Aspirin and Salicylates
Salicylate-induced acute lung injury has been observed in
humans.
mecanisem is increased pulmonary vascular permeability
This vascular injury also may involve the kidneys. Proteinuria
is a prominent early finding in salicylate toxicity, starting at a
serum salicylate concentration of >30 mg/dL, and it is directly
related to salicylate concentrations.
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glucose homeostasis: Although salicylate causes
mobilization of glycogen stores, resulting in hyperglycemia,
it is also a potent inhibitor of gluconeogenesis.
• Therefore, normoglycemia, hyperglycemia, or hypoglycemia
may occur in salicylate toxicity.
• Animal studies demonstrate that toxic doses of salicylate produce
a profound decrease in brain glucose concentration despite normal
serum glucose concentrations.
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This finding suggests that the supply of glucose to the brain in
salicylate poisoning may be inadequate, even though serum
glucose concentrations are normal.
Antiplatelet activity is a well-known effect of aspirin, but
hemorrhage is a rare complication of acute, single, massive
overdose.
typical clinical presentation includes :
nausea and vomiting
tinnitus
hearing loss
sweating
hyperventilation
• Tinnitus may develop in patients on chronic salicylate therapy
when the serum salicylate concentration is at the upper limit of
the therapeutic range of 20 mg/dL.
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Uncommon features of acute salicylism include :
fever
neurologic dysfunction
renal failure
acute lung injury
cardiac dysrhythmia
hypoglycemia
• Each of these uncommon manifestations indicates more
severe poisoning, with associated greater morbidity and
mortality
• Other rare complications include:
• rhabdomyolysis
• gastric perforation
• GI hemorrhage
Several commercially available tests can qualitatively detect
salicylate in the urine.
However, there are severe limitations associated with bedside
detection techniques for salicylic acid, their role has little
utility in most clinical settings, and positive results must be
confirmed with serum salicylate concentration.
Commercially available tests for serum
salicylate concentration are very accurate, and
the only reported significant interference has
been with diflunisal, which produces false
positive results for significantly high serum
salicylate concentrations.
Some enteric-coated medications are radiopaque and visible
on an abdominal radiograph.
Thus, a positive radiograph can confirm that pills are present,
but a negative radiograph does not exclude enteric-coated or
modified-release tablets in the GI tract.
Essential laboratory tests include :
serum salicylate concentrations
electrolytes
glucose
blood urea nitrogen and creatinin
Arterial blood gases
chest and abdominal radiograph
ECG
complete blood count
serum calcium level
urinalysis with urine pH determination
There is no specific antidote for salicylate toxicity.
The priority is immediate resuscitation with stabilization of
airway, breathing, and circulation.
Subsequent steps involve:
correction of volume depletion
metabolic derangements
GI decontamination
reduction in body salicylate burden
• Salicylates can induce pylorospasm and form gastric bezoars, so
that lavage may be beneficial even when performed more than 1
hour from the ingested overdose
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However, the large size of enteric-coated and modified-release
tablets may make them difficult to remove from the stomach
• Salicylate absorption is effectively reduced by the administration
of activated charcoal .
• A single dose of activated charcoal, 1 to 2 gr/kg should be
administered to patients who have ingested potentially toxic
amounts of salicylate.
There are no convincing data to support the use of repeated or
multiple doses of activated charcoal in salicylate overdose.
• Patients with severe salicylate intoxication are usually volume
depleted,and have serious acid-base disturbances
• Thrifor require IV volume and electrolyte replacement.
• Careful assessment of a patient's volume and electrolyte status
is important, particularly in the elderly and in patients with a
history of cardiac disease.
• Volume replacement is initially undertaken with normal saline,
and because hypokalemia is common, potassium should be
added to the infusion after adequate urine output has been
established.
• Serum potassium should be maintained in the 4.0 to 4.5 mEq/L
• Supplemental potassium may be required as correction of
acidemia further shifts potassium into cells.
Urinary alkalinization does enhance salicylate elimination and is an
effective treatment for salicylate toxicity, although the precise
mechanism is debated.
• Although a good outcome with urinary alkalinization as the
only method to enhance elimination was reported for a severely
poisoned patient
• most toxicologists would opine that urinary alkalinization is a
useful initial technique but should not be perceived as a
substitute for hemodialysis in severe salicylism
• A common approach is to volume restore patients with normal
saline to a target urine output of 1 to 2 mL/kg/h.
• Concurrently, in a second IV line, an IV bolus of sodium
bicarbonate (1 to 2 mEq/kg) is given followed by a continuous
infusion (three ampules of either 44 or 50 mEq/ampule of
sodium bicarbonate added to 1 L of 5% dextrose in water).
• The infusion is started at 2 to 3 mL/kg/h and adjusted to maintain
the urine pH >7.5.
• Except for the fluids used for initial resuscitation, all IV fluids
administered should contain a minimum of 50 gr/L of glucose
(5% dextrose in water) because hypoglycemia has been
implicated in the pathophysiology of salicylate neurologic injury.
• Patients with acute lung injury should be managed as are
patients with acute lung injury from other causes.
• Pulmonary edema begins to improve concomitantly with the
lowering of serum salicylate concentrations, and this suggests
that aggressive efforts toward rapid elimination by
hemodialysis
In addition, early hemodialysis enables removal of salicylate
without the volume challenge that accompanies sodium
bicarbonate administration, and it avoids the possibility of
aggravating lung injury.
Patients with clinically significant bleeding should be treated with
fresh frozen plasma.
Indications for hemodialysis include:
salicylism requiring respiratory and ventilatory support
clinical deterioration or failure of improvement despite
intensive supportive care and an alkaline diuresis
lack of success in establishing an alkaline urine
renal insufficiency
severe acid-base disturbance
altered mental status
patients with acute lung injury
A patient may be discharged from the ED if it can be
determined that the patient had an inconsequential salicylate
overdose.
It is recommended that a patient who has overdosed on
enteric-coated or modified-release preparations of aspirin be
treated regardless of initial serum salicylate concentrations,
be observed for at least 24 hours, and
obtain serial serum salicylate concentrations until a declining
level is confirmed.