Biochemistry and Clinical Toxicology

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Biochemistry and Clinical Toxicology

  1. 1. Biochemistry and Clinical Toxicology Mike Hallworth Royal Shrewsbury Hospital ACB North West Region Autumn Meeting – 18 October 2005
  2. 2. Poisoning - epidemiology • Incidence approx. 3 per thousand pa • Approx. 100 000 hospital admissions pa • <5% unconscious • <0.5% die
  3. 3. Most frequent enquiries to Toxbase [relative to paracetamol] 1. Paracetamol 1.00 2. Diazepam 0.30 3. Aspirin 0.28 4. Ibuprofen 0.26 5. Zopiclone 0.25 6. Ecstasy 0.23 7. Amitriptyline 0.20 8. Dothiepin 0.20 9. Temazepam 0.18 10. Coproxamol 0.17 (Camidge et al, 2003)
  4. 4. Commonest poisons on admission to hospital (Watson and Proudfoot, 2002) • Paracetamol 60% • Ethanol 35% • Salicylate 30% • Carbon monoxide 25% • Tricyclics & phenothiazines 12% • Others 30%
  5. 5. Laboratory support for drug-related emergencies: • standard laboratory tests • specific drug concentrations • drug screens
  6. 6. Standard laboratory tests • Arterial blood gases – Ventilation problems – Acid-base disturbances • Urea & electrolytes (incl Cl, HCO3, creat) – Hyper/hypo kalaemia – Anion gap • Osmolality – Alcohols • Calcium, albumin, Mg – Oxalate/fluorides
  7. 7. Standard laboratory tests ii • Glucose – Differential diagnosis of coma – Hypoglycaemic agents/EtOH/salicylates • LFTs – Paracetamol – Iron salts – Halogenated hydrocarbons
  8. 8. Standard laboratory tests iii • Creatine kinase – Rhabdomyolysis • FBC/INR – Paracetamol • Urine tests – Colour – Hb, (myoglobin) – Crystals
  9. 9. Emergency measurement of plasma drug concentrations • assessing severity of poisoning – if this is not possible clinically • determining need for specific treatment • monitoring efficacy of treatment • guiding therapy in severely ill patients in rapidly changing circumstances
  10. 10. Toxicological testing in overdose 1. Toxicity predictable based on serum levels. Drug-specific therapy can be instituted when levels dictate: Salicylate Theophylline Lithium Digoxin Paracetamol Methanol Ethylene glycol 2. Toxicity correlates with serum level, but supportive care only required: Ethanol Barbiturates Phenytoin
  11. 11. Toxicological testing in overdose 3. Toxicity and requirement for specific treatment depend on clinical parameters - testing only confirms: Tricyclics Narcotics (naloxone) Cyanide Organophosphates Benzodiazepines (flumazenil) 4. Toxicity poor correlation with serum level - supportive care only required: Neuroleptics Cocaine Hallucinogens Phenylpropanolamine Amphetamine Phencyclidine (Mahoney, 1990)
  12. 12. Reducing absorption • ((emesis)) • (lavage) • ORAL CHARCOAL
  13. 13. Increasing elimination • (forced diuresis) • Urine alkalinization • Dialysis • Charcoal/resin haemoperfusion • Multiple-dose oral charcoal
  14. 14. Specific antidotes • Paracetamol: N-acetylcysteine Methionine • Methanol/ ethylene glycol: Ethanol, fomepizole • Opiates: Naloxone • Metals: Chelators (DFO, EDTA, etc)
  15. 15. Laboratory analyses for poisoned patients: joint position paper National Poisons Information Service and the Association of Clinical Biochemists Ann Clin Biochem 2002; 39: 328-339
  16. 16. Concentration measurements required at any time: (NPIS/ACB, 2002) • Salicylate • Paracetamol • Iron • Lithium • Theophylline • Ethanol • CoHb, MetHb • Digoxin • Paraquat (qual) within 2h
  17. 17. Specialist assays that may be required urgently (ACB/NPIS, 2002) • Methanol • Ethylene glycol • Phenytoin • Carbamazepine • Phenobarbital • Methotrexate • Paraquat (quant. plasma) • AChE • As • Hg • Pb • Thyroxine • Unknown screen
  18. 18. Drug screens • Usually of very limited value
  19. 19. Mahoney et al., 1990 - Boston, USA Impact of qualitative toxic screening in management of suspected OD 176 cases of drug OD 164 screened by: GC, HPLC x3, acid GCMS, basic GCMS
  20. 20. Mahoney et al., 1990 - Boston, USA 81% screens POSITIVE 19% screens NEGATIVE
  21. 21. Mahoney et al., 1990 - Boston, USA Impact of screens on management: Treatment: n % No impact 146 90 Initiated 2 1 theophylline, salicylate Continued 12 7 salicylate x2, lithium x2 paracetamol x2, digoxin x1, Hg x1 Discontinued 4 2 paracetamol x4
  22. 22. Mahoney et al., 1990 - Boston, USA Impact of screens on disposition: 35/176 admitted to hospital: 20 because of clinical findings 7 because of clinical findings + drug screen (6 salicylate, 1 imipramine) 8 because of drug screen alone (3 paracetamol, 2 lithium, 1 salicylate, 1 carbamazepine, 1 diphenhydramine)
  23. 23. Utility of toxicology screening in paediatric ER (Sugarman; Pediatr Emerg Care 1997; 15: 194-7) • Full toxicological screens on 338 children • Unexpected results in 7% of screens • Management altered as a result of screening results in 3 patients (<1%) – All three had abnormal symptoms
  24. 24. Urgent drug screens • Poisoned patient very ill – ? Nature of poison • Deteriorating unconscious patient without ∆
  25. 25. “Routine” toxicology • Diagnosis of brain death • Suitability of organs for Tx • Medico-legal (e.g. “date rape”) • Forensic
  26. 26. Exposure to poisons Toxin Age <5 Age >15 Drugs 50.9% 74.8% Household prods. 20.4% 7.3% Toiletries 7.4% 1.4% Petroleum distill. 5.7% 1.4% Chemicals 6.2% 10.1% (SPIB, 1994)
  27. 27. Poisonings other than drugs • “Detection of poisonings by substances other than drugs: a neglected art” Badcock NR Ann Clin Biochem 2000; 37: 146-57
  28. 28. S.B., 40 years, F • On admission (1600, 18.1.97): – Na 147, K 4.4, Cl 103, urea 1.5, creat 91 – pH 6.73, pO2 51.2 , pCO2 6.2, bicarb 6, glucose 16.9 – Anion Gap = 42 mmol/L (12-20) – Osmolality: calc: 320, meas: 470 – Osmolar Gap = 150 mmol/L
  29. 29. Gaps • ANION GAP: Raised in: – lactic acidosis – ketoacidosis – salicylate poisoning – methanol/ethylene glycol poisoning – CRF • OSMOLAR GAP Raised with: – Unmeasured osmoles: • ethanol/methanol • (ethylene glycol) • mannitol/glycine – severe shock – high lipid/protein
  30. 30. Methanol / ethylene glycol • Usually latent period before symptoms (12-72h) • Headache • Pale, restless • Sweating • Convulsions • Nausea/vomiting • Visual symptoms • Severe metabolic acidosis • Cardiorespiratory failure • Crystalluria & renal tubular necrosis (glycol)
  31. 31. Ethanol (intoxication) Methanol (intoxication) Ethylene glycol (intoxication) Acetaldehyde (hangover, flushing) Formaldehyde (blindness, cerebral oedema) Glycoaldehyde (CNS effects) Acetic acid Formic acid (metabolic acidosis) Glycolic acid (metabolic acidosis) CO2 + H2O Glyoxylate (lactic acidosis) Oxalate (cerebral and renal damage, hypocalcaemia) Alcohol dehydrogenase Aldehyde dehydrogenase LDH orglycolic acid oxidase LDH or aldehyde oxidase
  32. 32. Diagnosis of methanol poisoning • Metabolic acidosis • High anion gap • High osmole gap • Eye signs ⇒ presumptive ∆
  33. 33. Estimation of alcohol concentration • Ethanol (mg/dL) / 4.6 = osmolality i.e. 80 mg/dL = 17 mmol/kg • Methanol (mg/dL) / 3.2 = osmolality • Ethylene glycol (mg/dL) / 6.2 = osmolality
  34. 34. M.McG, age 28, female • OD 20 tabs Theo-Dur (husband’s) + 7 cans strong lager • Anxious ++, pulse 130-160/reg • SWO 1h after ingestion • at 11h, Fits ++, pH = 6.9 : xfer to ITU • K+ 2.3 mmol/L • Theophylline @ 16h = 138 mg/L (760 µmol/L) • Start HD & CHP • CK 113,300 U/L, ARF developed (creat = 1355)
  35. 35. Key points (i) • Laboratory support for drug-related emergencies consists of standard biochemical/haematological tests, measurement of specific substances and drug screens for unknown poisons. • Standard laboratory tests are most important for determining immediate management in most patients. • Emergency measurement of specific substances is indicated in a small number of cases where specific therapy may be instituted depending on the nature and quantity of the poison ingested.
  36. 36. Key points (ii) • Laboratories in hospitals dealing with acute admissions need key toxicological analyses available 24/7 • Repeated measurement of specific substances may be used to guide therapy. • Drug screens rarely of immediate value but may be necessary when the patient is critically ill, or when the patient is ill and not improving, and the diagnosis is uncertain.

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