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Toxicology. Management of the Poisoned Patient. Background. DSP is a big problem Intentional self harm or suicide, was ranked 15th of all deaths registered in Australia in 2007 Poisoning accounted for ~ 25% of these deaths

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toxicology

Toxicology

Management of the Poisoned Patient

background
Background
  • DSP is a big problem
  • Intentional self harm or suicide, was ranked 15th of all deaths registered in Australia in 2007
  • Poisoning accounted for ~ 25% of these deaths
  • The primary aim in the treatment of poisoned patients is to reduce mortality and early and late morbidity
  • The first priority in the assessment of patients is the adequacy of ABC
    • Simultaneous investigation and treatment
so many drugs but so little time
So many drugs but so little time...
  • Paracetamol
  • Salicylates
  • TCA’s
  • Lithium
  • Other...
  • But first – some general principles
general principles
General Principles
  • The first priority in the assessment of patients is to ascertain the adequacy of their
      • Airway
      • Ventilation
      • Circulation
  • Subsequent management determined by the risk to the patient from the poisoning.
    • Need to know information regarding the toxin, the exposure, and the patient.
general principles1
General Principles
  • History
  • Examination
  • Investigations
  • Differential Diagnosis
  • General and Supportive Management
  • Specific Interventions
core info
Core Info
  • History
    • What drug, how much, when
    • Sources of info?
    • Prev DSP’s – what, when, where, treatment
  • Targeted Examination
    • Identify Toxidromes / life threatening abnormalities
  • Investigations
    • Routine bloods inc ABG
    • Drug levels
    • UDS
    • ECG
treatment
Supportive care

ICU admission for ABC’s

Who needs intubation?

Treatment
  • GI decontamination
    • AC – single vs multidose
    • Gastric lavage
    • WBI
  • Enhanced elimination
    • Ion trapping
    • Dialysis
    • MDAC
paracetamol1
Paracetamol
  • Common
  • Really common
  • Primarily an ED managed thing
  • Mostly won’t need ICU involvement if single agent but may be involved in polysubstance ingestions
  • Guideline changed in 2008
paracetamol 2
What changed?

Acute ingestion

One line nomogram

Above the line treat

Below the line don’t treat

Chronic ingestion

Based on dose per 24hr period and duration since commencement of ingestion

NAC infusion regime

Paracetamol 2
salicylate poisoning
Salicylate Poisoning
  • PK Review
    • Aspirin is a weak acid (pKa = 3.5).
    • [ASA] dependent protein binding and metabolism
    • Acidosis
      • Increased Vd
      • Increased CNS penetration
    • Hepatic clearance
      • Zero Order Kinetics / capacity limited elimination
      • Normal T(1/2) = 2-4.5h Overdose = 18-36h
    • Renal excretion more important in overdose
salicylates effects
Salicylates – Effects
  • Respiratory alkalosis
    • Salicylates directly stimulate the respiratory centre leading to hyperventilation and a respiratory alkalosis
  • Major feature is a Metabolic acidosis.
    • Raised AGMA – (acronyms anyone?)
    • This triggers
      • An increase in metabolic rate
      • Increased oxygen consumption
      • Increased CO2 formation
      • Increased heat production
      • Increased glucose utilisation
salicylates effects1
Salicylates – Effects
  • Other effects
    • CNS effects – mild / mod / severe
    • Electrolyte imbalances
      • Potassium depletion
    • Dehydration
    • Hepatic effects
    • Glucose metabolism
    • GIT disturbance
salicylates investigations
Salicylates – Investigations
  • FBC, EUC, Coags, Calcium, Glucose
  • Arterial blood gas
  • Urinalysis and urine pH
  • Plasma salicylate concentration and repeat Q2-4H
  • Q2H ABG’s for acidaemia, electrolytes and glucose
salicylates treatment 1
Salicylates – Treatment 1
  • Patients should be admitted to ICU if they fulfill any of the following criteria
      • An acute ingestion > 300 mg/kg
      • Moderate or severe clinical severity
      • Acid-base disturbances where pH < 7.4
      • Salicylate concentration > 4 mmol/L
  • Treatment consists of monitoring and correction of
      • Hydration
      • Metabolic acidosis
      • Hypokalaemia
      • Hypoglycaemia
salicylates treatment 2
Salicylates – Treatment 2
  • Correct acidaemia, potassium deficit and dehydration.
  • Urinary alkalinisation
    • The patient should be commenced on 1 mEq/kg/hour of bicarbonate added to the IV fluid. Bolus doses may be required in severe acidosis.
    • Causes ion trapping and increases excretion
  • Haemodialysis
salicylates dialysis
Salicylates – Dialysis
  • Indications for haemodialysis
    • Pre-existing cardiac or renal failure
    • Pulmonary oedema
    • Intractable acidosis or severe electrolyte imbalance
    • Salicylate concentrations
      • >9.4 mmol/L in ACUTE ingestions (when the concentration has been taken within 6 hours of ingestion)
      • >4.5 mmol/L in CHRONIC intoxication
    • Clinically serious toxicity regardless of concentration
tca s
TCA’s
  • In Australia they are the number one cause of fatality from drug ingestion and 90% of successful TCA suicides do not reach hospital but die at home (Buckley et al, 1995).
  • The ingestion of 15-20mg/kg of tricyclics is potentially fatal.
tca s pk
TCA’s – PK
  • Highly lipid soluble weak bases
    • Rapidly absorbed
      • Anticholinergic effects may prolong absorption
  • High volume of distribution
  • Protein binding > 95%
      • May saturate increasing free fraction
      • pH dependent
  • P450 Hepatic metabolism
      • Saturated in overdose therefore renal excretion vital
tca toxicity
TCA – Toxicity
  • 3 features
  • Anticholinergic toxidrome
    • Red / hot / mad / blind / dry
  • CNS toxicity
  • CVS toxicity
tca s cns toxicity
TCA’s – CNS Toxicity
  • Psychosis
  • Decreased level of consciousness / coma
  • Seizures
      • May trigger acute deterioration
      • Associated with increased mortality
  • Anticholinergic delirium during recovery
tca s cvs toxicity
TCA’s – CVS Toxicity
  • Tachycardia
  • Bradycardia
  • Hypotension
  • Arrhythmia
  • Prolonged QRS
tca s from bad to worse
TCA’s – from bad to worse
  • Predictors of severe toxicity
    • QRS > 100 milliseconds or more in a limb lead
    • Ventricular arrhythmia
    • Seizures
    • R in aVR > 3 mm
tca s treatment
TCA’s – Treatment
  • Supportive care – airway, aggressive IV Fluids resuscitation, continuous ECG monitoring for at least 6 hours post ingestion
  • GI Decontamination – for conscious patients who present within 1-2/24. for unconscious patients via OGT post intubation.
  • Avoid acidaemia.
  • Treat seizures promptly and beware of CVS collapse post seizure
  • Extended Resuscitation – until pH corrected (alkalaemic) and discussed with Toxicologist
tca s treatment 2
TCA’s – Treatment 2
  • Sodium bicarbonate / Systemic Alkalinisation
    • Multifactorial
      • Shifts pH towards pKa
    • In discussion with the Toxicologist
      • 1-3 meq/kg bolus (if not in shock)
        • 1-3 mls/kg of 8.4% solution (1 minijet of NaHCO3)
        • 3-6 meq bolus (if in shock)
    • Titrated by ECG
    • Monitored ABG target pH 7.55 -7.6
lithium1
Lithium
  • Narrow therapeutic range
  • Predominately CNS effects in toxicity
  • CVS toxicity is bad sign
  • Acute toxicity well tolerated
    • Treat those with renal failure or sodium depletion
  • Chronic toxicity is more severe than acute toxicity
  • Death and long term disability each occur in ~10% of chronic poisonings
lithium pk review
Lithium – PK review
  • A – well absorbed orally. Peak [Li] in 2-3/24
      • Beware sustained release preparations!
  • D – not protein bound therefore = body water
      • Equilibrium btw serum and tissues takes days to weeks
  • M / E – excreted unchanged in urine
      • Filtered, reabsorbed in PCT
      • ↓ Na reabsorption means ↑ Li reabsorption
      • Prolonged half-life in overdose
lithium effects
Lithium – Effects
  • Lithium has dose related toxicity in therapeutic use
  • Initial symptoms include tremor, polyuria.
  • Later symptoms
      • Impaired consciousness
      • Myoclonus
      • Dysarthria and ataxia
  • Severe toxicity
      • Coma / seizures / ARF / death
      • CVS – ventricular dysrhythmias, prolonged QT common
lithium treatment
Lithium – Treatment
  • Admission
    • anyone with CNS symptoms or level > 1.5mEq/L
    • ICU for those needing Dialysis or with ECG changes
  • GI decontamination
    • AC ineffective
    • WBI – in patients who present early following large OD
  • Enhanced Elimination
    • Indications for dialysis
      • Seizures or coma
      • Renal failure in acute or chronic poisoning
      • [Li] > 2.5-3.0mEq/L
      • Hypotension despite adequate fluid resuscitation
lithium treatment1
Lithium – Treatment
  • Dialysis - Intermittent VS Continuous
    • Intermittent HDx
      • Rebound phenomenon
      • Need to check levels to see if further HDx needed
    • CVVHD
      • No rebound
      • Useful in haemodynamically compromised where IHDx not appropriate
      • As ongoing treatment post initial HDx
      • Slower clearance than IHDx
summary
Summary
  • Toxicology is about doing the simple things
  • Supportive care most of the time
  • Treatment should be commenced in ED
  • ABC’s
  • Dialysis and alkalinisation are important and are ICU stuff.
  • TCA’s are bad.
  • Lithium and Aspirin aren’t great either.
references
References
  • Hypertox
  • WikiTox – online reference
    • http://curriculum.toxicology.wikispaces.net
  • Oh’s Intensive Care Manual
  • Katzung, Basic and Clinical Pharmacology
  • Beckmann, U. et al (2001) Efficacy of continuous venovenoushemodialysis in the treatment of severe lithium toxicity. Journal of Toxicology, Clinical toxicology; 39(4): 393-397.
  • The Clinical Toxicology Dept at CMN
  • ABS
  • Zimmerman, J. (2003) Poisonings and overdoses in the intensive care unit: General and specific management issues. Critical Care Medicine; 31(12): 2794-2801.
  • Daly et al. (2008) Consensus Statement: Guidelines for the management of paracetamol poisoning in Australia and New Zealand. Medical Journal of Australia; 188: 296–301