This document provides a summary of a teaching session on toxidromes. It discusses several case presentations and the key features of different toxidromes including: sympathomimetic toxicity, serotonin syndrome, opioid overdose, anticholinergic syndrome, neuroleptic malignant syndrome, and malignant hyperthermia. For each case, the document outlines vital signs, physical exam findings, differential diagnoses, management considerations, and important complications.

1. CME Teaching 12/11/15
Claire Plint
Toxidromes

2. › Toxicology Handbook
› Life in the fast lane
Resources

3. › Common toxidromes
› Specific management of complications
› Antidotes
Outline

4. Case 1 Miss M
› 34 year old woman brought to ED by police.
› Acting bizarrely at the shops.
› Agitated, screaming out. Surrounded by police and security
guards.
› Wanting to leave.
› No PMHx.
› Not cooperating with history.

5. Vital signs:
Temp 37.8
HR 145
BP 156/95
Sats 94% RA
Dilated Pupils
Sweaty
No obvious track marks
CASE 1 CONT…

6. WHAT IS THE TOXIDROME/differential??

7. › Enhance catecholamine release and block reuptake.
› Inhibition of monoamine oxidase also occurs.
› noradrenergic, dopaminergic and serotonergic stimulation
occurs.
› Long-term CNS effects
Sympathomimentic Toxidrome and
amphetamines

8. › CNS effect
– Euphoria, agitation, anxiety,
– Rigidity, myoclonus, seizures
– Psychotic symptoms
› CVS
– Tachycardia, hypertension
– Dysrhythmias
› Peripheral
– Mydriasis
– Sweating
– Tremor
Clinical Feature of sympathomimetic toxicity

9. Could this be another toxidrome?
Are we missing something?

10. Mental status changes Autonomic stimulation Neuromuscular excitation
•Apprehension
•Anxiety
•Agitation, psychomotor
acceleration and delirium
•Confusion
•Diarrhoea
•Flushing
•Hypertension
•Hyperthermia
•Mydriasis
•Sweating
•Tachycardia
•Clonus (esp. ocular and
ankle)
•Hyperreflexia
•Increased tone (lower limbs
> upper limbs)
•Myoclonus
•Rigidity
•Tremor
Serotinin syndrome

12. Central nervous system Autonomic instability Neuromuscular
•Confusion
•Delirium
•Stupor
•Coma
•Hyperthermia
•Tachycardia
•Hypertension
•Respiratory irregularities
•Cardiac dysrhythmias
•‘Lead-pipe’ rigidity
•Generalised bradykinesia or
akinesia
•Mutism and staring
•Dysarthria
•Dystonia and abnormal
postures
•Abnormal involuntary
movements
•Incontinence
Neuroleptic Malignant Syndrome

13. Now what do we do?

14. › Droperidol
› Up to 20mg in 24hrs unlikely to
cause QT prolongation
› Use early if
hallucinations/psychotic
symptoms
ANTIPSYCHOTICS
› Titrate
› Midazolam vs diazepam
BENZODIAZEPINES
Sedation……How much and what agent?

15. › Miss M changes her mind and agrees to take oral olanzapine.
› 15 minutes later she complains of chest pains and SOB.

16. › CVS
– ACS – vasospasm, dissection
– Acute cardiomyopathy
– APO
– HTN
› Neuro
– Carotid dissection/stroke
– IC bleed
– PRES
– Seizures
› Hyperthermia
Complications

17. › ACS
– Give aspirin
– No thrombolysis
– No B-blockers
› APO
– treat as you normally would. Can have profound hypotension and
cardiovascular collapse due to acute LV failure.
› HTN
– Benzos
– If unable to get BP <140 systolic then start GTN infusion or Na Nitroprusside
– Look for complications of severe HTN – IC bleed, Dissection, PRES
Management of complications…

18. › Seizures
– Benzos 1st line.
– Intubate
– If >4 boluses then change to barbiturate eg thiopentone
– Check for other causes of seizures
› BSL, Na+
› Hyperthermia
– Figure out cause ?seizures then intubate and paralyse early
– >38.5
› fans, tepid sponging
– >39
› Intubate, paralyse, active cooling

19. › BIBA
› Found unconscious by friend
› Not breathing
› Performed CPR
› When SJA arrived – pinpoint pupils and fresh track marks
Case 2 – Mr P

20. WHAT IS THE TOXIDROME?

21. › Agonist activity at µ-receptors
– euphoria,
– analgesia,
– physical dependence,
– sedation and
– respiratory depression
OPIOIDS

22. 1. 10 mg/kg likely to cause symptoms
20 mg/kg may cause CNS depression, seizures and cardiac
dysrhythmias (fast sodium channel blocking effect)
2. QT prolongation
3. Repeated therapeutic doses are associated with seizures
Implicated in serotonin syndrome
Special cases…

23. How would you manage Mr P?

24. › pure competitive opioid antagonist at mu, kappa and delta
receptors.
› reverses opioid effects, including sedation, respiratory
depression and hypoxia.
› Treatment dose varies (depends on type and dose of agonist
present)
ANTIDOTE - NALOXONE

25. › Give initial 100mcg IV
› Repeat dosing every 30 seconds until spontaneous respiration
present.
› Naloxone infusion.
– Commence rate 2/3 of initial dose required/hour
– Administration of 100 microgram/hour can be obtained by diluting
2 mg of naloxone in 100 mL normal saline and running at 5 mL/hour.
– Titrate according to response
› May require prolonged infusions – SR preparations,
transdermal patches…
Naloxone dosing

26. › 54 year old man, BIBA following deliberate overdose.
› Took 10 x 5mg diazepam, alcohol and some of his wife’s
medication.
› Drowsy GCS 12
› Few hours later becomes agitated, tachycardic, hallucinating
and found to be in urinary retention.
Mr D

27. › competitive inhibition of central and peripheral acetylcholine
muscarinic receptors
Anticholinergic toxidrome

28. Central Peripheral
•Agitated delirium characterised by:
● Fluctuating mental status
● Confusion
● Restlessness
● Fidgeting
● Visual hallucinations
● Picking at objects in the air
● Mumbling slurred speech
● Disruptive behaviour
•Tremor
•Myoclonus
•Coma
•Seizures (rare)
•Mydriasis
•Tachycardia
•Dry mouth
•Dry skin
•Flushing
•Hyperthermia
•Sparse or absent bowel sounds
•Urinary retention

29. •Encephalitis
•Hypoglycaemia
•Hyponatraemia
•Ictal phenomenon
•Neuroleptic malignant
syndrome
•Neurotrauma
•Sepsis
•Serotonin syndrome
•Subarachnoid Haemorrhage
•Wernicke’s encephalopathy
Other differentials

30. › reversible inhibition of acetylcholinesterase and accumulation
of acetylcholine.
› The increased concentration of acetylcholine overcomes the
postsynaptic muscarinic receptor blockade produced by
anticholinergic agents
ANTIDOTE PHYSOSTIGMINE

31. › Bradydysrhythmias
› Intraventricular block (QRS >100 ms)
› AV block
› Bronchospasm
contraindications

32. • Administer 0.5–1 mg as a slow IV push over 5 minutes and
repeat every 10 minutes until the desired clinical effect is
observed.
• It is rare for a total dose of more than 4 mg to be required.
• The duration of action of physostigmine is much shorter than
most cases of anticholinergic delirium
- delirium may reoccur 1–4 hours following initial clinical
response.
- Further carefully titrated doses may then be given

33. Case - Mr H
› 39 year old man BIBP from petrol station.
› Erratic behaviour, walking around in underwear.
› Confused, Temp 39.4, HR 148 BP 150/70.
– Differential?
– Management?
– Investigations?

34. › No known history of drug use.
› C/O headache the day before admission.
› Bloods….
– CRP 43, WCC 15
› CT head – NAD
› LP….
– 96 % Lymphocytes
– PCR – HSV
More Hx from Mother…..

35. › Hypoxia / hypercarbia
› Head injury
› Acute intoxication and withdrawal
› Metabolic disturbances: hypoglycaemia, hypoNa
› Infection: meningitis, encephalitis, sepsis
› Vascular: CVA, SAH
› Hyperthermia or hypothermia
› Seizures: post ictal or non-convulsive status epilepticus
In Summary
Differential diagnoses for agitation…

36. Condition Drug history Cadence Vital signs Pupils Skin Bowel
sounds
Neuromuscu
lar tone
Reflexes Mental
status
Serotonin
syndrome
5HT 2A or
5HT1A agonis
t
<12 hours ↑HR, BR
RR and Temp
Mydriasis Sweaty Hyperactive Increased,
esp. lower
limbs
Hyperreflexi
a and clonus
Agitation
progressing
to coma
Neuroleptic
malignant
syndrome
Dopamine
antagonist
Days ↑HR, BR
RR and Temp
Mydriasis or
normal
Sweaty but
pale
Normal Lead-pipe
rigidity
Bradyreflexia Mutism,
staring,
bradykinesia,
coma
Anticholiner
gic syndrome
Anticholiner
gic agent
<12 hours ↑HR, BR
RR and Temp
Mydriasis Hot, red and
dry
Decreased or
absent
Normal Normal Agitated
delirium
Malignant
hyperthermi
a
Inhalational
anaesthetic
Minutes–24
hours
↑HR, BR
RR and Temp
Normal Sweaty and
mottled
Decreased Generalised
rigidity
Hyporeflexia Agitation