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TOXICOLOGY
WORKSHOP
GENERAL APPROACH AND SPECIFIC AGENTS
MASTERS FIJI
30/10/15
General approach
RRSI DEAD
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Resus
Risk assessment (medical and psych)
Supportive cares/monitoring
Investigations
Decontamination
 charcoal & whole bowel irrigation
Enhanced elimination
 MDAC, urinary alkalinsation, dialysis
Antidotes
Disposition
Resuscitation

ABC

Detect and correct
 Hypoglycaemia
 Seizures
 Hypo/hyperthermia
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Emergency antidote
Risk assessment
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Medical and psychiatric
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Who?
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What?
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Time since ingestion
Where?
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Drug and dose; always ask about coingestants!!!
When?
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Patient characteristics – age/gender/PMHx/psych Hx
Likelihood of being found
Why?
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Precipitants – financial/social/marital etc

Ongoing suicidality/plans
Supportive cares/monitoring
 Full
non-invasive – monitoring for
development/worsening of toxicity
 Visual
– may attempt to leave; plan for
detainment?
Investigations


ECG
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Na channel blocker tox
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Prolonged QTc

tachycardia
CBG/BSL
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SPIESVQ – salicylates, propranolol, insulin, ethanol, sulfonylureas, valproate, quinine
BhCG

Precipitant

Child at risk
(paracetamol levels)

NB NAC 100% effective at preventing hepatotoxicity if administered within 8 hours
of overdose
Decontamination - 1
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Charcoal

1g/kg to max 50g

Indications for use
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Within 1 hr of toxic ingestion
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Benefits outweigh risks (eg aspiration)
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Toxin binds to charcoal
Agents that don’t bind

Hydrocarbons/alcohols – ethanol/methanol

Metals – Li/Fe/Pb

Corrosives – acids/alkalis
Decontamination - 2

Whole bowel irrigation

PEG via NGT at 2L/hr

Indications

Benefits outweigh risk

Appropriate overdose

S – slow release calcium channel blockers
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L – lead
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I – iron
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P – potassium tablets or packers
Enhanced Elimination - 1

MDAC (multi dose activated charcoal)

1g/kg to max 50g initially then q2h (up to 6hrs ie max 4 doses)

Interrupts enterohepatic circ; acts as GIT dialysis

Amenable agents

Quite Possibly Can’t Drink That Stuff

Q - quinine
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P – phenobarbitone
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C – carbamazepine
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D – dapsone
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T – theophylline

S – salicylates
Enhanced Elimination - 2

Urinary alkalinsation

1-2mmol/kg NaHCO3 bolus then 100mmol NaHCO3 in 1L 5% dextrose @
250ml/hr

Traps acidic drug in renal tubules and increases excretion in urine

Amenable drugs

Salicylates

Phenobarbitone (NB MDAC is superior)
Enhanced Elimination - 3

Hemodialysis

Consider in the following poisonings:

Lithium – chronic with renal impairment

Metformin induced lactic acidosis
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Potassium

Valproate

Alcohols
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Theophylline (treatment of choice in severe OD)
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Salicylates (treatment of choice in severe OD)

Carbamazepine

Barbiturates
Toxidromes - overview
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Hypermetabolic
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Serotonin syndrome
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Neuroleptic malignant syndrome
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Anticholinergic syndrome
Other
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Opiate

Sympathomimetics

Cholinergic
Toxidromes - 1
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Hypermetabolic (inc HR, BP, RR and temp)
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
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Serotonin syndrome
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Sweaty, increased tone/hyperreflexic/clonus, agitated -> coma

Intro/inc serotonergic drug, inadequate washout, deliberate OD

Eg fentanyl, TCAs, lithium, SSRIs (sertraline, fluoxetine)
Neuroleptic malignant syndrome

Sweaty, lead-pipe rigidity, bradyreflexia, mutism/staring

RFs – high dose, recent inc dose, >2 neuroleptic agents, dehydration

Eg haloperidol
Anticholinergic syndrome

Red, hot and dry; normal tone/reflexes; agitated delirium

Eg antihistamines, TCAs
Toxidromes - 2

Other


Opiate

Miosis, respiratory depression, reduced level of consciousness

Naloxone 100mcg q30-60 sec until adequate spont resp
Sympathomimetics


CNS – agitation, euphoria, paranoid psychosis; CVS – inc HR/BP, ACS, APO,
other – rhabdo, sweating, tremor
Cholinergic

CNS – agitation, coma, confusion, seizures; NM – fasciculation, muscle
weakness; M receptors – DUMBBELS; N receptors – HTN, inc HR, sweating

Organophosphates
Specific agents

Tried to identify most high yield for exam

Commonly available

Major toxicity

Antidote available

Decontamination/enhanced elimination important
Toxic Alcohols – Ethylene Glycol
Toxicity Glycolic acid & oxylate -> 1mL/kg = toxic
Severe metabolic acidosis + calcium oxylate deposition (kidneys/myocardium/ muscles &
brain)
Rapid progression to symptoms to shock, coma, seizures and death – early renal failure
Management
DEA  Antidote = ETOH; Haemodialysis
Resus/Supportive
 Intubation/hyperventilation (severe acidosis)
IV benzo’s for seizures
 Avoid hypoglycemia
 Correct hypocalcemia – oxylate calcium crystals (ECG prolonged QT)
Toxic Alcohols - Methanol
Toxicity > 0.5mL/kg = toxic
Intoxication – then latent period (12-24hrs)
Dizziness/vertigo, dyspnoea, blurred vision – progressive obtundation –
coma & seizures
Management
DEA - Antidote = ETOH; Haemodialysis
Resus/Supportive
Intubation/hyperventilation (severe acidosis)
IV benzo’s for seizures
 Avoid hypoglycemia
Amphetamines
Toxicity  sympathomimetic effects
Lethal complications – severe hyperthermia; Cardiac (ACS, aortic dissection,
arrhythmias); CNS (ICH)
Management
DEA – None
Titrated benzo’s  Treat tachycardia/hypertension with Hydralazine/GTN (second line)
B-BLOCKERS CONTRAINDICATED
Resus/Supportive
Agitation with IV benzo’s – may need to I&V for control CNS agitation
Hyperthermia – active cooling
Monitor for hyponatremia
Monitor for Rhabdo/ renal failure
B-blockers (propanolol/sotalol)
Toxicity  other b-blockers have minimal toxicity
Propranolol – 1g = toxic
CVS effects – hypotension/bradycardia; 1st – 3rd degree block. Propranolol
– QRS prolongation & CNS depression
Sotalol – QT prolongation – risk torsades
Management
DEA – none (charcoal if NOT propranolol- CNS)
Antidote – NaHCO3 for propranolol
Resus/Supportive – usual
Propranolol – manage as TCA prompt intubation, ventilation and NAHCO3
for VT/VF
Manage Hypotension & bradycardia – Fluids, inotropes, pacing
Calcium channel blockers
(verapamil/diltiazem)
Toxicity – little as 2-3 x therapeutic dose (10 tabs = toxic)
CVS – hypotension/ heart block; Metabolic hyperglycemia/lactic
acidosis
Management
DEA
Decontamination – Charcoal & WBI;
Antidote = Calcium & HIET ( 25g Glucose; 1U/Kg bolus)
Resus/Supportive
Calcium – 20ml of 10% CaCl over 15mins – repeat x 3
Escalated approach – hypotension & bradycardia (atropine –upto
3mg)
Carbamazepine
Toxicity - 20-50mg/kg (mild-mod); > 50mg/kg
CNS/anticholinergic – agitation/coma; CVS – hypotension;QRS VF/VT
Management
DEA – activated charcoal; MDAC (if intubated); Hemodialysis
Resus/Supportive
Arrhythmias – sodium bicarbonate; graded response to hypotension
Seizures/agitaiton – IV benzo’s
Carbon monoxide
Toxicity(% CoHb) – Non-specific/mild headache, N&V – progress ot
CNS disturbance, confusion/coma & syncope; > 50% - cardiovascular
& respiratory collapse
Management
High flow O2
Hyperbaric oxygen if available (especially pregnant pt’s)
Resus/specific
As per usual
Corrosives
Toxicity – direct chemical injury to tissues – dependent on type;
concentration & amount
Alkaline agents = liquefactive corrosives
Acidic agents = coagulative necrosis
Management
DEA – none
Resus/Supportive
Airway – high risk dysphonia/dyspnoea/stridor – secure early
NO NGT until AFTER endoscopy
S&S correlate poorly with extent of gastrooesophageal injury
Steroids = no evidence
Evidence of perforation = early surgical intervention (erect CXR)
Digoxin
Toxicity
Acute  10mg (adult); > 4mg (child) – CVS collapse/dysrhythmias &
severe hyperkalemia
Chronic  non-specific – N&V/GIT; headache; visual & CVS
Management
DEA – Antidote – digoxin immune Fab – formula to measure amount
Resus/Supportive
Cardiac arrest – standard measures futile without Antidote – prolonged
resuscitation indicated if digoxin given
Beware of IV calcium for hyperkalemia (controversial)
Atropine for heart block
IV lignocaine 1mg/kg for ventricular dysrhythmias
Glyphosate
Toxicity directly related to concentration (herbicide)
Effects – GIT – N&V/oropharyngeal erosions; RESP – upper airway
obstruction/burns; aspiration pneumonitis; CVS – myocardial
depression (systemic acidosis)
Management
DEA – only hemodialysis (but rarely indicated – 4 severe met acidosis)
Resus/Supportive
Airway- intubate early if airway compromise
CVS – escalated approach
Hydrocarbons
Toxicity – ingested or inhaled – cause rapid CNS depression; seizures &
(rarely) cardiac dysrhythmias. Ingestion can be complicated by
aspiration = aspiration pneumonitis
Management
DEA – decontamination (clothes)
Resus/Supportive
VT/VF – intubate & hyperventilate; Correct hypoxia
Administer Metoprolol IV/ ?labetalol
Correct hypokalemia/hypomagnesemia
With-hold catecholamine inotropes if possible
Hydrofluoric acid
Toxicity – dermal/inhaled/ocular OR oral
Fluoride ions bind directly to ca/mg+ and interfere with potassium
channels  Ventricular dysrhythmias
n.g. can have severe dermal injury despite minimal signs
(delayed presentation)
Management
DEA – decontaminate skin/irrigate with water; CALCIUM
nb. Can administer calcium GLUCONATE via s/c OR IV arterial infusion
Resus/Specific
CARDIAC MONITORING – prolonged QT correlates to hypocalcemia
Iron
Toxicity – < 20mg/kg – Asymptomatic; 20- 60mg/kg – GI; Systemic >
60mg/kg; > 120mg/kg – potentially lethal
Local GI and systemic effects =Direct GI toxicity and direct cellular toxicity
systemically – CVS system & liver (CVS instability and metabolic
derangements)
Management
DEA – WBI (if awake and toxic dose)- XRAY;
Antidote – Desferroxamine (if shock; metabolic acidosis or altered mental
state
Resus/Supportive
Circulation – emphasize fluid replacement (3rd spacing/GI loss)
HCO3 = surrogate marker for lactate/systemic poisoning
monitor CBG
Seek & treat electrolyte abnormalities – fluid losses
Lithium
Toxicity – acute versus chronic
Acute – GI toxicity – N&V/abdo pain etc
Chronic – Neurotoxicity – particularly cerebellar effects
NOTE: acute or chronic impairment of renal function, dehydration or
sodium depletion impairs lithium excretion
Management
DEA – Elimination via dialysis (not usually required if normal RFT’s)
Resus/Supportive
CVS – fluid resuscitation; monitor fluids and electrolytes
NB. Significant obtundation or seizure activity is an indicator of severe
toxicity (chronic) carrying permanent neurological sequale
Metformin
Toxic effects  > 10g OR therapeutic dose with ARF
Alters cellular glucose metabolism– toxic component = lactate
Patient has non-specific features of toxicity – altered sensorium, N&V,
diarrhea, dyspnea, hypotension
Management
Haemodialysis – corrects acidosis & removes metformin
Supportive
 seek and treat hypoglycemia
 Often precipitated by infection/sepsis if on therapeutic dose
Organophosphates
Toxicity
Inhibit ACH-esterase inhibitors – symptoms due to Ach at nicotinic & muscarinic
receptors
Cholinergic – DUMBELS; Nicotinic – fasciculations, tremor, respiratory muscle
paralysis; tachycardia and hypotension
Management
DEA – decontamination: remove clothes; wash skin etc; elimination: Atropine &
Pralidoxime (re-activates Ache b4 ageing occurs
Resus/Supportive
Potential early life threats – COMA; Hypotension; seizures; Respiratory failure
Atropine – 1.2g – double dose every 5 mins (drying of secretions)
Electrolytes – monitor and replace; hypoglycemia – seek and treat
Organophosphate induced delayed neuropathy (OPIDN)
Paraquat
Toxicity – mouthful only required – severe GI corrosive injury; pulmonary
fibrosis and fulminating MOF & death
Management
DEA – administer food/soil on scene; In hospital give activated
charcoal 50g asap
Resus/Supportive
Do NOT administer supplemental O2 unless <90% and aim for sats no
greater than 91%
Paracetamol
Toxic effects  NAPQ = toxic metabolite (>150mg/kg OR 10g in adult)
Phase 1 (<24hrs) - Mild – N&V/none
Phase 2 (1-3 days) – RUQ pain & hepatotoxicity
Phase 3 (3-4 days) – fulminant hepatic failure – Coagulopathy/ jaundice/
encephalopathy
Management
Antidote =NAC – commence within 8 hrs
Supportive
 Anti-emetics; anaphylactoid reactions to NAC
Salicylates
Toxicity > 300mg/kg – severe intoxication; > 500mg/kg – lethal
Vomiting; tinnitus & hyperventilation – resp alkalosis & metabolic
acidosis. Severe toxicity – seizures/coma
Management
DEA – Decontamination upto 8hrs post; Urinary alkalinisation &
haemodialysis (rarely required if charcoal/urine alk. are used)
Resus/Supportive
I&V (for coma/respiratory insufficiency) – maintain hyperventilation
Fluid – ensure replacement of losses
Closely monitor glucose & potassium
Sulfonylureas
Toxicity- unpredictable metabolism (particularly in overdose);
therapeutic dose if ARF
results in hyper-insulinaemic state
Management
Decontamination – if given within 1hr & normal mental state
Antidote – Octreotide
Supportive
 may have prolonged effect for DAYS – needs v.close monitoring
Theophylline
Toxicity – both acute overdose & chronic toxicity can be lifethreatening; >10mg/kg – potential toxicity; > 50mg/kg – life threatening
Effects – CVS – Tachyarrhythmias/Hypotension; Seizures; Metabolic –
hypokalemia; hyperglycemia and metabolic acidosis
Management
DEA – Decontamination – charcoal; Hemodialysis – life-saving
Resus/Supportive
Seizures- IV benzos
Tachyarrhythmias – SVT – control with b-blockade
Hypotension – IV fluid bolus usually enough
Seek & treat electrolyte abnormalities
Tricyclic antidepressants
Toxicity – sodium channel blockade > 10mg/kg = potential life threat
Onset of toxicity within 2 hrs
CNS – sedation/seizures/coma –needs early intubation
CVS – ventricular dysrhythmias; Anthicholinergic features
Management
DEA – Charcoal if intubated (toxic dose); Antidote – NaHCO3
Resus/Supportive
Immediate NaHCO3 – repeat doses & infusion (QRS <100msec)
Early intubation - & hyperventilation – pH 7.55
IV benzos for seizures
Monitor electrolytes; Catheter for fluid balance/urinary retention
Warfarin
Toxicity – BLEEDING.
Management
DEA – activated charcoal if within 1hr; Antidote – Vit K& FFP
Resus/Supportive
Dependent on bleeding & indication for warfarin
n.b. can be managed on outpt basis if asymptomatic & INR < 9.0
Sea Snakes 
Toxicity – post-synaptic neurotoxins & myotoxins
Rarely aggressive and most bites occur when handling to remove from
fish nets
Management
DEA – pressure immobilization; sea snake antivenom OR tiger snake
Resus/Supportive
Unlikely to be needed as apparently their mouths are so small they
can’t bite beyond webbing between fingers 