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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 CONTRAINDICATIONS
• Ingestion of a substance ■ Substance not meeting above
with high toxic potential indications
and: ■ Spontaneous emesis
■ Within 1 hour of ingestion ■ Diminished level of
consciousness/unprotected
■ Ingested substance is not
airway reflexes (intubate first)
bound by activated
charcoal or has no effective ■ Ingestion of hydrocarbons or
caustic agents
antidote.
■ Foreign body ingestion
■ Potential benefits outweigh
■ Patient is at high risk for
risks. 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 CONTRAINDICATIONS

• Activated charcoal (AC) is ■ Ingested substance is poorly


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

■ The recommended dose of ■ The primary risk of single-


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

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


transit timeof luminal contents, thereby limiting absorption .
INDICATIONS CONTRAINDICATIONS
■ Removal of ingested drug ■ Diminished level of
packets (eg, body stuffers) consciousness/unprotected
■ Large ingestion of a airway reflexes (intubate
sustained-release drug first)
■ Potentially toxic ingestion ■ Decreased GI motility or
that cannot be treated with bowel obstruction
activated charcoal (eg, ■ Significant GI hemorrhage
lithium, lead, iron) ■ Persistent emesis
DOSE COMPLICATIONS

 Polyethylene glycol (PEG)  The primary risk associated


solution is administered at with WBI is vomiting.
a rate of 1–2 L/hour.  Patient discomfort:
 This rate of administration Bloating, cramping, and
usually requires a naso- or flatulence
orogastric tube.  WBI with balanced PEG
 Endpoints for therapy are solutions does not
the appearance of clear generally cause electrolyte
rectal effluent or a total abnormalities.
irrigation 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


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
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