A case of psychiatric drug D.O.

A case of psychiatric drug D.O. Clinical Toxicology Course Dr. Cynthia Shum UCH AED

History • A 44-yr lady was brought in at 7:30pm by ambulance • Suicidal attempt • Took 20 tabs of drugs from 10am to 3pm and 10 tabs of another drug at 3pm

Vital signs: • BP 101/70 • Pulse 69/min • Temp. 36.5 • RR 20/min • SpO2 100% on RA

Physical Examination • GCS 15/15, pupils 3-4mm reactive • Skin normal, bowel sound normal, no bladder • Patient was upset, lethragic, tremor of hands was noted, but no weakness, no fasciculation, jerks not hyperactive

Bedside Investigation • H’stix 3.5 • ECG: SR normal QRS, QTc 0.46sec

PMH: • Bipolar depression FU YFS • On Lithium SR and clonazepam. • Empty bags of Lithium SR (400mg/tab) and clonazepam (1mg/tab) found • Total ingestion: Lithium SR 20tabs x 400mg = 8 gm Clonazepam 10tabs x 1mg = 10mg

Investigations: Li level RFT Paracetamol/salicylate CBP INR AXR Decontamination Lavage AC Forced diuresis WBI: PEG 2L/hr until clear return What is your management?

Supportive Fluid and electrolyte Adequate Hydration IVNS for good urine o/p Foley to BSB What’s your management?

Blood results: • Li level 4.2mmol/L • RFT normal • Na, K normal • CBP, INR normal • Paracetamol/salicylate negative • AXR: no tablets seen What else would you do?

Progress: • ICU admission • HD started 200-250ml/min x 3 hrs • Patient was closely monitored and given bolus of fluid to maintain BP during HD

Acute Toxicity Action Level WBI Chronic Toxicity Time (Hour) From time of AED attendance HD HD

Lithium Sustained-Release • Absorption: • Delayed for 6-12 hrs, completed for another 8hrs • Distribution • Vd 0.6-0.9L/kg, Rapidly to blood, liver, kidney • Metabolism • Nil • Elimination • 95% by kidneys, minority by sweat & saliva • T1/2 20-24hrs

Clinical manifestation • No/mild GI symptoms in SR form • CNS: Mild: weakness, fine tremor, light headedness Moderate: muscle twitching, tinnitus, hyperreflexia, slurred speech, drowsiness, apathy Severe: confusion, clonus, choreoathetoid movement, seizure, coma

Acute on chronic toxicity • CNS symptoms exclusively • High total body burden of Li in chronic use • Additional increase results in immediate toxicity • Predisposing factors • Continuation of high dose after acute mania • Na restriction • Intravascular volume depletion • Decreased GFR • Drug interation: NSAID, ACEI, SSRIs, antipsychotics

Laboratory testing • RFT • Look for the etiology of toxicity • Predict response to conservative Rx • Serial Li level • Monitor response to therapy • Reference • Therapeutic level: 0.6-1.2 mmol/L • Action level for acute toxicity: >4 mmol/L • Action level for chronic toxicity: >1.5 mmol/L

Haemodialysis • Who should get HD? • When to initiate HD? • Those who are initially poisoned and have high Li levels but no S/S of may benefit the most After Li has distributed the CNS, if is more difficult to remove by HD and permanent sequelae may occur

Who and when to HD? • Symptoms • Significant neurological symptoms • Level • Acute ingestion with Li >4mmol/L • Acute on chronic with Li >1.5 mmol/L • Failure of excretory pathway • Renal failure • Intolerable to Na repletion, e.g. CCF

Rebound Li level • HD clears only the plasma • Significant Li load in tissue • Levels • Immediate and 6hrs post HD • Look for rebound

Thank you Q & A

A case of psychiatric drug D.O.