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IN THE NAME OF GOD
AN APPROACH TO A
POISONED PATIENT
DR. FAZEL GOUDARZI;TRAUMATO
PATHOLOGIST AND CLINICAL
TOXICOLOGIST
SHIRAZ UNIVERCITY OF MEDICAL
SCIENCES
Introduction

What is a poison?


In common usage - poisons are
chemicals or chemical products that
are distinctly harmful to human
More precisely - a poison is a
foreign chemical (xenobiotic) that is
capable of producing a harmful
effect on a biologic system
Other terminology

What is a toxin?


It originally referred to a
poison of animal or plant
origin
Toxicant is the currently
preferred scientific term for
all poisons.
Epidemiology
Ingestion of a potentially poisonous
substance by a young child is common.
 American Association of Poison Control
Centers reported 1.2 million ingestions
in children < 6 years of age in 2001.
 Death is uncommon in this age group.
 Decline in death rate from 500
mortalities per year in the 1940s
to 25 mortalities in 1997

Epidemiology
Decline in mortality attributed to:
 child resistant containers
 safer medications
 anticipatory guidance
 public education
 legislation
 establishment of poison control centers
 sophisticated medical care
 antidotes
Clinical assessment
Approach to the Poisoned Patient
History
 Time
of ingestion
 Medications in the household
 Amount ingested
 Onset of symptoms
 Intentionality
 Underlying medical conditions
Approach to the Poisoned Patient
Physical Examination
Vital Signs
 Pupillary exam (miosis, mydriasis)
 Skin (dry, cyanotic)
 Lungs (crackles, wheezing)
 Cardiac (tachycardia, bradycardia)
 Abdomen (decreased bowel sounds,
tenderness)
 Neurologic (altered mental status, seizure)

Approach to the Poisoned Patient
Initial Management
 Airway
 Breathing
 Circulation
 Disability
 Exposure
Clinical assessment

Airway - ensure clear airway, clear secretions,
check for cough/gag

Breathing - check oxygenation, supplemental
O2, breathing pattern & adequacy

Circulation - heart rate, rhythm, blood pressure
Clinical assessment

Neurologic - GCS, seizures, agitation, spasms,
pupils, autonomic dysfunction

Miscellaneous - odour, temperature, pallor,
cyanosis, jaundice

Abdomen - rigidity, bleeding, urine output
Laboratory and
imaging(paraclinical) assessment
Approach to the Poisoned Patient
Diagnostic Evaluation
 CBCD
 Electrolytes
 ABG
 LFTs
 CXR
 ECG
 AXR
 Serum
Tox
 Urine Tox
 ASA level
 Tylenol level
 Serum OSM
 Cholinstrase
Laboratory assessment

Electrolytes

Hypokalemia
– Oduvanthalai poisoning (Clistanthis collinis)
– Diuretics, Methyl xanthine, Toluene

Hyperkalemia
– Digoxin
– Beta-blocker

Liver function tests
– Acetaminophen, Ethanol, Carbon tetrachloride

Renal function tests
– Ethylene glycol, NSAIDS
Anion Gap (AG)
Anion Gap = Na+ - [Cl- + HCO3 -]
Normal AG: 8-16
Toxins associated with increased AG
Methanol
 Paraldehyde
 INH
 Fe
 Ethylene glycol
 Salicylates
 CO
 Cyanide

Hydrogen Sulfide
 ETOH (ketones)
 Metformin
 Phenformin
 Sulfur
 Theophylline
 Toluene

Toxins associated with decreased AG
 Lithium
 Bromide
Osmolal Gap (OG)
Serum OSM: 2[Na] + [Glc]/18 + [BUN]/2.6
OG: Measured OSM-Calculated OSM
Normal OG: -3 to 10 mOSM/kg H2O
Toxins associated with increased OG
 Methanol
 Ethanol
 Ethylene
glycol
 Acetone
 Isopropanol
Useful Toxin Levels
Set time point
Acetaminophen
 Carbon Monoxide
 Ethanol
 Ethylene glycol
 Heavy metals
 Iron
 Methanol
 Methemoglobin

Serial levels
Salicylates
 Carbamazepine
 Digoxin
 lithium
 Phenobarbital
 Phenytoin
 Theophylline
 Valproate

ECG and Imaging Assessment

ECG




Digoxin toxicity
TCA overdose - sinus tachycardia, QT prolongation,
increased QRS
Beta-blockers - conduction abnormalities
Imaging
 Chest x-ray
 Abdominal x-ray
 Cervical x-ray (lateral)
 C.T scan or MRI in decrease L.O.C.
Radiopaque drugs









Bezoars/Bags
Calcium carbonate
Chloral hydrate
Enteric-coated tablets
Heavy metals
Iodine
Fe
Phenothiazines
Potassium compounds
Other terminology

What is a toxidrome?(TOXICOLOGIC
SYNDROME)?

It is the association of several clinically
recognizable features, signs, symptoms,
phenomena or characteristics which often occur
together, so that the presence of one feature
alerts the physician to the presence of the
others.
Common toxidromes
Opiate toxidrome
Opiate toxidrome
Opiate toxidrome
Toxidromes
Opiates
Miosis
 Respiratory depression
 Cns depression
 Hypotension
 Sedation
 Decreased GI motility
 Urinary retention

Toxidromes
Opiates
 Seizures-Meperidine;
occur secondary
to the metabolite normeperidine
 Dysrhythmias-Propoxyphene; occur
from the metabolite norpropoxyphene
 Rigid Chest-Fentanyl
Common toxidromes
The cholinergic toxidrome
The cholinergic toxidrome
The cholinergic toxidrome
Toxidromes
Cholinergics-Muscarinic Effects
 Salivation
 Lacrimation
 Urination
 Defecation
 Gastrointestinal
 Emesis
Distress
TOXIDROME
CHOLINERGIC CNS EFFECT
RESTLESSNESS
 AGITATION
 CONFUSION
 CONVULSION
 COMA
 DEATH

Toxidromes
Cholinergics-Nicotinic Effects
 Muscle
Fasciculations
 Weakness
 Paralysis
 Sympathomimetic effect
What toxidrome?
The anticholinergic toxidrome
Hot as a hare
Dry as a bone
Red as a beet
Mad as a hatter
Blind as a bat
The anticholinergic toxidrome
Hot as a hare
Dry as a bone
Red as a beet
Mad as a hatter
Blind as a bat
The anticholinergic toxidrome
Hot as a hare
Dry as a bone
Red as a beet
Mad as a hatter
Blind as a bat
Toxidromes
Anticholinergics
 “Red
as a beet”- Flushed skin
 “Hot as a hare”-Hyperthermia
 “Mad as a hatter”-Psychosis
 “Dry as a bone”-Dry skin, urinary
retention
 Tachycardia
 Mydriasis
What toxidrome?
Hallucinogenic
Toxidrome
disorientation
Amphetamine
hallucinations
Cocaine
hyperactive bowel
Pseudoephedrine
panic
Phencyclidine
seizure
Ephedrine
Hypertension
Tachycardia
Tachypnea
Benzodiazepenes
Hallucinogenic
Sympathomimetic toxidrome
disorientation
Amphetamine
hallucinations
Cocaine
hyperactive bowel
Pseudoephedrine
panic
Phencyclidine
seizure
Ephedrine
Hallucinogenic and
stimulants
Toxidrome
Hypertension
Tachycardia
Tachypnea
Benzodiazepenes
Hallucinogenic
Sympathomimetic toxidrome
Hallucinogenic
Toxidrome
disorientation
Amphetamine
hallucinations
Cocaine
hyperactive bowel
Pseudoephedrine
panic
Phencyclidine
seizure
Ephedrine
Hypertension
Tachycardia
Tachypnea
Benzodiazepenes
Hallucinogenic
Sympathomimetic toxidrome
Hallucinogenic
Toxidrome
disorientation
Amphetamine
hallucinations
Cocaine
hyperactive bowel
Pseudoephedrine
panic
Phencyclidine
seizure
Ephedrine
Hypertension
Tachycardia
Tachypnea
Benzodiazepenes
Hallucinogenic
Sympathomimetic toxidrome
Hallucinogenic
Toxidrome
disorientation
Amphetamine
hallucinations
Cocaine
hyperactive bowel
Pseudoephedrine
panic
Phencyclidine
seizure
Ephedrine
Hypertension
Tachycardia
Tachypnea
Benzodiazepenes
Common toxidromes
Sedative/hypnotic toxidrome
Sedative/hypnotic toxidrome
Sedative/hypnotic toxidrome
Common toxidromes
Serotonergic syndrome
Serotonergic syndrome
Serotonergic syndrome
Toxidromes
Sympathomimetics
 Hypertension
 Tachycardia
 Psychomotor
 Hyperthermia
 Diaphoresis
 Mydriasis
Agitation
Recognition of poisoning

May be difficult because of non-specific symptoms

High index of suspicion - especially occult
poisoning


history may be unreliable
look for corroborative history - missing pills, empty
container

Course that a poison runs (toxidromes) ! - may
help

Toxicology screening - helpful only in a few
Clinical manifestations

Very diverse and varied - depends on the
poison

Clinical examination should be focused on
the possible manifestations of common
poisons in the geographical area
Clinical manifestations

Skin and mucosal damage

Neurotoxic manifestations

Cardiovascular manifestations

Metabolic consequences

Eye manifestations

Hepatic dysfunction
When do you consider ICU?


Respiratory

Airway protection

Respiratory failure
Cardiovascular

Hypotension despite fluid challenge

Heart block, arrhythmias, QTc prolongation as in TCA
When do you consider ICU?

Neurologic



GCS < 8 (grade 3 and4)
Seizures
Metabolic





Hypoglycaemia
Significant electrolyte abnormalities
metabolic acidosis
Hepatic failure
Coagulopathy with bleeding
Goals of treatment
Goals of treatment

Reduce absorption of the toxin (xenobiotic)

Enhance elimination

Neutralise toxin
Reduce absorption of the toxin
Reduce absorption
Removal from surface skin & eye
 Emesis induction
 Gastric lavage
 Activated charcoal administration & cathartics
 Dilution - milk/other drinks for corrosives
 Whole bowel irrigation
 Endoscopic or surgical removal of ingested chemical

Reduce absorption

Skin decontamination
– Important aspect – not to be neglected
– Remove contaminated clothing
– Wash with soap and water (soaps
containing 30% ethanol advocated)
– However, no evidence for benefit even in
OP poisoning
Decontamination

Gastric decontamination
– Forced emesis if patient is awake by gag
stimulation or by ipecac(?)
– Gastric lavage
– Activated charcoal 1g/kg and MDAC in
some cases
– Sorbitol as cathartic
– Whole bowel irrigation
Ipecac
NO!!!!
 Had been previously been recommended
for administration at home immediately
following ingestion
 No longer recommended in the AAP policy
statement - Poison Treatment in the Home
(Pediatrics Vol. 112 No. 5, November 2003)

Why Not Ipecac?
Variable percentage of removal of toxic
medication
In adult volunteers:
51-83% removal (5 minutes after ingestion)
2-59% removal (30 minutes after ingestion)
 May cause persistent vomiting, lethargy, and
diarrhea
 Vomiting may preclude later administration of
oral antidotes

Why Not Ipecac?
 Lethargy
and vomiting together
increase risk of aspiration
 Inappropriate use-following
ingestion of acid or lye
 Misuse-children with eating
disorders
 Misuse-Munchausen by proxy
Gastric Lavage
 Early
following ingestion
 Airway must be protected
 Use the largest available tube
(40 French)
 Contraindicated in caustic ingestions,
hydrocarbons, previous vomiting
Reduce absorption

Gastric lavage







Gastric lavage decreases absorption by 42% if done
20 min and by 16% if performed at 60 min
Performed by first aspirating the stomach and then
repetitively instilling & aspirating fluid
Left lateral position better - delays spont. absorption
No evidence that larger tube better
Simplest, quickest & least expensive way - funnel
Choice of fluid is tap water - 5-10 ml/kg
Choice of fluid is NL SALIN for children
Reduce absorption

Gastric lavage


Preferrably done on awake patients
Presence of an ET tube does not preclude
aspiration, though preferred if GCS is low
Activated Charcoal
Single Dose
Toxic ingestions that adhere to charcoal
 Dose is 1 g/kg PO or NGT
 Administered with Sorbitol
 Airway must be protected
 Contraindicated in caustics,
hydrocarbon, foreign body, ileus or
gastric perforation

Activated Charcoal
Multiple Doses
 Large
ingestions
 Drugs that undergo enterohepatic
circulation
 Drugs with low Vd
 Drugs with low protein binding
 Drugs with long t1/2
Activated Charcoal
Multiple Doses
 Only
the FIRST dose should be
administered with Sorbitol
 Dose 1 g/kg PO or NGT Q6 x 24
hours or until charcoal is passed in
the stool
Which drugs do not adsorb to charcoal?
Lithium
 Iron
 Alcohols
 Acids
 Alkalis
 Cyanide
 Hydrocarbons

Whole Bowel Irrigation
 Life
threatening ingestion
 Sustained-release toxin
 Prolonged absorption time of the toxin
 Must protect the airway
 Contraindicated in caustic, hydrocarbon,
foreign body, ileus, gastric perforation
Whole Bowel Irrigation
Polyethylene Glycol
 Dose:
up to 500 ml/h
 Continue until stool is clear
 Patient may get bloated and vomit
 Antiemetics (metoclopramide or
ondansetron) may be helpful
 Monitor electrolytes closely
Toxins and their Antidotes
Acetaminophen
N-acetylcysteine
Anticholinergics
Physostigmine
Atropine
Anticholinesterases/
Cholinergics
(muscarinic effects)
Pralidoxime
(nicotinic effects)
-controversial in
carbamate
ingestions
Toxins and their Antidotes
Benzodiazepines
Botulism
Flumazenil
Botulinum antitoxin
Beta-blockers
Calcium channel blockers
Glucagon
Calcium
Carbon monoxide
Hyperbaric O2, O2
Cyanide, Nitrites
Amil nitrit;Na nitrit(3
thiosulfate(12.5g/50m
Toxins and their Antidotes
Digoxin
Digibind aka Digoxin Fab antibodies
Ethylene Glycol
Heparin
Iron
Isoniazid
Ethanol
Protamine
Deferoxamine
Pyridoxine
Toxins and their Antidotes
Lead
EDTA, BAL, DMSA
Methanol
Ethanol
Methemoglobin
Opioids
Methylene blue
Naloxone
Tricyclic antidepressants
Warfarin (Superwarfarins)
NaHCO3
Vitamin K
Enhance elimination
Enhance elimination

Increased elimination is possible only if




the drug is distributed predominantly in the ECF
has a low protein binding
the induced rate of elimination is faster than the
normal rate
hazards of having a longer time of exposure to the
drug are potentially fatal
Enhance elimination

Methods



Keep a good urine output 150-200 ml/hr
Alkalinisation of urine - clinical efficacy accepted
for salicylate & phenobarbital poisoning
Extracorporeal removal
– Hemodialysis - Barbiturates, Salicylates,
Acetaminophen, Valproate, Alcohols, Glycols
– Hemoperfusion - theophylline, digitalis, lipid
soluble drugs
Enhance Elimination
Methods
 Alkalinization
and Urinary ion trapping
 Hemodialysis
 Charcoal
hemoperfusion
Alkalinization/Urinary Ion Trapping
Effective for drugs that are excreted
renally
 The drugs must be either weak acids or
weak bases e.g. ASA and Phenobarbital

HA  H+ +ApKa
At a Urine pH < pKa
Non-ionized form
*Not excreted in urine
At a Urine pH > pKa
Ionized form
*Excreted in urine
Hemodialysis
 Low
volume of distribution less than 1L/Kg
 Low protein binding
 Low molecular weight less than 500 DAL.
 Also helpful in managing acidosis,
electrolyte abnormalities
 Low fat solubility
 High Water Solubility
Which drugs are high dialyzable?
 Salicylates
 Methanol
and ethanol
 Lithium
 Ethylene
glycol
 Amphetamines
 Theophylline
 Vancomycin
(p. brophy)
CVVHD following HD for Lithium
6
L poisoning
Pt #1
HD started
Li Therapeutic range
i
0.5-1.5 mEq/L
5
CVVHD started
m 4
E
q 3
/
2
L
CT-190 (HD)
Multiflo-60
both patients
BFR-pt #1 200 ml/min
HD & CVVHD
-pt # 2 325 ml/min
HD & 200 ml/min
CVVHD
PO4 Based dialysate at
2L/1.73m2/hr
1
0
Pt #2
Hours
24
12
6
5
0
Hemoperfusion
 Blood
is passed through a cartridge
containing charcoal or carbon
 Drugs with low Vd
 Toxins can be larger than those
removed by hemodialysis
 Can be more protein bound than
those cleared by hemodialysis
 Toxin must bind well to charcoal
Which drugs can be removed by
hemoperfusion?
 Theophylline
 Phenobarbital
 Carbamazepine
 Phenytoin
 Salicylates
 Paraquate
Complications of Hemoperfusion
 Thrombocytopenia
 Hypocalcemia
 Leukopenia
 Rigors
(p. brophy)

HEMOFILTRATION

optimal drug characteristics for removal:
relative molecular mass less than the cut-off of
the filter fibres (usually < 40,000)
 small Vd (< 1 L/Kg)
 single compartment kinetics
 low endogenous clearance (< 4ml/Kg/min)


(Pond, SM - Med J Australia 1991; 154: 617-622)
(p. brophy)
Continuous Detoxification methods
 CAVHF, CAVHD, CAVHP, CVVHF,
CVVHD, CVVHP
 Indicated in cases where removal of
plasma toxin is then replaced by
redistributed toxin from tissue
 Can be combined with acute high flux
HD

(p. brophy)

Intoxicants amenable to Hemofiltration
vancomycin
 methanol
 procainamide
 hirudin
 thallium
 lithium
 methotrexate

(p. brophy)

Plasmapheresis / Exchange Blood
Transfusions

Plasmapheresis
(Seyffart G. Trans Am Soc Artif Intern
Organs 1982; 28:673)
role in intoxication not clearly established
 most useful for highly protein bound agents


Exchange Blood Transfusions
Pediatric experience > than adult
 Methemoglobinemia
 overall very limited role in poisoning

Summary

Poisoning a common problem in our country

A high index of suspicion required to diagnose

Know common toxidrome

Don’t panic and follow a plan of action




Decreasing absorption
Enhancing elimination
Neutralising toxins
Avoid potentially harmful Rxs - risk vs benefit
Thank you
Case Presentation 1
A 15 year old girl presents to the ED four hours
after taking 20 extra-strength (500 mg/tablet)
Tylenol tablets. The ingestion was prompted by a
fight with her boyfriend earlier that day. She has
a history of an attempted suicide in the past.
She is awake and alert with stable vital signs.
She complains of nausea and has had one
episode of vomiting. Physical exam is normal.
Baseline labs show normal electrolytes, with
normal LFTs, normal coags and a Tylenol level of
120 microgram/ml.
What would you do?
A. Call psychiatry to evaluate the patient. No
medical intervention is required.
 B. Administer 1g/kg of activated charcoal
with sorbitol every 6 hours and 17 doses of
oral N-acetylcysteine.
 C. Administer one dose of activated charcoal
with sorbitol followed by intravenous
N-acetylcysteine for 21 hours.
 D. Gastric lavage in an attempt to recover pill
fragments.

Acetaminophen Poisoning
 Toxic
dose: 150 mg/kg or a
total dose of 7.5 g
 Toxic level: 150 microgram/ml
at 4 hours
 Antidote: N-acetylcysteine
Acetaminophen Metabolism
90% undergoes glucuronidation and
sulfate conjugation in the liver to
harmless metabolites excreted in the
kidney
 < 5%, together with some insignificant
metabolites are excreted in the kidney
unchanged
 Remainder undergoes oxidation by
the cyt-p450 system to N-acetyl-pbenzoquinoneimine (NAPQI)

NAPQI

Electrophile

Covalently binds to hepatocytes

Results in cell death

Half life is about
POTENTIAL TOXICITY

Acute: 7g (10g)

Chronic: 4g per day (7g)

Susceptible patients (alcoholics,
ACs, INH)
Similar risk for acute ingestion
 Potential higher risk in chronic
ingestions (4g)

Phases of Toxicity
I: (½-24 h):nausea, vomiting, diaphoresis
May be normal
 II: (24-72 h): less nausea, vomiting; RUQ pain;
LFTs and coags begin to rise
 III: (72-96 h): Coagulation abnormalities, renal
failure, encephalopathy, death related to
hepatic failure
 IV: (4 d-2 wk):If stage III damage is
reversible, resolution of hepatic dysfunction

N-ACETYLCYSTEINE

Very effective – 100% within 8 hours

Oral in U.S. – IV in Europe

Dose: 140mg/kg load, 70mg/kg Q 4hrs


Traditional – 72 hours
Short course – reassess at 20 hours
INTRAVENOUS NAC

Oral preparation vs Acetadote®

Concern is anaphylactoid reactions

Indications:
Can’t tolerate oral NAC
 Contraindication to oral therapy
 Ongoing GI decon (coingestant)
 Fulminant hepatic failure?
 Pregnant patient?

N-acetylcysteine (NAC)
mechanism
 Prevents
binding of NAPQI to
hepatocytes
 Reduces NAPQI
 Conjugates NAPQI
 Increases sulfation metabolism***
NAC
Must be administered within 8 hours
 IV dose: 150 mg/kg infused over 60 minutes;
followed by a 4-hour infusion of 50 mg/kg;
followed by a 16-hour infusion of 100 mg/kg;
equivalent to a total dose of 300 mg/kg infused
over 21 hours
 Oral dose: 140 mg/kg x 1 followed by
70 mg/kg x 17 doses

NAC
Smells like rotten eggs
 Oral formulation may need to be given
via NGT
 Dilute with juice
 Use metoclopramide or ondansetron if
not tolerated due to vomiting
 Use hydrocortisoe and antihistamin in
sensitvity cases


Review of case
A 15 year old girl presents to the ED four hours
after taking 20 extra-strength (500 mg/tablet)
Tylenol tablets. The ingestion was prompted by a
fight with her boyfriend earlier that day. She has
a history of an attempted suicide in the past.
She is awake and alert with stable vital signs.
She complains of nausea and has had one
episode of vomiting. Physical exam is normal.
Baseline labs show normal electrolytes, with
normal LFTs, normal coags and a Tylenol level of
120 microgram/ml.
What would you do for our patient?
A. Call psychiatry to evaluate the patient. No
medical intervention is required.
 B. Administer 1g/kg of activated charcoal
with sorbitol every 6 hours and 17 doses of
oral N-acetylcysteine.
 C. Administer one dose of activated charcoal
with sorbitol followed by intravenous
N-acetylcysteine for 21 hours.
 D. Gastric lavage in an attempt to recover pill
fragments.

The correct answer is:
C.
Administer one dose of activated
charcoal with sorbitol followed
by intravenous N-acetylcysteine
for 21 hours.
Key Points
Despite the fact that our patient’s Tylenol level
was only 120 microgram/ml at four hours and
falls below the toxic level on the nomogram,
she must be treated with NAC. She ingested
a total of 10 g (20 tablets x 500 mg) which is
> 7.5 g and toxic.
 NAC may be given orally or IV.
 IV NAC has only recently been approved for
use in the US.

Key Points
The administration of activated charcoal in
Tylenol ingestion has been controversial as it
may interfere with oral NAC.
 Some studies have shown decreased
absorption of Tylenol when activated charcoal
is given in a timely fashion.
 Activated charcoal will not interfere with
administration of IV NAC and therefore may be
given.

Key Points
If activated charcoal is administered, only
one dose should be given.
 For ingestions requiring administration of
multiple doses of charcoal, only the first
should be given with sorbitol.
 Gastric lavage is not likely to be efficacious
four hours following ingestion.
