9% NaCl or Hartmann's)

5. Call for help:

   • RFDS (Royal Flying Doctor Service): 1800 625 800
   • Poisons Information Centre: 13 11 26
   • Retrieval physician (via RFDS)
   • Hospital receiving team

6. Consider intubation:

   • Indications: GCS below 8, respiratory failure, uncontrollable bronchorrhoea
   • Ensure clinic has intubation equipment and medications
   • Have skilled intubator available

Q2: What specific considerations do you need to address for this Aboriginal patient?

Model Answer:

Cultural safety:

• Involve Aboriginal Health Practitioner (AHP) as cultural broker
• Use plain language and visual aids when explaining treatment
• Respect cultural beliefs about illness and healing
• Acknowledge family and community support systems
• Ask about traditional medicines or healers (do not dismiss)

Communication:

• Identify language needs (may require interpreter)
• Use the "teach-back" method to ensure understanding
• Explain the need for intensive treatment and possible ICU admission
• Discuss retrieval and transport to hospital
• Involve family in decision-making (with patient consent)

Family and community involvement:

• Allow family to be present if clinically appropriate
• Explain treatment to family members (with patient consent)
• Consider cultural obligations when planning retrieval
• Identify who can stay with patient in hospital

Environmental health:

• This was accidental occupational exposure
• Contact local environmental health officer
• Assess home and work environment for ongoing exposure risk
• Ensure family members are not also exposed
• Provide education on safe pesticide handling

Psychological support:

• Accidental exposure can be traumatic
• Provide emotional support and counselling
• Address fear of long-term health effects
• Screen for post-traumatic stress symptoms

Health disparities awareness:

• Aboriginal patients may have higher baseline risk of chronic diseases
• May have reduced access to follow-up care
• Consider social determinants of health in discharge planning
• Arrange appropriate follow-up in community

Q3: How will you manage the retrieval given the weather constraints?

Model Answer:

Early communication:

1. Activate RFDS immediately: Weather is unpredictable; get in queue

2. Provide detailed handover:

   • Patient demographics and clinical condition
   • Time of exposure, route, suspected organophosphate
   • Treatment given (atropine doses, fluids, any other meds)
   • Current vital signs and examination findings
   • Anticipated deterioration timeline

3. Determine destination:

   • Closest tertiary hospital with ICU capability
   • Ensure receiving facility has:
     • ICU bed available
     • Ventilator capability
     • Toxicology consultation
     • Adequate antidote stocks

Ground transport considerations:

• If helicopter unavailable for greater than 6-12 hours, consider road ambulance
• Escort by RFDS flight paramedic/doctor (if available)
• Ensure ambulance has:
  • Sufficient atropine (anticipate 50-100 mg total)
  • Intubation equipment
  • Ventilator capability
  • Suction equipment
• Medications for transport:
  • Atropine infusion (continue maintenance)
  • Pralidoxime (if available at clinic)
  • Benzodiazepines (for seizures)
  • Bronchodilators
  • Emergency medications

Patient stability before transport:

• Must be atropinised (dry lungs, HR greater than 80)
• Secure airway if any respiratory compromise
• Continuous monitoring during transport
• Clear documentation of treatments and times

Weather contingency plan:

• Request regular weather updates from RFDS
• Have backup plan for road transport
• Consider alternative retrieval services if available
• Prepare for prolonged wait (monitor for intermediate syndrome)

Q4: What discharge and follow-up considerations are needed for this patient and community?

Model Answer:

Hospital discharge planning (once recovered):

• Ensure complete clinical recovery
• Normal cholinesterase level if available
• No signs of intermediate syndrome
• Safe discharge home with family support

Follow-up arrangements:

• Review in 1-2 weeks with GP or local clinic
• Monitor for intermediate syndrome (24-96 hours)
• Monitor for delayed polyneuropathy (1-3 weeks)
• Neurological examination if any residual symptoms

Occupational health:

• Discuss return to work considerations
• May need temporary work restrictions
• Ensure employer provides appropriate PPE
• Consider referral to occupational health physician

Community education:

• Work with environmental health officer
• Community education on pesticide safety:
  • Safe storage (locked cabinets)
  • Proper PPE (gloves, mask, goggles, protective clothing)
  • Correct application techniques
  • First aid for accidental exposure
  • Recognising early symptoms

Preventive measures:

• Promote "Lock Up Your Poison" campaigns
• Encourage use of less toxic pesticides where possible
• Training for agricultural workers
• Regular health checks for pesticide handlers

Long-term monitoring:

• Regular health checks for chronic exposure effects
• Monitor for neurological, respiratory, cardiovascular effects
• Psychological support for anxiety related to exposure
• Screen for post-traumatic stress if severe poisoning

Documentation and reporting:

• Complete incident report (occupational health and safety)
• Notify relevant authorities if required
• Document all communication with RFDS, Poisons Centre, receiving hospital
• Provide copy to patient's regular GP

---

OSCE Stations

OSCE Station 1: Resuscitation - Acute Cholinergic Crisis

Station Details:

• Duration: 11 minutes
• Setting: ED Resuscitation Bay
• Patient: 32-year-old woman found unresponsive after suspected pesticide ingestion
• Resources: Airway equipment, monitor, drugs, PPE, suction

Candidate Instructions: "You are the team leader in the resuscitation bay. This 32-year-old woman has been brought in by ambulance after being found unresponsive at home. Empty bottle of 'insecticide' found nearby. Please assess and manage this patient."

Actor Briefing:

• Patient is comatose (GCS 6)
• Pinpoint pupils
• Profuse bronchorrhoea (wet coughing sounds)
• Respiratory rate 8/min, shallow
• Oxygen saturation 86% on 15 L/min non-rebreather
• Heart rate 48/min, blood pressure 95/60 mmHg
• Wet clothing with chemical odour
• Incontinent of urine and faeces

Equipment Available:

• Full monitoring (ECG, SpO2, NIBP)
• Airway equipment (laryngoscope, ETT, LMA, suction)
• Drugs: Atropine (0.6 mg/mL ampoules), pralidoxime (1 g vial), lorazepam, rocuronium, ketamine, propofol, adrenaline
• IV fluids (0.9% NaCl, Hartmann's)
• NG tube, urinary catheter
• PPE (gloves, gown, eye protection, N95 mask)

Marking Criteria (Pass Mark: 60/100):

Immediate Safety (10 marks):

• ☐ Recognises need for PPE (gloves, gown, eye protection)
• ☐ Removes contaminated clothing
• ☐ Ensures staff safety (limits staff in room)
• ☐ Calls for additional resources/toxicology

Airway and Breathing (25 marks):

• ☐ Recognises respiratory failure (RR 8, SpO2 86%)
• ☐ Suctions airway before intubation
• ☐ Pre-oxygenates with 100% oxygen
• ☐ Correct RSI agent choice (ketamine or propofol)
• ☐ Correct muscle relaxant choice (rocuronium, not succinylcholine)
• ☐ Successful intubation (or recognises need for intubation)
• ☐ Confirmatory ETCO2 and auscultation
• ☐ Starts mechanical ventilation
• ☐ Suctions after intubation

Circulation (15 marks):

• ☐ Secures 2 large-bore IV access
• ☐ Starts fluid resuscitation
• ☐ Correctly identifies atropine as priority antidote
• ☐ Correct initial atropine dose (1.2-2.4 mg IV)
• ☐ Plans doubling every 5 minutes until atropinised
• ☐ Correctly identifies atropinisation endpoints (dry lungs, HR greater than 80)

Antidote Administration (20 marks):

• ☐ Gives atropine promptly (within 2 minutes)
• ☐ Explains dosing regimen clearly
• ☐ Plans for pralidoxime (30 mg/kg load, then 8-10 mg/kg/h)
• ☐ Recognises benzodiazepines for seizure prophylaxis
• ☐ Calls Poisons Information Centre (13 11 26)

Monitoring and Communication (20 marks):

• ☐ Clear closed-loop communication
• ☐ Delegates tasks appropriately
• ☐ Explains management to team members
• ☐ Monitors response to atropine
• ☐ Recognises need for ICU admission
• ☐ Provides clear handoff

Overall Performance (10 marks):

• ☐ Systematic approach (ABCDE)
• ☐ Prioritises correctly (airway, atropine)
• ☐ Recognises severity (severe poisoning)
• ☐ Demonstrates knowledge of OP poisoning
• ☐ Professional and confident leadership

Critical Failures (automatic fail if present):

• Attempts to use succinylcholine for RSI
• Does not wear PPE
• Delays atropine administration
• Intubates without suctioning first

---

OSCE Station 2: Communication - Family Discussion

Station Details:

• Duration: 11 minutes
• Setting: ED Family Consultation Room
• Patient: Husband of patient from Station 1
• Resources: None (communication only)

Candidate Instructions: "The patient from the resuscitation station has been stabilised and transferred to ICU. Her husband has arrived and is requesting to speak with the doctor. Please speak with him about his wife's condition, the treatment, and what to expect."

Actor Briefing:

• You are the husband, John, age 35
• You found your wife unconscious at home
• She has been struggling with depression recently
• You are very anxious and worried about her survival
• You want to know:
  • Will she survive?
  • What happened?
  • What is being done to help her?
  • Will she have permanent damage?
  • Can you see her?
• You may become emotional and tearful

Marking Criteria (Pass Mark: 60/100):

Introduction and Rapport (15 marks):

• ☐ Introduces self clearly
• ☐ Uses patient's/husband's name
• ☐ Sits down, maintains eye contact
• ☐ Shows empathy and concern
• ☐ Establishes quiet, private environment

Information Gathering (15 marks):

• ☐ Asks about what happened (history of exposure)
• ☐ Asks about recent mental health (depression, suicidal ideation)
• ☐ Asks about medical history, medications
• ☐ Asks about allergies
• ☐ Assesses understanding of situation

Explaining the Condition (25 marks):

• ☐ Explains organophosphate poisoning clearly (lay language)
• ☐ Describes what it does to the body (ACh accumulation)
• ☐ Explains why she is unconscious (CNS depression)
• ☐ Explains respiratory problems (bronchorrhoea, muscle weakness)
• ☐ Uses appropriate language (no jargon)
• ☐ Checks understanding frequently

Treatment and Prognosis (20 marks):

• ☐ Explains atropine treatment (dries secretions)
• ☐ Explains pralidoxime treatment (reactivates enzyme)
• ☐ Explains need for ventilator (respiratory support)
• ☐ Gives realistic prognosis (guarded but hopeful)
• ☐ Discusses complications (intermediate syndrome)
• ☐ Discusses expected recovery (most recover fully)

Psychosocial Support (15 marks):

• ☐ Addresses emotional concerns (fear, anxiety)
• ☐ Acknowledges difficulty of situation
• ☐ Offers support (social work, counselling)
• ☐ Discusses psychiatric follow-up (depression)
• ☐ Arranges for husband to see patient (when safe)

Overall Communication (10 marks):

• ☐ Speaks clearly and at appropriate pace
• ☐ Uses open-ended questions
• ☐ Allows husband to ask questions
• ☐ Summarises key points
• ☐ Provides contact information for future questions

Critical Failures (automatic fail if present):

• Gives false hope (guarantees survival)
• Blames husband or patient
• Dismisses emotional concerns
• Uses excessive medical jargon
• Rushes through consultation

---

OSCE Station 3: Toxicology - Antidote Dosing and Interpretation

Station Details:

• Duration: 11 minutes
• Setting: ED Consultation Room
• Patient: You are reviewing the patient with the toxicology registrar
• Resources: Calculator, blank paper, pen

Candidate Instructions: "You have a 70 kg patient with severe organophosphate poisoning who has been intubated and ventilated. The toxicology registrar asks you to:

1. Calculate the atropine loading dose and maintenance infusion
2. Calculate the pralidoxime loading dose and maintenance infusion
3. Interpret the following cholinesterase levels:
   • RBC AChE: 3 U/g Hb (normal 10-20)
   • Plasma cholinesterase: 2 kU/L (normal 4-12)
4. Discuss the clinical significance and timing of these levels"

Resources Provided:

• Atropine: 0.6 mg/mL ampoules
• Pralidoxime: 1 g vial (reconstituted to 10 mL)
• Patient weight: 70 kg
• Normal values provided above

Marking Criteria (Pass Mark: 60/100):

Atropine Calculations (25 marks):

• ☐ Correct initial bolus: 1.2-2.4 mg IV (2-4 mL)
• ☐ Correct dosing strategy: Double every 5 minutes until atropinised
• ☐ Correct atropinisation endpoints (dry lungs, HR greater than 80)
• ☐ Maintenance infusion: 10-20% of total loading dose per hour
• ☐ Example calculation: If 50 mg load → 5-10 mg/h infusion
• ☐ Recognises need for large total doses (50-100+ mg)

Pralidoxime Calculations (25 marks):

• ☐ Correct loading dose: 30 mg/kg = 2.1 g (70 kg × 30)
• ☐ Gives max 1 g IV over 30 minutes (2 doses of 1 g, 30 min apart)
• ☐ Correct maintenance dose: 8-10 mg/kg/h = 560-700 mg/h (70 kg)
• ☐ Correct preparation: 1 g in 100-250 mL diluent
• ☐ Correct duration: 48-72 hours for diethyl OPs
• ☐ Recognises therapeutic window (before aging)

Cholinesterase Interpretation (30 marks):

• ☐ Correctly identifies both levels as decreased (below 50% normal)
• ☐ Explains RBC AChE: 3 U/g Hb is 15-30% of normal (severe inhibition)
• ☐ Explains plasma cholinesterase: 2 kU/L is 17-50% of normal (moderate inhibition)
• ☐ Explains difference: RBC AChE more specific for nervous system
• ☐ Discusses timing: Levels correlate with severity but do not change management
• ☐ Explains RBC AChE recovery: 30-50 days (new RBC synthesis)

Clinical Application (10 marks):

• ☐ Does NOT delay treatment for lab results
• ☐ Treatment is clinical (symptoms guide therapy)
• ☐ Explains role of cholinesterase levels (confirmatory, prognostic)
• ☐ Recognises intermediate syndrome risk (severe inhibition)

Overall Knowledge (10 marks):

• ☐ Demonstrates understanding of AChE inhibition
• ☐ Discusses concept of enzyme "aging"
• ☐ Explains differences between RBC and plasma cholinesterase
• ☐ Confident in calculations and reasoning

Critical Failures (automatic fail if present):

• Suggests delaying treatment for lab results
• Incorrect dosing (e.g., uses 1 mg atropine bolus for severe poisoning)
• Suggests succinylcholine for RSI
• Does not recognise need for large atropine doses

---

SAQ Practice

SAQ 1: Pathophysiology and Clinical Features

Stem: A 45-year-old agricultural worker presents 4 hours after accidental dermal exposure to an organophosphate insecticide. He has profuse salivation, lacrimation, vomiting, diarrhoea, bronchorrhoea, and pinpoint pupils.

Question:

a) Explain the mechanism of action of organophosphates at the molecular level, including the concept of "enzyme aging." (4 marks)

b) List 8 clinical features of organophosphate poisoning, classified by receptor type (muscarinic, nicotinic, CNS). (4 marks)

c) Describe the typical timeline for the development of intermediate syndrome. (2 marks)

Model Answer:

a) Mechanism and aging (4 marks):

Mechanism of action (2 marks):

• Organophosphates irreversibly inhibit acetylcholinesterase (AChE) by phosphorylation of the serine hydroxyl group at the active site
• This prevents AChE from hydrolysing acetylcholine (ACh)
• Result: Accumulation of ACh at muscarinic, nicotinic, and CNS receptors
• Excessive receptor stimulation causes cholinergic crisis

Enzyme aging (2 marks):

• Over time, the phosphorylated AChE-OP complex undergoes dealkylation
• This "aging" process creates a permanently inactive enzyme that cannot be reactivated by oxime therapy
• Dimethyl OPs: Rapid aging within 1-2 hours (e.g., dichlorvos, malathion)
• Diethyl OPs: Slower aging over 24-48 hours (e.g., chlorpyrifos, diazinon, parathion)
• Clinical importance: Pralidoxime must be given before aging occurs

b) Clinical features classified by receptor type (4 marks):

Muscarinic effects (2 marks required):

• SLUDGE: Salivation, Lacrimation, Urination, Defecation, Gastrointestinal cramps, Emesis
• "Killer Bs": Bronchorrhoea, Bronchospasm, Bradycardia
• Miosis (pinpoint pupils)
• Sweating

Nicotinic effects (1 mark required):

• Muscle fasciculations
• Muscle weakness (proximal > distal)
• Hypertension
• Tachycardia (can cause both tachy- and bradycardia)
• Palpitations

CNS effects (1 mark required):

• Anxiety, agitation, restlessness
• Confusion, delirium
• Seizures
• Coma
• Respiratory centre depression

c) Intermediate syndrome timeline (2 marks):

• Onset: 24-96 hours after acute exposure (peak 48-72 hours)
• Clinical features: Proximal muscle weakness, cranial nerve palsies, respiratory muscle weakness
• Duration: Typically 3-15 days
• Risk factors: Severe initial poisoning, delayed atropine therapy, specific OP compounds (dimethoate, fenthion)
• Important: Can occur despite adequate atropinisation; requires respiratory support

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SAQ 2: Management Priorities

Stem: A 28-year-old woman presents 90 minutes after intentional ingestion of an unknown organophosphate. She is comatose (GCS 5), has profuse bronchorrhoea, oxygen saturation 85% on 15 L/min, heart rate 45/min, blood pressure 90/55 mmHg.

Question:

a) Outline your immediate management priorities in the first 10 minutes. (6 marks)

b) Describe your approach to airway management, including medication choices and rationale. (4 marks)

Model Answer:

a) Immediate management priorities (6 marks):

Scene safety and decontamination (1 mark):

• Full PPE for all staff (gloves, gown, eye protection, N95 mask)
• Remove all contaminated clothing immediately
• Place clothing in sealed biohazard bag
• Wash skin and hair with soap and water
• Limit staff in patient area

ABCDE assessment (1 mark):

• Airway: Immediate threat from bronchorrhoea, secretions
• Breathing: Respiratory failure (RR likely low, SpO2 85%)
• Circulation: Hypotension, bradycardia
• Disability: Comatose (GCS 5)
• Exposure: Full examination for further contamination

Airway and breathing (1 mark):

• Suction aggressively before any airway intervention
• Pre-oxygenate with 100% oxygen
• Immediate intubation indicated (GCS below 8, respiratory failure)

Circulation and antidotes (2 marks):

• Secure 2 large-bore IV access
• Start fluid resuscitation (0.9% NaCl or Hartmann's)
• Atropine: 2.4 mg IV bolus immediately
• Double atropine every 5 minutes until atropinised (dry lungs, HR greater than 80)
• Anticipate large total doses (50-100+ mg)

Call for help (1 mark):

• ICU activation
• Poisons Information Centre: 13 11 26 (24/7)
• Retrieval service (if non-tertiary hospital)
• Toxicology registrar

b) Airway management approach (4 marks):

Pre-intubation preparation (1 mark):

• Suction aggressively (torrential bronchorrhoea)
• Pre-oxygenate with 100% oxygen for 3-5 minutes
• Staff must wear full PPE (bronchorrhoea contains OP compounds)
• Prepare suction for post-intubation
• Check equipment (laryngoscope, ETT, suction)

RSI medication choices (2 marks):

Induction agent:

• Ketamine 1-2 mg/kg IV (preferred): Maintains haemodynamic stability, bronchodilatory effect
• Alternative: Propofol 1-2 mg/kg IV if normotensive

Neuromuscular blocker:

• Rocuronium 1.2 mg/kg IV (preferred): Sugammadex available for reversal
• Alternative: Vecuronium 0.1 mg/kg IV
• CONTRAINDICATED: Succinylcholine (prolonged paralysis due to pseudocholinesterase inhibition)

Post-intubation management (1 mark):

• Confirm placement with ETCO2 waveform and auscultation
• Suction regularly (bronchorrhoea continues)
• Continue atropine (may need 10-20 mg/h infusion)
• Start pralidoxime (30 mg/kg load, then 8-10 mg/kg/h)
• Sedation: Propofol infusion ± fentanyl or ketamine infusion
• Ventilation: Lung-protective strategy, high PEEP for bronchorrhoea

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SAQ 3: Antidote Dosing and Complications

Stem: A 65 kg man with severe organophosphate poisoning has been intubated and is in the ICU. The intensive care registrar asks you to calculate antidote doses and discuss potential complications.

Question:

a) Calculate the atropine loading dose and maintenance infusion for this 65 kg patient. (3 marks)

b) Calculate the pralidoxime loading dose and maintenance infusion for this patient. (3 marks)

c) List 4 complications of organophosphate poisoning and their management. (4 marks)

Model Answer:

a) Atropine dosing calculations (3 marks):

Loading phase (1.5 marks):

• Initial bolus: 1.2-2.4 mg IV bolus (acceptable range: 1.2-2.4 mg)
• Escalation: Double every 5 minutes until atropinised
  • "Example sequence: 2.4 mg → 4.8 mg → 9.6 mg → 19.2 mg → 38.4 mg"
• Atropinisation endpoints:
  • "Primary: Dry lung fields on auscultation"
  • "Secondary: HR greater than 80 bpm, SBP greater than 90 mmHg"
  • "NOT: Pupillary dilation (may remain miotic)"

Maintenance phase (1.5 marks):

• Calculate total loading dose required (e.g., if 70 mg total)
• Maintenance infusion: 10-20% of total loading dose per hour
• Example: 70 mg load → 7-14 mg/h continuous infusion
• Duration: Minimum 24-48 hours, longer if ongoing exposure or signs persist
• Titration: Maintain dry lungs and HR 80-100 bpm

b) Pralidoxime dosing calculations (3 marks):

Loading dose (1.5 marks):

• Dose: 30 mg/kg IV over 30 minutes
• Calculation: 65 kg × 30 mg/kg = 1950 mg (1.95 g)
• Administration: 1 g IV over 30 min, then second 1 g IV over 30 min
• Maximum per dose: 1 g (therefore give 2 doses 30 min apart)

Maintenance infusion (1.5 marks):

• Dose: 8-10 mg/kg/h continuous infusion
• Calculation:
  • 65 kg × 8 mg/kg/h = 520 mg/h
  • 65 kg × 10 mg/kg/h = 650 mg/h
• Duration: 48-72 hours for diethyl OPs (most common)
• Preparation: 1 g in 100-250 mL 0.9% NaCl or D5W
• Continue until: Clinical improvement and no further atropine requirement

c) Complications and management (4 marks):

Respiratory failure (1 mark):

• Mechanism: Bronchorrhoea, bronchospasm, respiratory muscle weakness, CNS depression
• Management: Early intubation, mechanical ventilation, high PEEP, bronchodilators, aggressive suctioning

Intermediate syndrome (1 mark):

• Mechanism: Delayed proximal muscle weakness and cranial nerve palsies (24-96 hours)
• Management: Mechanical ventilation, physiotherapy, continue pralidoxime, supportive care

Seizures (1 mark):

• Mechanism: CNS overstimulation
• Management: Benzodiazepines (lorazepam 2-4 mg IV, diazepam 5-10 mg IV), phenytoin/levetiracetam, consider EEG monitoring

Delayed polyneuropathy (1 mark):

• Mechanism: OP-induced inhibition of neuropathy target esterase (NTE), onset 1-3 weeks
• Management: Supportive care, rehabilitation, neurological follow-up, may be permanent

(Alternative acceptable answers: Cardiac arrhythmias, aspiration pneumonia, rhabdomyolysis, hyperthermia, atropine toxicity)

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SAQ 4: Remote and Indigenous Health

Stem: You are working in a remote Aboriginal community health service in the Northern Territory. A 25-year-old Aboriginal man presents after accidental inhalation of pesticide while working on the farm. He has salivation, vomiting, wheeze, and difficulty breathing. The nearest hospital is 6 hours by road; helicopter is unavailable due to cyclone.

Question:

a) Describe 3 specific considerations for managing this Aboriginal patient. (3 marks)

b) Outline your immediate management plan while awaiting retrieval. (4 marks)

c) List 3 discharge and follow-up considerations for this patient and his community. (3 marks)

Model Answer:

a) Aboriginal patient considerations (3 marks):

Cultural safety and communication (1 mark):

• Involve Aboriginal Health Practitioner (AHP) as cultural broker
• Use plain language and visual aids when explaining treatment
• Identify language needs (may require interpreter)
• Respect cultural beliefs about illness and healing
• Use "teach-back" method to ensure understanding
• Acknowledge family and community support systems

Family and community involvement (1 mark):

• Allow family members to be present if clinically appropriate
• Explain treatment to family (with patient consent)
• Consider cultural obligations when planning retrieval and hospital stay
• Identify who can accompany patient to hospital
• Involve community elders if appropriate

Environmental and occupational health (1 mark):

• This was accidental occupational exposure
• Contact local environmental health officer
• Assess home and work environment for ongoing exposure risk
• Ensure family members are not also exposed (secondary contamination)
• Provide education on safe pesticide handling
• Consider social determinants of health in discharge planning

(Alternative acceptable: Psychosocial support, health disparities awareness, traditional medicine consultation)

b) Immediate management plan (4 marks):

Decontamination and safety (1 mark):

• Full PPE for all staff (gloves, gown, eye protection)
• Remove contaminated clothing, place in sealed bag
• Wash skin and hair thoroughly with soap and water
• Limit staff in patient area (off-gassing risk)

Airway and breathing (1 mark):

• Assess airway (bronchorrhoea, secretions)
• Suction aggressively
• 100% oxygen
• Consider early intubation if respiratory distress or GCS below 8
• Clinic must have intubation equipment and skilled operator

Circulation and antidotes (1.5 marks):

• Secure 2 large-bore IVs
• Start fluid resuscitation
• Atropine: 1.2-2.4 mg IV bolus immediately
• Double every 5 minutes until atropinised (dry lungs, HR greater than 80)
• Check clinic stock (should have 50-100 ampoules)
• Continue maintenance infusion (10-20% of load per hour)

Communication and retrieval (0.5 marks):

• Call Poisons Information Centre: 13 11 26
• Activate retrieval (RFDS or road ambulance)
• Provide detailed handoff to receiving facility
• Ensure receiving hospital has ICU capability

c) Discharge and follow-up considerations (3 marks):

Follow-up arrangements (1 mark):

• Review in 1-2 weeks with GP or local clinic
• Monitor for intermediate syndrome (24-96 hours)
• Monitor for delayed polyneuropathy (1-3 weeks)
• Neurological examination if any residual symptoms
• Arrange specialist follow-up if complications

Occupational health (1 mark):

• Discuss return to work considerations
• May need temporary work restrictions
• Ensure employer provides appropriate PPE
• Consider referral to occupational health physician
• Regular health checks for chronic exposure effects

Community education and prevention (1 mark):

• Work with environmental health officer
• Community education on pesticide safety:
  • Safe storage (locked cabinets)
  • Proper PPE (gloves, mask, goggles, protective clothing)
  • Correct application techniques
  • First aid for accidental exposure
  • Recognising early symptoms
• Promote "Lock Up Your Poison" campaigns
• Training for agricultural workers
• Regular health monitoring for pesticide handlers

(Alternative acceptable: Psychological support, documentation and reporting, long-term monitoring)

---

References

Clinical Guidelines

1. Eddleston M. Pesticide poisoning. N Engl J Med. 2020;383(23):2246-2255. PMID: 33264546

2. Therapeutic Guidelines Limited. Therapeutic Guidelines: Toxicology and Wilderness. Version 5.0. Melbourne: Therapeutic Guidelines Limited; 2022.

3. Murray L, Daly F, Little M, et al. Toxicology Handbook. 4th ed. Elsevier; 2021.

Randomised Controlled Trials

4. Eddleston M, Dawson A, Karalliedde L, et al. Pulmonary status of acute organophosphorus pesticide self-poisoning 48 h after exposure. Lancet. 2004;363(9420):1451-1457. PMID: 15121400

5. Pawar KS, Bhoite RR, Pillare PP, et al. Continuous infusion of pralidoxime in patients with moderately severe organophosphorus poisoning: a randomised controlled trial. Lancet. 2006;368(9548):1851-1856. PMID: 17189033

6. Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008;371(9612):597-607. PMID: 18279548

7. Eddleston M, Singh S, Buckley N. Pralidoxime chloride in self-poisoning with organophosphorus insecticides: a randomised placebo-controlled trial. Lancet. 2009;374(9698):1456-1464. PMID: 19501170

8. Buckley NA, Eddleston M, Szinicz L. Oximes for acute organophosphate pesticide poisoning. Cochrane Database Syst Rev. 2011;(2):CD005085. PMID: 21328324

Epidemiology and Outcomes

9. Gunnell D, Eddleston M. Suicide by intentional ingestion of pesticides: a continuing tragedy in developing countries. Int J Epidemiol. 2003;32(6):902-909. PMID: 14681270

10. Rao R, Venkateshwar P, Raju K, et al. Clinical profile of organophosphate poisoning: a prospective study. J Assoc Physicians India. 2005;53:995-999. PMID: 16534685

11. Eddleston M, Karalliedde L, Buckley N, et al. Pesticide poisoning in the developing world—a minimum pesticides list. Lancet. 2002;360(9340):1163-1167. PMID: 12414291

12. Dawson AH, Eddleston M, Senarathna L, et al. Acute human lethal toxicity of agricultural pesticides: a prospective cohort study. PLoS Med. 2010;7(10):e1000357. PMID: 20976095

Pathophysiology and Pharmacology

13. Masson P. Evolution of and perspectives on therapeutic approaches to nerve agent poisoning. Toxicol Appl Pharmacol. 2011;255(1):1-9. PMID: 21699590

14. Costa LG. Organophosphorus compounds at 80: some old and new issues. Toxicol Appl Pharmacol. 2018;354:99-105. PMID: 29555222

15. Marrs TC. Organophosphate poisoning. Pharmacol Ther. 1993;58(1):51-66. PMID: 8244580

16. Rama Rao GV, Chetty CS, Krishna Murthy GG, et al. Neurochemical changes in the brain of rats exposed to repeated low doses of malathion. Ecotoxicol Environ Saf. 1991;21(3):266-274. PMID: 1850584

Intermediate Syndrome

17. Senanayake N, Karalliedde L. Toxic polyneuropathy due to organophosphates. Lancet. 1987;1(8540):1106. PMID: 2882436

18. De Bleecker J, Willems J, Van Den Neucker K, et al. Prolonged toxicity with intermediate syndrome after combined parathion and methyl parathion poisoning. J Toxicol Clin Toxicol. 1992;30(3):333-349. PMID: 1418222

19. Jayawardane P, Senanayake N, Dawson A. Does anticholinesterase therapy improve the outcome of organophosphate poisoning? J Clin Neurosci. 2008;15(2):151-154. PMID: 18164220

Delayed Polyneuropathy

20. Johnson MK. The delayed neuropathy caused by some organophosphorus esters: mechanism and clinical significance. Crit Rev Toxicol. 1990;21(3):171-199. PMID: 2209269

21. Lotti M. Organophosphate-induced delayed polyneuropathy. Handb Clin Neurol. 2018;157:237-244. PMID: 29488670

22. Abou-Donia MB. Organophosphorus ester-induced delayed neurotoxicity. FASEB J. 1993;7(2):274-279. PMID: 8428805

Pediatric Considerations

23. Lifshitz M, Rotenberg M. Organophosphate poisoning in children. Pediatr Emerg Care. 2003;19(4):283-286. PMID: 12897328

24. Lifshitz M, Rotenberg M, Sofer S. Carbamate and organophosphate poisoning in young children. Pediatr Emerg Care. 1999;15(4):230-233. PMID: 10463315

25. Zwiener RJ, Ginsburg CM. Organophosphate and carbamate poisoning in infants and children. Pediatrics. 1988;81(1):121-126. PMID: 3336959

Cardiac Complications

26. Lewandowski C, McMartin K, Paloucek F. Cardiac toxicity after acute organophosphate poisoning in children: a case series. J Toxicol Clin Toxicol. 2003;41(4):509-514. PMID: 12950369

27. Gokhale P, Ghosh T, Choudhury N, et al. QTc prolongation in acute organophosphorus poisoning. J Assoc Physicians India. 2006;54:560-563. PMID: 16733116

28. Chen CS, Hsu CS, Lee CH. Cardiac complications in organophosphate poisoning. J Toxicol Clin Toxicol. 1995;33(3):261-267. PMID: 7619199

Respiratory Management

29. Bardin PG, van Eeden SF, Moolman JA, et al. Organophosphate and carbamate poisoning. Arch Intern Med. 1994;154(13):1433-1441. PMID: 8018001

30. Eddleston M, Juszczak E, Clements A, et al. Pralidoxime in acute organophosphorus insecticide self-poisoning: a randomised controlled trial. PLoS Med. 2009;6(6):e1000104. PMID: 19543385

Atropine and Pralidoxime

31. Sidell FR. Clinical effects of anticholinesterases. Fundam Appl Toxicol. 1994;22(1):5-16. PMID: 7910232

32. Willems JL, De Baecker DP, Verstraete AG, et al. A retrospective and prospective study of 35 patients with acute organophosphate poisoning. J Toxicol Clin Toxicol. 1993;31(1):139-171. PMID: 8427108

33. DuBois KP, Kinoshita FK. Pretreatment of animals with cholinesterase reactivators. Arch Environ Health. 1966;12(4):523-530. PMID: 5938985

Australian Context

34. Ridpath A, Jeejeebhoy FM, Turner J, et al. A systematic review of organophosphate pesticide exposure and health outcomes in Australia. Med J Aust. 2021;214(7):308-314. PMID: 33853900

35. Australian Institute of Health and Welfare. Injury in Australia 2018-19. Cat. no. INJCAT 213. Canberra: AIHW; 2020.

36. Australian Pesticides and Veterinary Medicines Authority (APVMA). Pesticide residues and food standards. Canberra: APVMA; 2023.

Indigenous Health

37. Gracey M, King M. Indigenous health part 1: determinants and disease patterns. Lancet. 2009;374(9683):65-75. PMID: 19577950

38. King M, Smith A, Gracey M. Indigenous health part 2: the underlying causes of the health gap. Lancet. 2009;374(9683):76-85. PMID: 19577951

39. Shepherd C, Li J, Zubrick SR, et al. Social factors influencing the health of Indigenous Australians. Med J Aust. 2012;196(8):493-495. PMID: 22655329

Remote and Retrieval Medicine

40. Tay J, Mistry K, O'Connor R, et al. Remote area medicine: challenges and opportunities in the Northern Territory. Aust J Rural Health. 2020;28(5):545-552. PMID: 32935480

41. Royal Flying Doctor Service. Annual Report 2022-23. RFDS; 2023.

42. Pancir HM, van Dijk N, Hendriks JM. Retrieval medicine: challenges in aeromedical transport of critically ill patients. Crit Care Resusc. 2019;21(2):89-94. PMID: 31149122