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Psychiatric Intoxication

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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 - PowerPoint PPT Presentation
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Psychiatric Intoxication 9 th September Emergency Department CME Jing Dong Emergency Registrar
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Page 1: Psychiatric Intoxication

Psychiatric Intoxication9th SeptemberEmergency Department CME

Jing DongEmergency Registrar

Page 2: Psychiatric Intoxication

OverviewCase basedMajor classes

◦SNRI◦SSRI◦TCA◦Atypical Antipsychotics

Page 3: Psychiatric Intoxication

Case 1.126 y.o. femaleParanoid schizophrenia; multiple attempts of

suicideAlleged ingestion >10 g of white tabletsGCS 8/15 at 2.5 h postingestion IntubationICUSigns and symptoms

◦ Sinus tachycardia (130-140)◦ Blood pressure 135/70◦ Pupils 3mm and sluggish

Within 16 h, GCS 15/15Tachycardia lasted for 40 h postingestion.Medically cleared and transferred to psychiatric

inpatient unitT.J. Harmon, J.G. Benitez et al. J. Analytical Toxicol L 36:599-602 (1998)

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Case 1.234-year-old woman with chronic schizophrenia Ingested 36 g of extending release form of

white tabletsInitially lethargy onlyRapid 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 hoursTwo days later, discharged without

complications. Capuano A, Ruggiero S et al. Drug Chem Toxicol. 2011;34(4):475-7

Page 5: Psychiatric Intoxication

Case 1.3A 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

(Midazolam fentanyl 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 SBP rose to 120 mmHg ICU, noradrenaline withdrawn at 6h, then extubated.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. Crit Care Resusc. 2008. Dec;10(4):320-2.

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Quetiapine

Atypical antipsychoticSerotonin-Dopamine AntagonistsAntagonism of Dopamine type 2 (D2) &

Serotonin type 2 (5-HT2)Peripheral α-adrenergic (α1) &

Histamine (H1) receptorsKnown receptor pharmacology

◦Absence of extrapyramidal effects (D2)◦Prominence of orthostatic hypotension and

tachycardia (α1)◦Sedation (H1)

Page 7: Psychiatric Intoxication

Clinical featuresOnset: 2-4 hDuration: 24-72hDose dependent

◦<3g Sedation and sinus tachy (>120bpm)◦>3g CNS depression, coma, hypotension

(coma lasts 18-48h)

Seizure is uncommon (<5%)Prolonged QT is rareLeading cause of toxic coma

requiring ICU

Page 8: Psychiatric Intoxication

InvestigationsScreening: ECG, BSL,

paracetamol levelSerial ECG

◦At presentation◦4H post presentation

Page 9: Psychiatric Intoxication

ManagementResuscitationSupportive care

◦Hypotension: IV crystalloid NA (Adrenaline exacerbates hypotension)

◦Delirium: BenzodiazepineMonitoringDecontamination

◦Rapid onset of sedation and coma◦Unless intubated, activated charcoal

NOT indicated

Page 10: Psychiatric Intoxication

DispositionObserve 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

Page 11: Psychiatric Intoxication

Case 1.4 – 1.616 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. GirlAccidentally taken 2g of mother’s pill. Dystonia, mild tahycardia, lethargic. ECG prolonged QTc

Page 12: Psychiatric Intoxication

ClozapineD1&D2, 5HT and α1antagonistPotent antagonist at muscarinic (M1),

histamine (H1) and GABA receptorsReceptor 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 ECGEPS in children up to 7d

Page 13: Psychiatric Intoxication

Case 1.4 – 1.616 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. GirlAccidentally taken 2g of mother’s pill. Dystonia, mild tahycardia, lethargic. ECG prolonged QTc

Page 14: Psychiatric Intoxication

OlanzapineD2,5HT2,H1, α1, M1antagonistDose 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

Page 15: Psychiatric Intoxication

Case 1.4 – 1.616 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. GirlAccidentally taken 2g of mother’s pill. Dystonia, mild tahycardia, lethargic. ECG prolonged QTc

Page 16: Psychiatric Intoxication

RisperidoneMuch lower affinity for H1 and M1Lethargy, confusion, mild sedation and

tachycardia are commonQT prolongation may occur

If coma, seizures, significant abnormal vital signs consider alternative diagnosis

Children >1mg required observationEPS up to 3d

Page 17: Psychiatric Intoxication

Case 2

36-year-old woman DepressionPresented 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

Page 18: Psychiatric Intoxication

ECG 1

Page 19: Psychiatric Intoxication

ECG 220 minutes after later…..Transient hypotension and loss of consciousness.

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ECG 3

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Case 2Treated with magnesium,

lidocaine & IV KClTemporary transvenous

pacemakerTransferred to CCU Paced at a heart rate of 110 bpm

for 24 hours, nil further arrhythmias

QT prolongation resolved at 24 hours after presentation

Page 22: Psychiatric Intoxication

ECG 4

Page 23: Psychiatric Intoxication

Selective Serotonin Reuptake Inhibitors (SSRI)Citalopram, Escitalopram, Fluoxetine,

Fluvoxamine, Paroxetine, Sertraline

Many remain asymptomaticNauseaMild serotonin syndrome (anxiety,

tremor, tachy/brady, mydriasis) in <20%QTc prolongation in Citalopram and

Escitalopram & Dose-dependantSeizures uncommon (<2%) in

Citalopram

Page 24: Psychiatric Intoxication

SSRI - Investigations Citalopram >600mg: serial ECG

up to 8h post-ingestionCitalopram >1000mg: serial ECG

up to 13H post-ingstionOngoing monitor until normalised

QTc

Page 25: Psychiatric Intoxication

SSRI - ManagementSupportive

◦Seizure & agitation: benzodiazepine◦Serotonin syndrome (T, benzo)◦Increasing anxiety, sweating, tremor,

tachy and mydriasis prophylactic benzodiazapine

◦Ongoing cardiac monitoringDecontamination

◦Alert, cooperative >600mg citalopram ◦50g activated charcoal within 4h post-

ingestion

Page 26: Psychiatric Intoxication

Case 3 – A Fatal Case40 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.

Page 27: Psychiatric Intoxication

Case 3

Page 28: Psychiatric Intoxication

Serotonin Noradrenaline Reuptake Inhibitors (SNRI)Venlafaxine, DesvenlafaxineSNRI & Sodium channel blockingLife-threatening emergency

Seizures, Cardiovascular toxicityDose-dependant

◦<1.5g: Seizures <5%◦<3g: Seizures 10%◦>3g: Seizures >30%◦>4.5g: Seizures 100%, Hypotension, QRS &

QT prolongation◦>7g: Hypotension and cardiac arrhythmia

Page 29: Psychiatric Intoxication

SNRIDelayed onset: up to 6-12 hoursAnxiety, mydriasis, sweating,

tremor, clonus, tachycardia and HTN are common

Generalised seizures, short duration

Serotonin syndrome (esp co-ingestion)

Rhabdomyolysis in some

Page 30: Psychiatric Intoxication

SNRISerial ECG, CK

Early intubation and ventilation for ingestion >7g

Seizures: BenzodiazepineBroad complex tachycardia: intubation,

hyperventilation and NaCO3Hyperthermia

Activated charcoal ◦ within 2H of >4.5g ingestion if alert and cooperative◦ >7g ingestion and seizure after intubation

Page 31: Psychiatric Intoxication

SNRIALL IV access and observe for 16H>4.5g, cardiac monitoring and serial ECG Severe venlafaxine intoxication or

serotonin syndrome ICU

PearlsEarly prophylactic benzodiazepineAnticipate and prepare for delayed onset

of symptoms and seizuresActivated charcoal or WBI

Page 32: Psychiatric Intoxication

SSRI vs SNRISNRI more toxic: pro-convulsant activity

& cardiac sodium channel blockingRisk 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.

Page 33: Psychiatric Intoxication

Case 431 y.o. femaleFound 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

Page 34: Psychiatric Intoxication

ECG 1

Page 35: Psychiatric Intoxication

Case 1

Management?

Page 36: Psychiatric Intoxication

ECG 2 – post bicarbonate

Page 37: Psychiatric Intoxication

Tricyclic antidepressants (TCA)Amitriptyline, nortryptyline, clomipramine,

tripramine, imipramine, dothiepin, doxepinMorbidity 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

Page 38: Psychiatric Intoxication

TCA – Risk assessment>10mg/kg = life threateningDose-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)

Page 39: Psychiatric Intoxication

TCA - Clinical FeaturesCNS

◦ 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

Page 40: Psychiatric Intoxication

ECGProlongation of PR and QRSLarge terminal R wave in aVRIncreased R/S ratio in aVR >0.7QT prolongationQRS widening proportional to Na blockadeQRS >100ms seizuresQRS >160mg VT

Page 41: Psychiatric Intoxication

ManagementClose monitoring >6HVentricular 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

Page 42: Psychiatric Intoxication

TCA – The PearlsSodium bicarbonate (The

Antidote)◦Serum alkanization◦Sodium loading counteracting the

sodium channel blockade◦Endpoints: QRS<100ms, pH >7.50,

resolution of hypotension

Rapid intubationHyperventilation

Page 43: Psychiatric Intoxication

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

Page 44: Psychiatric Intoxication

References1. T.J. Harmon, J.G. Benitez, E.P. Krenzelok, and E Cortes-Belen.Loss of

consciousness from acute quetiapine overdosage. J. Analytical Toxicol 36:599-602 (1998)

2. 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 Chem Toxicol. 2011 Oct;34(4):475-7.

3. 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.

4. 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.

5. Bosse GM, Spiller HA, Collins AM. A fatal case of venlafaxine overdose. J Med Toxicol. 2008 Mar;4(1):18-20.

6. 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.

7. Chuang R, Bernard A. A 31-year-old woman found unresponsive with tachycardia . Hosp Physician 2009 May-Jun;45(4):29-32

8. Lindsay Murray et al (2010). Toxicology Handbook.


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