Transcript MMH ED presentation

Psychiatric Intoxication
9th September
Emergency Department CME
Jing Dong
Emergency Registrar
Overview
Case based
 Major classes
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SNRI
SSRI
TCA
Atypical Antipsychotics
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
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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)
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 Chem Toxicol. 2011;34(4):475-7
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 (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 ICU, noradrenaline withdrawn at 6h, then extubated.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
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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)
Clinical features
Onset: 2-4 h
 Duration: 24-72h
 Dose dependent
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◦ <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
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Investigations
Screening: ECG, BSL, paracetamol level
 Serial ECG
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◦ At presentation
◦ 4H post presentation
Management
Resuscitation
 Supportive care
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◦ Hypotension: IV crystalloid  NA
(Adrenaline exacerbates hypotension)
◦ Delirium: Benzodiazepine
Monitoring
 Decontamination
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◦ Rapid onset of sedation and coma
◦ Unless intubated, activated charcoal NOT
indicated
Disposition
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Observe 4H with serial ECG
◦ Children >100mg (Warn EPS up to 3d)
◦ Adult <3g
◦ Clinically well
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Admission for supportive care
◦ Adult >3g
◦ Or clinical features of intoxication
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
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Clozapine
D1&D2, 5HT and α1antagonist
Potent antagonist at muscarinic (M1), histamine (H1)
and GABA receptors
 Receptor pharmacology
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◦ 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)
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Observe for 6H and serial ECG
EPS in children up to 7d
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
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Olanzapine
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D2,5HT2,H1, α1, M1antagonist
Dose dependent
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<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%)
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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 – 1.6
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
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Risperidone
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Much lower affinity for H1 and M1
Lethargy, confusion, mild sedation and
tachycardia are common
QT prolongation may occur
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If coma, seizures, significant abnormal vital signs
 consider alternative diagnosis
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Children >1mg required observation
EPS up to 3d
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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
ECG 1
ECG 2
20 minutes after later…..
 Transient hypotension and loss of consciousness.
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ECG 3
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
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ECG 4
Selective Serotonin Reuptake
Inhibitors (SSRI)
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Citalopram, Escitalopram, Fluoxetine,
Fluvoxamine, Paroxetine, Sertraline
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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
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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
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SSRI - Management
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Supportive
◦ Seizure & agitation: benzodiazepine
◦ Serotonin syndrome (T, benzo)
◦ Increasing anxiety, sweating, tremor, tachy and
mydriasis  prophylactic benzodiazapine
◦ Ongoing cardiac monitoring
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Decontamination
◦ Alert, cooperative >600mg citalopram
◦ 50g activated charcoal within 4h postingestion
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.
Case 3
Serotonin Noradrenaline Reuptake
Inhibitors (SNRI)
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Venlafaxine, Desvenlafaxine
SNRI & Sodium channel blocking
Life-threatening emergency
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Seizures, Cardiovascular toxicity
Dose-dependant
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<1.5g:
<3g:
>3g:
>4.5g:
◦ >7g:
Seizures <5%
Seizures 10%
Seizures >30%
Seizures 100%, Hypotension, QRS &
QT prolongation
Hypotension and cardiac arrhythmia
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
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SNRI
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Serial ECG, CK
Early intubation and ventilation for ingestion >7g
 Seizures: Benzodiazepine
 Broad complex tachycardia: intubation,
hyperventilation and NaCO3
 Hyperthermia
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Activated charcoal
◦ within 2H of >4.5g ingestion if alert and cooperative
◦ >7g ingestion and seizure after intubation
SNRI
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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
SSRI vs SNRI
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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.
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Positive risk benefit profile for depression
and GAD, esp second line to SSRIs.
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
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ECG 1
Case 1
Management?
ECG 2 – post bicarbonate
Tricyclic antidepressants (TCA)
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Amitriptyline, nortryptyline, clomipramine,
tripramine, imipramine, dothiepin, doxepin
Morbidity and Mortality
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A BAD DRUG
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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 threatening
 Dose-dependant risk
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◦ <5mg/kg
◦ 5-10mg/kg
◦ >10mg/kg
◦ >30mg/kg
(last>24h)
Min symptoms
Drowsiness, mild anticholinergic
Coma, Hypotension, seizures,
arrhythmia (onset 2-4h)
Severe cardiotoxicity and coma
TCA - Clinical Features
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CNS
◦ Coma/sedation (H1)
◦ Seizures (GABAa)
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CVS
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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
ECG
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
Management
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Close monitoring >6H
Ventricular arrhythmia
◦ Sodium Bicarbonate 2mmol/kg Q1-2mins
◦ Then infusion in D5
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Hypotension
◦ Crystalloid, NaCO3
◦ A or NA infusion
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Seizures
◦ Benzodiazepines
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Intubated  hyperventilation aiming pH7.50-7.55
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Activated Charcoal: only if >10mg/kg and intubated
TCA – The Pearls
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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
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ECG 3
Our Patient:
•ICU
•Continuous NaCO3 infusion
•Extubated on Day 2
•Serial ECG on Day 3
References
1.
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.