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Toxidromes

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Toxidromes

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Toxidromes

  1. 1. CME Teaching 12/11/15 Claire Plint Toxidromes
  2. 2. › Toxicology Handbook › Life in the fast lane Resources
  3. 3. › Common toxidromes › Specific management of complications › Antidotes Outline
  4. 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. 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. 6. WHAT IS THE TOXIDROME/differential??
  7. 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. 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. 9. Could this be another toxidrome? Are we missing something?
  10. 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
  11. 11. 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
  12. 12. Now what do we do?
  13. 13. › 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?
  14. 14. › Miss M changes her mind and agrees to take oral olanzapine. › 15 minutes later she complains of chest pains and SOB.
  15. 15. › CVS – ACS – vasospasm, dissection – Acute cardiomyopathy – APO – HTN › Neuro – Carotid dissection/stroke – IC bleed – PRES – Seizures › Hyperthermia Complications
  16. 16. › 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…
  17. 17. › 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
  18. 18. › BIBA › Found unconscious by friend › Not breathing › Performed CPR › When SJA arrived – pinpoint pupils and fresh track marks Case 2 – Mr P
  19. 19. WHAT IS THE TOXIDROME?
  20. 20. › Agonist activity at µ-receptors – euphoria, – analgesia, – physical dependence, – sedation and – respiratory depression OPIOIDS
  21. 21. 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…
  22. 22. How would you manage Mr P?
  23. 23. › 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
  24. 24. › 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
  25. 25. › 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
  26. 26. › competitive inhibition of central and peripheral acetylcholine muscarinic receptors Anticholinergic toxidrome
  27. 27. 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
  28. 28. •Encephalitis •Hypoglycaemia •Hyponatraemia •Ictal phenomenon •Neuroleptic malignant syndrome •Neurotrauma •Sepsis •Serotonin syndrome •Subarachnoid Haemorrhage •Wernicke’s encephalopathy Other differentials
  29. 29. › 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
  30. 30. › Bradydysrhythmias › Intraventricular block (QRS >100 ms) › AV block › Bronchospasm contraindications
  31. 31. • 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
  32. 32. 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?
  33. 33. › 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…..
  34. 34. › 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…
  35. 35. 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

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