Poisoning

Acute poisoning is common and usually intentional. Key principles of management include:

This covers the general principles of approaching a poisoned patient. Management of specific agents is covered elsewhere.

Resuscitation

Most poisonings should be treated on the basis of observed clinical toxicity rather than measured plasma drug concentrations.

  • A
    • Remove dentures
    • Clear oropharynx
    • Tracheal intubation for patients with compromised respiratory or neurological state
  • B
    • Supplemental oxygen
    • Respiratory acidosis generally indicates need for assisted ventilation
  • C
    • Venous access
    • Fluid resuscitation is first line for hypotension
    • Arrhythmias should generally not be treated with antiarrythmics as a first line approach
      Many antiarrythmics are pro-arrhythmic and negatively inotropic.
    • Cardiovascular monitoring
    • Consider invasive haemodynamic monitoring
  • D
    • Benzodiazepines
      Are beneficial in many toxidromes for managing:
      • Seizures
      • Agitation
      • Hyperthermia
    • Correct severe hypoglycaemia with 50mL 50% dextrose
    • Naloxone can be used as a diagnostic tool
  • E
    • Cool if >39°C
  • F
    • Maintain good UO
      Will optimise renal clearance.
    • Correct electrolyte abnormalities
      Minimise any arrhythmias.

Intubation is reasonable to avoid in patients with a GHB or GBL overdose who will reliably resume consciousness in 2-4 hours.

Hyperthermia may precipitate rhabdomyolysis, acute renal failure, and DIC.

Risk Assessment

  • Ascertain nature and severity of poisoning
  • Requirement for specific therapy or time-limited interventions

History

Collateral and circumstantial history can be ascertained from:

  • Family
  • Medicine cabinet
    • Counting missing tablets
    • Checking medical records and pharmacy prescription
  • Drug factors
    • Drugs taken
      • May be multiple or unknown (children)
      • Always assume the maximum amount if uncertain
    • Dose
    • Time since ingestion
    • Dose
  • Patient factors
    • Liver impairment
    • Renal impairment
    • Psychological morbidity

Consider NAI in children.

Examination

Differential diagnoses of coma should include:

  • ICH
    • SAH
    • EDH
    • SDH
  • Meningitis
  • Encephalitis
  • Diabetic coma
  • Uraemic encephalopathy
  • General
    • Needle marks
    • Self-harm
    • Heart rate
    • Blood pressure
    • Respiratory rate
  • Neurological exam
    • GCS
    • Qualitative evaluation of conscious state
    • Pupil size
    • Tone, reflexes, and clonus

Investigations

Bedside:

  • BSL
  • ABG/VBG
    • Acid-base status
      • Metabolic acidosis
      • Respiratory acidosis
      • Respiratory alkalosis
        Classically in early salicylate overdose.
    • Anion gap
  • ECG

Laboratory:

  • Biochemistry
    • Renal function
      Affects clinical course of most drug overdoses.
  • Drug levels
    For specific poisonings.
  • Urine
    Retain sample for later analysis.

Routine toxin dipsticks are not recommended due to the high false-positive rate and cross-reactivity with prescription medicine.

Imaging:

  • CXR
    • Aspiration

Decontamination

Viable methods include:

  • Activated charcoal
  • Whole bowel irrigation
  • Surface decontamination

Historically, two other methods were used but no longer recommended:

  • Induced emesis
    Removes only limited volumes and ↑ aspiration risk.
  • Gastric lavage
    Removes insignificant volume, may propel unabsorbed poison into small intestine.

Activated Charcoal

  • Very effective absorber of toxins in GIT due to high surface area and porous structure
  • 1st line for most poisonings
    • Effective absorber of 100–1000Da compounds that present early, or delay gastric emptying
    • Drugs that are not effectively removed include:
      • Alcohols
      • Metals
      • Corrosives
        Acids and alkalis.
      • Pesticides
      • Cyanide
  • Single dose should be given to all patients within 1 hour of ingestion of a toxic dose
    Efficacy falls with time since ingestion - give early.
  • 1g/kg up to 50g
    • May still be given if overdose ↓ gastric emptying or slow-release preparation
      e.g. Opioids, anticholinergics, TCA.
  • Multi-dose activated charcoal is useful for drugs that are enterohepatically recirculated or a slow-release preparation
    Repeated dose of charcoal used Q4H, with concurrent use of sorbitol with the first dose to ↓ risk of obstruction.
  • Serious complications are rare, however:
    • Should not be given if ↓ GCS due to risk of aspiration
      Intubate, then administer via NG.
    • May cause bowel obstruction
      • Rare
      • More common with multi-dose and ↓ gut motility
    • May absorb therapeutic medications

Whole Bowel Irrigation

  • Gut decontamination with non-absorbable polyethylene glycol solution
  • ↓ GI absorption by creating high volume of liquid stool
  • Indicated for limited number of poisons:
    • Iron
    • Lithium
    • ‘Body packers’
    • Slow-release preparations
      • Potassium
      • Calcium channel blockers
      • β-blockers
      • Theophylline
  • Requires monitoring of electrolyte concentrations
  • Administer 25mL/kg/hr up to 2L/hr via NGT
    • Place patient on commode
    • Continue until effluent is clear
    • Stop irrigation if abdominal distension occurs

Endoscopic Removal

  • Direct removal is indicated for:
    • Obstruction
    • Iron tablets
    • “Body packing”
      Swallowed packets of high doses of drugs that may precipitate extreme overdose if they rupture.

Surface Decontamination

  • Indicated for cutaneously absorbed drugs including:
    • Glycerol
    • Industrial solvents
    • Mercury salts
    • Lead salts

Enhanced Elimination

Urinary Alkalinisation

Urinary alkalinisation is also known as forced alkaline diuresis.

  • Creating an alkaline urine to trap ionised drug in the renal tubule and prevent tubular reabsorption
  • Effective if the drug is:
    • A weak acid
    • Predominantly renally eliminated
    • Creating significant toxicity
  • In practice, used for:
    • Salicylates
    • Phenobarbital
    • Methotrexate
    • Chlorpropamide
  • Achieved by sodium bicarbonate IV
    • Infuse isotonic bicarbonate at 250mL/hr
      Dilute 150mL of 8.4% in 850mL of D5W to produce isotonic bicarbonate.
    • Adjust infusion to maintain urinary pH of 7.5-8.5
  • Complications:
    • Hypokalaemia
      • Requires regular monitoring and replacement of serum potassium
      • Occurs as potassium is exchanged for hydrogen in the tubule
        This leads to both:
        • Clinically significant hypokalaemia
        • ↓ Urinary pH and ↑ reabsorption of the offending substance
    • Hypocalcaemia

Urinary alkalinisation relies on the following:

  • Drugs can only pass through lipid membranes in their unionised form
  • Ionised drugs are water soluble and trapped by surrounding lipid membranes
    e.g. In the renal tubule.
  • Weak acids will lose their hydrogen ion in a basic environment, becoming a (ionised) conjugate base
    \(AH \leftrightarrow A^- + H^+\)
    • This conjugate base is then trapped in the renal tubule, and is eliminated
  • The Henderson-Hasselbach equation:
    • Describes the relationship between the:
      • Environmental pH
      • Drug pKA
      • Concentration of ionised and unionised forms
    • \(pH = pKa + {\log_{10} {[A^-] \over [HA]}}\)
      If concentrations are equal, then pH = pKa as \(\log_{10} 0 = 1\)

Haemodiafiltration

Haemodialysis is recommended for severe overdose of:

  • Barbiturates
  • Salicylates
  • Lithium
    Chronic.
  • Theophylline
  • Carbamazepine
  • Metformin
  • Paracetamol
  • Toxic alcohols
  • Phenytoin
    Some preparations.
  • Valproate
  • Potassium salts
  • Extracorporeal filtration is effective for drugs with:
    • Small VD
      Essentially confined to plasma.
    • Small molecule
      Able to cross semi-permeable membrane.
    • Rapidly redistribution from tissue to plasma
      Not trapped in tissues.
    • Slow endogenous clearance
  • Considered worthwhile if clearance ↑ by ⩾30%
  • Ultrafiltration rate is the prime determinant for removal of larger molecules
  • Dialysate flow rate is the prime determinant for removal of smaller molecules
  • The extracorporeal circuit may directly adsorb some drugs in idiosyncratic fashion

Haemoperfusion

Use of an extracorporeal circuits to bind drugs to a filter, which:

  • Facilitates ↑ clearance by adsorption
  • Have a high-surface area, and made from:
    • Resin
      • Bind lipophilic substances
      • May be designed with drug-specific antibodies
    • Activated charcoal
      • Broad-spectrum

Complicated by:

  • Electrolyte derangements
  • Coagulopathy
    • Thrombocytopaenia
    • Removal of clotting factors
  • Immunosuppression
  • Loss of micronutrients
  • Charcoal embolisation

Plasmapheresis

Plasma exchange is:

Plasma exchange is also beneficial in any setting where haemodialysis or haemoperfusion are helpful.

  • Beneficial when toxins are confined to plasma proteins
    Both:
    • Highly protein bound
    • Low VD
  • Possibly beneficial when a toxin is highly protein bound with a high VD
    Several exchange runs may be required.

Lipid Emulsion Therapy

  • Role in local anaesthetic toxicity
  • Unclear mechanism, may relate to either:
    • Large lipid volume that lipid soluble drugs dissolve into
    • Energy substrate for shocked myocardium
  • 20% lipid emulsion given:
    • At 1.5mL/kg followed by infusion at 15mL/kg/hr
    • If further instability:
      • 1.5mL/kg Q5M
      • ↑ Rate to 30mL/kg/hr
    • Up to 12mL/kg

Supportive Care

  • B
    • Mandatory mode of mechanical ventilation
      Compensate for any acid-base disturbances.
  • D
    • Thiamine 300mg for patients at risk of Wernicke’s encephalopathy

References

  1. Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.
  2. Greene SL, Dargan PI, Jones AL. Acute poisoning: understanding 90% of cases in a nutshell. Postgraduate Medical Journal. 2005;81(954):204-216. doi:10.1136/pgmj.2004.024794