Toxicology Approach

Toxicology

Risk assessment-based Approach: (Murray)

Resus-RSI-DEAD

Resuscitation (ABCDE)

• ABC
• Detect and correct (Hypogly, Sz, Hyper/hypothermia)
• Emergency Antidote Administration

Risk Assessment (ADTCP)

• Agent
• Dose
• Time since ingestion
• Clinical features and course
• Patient factors (weight and co-morbidities)

Supportive care and monitoring

Investigations

• Screening: 12 lead ECG, paracetamol
• Specific

Decontamination

Enhanced Elimination

Antidotes

Disposition

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RESUSCITATION

- acute poisoning associated with good neuro outcome (vs cardiac arrest in older patients) even after prolonged resus (hours)

- continue resus while obtaining expert advice

- cardiopulmonary bypass has been successful in some cases

- resus + supportive care are the priority NOT skin/GI decontamination

ABC

- with focus on AMS, loss of airway reflex, hypotension

- GCS <12 associated with increased risk of aspiration

AIRWAY

1. Airway Compromise

Mech: Corrosive injury to oropharynx

Agents: Alkalis, Acids, Glyphosate, Paraquat

Comments:

- Stridor, dysphagia and dysphonia indicate airway injury and potential for imminent airway compromise

- Early ET intubation or surgical airway often required

BREATHING

1. Acidosis/Acidemia

Mech: various

Agents: Ethylene glycol, Methanol, Salicylates

Comments:

- Until late in the clinical course there is usually prominent respiratory compensation

- Intubation and ventilation at standard settings may worsen acidemia and precipitate rapid clinical deterioration, if not death

- Avoid normo- or hypoventilation

- Maintain hyperventilation and consider bolus IV NaHCO3 1-2 mmol/kg to prevent worsening of acidemia

2. Hypoventilation

Mech: Opioid mu receptor stimulation

Agents: Opioids

Comments: Prompt administration of naloxone may obviate need for intubation and ventilation

3. Respiratory Failure

Mech: Cholinergic crisis

Agents: Carbamates, Nerve agents, OrganoPO4

Comments: Rapid administration of atropine by serial doubling of atropine dose to achieve dry respiratory secretions may restore adequate oxygenation

4. Acidosis, Hypoxaemia, Multi Organ Failure (MOF)

Mech: Oxygen-free radical mediated cellular injury, particularly type II pneumocytes

Agents: Paraquat

Comments:

- Avoid supplemental oxygen

- If hypoxia occurs, titrate supplemental oxygen to maintain oxygen saturation of ~ 90% or PaO2 60mmHg

CIRCULATION

1. Ventricular fibrillation

Mech: Hypocalcaemia

Agents: Hydroflouric acid ingestion or massive cutaneous burn

Comments:

- Defibrillation alone unlikely to be efficacious

- Bolus IV calcium (eg 60-90 mL of 10% calcium gluconate) repeated as required every 2 minutes until defibrillation restores perfusing rhythm

2. Ventricular tachycardia

Mech: Fast Na+ channel blockade

Agents: Chloroquine, Cocaine, Flecainide, Local anaesthetic agents, Procainamide, Propranolol, Quinine, TCA

Comments:

- Cardioversion or defibrillation unlikely to be efficacious

- Urgently intubate and hyperventilate

- Bolus IV NaHCO3 1-2 mmol/kg repeat every 1-2 minutes until restoration of perfusing rhythm

- Do not await serum pH determination prior to intubation and NaHCO3 boluses

- Lignocaine is third-line therapy when pH is established at >7.5

- Amiodarone and Vaughn Williams type 1a antiarrhythmics (eg procainamide) are contraindicated

3. Ventricular ectopy/tachycardia

Mech: Halogen-induced myocardial sensitisation to catecholamines

Agents: Chloral hydrate, Organochlorines

Comments:

- Cardioversion or defibrillation unlikely to be efficacious

- Administer IV beta-blockers, titrate to ectopy response

4. SVT

Mech: Adenosine antagonism

Agents: Theophylline

Comments: Urgent haemodialysis

5. Tachycardia

Mech: Central and peripheral sympathomimetic response

Agents: Amphetamines, Cocaine

Comments:

- Beta-blockers contraindicated

- Administer IV benzodiazepines, titrated to gentle sedation and HR control

6. Asystole, Bradycardia, Tachycardia

Mech: Na+/K+ ATPase pump inhibition

Agents: Digoxin

Comments:

- Usual resuscitative interventions futile

- Digoxin-specific antibodies

7. Bradycardia, Hypotension, Conduction defects

Mech: Calcium Channel blockade

Agents: CCB

Comments:

- Atropine and pacing unlikely to be efficacious

- Bolus IV Calcium (eg 60 mL of 10% calcium gluconate) may provide temporary haemodynamic stability by increasing HR and BP, while other treatments are organised

- High-dose insulin-dextrose therapy

8. Refractory hypotension

Mech: Various

Agents: Beta-blockers, CCB, local anaesthetics

Comments: High-dose insulin-dextrose therapy

9. Hypertension

Mech: Central and peripheral sympathomimetic response

Agents: Amphetamines, Cocaine

Comments:

- Beta-blockers contraindicated

- Administer IV benzodiazepines, titrated to gentle sedation and HR control

- If further treatment necessary, use titratable agents like:

GTN, Nitroprusside, Phentolamine

10. ACS

Mech: Central and peripheral sympathomimetic response

Agents: Amphetamines, Cocaine

Comments:

- Beta-blockers contraindicated

- Benzo

- GTN

- Antiplatelet adn anticoagulation therapy if no neurological deficits (otherwise cranial CT first)

- Reperfusion therapy along conventional lines

OTHER

1. Hyperkalaemia

Mech: Na+/K+ ATPase pump inhibition

Agents: Digoxin

Comments:

- Calcium salts contraindicated

- Digoxin-specific antibodies

2. Hypoglycaemia

Mech: Hyperinsulinaemia

Agents: Sulfonylureas

Comments:

- difficult to maintain euglycaemia with dextrose alone

- Ocreotide administration obviates need for dextrose supplementation

3. Refractory Seizures

Mech: Inhibition of GABA production

Agents: Isoniazid

Comments: IV pyridoxine: 1 gram per gram of isoniazid ingested, up to 5 grams

4. Seizures

Mech: Adenosine antagonism

Agents: Theophylline

Comments: Urgent haemodialysis

Detect and Correct Seizures

- Toxic seizures are generalised

- Usually controlled by benzos (diazepam, midazolam, lorazepam or clonazepam)

- most commonly caused in Australasia by:

1. Venlafaxine

2. Bupropion

3. Tramadol

4. Amphetamines

- focal/partial seizure is either a complication of poisoning or needs further consideration of non-tox cause

- 2nd line: Barbiturate

- 3rd line: Pyridoxine due to INZ poisoning

- Phenytoin is contraindicated for toxic seizures

Detect and Correct Hypoglycaemia

- if <4 mmol/L = give 50-50 (50 mls of 50% Dextrose), 5mL/kg of 10% Dextrose in kids

- Associated with:

1. Insulin and Sulfonylurea OHA

2. Beta-blockers

3. Quinine

4. Chlorquine

5. Salicylates

6. Valproic acid

Detect and Correct Hyper-/Hypothermia

- Hyperthermia is associated with life-threatening poisonings and poor outcome

- >38.5'C: needs continuous core-temperature monitoring

- >39.5'C: emergency to intervene and prevent MOF and neuro injury; NM paralysis with intubation and ventilation helps to stop muscle-generated heat production and rapid reduction of temperature

- Profound hypothermia (<29'C core): mimics or cause cardiac arrest: coma, fixed pupils, brady (usually Af), hypotension; Aggressive exogenous rewarming while CPR. Most effective is CP bypass. Alternative is pleural lavage through intercostal catheter with large volumes of fluid warmed to 40-45'C.

Emergency Antidote Administration

- sometimes indicated during resus

- examples: DANS

1. Sodium Bicarb for TCA

2. Naloxone for Opioids

3. Atropine for OrganoPO4

4. Digoxin-specifc antibodies for Digoxin with cardiovascular compromise

RSI

Risk Assessment (ADTCP)

1. Agent

2. Dose and type (eg ?sustained release)

3. Time since ingestion:

eg. TCA life threats occur within 6 hours (usu. within 2 hours), therefore low-risk patients can be identified 6 hours post ingestion)

4. Clinical features and course/progress

5. Patient factors (weight and co-morbidities)

Backup history:

1. Ask ambulance officers or family to search for agents

2. Counting missing tablets

3. Checking medical records for previous prescriptions

4. Question relatives about agents available to patient