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 membrane exposure, and
 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 patient’s
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 evaluation:
examination – Anion gap
• Vital signs – Osmolal gap
• Ocular findings – Oxygen saturation gap
– Toxicology screening
• Mental status,
behaviour and muscle
tone
• 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, β-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
• Vasopressors may be required for refractory
hypotension.
• 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

• Hypertension-induced (reflex) bradycardia generally

should not be treated.
 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.
does not recommend routine use of GL in the
management of poisoning unless a patient has
AMERICAN
ingested ACADEMY
a potentially OF CLINICAL
life-threatening amount of a
poison and the procedure can be undertaken
TOXICOLOGY
within 60 min of ingestion
 B. Gastric Lavage
INDICATIONS
• Ingestion of a substance
with high toxic potential
and:
■ Within 1 hour of ingestion
■ Ingested substance is not
bound by activated
charcoal or has no effective
antidote.
■ Potential benefits outweigh
risks.
CONTRAINDICATIONS
■ Substance not meeting above
indications
■ Spontaneous emesis
■ Diminished level of
consciousness/unprotected
airway reflexes (intubate first)
■ Ingestion of hydrocarbons or
caustic agents
■ Foreign body ingestion
■ Patient is at high risk for
esophageal or gastric injury (GI
hemorrhage, recent surgery,
etc.).
TECHNIQUE
■ Recommended tube size is 36–40 French for adults,
22–28 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 (10–15 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
• Activated charcoal (AC) is
ingested by the patient in
order to adsorb poisons
within the GI tract lumen.
■ Patient presents within 1 to
2 hours after ingestion.
■ Patient has ingested a
potentially dangerous
amount of a poison
adsorbed by charcoal
CONTRAINDICATIONS
■ Ingested substance is poorly
adsorbed by AC (eg, iron,
lithium, heavy metals,toxic
alcohols).
■ Diminished level of
consciousness/unprotected
airway reflexes (AC can be given
by naso- or orogastric tube
following intubation)
■ Patient presents over 2 hours
after ingestion.
■ Ingestion of caustic agents
■ Cases where endoscopy will be
required
 INDICATIONS
DOSE
■ The recommended dose of
AC is a 10:1 ratio relative to
the ingested poison(ie,
ingestion of 1 g of poison
requires 10 g of AC). Hence,
the commonED practice of
administering 50 to 100 g (1
g/kg) of AC to an overdose
patient may be inadequate
for larger ingestions.
CONTRAINDICATIONS
RISKS
■ The primary risk of single-
dose AC is vomiting.
■ Constipation and diarrhea
■ Bowel obstruction does not
occur from single-dose AC.
■ Repeated doses of
cathartics given with
charcoal may cause
dehydration or electrolyte
abnormalities.
 D. Whole -Bowel Irrigation

Whole-bowel irrigation (WBI) flushes the GI tract to decrease the

transit timeof luminal contents, thereby limiting absorption
INDICATIONS
■ Removal of ingested drug
packets (eg, body stuffers)
■ Large ingestion of a
sustained-release drug
■ Potentially toxic ingestion
that cannot be treated with
activated charcoal (eg,
lithium, lead, iron)
.
CONTRAINDICATIONS
■ Diminished level of
consciousness/unprotected
airway reflexes (intubate
first)
■ Decreased GI motility or
bowel obstruction
■ Significant GI hemorrhage
■ Persistent emesis
 DOSE
 Polyethylene glycol (PEG)
solution is administered at
a rate of 1–2 L/hour.
 This rate of administration
usually requires a naso- or
orogastric tube.
 Endpoints for therapy are
the appearance of clear
rectal effluent or a total
irrigation volume of 10 L.
COMPLICATIONS
 The primary risk associated
with WBI is vomiting.
 Patient discomfort:
Bloating, cramping, and
flatulence
 WBI with balanced PEG
solutions does not
generally cause electrolyte
abnormalities.
 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

2–4 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 MDAC is contraindicated in

enterohepatic circulation and the same settings as AC.
can possibly be treated with
MDAC include:

■ Phenobarbital
■ Carbamazepine (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 agents that

affects the clearance of are not weak organic acids
drugs that are weak organic and are not primarily
acids. cleared by the kidneys
■ Patients who cannot
■ Aspirin (most common use tolerate excess
for alkalinization) sodium/water loading (eg,
■ Phenobarbital CHF, renal failure)
■ Formic acid
 C. Hemodialysis
Hemodialysis (HD) directly removes toxins from a
patient’s 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 ■ Toxins that do not satisfy

poisoned patient, the the conditions listed
ingested poison should have above.
the following characteristics:

■ Low molecular weight

■ Low plasma protein-binding
■ Small volume of 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
• SIKer Nas BADAN POM RI
Jln. Percetakan Negara No. 23 Jakarta 10560
Telp :021-4259945
Fax : 021-42889117 ( setiap hari kerja )
HP : 0813-10826879 ( di luar jam kerja ) Email
SIKer: informasi@pom.go.id
pusatiomker@cbn.net.id
• SIKER DAERAH SURABAYA
Jl. Karangmenjangan No.20 - Surabaya 60286
Telp : 031- 5048833 Fax : 031- 5048833
e-mail : ulpksby@sby.prima.net.id