Title: Toxicology

Q: CAGE questions
A: Cut down
Annoyed
Guilty
Eye-opener

Q: FRAMES approach to alcohol disorders
A: Feedback: Review problems caused by alcohol
Responsibility of patient
Advice
Menu of options
Empathic approach
Self-efficacy: Encourage optimism

Q: When does alcohol withdrawal arise?
A: 6-24 hours from last drink

Q: When does alcohol withdrawal autonomic excitation peak?
A: 24-48 hours

Q: Mortality of delirium tremens?
A: 8%

Q: Definition of delirium tremens?
A: Global confusion, delirium, hallucinations, respiratory and cardiovascular collapse +- death

Q: Complications of alcohol disorders
A: Social issues
Alcohol withdrawal
Wernicke-Korsakoff
Pancreatitis
Hypoglycaemia
Alcoholic ketoacidosis
Aspiration pneumonia
Acute hepatitis
Chronic liver disease
Trauma

Q: Wernicke's encephalopathy triad
A: Confusion, ophthalmoplegia, ataxia

Q: When is inpatient detoxification more suitable from alcohol
A: Previous severe withdrawal or seizures
Symptoms unmanageable in ED with oral diazepam
Poor social support
Severe withdrawal on presentation
Significant psychiatric or medical comorbidities

Q: Management of delirium tremens
A: Diaz 5-10mg IV q15min
Treat hypoglycaemia
Thiamine 200mg IV TDS for first 24 hours then 100mg IV daily for 3 days then 100mg PO daily
Monitor fluid balance/electrolytes
Consider ICU

Q: Management of Wernicke
A: Thiamine 500mg IV over 30 minutes TDs for 3 days
Then 250mg IV daily for 3-5 days until clinical improvement
Then 100mg PO daily

Q: How does anticholinergic syndrome present?
A: Agitated delirium with peripheral antimuscarinic blockade
 - Dry skin
 - Flushed
 - Tachycardia/hypertension
 - Dry mucous membranes
 - Dilated pupils
 - Hyperthermia
 - Sparse or absent bowel sounds
 - Urinary retention

Q: Agents that can lead to anticholinergic delirium
A: Antiparkinsonian - Benztropine
Typical antipsychotics - Haloperidol
Atypical antipsychotics - Olanzapine
Antihistamines
TCAs
Oxybutynin
Carbamezapine

Q: Management of anticholinergic syndrome
A: Airway control if required
Fluid resuscitation
IDC
Diazepam 5-10mg PO or IV q10-15min
Screening ECG, BSL, paracetamol level
Physostigmine 1mg IV slow push over 5 minutes q10min until desired effect

Q: Risk assessment for newer anticonvulsants
A: Mild transient CNS depression
Usually symptoms within 2 hours and resolve within 24
Coma and seizures are rare

Q: Which newer anticonvulsants pose specific problems?
A: Lamotrigine can cause ataxia, nystagmus for up to 48 hours
Topiramate can cause NAGMA (carbonic anhydrase inhibition) for up to 7 days and carries risk of ataxia and seizures

Q: Effects of carbamazepine
A: Dose-dependent CNS depression and anticholinergic effects + Na channel blockade at extreme doses

Q: Effect of carbamazepine 20-50mg/kg
A: Mild to moderate CNS depression + Anticholinergic

Q: Dangerous dose of carbamazepine
A: >50mg/kg

Q: Expected progression in carbamazepine overdose
A: Cardiotoxic at very high doses
Prolonged coma due to pharmacobezoar formation, slow elimination

Q: Toxic dose in children of carbamazepine
A: >= 400mg (one tablet) or >50mg/kg whichever is lower

Q: When can coma arise after carbamazepine overdose?
A: Up to 8-12 hours from ingestion

Q: Effects of large carbamazepine overdoses
A: Coma, seizures, ventricular dysrhythmias, hypotension

Q: Therapeutic carbamazepine levels?
A: 8-12mcg/L

Q: Expected symptoms with carbamazepine level 12mcg/L - 20mcg/L
A: Nystagmus and ataxia

Q: Expected effects of CBZ >40mcg/L
A: Coma, seizure, ventricular dysrhythmias, hypotension

Q: How does CBZ cause ventricular dysrhythmias?
A: Sodium channel blockade
(structurally similar to TCA imipramine)

Q: Management of CBZ ventricular dysrhythmias
A: Bicarb as for TCA

Q: What enhanced elimination methods are indicated for CBZ overdose?
A: Multiple dose AC 25g q2h if intubated, bowel sounds and not high aspirates
Haemodialysis if level >40mcg/L at 48 hours or haemodynamic instability

Q: Expected effects of phenytoin >20mg/kg
A: Ataxia, dysarthria, nystagmus

Q: Expected effects of phenytoin >100mg/kg
A: Coma and seizures

Q: What type of metabolism does phenytoin show?
A: Saturable kinetics whereby small increase in dose can cause toxic effects

Q: How long do symptoms of phenytoin acute toxicity usually last?
A: 2-4 days

Q: How does chronic phenytoin toxicity present?
A: Ataxia, nystagmus, dysarthria

Q: Are phenytoin levels helpful in toxicity?
A: Yes. Confirm diagnosis and correlate with symptoms.

Q: Expected symptoms with phenytoin level 30-40mg/L
A: Ataxia

Q: What methods of enhanced elimination are indicated in phenytoin OD?
A: Charcoal haemoperfusion if refractory/prolonged

Q: Does phenytoin cause coma?
A: Rarely. Consider other things

Q: How does chronic valproate toxicity present?
A: Idiopathic hyperammonaemia and hepatotoxicity

Q: When does valproate-induced CNS depression occur?
A: Can be delayed up to 12 hours

Q: Expected symptoms of valproate OD <200mg/kg
A: Asymptomatic or mild drowsiness/ataxia

Q: At what dose of valproate is intubation likely required?
A: >400mg/kg

Q: Potentially lethal OD of valproate?
A: >1g/kg

Q: Effects of >1g/kg of valproate
A: Coma, MODS, cerebral oedema, hypotension, lactic acidosis, hypoglycaemia, hyperammonaemia, bone marrow suppression

Q: Toxic dose of valproate
A: >200mg/kg

Q: How are valproate levels helpful?
A: Correlate with symptoms
If comatose, levels dictate need for haemodialysis

Q: When should valproate levels be done?
A: On presentation and q4-6hr until decreasing if CNS depression or >400mg/kg

Q: When is activated charcoal indicated for valproate?
A: >400mg/kg once intubated
Repeat dose at 4 hours if bowel sounds present and rising serum levels

Q: When is HD indicated for valproate toxicity?
A: Ingestion >1g/kg with level >1000mg/L
Serum level >1500mg/L at any time
Lactic acidosis or haemodynamic instability

Q: Management of valproate <200mg/kg
A: Monitor for 8 hours and discharge once alert and ambulant

Q: Hints of valproate toxicity
A: Unexplained coma, hypernatraemia, hypocalcaemia, lactic acidosis, hyperammonaemia without LFT derangement

Q: Which MAOi are most at risk of serotonin syndrome?
A: Irreversible, non-selective (tranylcypromine, phenelzine)
Any MAOi with other serotonergic agent = high-risk

Q: What is the tyramine reaction?
A: Tyramine-containing feed e.g. cheese, get severe occipital headache, hypertension, sweating, agitation +- hypertensive crisis

Q: Which MAOi can cause ECG changes?
A: Moclobemide (prolonged QT)

Q: Management of MAOi toxicity
A: AC if indicated
IV diazepam 5-15mg IV q15min for agitation/seizures
Fluid rehydration
Alpha-blockade (GTN, SNP, hydralazine) if severe HTN
Active cooling
Cyproheptadine 8mg PO/NG q8h if mild-moderate serotonin syndrome
Consider I&V

Q: How long should patient be monitored after MAOi overdose?
A: At least 12 hours

Q: Which SSRI are at risk of seizures/QT prolongation?
A: Escitalopram/citalopram

Q: What proportion of SSRI OD suffer serotonin syndrome?
A: <20%

Q: What dose of citalopram and escitalopram risks QT prolongation?
A: >600mg and >300mg respectively

Q: How many tabs can a child take of SSRI without toxic effects?
A: Up to 3

Q: What proportion of citalopram/escitalopram OD suffer seizures?
A: <2%

Q: How long do escitalopram/citalopram OD need ECG monitoring?
A: 8 hours or until QT under nomogram
12 hours if >1g citalopram or >500mg escitalopram

Q: Which SSRI OD warrant AC?
A: Within 4 hours of >600mg citalopram/300mg escitalopram

Q: How long do non-citalopram/escitalopram OD need monitoring?
A: 6 hours or until well

Q: Name 7 TCA's
A: Amitryptiline, imipramine, clomipramine, dothiepin, nortryptiline, trimipramine

Q: How long does severe toxicity take to arise following TCA overdose?
A: Usually within 2 hours

Q: Life-threatening OD of TCA?
A: >10mg/kg

Q: Expected effects of 5-10mg/kg of TCA?
A: Drowsiness and mild anticholinergic

Q: Clinical effects of TCA overdose
A: Anticholinergic
Delirium
Coma
Ventricular dysrhythmias via sodium-channel blockade
Seizures

Q: Predictive nature of QRS duration in TCA overdose
A: >100ms predictive of seizures
>160ms predictive of VT

Q: How sensitive and specific is terminal R wave in aVR >3mm for seizures/arrhythmia?
A: 80%sensitive and 73% specific

Q: ECG signs of TCA overdose
A: Terminal R wave aVR >3mm
R/S ratio aVR >0.7
Broad QRS
Sinus tachycardia
VT
Right axis deviation
QT prolongation
AV block
Non-specific ST/T wave changes
Brugada pattern

Q: When should TCA overdose be intubated?
A: GCS <12 at any stage

Q: Management of ventricular dysrhythmia from TCA overdose?
A: Sodium bicarbonate 100mmol IV q1-2min until pH 7.5-7.55 and perfusing rhythm
Lignocaine is second-line 1.5mg/kg

Q: When is AC indicated for TCA overdose?
A: >10mg/kg after intubation

Q: When should resuscitation efforts of TCA overdose be ceased?
A: pH >7.5, hyperventilated, sodibic and I&V

Q: Risk of seizures with SNARI's?
A: 14% (vs 2% SSRI)

Q: When can seizures occur following SNARI overdose?
A: Up to 16 hours delayed

Q: Risk of seizures with SNARI overdose <1.5g
A: <5%

Q: Risk of seizures with SNARI overdose <3g
A: 10%

Q: Risk of seizures with SNARI overdose >3g
A: 30%

Q: Risk of seizures if SNARI dose >4.5g
A: 100%

Q: At what dose of SNARI do ECG changes occur?
A: >4.5g. QRS and QT prolongation

Q: How does SNARI toxicity present?
A: Dysphoria, mydriasis, hypertension, tremor, tachycardia and seizures
*Serotonin syndrome*

Q: Are comas common or rare in SNARI overdose?
A: Rare. Consider alternative coingestants

Q: Management of SNARI overdose
A: Titrated benzos for agitation/tachycardia/hypertension
Aggressively treat hyperthermia
Cyproheptadine 8mg PO/NG q8h
AC if presents within 2 hours of >4.5g

Q: How long must SNARI overdose be watched?
A: >16 hours

Q: How long does SNARI overdose need cardiac monitoring?
A: <4.5g = 6 hours
>4.5g = 12 hours

Q: Pitfalls of SNARI overdose management
A: Failure to appreciate delayed seizures up to 16 hours
Inadequate early benzos
AC around time of seizure (>2 hours from ingestion)

Q: What is the greatest risk of bupropion overdose?
A: Seizures

Q: How long can seizures occur up to after bupropion oD?
A: 24 hours

Q: What is the seizure risk of bupropion overdose >4.5g?
A: 50%

Q: What is the seizure risk of bupropion dose >9g
A: 100% + Haemodynamic instability, broad QRS, prolonged QT

Q: Management of bupropion overdose
A: AC once airway secured
Cardiac monitoring
ECG every 2 hours if >4.5g
Early intubation if >9g
IV diazepam titrated for agitation/seizures
Broad-complex tachy - I&V, bicarb as for TCA

Q: Do benzos prevent seizures in bupropion overdose?
A: Yes. If given early and titrated

Q: Effects of non-sedating antihistamines in OD
A: Some sedation +- anticholinergic
QT prolongation rarely

Q: How long do non-sedating antihistamine OD need ECG's?
A: Every 4 hours for at least 12 hours if symptomatic in case of QT prolongation

Q: When is AC indicated for non-sedating antihistamine OD?
A: Never

Q: Management of non-sedating antihistamine OD?
A: Replace Ca/Mg/K in case of prolonged QT
IV diazepam for anticholinergic agitation
Physostigmine 0.5-1mg IV slow push over 5 minutes q10min for anticholinergic delirium
ECG q4h hours if symptomatic for QT prolongation

Q: Effects of sedating antihistamines in overdose
A: Dose-dependent sedation
Anticholinergic delirium
Prolonged QT/QRS and hypotension in massive OD
Seizures rarely

Q: Management of prolonged QT/QRS in sedating antihistamine OD?
A: Sodibic, hyperventilation like TCA

Q: What is amisulpride?
A: Atypical antipsychotic

Q: Risks of amisulpride overdose?
A: QT prolongation and CNS depression

Q: Toxic dose of amisulpride?
A: >4g

Q: Risk assessment of amisulpride?
A: <4g - Mild Cns depression, mild anticholinergic
>4g - Risk of QT prolongation, bradycardia, hypotension and CNS depression

Q: When does amisulpride toxicity usually arise?
A: Delayed 5-20 hours

Q: How long do amisulpride overdoses need serial eCG's for?
A: At least 16 hours if >4g ingestion and continuous monitoring if prolonged QT

Q: When is AC indicated for amisulpride oD?
A: If presents within 4 hours

Q: Disposition of amisulpride <4g overdose
A: If normal ECG and alert - discharge

Q: What does bradycardia suggest in amisulpride overdose?
A: High risk of prolonged QT and torsades

Q: Clinical features of clozapine overdose
A: More severe if not on normally
CNS depression within 4 hours
Tachycardia, orthostatic hypotension
Anticholinergic
Small pupils ?
Hypersalivation is pathognomonic
Seizures (5-10%)
EPSE in children

Q: How common are seizures in clozapine overdose?
A: 5-10%

Q: Does clozapine cause QT prolongation?
A: Rarely

Q: Are clozapine levels useful in acute overdose?
A: Only to confirm overdose. Levels do not correlate to risk assessment

Q: How long do EPSE continue in children in clozapine overdose?
A: Up to 7 days

Q: Typical presentation of clozapine overdose
A: Anticholinergic presentation with small pupils and hypersalivation

Q: Does agranulocytosis occur in clozapine overdose?
A: No. Chronic use

Q: Does myocarditis occur in clozapine overdose?
A: No. Chronic

Q: Toxic overdose of olanzapine?
A: >40mg

Q: Clinical features of olanzapine overdose
A: Sedation, anticholinergic +- agitation, coma, hypotension

Q: Dose of olanzapine above which coma and hypotension are likely?
A: >300mg

Q: Toxic dose of olanzapine in children?
A: >0.5mg/kg

Q: When do clinical features arise in olanzapine overdose?
A: Wthin 2-4 hours

Q: Does olanzapine cause QT prolongation?
A: Rarely

Q: When is AC indicated for olanzapine overdose?
A: Never

Q: Clinical features of typical antipsychotic overdose?
A: Sedation, tachycardia, hypotension and anticholinergic effects

Q: Do typical antipsychotics cause cardiac dysrhythmias?
A: Rarely. Risk of QT prolongation but not clinically significant

Q: Do typical antipsychotics cause seizures?
A: Very rarely

Q: How long can EPSE occur in children after typical antipsychotic overdose?
A: Up to 3 days

Q: When is AC indicated in typical antipsychotic overdose?
A: Only if needing intubation

Q: Clinical features of quetiapine OD <3g
A: Mild-moderate sedation and sinus tachycardia

Q: Clinical features of quetiapine >3g
A: Cns depression, coma, hypotension, delirium and seizures

Q: Does quetiapine cause QT prolongation?
A: Yes. No reports of Torsades

Q: How long does sedation last following quetiapine overdose?
A: Up to 72 hours

Q: How long should adult patient be kept following quetiapine overdose?
A: <3g - Until well or at least 4 hours (IR) or 8 hours (XR) with normal ECG
>3g - Admit for observation

Q: Which vasopressor/inotrope is preferred in quetiapine-induced hypotension?
A: Noradrenaline as adrenaline can cause predominant beta-2 agonism and subsequent paradoxical hypotension

Q: Clinical features of risperidone overdose
A: Sinus tachycardia
Mild sedation
Acute dystonias
QT prolongation (no torsades)

Q: How long does risperidone toxicity last?
A: <24 hours

Q: Antidote for risperidone toxicity?
A: For acute dystonias - Benztropine 1mg IV slow injection

Q: Most common causes of toxicological seizures in Australia?
A: Tramadol
Venlafaxine
Amphetamines
Bupropion
Withdrawal

Q: Hypoglycaemia associated with which toxidromes?
A: Insulin
Beta-blocker
Sulfonylureas
Salicylic acid
Valproate
Quinine
Chloroquine

Q: General supportive measures for tox patients
A: Sedation
Seizure control
Glucose monitoring/management
Temperature monitoring/control
Nutrition
Respiratory toilet
IDC
VTe prophylaxis
Prevention of pressure areas

Q: Why is salicylate screening not advised in Australia?
A: Rare and not occult given acid-base changes

Q: Potential risks of GI decontamination
A: Aspiration
Bowel obstruction
Diversion of resources
Fluid shifts
Electrolyte imbalances
Reduced absorption of subsequent oral agents

Q: Agents not bound to activated charcoal
A: Iron
Lithium
Potassium
Mercury
Lead
Acids/alkalis
Alcohols

Q: Dose of AC in children?
A: 1g/kg

Q: How can AC be given to children?
A: Mix with ice cream

Q: Indications for whole bowel irrigation
A: Iron
Lead
Potassium
Verapamil/diltiazem XR
Body packers

Q: Complications of whole bowel irrigation
A: Nausea, vomiting
Abdominal bloating
NAGMA
Aspiration
Distraction
Electrolyte and fluid shifts

Q: Dose of WBI
A: PEG 2L/hr by continuous infusion (25mL/kg/hr)

Q: Benefits of multiple dose AC
A: Interrupts enterohepatic circulation
GI dialysis effect
Adsorbs sustained release preparations/pharmacobezoars

Q: Indications for MAC
A: Carbamazepine coma
Phenobarbitone coma
Dapsone overdose with methaemoglobinaemia
Quinine
Theophylline (HD more important)
Phenytoin
Piroxicam

Q: Dose of MAC
A: 25g q2h

Q: How does urinary alkalinisation help?
A: Promotes ionisation of weak acids in the renal tubules to enhance elimination

Q: Indications for urinary alkalinisation
A: Salicylate toxicity
Phenobarbitone coma (MDAC superior though)

Q: Method of urinary alkalinisation
A: Correct hypokalaemia
1-2mmol/kg sodibic
Infusion 150mmol sodium bicarb in 850mL dextrose at 250ml/hr
Target urinary pH >7.5 and monitor serum pH/K/Ca/Mg

Q: Does urinary alkalinisation risk acidosis or dehydration?
A: No

Q: Methods of extracorporeal elimination
A: Haemodialysis
Haemoperfusion
haemofiltration
Plasmapheresis
Exchange transfusion

Q: Agents for which HD may be beneficial
A: Lithium
Salicylates
Iron
Toxic alcohols
Theophylline
Phenobarbitone
Metformin lactic acidosis
Massive valproate OD
Massive carbamezapine OD (charcoal haemoperfusion may be better)
Potassium salt

Q: Indications for sodium bicarbonate?
A: TCA overdose with QRS >100ms
Propranolol OD with ventricular arrhythmias
Carbamezapine OD with ventricular arrhythmias
Flecainide
Quinidine
Urinary alkalinisation for salicylate or phenobarbitone coma
Cyanide toxicity
Isoniazid
Toxic alcohol poisoning
Severe NAGMA
Severe hypobicarbonataemia
pH <7.1

Q: Which agents have a narrow therapeutic window in renal impairment?
A: Diazepam (active metabolites)
Morphine
Aminoglycosides
Vancomycin
Imipenem
Digoxin
Metformin
Salicylates
Lithium

Q: Indications for intralipid
A: Bupivacaine
Other LA
Verapamil/diltiazem
Propranolol
TCA

Q: Does HIET have a chronotropic effect?
A: No. Only inotropic

Q: Complications of HIET
A: Hypoglycaemia, hypokalaemia, hypoMg, hypophosphataemia

Q: What is the difference between body packers and stuffers?
A: Body packers are meticulously wrapped agents
 - Far higher doses
 - Usually in intestine by time of ED presentation and present with law enforcement or due to packet rupture
Body stuffers haphazardly rush to internally conceal drugs
 - Usually present with law enforcement without toxidromes but more likely to leak

Q: Management of body stuffers?
A: AC if within 1 hour
Non-con CT to localise all packets
Discharge if no packets found
Urinary drug screening does not alter management

Q: Management of body packers
A: Resus
Any toxidrome spells onset of severe toxicity
Non-contrast CT abdo/pelvis
Continuous monitoring
If asymptomatic can eat normal diet
Ambulation is encouraged to prevent bowel obstruction
Observe until all expected packets counted or three packet-free stools passed and no further packets on repeat CT

Q: What is the mean time to pass all packs in body packers?
A: 5 days

Q: Does negative urinary drug test help in body packers?
A: No. Does not rule out ingestion of packets or safety

Q: Sensitivity and specificity of non-con CT for body packers?
A: 100%

Q: Is the packet count on CT accurate?
A: <15 = YEs
>15  = No

Q: Do body packers need a repeat CT once all suspected packets are passed?
A: Yes. Mandatory

Q: What is the risk of serious complications with conservative management of body packers?
A: <5%

Q: When is endoscopy indicated for body packers?
A: Stuck in stomach
stuck in colonic flexure
Carries risk of rupture

Q: When is surgery indicated for body packers?
A: Cocaine intoxication
Bowel obstruction/perf

Q: Clinical effects of acute overdose of amiodarone
A: Delayed hypotension, A flutter, TWI only

Q: Chronic toxicity of amiodarone
A: Corneal deposits
Lung fibrosis
Thyroid dysfunction
Bradycardia/negative inotropy/AV blockade/Torsades
Hepatic toxicity

Q: Elimination of amiodarone
A: Biliary. Up to 80 hours after acute ingestion or 100 days for chronic therapy

Q: Management of oral amiodarone OD
A: AC if within 2 hours
Cardiac monitoring for at least 24 hours (some say longer)
Supportive care +- adrenaline/fluids

Q: Clinical features of ACEi overdose?
A: Mild hypotension, mild hyperkalaemia, mild renal impairment

Q: Which beta-blockers are most dangerous?
A: Propranolol and sotalol

Q: What factors increase the risk of toxicity in beta-blocker OD?
A: Sotalol/propranolol
Co-ingestant cardiac meds
Elderly
Comorbid heart/lung disease

Q: Toxic dose of propranolol
A: >1g

Q: Early ECG sign of beta-blocker toxicity?
A: PR prolongation

Q: Why is propranolol dangerous
A: Sodium channel blockade at heart AND CNS as lipid soluble

Q: Why is sotalol dangerous?
A: K channel blocker in heart causing prolonged QT/torsades

Q: Which beta-blocker is lipid soluble?
A: Propranolol

Q: Presentation of beta-blocker overdose
A: PR prolongation, AV block, bradycardia, hypotension, bronchospasm, pulmonary oedema, hyperkalaemia, hypoglycaemia
Propranolol - QRS widening, ventricular dysrhythmias, dominant terminal R wave, R/S >0.7 in aVR, right axis, delirium, coma, seizures
Sotalol - QT prolongation, Torsades

Q: When is AC indicated in beta-blocker overdose?
A: Within 2 hours (careful if propranolol as potential seizure/coma)

Q: Management of metoprolol OD
A: ABCDE
Supportive care
Fluids
Atropine 500mcg q5min
Adrenaline/isoprenaline infusions
Pacing
HIET 1U/kg actrapid with 50mL 50% dextrose then 0.5U/kg/hr uptitrated as required with covering 50% dextrose
Consider intralipid (although not very lipid soluble)

Q: What dose of verapamil/diltiazem XR can cause severe toxicity?
A: 2-3x normal dose or >10 tabs

Q: How long can CCB toxicity be delayed in XR preparations?
A: 16 hours

Q: Risk factors for increased toxicity in CCB overdose?
A: Other cardiac med coingestants, comorbidities, elderly

Q: When do CCB XR preparations have peak effects
A: >24 hours

Q: Clinical features of CCB toxicity
A: Bradycardia, AV block, hypotension
Seizures, coma are rare (look for co-ingestants)
Hyperglycaemia
Lactic acidosis

Q: Do dihydropyridines cause severe toxicity?
A: In large doses can cause negative inotropy/chronotropy and heart block also

Q: Management of CCB toxicity
A: ABCDE
Calcium gluconate 10% 60mL over 10 min every 20 minutes up to 3 times
Fluids
Adrenaline infusion
Transcutaneous pacing at 60/min
HIET 1U/kg actrapid with 50mL 50% dextrose then 0.5U/kg/hr with dextrose infusion
AC if intubated
AC if alert within 1 hour of IR or 4 hours XR
Consider CPB/ECMO/IABP

Q: When is whole bowel irrigation indicated in CCB toxicity?
A: After AC if not established toxicity within 4 hours of >10 tabs of verapamil or diltiazem XR

Q: Pitfalls of CCB overdose
A: Fail to appreciate delayed deterioration in XR ingestion
Failure to initiate aggressive decontamination (AC and WBI) if presenting early with life-threatening XR preparation overdose
Delay in HIET

Q: When does clonidine toxicity arise?
A: Always within 6 hours

Q: Toxic dose of clonidine in children?
A: >10mcg/kg or 2 tabs

Q: Clinical features of clonidine toxicity
A: Transient early HTN
Lethargy, miosis, slurred speech, ataxia
Severe intoxication - Coma, bradycardia, hypotension

Q: When is bradycardia treated in clonidine toxicity?
A: Only if hypotensive or reduced end-organ perfusion

Q: Management of clonidine toxicity
A: IV fluids
Adrenaline infusion if bradycardic AND hypotensive
Can consider pacing
Naloxone 100mcg every 30-40 seconds up to four times (may not work and probably better just to I&V if sedated)

Q: Potentially lethal digoxin ingestion
A: >10mg (adult) or 4mg (child)
Serum dig level >15nmol/L (12ng/mL)
Serum K > 5.5

Q: Peak effect of digoxin
A: 6 hours

Q: Clinical features of digoxin overdose?
A: GI early
CVS: Bradycardias, AV block, atrial tachyarrhythmias, VT, hypotension
CNS: Lethargy, confusion, coma

Q: How long after digibind is provided should ACLS efforts continue?
A: 30 minute

Q: Temporising measures for digoxin toxicity (other than digibind)
A: Treat hyperkalaemia as usual (avoid calcium unless necessary)
Atropine 600mcg up to 3 times
Lignocaine 1mg/kg over 2 minutes for ventricular dysrhythmias

Q: When is AC indicated in digoxin overdose?
A: If within 1 hour and cooperative or after intubation

Q: Digifab dosing in acute overdose
A: Arrest - 20 ampoules + 5 amps q30min
Unstable - 10 amps + 5 amps q30min
Stable - 5 amps + 5 amps q30min

Q: How long does digibind take to work?
A: 20 minutes and maximal at 4 hours

Q: Endpoints of digibind therapy
A: Normal cardiac rhythm and conduction + resolution of GI symptoms

Q: Is there a place for repeat dig levels after digibind?
A: No. Assays measure both bound and unbound

Q: Mortality of serum K >5.5 in digoxin toxicity?
A: 100% without digibind

Q: Mortality of chronic digoxin toxicity without treatment?
A: Up to 30% within 1 week

Q: Presentation of chronic digoxin toxicity
A: Elderly, intercurrent illness, GI symptoms, lethargy, confusion, bradycardias, increased automaticity and reduced visual acuity, xanthopsia, chromatopsia

Q: Are digoxin levels helpful in chronic overdose?
A: If significantly elevated, yes
If around therapeutic level correlate poorly with severity of symptoms
Likelihood of digoxin toxicity depends on symptoms and serum level

Q: Dose of digibind in chronic digoxin toxicity
A: 2 ampoules q30min usually sufficient
5 amps if cardiac arrest

Q: How long does digibind take to work in chronic toxicity?
A: Within 12 hours

Q: Best test for dabigatran overdose
A: Serum level
Normal APTT suggests minimal drug present

Q: Best test for Factor Xa inhibitors?
A: Factor Xa assay

Q: Does normal PT and APTT mean anything in Direct Factor X inhibitor overdose?
A: Suggests very low levels of drug present

Q: Management of NOAC overdose
A: Consider AC if within 4 hours of ingestion and cooperative or if intubated
Haematology consult
Stop any bleeding (including IR)
FBC, Coags, Factor Xa assay/Dabigatran level
ROTEM (not validated)
Plt >70
Antidotes
 - Dabigatran: Idarucizumab 5g IV over 10min
 - Factor Xa: Prothrombinex 50IU/kg IV, TXA, recombinant Factor VIIa 50mcg/kg if critical
Consider dialysis (dabigatran)

Q: When can NOAC overdoses be medically cleared?
A: No ongoing bleeding
Asymptomatic
Normal PT/APTT at 12 hours post-ingestion

Q: Toxic dose of warfarin if not normally on it?
A: >2mg/kg

Q: When is warfarins peak effect?
A: 72 hours

Q: Does normal INR after warfarin overdose rule out clinical intoxication?
A: No. Need normal INR at 48 hours

Q: Management of warfarin overdose in children?
A: >0.5mg/kg --> Give Vitamin K 10mg PO and discharge. No need for iNR or f/u

Q: Management of patients with no indications for warfarin who take warfarin overdose?
A: Vitamin K 5mg BD PO for 2 days then medically cleared. Repeat iNR at 48 hours

Q: Therapeutic overwarfarinisation without bleeding
A: INR <4.5 - Omit dose and re-test tomorrow
INR 4.5-10
 - Omit dose
 - Consider why
 - Vitamin K 1mg IV
INR >10
 - Omit doses
 - Repeat INR
 - Consider why
 - Vitamin K 5mg IV and consider prothrombinex 15-30IU/kg if high bleeding risk

Q: Causes of cholinergic syndrome
A: Acetylcholinesterase inhibitors
 - Organophosphates
 - Carbamates
 - Sarin
 - Dementia agents: Donepezil, rivastigmine
 - Myaesthenic agents: Edrophonium, neostigmine, physostigmine, pyridostigmine
Acetylcholines
 - Muscarinic: Acetylcholine, pilocarpine
 - Nicotinic: Nicotine
 - Mushrooms

Q: Clinical presentation of cholinergic syndrome
A: Copious secretions
Diarrhoea
Vomiting
Lacrimation
Urinary incontinence
Bradycardia (or hypertension/tachycardia if nicotinic effect)
Delirium, agitation, seizures
Muscle weakness

Q: Management of cholinergic crisis
A: Atropine 1.2mg IV doubled every 2-3 minutes targeting dried secretions
IV midazolam for seizures
Fluids + IDC
Pralidoxime 2g in 100mL N/S over 15 minutes then 500mg/hr

Q: Lethal complications of amphetamines
A: Aortic dissection
MI
ICH
Severe hyperthermia
Hyponatraemia
Cardiac arrhythmias

Q: How is ACS managed secondary to amphetamines?
A: same as usual but beta-blockers CI due to unopposed alpha thrombolysis relatively contraindicated

Q: How is tachycardia and hypertension managed secondary to amphetamines?
A: IV diazepam 5-15mg q10min +- alpha-blockers/nitrates

Q: When is AC indicated for amphetamine overdose?
A: Never

Q: Toxic dose of phenobarbitone?
A: >8mg/kg

Q: Enhanced elimination for phenobarbitone
A: MDAC
Dialysis

Q: When is AC indicated for benzodiazepine overdose?
A: Never

Q: Is cannibis dangerous in children?
A: Yes. Life-threatening CNs depression

Q: How long can cannibis coma last in children?
A: 36 hours

Q: Lethal dose of cocaine?
A: >1g

Q: Usual dose in one line of cocaine?
A: 20-30mg

Q: Toxic mechanism of cocaine?
A: Sympathomimetic
Vasoconstriction
Sodium channel blocker

Q: Clinical features of cocaine toxicity
A: Usual + sodium channel blockade at heart, QT prolongation

Q: Does cocaine affect the sensitivity of ECG?
A: Yes. Lower sensitivity for MI in the setting of cocaine OD

Q: Management of cocaine overdose
A: ABCDE
Supportive cares
IV diazepam 5-15mg q10min
Treat ventricular arrhythmias as for TCA
Lignocaine for ventricular arrhythmias (refractory to bicarb as for TCA)
Usual ACS management if suspected
Verapamil if refractory SVT
GTN/SNP if refractory HTN
Treat hyperthermia aggressively

Q: Which cocaine intoxications need a CT brain?
A: Any altered neurology, focal neurology or headache

Q: How long does GHB last?
A: 4-8 hours

Q: Peak effect of GHB
A: 30-60 min

Q: Clinical presentation of GHB overdose
A: Brief euphoria, then coma
Rousable but then somnolent again
Sudden recovery at 2-3 hours (if doesn't die)

Q: Which opioids cause QT prolongation
A: Methadone and oxycodone

Q: Toxic dose of codeine in children
A: >2mg/kg

Q: Indications for naloxone in dependence?
A: GCS <12, RR <8, hypoxia

Q: Elimination half-life of naloxone?
A: 60-90 min

Q: Initial dose of naloxone
A: Drowsy - 40mcg IV boluses titrated to effect every 30-60 seconds
Unconscious - 100mcg IV / 400mcg IM/SC repeated every 30-60 seconds
May need larger doses if partial opioid agonist overdose

Q: Rate of naloxone infusion
A: 2/3 of required dose over prior hour

Q: Does oxycodone usually need repeat naloxone dosing?
A: Yes

Q: Endpoint of naloxone
A: Naive patient - Full alertness
Dependent - GCS >12, RR >8, rousable

Q: How long can respiratory depression be delayed following SR opioid overdose?
A: 12 hours

Q: When do seizures usually occur with tramadol?
A: >6 hours after ingestion

Q: Toxic dose of tramadol?
A: >1.5g

Q: Toxic dose of tramadol in children?
A: >10mg/kg
Same as TCA and hydroxychloroquine

Q: Clinical features of tramadol overdose
A: Serotonergic and noradrenergic syndrome
Nausea/vomiting
Delayed seizures

Q: Management of tramadol overdose
A: Oral AC if within 2 hours of >1.5g overdose and alert OR if intubated
IV diazepam 5-15mg q10min for agitation/sympathomimetic/serotonergic symptoms
Cyproheptadine 8mg q8h PO/NG for serotonin syndrome
Consider naloxone

Q: Do benzos prevent seizures in tramadol overdose?
A: Yes

Q: When is AC indicated in tramadol overdose?
A: Within 2 hours if >1.5g taken OR if intubated

Q: Sodium channel blockers
A: TCA
Quinine
Propranolol
Flecainide
Carbamazepine
Procainamide
Local anaesthetic toxicity
Dextropropxyphene

Q: QT prolonging agents
A: Typical antipsychotics - Haloperidol
Atypical - Quetiapine
Sotalol
Amiodarone
Antihistamines - Diphenhydramine
Erythromycin
Metoclopramide
Methadone
Antidepressants - Escitalopram
Moxifloxacin

Q: Pharmacokinetic changes in the elderly
A: Reduced and delayed GI absorption
Decreased protein binding
Impaired hepatic metabolism
Impaired renal clearance

Q: Does the dose of insulin taken in overdose correlate with hypoglycaemia?
A: No. Unpredictable

Q: Does the type of insulin injected alter the duration of hypoglycaemia following overdose?
A: No. The duration extends to days irrespective of type

Q: What determines the duration of hypoglycaemia in insulin overdose?
A: Slow and erratic absorption of injected insulin + prolonged clearance

Q: Clinical features of insulin overdose
A: Hypoglycaemia
Agitation, sweating, coma, tachycardia, nausea, vomiting, seizures, hemiplegia, coma

Q: Management of insulin overdose
A: Treat hypoglycaemia with bolus
 - 50mL 50% in adults
 - 2mL/kg 10% in children
Commence 10% infusion at 100mL/hr and monitor glucose 15min until stabilised
Uptitrate to 25% or 50% as required

Q: When can insulin overdose be discharged?
A: Asymptomatic with normal glucose at 6 hours without supplementation

Q: Will diabetic or non-diabetic patients require higher glucose regimes after insulin overdose?
A: Diabetic as have impaired counter-regulatory responses

Q: Mortality rate of metformin-induced lactic acidosis?
A: >50% due to concomitant AKI and sepsis usually

Q: Toxic dose of metformin?
A: >10g

Q: Clinical features of metformin overdose
A: Asymptomatic until hours later when lactic acidosis arises with ALOC, nausea, vomiting, diarrhoea, hypotension, coma and death

Q: Does metformin cause hypoglycaemia
A: No

Q: When is AC indicated in metformin OD?
A: Within 2 hours of ingestion >10g if well

Q: Management of metformin-induced lactic acidosis
A: Fluids
Replace glucose if required
Bicarb if required
Haemodialysis if:
 - Unwell with lactic acidosis from therapeutic use
 - Worsening lactic acidosis following acute overdose with clinical instability

Q: When can metformin overdose be discharged?
A: If well at 8 hours with normal lactate and bicarb

Q: Name 3 sulfonylureas
A: Glibenclamide, gliclazide, glipizide

Q: Clinical features of sulfonylurea overdose
A: Profound and prolonged hypoglycaemia

Q: Management of sulfonylurea overdose
A: Supportive care
50mL 50% dextrose bolus
Glucose infusion until octreotide
Octreotide 50mcg IV bolus then 25mcg/hr
AC if within 1 hour and stable or up to 4 hours if XR preparation or if intubated

Q: Dose of octreotide in children for sulfonylurea overdose?
A: 1mcg/kg stat then 1mcg/kg/hr

Q: How long do children need to be kept following sulfonylurea overdose?
A: Up to 48 hours of normal bedside BSL

Q: How long do adults need to be kept following sulfonylurea overdose
A: Up to 8 hours if IR or 12 hours if SR
12 hours once octreotide/glucose ceased

Q: Toxic dose of lithium
A: >25g (if normal renal fx)

Q: Symptoms of >25g lithium
A: GI upset but rarely neurological symptoms

Q: Factors that increase risk of neurological symptoms in acute lithium OD
A: Renal impairment, hyponatraemia, dehydration

Q: Peak levels of slow release lithium
A: 12 hours

Q: How does hyponatraemia alter lithium toxicity?
A: Kidneys retain lithium as if it was sodium

Q: Serum lithium interpretation in acute overdose
A: Useful for risk assessment, confirmation of overdose and monitoring of therapy

Q: Management of acute lithium OD
A: ABCDE
Fluid therapy targeting UO >1mL/kg/hr
Normal Na
Cardiac monitoring NOT required
Consider HD if massive oD, renal failure or late presenters with neurotoxicity

Q: When can acute lithium OD be discharged?
A: No neurotoxicity, level <2.5mmol/L and falling

Q: Is coma a consequence of acute lithium OD?
A: No. If present, must be coingestant

Q: How are those on long-term lithium managed after acute overdose?
A: Exactly the smae

Q: Presentation of chronic lithium toxicity
A: Chronic dosing with intercurrent illness and subsequent neurological symptoms

Q: Are lithium levels helpful in chronic toxicity?
A: Only aid early diagnosis
Do not correlate with symptoms

Q: Hansen-Amdisen Grade 1 chronic lithium toxicity
A: Tremor, hyperreflexia, agitation, weakness, ataxia

Q: Hamsen-Amdisen Grade 2 chronic lithium toxicity
A: Stupor, rigidity, hypertonia, hypotension

Q: Hamsen-Amdisen grade 3 chronic lithium tox
A: Coma, seizures, myoclonus

Q: Drugs that impair lithium clearance
A: NSAID's
ACEi
Thiazides
Topiramate

Q: Why are TFT's indicated in chronic lithium toxicity?
A: Hypothyroidism can lead to failure to clear lithium

Q: When is HD considered for chronic lithium toxicity?
A: Neurological dysfunction and level >2.5mmol/L

Q: Local anaesthetics that cause methaemoglobinaemia?
A: Prilocaine, lignocaine, benzocaine

Q: Early signs of LA toxicity
A: Perioral tingling, tinnitus, dizziness, anxiety, confusion

Q: How does methaemoglobinaemia present?
A: Blue mucous membranes, SpO2 85-90% consistently, chocolate brown blood on sampling, normal PaO2
Confirm via metHb on ABG

Q: Drugs that cause methaemoglobinaemia
A: Prilocaine, benzocaine, lignocaine
Dapsone
Metoclopramide
GTN/SNP
Sulphonamides

Q: Management of methaemoglobinaemia
A: 100% O2
Methylene blue 2mg/kg over 5 min q30min
 - If symptomatic
 - If asymptomatic but >20% MetHb or >10% and anaemic/IHD

Q: Management of LA toxicity
A: ABCDE
Fluids/inotropes
Sodibic 100mmol q1-2min until perfusing rhythm, QRS <120ms
Benzos for seizures
Intralipid 1.5mL/kg then 0.25mL/kg/hr
Consider methylene blue for methaemoglobinaemia

Q: Adverse reactions to intralipid
A: Anaphylaxis
Pulmonary HTN
ALI
Haematuria
Hypertriglyceridaemia
Difficulty interpreting blood tests
Pancreatitis

Q: Clinical presentation of mushroom toxicity
A: Benign GI upset through to liver failure

Q: Dangerous mushroom
A: Amanita phalloides

Q: When to suspect Amanita phalloides intoxication
A: GI symptoms >6 hours after consuming mushrooms

Q: Mortality of delayed onset mushroom hepatotoxicity
A: 30%

Q: When is AC indicated for mushroom poisoning?
A: If GI symptoms >6 hours from ingestion
MDAC recommended as undergoes enterohepatic circulation

Q: Management of suspected amanita philloides toxicity
A: AC with MDAC
NAC
Silibinin or BenPen antidotes
Atropine for cholinergic symptoms

Q: Incidence of NMS
A: ~1% of patients on neuroleptics

Q: Mortality rate of NMS
A: 10-20%

Q: Classic neuromuscular changes in NMS
A: Leadpipe rigidity, brady/akinesia, mutism, abnormal posturing, involuntary movements

Q: Onset of NMS
A: 24-72 hours

Q: Criteria for NMS diagnosis
A: Recent exposure to dopamine antagonist or dopamine agonist withdrawal
Hyperthermia
Rigidity
ALOC
CK >4x ULN
At least 2 of:
 - BP >25% rise
 - Labile BP
 - Diaphoresis
 - Urinary incontinence
Tachycardia/tachypnoea
No other cause

Q: Risk factors for NMS
A: High doses of neuroleptics
Recent dose change in last 5 days
Large dose increase
Parenteral delivery
2 or more neuroleptics
Haloperidol or IM fulphenazine
Young age
Male
Psychiatric comorbidity
Genetic factors
Pre-existing brain disorder
Dehydration
High CK Levels during psychosis
Comorbid trauma, infection, premenstrual, thyrotoxicosis

Q: DDx of NMS
A: Acute lethal malignant catatonia (waxy flexibility)
Malignant hyperthermia
Serotonin syndrome
Heat stroke
Anticholinergic syndrome
Sympathomimetic toxicity
Encephalitis
Metabolic encephalopathy

Q: Recurrence rate of NMS with re-challenge?
A: 30-50%

Q: Management of NMS
A: Supportive care
Mild-moderate - Benzos
GTN if significant HTN
Bromocriptine 2.5mg PO/NG q8h if severe

Q: How does bromocriptine work?
A: Dopamine agonist

Q: Dantrolene use in NMS?
A: For severe muscle rigidity and fever
2.5mg/kg/day

Q: Treatment of amphetamine withdrawal
A: Supportive care only

Q: Do seizures occur in opiate withdrawal?
A: No. Search for other cause

Q: Supportive care for opioid withdrawal
A: Fluids, antiemetics, hyoscine butylbromide, paracetamol, diazepam, clonidine 50mcg TDS

Q: Consequences of solvent abuse
A: Pneumonitis
Myelin toxicity with long-term neuropsychiatric sequelae
Myocardial sensitisation to catecholamines - arrhythmogenic

Q: Management of acute solvent toxicity
A: ABCDE
Fluids
IV diazepam 5-15mg q10min
IV beta-blockers for tachyarrhythmias (reduces myocardial irritability)
Check for NAGMA secondary to RTA

Q: 2 tabs can kill list for paediatric overdose
A: Clonidine
Sulfonylurea
Metformin
Methadone
Clonidine
Amphetamines
Baclofen
CCB
Camphor
Carbamazepine
Clozapine
Dextropropxyphene
Propranolol
Salicylates
Theophylline
Dothiepin
Venlafaxine

Q: Non-pharmaceuticals one sip can kill
A: Naphthalene
Camphor
Organophosphates
Paraquat
Eucalyptus oil
Kerosene
Carbamates
Sodium hydroxide
Strong acids
Strychnine

Q: How is risk assessment performed for children accidental overdoses?
A: Worst case scenario planning
 - Assume all taken immediately prior to presentation (except paracetamol)
 - Assume any missing has been taken
 - Assume one child took all

Q: Management of unknown ingestion of a tablet e.g. picked off ground
A: Assume one of the one tab can kill agents
Admit and observe for 12 hours
IV access deferred unless toxicity arises
Check BSL on admission and on discharge
Brief staff on potential complications e.g. vital signs, ALOC, seizures, sweating, pupillary changes
Cardiac monitoring if any change in conscious state or vital signs
Discharge in daylight hours

Q: Is thermometer mercury dangerous?
A: No

Q: Are oral contraceptives dangerous for children?
A: No

Q: Are perfumes dangerous for children?
A: no

Q: Early levels of which drugs can exclude significant ingestion and allow discharge in children?
A: Paracetamol 1 hour, digoxin 1 hour, theophylline 1 hour

Q: Naloxone dose in children
A: 100mcg/kg IV

Q: Dose of calcium chloride in children
A: 0.2mL/kg of 10%

Q: Dose of calcium gluconate in children
A: 0.6mL/kg 10%

Q: Dose of atropine in children
A: 20mcg/kg

Q: Dose of sodibic in children
A: 1mmol/kg

Q: Management of accidental petrol ingestion by child
A: Monitor for 6 hours
CXR

Q: Toxic dose of eucalyptus oil in children?
A: >5mL

Q: Toxic dose of turpentine in children?
A: >15mL

Q: Toxic dose of iron in children
A: >20mg/kg elemental iron

Q: Probability of hepatotoxicity with paracetamol level <200mg/L at 4 hours
A: 1-2%

Q: Probability of hepatotoxicity with paracetamol level 200-300mg/L at 4 hours
A: 30%

Q: Probability of hepatotoxicity with paracetamol level >300mg/L at 4 hours
A: 90%

Q: Survival if NAC commenced within 8 hours
A: 100%

Q: Benefits of NAC in fulminant hepatic failure
A: Even if delayed initiation, reduces cerebral oedema, inotrope requirement and mortality

Q: Toxic dose of paracetamol
A: >200mg/kg or >10g (whichever is lower) over a period <8 hours

Q: Toxic repeated supratherapeutic dose of paracetamol
A: >200mg/kg or >10g (whichever is lower) over 24 hours
>150mg/kg or 6g per 24 hours over 48 hours
>100mg/kg or 4g per 24 hours over >48 hours with symptoms indicating possible liver injury

Q: What is the risk of paracetamol-induced hepatotoxicity if presents >24 hours after ingestion with normal LFT's and no detectable paracetamol level?
A: Zero

Q: Define massive ingestion of paracetamol
A: >500mg/kg or >30g

Q: How does paracetamol cause hepatotoxicity?
A: Elevated N-acetylparabenzoquinone imine leads to depletion of hepatic glutathione stores
Once glutathione <30% of normal, NAPBQI binds other proteins and causes centrilobar necrosis

Q: Peak levels for oral paracetamol
A: 1-2 hours for tablets
30 minutes for liquids
12 hours for XR

Q: Phases of paracetamol toxicity
A: Phase 1 - Day 1 - Asymptomatic or nausea/vomiting
Phase 2 - Day 2 - RUQ tenderness, ALT/AST/PT rise to peak at 48-72 hours +- renal impairment
Phase 3 - Day 3 - Fulminant hepatic failure with lactic acidosis and uraemia
Phase 4 - >4 days - Recovery phase

Q: How does massive OD of paracetamol differ?
A: Early metabolic acidosis and coma can occur
200mg/kg 16 hour bag
Repeat paracetamol level and LFT at end of 20 hr NAC course
Activated charcoal up to 4 hours for IR and any XR

Q: When ALT/AST levels indicated in paracetamol overdose?
A: At presentation if presents >8hours from ingestion and near end of NAC if given

Q: Which paracetamol OD require activated charcoal?
A: If <200mg/kg: Non-toxic
If >200mg/kg: Within 2 hours of IR or 4 hours of XR
If >500mg/kg: Within 4 hours of IR and all patients if XR irrespective of timing

Q: When should NAC be started if present within 8 hours of ingestion?
A: If IR and will have level back before 8 hours - Start only if above nomogram
If IR and level WILL NOT be back by 8 hours - Start
If XR and SECOND LEVEL will not be back by 8 hours - Start

Q: When should NAC be started if present 8-24 hours after paracetamol ingestion?
A: Only if >200mg/kg or 10g whichever is lower
On arrival and then cease if under nomogram and normal ALT.
If under treatment line and raised ALT - Continue and re-measure ALT at end of NAC

Q: When should NAC be initiated if presents >24 hours from ingestion of paracetamol?
A: Clinical RUQ tenderness, abdominal pain, encephalopathy, detectable paracetamol level or ALT/AST >50

Q: Which patients need repeat transaminases at end of NAC?
A: Those that present >8 hours from ingestion or >500mg/kg dose
Sustained release preparations
Measured level > double nomogram line

Q: What do you do if repeat ALT at end of NAC in delayed presentation is >50?
A: Continue NAC 100mg/kg/16 hours until ALT falling (rpt testing 12-24hrly)

Q: What is time anchoring in paracetamol overdose?
A: If unknown time of ingestion, work out how early ingestion could have happened to be of concern based on nomogram and then work out if ingestion could have happened then or earlier.
If multiple ingestions over hours, assume entire dose taken at the beginning (vs. all other drugs when you assume all taken as recently as possible)

Q: Over what time period has the paracetamol nomogram been validated?
A: Up to 15 hours

Q: What increases the risk of hepatotoxicity from paracetamol overdose?
A: Chronic alcoholism
Prolonged fasting
Isoniazid/rifampicin/carbamazepine (CytP450 inducers)

Q: How does NAC work?
A: Sulfhydryl donor to replete glutathione stores
Directly binds NAPBQI
Reduces NAPBQI back to paracetamol
Antioxidant

Q: Traditional NAC regime
A: 15 min bag: 150mg/kg in 200mL 5% dextrose
4 hour bag: 50mg/kg in 500mL 5% dextrose
16 hour bag: 100mg/kg in 1000mL 5% dextrose (can repeat indefinitely if required)

Q: Who gets >20 hours of NAC?
A: ALT/AST >50
Late presenters
Supratherapeutic intoxication

Q: Rate of angioedema with NAC?
A: 10-15%

Q: Management of angioedema in NAC?
A: Loratadine 10mg PO
Cease if severe and re-start as soon as reaction settling
Consider bronchodilators
Treat severe anaphylactoid reactions as anaphylaxis

Q: NAC dose in pregnancy
A: Unchanged

Q: Paediatric NAC regime
A: 15min bag: 150mg/kg in 5% dextrose (more concentrated)
4hr bag: 50mg/kg in 5% dextrose
8hr bag: 50mg/kg
8hr bag: 50mg/kg

Q: Does giving the first bag of NAC over 15 minutes or 60 minutes make any difference?
A: Extending to 60 minutes makes no difference to rate of anaphylactoid reaction

Q: Paracetamol levels if SR preparation
A: Take one at 4 hours and one 4 hours later - need both below treatment line and falling
Given need delayed 4 hour level, will always be starting NAC >8 hours so just start on arrival

Q: Do SR preperations of paracetamol require further testing after 20 hours NAC?
A: Yes. Need repeat paracetamol level (must be unrecordable) and falling LFT's

Q: Management of SR preparation paracetamol 8-24 hours
A: If <200mg/kg: Nothing
If >200mg/kg: Start NAC, take level and another in 4 hours. If normal ALT/AST and both levels below treatment line AND falling - can cease NAC
If NAC is continued - Repeat ALT/ASt at end of 20 hours - If ALT/AST falling and undetectable paracetamol can cease. If not, continue NAC and repeat testing at 12-24hrs

Q: Management of SR paracetamol presentign >24 hours
A: If detectable paracetamol level, ALT/AST >50 or clinical signs of toxicity - start NAC
Otherwise not required

Q: What form of paracetamol overdose is responsible for all paediatric deaths?
A: Repeated supratherapeutic dosing

Q: Management of suspected toxic repeated supratherapeutic paracetamol dosing?
A: ALT or AST <50 and para <20 - Good prognosis. No treatment required
ALT or AST >50 and para >10 - Commence NAC

Q: When are repeat bloods done in repeated supratherapeutic paracetamol dosing if NAC has been started?
A: At 8 hours
 - If ALT/AST rising - Continue NAC as evolving hepatotoxicity
 - If ALT/AST falling or static - Resolving injury or alternative diagnosis- Can cease NAC

Q: Clinical triad of serotonin syndrome
A: ALOC, Autonomic changes and Neuromuscular excitation

Q: What clinical features are significantly associated with serotonin syndrome?
A: Delirium, diarrhoea, mydriasis, sweating, tachycardia, hyperreflexia, clonus, myoclonus, hypertonia

Q: Is hyperthermia seen in serotonin syndrome?
A: Severe cases only

Q: Complications of serotonin syndrome
A: Rhabdo, AKI, DIC, death

Q: How long does serotonin syndrome last?
A: Usually 24-48 hours from cessation of agent

Q: Agents that cause serotonin syndrome
A: SSRI (with something else)
Tramadol/Fentanyl/Pethidine
MAOi
SNARI (with something else)
Methadone
TCA
MDMA
Amphetamines
St Johns Wort
Lithium
Tryptophan

Q: Antidotes to serotonin syndrome
A: Cyproheptadine 8mg q8h PO/NG
Olanzapine 5-10mg SL
Chlorpromazine 25-100mg in 100mL N/S
If severe - just I&V, sedate and cool

Q: Important differences between serotonin syndrome and NMS
A: SS rapid onset from intake vs. NMS days to weeks
SS clonus hyperreflexia, clonus, myoclonus, hyperthermia RARE vs. NMS lead pipe rigidity, hyperthermia, rhabdo
SS due to serotonergic vs. NMS due to dopamine antagonists or withdrawal of dopamine agonist

Q: How is ethanol metabolised?
A: By alcohol dehydrogenase to acetaldehyde then (by aldehyde dehydrogenase) to acetate

Q: What sort of kinetics does ethanol show?
A: Zero-order above 4mmol/L (so 4mmol/L/hr no matter what)

Q: How does ethanol cause hypoglycaemia?
A: Rise in NADH pushes pyruvate to lactate (lactic acidosis), which in turn means less pyruvate to undergo gluconeogenesis and fatty acid oxidation (hypoglycaemia)

Q: What serum ethanol level correlates to 0.05%?
A: 11mmol/L

Q: Potentially lethal dose of ethylene glycol?
A: >1mL/kg (1g/kg)

Q: Toxic effects of ethylene glycol
A: Severe HAGMA - Glycolic acid, lactate (by increased NADH driving lactate to pyruvate)
Calcium oxalate crystals in kidneys, heart, brain and muscle
 - Hypocalcaemia as a result
Acute oliguric renal failure due to nephrotoxic glycolic acid and calcium oxalate

Q: Toxic byproducts of ethylene glycol
A: Glycolic acid
Lactate
Calcium oxalate crystals

Q: How does ethylene glycol toxicity present?
A: Drunk then tachypnoea/tachycardia/HTN/seizures/coma/death
Lactic acidosis HAGMA
Hypocalcaemia
Flank pain and oliguria/AKI
CN palsies 5-20 days later

Q: Surrogate markers of ethylene glycol toxicity
A: Raised osmolar gap
Lactic acidosis
Raised anion gap acidosis
Hypocalcaemia
Raised creatinine

Q: Management of ethylene glycol toxicity
A: Intubation and hyperventilation
Sodibic 1mmol/kg pending dialysis
Treat seizures with benzos
Treat hypoglycaemia, hyperkalaemia, hypomagnesaemia
Only treat hypocalcaemia if prolonged QT or refractory seizures

Q: Indications for HD in ethylene glycol poisoning
A: Large ingestion with OG >10
pH <7.3
Acute renal failure
ethylene glycol level >8mmol/L

Q: When can patients be discharged after ethylene glycol ingestion?
A: After 4 hours if bicarb >20 and normal renal function
Need f/u for CN palsy

Q: How does ethanol limit assessment of ethylene glycol toxicity?
A: Competes for metabolism so get delayed glycolic acid production and lactic acidosis

Q: How does isopropyl alcohol intoxication present?
A: Drunk with GI irritation and ketosis but NOT HAGMA

Q: What blood results would indicate isopropyl alcohol intoxication?
A: Raised osmolar gap WITHOUT HAGMA
Raised serum acetone

Q: What is isopropyl alcohol metabolised to?
A: Acetone

Q: Management of isopropyl alcohol intoxication
A: Supportive care
Thiamine 200mg IV TDS as cofactor in metabolism to acetone

Q: Why doesn't isopropyl alcohol cause a HAGMA?
A: Causes acetone production but NOT bicarbonate consumption

Q: Toxic dose of methanol
A: >0.5mL/kg of 100% methanol

Q: Toxic mechanism of methanol
A: Formic acid production with HAGMA and direct cellular toxicity
Late hyperlactataemia
Retinal injury and oedema - blindness
Subcortical white matter haemorrhages and putamen oedema

Q: How does methanol toxicity present?
A: Intoxicated but then delayed (12-24 hours) headache, blurred vision, dizziness, vertigo and photophobia
Subsequent tachypnoea, drowsiness and blindness
Coma and seizures herald cerebral oedema

Q: Blood presentation of methanol toxicity
A: HAGMA, lactic acidosis, raised osmolar gap

Q: Management of methanol toxicity
A: Hyperventilate
Target pH >7.30 (acidosis enhances formic acid suppression of cytochrome oxidase)
Treat seizures with midazolam
Folic acid 50mg IV q6h (cofactor for formic acid metabolism)
Haemodialysis
Ethanol 3 shots load then 1 per hour and fomepizole 15mg/kg IV then 10mg/kg BD while awaiting HD

Q: Indications for HD in methanol poisoning
A: pH <7.3
Visual symptoms
Any patient that meets criteria for ADH blockade
Renal failure
Deterioration in vital signs or electrolytes despite supportive care
Methanol level >16mmol/L

Q: How do you differentiate methanol from ethylene glycol poisoning?
A: Both have HAGMA and raised osmolar gap
Ethylene glycol has hypocalcaemia

Q: Dose of fomepizole
A: 15mg/kg IV then 10mg/kg q12h for 2 days, then 15mg/kg BD until undetectable levels of methanol/ethylene glycol

Q: Mimics of toxic delirium
A: ICH
Stroke
Thyrotoxicosis
Myxoedema crisis
CNS infection
Autoimmune encephalitis
Dementia
Electrolyte disturbance e.g. hypocalcaemia/hypoNa
NCSE
Hypoglycaemia
Hepatic/uraemic encephalopathy
Psychosis
Withdrawal

Q: In which toxicological presentations do seizures herald a grave prognosis
A: TCA
Chloroquine
Propranolol
Salicylates
Theophylline

Q: Causes of toxic seizures
A: TCA
Propranolol
Theophylline
Salicylates
Tramadol
Carbamazepine
Bupropion
Escitalopram/citalopram
Venlafaxine
Hypoglycaemic agents
Local anaesthetics
Amphetamines
Withdrawal

Q: Dose of pyridoxine in suspected isoniazid-induced or Vit B6 deficiency seizures?
A: 5g IV (or 70mg/kg in children)

Q: Normal methaemoglobin level?
A: MetHb <1.5%

Q: When does delirium tremens occur?
A: Day 3-12

Q: How long does delirium tremens last?
A: Usually around 3 days

Q: When do seizures often occur in alcohol withdrawal?
A: 48 hours

Q: What must the serum paracetamol level be below to cease Ix and Rx 2 hours after liquid ingestion?
A: <150mg/L - If above this, need to repeat at 4 hours

Q: When can initial para level be taken at 2 hours?
A: Liquid preparation

Q: In repeated supratherapeutic paracetamol dosing, how do you decide if NAC is warranted?
A: Work out if toxic dose range
If so, check AST/ALT and paracetamol level
AST/ALT <50 and para <20 = Good prognosis. No therapy
AST/ALT >50 and para >10 = Start NAC

Q: When does NAC need to be initiated immediately in repeated supratherapeutic dosing?
A: Signs of toxicity

Q: If NAC is initiated for repeated supratherapeutic paracetamol dosing, what happens next?
A: Measure LFT at 8 hours
 - If rising, continue 16 hr bag until clinically well and LFT normal
 - If falling or static, suggests NAC can be ceased

Q: Indications for digibind in chronic dig toxicity
A: Indications:
Clinical features of toxicity with elevated steady state level (6 hours after last dose)
cardiac arrest/arrhythmia
Moderate-severe GI symptoms
Any symptom in presence of renal impairment

Q: Why is adrenaline CI in quetiapine OD?
A: Paradoxical hypotension due to quetiapine-induced alpha-blockade and subsequent excessive unopposed beta-2 mediated vasodilation
NA is preferred

Q: Salicylism?
A: Vomiting, tinnitus, hyperventilation, metabolic acidosis, respiratory alkalosis

Q: How does chronic salicylate poisoning present?
A: Like sepsis in the elderly - Confused, febrile, dehydrated and unexplained metabolic acidosis

Q: Are salicylate levels helpful?
A: Does not correlate with symptoms but can confirm toxicity and identify ongoing absorption if repeat levels taken

Q: What does acidaemia in salicylate poisoning suggest?
A: Imminent demise as up until then respiratory alkalosis has normalised pH

Q: Management of salicylate toxicity
A: Controlled hyperventilation throughout
Replace glucose for all (neuroglycopaenia)
Benzos for seizures
AC up to 8 hours from ingestion >150mg/kg with repeat dose if levels continue to rise
Urinary alkalinisation for all (150mL 3% sodibic in 850mL 5% dextrose over 4 hours)
 - Target urine pH >7.5
 - Monitor K
Consider haemodialysis

Q: When is dialysis advised for salicylate poisoning?
A: Urgently if intubated
Serum salicylate level > 4.4mmol/L despite urinary alkalinisation and decontamination
ALOC, acidaemia or renal failure
Acute level > 7.2mmol/L (>4.4 in elderly)
>4.4mmol/L in chronic toxicity

Q: Why might salicylate poisoning present with a NAGMA?
A: Bedside gas machines measure salicylate as chloride

Q: What is the most common envenoming in Australia?
A: Redback spider

Q: What proportion of patients on lithium have goitre?
A: Up to 50%

Q: How common is hypothyroidism with lithium therapy?
A: Up to 50%

Q: Diazepam plan for mild alcohol withdrawal
A: Diazepam 5-10mg QID for 48 hours as outpatient

Q: Plan for moderate to severe alcohol withdrawal
A: Initial 20mg q1h until AWS <10 then 10mg QID for 48 hours
SSW initially

Q: Plan for severe alcohol withdrawal
A: IV diazepam 5mg slow injection up to 10 minutely for first 30 minutes then 30 minutely PRN
After 24 hours, 10-20mg QID with reducing doses over 3-5 days
Needs inpatient care

Q: What is the most toxic antimalarial?
A: Hydroxychloroquine

Q: Potentially fatal dose of hydroxychloroquine?
A: >10mg/kg
Same as TCA

Q: Clinical features of hydroxychloroquine toxicity
A: Rapid onset hypotension, QRS/QT prolongation, seizures and hypokalaemia

Q: Management of hydroxychloroquine toxicity
A: Intubate and ventilate at first sign of clinical deterioration
Activated charcoal once intubated
Replace K up to 3.0
Treat broad-complex tachyarrhythmias as TCA overdose
 - Sodibic, hyperventilation
Treat seizures with diazepam
 - 0.5mg/kg IV bolus then 1mg/kg/hr for 24 hours

Q: Agents that cause miosis
A: COPS
 - Cholinergics
 - Organophosphates
 - Pontine haemorrhage
 - Sedatives/opioids

Q: Nicotinic symptoms
A: Days of the week
 - Mydriasis
 - Tachycardia
 - Weakness
 - Tremor
 - Fasciculations
 - Seizures
 - Somnolent

Q: Dialysable toxins
A: PLASMA TV
 - Phenobarbitone
 - Lithium
 - Alcohols
 - Salicylates
 - Metformin
 - Acidosis
 - Theophylline
 - Valproic acid

Q: MDAC useful for?
A: ABCDQ
- Aminophylline/theophylline
 - Barbiturates
 - Carbamazepine
- Dapsone
 - Quinine

Q: Does lithium prolong the QTc?
A: Yes

Q: What is a butyrophenone?
A: Haloperidol

Q: How does benztropine work?
A: Anticholinergic

Q: When should cyanide poisoning be suspected in inhalation?
A: Inhalational injury with lactate >10

Q: Colchicine toxicity progression
A: 2-24 hours - Asymptomatic then GIT symptoms incl. haemorrhage
24-72 hours - CNS toxicity, bone marrow suppression, MODS, agranulocytosis, DIC, death
>7 days in survivors - Alopecia, leukocytosis

Q: 1mL of oil of wintergreen =
A: 1400mg aspirin

Q: Which pathological effects of snake toxin are reversed by antivenom?
A: Established pre-synaptic neurotoxicity
Post-synaptic paralysis (e.g. Death adder)
Anticoagulant coagulopathy
Rhabdo
MAHA

Q: Cobalt toxicity
A: Nausea, vomiting, anaphylaxis, hypotension and ventricular arrhythmias