Toxicology

PWM Olly Indrajani

2012
 Introduction
Given a large enough exposure, all
substances have the potential to be poisons.
Poisoning occurs when exposure to a
substance adversely affects the function of
any system within an organism.
The setting of the poison exposure may be
occupational, environmental, recreational,
or medicinal.
Poisoning may result from varied portals of
entry, including inhalation, insufflation,
ingestion, cutaneous and mucous
 DIFFERENTIAL DIAGNOSIS
BY CHIEF COMPLAINT

Although the poisoned patient may

present with varied symptoms and
complaints, the chief presenting complaint
or symptom may suggest a diagnosis
Recognition of grouped symptoms and
findings consistent with a toxidrome can
guide diagnosis and treatment in the
poisoned patient.
 Primary Considerations for
Presenting Chief Complaint in the
Poisoned Patient
Toxidromes
 Oral ingestion was the commonest
route of exposure (Fig 1)
Most exposures occurred at the
patients own residence, and most
patients (75%) were managed on-site
with assistance from a poison
information center and did not require
an emergency department visit
Only 3% of patients required critical
care.
 Largest number of deaths were:
analgesics
Antidepressants
sedative/hypnotics/antipsychotics
Stimulants
street drugs
cardiovascular drugs
alcohols
 Of all deaths:
5% increase compared to 1999
88% occurred in 20- to 99-year old
individual
The mortality rate was higher in
intentional rather than unintentional
exposures (79% vs 10.5%, respectively).
 DIAGNOSIS
History and
physical Laboratory
examination evaluation:
Vital signs Anion gap
Ocular findings Osmolal gap
Mental status, Oxygen saturation
behaviour and gap
Toxicology
muscle tone
screening
Poison control
center consultation
 History and Physical
Examination
Although the history is important, it
may be unreliable or incomplete
Consider that family members,
friends, and pharmacists may have
additional information
 In the absence of a classic presentation or
toxidrome, separating patients with
suspected poisoning into broad categories
based on:
vital signs
ocular findings
mental status
muscle tone
can help determine drug or toxin
class
 Vital Signs
Anticholinergic and sympathomimetic
substances increase heart rate, BP, and
temperature

In contrast organophosphates, opiates,

barbiturates, -blockers,
benzodiazepines, alcohol, and clonidine
cause hypothermia, bradycardia, and
respiratory depression.
 Ocular Findings
Anticholinergics and sympathomimetics cause
mydriasis
In contrast to anticholinergics overdose, the
pupils remain somewhat light responsive in
cocaine intoxication
Horizontal nystagmus is common in alcohol
intoxication
Other drugs causing nystagmus are lithium,
carbamazepine, solvents, meprobamate,
quinine, and primidone
Phencyclidine and phenytoin cause horizontal,
vertical, and rotary nystagmus
Mental Status, Behavior, and Muscle Tone
Initial Supportive Measures
 Airway, Breathing, Circulation

Often required before confirmation of

intoxication
With cervical spine precautions in place
(unless trauma has been excluded), airway
patency must be ensured in all cases
Endotracheal intubation is not always
necessary when cough and gag reflexes
are present and there is adequate
spontaneous ventilation, but when there is
concern regarding airway protection and
clinical deterioration it is better to secure
the airway
Intubation is indicated in acute respiratory
failure
 Other specific indications include the
need for high levels of supplemental
oxygen in carbon monoxide
poisoning and the need to protect
the airway for gastric emptying
Endotracheal intubation decreases
(but does not eliminate) the risk of
aspiration
which is approximately 11% in the
comatose patient with drug
overdose)
 Depending on the intoxication, patients
may present with hypotension or
hypertension, bradyarrhythmias or
tachyarrhythmias
The pathogenesis of hypotension varies
and may include hypovolemia,
myocardial depression, cardiac
arrhythmias, and systemic vasodilation
Treatment should be individualized, but
an initial strategy of rapid IV normal
saline solution infusion is indicated in
most instances
 The vasopressor of choice depends on the
type of intoxication

Hypertension occurs in the setting of

sympathomimetic drugs, anticholinergics,
ergot derivatives, phenylpropanolamine
overdose, and withdrawal from nicotine,
alcohol, and sedatives

Treatment of the hypertension depends on

its chronicity and severity and the inciting
agent

 Coma Cocktail

Thiamine (100 mg by vein) is administered to

treat and/or avoid Wernicke-Korsakoff
syndrome in comatose patients
Comatose patients should receive dextrose,
50 g IV
Naloxone rapidly reverses coma, respiratory
depression, and hypotension induced by
opioids. An initial dose of 0.2 to 0.4 mg is
administered IV (or endotracheally).
 Prevention of Absorption

Skin decontamination requires removal of

the toxin with nonabrasive soap and water
Contaminated clothing may serve as a
reservoir for continued exposure and must
be removed with caution and placed in
plastic bags or other containers that are
impervious to the toxin
Ocular decontamination may require
prolonged periods of irrigation with normal
saline solution
 PRINCIPLES OF
GASTROINTESTINAL
DECONTAMINATION
Gastrointestinal (GI) decontamination refers to
therapies that may decrease the amount of
poison absorbed from the GI tract lumen.

The following methods of GI decontamination

are available:

A. Induced emesis
B.Gastric emptying or Gastric lavage (GL)
C. Activated charcoal combined with a cathartic
D.Whole-bowel irrigation(WBI)
 Emesis
Considered only in fully alert
patients, and is virtually never
indicated after hospital admission
Contraindications to its use include
poisoning with corrosives, petroleum
products, or antiemetics.
 A. Induced Emesis
Induced emesis utilizes syrup of ipecac to induce
vomiting, theoretically emptying the stomach and
reducing absorption of an ingested agent.
Syrup of ipecac induces vomiting by activation of
both local and central emetic sensory receptors.
Induced emesis has largely been abandoned in
clinical practice.
The most recent policy statements released by both
the American Academy of Pediatrics(2003) and the
American Association of Poison Control Centers
(2005) discourage the use of syrup of ipecac in the
out-of-hospital setting.
 Gastric Emptying
GL through a 28F to 40F Ewald tube is
similarly aimed at physically removing a
toxin
Prior to inserting the Ewald tube, the
mouth should be inspected for foreign
material and equipment should be ready
for suctioning
Large gastric tubes (37F to 40F) are less
likely to enter the trachea than smaller
nasogastric tubes, and are necessary to
facilitate removal of gastric debris
 Nonintubated patients must be alert
(and be expected to remain alert)
and have adequate pharyngeal and
laryngeal protective reflexes
In semicomatose patients, GL should
be performed only after a cuffed
endotracheal tube has been inserted.
 GL is performed by instilling 200-mL aliquots of
warmed tap water until there is clearing of
aspirated fluid
Stomach contents should be retained for analysis
Tap water may avoid unnecessary salt loading
compared to normal saline solution
Neither irrigant has been shown to significantly
alter blood cell or electrolyte concentrations
After clearing, the Ewald tube may be replaced by
a nasogastric tube for subsequent intermittent
suctioning and/or administration of activated
charcoal.
B. Gastric Lavage
INDICATIONS CONTRAINDICATIONS
Ingestion of a Substance not meeting
substance with high above indications
toxic potential and: Spontaneous emesis
Diminished level of
Within 1 hour of consciousness/unprotected
ingestion airway reflexes (intubate
Ingested substance first)
is not bound by Ingestion of hydrocarbons
activated charcoal or caustic agents
or has no effective Foreign body ingestion
antidote. Patient is at high risk for
esophageal or gastric
Potential benefits injury (GI hemorrhage,
outweigh risks. recent surgery, etc.).
TECHNIQUE
Recommended tube size is 3640 French for adults,
2228 French for children.
Secure airway via intubation, if necessary.
Position patient in left-lateral decubitus position, with head
lowered below level of feet.
Confirm tube placement following insertion.
Aspirate any available stomach contents.
Lavage with 250 mL (1015 mL/kg in children) aliquots of
warm water or saline.
Continue until fluid is clear and a minimum of 2L has been
used.
Instill activated charcoal through same tube, if indicated.

COMPLICATIONS
The primary risks are vomiting, aspiration, and esophageal
injury or perforation.
 C. Activated Charcoal
INDICATIONS CONTRAINDICATIONS

Activated charcoal (AC) Ingested substance is

is ingested by the poorly adsorbed by AC (eg,
patient in order to iron, lithium, heavy
adsorb poisons within metals,toxic alcohols).
the GI tract lumen. Diminished level of
consciousness/unprotected
Patient presents within airway reflexes (AC can be
1 to 2 hours after given by naso- or orogastric
tube following intubation)
ingestion.
Patient presents over 2
Patient has ingested a
hours after ingestion.
potentially dangerous
Ingestion of caustic agents
amount of a poison
adsorbed by charcoal Cases where endoscopy
will be required
 INDICATIONS CONTRAINDICATIONS
DOSE RISKS

The recommended The primary risk of

dose of AC is a 10:1 single-dose AC is
ratio relative to the vomiting.
ingested poison(ie, Constipation and diarrhea
ingestion of 1 g of Bowel obstruction does
poison requires 10 g of not occur from single-
AC). Hence, the dose AC.
commonED practice of Repeated doses of
administering 50 to cathartics given with
100 g (1 g/kg) of AC to charcoal may cause
dehydration or electrolyte
an overdose patient
abnormalities.
may be inadequate for
larger ingestions.
 D. Whole -Bowel Irrigation

Whole-bowel irrigation (WBI) flushes the GI tract to decrease the transit timeof luminal contents, thereby limiting absorption .

Removal of
INDICATIONS CONTRAINDICATIONS
ingested drug
packets (eg, body
stuffers) Diminished level of
consciousness/unprote
Large ingestion of a cted airway reflexes
sustained-release (intubate first)
drug Decreased GI motility
Potentially toxic or bowel obstruction
ingestion that Significant GI
cannot be treated hemorrhage
with activated Persistent emesis
charcoal (eg,
 DOSE COMPLICATIONS

Polyethylene glycol The primary risk

(PEG) solution is associated with WBI
administered at a rate is vomiting.
of 12 L/hour. Patient discomfort:
This rate of Bloating, cramping,
administration usually and flatulence
requires a naso- or
WBI with balanced
orogastric tube.
Endpoints for therapy PEG solutions does
are the appearance of not generally cause
clear rectal effluent or electrolyte
a total irrigation abnormalities.
volume of 10 L.
 PRINCIPLES OF ENHANCED
ELIMINATION
The goal of enhanced elimination is to increase
the clearance of a poison from the body after it
has been systemically absorbed.

The following methods of enhanced elimination

are available:
A. Multiple-dose activated charcoal
B. Urinary alkalinization
C. Hemodialysis
 Enhanced Elimination:
Drug Characteristics and
Examples
A. Multiple-Dose Activated Charcoal

Uses repeated doses of activated charcoal

(every 24 hours) to increase poison
clearance.
MDAC exerts its effects through disruption of
enterohepatic circulation or direct adsorption
across the GI mucosal surface.

RISKS
The risks associated with MDAC are similar to
those with AC; however,there is a greater risk
of bowel obstruction with MDAC.
 INDICATIONS CONTRAINDICATIONS

Drugs that have

enterohepatic circulation
and can possibly be
treated with MDAC
include: MDAC is
contraindicated in
Phenobarbital the same settings
Carbamazepine
as AC.
(Tegretol)
Theophylline
Aspirin
Dapsone
 B. Urinary Alkalinization
Urinary alkalinization attempts to increase renal
elimination of a drug by increasing urine pH.

Urinary acidification to increase the clearance of

weak bases is not recommended due to the risk
of renal injury.

RISKS
Can precipitate hypokalemia and decrease
ionized calcium levels
 INDICATIONS CONTRAINDICATIONS

Urinary
alkalinization only Poisoning with
affects the agents that are not
clearance of drugs weak organic acids
that are weak and are not primarily
organic acids. cleared by the
kidneys
Patients who cannot
Aspirin (most
tolerate excess
common use for sodium/water loading
alkalinization) (eg, CHF, renal
Phenobarbital failure)
Formic acid
 C. Hemodialysis
Hemodialysis (HD) directly removes toxins from
a patients plasma, using the same technology
applied to renal failure.

RISKS
HD requires central venous access, with all the
usual accompanying risks
(bleeding, pneumothorax, etc.).
HD must be used cautiously in patients that are
hemodynamically unstable.
 INDICATIONS CONTRAINDICATIONS

For HD to be useful in a
poisoned patient, the
ingested poison should
have the following
characteristics:
Toxins that do not
Low molecular weight
satisfy the
Low plasma protein-
binding conditions listed
Small volume of above.
distribution
Poor endogenous clearance
HD can also treat severe
acidosis caused by a toxin,
even if the toxin it self is
not readily dialyzable.
 Poison Control Center
Consultation
Regional poison control center
consultation is highly recommended in
cases of suspected poisoning and to help
guide management in confirmed cases
These centers provide 24-h emergency
and up-to date technical information.
They are staffed by nurses, pharmacists,
pharmacologists, and physicians trained
and certified in toxicology