Clinical Toxicology and the role of the Laboratory Flashcards
What are standard laboratory investigations for Clinical Toxicology?
- U&E’s: Sodium, Potassium, Urea, Creatinine, Chloride, Bicarbonate
- FBC
- Glucose: Differential diagnosis of a coma, ?hypoglycaemic agents. Ethanol etc
- Calcium, Albumin, Magnesium
- Liver function Tests: ALT/AST, GGT, Bilirubin
- Osmolality
- Arterial Blood Gases
- CK
- Anion Gap
- Osmolar Gap
Why are there specific poison assays?
- To confirm the diagnosis of poisoning when this is in doubt
- To influence patient management and guide the need for: Further investigations, Antidotes
- Haemodialysis
- Cessation of treatment
- Diagnosis of brain death
- Medicolegal/forensic reasons
- Out of hours testing should be restricted to those tests needed to inform immediate patient management
- Note samples may be taken and stored for later use
What are the Specific Poison Assays Group 1?
Available on a 24-hour basis in house (result within 2 hours)
- Paracetamol
- Salicylate
- Ethanol
- Carboxyhaemoglobin
- Methaemoglobin
- Paraquat (qual)
- Iron
- Digoxin
- Lithium
- Theophylline
- (Valproate)
What are the Specific Poison Assays Group 2?
Specialist – sendaway (? within 24 hours)
- Carbamazepine
- Methotrexate
- Phenobarbital
- Phenytoin
- Thyroxine
- Urine Tox screen
- Cholinesterase
- Toxic alcohols (meth/eth glyc)
- Cyanide
- Lead
- Mercury
- Thallium
- Paraquat (quant)
What are treatment approcahes towards poisoning?
- Supportive Care
- ABC
- Electrolyte imbalances
- Reduce Absorption
- Increase Elimination
How is absorption decreased in treatment?
Early treatments
- Forced emesis (ipecac syrup)
- Gastric Lavage
Single dose activated charcoal: Useful generally within 1 hour of reported OD
How is Elimination increased in treatment of poisoning?
- Forced Diuresis: Administer large volumes of liquid to increase urine elimination and prevent reabsorption. Rarely used in isolation.
- Urine Alkalinisation
- Urine acidification: No longer recommended but was thought to be useful for basic drugs eg amphetamines
- Haemodialysis: High water solubility, low mw, low Vd, low protein binding. Better at treating associated acid-base disorders
- Haemoperfusion: Generally gives higher clearance rates – uses activated charcoal or resin to adsorb toxins. More effective for protein bound drugs
- Multiple Dose activated charcoal
- Intravenous Lipid Emulsion (ILE): Useful for highly lipid soluble drugs eg carbamazepine, lamotrigine, sertraline, quetiapine
What is Urine Alkalinisation?
- Administer Sodium bicarbonate (iv) over 3 hours often used in combination with forced diuresis. Leads to ↑ ionisation, ↓ reabsorption
- Common for salicylate poisoning
- Beware hypokalaemia
What multiple dose activated charcoal?
- Useful when treating very large overdoses
- Sustained release preparations
- Prevent reabsorption in GI tract by interfering with enteroenteric, gastric and hepatic recirculation
- At least 2 doses of charcoal are given
hat are antidotes used in poisoning?
- N-acetylcysteine → Paracetamol
- Ethanol → Ethylene Glycol
- Naloxone → Opiates
- EDTA → Heavy Metal
- Fomepizole → Ethylene Glycol
- Digibind → Digoxin
- Oxygen → Carbon Monoxide
- Methylene Blue → Methaemoglobin
- Flumazenil → Diazepam
What are features of Paracetamol overdose?
- Very few early symptoms (does not cause drowsiness) and often taken with other drugs and/or alcohol (enhances toxicity). Symptomatic at 3-4 days yet hepatic toxicity may develop within 12-36 hours (ALT, INR)
- Leading cause of acute liver failure
- Pack size reduction has reduced mortality (limited by law in 1998)
What are symptoms of Paracetamol Overdose?
- Nausea/vomiting
- Abdo pain
- Tender hepatic edge
- Hepatic necrosis manifesting as jaundice
- Hypoglycaemia
What is the management of Paracetamol overdose?
Depends on time of presentation (Toxbase)
- Up to 8 hours, 8-24 hours, > 24 hours
Take sample for paracetamol (> 4 hours post ingestion), U&E, LFT, FBC, bicarb, glucose
Check normogram and treat when indicated
- If patient admits to taking > 150mg/kg (20 tablets) and presents within 1 hour – consider activated charcoal initially
- If NAC is given within the first 8 hours – virtually complete protection
- Considerable protection between 8-12 hours
- If paracetamol is below the treatment line but ALT increased – still treat
What are special problems encountered in paracetamol overdose?
- Staggered doses: assume all taken at earlier time
- Pregnant women: treat, NAC is no risk to the foetus
- Young children: generally not large OD, increased GSH stores
What are features of Salicylate poisoning?
- Uncommon and diagnosis usually straightforward
- Levels increase after admission in 10% of cases
- Beware of bezoar formation – continued absorption of enteric coated tablets
What are symptoms of Salicylate poisoning?
Mild (< 300mg/l):
- Nausea, vomiting, tinnitus, deafness
Moderate (300-700):
- Sweating, restlessness, hyperventilation (resp alk), metabolic acidosis
Severe (> 700):
- Cardiac dysrhythmias, convulsions, worsening acidosis, renal failure
What is the management of slicylate poisoning?
350 mg/L (2.5 mmol/L) - children
<450 mg/L (3.3 mmol/L) - adults
- Increased fluid intake
<700 mg/L (5.0 mmol/L):
- Charcoal / I.V. bicarbonate
>700 mg/L (5.0 mmol/L)
- Consider urgent haemodialysis
What are features of Ethylene glycol poisoning?
- Ethylene glycol is a component of anti-freeze and vehicle screen wash – often in association with Methanol
- Diagnosis requires a high index of suspicion and early intervention required
- Latent period of 12-72 hours before symptoms appear
- Apparent alcohol intoxication but no smell of alcohol
- Ethylene Glycol is non-toxic in itself – toxicity arises from the metabolites
What are symptoms of Ethylene Glycol Poisoning?
- Headache
- Restless
- Nausea and Vomiting
- Visual symptoms
- Severe metabolic acidosis
- Cardiac failure
- Renal failure
What is the Biochemistry of Ethylene Glycol?
- First few hours – osmolar gap – alcohol
- Osmolar gap declines and anion gap increases
- Important: absence of an anion gap and acidosis does not exclude the diagnosis – patient may be early presenting – only abnormality will be osmolar gap
- High anion gap metabolic acidosis at presentation means presentation is late
- Acidosis worsens
- Hypocalcaemia
- Measure ethanol
What is the treatment for Ethylene Glycol Poisoning?
- Take a sample for Ethylene Glycol/Methanol (>2 hours)
- Commence treatment with Fomepizole/Ethanol (do not wait for Ethylene glycol results)
- Severe poisoning should be treated with haemodialysis
What are indications for treatment in Ethylene Glycol poisoning?
- Severe acidosis
- Renal failure
- Severe electrolyte imbalance
- Deterioration despite supportive measures
- Continue treatment until levels are below 50mg/l (often the limit of detection of the assay.
