ACUTE POISONING Major C J Porter RAMC Emergency Medicine Registrar Army Medical Directorate Emergency Medicine Registrar Bristol Royal Infirmary

Outline of lecture Epidemiology Toxidromes History, examination and detective work General management Specific management Antidotes Scenarios

EPIDEMIOLOGY 4000 UK deaths per year (1/3 CO) Most deaths outside hospital 100,000 Hospital admissions (12%) Not just overdoses: Illicit drugs, Alcohol

EPIDEMIOLOGY Self poisoning: F>M 1/3 >one drug Taken with alcohol: F: 40% M: 60% Repeated self-poisoning: 11% of admissions

SUICIDE 2% of male deaths 1% of female deaths Method: Female: Poisoning 40% Male: Gas / Hanging / Suffocation Self-harm parasuicide: 1% dead after 12 months 3-5% dead after 5-10 years

Toxidromes Patterns of signs and symptoms Useful to help in diagnosis and treatment of unknown poisons

Opiates Respiratory depression Cardiovascular depression Reduced level consciousness Pinpoint pupils Pulmonary oedema Hypothermia (Rapid response to Naloxone)

Common causes Opiates – heroin, morphine etc

Sympathomimetics / Stimulants Agitation/delusions/paranoia Fight/Flight response Tachycardia Hypertension Arrhythmias Dilated pupils Seizures Hyperpyrexia

Common causes Cocaine Amphetamines Decongestants Ecstasy

Anticholinergic Tachycardia Arrhythmias Pupils: mid-point or dilated / divergent Confusion / drowsiness / coma Seizures Dry flushed skin Urine retention Hypertonia, Hyper-reflexia, Myotonic jerks

Anticholinergic signs Hot as a hare Blind as a bat Dry as a bone Red as a beet Mad as a hatter

Common causes Antidepressants-Tricyclics Antihistamines Atropine Antipsychotics Antispasmodics

Serotonin Syndrome Similar to anticholinergic syndrome Agitation loss of consciousness: uncommon sweating and tremor: common Agitation Delirium Hypertonia / myoclonus Tachycardia Tachypnoea

Common Causes SSRIs MAOIs (Hyperpyrexia / Hypertensive crisis)

Cholinergic Brady/tachycardia Confusion/reduced GCS Pinpoint pupils Seizures Weakness SLUDGE Pulmonary oedema

SLUDGE S sweating salivation L lacrymation U urinary frequency urgency D diarrhoea G gastrointestinal discomfort E eyes pinpoint

Common causes Organophosphates Physostigmine Some mushrooms Nerve agents

Salicylism: Aspirin Impaired hearing Tinnitus Sweating Warm skin Hyperventilation Cinchonism: Quinine (salicylism + blindness)

MANAGEMENT

Management Overview A B C D DEFG Supportive care (O2, IV Fluids) History & assessment of vital signs ANY concerns: move patient to RESUS A B C D DEFG Supportive care (O2, IV Fluids) Prevent absorption Increase elimination Antidotes PSYCHOLOGICAL ASSESSMENT

History What? When? How much? (mg/kg) What else? Why?

Collateral history Paramedics Family / friends Notes Look in pockets – carefully!!!

Detective work BNF Toxbase Tablet identification aids: TICTAC Poisons advice: NPIS Plant identification books National teratology information service

Initial examination Treat problems as you find them!! Airway Breathing Circulation Disability – GCS/AVPU and Pupils DON’T EVER FORGET GLUCOSE

Observations Saturations and respiratory rate Pulse and blood pressure GCS Pupils Temperature GLUCOSE

Investigations All Patients As indicated Urine toxicology screen Glucose U&E Paracetamol & Salicylate As indicated LFT Co-ag / INR CK ABG / VBG ECG CXR Urine toxicology screen

Reduce absorption Emesis – No role Activated charcoal within 1 hour Gastric lavage – rarely Whole bowel irrigation - rarely

Increase elimination Urinary alkalinisation Multi-dose Activated Charcoal Haemodialysis Haemoperfusion Plasma exchange Forced alkaline diuresis (no longer recommended)

Paracetamol Very common: 40% poisons admissions Often asymptomatic Can be lethal – 200-300 deaths/year Check blood level at 4 hours Two treatment lines normal and high risk Given IV N-acetylcysteine

Paracetamol metabolism Metabolised by glucuronidation (60%), Sulphation (35%) and oxidation (10%) Cytochrome p450 produces NAPQI NAPQI toxic causes hepatocellular necrosis – irreversible binding NAPQI detoxified by conjugation with glutathione

Prescott Nomogram

High Risk Increased oxidation Reduces glutathione stores Chronic alcohol use Drugs Reduces glutathione stores Malnutrition Eating disorders Chronic liver disease

N-acetylcysteine Most effective within 8 hours Precursor for glutathione production Can cause anaphylactoid reactions Consider starting before paracetamol result if: Presenting > 8 hrs & >150mg/kg taken Staggered overdose

To treat or not to treat?

Patient 1 20 year old woman who takes a handful of paracetamol tablets No drug history No alcohol use Fit and well Blood level is 80mg/l

No need to treat Patient is not high risk Level at 4 hours is below even the high risk line

Patient 2 70 year old man Takes 20 paracetamol 6 hours before presenting Alcoholic No drug history Blood level 100mg/l

Treat Patient is high risk Level is above the high risk line Delayed presentation means need to act fast

Patient 3 17 year old epileptic 25 codydramol 2 hours before attendance Taking carbamazepine Blood level at 4 hours is 120mg/l

Treat High risk patient Level above the high risk line

Patient 4 35 year old man who presents after taking 24 paracetamol over a period of 24 hours No drug history Fit and well Blood level 20mg/l

Treat Staggered overdoses are difficult Poisons advice is to give IV acetylcysteine Levels are not that helpful Need to monitor Liver function, clotting and renal function May need discussing with Liver Unit if abnormal

PARACETAMOL DEADLY PITFALLS The Prescott Nomogram High Risk Line Staggered Overdoses Management of late presentation Recheck U&E, LFT, INR after N-acetylcysteine

Tricyclics Antidepressants Dangerous: US 60-70% fatal ODs UK commonest fatal OD per prescription 10% unconscious patient will fit Treat fits with diazepam/lorazepam

Tricyclic effects Anticholinergic toxidrome The 3 C’s Coma Convulsion Cardiac

Tricyclics cardiac effects Quinidine effects lead to arrhythmias ECG Sinus tachycardia Broad QRS: RBBB Prolonged QT interval Right axis deviation Severe poisoning – VT, bradycardia, heart block QRS > 160mS = ↑↑risk of seizures and cardiac toxicity

Tricyclics ABG Hypoxaemia Metabolic acidosis Respiratory acidosis

Tricyclics Management: EARLY ITU REFERRAL SODIUM BICARBONATE If hypotension resistant to fluid challenge Dysrhythmias Convulsions Consider IV Magnesium for resistant dysrhythmia

Salicylate Salicylism Dehydration Confusion /coma Seizures Haemetemesis Hypoglycaemia

Salicylate Metabolic and acid-base disturbance Complex Respiratory alkalosis – direct stimulation to over breathe Metabolic acidosis- acid, impaired normal metabolism, production of lactic acid Check ABG / VBG

Salicylate Severity of ingested dose: >150 mg/kg: mild >250 mg/kg: moderate >500 mg/kg: severe

Salicylate management Tailor treatment to symptoms Fluids Reduce absorption: Activated charcoal Gastric lavage (>500 mg/kg and <1 hour) Increase elimination: Urinary alkalinisation Cooling Glucose if hypoglycaemic

Salicylate management <350mg/L: oral fluids >350mg/L: urinary alkalinisation >700mg/L: haemodialysis DISCUSS WITH NPIS

Salicylate DEADLY PITFALL Salicylate levels can continue to rise following admission (10% of cases) Repeat levels every until peaked

Opiates Common Act on μ-receptors Reversible with Naloxone Naloxone pure opioid antagonist Naloxone Short half life: may need repeated doses Give IV +/- IM & may need IVI

Antidotes Opiates – naloxone Paracetamol – acetylcysteine/methionine Beta-blockers – glucagon Insulin – glucose Iron – desferrioxamine Carbon monoxide – oxygen Methanol - ethanol (Benzodiazepines – flumazenil)

Scenario 1 20 year old IVDU found by ambulance crew unconscious Needle lying by side Resp rate 6, Sats 94% on air 60bpm BP 100/55 Responds to pain

What next? A – Give naloxone B – Check airway C – Take history D – Give flumazenil

Check airway Check airway patent Give oxygen Call for senior help Check glucose Give naloxone IM and IV

Scenario 2 30 year old woman Taken some white tablets 4 hours earlier Feels completely well Felt depressed after argument with partner Usually fit and well

What next? A – Start N-Acetylcysteine B – Discharge as she is obviously well C – Find out what the tablets are D –Take blood for paracetamol levels

Take bloods Early treatment is essential in paracetamol overdose Need to know what her levels are as soon as possible

Scenario 3 45 year old man works in local aquarium Put right hand into tank and got stung by a lion fish Respiratory rate 16 sats 100% on air Pulse 100 bpm 160/80 Fully conscious Extreme pain in hand

Lion fish

What next? A – Panic you know nothing about lion fish! B – Look on Toxbase C – Ring local zoo D – Ask a senior who also knows nothing about Lion fish!

Toxbase Patient needs cardiovascular monitoring Analgesia Hand in water as hot as can tolerate Lion fish toxin is heat labile Carefully remove spines if present Few hours later patient feels much better goes home

Summary Common Approach using: A B C D DEFG Consider the toxidromes Early senior help / Early ITU referral Supportive Care Antidotes Psychological assessment

Questions ?