Psychiatric Intoxication 9 th September Emergency Department
CME Jing Dong Emergency Registrar
Slide 2
Overview Case based Major classes SNRI SSRI TCA Atypical
Antipsychotics
Slide 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)
Slide 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 Chem Toxicol. 2011;34(4):475-7
Slide 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 (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 5 g/min, then 20 5
g/min, SBP 53 Called toxicologist, withdrew adrenaline,
noradrenaline infusion at15 g/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noradrenaline withdrawn at 6h, then extubated.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.
Slide 6
Quetiapine Atypical antipsychotic Serotonin-Dopamine
Antagonists Antagonism of Dopamine type 2 (D2) & Serotonin type
2 (5-HT2) Peripheral -adrenergic ( 1) & Histamine (H1)
receptors Known receptor pharmacology Absence of extrapyramidal
effects (D2) Prominence of orthostatic hypotension and tachycardia
( 1) Sedation (H1)
Slide 7
Clinical features Onset: 2-4 h Duration: 24-72h Dose dependent
120bpm) >3g CNS depression, coma, hypotension (coma lasts
18-48h) Seizure is uncommon (
Disposition Observe 4H with serial ECG Children >100mg (Warn
EPS up to 3d) Adult 3g Or clinical features of intoxication
Slide 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
mothers pill. Dystonia, mild tahycardia, lethargic. ECG prolonged
QTc
Slide 12
Clozapine D1&D2, 5HT and 1antagonist 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 ( 1) Seizures (GABA) 5-10% EPS more common in
children (D1) Observe for 6H and serial ECG EPS in children up to
7d
Slide 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
mothers pill. Dystonia, mild tahycardia, lethargic. ECG prolonged
QTc
Slide 14
Olanzapine D2,5HT2,H1, 1, M1antagonist Dose dependent 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
Slide 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
mothers pill. Dystonia, mild tahycardia, lethargic. ECG prolonged
QTc
Slide 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
Slide 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, HR102150 bpm, RR 17, T 37.3 First
ECG
Slide 18
ECG 1
Slide 19
ECG 2 20 minutes after later.. Transient hypotension and loss
of consciousness.
Slide 20
ECG 3
Slide 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
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
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.
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
Slide 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
Slide 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
Slide 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, p0.001) Higher suicidal intent (p0.017). 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.
Slide 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
Slide 34
ECG 1
Slide 35
Case 1 Management?
Slide 36
ECG 2 post bicarbonate
Slide 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
Slide 38
TCA Risk assessment >10mg/kg = life threatening
Dose-dependant risk 10mg/kgComa, Hypotension, seizures, arrhythmia
(onset 2-4h) >30mg/kgSevere cardiotoxicity and coma
(last>24h)
Slide 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
Slide 40
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
Slide 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
Slide 42
TCA The Pearls Sodium bicarbonate (The Antidote) Serum
alkanization Sodium loading counteracting the sodium channel
blockade Endpoints: QRS 7.50, resolution of hypotension Rapid
intubation Hyperventilation
Slide 43
ECG 3 Our Patient: ICU Continuous NaCO3 infusion Extubated on
Day 2 Serial ECG on Day 3
Slide 44
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.