General Toxicology Mng
Epidemiology
Dangerous poisons
In pregnancy
In paeds
1. Resus
Incidence 2%; 12.5% are symptomatic; 6-30% recurrence within 1yr
60% managed at home; >10% that come to hospital get admitted; 5% ICU; 20% general ward; 30% SSU; 45%
discharged directly from ED
90% accidental, 10% intentional
60% >1 substance; 5% >3 substances; paracetamol in 15%
ETOH present in 40% deaths
60% <5yrs (<12yrs in TinTin); peak 2-3yrs; accidental ingestion unusual >5yrs; lowest mortality 5-14yrs (40%
drugs, 14% cleaning products, 13% plants, 10% cosmetics, 6% pesticides)
80% PO, 6% skin, 5% eye, 5% INH, 1% IV
Leading cause of death <40yrs; <0.05% overall mortality; 90% deaths prior to any trt; 50% deaths are
intentional; 1/3 hospital deaths due to PE; <1% mortality rate if admitted
Resus can be assoc with good outcome even if prolonged
CV: Ca channel blockers, beta-blockers, antiarrhythmics
NS: TCA, cocaine
Tox: paraquat, CO, OP, ETOH’s, acid/alkalis, cyanide, mushroom, HC’s, strychnine
Other: chloroquine, colchicine, isoniazid, theophylline, metals
Death despite good trt: paraquat, colchicine, OP, Ca channel blockers, beta blockers, antiarrhyhmic,
cyanide, isoniazid, mushroom, theophylline
Delayed toxicity: via bezoar / delayed gastric emptying / SR, EC / slow onset of action; paracetamol,
theophylline, Ca blockers, opiates, Fe, Li, MAOI, anticonvulsants, dig, OP, amiodarone, oral hypoG,
colchicine, warfarin, thyroxine
Incr risk to fetus than mother in: CO, MetHb, lead, aspirin
If fetus survives, risk of teratogenicity low; higher risk in 1st trim; charcoal safe
2 tabs can kill: amphetamines, Ca channel blockers, chloroquine, opioids, propanolol,
sulfonylureas, theophylline, TCA (dothiepine)
A sip can kill: OP’s, paraquat, HC’s, camphor, mothball
2 tabs is fine: paracetamol, Fe, colchicine, dig, rodenticide
A: GCS not validated in poisoning; risk if GCS <12; may change quickly
B
C: give fluid bolus (large fluid resus may be needed in Fe, colchicine, theophylline, aspirin; beware pul oedema
in Ca antagonist OD); may need inotrope
Seizures: generalised; controlled with benzo’s (5-10mg diazepam (0.2mg/kg) rpt at necessary)  phenobarb
(100-300mg slow IV (10-20mg/kg) or thiopentone (3-5mg/kg); phenytoin CI’ed
Most common causes: venlafaxine, buproprion, tramadol, amphetamines
Signal of severe poisoning: chloroquine, propanolol, aspirin, theophylline, TCA
HypoG: trt if BSL <4  50ml 50% dex (5ml/kg 10% dex)
Most common causes: insulin, sulphonylurea, beta-blockers, quinine, chloroquine, salicylates, valproic acid
Hyper / hypothermia: continuously measure core T if >38.5; emergent trt if T >39.5
Do emergency decontamination: paraquat, OP’s
Give emergency antidote: digibind, calcium, cyanide
2. Risk
assessment
3. Supportive care
and monitoring
4. Investigations
Agent (?dangerous one), dose (toxic dose is usually >10x therapeutic dose), formulation, route of exposure,
time since ingestion, clinical features and progress, patient factors
Consider drug combinations, tolerance
Evaluate extent of toxicity, complications
Establish reason for poisoning
Causes of meiosis: opioids, cholinergics, olanzapine, clonidine, phenothiazines, barbs
Causes of mydraisis: anticholinergics, stimulants
Document: expected clinical course, potential complications, type of observation and monitoing, endpoints to
consult doc, mng plans for agitation, criteria for changing mng, psychosocial risk assessment
If coma, beware: aspiration, rhabdo, ARF, compartment syndrome, p area, hypoxic brain inj
ECG; paracetamol (if non-detectable >1hr after ingestion = not significant)
Drug levels helpful in: carbamazepine, phenobarb, valproic acid, phenytoin
Dig
ETOH, ethylene glycol, meth, CO, MetHb, paraquat (NOT cyanide – takes too long)
Fe, lead, mercury, Li, arsenic
methotrexate, paracetamol, aspirin, theophylline
5. Decontamination
Osmolality = (2 x Na) + Ur + Glu
Normal = 270-290
Osmolar gap = calculated – measured
Normal -4 to +10
= amount of osmotically active substances in serum not measured by test
Eg. Ca, Li, proteins (eg aa’s in ESRF), lipids, ETOH’s (normal OG does not exclude this if late presentation, as
metabolised to less osmotically active substance), mannitol, acetone, formaldehyde, paraldehyde
Use if: risk assessment predicts severe / life threatening toxicity, and supportive care / antidotes insufficient
to ensure a satisfactory outcome; grounds to believe reasonable amount of agent remains unabsorbed and is
amenable to removal
In most agents, absorption complete within 1hr
Pros: improved mortality and morbidity; more benign clinical course requiring decr level of care; decr need
for hazardous / expensive interventions; decr hospital LOS
Cons: aspiration; GI complications (eg. Perf, obstruction); distraction from resus / supportive care; diversion
of departmental resources
Induced emesis (Syrup of Ipecac): 90% V within 20mins 1st dose, 97% after 2nd dose; resolves in 2hrs
Dose: 15-30ml with glass of water  rpt at 30mins if no vomiting
Indication: significant toxicity likely, no seizure / decr LOC risk, charcoal won’t work / not available, <1hr
since ingestion; pill won’t fit into holes of NG tube eg. In remote areas
CI: seizures, decr LOC, charcoal works, <1yr, corrosive / HC ingestion, rapid onset poisoning (eg. TCA),
active/prior V
Cons: interferes with charcoal administration, other therapeutic measures, 20mins delay; unreliable;
Negligble effect by 1hr (decr absorption by up to 30% if given within 1hr); risks > benefits; no advantage
over charcoal; prolonged vomiting (10-20%), diarrhoea (20-30%), lethargy (10%), pul aspiration, physical
inj from vomiting
Gastric lavage:
Indication: as above; also in non-elemental mercury, arsenic, chloroquine, some HC’s
Technique: lie on side, 20deg head down  large bore NGT  200ml (10ml/kg) warm water  drain  rpt
until clear effluent  maybe put activated charcoal down at end
CI: unprotected airway; small children; corrosive ingestion; oesophageal perf; pills that won’t fit into NGT
Cons: unreliable; negligble by 1hr (25% if at 30mins, 10% if at 60mins); no advantage over charcoal;
aspiration; hypoxia, laryngospasm; mechanical inj; water intoxication; hypothermia; perf
Pros: immediately recovers gastric contents
Single dose activated charcoal:;
Doesn’t work in: alcohols, metals, acids / alkalis, OP’s, pesticides / petroleum products,
ionic compounds (Li, arsenic, cyanide)
Pathophysiology: adsorbs drug onto surface; 45% decr absorption if given after 30mins, 40% at
60mins, 15% at 120mins
Dose: 25-50g in children (0.5-1g/kg if <1yr), 50-100g in adults PO / NG; ideally 10:1
CI: seizures, decr LOC; agent not bound; corrosive; bowel obstruction / perf
Pros: more effective than above 2 if responsive substance; may absorb up to 50% product
Cons: no good studies have shown benefit from this; vomiting (30%; unrelated to administration rate;
prevented with antiemetics); aspiration (0.5%; potentially fatal); impaired absorption of antidotes; corneal
Abrasion; decr OCP effectiveness; some preps contain propylene glycol; hyperNa (5%); hyperMg (3%);
obstruction; messy
Whole bowel irrigation:
Indication: life threatening ingestion of SR/EC preps or Agents that don’t bind charcoal
+ good outcome not expected with supportive care and antidotes
+ patient presented before severe toxicity
eg. Fe >60mg/kg, SR Li, lead, symptomatic arsenic
SR KCl >2.5mmol/kg, Life threatening SR verapamil / diltiazem
Body packers, pharmacobezoars
Severe ingestion of other charcoal resistant substance
Pathophysiology: PEG acts as osmotic agent and cleanses bowel rapidly; little net ion absorption / loss
Technique: give charcoal  patient seated or head of bed elevated to at least 45deg  PEG via NG at
2L/hr (25ml/kg/hr infant, 0.5L/hr <6yrs, 1L/hr 6-12yrs)  maxalon to control V, if sustained,
decr inf rate by 50% for 30mins  continue until effluent clear (may take up to 6hrs; stop if abdo
distension / loss of bowel sounds)
CI: uncooperative patient; can’t place NG; uncontrolled V; possibilty of decr LOC / seizure; ileus /
obstruction; intubated (relative CI); GI haem; caution in infants and elderly; preceding diarrhoea
Complications: N+V, NAGMA, aspiration, abdo cramps, rectal irritation
Pros: no significant change in electrolytes / osm reported
Cathartics:
Pros: speed up GI transit
Cons: osmotic effects may incr absorption; dehydration and LFT abnormalities in paeds
Lipid partitioning therapy:
Indication: LA’s, propanolol, TCA, verapamil; life-threatening OD of lipid-soluble drug where conventional trt
failed
Dose: 1ml/kg of 20% intralipid over 1min (max 100ml)  rpt if needed  10ml/hr infusion
Alternative: 400ml over 20mins  0.25ml/kg until stable
Pathophysiology: acts as fluid compartment into which drug diffuses; good for high VOD, highly lipid soluble
drugs
CI: egg, soya, peanut allergy
SE: shivers, N+V, fat overload syndrome (BM dep, hepatosplenomegaly, seizures), allergy, pul HTN, ALI
6. Enhanced
elimination
Others: wash skin
Sorbitol: acts as osmotic laxative; can be given with charcoal but no evidence of improved efficacy; CI in preg,
absent bowel sounds, obstruction / perf, ingestion of corrosive substance, vol depletion, significant
electrolyte imbalance, <1yr, elderly; SE = incr absorption of some substances, decr BP, aspiration, N+V+D
Indicated if: severe toxicity + poor outcome likely with supportive care / antidotes
+ slow endogenous rates of elimination or impaired method of distribution (and clearance can be
increased by >30%)
+ suitable pharmacokinetic properties (small VOD)
MDAC:
Indication: substances that form bezoars, that slow GI fx, have entero-hepatic circn
Effective: carbamazepine coma (most common indication)
phenobarb coma (1st line)
theophylline, phenytoin, aspirin, dapsone metHb, quinine, mushrooms
Probably effective in: amitriptyline, dig, verapamil, sotalol
Pathophysiology: interrupts entero-hepatic circ (works if entero-hepatic circ + small VOD); GI dialysis (works
if small molecule, small VOD, low protein binding, long elimination HL, low endogenous clearance); may
enhance elimination of substances even after absorption complete (by GI dialysis)
Technique: 50g (1g/kg) PO  25g (0.5g/kg) Q2hrly (or 50g Q4hrly); check for bowel sounds
before each dose and stop if gone; rarely required beyond 6hrs
Endpoint: continue until improved condition / bloods
CI: decr LOC, seizures, bowel obstruction
Complications: V (30%); aspiration; constipation; bezoar formation  obstruction, perf; corneal abrasion
Urinary alkalinisation:
Indication: phenobarb coma (2nd line; do if toxic despite MDAC)
aspirin (do if symptomatic / mod severe, pH <7.1; if severe established toxicty, do haemodialysis)
methotrexate
Pathophysiology: drug must be filtered at glomerulus, small VOD, be weak acid, low pKa, mainly distributed
in ECF, low protein binding, excreted renally in unchanged form; drug is ionised in alkaline urine 
excreted
Technique: correct hypoK  1-2mmol/kg NaHCO3 IV bolus  10-100mmol NaHCO3 in 1L 5%
dex at 250ml/hr; can add 20mmol KCl to infusion to prevent hypoK; check HCO3 and K Q4hrly; aim
urine pH >7.5 and serum pH 7.5-7.55
Endpoint: continue until evidence toxicity is resolving
CI: fluid overload, hypoK, renal failure
Complications: alkaemia, hypoK, hypoCa, vol overload, pH shifts
Haemodialysis / filtration:
Indication: severe Li (>6mmol/L in acute, >2.5mmol/L in chronic)
severe aspirin, theophylline, alcohols, metformin lactic acidosis, life threatening K, severe
valproic acid, severe carbamazepine, phenobarb coma
Other: amphetamines, camphor, chloral hydrate, metals
Generally reserved for when other methods are failing and progressive end organ failure occuring, in ICU
setting
Doesn’t work for: Fe
Pathophysiology: must be small molecule, small VOD, rapid resditrubtiuon from tissues and plasma, slow
endogenous elimination, water soluble, low molecular weight, low protein binding, renal elimination, pKa
less than serum pH
Pros: corrects electrolyte abnormalities, can remove substances that don’t bind charcoal, removes
substances already absorbed
CI: CV instability, very small children, profound bleeding
Complications: fluid shifts, electrolyte imbalances, infection and bleeding at catheter site, intracranial haem
7. Antidotes
8. Disposition
NaHCO3 Use
Charcoal haemoperfusion: superior to haemodialysis if charcoal adsorbs; can also do Fuller’s earth
haemoperfusion in paraquat poisoning
Indication: theophylline, paraquat, paracetamol, aspirin, carbamazepine, quinine, amanita, phenobarb,
phenytoin
Pathophysiology: agent must be lipophilic, adsorbed by charcoal, low protein binding
Complications: requires systemic heparinisation; low plt, decr neuts, decr BP, blood loss, air embolic, hypoCa
Required in <2% poisonings
Admit SSU: ongoing cardiac monitoring not needed, adequate sedation achieved, clinical deterioration not
expected; 4hrs observation provides medical clearance in 75%
Pros: ready availability of appropriate staff, resources, training 24hrs; open plan environment for
observation; ethos geared towards assessment and disposition; prevents self harm; dedicated SW; psych;
monitors and telemtry; resus; duress alarms; nurse-pt ratio; tox concentrated in one area; security
Admit ICU: airway control, ventilation, prolonged / invasive haemodynamic monitoring / support,
haemodialysis
A, B, C, sedation, seizure control, Glu, fluids, nutrition, pressure areas, thromboembolism prophylaxis, bladder
care
Other: psych, CYFS, SW, CADS
Indication and dose:
Hydrofluoric acid toxicity
Correction of severe metabolic acidosis: 0.5mmol/kg for each desired incr in HCO3; endpoint HCO3 >8,
clinical improvement of shock / dysrhythmias; incr pH to no greater than 7.2
HCO3 <3, pH <7.2, severe hyperchloraemic acidaemia
Cyanide poisoning
Isoniazid OD
Ethylene glycol, methanol, other toxic alcohols
Cardiotoxicity (arrest, VF/VT, hypoT) 2Y to fast Na channel blockade: repeated doses of 2mmol/kg IV until
stability achieved  100mmol diluted in 1L N saline at 100-250ml/hr; aim pH 7.5-7.55; stop when no longer
cardiotoxic; will likely need K supplementation
TCA
Type 1a and 1c antiarrhythmics: flecainide, quinidine, quinine
Chloroquine / hydroxychloroquine
Propanolol
Urinary alkalinisation in OD  enhanced elimination: 1-2mmol/kg IV bolus  100mmol in 1L 5% dex at
250ml/hr; add 20mmol KCl to infusion to maintain normal K; aim urinary pH >7.5
Salicylate – moderate severity not requiring haemodialysis (pH <7.1)
Phenobarbitone – if continued toxicity despite MDAC
Methotrexate
Rhabo
Prevention of drug redistribution to CNS – incr unionized amount of drug
Salicylate
SE: extravasation, gastric distension, hyperNa, hyperosmolality, vol overload, pul oedema, alkalosis (pH >7.6
bad for CV function), L shift of O2-Hb diss curve (impaired O2 unloading), hypoK, hypoCa (usually not clinically
significant); incr lactate production; resp acidosis (ventilation must account for incr CO2 production)
CI: hypoK, hypoCa, alkalosis, acute pul oedema, renal failure, severe hyperNa
Notes from: Tox book, Dunn, TinTIn, Cameron