Aspirin Toxicity

Overview
Aspirin and other salicylates are among the
oldest medications remaining in clinical practice.

The use of aspirin has declined due to its

association with Reye's syndrome in children,
and the development of other nonsteroidal anti
inflammatory drugs (NSAIDs).
 aspirin remains a common analgesic and a
widely prescribed antiplatelet therapy for
patients with cardiovascular and
cerebrovascular disease, and thus aspirin
toxicity remains an important clinical problem
 Principle of the disease
Mechanism of action:

Inhibition of cyclooxygenase results in decreased

synthesis of prostaglandins, prostacyclin, and
thromboxanes.
This will lead to platelet dysfunction and gastric
mucosal injury.
Stimulation of the chemoreceptor trigger zone
in the medulla causes nausea and vomiting.

Activation of the respiratory center of the

medulla results in hyperventilation and
respiratory alkalosis.
Interference with cellular metabolism (eg, Krebs
cycle, oxidative phosphorylation) leads to
metabolic acidosis.
Absorption and metabolism
_ rapidly absorbed .
_ peak blood concentrations are usually reached
within one hour.
_ Aspirin is metabolized in the liver.
_ half-life of two to four hours.
At therapeutic levels, 90 percent of salicylate is
protein bound and therefore limited to the
vascular space
The drug is metabolized in the liver to salicyluric
acid, which is both less toxic and more rapidly
excreted by the kidney than salicylate.

Only a small amount of drug is excreted

unchanged in the urine.
In OVERDOSE

Peak levels are frequently delayed, up to six

hours.

The degree of protein binding falls and hepatic

detoxification becomes saturated.
As the normal hepatic detoxification is
saturated, elimination becomes dependent
upon (slow) renal excretion and drug half-life
increases from 2 to 4 hours to as long as 30
hours
Clinical features
toxic dose of aspirin
200 to 300mg/kg

Lethal dose
500mg/kg
Labs
CBC
U&Es
VBG
SERUM LEVEL
MSU
LFTS
LACTATE
COAGULATIONS
Serum salicylate:

Therapeutic serum salicylate concentrations fall between

10 to 30 mg/dL (0.7 to 2.2 mmol/L).

values above 40 mg/dL (2.9 mmol/L) are associated with

toxicity.

Fatal aspirin intoxication can occur after the ingestion of

10 to 30 g by adults and as little as 3 g by children.
Although toxicity does not correlate exactly with
serum salicylate concentrations and symptoms,
most patients exhibit signs of intoxication when
the serum concentration exceeds 40 to 50
mg/dL (2.9 to 3.6 mmol/L).
In patients with clinical signs of salicylate
poisoning, serum concentrations should be
measured every two hours until two
consecutive levels show a continuing decrease
from the peak measurement.
 Management
Treatment of salicylate poising has two main
objectives:

1st is to correct fluid deficits and acid-base

abnormalities
2nd is to increase excretion.
Airway and breathing:

Intubation is indicated for patients with

refractory shock, pulmonary or cerebral edema,
or other manifestations of severe salicylate
poisoning.
Activated Charcoal:
activated charcoal (AC), in a single dose or
multiple doses, somewhat reduces salicylate
absorption.

May be used in 1st hour with large lethal dose

provided the airway is well protected.
Intravenous fluids:
Aggressive volume resuscitation is warranted in
such patients, unless cerebral edema or
pulmonary edema is present.

Potassium depletion must be corrected.

Fluid administration should be guided by the
patient’s apparent deficit to maintain
urine output of 2 to 3 mL/kg/hr

should NOT exceed the estimated replacement

because overly excessive fluid administration
can worsen cerebral and pulmonary edema.
Supplemental glucose:

Aspirin intoxication may decrease cerebral

glucose concentrations despite a normal serum
glucose.

supplemental glucose should be given to

patients with an altered mental status
regardless of the serum glucose concentration.
Urine Alkalinization:
Because salicylates are weak acids and are
renally excreted, alkaline urine traps the
salicylate ion and increases excretion.

Alkalinization with sodium bicarbonate is an

essential component of management of the
aspirin-poisoned patient.
Urine alkalinization is advisable in patients with
salicylate levels greater than 35 mg/dL,
significant acid-base disturbance, or increasing
salicylate level
The usual initial dose of sodium bicarbonate is 1
to 2 mEq (or mmol) per kg given as an
intravenous bolus.
followed by a sodium bicarbonate infusion of
100 to 150 mEq (or mmol) in one liter of sterile
water with 5 percent dextrose.
The rate of the infusion is titrated to a urine pH
of 7.5 to 8.
Hemodialysis
Disposition:
In patients with acute intoxication, hospital
admission is required for pulmonary edema,
CNS symptoms , seizures ,acidosis, electrolyte
disorders, dehydration, renal insufficiency,
or increasing serum levels during serial testing.
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