Psychiatric Intoxication9th SeptemberEmergency Department CME
Jing DongEmergency Registrar
OverviewCase basedMajor classes
◦SNRI◦SSRI◦TCA◦Atypical Antipsychotics
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)
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
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 SBP rose to 120 mmHg ICU, noradrenaline withdrawn at 6h, then extubated.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.
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)
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
InvestigationsScreening: ECG, BSL,
paracetamol levelSerial ECG
◦At presentation◦4H post presentation
ManagementResuscitationSupportive care
◦Hypotension: IV crystalloid NA (Adrenaline exacerbates hypotension)
◦Delirium: BenzodiazepineMonitoringDecontamination
◦Rapid onset of sedation and coma◦Unless intubated, activated charcoal
NOT indicated
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
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
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
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
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
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
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
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
ECG 1
ECG 220 minutes after later…..Transient hypotension and loss of consciousness.
ECG 3
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
ECG 4
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
SSRI - Investigations Citalopram >600mg: serial ECG
up to 8h post-ingestionCitalopram >1000mg: serial ECG
up to 13H post-ingstionOngoing monitor until normalised
QTc
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
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.
Case 3
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
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
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
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
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.
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
ECG 1
Case 1
Management?
ECG 2 – post bicarbonate
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
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)
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
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
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
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
ECG 3Our Patient:•ICU•Continuous NaCO3 infusion•Extubated on Day 2•Serial ECG on Day 3
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.