HKCEM College Tutorial Seizure after an overdose AUTHOR Dr Chan Chi Keung August, 2013 Case ▪ M/72 ▪ Known history of COAD ▪ Convulsion in street, and a partially emptied pack of unlabeled drug besides ▪ Vitals: - GCS 7/15 BP 149/106 P 202/min T - 36.8 SpO2 98 H’stix 6.5mmol/L A&E initial management & investigations? ECG findings? Arterial blood gas (ABG) ▪ pH 7.14 ▪ CO2 5.5kPa ▪ O2 39.5kPa ▪ HCO3 14 mmol/L ▪ BE -14.5 ▪ Na 145 mmol/L ▪ K 2.6 mmol/L ▪ Cl 98 mmol/L How to interpret? ▪ Another episode of generalized tonic clonic convulsion in resuscitation room now… ▪ What to look for in cardiac monitor? ▪ What are the anticonvulsant(s) of choice? Anticonvulsants for drug induced seizures ▪ First line: - Diazepam 0.2mg/kg IV or midazolam 0.1mg/kg IV ▪ Second line: - Lorazepam 4mg in adult, 0.1mg/kg in child ▪ Third line: - Phenobarbitone 10mg/kg IV at max. rate 100mg/min - Propofol 1-2mg/kg IV with airway protection ▪ Phenytoin is NOT used in drug induced seizure Patient progress (1) ▪ Seizure terminated with Valium 10mg IV ▪ 3rd episode seizures now, no regain of consciousness in between. ▪ Which drugs can cause status epilepticus upon overdose? Status Epilepticus List ▪ Isoniazid ▪ Theophylline ▪ OHA (Hypoglycaemia) ▪ Bupropion (antidepressant for smoking cessation) ▪ Tetramine (banned rodenticide in China) ▪ Carbon monoxide (CO) … and a much longer list for common drug induced seizure Drug induced seizure (OTIS CAMPBELL) ▪ ▪ ▪ ▪ Organophosphate, OHA Tricyclic antidepressant (TCA) Isoniazid, Insulin Sympathomimetic ▪ ▪ ▪ ▪ ▪ ▪ ▪ ▪ Camphor, cocaine, Carbamazepine ,Cyanide ,CO Amphetamine, alcohol withdrawal Methylxanthines Phencyclidine Benzodiazepine withdrawal, Bupropion Ethanol withdrawal Lithium, lignocaine Lead, lindane Patient progress (2) ▪ Drug history from electronic patient record: - Using theophylline, Ventolin and Becotide puff for COAD ▪ Drug identification by on-duty pharmacist: theophylline Methylxanthines ▪ Theophylline ▪ Aminophylline (the water soluble derivative of theophylline) ▪ Caffeine ▪ Theobromine (from cocoa and cholcolate) ▪ All are structurally similar to adenosine ▪ Mechanism of toxicity: Adenosine antagonist ▪ Adenosine is an inhibitory neurotransmittor responsible for terminating seizures. Adenosine antagonism accounts for refractory seizures in methylxanthines overdose. ▪ Other effects of adenosine antagonism: ▪ inhibit histamine release, bronchodilatation (therapeutic effect in COAD/asthma) ▪ Release of endogenous catecholamines Theophylline overdose: Signs & symptoms CVS CNS GI Wide pulse Tremor Agitation N & V pressure Seizure Hypotension Tachyarrthymias Metabolic Hypokalaemia Hyperglycaemia Resp. alkalosis Died from: refractory seizure, tachyarrhythmias, hypotension Investigation ▪ Urgent serum theophylline conc. - Correlate well with clinical toxicity - However turnover time may take several hours ▪ Look for hypokalaemia - Severe hypoK indicates severe theophylline poisoning Management ▪ Supportive ▪ ABC ▪ For seizures ▪ For tachyarrhythmia Specific Treatment Antidote Decontamination ▪ Decontamination ▪ Specific: enhance elimination Supportive Management Exposure Termination Supportive management ▪ ABC ▪ For seizure: 1st line is benzodiazepine ▪ For tachyarrhythmia: - 1st line is also benzodiazepine reduce CNS excitation decrease endogenous catechalamines release. - 2nd line: diltiazem or esmolol ▪ Antiemetic for repeated vomiting ▪ Cautious IV potassium replacement GI decontamination ▪ Consider gastric lavage if: - Toxic ingestion (ie: not taking several tablets only!) - Present within 1 hour ▪ Multiple dose activated charcoal (MDAC) if presented early or clinically symptomatic: - Activated charcoal 50g, followed by repeated dose 25g Q2-4H for 4-6 doses. MDAC is useful in what overdose? MDAC with proven efficacy on Tx of following poisoning ( ABCDEQ ) -A -B -C -D -E -Q Aspirin, aminophylline (=theophylline) Barbiturate Carbamazepine Dapsone, dilantin, digoxin Epilim, extended release preparation Quinine MDAC ▪ Mechanism: - GI decontamination - Enhanced elimination by breaking enterohepatic recirculation - Enhanced elimination by gut dialysis ▪ Contraindication: - Unprotected airway (e.g.: drowsy patient without intubation) - Intestinal obstruction Enhanced elimination ▪ Charcoal haemoperfusion (HP) or haemodialysis (HD) are recommended for life-threatening poisoning ▪ ▪ ▪ ▪ Recurrent seizures Ventricular arrhythmia Refractory hypotension Bld theophylline >90mg/L ▪ Use together with MDAC Clearance of Theophylline END