Transcript Rural_Matters_2016_

RURAL MATTERS 2016:
POST PRANDIAL PRESENTATION
HARAN SATHIANATHAN
25TH NOVEMBER 2016
RURAL MATTERS 2016:
THE POISONED PATIENT
HARAN SATHIANATHAN
25TH NOVEMBER 2016
THE PLAN …
• Definitions
• Supportive Care
• Context / Background
• [Toxidromes]
• Principles of management
• Stabilisation / Resuscitation
• Reduce Absorption
• Enhance Elimination
• [Antidotes]
• [Case Study]
• Resources
DEFINITIONS
“All things are poison and nothing is without poison;
only the dose makes a thing not a poison.”
-- Paracelsus
Image credit - Touchstone Pictures
DEFINITIONS
• POISON = a substance that is harmful if ingested, inhaled, injected, or absorbed through the skin
• TOXIN = a poison that is produced by living organisms
• VENOM = a toxin that is injected by living organisms
• TOXICOLOGY = Study of Poisons
• TOXINOLOGY = Study of Toxins (Usually venoms)
[Credit Unknown]
DEFINITIONS
• POISON = a harmful substance
• TOXIN = a poison that is produced by living organisms
• VENOM = a toxin that is injected by living organisms
• TOXICOLOGY = Study of Poisons
• TOXINOLOGY = Study of Toxins (Usually venoms)
[Credit Unknown]
BACKGROUND
• Poisoning / overdose / intoxication at LRH (01-06/2016):
• LRH ED Presentations = 153 (1% of total presentations)
•
• LRH ICU Admissions = 21
• 13.7% of ED presentations
• 8% of non-elective ICU admissions
BACKGROUND
• Poisoning / overdose / intoxication at LRH (01-06/2016):
• LRH ED Presentations = 153 (1% of total presentations)
• 254, if you include alcohol intoxication
(1.5% of total presentations)
• LRH ICU Admissions = 21
• 13.7% of ED presentations
• 8% of non-elective ICU admissions
[Please don’t tell Sasha!]
BACKGROUND
• Poisoning / overdose / intoxication in Victoria (01-12/2015):
• Victorian Poisons Information Centre (a.k.a. Poisons Hotline) :
• VPIC = 39230 calls (i.e., 107/day!)
• VPIC toxicologist or registrar = 496 calls
• [Calls from medical staff = 3976 (13%)]
BACKGROUND
• Poisoning / overdose / intoxication in U.K.:
• Poisoning accounts for 10% of all acute medical admissions
• In-hospital mortality = 1%
• Total amount continues to increase @ 4-5%/year
• Two-thirds of deaths do not reach hospital
• 11.2% of survivors represent within 12 months
BACKGROUND
• Accidental poisoning:
• Peak incidence = 2 years
• Boys > Girls
• 80% of poisonings occur in own home
• 20% analgesics
• 40% other medications
• 40% other chemicals
• Most deaths due to carbon monoxide poisoning
BACKGROUND
• Deliberate self-poisoning:
• Attempted poisoning: Women > Men (But gap is reducing)
• Successful poisoning: Men > Women (But gap is reducing)
• 1st (or 2nd) most common cause of suicide in women (40% in age > 15)
• 4th (of 3rd) most common cause of suicide in men (after gassing, hanging, and firearms)
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
BACKGROUND
• Iatrogenic poisoning:
• Medication errors occur in 5% of all admissions
[Credit Unknown]
BACKGROUND
• Homicidal poisoning:
• Only on TV!
Image credit - Universal Television
BACKGROUND
• Top Ten (VPIC)
• Paracetamol
2113
• Benzodiazepines
1231
• Ibuprofen
1113
• SSRI antidepressants
889
• Topical antiseptics, hand-sanitisers, etc.
668
• Bleach (hypochlorite based)
640
• Quetiapine
627
• Paracetamol/narcotic combination analgesic
587
• Silica gel
482
• Toilet bowl cleaner/deodoriser: cage/disc type
464
PRESENTATION
• Wide range of symptoms. E.g.:
• Unconsciousness, nausea, vomiting, burning pain in the mouth or throat, headache, blurred vision, seizures, difficulty
• Poisoning may be obvious from the chronology
• Some poisons have typical toxidromes
• Some poisons have a rapid effect
breathing, respiratory arrest, cardiac arrest, …
PRESENTATION
• Wide range of symptoms. E.g.:
• Unconsciousness, nausea, vomiting, burning pain in the mouth or throat, headache, blurred vision, seizures, difficulty
• Poisoning may be obvious from the chronology (or not)
• Some poisons have typical toxidromes
• Some poisons have a rapid effect
breathing, respiratory arrest, cardiac arrest, …
PRESENTATION
• Wide range of symptoms. E.g.:
• Unconsciousness, nausea, vomiting, burning pain in the mouth or throat, headache, blurred vision, seizures, difficulty
• Poisoning may be obvious from the chronology (or not)
• Some poisons have typical toxidromes (others don’t)
• Some poisons have a rapid effect
breathing, respiratory arrest, cardiac arrest, …
PRESENTATION
• Wide range of symptoms. E.g.:
• Unconsciousness, nausea, vomiting, burning pain in the mouth or throat, headache, blurred vision, seizures, difficulty
• Poisoning may be obvious from the chronology (or not)
• Some poisons have typical toxidromes (others don’t)
• Some poisons have a rapid effect (others delayed)
breathing, respiratory arrest, cardiac arrest, …
PRESENTATION
• Poor evidence base
• Hard to undertake randomised prospective trials
• “Unethical”
• Mainly animal studies (rats/rabbits), or human case reports
[Credit Unknown]
CASE
(PART 1)
CASE
(PART 1)
• 33 y/o female BIBA with decreased conscious state
• History from AV:
• Had argument with boss (~1300),
and then went home
• Husband found her poorly rousable (~1630),
and called AV
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
PRINCIPLES OF MANAGEMENT
1.
Stabilisation [i.e., Resuscitation]
2.
Reduce Absorption
3.
Enhance Elimination
4.
Supportive Care
• [Toxidromes]
• [Antidotes]
[Credit Unknown]
STABILISATION
STABILISATION
DR
SCAB
STABILISATION
D
R
S
C
A
B
STABILISATION
Danger
R
S
C
A
B
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
• Prevent poisoning of rescuer
• Prevent further exposure/injury to patient
STABILISATION
Danger
R
S
C
A
B
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
• Prevent poisoning of rescuer
• The poison can be transferred to the rescuer
• (e.g., by contact or inhalation in
organophosphate poisoning)
• If more than one person affected, consider
environmental contamination
• (e.g., carbon monoxide poisoning)
STABILISATION
Danger
R
S
C
A
B
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
• Prevent poisoning of rescuer
• Ensure adequate personal protective
equipment (PPE) during
decontamination and resuscitation
• If PPE not available, rescue may not be
possible
STABILISATION
Danger
R
S
C
A
B
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
• Prevent poisoning of rescuer
• Do NOT put yourself at risk
• Avoid inhaling fumes
• Avoid direct contact
STABILISATION
Danger
R
S
C
A
B
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
• Prevent further exposure/injury to patient
• I.e., reduce absorption (see later)
STABILISATION
D
Response
S
C
A
B
• Check for responsiveness
[Credit Unknown]
STABILISATION
D
Response
S
C
A
B
• According to ARC:
• “If unresponsive, commence CPR”
[Credit Unknown]
STABILISATION
D
Response
S
C
A
B
• May be drug related, or
• May have pathological cause
[Credit Unknown]
STABILISATION
D
R
Send for help
C
A
B
• If out of hospital, call 000
• If in hospital, call MET / or Code Blue
• Also, consider Victorian Poisons
Information Centre on 13 11 26
[Credit Unknown]
STABILISATION
D
R
S
Circulation
A
B
• Is circulation adequate?
[Credit Unknown]
STABILISATION
D
R
S
Circulation
A
B
• Certain drugs have cardiotoxic effects:
• Hypotension (most common)
(e.g., calcium channel blocker)
• Hypertension
(e.g., clonidine)
• Arrhythmias
(e.g., tricyclic antidepressants)
[Credit Unknown]
STABILISATION
D
R
S
Circulation
A
B
• Consider:
• CPR!
• Vascular access
• Cardiac monitoring
• Chemical supports
(e.g., inotropes)
• Mechanical supports
(e.g., extracorporeal support)
[Credit Unknown]
STABILISATION
D
R
S
C
Airway (+ c-spine)
B
[Credit Unknown]
• Is airway patent?
STABILISATION
D
R
S
C
Airway (+ c-spine)
B
[Credit Unknown]
• Depressed conscious state
• Airway burns
• Foreign body
• [C-spine]
STABILISATION
D
R
S
C
Airway (+ c-spine)
B
[Credit Unknown]
• Depressed conscious state:
• e.g., benzodiazepine overdose
• Position the patient or establish a definitive
airway
STABILISATION
D
R
S
C
Airway (+ c-spine)
B
[Credit Unknown]
• Airway burns:
• e.g., caustic substance aspiration
• Establish definitive airway
• May be time critical
STABILISATION
D
R
S
C
Airway (+ c-spine)
B
[Credit Unknown]
• Foreign body obstruction:
• e.g., vomitus, dentures
• Establish definitive airway
• Be careful not to convert ‘partial’ to
‘complete’ obstruction
STABILISATION
D
R
S
C
A
Breathing
• Is breathing adequate?
[Credit Unknown]
STABILISATION
D
R
S
C
A
Breathing
• I.e., Adequacy of oxygenating and
ventilation
• Causes:
• Central depression
(e.g., opiate or benzo overdose)
• Inhaled toxin
[Credit Unknown]
• Aspiration
STABILISATION
D
R
S
C
A
Breathing
• I.e., Adequacy of oxygenating and
ventilation
• Management:
• If hypoxic, oxygenate
• If hypercapnic, ventilate
[Credit Unknown]
STABILISATION
• Concurrent History / Examination / Management
• [Nb: Only once patient is stable]
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
STABILISATION
• Concurrent History / Examination / Management
• Exclude other organic causes
• History is often not possible (e.g., the unconscious or uncooperative patient)
• Consider collateral history
• ‘Top-to-toe’ examination
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
STABILISATION
• Concurrent History / Examination / Management
• Investigations are many (may by streamlined if obvious toxidrome):
• arterial blood gas (Inc. BSL & anion gap)
• electrolytes/urea/creatinine, (Inc. osmolar gap)
• liver function tests
• coagulation profile,
• full blood count
• ECG
• CXR
• CT Brain (a.k.a. “CAT” SCAN)
• urinalysis
[Credit Unknown]
STABILISATION
• Concurrent History / Examination / Management
• Availability of onsite drug levels for:
• Paracetamol
Salicylate
• Carboxyhaemoglobin
Methaemoglobin
• Ethanol
Iron
• Lithium
Theophylline
• Digoxin
Paraquat
• Valproate
[Credit Unknown]
CASE
(PART 2)
CASE
(PART 2)
• Pre-hospital:
• Ambulance Victoria (1630):
• D – Nil obvious exposure/contamination risk
• R – GCS 9-11 at scene
• S – LRH ED pre-warned
• C – SBP 112/76, P 98, PIVC x2, NS x1L
• A – Unsupported
• B – RR 8, SaO2 93% (RA) -> 90% (NRB)
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
CASE
(PART 2)
• Pre-hospital:
• Emergency Department (1730):
• D – Nil apparent
• R – GCS 8 (E4V1M3) on arrival -> Decision made to intubate
• S – ICU pre-warned
• C – SBP 113/62, P109, (T33, BSL 6.2)
• A – Unsupported
• B – RR 8, SaO2 90% (NRB)
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
CASE
(PART 2)
• ICU R/V:
• A:
• 7.5mm ETT @ 22cm
• 14F NGT inserted
• B:
• SIMV
• AE L=R
• SaO2 100% on FiO2 50%
• Nil sputum on suctioning
• [Nil ‘vomitus on cords’]
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
CASE
(PART 2)
• ICU R/V:
• C:
• P 120
• MAP 60 (Aramine started. CVC/Artline pending)
• Peripherally cool
• D:
• GCS 3/15 (Propofol @ 50mg/hr)
• Pupils equal, reactive, and dilated (5)
• No asymmetry in UL or LL
• I.e., symmetrical tone and reflexes
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
CASE
(PART 2)
• ICU R/V:
• E:
• Nil external signs of trauma/rash/etc.
• Nil track marks
• Afebrile (35.5)
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
CASE
(PART 2)
• Collateral history:
• PMHx:
• Major Depression (Inc. previous overdose attempts)
• Medications:
• Escitalopram
• Lorazepam
• Mersyndol Forte (PRN - 2-3 times/week)
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
CASE
(PART 2)
• DDx:
• Likely drug ingestion
• However unwitnessed, so need to exclude other
pathologies:
• Head trauma
• CVA (or other central cause)
• Dyselectrolytaemia / Hypoglycaemia
• Sepsis (Both CNS & systemic)
• Metabolic (e.g., hepatic/uraemia encephalopathy)
• Post-ictal
• Etc.
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
CASE
(PART 2)
• Ix:
• HCG / ABG / ECG / CXR / CTB
NAD
• BSL / FBC / UEC / LFT / Coags
NAD
• Procalcitonin –
NAD
• Ammonia –
?
Image credit - NBC Universal Television (2004-2007) and Universal Media Studios (UMS) (2007-)
CASE
(PART 2)
• Ix:
• Drug screen:
• Paracetamol
2064 micromol/L (> 1000)
312 mg/L (> 150)
• Methamphetamine
neg
• Methadone
neg
• Ethanol
9.3 mmol/L
• Amphetamine
neg
• Salicylates
neg
• Barbiturates
neg
• Cannabinoids
neg
• Benzodiazepines
pos
• Cocaine
neg
• Tricyclics
neg
• Opiates
pos
CASE
(PART 2)
• Ix:
• Drug screen:
• Paracetamol
2064 micromol/L (> 1000)
312 mg/L (> 150)
• Methamphetamine
neg
• Methadone
neg
• Ethanol
9.3 mmol/L
• Amphetamine
neg
• Salicylates
neg
• Barbiturates
neg
• Cannabinoids
neg
• Benzodiazepines
pos
• Cocaine
neg
• Tricyclics
neg
• Opiates
pos
CASE
(PART 2)
• Summary:
• Likely ingestion of own medications:
• Mersyndol Forte (paracetamol & opiate positive)
• Escitalopram (suspected)
• Lorazepam (benzo positive)
• [Other obvious pathologies excluded]
SUPPORTIVE CARE
SUPPORTIVE CARE
• Time necessary is dependent on:
• The drug’s pharmacokinetics
• [I.e., med school stuff, like absorption, distribution, metabolism, excretion, T1/2, etc.]
• The patient’s organ function
• [E.g., renal clearance or hepatic metabolism or even presence of red blood cells]
• Ability to reduce absorption
• [Next]
• Ability to enhance elimination
• [Next Next]
[Credit Unknown]
REDUCED ABSORPTION
(A.K.A. DECONTAMINATION)
REDUCED ABSORPTION
(A.K.A. DECONTAMINATION)
• Do NOT put yourself at risk:
• Avoid inhaling fumes
• Avoid contact contamination
REDUCED ABSORPTION
• Separate the victim from the poison
• Inhalation:
• Immediately get the person to fresh air, or ventilate the room (open doors & windows)
• If available, provide oxygen (highest flow possible)
REDUCED ABSORPTION
• Separate the victim from the poison
• Corneal exposure:
• Remove contacts
• Irrigate the eye with running saline or cold water for 15min
REDUCED ABSORPTION
• Separate the victim from the poison
• Skin contact
• Remove contaminated clothing
• Irrigate the skin with running saline or cold water for 15min
REDUCED ABSORPTION
• Separate the victim from the poison
• Ingestion:
• Activated Charcoal
• Whole Bowel Irrigation
• Gastric Lavage
• Induce emesis
• Cathartics
REDUCED ABSORPTION
• Separate the victim from the poison
• Ingestion:
• Activated Charcoal:
• Should NOT be administered routinely
• [NO evidence that it improves outcome (if used indiscriminately)]
• Single dose activated charcoal only if:
•
potentially toxic amount of a poison, AND
•
within an hour of ingestion, AND
•
airway is secure
• Charcoal is NOT effective if:
•
ingested substance is an elemental metal (e.g., iron supplement)
•
ingested substance is a strong acid or base (e.g., solvents)
REDUCED ABSORPTION
• Separate the victim from the poison
• Ingestion:
• Whole Bowel Irrigation:
• Should NOT be administered routinely
• Considered if:
•
MORE than two hours post ingestion, AND
•
Potentially toxic ingestions of :
•
Sustained-release or enteric-coated drugs (e.g., “OxyContin SR”)
•
Metals (e.g., iron, lead, lithium)
•
Ingested packets of illicit drugs (I.e., “Body packers”)
REDUCED ABSORPTION
• Separate the victim from the poison
• Ingestion:
• Gastric Lavage:
• No ‘strong’ evidence showing either benefit or harm
• Recommended up to an hour post ingestion
• “Should not be performed routinely”
[Credit Unknown]
REDUCED ABSORPTION
• Separate the victim from the poison
• Ingestion:
• Gastric Lavage:
• No ‘strong’ evidence showing either benefit or harm
• Recommended up to an hour post ingestion
• “Should not be performed routinely”
• NO ROLE for Gastric Lavage
•
Aspiration risk
•
May increase absorption
[Credit Unknown]
REDUCED ABSORPTION
• Separate the victim from the poison
• Ingestion:
• Induce emesis:
• e.g., syrup of ipecacuanha
• NO ROLE for inducing emesis
• Reduces the effectiveness of activated charcoal, oral antidotes, and
whole bowel irrigation
• Aspiration risk
• Forces poison beyond pylorus, and thus can increase absorption
• Certain specific contraindications (e.g., corrosives)
REDUCED ABSORPTION
• Separate the victim from the poison
• Ingestion:
• Cathartics:
• “The administration of a cathartic alone has no role”
REDUCED ABSORPTION
• Separate the victim from the poison
• Ingestion (Summary):
• Activated Charcoal – selective (i.e., not routine)
• Whole Bowel Irrigation – selective (i.e., not routine)
• Gastric Lavage – No
• Induce emesis – No
• Cathartics – No
ENHANCED ELIMINATION
• Elimination can be enhanced by:
• Urinary alkalinisation (urine pH > 7)
• Multi-dose activated charcoal
• Extracorporeal techniques
ENHANCED ELIMINATION
• Elimination can be enhanced by:
• Urinary alkalinisation (urine pH > 7)
• Hasten the clearance of acids
• E.g., salicylates
ENHANCED ELIMINATION
• Elimination can be enhanced by:
• Multi-dose activated charcoal
• Hasten clearance of drugs with enterohepatic circulation
• E.g., carbamazepine, phenobarbitone, digoxin
ENHANCED ELIMINATION
• Elimination can be enhanced by:
• Extracorporeal techniques
• Haemodialysis
• Useful in salicylates, lithium, methanol
• Not effective if high volume of distribution, or highly protein bound
• Haemoperfusion
• Useful in theophylline, phenytoin, carbamazepine
• Not effective if high volume of distribution
• Plasma exchange (theoretic benefit only)
CASE
(PART 3)
CASE
(PART 3)
• Potential Ingestants:
• Mersyndol Forte
• Escitalopram
• Lorazepam
• What is Mersyndol?:
Tablets
‘Daytime’
‘Forte’
Paracetamol (mg)
450
500
450
Codeine Phosphate (mg)
9.75
9.6
30
5
-
5
Doxylamine Succinate (mg)
CASE
(PART 3)
• Potential Ingestants:
• Concerns:
• Paracetamol
• Analgesic. “Liver drug”
Liver metabolised (Multiple pathways)
• Codeine phosphate
• Opiate. Liver metabolised (CYP2D6, CYP3A4,
UDP-glucuronosyltransferase).
• Doxylamine succinate
• Antihistaminic & Antimuscarinic
Liver metabolised (N-demethylation + others)
• Escitalopram
• SSRI. Liver metabolised (CYP2D6, CYP3A4,
N-demethylation).
• Lorazepam
• Benzodiazepine.
Liver metabolised (conjugation)
CASE
(PART 3)
• I.e.:
• Potential liver injury (paracetamol)
• Multiple liver metabolised drugs (ALL!)
• Decreased gut motility (Codeine & Doxylamine)
• Therefore:
• Prolonged absorption
• Prolonged metabolism
• [Prolonged ICU stay]
[Credit Unknown]
TOXIDROMES
TOXIDROMES
• A toxidrome, or a “toxic syndrome”, is a “constellation of symptoms and signs characteristic of
poisoning from a given class of drug”
• May help in rapid diagnosis and treatment
• Useful when serum drug levels not possible (or not possible in a timely manner)
• Streamline management
Image credit - Walt Disney Pictures
TOXIDROMES
• Not all toxidrome features will be present
• Polypharmacy OD
• E.g., in a patient with sympathomimetic poisoning, who is normally on beta blockers, tachycardia may not be
present
• Atypical drugs
• E.g., unlike other opiates, meperidine does not cause miosis
TOXIDROMES
• Common toxidromes include:
• Anticholinergic syndrome (e.g., doxylamine)
• Cholinergic syndrome
• Narcosis (e.g., codeine)
• Sedative – hypnotic (e.g., lorazepam)
• Hyperthermic syndromes:
• sympathomimetic syndrome
• serotonin syndrome (e.g., Escitalopram)
• neuroleptic malignant syndrome
• [and anticholinergic syndrome]
• [And many many more]
Image credit - Walt Disney Pictures
TOXIDROMES
• Anticholinergic syndrome (e.g., amanita muscarina)
• Cause:
antagonism of muscarinic receptors
• Result:
delirium
coma
fever
tachycardia
urinary retention
dry eyes
agitation
gastrointestinal stasis
mydriasis
skin flushing
dry mouth
dry skin
Image credit - Walt Disney Pictures
TOXIDROMES
• Cholinergic syndrome (e.g., sarin)
• Cause:
activation of muscarinic receptors (essentially causing the opposite)
• Result:
increased secretion (e.g., salivary, tears & sweat)
bradycardia
hypotension
bronchoconstriction
miosis
seizures
flaccid paralysis
incontinence (both urinary & faecal) increased gastrointestinal motility
TOXIDROMES
• Narcosis (e.g., heroine)
• Cause:
activation of opioid receptors
• Result:
miosis
central nervous system (CNS) depression
respiratory depression
decreased gastrointestinal motility
[Credit Unknown]
TOXIDROMES
• Sedative – hypnotic (e.g., Xanax)
• Cause:
activation of GABA receptors
• Result:
sedation
normal pupils
decreased respirations
TOXIDROMES
• Hyperthermic syndromes
• Sympathomimetic stimulation (e.g., cocaine)
• Cause:
Sympathetic stimulation
• Result:
Hyperthermia
Agitation
Seizures
Coma
Tachycardia
Hypertension
Diaphoresis
[Credit Unknown]
TOXIDROMES
• Hyperthermic syndromes
• Neuroleptic malignant syndrome (e.g., Maxolon)
• Cause:
Relative deficiency of dopamine
• Result:
Hyperthermia
Hyperreflexia
Hypertonia
Altered mental state
[Credit Unknown]
TOXIDROMES
• Hyperthermic syndromes
• Serotonin syndrome (e.g., Zoloft)
• Cause:
Relative excess of serotonin
• Result:
Hyperthermia
Hyperreflexia
Hypertonia
Clonus
[Credit Unknown]
TOXIDROMES
• Anticholinergic syndrome results from antagonism of muscarinic receptors:
• delirium, agitation, coma, gastrointestinal stasis, fever, mydriasis, tachycardia, skin flushing,
urinary retention, dry mouth, dry eyes and dry skin.
• Narcosis can result from all drugs that activate opioid receptors
• miosis, central nervous system (CNS) depression, respiratory depression and decreased
gastrointestinal motility
• Serotonin syndrome (e.g., monoamine oxidase inhibitors) results from excess serotonin
at receptor sites
• fever, hyperreflexia, hypertonia and clonus
ANTIDOTES
ANTIDOTES
• Specific antidotes only available for a small number of medications
• Top Seven:
1. N-Acetylcysteine (NAC)
- Paracetamol
2. Naloxone
- Opiates
3. Atropine
- Beta blocker / organophosphate
4. Desferioxamine
- Iron
5. Antivenoms
- Venom
6. Flumazenil
- Benzodiazepines
7. Ethanol
- Toxic alcohols (e.g., methanol & ethylene glycol)
[Credit Unknown]
ANTIDOTES
• Specific antidotes only available for a small number of medications
• Grouped into:
• Receptor antagonists (or agonists)
• Physiological
• Chelating agents
• Metabolic pathway manipulation
• Antibodies
[Credit Unknown]
ANTIDOTES
• Receptor antagonists
• Competitive antagonists at the target receptor. E.g.,:
• Flumazenil
• competitive antagonist at benzodiazepine receptors
• Naloxone
• competitive antagonist at opiate receptors
• Atropine
• competitive antagonist at muscarinic receptors
• All three are short acting, and thus may need to be infused or switched
[Credit Unknown]
ANTIDOTES
• Receptor agonists
• Competitive agonists at the target receptor. E.g.,:
• Adrenalin in beta blocker overdose
• Calcium chloride in calcium channel blocker overdose
[Credit Unknown]
ANTIDOTES
• Physiological antidotes
• Do not act on the same receptor as the causative agent. E.g.:
• Benzodiazepines in amphetamine poisoning
• Atropine in beta blocker overdose
[Credit Unknown]
ANTIDOTES
• Chelating agents
• Used to ‘mop-up’ poisoning from metals. E.g.:
• Prussian blue for thallium poisoning
• Desferioxamine for iron overdose
[Credit Unknown]
ANTIDOTES
• Metabolic pathway manipulation
• Act on metabolic pathways to prevent the creation of toxic metabolites. E.g.:
• Ethanol for methanol and ethylene glycol poisoning
• prevents formation of formic acid (from methanol) and glycolic acid (from ethylene glycol)
• N-acetylcysteine for paracetamol poisoning
• N-acetylcysteine is a glutathione precursor that prevents the metabolism of paracetamol to its toxic
metabolites
[Very nice drop!]
ANTIDOTES
• Antibodies:
• Antibodies can be used as antidotes to specific poisons. E.g.:
• Digoxin specific FAB antibodies (e.g., digibind) for severe digoxin poisoning
[Credit Unknown]
ANTIDOTES
• The antidotes mentioned are by no means exhaustive
• Most poisons do not have specific antidotes
• Good supportive care remains the cornerstone of the management of the poisoned patient,
even if antidote available
ANTIDOTES
• The antidotes mentioned are by no means exhaustive
• Most poisons do not have specific antidotes
• Good supportive care remains the cornerstone of the management of the poisoned patient,
even if antidote available
• [There is no antidote for Zombie!]
CASE
(FINAL PART)
CASE
(FINAL PART)
• Progress in ICU
• N-Acetylcysteine
• Started ‘as per protocol’ as paracetamol level above nomogram
• Ceased @ 24 hours upon consultation with VPIC (following drop in levels)
• Restarted @ 40 hours upon rising paracetamol levels (why checked?)
• Slow gut motility, and thus delayed absorption
• Ceased @ 80 hours
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
CASE
(FINAL PART)
• Progress in ICU
• 72 hours:
• Sepsis
• Developing fever and increased sputum production
• Treated for Aspiration pneumonia
• Runs of wide-complex-tachycardia
• Improving conscious state
• Decision to remain intubated because of pneumonia
[and “control”]
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
CASE
(FINAL PART)
• Progress in ICU
• 96 hours:
• Liver:
• Paracetamol level normalised
• However, rising ALT/AST
• INR peaked at 1.7
• Multiple ventricular ectopics
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
CASE
(FINAL PART)
• Progress in ICU
• 120 hours:
• Extubated
• Remained in ICU for cardiac monitoring
• Still multiple ectopics
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
CASE
(FINAL PART)
• Progress in ICU
• 144 hours:
• LFTs improving
• INR normalised
• Liver U/S revealed ‘fatty liver’
• Ectopics less frequent
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
CASE
(FINAL PART)
• Progress in ICU
• 168 hours:
• A/W psych review
Image credit - Touchstone Television (2005-2007) and ABC Studios (2007-)
CASE
(PART 3)
2500
3.5
2000
3
1500
2.5
1000
2
500
1.5
0
1
0.0
4.5
9.0
20.5
26.5
40.0
49.0
57.0
Paracetamol (micromol/L)
64.5
73.0
ALT
81.0
INR
89.0
100.0
112.0
137.0
161.0
SUMMARY
SUMMARY
• Stabilise/Resuscitate
• Reduce absorption
• Enhance elimination
• Reverse the reversible
• Support the supportable
Image credit - NBC Universal Television (2004-2007) and Universal Media Studios (UMS) (2007-)
RESOURCES
• Aus:
• www.austin.org.au/poisons
• NZ:
• www.toxinz.com
• UK:
• www.toxbase.org
• US:
• (via intranet)
COURSES
• Wikitox
• www.toxicology.wikispaces.net
• Cardiff Toxicology:
• www.cardiff.ac.uk
• American College of Medical
Toxicology
• www.acmt.net
HELP IS AVAILABLE 24/7!
VICTORIAN POISONS INFORMATION CENTRE (VPIC)
[A.K.A.: POISONS HOTLINE]
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