Approach to the poisoned

Risk-assessment approach

• Resuscitation
  • Airway
  • Breathing
  • Circulation
  • Detect and correct – Hypoglycaemia, seizures, hyper/hypothermia
  • Emergency antidote
• Risk assessment
  • Agent, dose, timing, clinical features/course and patient factors
  • Supportive care and monitoring
  • Investigations  – Screening 12-lead, paracetamol, BSL + Specific Ix
• Decontamination
• Enhanced elimination
• Antidotes
• Disposition

Resuscitation

• Resuscitation following acute poisoning can often have good neurological outcomes despite prolonged periods of CPR
• ECMO should always be considered and specific situations may mean conventional algorithms do not apply
• Airway
  • Corrosive injury to oropharynx from alkalis/acids/glyphosate and paraquat may warrant early intubation
• Breathing
  • Acidosis/acidaemia from ethylene glycol, methanol, salicylates may mean standard ventilator settings can cause deterioration/death. Maintain hyperventilation and consider IV bicarb 1-2mmol/kg to prevent worsening acidaemia
  • Hypoventilation from opioids can be rapidly resolved with naloxone
  • Respiratory failure in cholinergic crisis from carbamates, nerve agents or organophosphates may be rapidly titrated by serial doubling of atropine dosing to achieve dry respiratory secretions and obviate need for intervention
  • In paraquat poisoning, titrate to SpO2 90%/PaO2 60mmHg as hyperoxygenation can worsen lung inflammation

Resuscitation

• Circulation
  • VF in the setting of hypocalcaemia from hydrofluoric acid requires IV calcium boluses repeated every 2 minutes with defibrillation
  • VT due to fast Na+ channel blockade (chloroquine, cocaine, flecainide, local anaesthetics, procainamide, propanolol, quinine or TCA requires early intubation and hyperventilation, bolus IV sodium bicarb 1-2mmol/kg q1-2min until perfusion rhythm obtained, lignocaine therapy third-line once pH >7.5 and amiodarone is contraindicated

Resuscitation

• Circulation continued…
  • Ventricular ectopy or  VT due to toxin-induced myocardial sensitisation to catecholamines as seen with chloral hydrate, hydrocarbons or organochlorines warrants IV beta-blockers titrated to response
  • Intralipid for LA toxicity
  • High-dose insulin therapy for CCB/propanolol/local anaesthetic agents with refractory cardiogenic shock
  • IV benzodiazepines for stimulant-induced tachycardia (beta-blockers CI)
  • SVT due to theophylline – beta-blockers titrated to effect rather than adenosine. Urgent haemodialysis warranted
  • Stimulant induced hypertension – Beta-blockers CI so IV benzo’s – GTN infusion, phentolamine or sodium nitroprusside

Resuscitation

• Circulation…
  • Digoxin toxicity asystole/bradycardia/tachycardia requires digibind
  • CCB toxicity – Atropine and pacing unlikely to be effective. Bolus IV calcium 60mL 10% calcium gluconate +- high-dose insulin therapy
  • ACS due to stimulants – Beta-blockers CI. IV benzos, GTN, antiplatelets/anticoagulants if no neurological defects (otherwise need to rule ICH) and conventional reperfusion still indicated
  • Octreotide infusion in sulfonylurea toxicity may decrease dextrose requirements
  • Isoniazid-associated seizures warrants IV pyridoxine
  • Theophylline-associated seizures requires urgent haemodialysis

Resuscitation

• Seizures
  • Toxic seizures are always generalised
  • Most common causes of seizures in Australia are venlafaxine, tramadol, amphetamines, bupropion and withdrawal
  • Benzo’s first-line, barbiturates are second-line and IV pyridoxine for isoniazid
  • Phenytoin is contraindicated in toxic seizures as may exacerbate sodium-channel blockade (which may be causative)

Resuscitation

• Detect and correct hypoglycaemia
  • If BSL <4: 50mL 50% dextrose (5mL/kg 10% in children)
  • Associated with insulin, sulfonylureas, beta-blockers, quinine, chloroquine, salicylates and valproic acid
• Temperature
  • >38.5 warrants continuous core temp monitoring
  • >39.5 requires prompt management with paralysis, I&V and rapid reduction in temperature

Management plan

• Expected clinical course
• Potential complications according to individual risk assessment
• Type of observation and monitoring required
• End point that trigger notification
• Management plans for agitation or delirium
• Criteria for changing management
• Provisional psychosocial risk assessment with contingency plan if patient attempts to abscond prior to formal assessment

General supportive measures

• ABC
• D
  • Sedation
  • Seizure control/prophylaxis
  • Ensuring normoglycaemia
• E
  • Ensuring temperature monitoring
• General
  • Nutrition
  • Respiratory toilet
  • Bladder care +- IDC/bladder scan
  • Prevention of pressure areas
  • Thromboembolism prophylaxis
  • Mobilisation as mental status changes

Screening

• ECG – Rate, rhythm, PR, QRS, QT, dominant R wave in aVR
• Bedside BSL
• Paracetamol level
  • Cost of thousands of tests offset by preventing one death/transplant
  • Recommended in all deliberate self-poisonings
  • Can be performed at presentation and does not need to wait until 4 hours
    • If suspected based on initial risk assessment, screening test not required and need a 4 hour test as per nomogram
  • Non-detectable level at 1 hour after ingestion excludes significant ingestion
• Salicylate levels
  • Not recommended in Australia as rare and not usually occult given acid-base disturbance and symptoms
• Qualitative urine drug testing rarely changes management and positive results without corresponding signs of intoxication rarely changes things
• Drug levels that matter
  • Lithium, carbamazepine, digoxin, ethanol, ethylene gycol, iron, methanol, methotrexate, paracetamol, phenobarbitone, salicylate, theophylline and valproic acid

GI decontamination

• Potential benefits
  • Reduced morbidity/mortality, lower level of care, reduced need for antidotes and reduced length of stay
• Potential risks
  • Aspiration, bowel obstruction/perforation, distraction from other priorities and diversion of resources for performance of procedure
• Ipecac and gastric lavage all but abandoned

GI decontamination

• Single dose activated charcoal
  • Reduces absorption up to 4 hours after ingestion
  • Does not improve outcomes in unselected group of patients
  • Reasonable to administer following intubation as risk-benefit balance is almost always in favour of administration
  • Rarely justifiable in the uncooperative conscious patient
  • Complications – Aspiration, direct administration into lung, impaired absorption of subsequent oral antidotes or other agents, corneal abrasions

GI decontamination

• Single dose activated charcoal
  • Contraindications
    • Incomplete initial resuscitation
    • Non-toxic ingestion
    • Sub-toxic dose
    • Likely good outcome with supportive care and antidote therapy alone
    • Reduced LOC/agitation/delirium (unless intubated)
    • Imminent onset of seizure or reduced LOC (unless intubated)
    • Agent not bound to AC
    • Corrosive ingestion
  • Ileus IS NOT a contraindication to single dose use

GI decontamination

• Single dose activated charcoal
  • Agents not well bound
    • Hydrocarbons: Ethanol, isopropyl alcohol, ethylene glycol, methanol
    • Metals: Lithium, Iron, Potassium, Lead, Arsenic, Mercury
    • Corrosives: Acids/Alkalis
  • Technique
    • 50g (adults) or 1g/kg (children)
    • Mix with ice cream for children

GI decontamination

• Whole bowel irrigation
  • Large volume PEG
  • Indicated for life-threatening ingestions of sustained-release or enteric-coated preparations or agents that do not bind to charcoal and good clinical outcome not expected with supportive/antidote care
  • Hazardous even in intubated patients
  • Indications
    • Iron overdose >60mg/kg
    • Slow release KCl ingestion >2.5mmol/kg
    • Life-threatening slow-release verapamil or diltiazem
    • Symptomatic arsenic trioxide ingestion
    • Lead ingestion
    • Body packers
  • Complications
    • Nausea, vomiting, abdominal bloating, NAGMA, aspiration, distraction

GI decontamination

• Whole bowel irrigation
  • CI
    • Risk assessment suggesting potential reduced LOC or seizure in next 4 hours
    • Uncooperative
    • Predicted good outcome
    • Inability to pass NG
    • Uncontrolled vomiting
    • Ileus/obstruction
  • Process
    • NG, confirm placement, single nurse to perform for up to 6 hours, activated charcoal (unless does not bind), PEG 2L/hr (25mL/kg/hr) by continuous infusion
    • Maxolon
    • Position on commode if possible
    • Continue until effluent clear (can take up to 6 hours)
    • Cease if abdominal distension or loss of bowel sounds
    • Can then count packages if body packer or AXR if radio-opaque tablets

Enhanced elimination

• Multiple-dose activated charcoal
  • Interrupts enterohepatic circulation
    • For drugs excreted in bile and reabsorbed in distal ileum and has small volume of distribution
  • GI dialysis
    • Drug may pass across gut mucosa from high concentration intravascular compartment to low concentration in lumen
    • Only effective if small molecule, lipid soluble, small volume of distribution and low protein binding
  • Indications
    • Carbamazepine coma (most common) – reduces period of ventilation/ICU = Simultaneous haemoperfusion due to high protein binding
    • Phenobarbitone coma
    • Dapsone overdose with methaemoglobinaemia
    • Quinine overdose
    • Theophylline overdose (should NEVER delay haemodialysis)
    • Phenytoin
    • Piroxicam

Enhanced elimination

• Multiple-dose actived charcoal
  • CI: Predicted or decreased LOC without airway control, bowel obstruction
  • Complications: Vomiting, charcoal aspiration, constipation, charcoal bezoar formation, corneal abrasion, distraction
  • Technique: Initial 50g (1g/kg) dose then 25g (0.5g/kg) every 2 hours
  • Check for bowel sounds or high NG aspirates before each administration and cease if bowel sounds inaudible or high aspirate volumes
  • Reconsider every 6 hours

Enhanced elimination

• Urinary alkalinisation
  • Promotes ionisation of acidic drugs and prevents reabsorption across renal tubular epithelium, thus promoting urinary excretion
  • Drug must be filtered at glomerulus, have a small volume of distribution and be a weak acid
  • Indications:
    • Salicyclate overdose
      • In overdose, hepatic metabolism is saturated and elimination half-life greatly prolonged. Urinary alkalinisation is indicated in any symptomatic patient as greatly enhances elimination unless already severe (haemodialysis)
    • Phenobarbitone coma (MDAC superior though)
  • CI in alkalaemia, hypokalaemia or hypocalcaemia

Enhanced elimination

• Urinary alkalinisation
  • Technique:
    • Correct any hypokalaemia (difficult to alkalinise urine in this setting)
    • 1-2mmol/kg sodium bicarb IV bolus
    • Commence infusion of 150mmol sodium bicarb in 850mmol dextrose at 250mL/hr
    • 20mmol KCl can be added to infusion
    • Monitor bicarb and K at least every 4 hours
    • Target urinary pH >7.5
    • Continue until resolving toxicity
  • Monitor for alkalaemia, hypokalaemia, hypocalcaemia and hypomagnesaemia
  • Does not risk dehydration or acidosis

Enhanced elimination

• Extracorporeal elimination
  • Haemodialysis (intermittent and continuous)
  • Haemofiltration
  • Haemoperfusion
  • Plasmapheresis
  • Exchange transfusion
• Haemodialysis effective for:
  • Small  molecule
  • Small Vd,
  • Rapid redistribution from tissues/plasma
  • Slow endogenous elimination

Enhanced elimination

• Dialysable
  • Toxic alcohols
  • Theophylline
  • Severe salicylate intoxication: Chronic with ALOC or late presentation acute OD
  • Severe chronic lithium OD
  • Phenobarbitone coma
  • Metformin lactic acidosis
  • Massive valproate OD
  • Massive carbamazepine OD
  • Potassium salt OD with life-threatening hyperkalaemia
• Intermittent HD preferred in most settings as has most efficacious elimination

COP I’VE STUMBLED (HD or HP)

• Carbamazepine
• Osmolar gap
• Propylene glycol
• Isopropanolol
• Valproic acid
• Excess acid (of toxic origin) e.g. metformin
• Salicylates
• Theophylline (HP more effective)
• Uraemic (nephrotoxins)
• Methanol
• Barbiturates
• Lithium
• Ethylene glycol/ethanol
• Diethylene and triethylene glycol

Disposition

• Emergency observation units
  • Streamline treatment
  • Reduce total bed days
  • Increased patient satisfaction
  • Reduced inappropriate discharges and litigation
• Issues with admission to general wards
  • Frequent security issues
  • Less experienced nursing and medical staff
  • Longer admissions

Retrieval of poisoned patients

• Risk assessment is vital
• Identify possible retrieval patients as soon as possible
• Patient should never be subjected to lower level of care at any phase of transfer
• Potential complications must be proactively sought and managed
• If antidote considered likely to provide benefit, should transfer antidote to patient, administer and then move patient only if necessary
• All patients should undergo psychosocial assessment prior to discharge, ideally beginning before medical treatment is complete so that final disposition can be facilitated

Sodium bicarbonate

• Indications
  • Severe metabolic acidosis
    • Cyanide poisoning
    • Isoniazid
    • Toxic alcohol poisoning
  • Cardioprotective
    • Propranolol, TCA, flecainide, quinidine
  • Prevents redistribution of drug to CNS
    • Salicylate toxicity
  • Increases urinary solubility of methotrexate
  • Urinary alkalinisation
  • Ventricular arrhythmia management in Carbamazepine toxicity

Renal impairment and narrow therapeutic windows

• Antibiotics
  • Aminoglycosides, inipenem, vancomycin, pyrazinamide
• Benzodiazepines with active metabolites
  • Diazepam
• Digoxin
• Metformin
• Salicylates
• Lithium

Intralipid

• Only effective for highly fat soluble agents
  • Propranolol
  • Verapamil
  • TCA
  • Local anaesthetic toxicity

HIET

• NO chronotropic effect and possibly a vasodilatory effect
  • Need to consider concomitant inotrope use
• Hypoglycaemia, hypokalaemia, hypoMg and hypophosphataemia must be watched
• May not get hypoglycaemia in CCB toxicity

Mnemonics

• Miosis (COPS)
  • Cholinergic
  • Organophosphates
  • Pontine haemorrhage
  • Sedatives- Opioids

Mnemonics

• Mydriasis (SAW)
  • Sympathomimetics
  • Antihcholinergics
  • Withdrawal

Mnemonics

• Nicotonic symptoms (Days of the week)
  • Mydriasis
  • Tachycardia
  • Weakness
  • Tremor
  • Seizures
  • Somnolent

Mnemonics

• Dialysable toxins (PLASMA TV)
  • Phenobarb
  • Lithium
  • Acidosis
  • Salicylates
  • Metformin
  • Alcohols
  • Theophylline
  • Valproic acid/Carbamazepine

Mnemonics

• Multidose activated charcoal (ABCDQ)
  • Aminophylline/theophylline
  • Barbiturates
  • Carbamazepine
  • Dapsone
  • Quinine

Last Updated on October 28, 2020 by Andrew Crofton