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Update in Clinical Toxicology

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Update in Clinical Toxicology The father of toxicology: Philippus Aureolus Theophrastus Bombastus von Hohenheim Update in Clinical Toxicology Dr David Wood Consultant Physician & Clinical Toxicologist Guy’s and St Thomas’ NHS Foundation Swiss German philosopher, physician, botanist, astrologer and Trust, London, UK general occultist (1493 – 1541) “Sola dosis facit venenum”…..” The dose makes the poison” The poisoned patient The poisoned patient . ~200,000+ poisoning cases/year present to ED . ~200,000+ poisoning cases/year present to ED – 100,000 poisoning admissions – 100,000 poisoning admissions R00-R09 Symptoms & signs inv. the circulatory/respiratory system R10-R19 Symptoms & signs inv. the digestive system & abdomen R50-R68 General symptoms & signs J40-J47 Chronic lower respiratory diseases I20-I25 Ischaemic heart diseases I30-I52 Other forms of heart disease S00-S09 Injuries to the head K55-K63 Other diseases of intestines L00-L14 L55-L99 Other infections and disorders of the skin J20-J22 Other acute lower respiratory infections T36-T50 Poisonings by drugs medicaments & biological substances J10-J18 Influenza & pneumonia N30-N39 Other diseases of the urinary system J00-J06 Acute upper respiratory infections O10-O75, O85-O92, O95-O99 Complications of labour and delivery I60-I69 Cerebrovascular diseases T80-T88 Complications of surgical & medical care nec. R69 Unknown & unspecified causes of morbidity K50-K52 Noninfective enteritis & colitis S70-S79 Injuries to the hip & thigh 0 50,000 100,000 150,000 200,000 250,000 300,000 350,000 400,000 Prescott K et al, Br J Clin Pharmacol 2009; 68: 260-8 Question Question Which drug is the commonest taken in intentional Which drug is the commonest taken in intentional overdoses in the UK? overdoses in the UK? 1. Paracetamol 1. Paracetamol 2. Venlafaxine 2. Venlafaxine 3. Ibuprofen 3. Ibuprofen 4. Aspirin 4. Aspirin 5. Fluoxetine (Prozac®) 5. Fluoxetine (Prozac®) 1 Managing poisoned patients Help in managing poisons patients . ~200,000+ poisoning cases/year present to ED – 100,000 poisoning admissions – 300 in-hospital deaths (in-hospital mortality < 0.5%) – Most overdose patients in UK develop minor or no clinical features (<5% is clinically serious) What causes “severe” toxicity? Types of exposure . Un-intentional – Exploratory exposures in children (18m - 3y) – Rarely result in severe clinical features – A few exceptions (TCA, chloroquine, calcium channel blockers, methadone, sulphonylureas, toxic alcohols) . Accidental and occupational exposures – e.g. house fires . Intentional – Deliberate self-poisoning (70% of DSH – >12-14 years, peaks in teens/20s – Female>male Most Common Agents for DSP Assessment of the poisoned patient . UK, Europe, North America, Australasia History: – Analgesics (paracetamol 50%, NSAID, aspirin), . The drugs / chemicals ingested Good documentation benzodiazepines, antidepressants, antipsychotics . Dose ingested and time of ingestion is important – Chemical, pesticide and plant ingestion uncommon BUT – < 5% clinically serious, in-hospital mortality << 1% . Patient often drowsy, confused, drunk, withdrawn . South/Southeast Asia, Africa, Middle East . Often necessary to get additional history from friends, family, ambulance crew – Pesticide, chemical and plant ingestion are common CHECK THE PATIENT’S – Pharmaceutical poisoning less common BELONGINGS! – Pesticide poisoning is a major cause of early mortality . Also begin the psychosocial assessment early – In-hospital mortality >> 10% 2 Assessment of the poisoned patient Toxidromes Examination Bowel Symptoms BP HR RR Temp Pupil size Diaphoresis . A good baseline general examination is important sounds - ↑ - ↑ ↑ ↓ ↓ – Neurological: mental status, GCS, pupil size, focal Anticholinergic neurology - - ↔ ↔ ↓ ↑ ↑ – Cardiovascular: heart rate, blood pressure Cholinergic – Temperature ↓ ↓ ↓ ↓ ↓ ↓ ↓ – Respiratory: ?aspiration Opioid ↑ ↑ ↑ ↑ ↑ ↑ ↑ . A few drugs give a specific toxidrome that may help Sympathomimetic make diagnosis ↓ ↓ ↓ ↓ - ↓ ↓ – Anticholinergics, opioids, caustics Sedative Management of the Poisoned Patient Paracetamol & Salicylate Concentrations . Resuscitation & Supportive Care . Paracetamol poisoning common and initially asymptomatic . Only then consider specific measures . Paracetamol concentration if: - (these are used in the minority of patients) – History of paracetamol overdose - Measures to decrease absorption: – Opioid toxidrome - gastric lavage, activated charcoal, whole bowel – Uncertain history irrigation – Patient drowsy or confused or uncertain history - Measures to increase elimination: . Salicylate poisoning uncommon but often symptomatic - repeat dose charcoal, urinary manipulation . Salicylate concentration if: - extracorporeal techniques – History of salicylate / aspirin overdose - Use of antidotes – Symptoms/signs / metabolic features of salicylate toxicity Other blood tests … 12-lead ECG . General biochemistry/haematology: dependent on the toxin involved • Who should get a 12 lead ECG: . Full toxicological screen rarely influences outcome − Ingested a cardiotoxic drug – Only for medicolegal (or academic) purposes − Presence of cardiovascular or neurological features . Other poisonings where serum concentrations guide • Important findings include: treatment − Tachycardia: non-specific – e.g. COHb, aspirin, lithium, iron, theophylline, toxic − QRS prolongation: increased risk of VT alcohols/glycols − QT prolongation: increased risk of torsade de pointes − Heart-block: increased risk of bradyarrhythmias • These patients should also be on a cardiac monitor 3 QT Prolongation Question • The QT interval is the time from the start of the Q wave to the end of the T wave If someone presented within an hour of an overdose, which of the following methods of gut decontamination • QTc corrects for heart rate (using Bazett’s formula) would you consider? • Use of QT nomogram to predict risk 1. Activated charcoal 2. Gastric lavage QT Interval Nomogram 600 3. Whole bowel irrigation 550 500 4. Induced vomiting 450 400 350 300 250 QT interval (msec) interval QT 200 20 40 60 80 100 120 140 160 Heart Rate (bpm) Question If someone presented within an hour of an overdose, which of the following methods of gut decontamination . Very rarely indicated in overdose management would you consider? . Significant morbidity related to gastric lavage 1. Activated charcoal – Arrhythmias, hypoxia, convulsions, cardiac arrest 2. Gastric lavage – Increased tablet absorption 3. Whole bowel irrigation – Physical restraint for lavage 4. Induced vomiting – Aspiration Activated charcoal How do you get a toddler to drink something . Burnt then steamed coconut shell, wood, coal etc. that looks like this .. ?? – producing small particle sizes with intricate internal pore structure & surface area ~ 2000m2/g . Adsorbs most compounds – except metals (iron, lithium, lead), acids/alkalis, alcohols . 50G adults, 1G/kg children orally or via NG tube – Give to all patients presenting within one hour – Ingestion of a potentially toxic dose . Multi-dose administration – Slow/modified release drug, aspirin – Give every 3-4 hours with laxatives 4 Activated Charcoal: The Future ?? Whole Bowel Irrigation . Kleenprep (polyethylene glycol) – 500ml/hr children, 2L/hr adults – evidence is largely based on case reports . Consider WBI for large ingestions of: – Iron & lithium – MR/SR preparations – Body packers Antidotes Commonly used antidotes . Relatively small number of antidotes available Toxin Antidote . Apart from N-acetylcysteine and naloxone these are Paracetamol N-acetylcysteine largely for rare poisonings Opioids Naloxone . It is important to know where your antidotes are stocked Methanol, Ethylene glycol Ethanol / 4-MP and that they are stocked! Iron Desferrioxamine Beta-blockers Glucagon Digoxin ‘Digibind’ Cyanide Thiosulphate, nitrite, diCo EDTA Methaemoglobinaemia Methylene Blue Heavy metals EDTA, DMSA, DMPS Benzodiazepines Flumazenil: NOT routine use ! At normal dose Paracetamol Paracetamol metabolism after (1g QDS) overdose Liver Liver X saturated PHASE II Metabolism by PHASE II Metabolism by METABOLISM CYP450 isoforms METABOLISM CYP450 isoforms (2E1/3A4) to N- to N-acetyl-p Conjugation with acetyl-p Potentially Conjugation with benzoquinone- Glucuronide, Sulphate benzoquinone- hepatotoxic Glucuronide, Sulphate imine (NAPQI) HEPATO (>90%) imine (NAPQI) (>90%) TOXICX X X depleted Non-toxic Under normal condition Non-toxic Under normal conditions metabolites detoxified through metabolites detoxified through conjugation with conjugation with glutathione glutathione Kidney Kidney Elimination Elimination N-acetyl-cysteine (a glutathione donor) 5 Paracetamol management in UK Pre-3rd September 2012 Reduced threshold for treating staggered / supra-therapeutic ingestions Paracetamol overdose . The paracetamol level 96 mg/L. Initial history . How many people would treat this patient? – Time of ingestion – Single -vs- staggered overdose → . Consider AC if within 1 (poss 2) hours of overdose . Blood tests required – Timing based on time of ingestion – Renal and liver profile, INR, paracetamol concentration . Determining whether treatment required – Single-time point based on nomogram plotting – Other presentations based on mg/Kg ingested “Classical” Recreational Drugs NAC Treatment . Intravenous N-acetylcysteine is the treatment of choice in the UK Stimulants Depressants . UK Regimen is given over 21 hours: Heroin Amphetamines – 150mg/kg in 200ml 5% dextrose over 1 hour Opioids MDMA (ecstasy) – Then 50mg/kg in 500ml 5% dextrose over 4 hrs Benzodiazepines Cocaine
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