EmergencyPedia

Clinical Toxicology 1

The Approach to the Poisoned Patient (Dr Lau Fei-lung)

• (1) Dose – It’s the Dose “that makes the poison“
  • LD50 = Lethal dose that kills 50%
• (2) Patient factors – individual factors that affect the likelihood of toxicity

• Resuscitation of the Poisoned Patient
  • Self Protection (Universal Precautions) – consider your own safety first
  • In the initial phase of management it is important to address the patients “ABC” which may include intubation with mechanical ventilation
  • Administration of emergency treatment in the Emergency Department (ED) may be required

• Types of Poisoning
  • Accidental
  • Self-harm
  • Recreational
  • Forensic

• Rapid Assessment of the Poisoned Patient in the ED
  • History (which substance, which form, how much, when and why)
  • Vital Signs (key initiation of immediate intervention in theEmergency Department)
    • For Example for Bradycardia remember “PACED“
    • Propranolol, Anticholinesterase, Calcium Channel Blocker, Ethanol, Digoxin
  • Examination (i.e. pupils, neurological, skin etc.)
  • Investigations (ECG, Blood Sugar, Paracetamol Levels, Blood Gas)
  • Consider Specific Toxidromes
    • Opioid
    • Anticholinergic
    • Cholinergic
    • Sympathomimetic (can be hard to distinguish from Anticholinergic – look for sweating)
  • It is important to determine a risk assessment and likely severity of the poisoning:

• Initiate management of the patient based on assessment of risk versus benefit to the patient
• Consult expert help early

• Further Management of the Poisoned Patient
  • Specific Treatment and “Antidotes”
  • Supportive Care
  • Decontamination
  • Re-exposure Termination (Enhanced Elimination)

Clinical Toxicology 2

Update on Antidotes (Dr Robert Hoffman)

Overdose has passed Traffic Accidents in term of the number of deaths in the USA

Prescription Opioids and IV Opioids are a major issue – Naloxone is often used as an “Antidote“

• Naloxone
  • Pure competitive antagonist
  • The consequence of this is it “does nothing” in those who have no opioids on board
  • The drug is very short acting so may required an infusion (give 2/3 of the effective bolus per hour)
  • Naloxone doesn’t work oral but is effective by multiple other routes (IV, SC, IM, trachea, nasal)
  • Avoid or reduced the dose for Opioid Dependent
  • Dr Hoffman suggests 0.05mg IV unless impending respiratory arrest in the dependent patient
  • Large doses have been associated with Acute Respiratory Distress Syndrome (ARDS)

Anticholinergic Syndrome can have a wide variety of causes – some consider Physostigmine the antidote

• Physostigmine
  • A good ‘reversal agent’ for anticholinergic syndrome – many toxicologists are reluctant to give
  • Not a competitive antagonist – increases acetylcholine – will make anyone cholinergic and therefore can have significant side effects
  • Case reports in the 1980s suggested significant cardiac toxicity – however, this was in the context of aberrant ECG findings and mixed overdoses
  • More recent studies (retrospective) favour its controlled use
  • If we are going to use this we need
    • a relatively normal ECG
    • slow infusion (over 5-10 minutes)
    • any cholinergic effects or patient back to normal should trigger you to stop

Organophosphates – massive issue in developing countries

• Atropine
  • Reversal of Muscarinic Symptoms
  • Dose – it is suggested that we start relatively high with our Atropine dosing and double the dose every 3-5 minutes (does over 32mg are often required)
  • End Points  – Drying of Secretions (don’t worry about pupils)

• Praladoxime
  • Shown to work in the “test tube” environment – can reactivate the Cholinesterase enzyme in the lab
  • In human studies significant contradiction in two studies
    • The case for –
    • The case against –
  • Using the treatment – not for “bolus” – will cause acute weakness

Cyanide – rapidly acting poison (rarely survive to hospital)

• Cyanide blocks the last step in oxidative phosphorylation
  • = catastrophic effect on energy metabolism
  • = rapid death
• Various Antidotes
  • Sodium Nitrite – can be effective but drops BP
  • Thiosulphate – can be effective but a risk of Methhaemoglobinaemia
  • B12 – ‘Hydroxocobalamin’ – mops upCyandide 2.5 -5grams IV – first choice in USA
    • Can be given with (in addition to) Thiosulphate
    • Causes Red Urine, Red Skin etc.
      • ‘Everything turns red‘ (warn nurses and the lab!) – this will have a significant effect lab results (troponin, creatinine) as well as the pulse oximeter and COHb

Methaemoglobinemia

• Methhaemaglobinaemia
  • Methylene Blue – can be an effective therapy
  • G6PD – is not contraindication or reason for failure of this treatment (the speakers cited issues with 1970s case report by Rosen et al that has created a myth that the treatment is ineffective in the absence of NAPDH – in fact the poisoning caused a reduction in the levels of NAPDH)

Clinical Toxicology 3

Decontamination (Dr Robert Hoffman)

‘Appears to be Common Sense‘

Lavage, Charcoal and Bowel Irrigation should be effective  (at least in theory)

In reality mixed results in literature

• Ipecac – not recommended by the ICEM conference speakers (for use in developed countries)

• Gastric Lavage – this area is a controversial issueamoungst toxicologists
  • Dr Hoffman and the other ICEM speakers disagree with the “position statements” of the Clinical Toxicologists “never to use Lavage”
  • They believe that early lavage may be used selectively
  • Of note, a paper by Li Yi in 2009 suggested that early lavage in critically unwell poisoned patients in China resulted in a reduced mortality but the authors did not conclude that lavage was indicated
  • A massive Colchicine overdose, chemotheraphy OD or lethal Aspirin OD would be examples of overdoses when Dr Hoffman and the other speakers would consider Gastric Lavage

• Activated Charcoal – multiple studies showing benefit in various scenarios – “charcoal is not dead”
  • QT in Citalopram
  • Yellow Oleander (Sri Lanka)
  • Paracetamol Poisoning
  • Stomach emptying speed is really quite variable – and may be slower in large overdoses.
  • Time is an issue but don’t always use one hour as a cut off!
    • Juergens et al showed benefit up to 4 hours so Charcoal should be considered beyond 1 hour in selected patients

• Whole Bowel Irrigation
  • a good way to “alienate your nurses” –  but can be used in specific circumstances:
    • Consider in large metal (e.g. iron) overdoses and sustained release drugs

• Enhanced Elimination (EE)
  • Dialysis – effective with drugs of small molecular weight, lack of intracellular binding, low protein binding and low volume of distributions
  • The Extracorporeal Treatments in Poisoning Workgroup (EXTRIP) – currently looking at evidence
    • Indications may include – Aspirin OD, Severe Paracetamol OD, Lithium OD, Carbamazepine OD,  Methanol OD,
    • No evidence in TCA and a variety of other toxins – the results of the EXTRIP analysis will be published in the coming months to help us rationalise the use of EE and dialysis