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Psychiatric Intoxication

Psychiatric Intoxication. 9 th September Emergency Department CME Jing Dong Emergency Registrar. Overview. Case based Major classes SNRI SSRI TCA Atypical Antipsychotics. Case 1.1. 26 y.o . female Paranoid schizophrenia; multiple attempts of suicide

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Psychiatric Intoxication

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  1. Psychiatric Intoxication 9th September Emergency Department CME Jing Dong Emergency Registrar

  2. Overview • Case based • Major classes • SNRI • SSRI • TCA • Atypical Antipsychotics

  3. Case 1.1 26 y.o. female • Paranoid schizophrenia; multiple attempts of suicide • Alleged ingestion >10 g of white tablets • GCS 8/15 at 2.5 h postingestion IntubationICU • Signs and symptoms • Sinus tachycardia (130-140) • Blood pressure 135/70 • Pupils 3mm and sluggish • Within 16 h, GCS 15/15 • Tachycardia lasted for 40 h postingestion. • Medically cleared and transferred to psychiatric inpatient unit T.J. Harmon, J.G. Benitez et al. J. Analytical Toxicol L 36:599-602 (1998)

  4. Case 1.2 34-year-old woman with chronic schizophrenia • Ingested 36 g of extending release form of white tablets • Initially lethargy only • Rapid deterioration and collapsed unconscious at 2 hours: Deep coma GCS 9/15. • Intubated ICU for ventilatory support and close monitoring • Restored spontaneous breathing at 36 hours • Two days later, discharged without complications. Capuano A, Ruggiero S et al. Drug ChemToxicol. 2011;34(4):475-7

  5. Case 1.3 A 59-year-old woman with schizophrenia • 2 hours after intentionally ingesting 20 g • On arrival, GCS 14/15, HR125, 82/51mmHg. ECG sinus tachycardia only • 1L 0.9% saline  BP 90/60 mmHg • An hour later, GCS11/15 Tracheal intubation (Midazolamfentanyl and suxamethonium). Morphine and midazolam infusion. • After intubation, BP 70/40mmHg • Hypotension not responding to 3L normal saline • Central venous access & an adrenaline infusion at 5μg/min, then 20 5μg/min, SBP 53 • Called toxicologist, withdrew adrenaline, noradrenaline infusion at15 μg/min. SBP rose to 120 mmHg • ICU, noradrenaline withdrawn at 6h, then extubated. Hawkins DJ, Unwin P. CritCare Resusc. 2008. Dec;10(4):320-2.

  6. Quetiapine • Atypical antipsychotic • Serotonin-Dopamine Antagonists • Antagonism of Dopamine type 2 (D2) & Serotonin type 2 (5-HT2) • Peripheral α-adrenergic (α1) & Histamine (H1) receptors • Known receptor pharmacology • Absence of extrapyramidal effects (D2) • Prominence of orthostatic hypotension and tachycardia (α1) • Sedation (H1)

  7. Clinical features • Onset: 2-4 h • Duration: 24-72h • Dose dependent • <3g Sedation and sinus tachy (>120bpm) • >3g CNS depression, coma, hypotension (coma lasts 18-48h) • Seizure is uncommon (<5%) • Prolonged QT is rare • Leading cause of toxic coma requiring ICU

  8. Investigations • Screening: ECG, BSL, paracetamol level • Serial ECG • At presentation • 4H post presentation

  9. Management • Resuscitation • Supportive care • Hypotension: IV crystalloid  NA (Adrenaline exacerbates hypotension) • Delirium: Benzodiazepine • Monitoring • Decontamination • Rapid onset of sedation and coma • Unless intubated, activated charcoal NOT indicated

  10. Disposition • Observe 4H with serial ECG • Children >100mg (Warn EPS up to 3d) • Adult <3g • Clinically well • Admission for supportive care • Adult >3g • Or clinical features of intoxication

  11. Case 1.4 – 1.6 • 16 y.o. female, schizophrenia. Hypersalivation, sedation, agitation, SBP 90, HR 130, pupils 2mm and reactive. • 21 y.o. male, BPAD. Agitation, constricted pupils and a GCS fluctuating between 6 to 11. ECG showed sinus tachycardia, ST depression and tall T-waves. • 6 y.o. Girl Accidentally taken 2g of mother’s pill. Dystonia, mild tahycardia, lethargic. ECG prolonged QTc

  12. Clozapine • D1&D2, 5HT and α1antagonist • Potent antagonist at muscarinic (M1), histamine (H1) and GABA receptors • Receptor pharmacology • Anticholinergic effects: Hypersalivation, agitation, urinary retention, mydirasis or miosis • Sedation (H1) • Tachycardia and hypotension (α1) • Seizures (GABA) 5-10% • EPS more common in children (D1) • Observe for 6H and serial ECG • EPS in children up to 7d

  13. Case 1.4 – 1.6 • 16 y.o. female, schizophrenia. Hypersalivation, sedation, agitation, SBP 90, HR 130, pupils 2mm and reactive. • 21 y.o. male, BPAD. Agitation, constricted pupils and a GCS fluctuating between 6 to 11. ECG showed sinus tachycardia, ST depression and tall T-waves. • 6 y.o. Girl Accidentally taken 2g of mother’s pill. Dystonia, mild tahycardia, lethargic. ECG prolonged QTc

  14. Olanzapine • D2,5HT2,H1, α1, M1antagonist • Dose dependent • <40mg: Sedation • 40-100mg: Sedation + Anticholinergic • 100-300mg: Fluctuating GCS + intermittent marked Agitation • >300mg: Coma (last 18-48h), hypotension • Sedation, ataxia, miosis, hypotension and tachy are common • Non-specific ST-T wave changes (15%) • Disposition • Children >0.5mg/kg: 4 h observation • Discharge when clinically well • Intubated for agitation or delirium  ICU for up to 48h

  15. Case 1.4 – 1.6 • 16 y.o. female, schizophrenia. Hypersalivation, sedation, agitation, SBP 90, HR 130, pupils 2mm and reactive. • 21 y.o. male, BPAD. Agitation, constricted pupils and a GCS fluctuating between 6 to 11. ECG showed sinus tachycardia, ST depression and tall T-waves. • 6 y.o. Girl Accidentally taken 2g of mother’s pill. Dystonia, mild tahycardia, lethargic. ECG prolonged QTc

  16. Risperidone • Much lower affinity for H1 and M1 • Lethargy, confusion, mild sedation and tachycardia are common • QT prolongation may occur • If coma, seizures, significant abnormal vital signs  consider alternative diagnosis • Children >1mg required observation • EPS up to 3d

  17. Case 2 36-year-old woman • Depression • Presented with shakiness, numbness in the arms, and palpitations at 32 hours after ingesting 50 (20-mg) tablets. • BP84/44 mmHg, HR102–150 bpm, RR 17, T 37.3 • First ECG

  18. ECG 1

  19. ECG 2 • 20 minutes after later….. • Transient hypotension and loss of consciousness.

  20. ECG 3

  21. Case 2 • Treated with magnesium, lidocaine & IV KCl • Temporary transvenous pacemaker • Transferred to CCU • Paced at a heart rate of 110 bpm for 24 hours, nil further arrhythmias • QT prolongation resolved at 24 hours after presentation

  22. ECG 4

  23. Selective Serotonin Reuptake Inhibitors (SSRI) • Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline • Many remain asymptomatic • Nausea • Mild serotonin syndrome (anxiety, tremor, tachy/brady, mydriasis) in <20% • QTc prolongation in Citalopram and Escitalopram & Dose-dependant • Seizures uncommon (<2%) in Citalopram

  24. SSRI - Investigations • Citalopram >600mg: serial ECG up to 8h post-ingestion • Citalopram >1000mg: serial ECG up to 13H post-ingstion • Ongoing monitor until normalised QTc

  25. SSRI - Management • Supportive • Seizure & agitation: benzodiazepine • Serotonin syndrome (T, benzo) • Increasing anxiety, sweating, tremor, tachy and mydriasis prophylactic benzodiazapine • Ongoing cardiac monitoring • Decontamination • Alert, cooperative >600mg citalopram • 50g activated charcoal within 4h post-ingestion

  26. Case 3 – A Fatal Case 40 y.o. Male • Depression and TIIDM • 45mins post ingesting 90 (150mg tablets, XR) total 19g • Nausea only • HR 136, BP 133/90, RR 16, T36.3 • 50g activated charcoal, WBI with PEG • 2h tonic-clonic seizures. Lasted 3mins (2mg IV lorazepam) • Second seizure at 4.5h (2mg IV lorazepam) • Admitted to ICU • Clear progression of prolonged QRS and QTc • VF at 9h and then deceased Bosse GM, Spiller HA, Collins AM. J Med Toxicol. 2008 Mar;4(1):18-20.

  27. Case 3

  28. Serotonin Noradrenaline Reuptake Inhibitors (SNRI) • Venlafaxine, Desvenlafaxine • SNRI & Sodium channel blocking • Life-threatening emergency • Seizures, Cardiovascular toxicity • Dose-dependant • <1.5g: Seizures <5% • <3g: Seizures 10% • >3g: Seizures >30% • >4.5g: Seizures 100%, Hypotension, QRS & QT prolongation • >7g: Hypotension and cardiac arrhythmia

  29. SNRI • Delayed onset: up to 6-12 hours • Anxiety, mydriasis, sweating, tremor, clonus, tachycardia and HTN are common • Generalised seizures, short duration • Serotonin syndrome (esp co-ingestion) • Rhabdomyolysis in some

  30. SNRI • Serial ECG, CK • Early intubation and ventilation for ingestion >7g • Seizures: Benzodiazepine • Broad complex tachycardia: intubation, hyperventilation and NaCO3 • Hyperthermia • Activated charcoal • within 2H of >4.5g ingestion if alert and cooperative • >7g ingestion and seizure after intubation

  31. SNRI • ALL IV access and observe for 16H • >4.5g, cardiac monitoring and serial ECG • Severe venlafaxine intoxication or serotonin syndrome  ICU Pearls • Early prophylactic benzodiazepine • Anticipate and prepare for delayed onset of symptoms and seizures • Activated charcoal or WBI

  32. SSRI vs SNRI • SNRI more toxic: pro-convulsant activity & cardiac sodium channel blocking • Risk assessment: • Older (mean age 37.4 vs 28.8 years, p≤0.001) • Higher suicidal intent (p≤0.017). • High dose: Median venlafaxine dose taken was 35 defined daily doses (DDDs) vs19.4 DDDs in SSRI. • Positive risk benefit profile for depression and GAD, esp second line to SSRIs.

  33. Case 4 • 31 y.o. female • Found unresponsive by husband, took an unknown medication for headache. • HR 136, SBP 82, RR 21, T 36.3, 7mm pupils sluggish, GCS 8/15 (1/2/5) • First ECG

  34. ECG 1

  35. Case 1 Management?

  36. ECG 2 – post bicarbonate

  37. Tricyclic antidepressants (TCA) • Amitriptyline, nortryptyline, clomipramine, tripramine, imipramine, dothiepin, doxepin • Morbidity and Mortality • A BAD DRUG • Noradrenaline & serotonin reuptake inhibitors • GABAa blockers • Blockade of inactivated fast sodium channels • Blockade of M1, H1, peripheral A1 • Reversible inhibition of K channels • Direct myocardial depression

  38. TCA – Risk assessment • >10mg/kg = life threatening • Dose-dependant risk • <5mg/kg Min symptoms • 5-10mg/kg Drowsiness, mild anticholinergic • >10mg/kg Coma, Hypotension, seizures, arrhythmia (onset 2-4h) • >30mg/kg Severe cardiotoxicity and coma (last>24h)

  39. TCA - Clinical Features • CNS • Coma/sedation (H1) • Seizures (GABAa) • CVS • Sinus tachycardia • Hypotension (A1 and impaired contractility) • Broad-complex tachycardia/bradycardia(Na channel) • QT prolongation (K channel) • Anticholinergic Effects (M1) Leading causing of death: arrhythmia & hypotension

  40. Prolongation of PR and QRS Large terminal R wave in aVR Increased R/S ratio in aVR >0.7 QT prolongation QRS widening proportional to Na blockade QRS >100ms  seizures QRS >160mg  VT ECG

  41. Management • Close monitoring >6H • Ventricular arrhythmia • Sodium Bicarbonate 2mmol/kg Q1-2mins • Then infusion in D5 • Hypotension • Crystalloid, NaCO3 • A or NA infusion • Seizures • Benzodiazepines • Intubated hyperventilation aiming pH7.50-7.55 • Activated Charcoal: only if >10mg/kg and intubated

  42. TCA – The Pearls • Sodium bicarbonate (The Antidote) • Serum alkanization • Sodium loading  counteracting the sodium channel blockade • Endpoints: QRS<100ms, pH >7.50, resolution of hypotension • Rapid intubation • Hyperventilation

  43. Our Patient: • ICU • Continuous NaCO3 infusion • Extubated on Day 2 • Serial ECG on Day 3 ECG 3

  44. References • T.J. Harmon, J.G. Benitez, E.P. Krenzelok, and E Cortes-Belen.Loss of consciousness from acute quetiapineoverdosage. J. Analytical Toxicol 36:599-602 (1998) • Capuano A, Ruggiero S, Vestini F, Ianniello B, Rafaniello C, Rossi F, Mucci A. Survival from coma induced by an intentional 36-g overdose of extended-release quetiapine. Drug ChemToxicol. 2011 Oct;34(4):475-7. • Hawkins DJ, Unwin P. Paradoxical and severe hypotension in response to adrenaline infusions in massive quetiapine overdose. Crit Care Resusc. 2008. Dec;10(4):320-2. • Tarabar AF, Hoffman RS, Nelson L. Citalopram overdose: late presentation of torsades de pointes (TdP) with cardiac arrest. J Med Toxicol. 2008 Jun;4(2):101-5. • Bosse GM, Spiller HA, Collins AM. A fatal case of venlafaxine overdose. J Med Toxicol. 2008 Mar;4(1):18-20. • Chan AN, Gunja N, Ryan CJ. A comparison of venlafaxine and SSRIs in deliberate self-poisoning. J Med Toxicol. 2010 Jun;6(2):116-21. • Chuang R, Bernard A. A 31-year-old woman found unresponsive with tachycardia . Hosp Physician 2009 May-Jun;45(4):29-32 • Lindsay Murray et al (2010). Toxicology Handbook.

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