Clinical Toxicology and the role of the Laboratory Flashcards

1
Q

What are standard laboratory investigations for Clinical Toxicology?

A
  • 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
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2
Q

Why are there specific poison assays?

A
  • 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
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3
Q

What are the Specific Poison Assays Group 1?

A

Available on a 24-hour basis in house (result within 2 hours)

  • Paracetamol
  • Salicylate
  • Ethanol
  • Carboxyhaemoglobin
  • Methaemoglobin
  • Paraquat (qual)
  • Iron
  • Digoxin
  • Lithium
  • Theophylline
  • (Valproate)
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4
Q

What are the Specific Poison Assays Group 2?

A

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)
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5
Q

What are treatment approcahes towards poisoning?

A
  • Supportive Care
  • ABC
  • Electrolyte imbalances
  • Reduce Absorption
  • Increase Elimination
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6
Q

How is absorption decreased in treatment?

A

Early treatments

  • Forced emesis (ipecac syrup)
  • Gastric Lavage

Single dose activated charcoal: Useful generally within 1 hour of reported OD

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7
Q

How is Elimination increased in treatment of poisoning?

A
  • 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
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8
Q

What is Urine Alkalinisation?

A
  • Administer Sodium bicarbonate (iv) over 3 hours often used in combination with forced diuresis. Leads to ↑ ionisation, ↓ reabsorption
  • Common for salicylate poisoning
  • Beware hypokalaemia
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9
Q

What multiple dose activated charcoal?

A
  • 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
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10
Q

hat are antidotes used in poisoning?

A
  • N-acetylcysteine → Paracetamol
  • Ethanol → Ethylene Glycol
  • Naloxone → Opiates
  • EDTA → Heavy Metal
  • Fomepizole → Ethylene Glycol
  • Digibind → Digoxin
  • Oxygen → Carbon Monoxide
  • Methylene Blue → Methaemoglobin
  • Flumazenil → Diazepam
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11
Q

What are features of Paracetamol overdose?

A
  • 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)
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12
Q

What are symptoms of Paracetamol Overdose?

A
  • Nausea/vomiting
  • Abdo pain
  • Tender hepatic edge
  • Hepatic necrosis manifesting as jaundice
  • Hypoglycaemia
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13
Q

What is the management of Paracetamol overdose?

A

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
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14
Q

What are special problems encountered in paracetamol overdose?

A
  • 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
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15
Q

What are features of Salicylate poisoning?

A
  • Uncommon and diagnosis usually straightforward
  • Levels increase after admission in 10% of cases
  • Beware of bezoar formation – continued absorption of enteric coated tablets
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16
Q

What are symptoms of Salicylate poisoning?

A

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
17
Q

What is the management of slicylate poisoning?

A

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
18
Q

What are features of Ethylene glycol poisoning?

A
  • 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
19
Q

What are symptoms of Ethylene Glycol Poisoning?

A
  • Headache
  • Restless
  • Nausea and Vomiting
  • Visual symptoms
  • Severe metabolic acidosis
  • Cardiac failure
  • Renal failure
20
Q

What is the Biochemistry of Ethylene Glycol?

A
  • 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
21
Q

What is the treatment for Ethylene Glycol Poisoning?

A
  • 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
22
Q

What are indications for treatment in Ethylene Glycol poisoning?

A
  • 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.
23
Q
A