Toxicology 4: Aspirin Overdose Portal
Aspirin (acetylsalicylic acid or ASA) is the most common agent associated with salicylic acid poisoning. Types of salicylic acid are found in numerous over-the-counter products including methyl salicylate (oil of wintergreen), bismuth subsalicylate (Pepto-Bismol®), enteric-coated aspirin (Ecotrin®). Aspirin accounts for a significant number of deaths from over-the-counter drug overdoses.
Salicylates irritate gastric mucosa, stimulate medullary centers (increased respiratory rate and vomiting), depress the CNS, inhibit Krebs cycle enzymes and uncouple oxidative phosphorylation, increase tissue glycolysis, stimulate lipid metabolism, and inhibit amino acid metabolism. Metabolic toxicity results in mixed metabolic acidosis/respiratory alkalosis, hyperthermia, altered glucose metabolism (both hypoglycemia and hyperglycemia), fluid depletion, and electrolyte disturbances. Acidosis promotes salicylate penetration of CNS, which worsens toxicity. Elimination half-life increases from 3 to 4 hours with therapeutic dosing to as long as 24 hours after acute overdose or chronic intoxication.
Estimated Toxic Dose
| Ingested Dose (mg/kg) | Estimated Toxicity |
| <150 | No toxicity reaction expected |
| 150 to 300 | Mild to moderate toxicity |
| 300 to 500 | Serious toxicity |
| > 500 | Potentially lethal toxicity |
Presentation of Signs and Symptoms
Patients with mild to moderate intoxication may develop nausea and vomiting, tinnitus, tachypnea, respiratory alkalosis, mild dehydration, fever, metabolic acidosis, and/or lethargy. Patients with severe overdoses have altered mental status ranging from confusion to coma and seizures. The classic metabolic picture is respiratory alkalosis mixed with metabolic acidosis. Critically ill patients tend to develop severe metabolic acidosis and shock secondary to salicylate intoxication. Hyperthermia with temperature exceeding 104°F can occur in the acute setting and needs immediate cooling. Pulmonary edema, coagulopathy, cerebral edema, and dysrhythmias may also develop, but are uncommon. There are rare reports of gastric perforation following massive aspirin overdose.
Toxicity is generally more severe in patients with chronic overdose, the elderly, those with underlying medical problems, and (PEDS) infants. Onset of clinical toxicity and peak serum levels may be delayed in patients with ingestion of sustained release or enteric-coated aspirin, or if pylorospasm or pharmacobezoar develops. Patients should be monitored until serial serum salicylate levels are declining and clinical symptoms are improving.
Gastrointestinal
Nausea, vomiting, and epigastric pain usually occur soon following
acute aspirin ingestion. Hematemesis is infrequent.
Central Nervous System
Typical symptoms of mild CNS toxicity include nausea and
vomiting, tinnitus, tachypnea, and lethargy. Patients may be irritable
and disoriented, signifying moderate CNS toxicity. Patients with
serious CNS toxicity develop asterixis, hallucinations, seizures, and
coma. The presence of seizures indicates a serious prognosis that may
be attributed to an electrolyte and/or metabolic disorder in addition
to direct salicylate-induced toxicity.
Respiratory
Tachypnea and hyperpnea are secondary to the stimulation of the
respiratory center in the midbrain, as well as compensation for
metabolic acidosis.
Non-cardiogenic pulmonary edema risk factors include the
following:
Age > 40 years
Smoking
Chronic salicylate ingestion
Metabolic acidosis
Neurologic symptoms
Salicylate levels > 60 mg/dL
Cardiovascular
Tachycardia is common but is not usually hemodynamically
significant. Hypotension, shock, and dysrhythmias are not common but
may develop in patients with severe toxicity.
Diagnosis and Management of Intoxication
Call the Poison center, 1-800-222-1222, to help determine risk
of toxicity and management.
Initial Therapeutic Actions
Maintain airway and assist ventilation if necessary.
Administer supplemental oxygen and establish intravenous access.
Initial Diagnostic Actions
Hypokalemia is a common finding in severe overdoses. Anion-gap
metabolic acidosis is a significant finding due to increased
production, accumulation, and excretion of organic acids. Blood glucose
concentrations may be elevated, normal, or low; CNS glucose
concentrations may be low in spite of normal or even high blood glucose
concentrations, thus contributing to cerebral dysfunction.
Laboratory
- Salicylate (aspirin) serum concentrations
- Electrolytes (calculation of an anion gap)
- Glucose
- ABGs
- Chest x-ray if evidence of pulmonary complications
Obtain in patients with clinical evidence of moderate to severe toxicity:
- CBC
- INR or PT/PTT
- LFTs
- BUN/creatinine (Salicylate is renally excreted.)
Monitor serum salicylate level, glucose, and electrolytes every 2 hours until the salicylate level is consistently falling and acid-base abnormalities are improving. Follow ABGs in symptomatic patients. Peak salicylate concentrations may not be achieved for 12 or more hours post-ingestion.
A salicylate level > 60 mg/dL accompanied by anion gap acidosis and significant neurologic findings is considered particularly serious.
GI Decontamination
Activated Charcoal
The method of choice for GI decontamination is the administration of
Activated Charcoal (AC). AC is most useful if administered within 4
hours of ingestion.
Adult dose: 50 to 100 g AC in aqueous slurry (Actidose®, EZ Char®, LiquiChar®, etc). PEDS: 1 g/kg AC in aqueous slurry
Do not give AC to patients with altered mental status unless the patient’s airway is protected.
Multiple Dose AC
Patients with concretions and delayed absorption are common. Consider
multiple dose AC (MDAC) in these patients. This may require that AC be
given in 25- to 50-g doses every 4 hours until the serum salicylate
level begins to decline significantly. If using MDAC, ensure that the
patient is maintaining active gut motility. Bowel obstruction is a
contraindication to MDAC.
Gastric Lavage
Gastric lavage may be used to evacuate the stomach in patients who have
ingested potentially life-threatening amounts. Consider gastric lavage
up to 4 or more hours post-ingestion. Gastric lavage can cause
significant morbidity; it should not be performed routinely in all
poisoned patients. Airway protection and seizure control are mandatory
before gastric lavage.
Perform gastric lavage with a large-bore orogastric tube
(Adults: 30 to 40 French, PEDS: 16 to 26 French) utilizing warm water
or normal saline. Use small aliquots: 150 to 200 mL/ wash in adults and
(PEDS) children over 5 years. For children < 5 years, use 10
mL/kg normal saline). Continue until lavage return is clear.
Whole Bowel Irrigation
In a massive salicylate overdose, with clumps of aspirin in the stomach
(especially with enteric-coated tablets), consider whole bowel
irrigation. (See Vol III—TOX1 Systematic Approach.)
Treatment
Antiemetics
5-HT3 receptor antagonists are most effective as antiemetics.
Examples:
- Kytril (granisetron HCl), 10 μg/kg IV over 5 minutes in adults and (PEDS) children 2 years and older
- Zofran (ondansetron), 8 mg IV over 15 minutes (PEDS: > 2 years 0.15 mg/kg)
- Anzemet (dolasetron), 100 mg IV over 30 seconds (PEDS: > 2 years 1.8 mg/kg)
Correct Acidosis
Sodium bicarbonate is frequently required to treat acidemia and to
promote salicylate elimination by the kidneys. To correct metabolic
acidosis caused by salicylate intoxication, administer 0.5 to 1.0
mEq/kg/IV bolus over 2 minutes and repeat as needed to maintain a blood
pH of 7.4 to 7.5.
Hydration
Initial Hydration
Fluid and electrolyte deficits may be significant due to vomiting,
hyperventilation, and sweating. Optimal hydration is of paramount
importance in treating salicylate intoxication. Although aggressive
fluid therapy is recommended, use caution because excessive fluid
administration may contribute to pulmonary edema.
If clinical signs and symptoms of dehydration are present, rehydrate with 1 liter Ringer’s Lactate or normal saline over 30 to 60 minutes. (PEDS: For pediatric patients, use 10 to 20 mL/kg.) Reassess after first flush and give second if indicated until there is good urine output (2 to 3 mL/kg/h). In patients in whom urinary alkalinization is being considered, initial hydration may be with D5W with sodium bicarbonate 2 to 3 amps (88 to 132 mEq) added per liter. Patients who display clinical evidence of potentially severe salicylate intoxication require a Foley catheter to monitor urine output as well as urine pH.
Administer intravenous fluids containing glucose and give a concentrated glucose bolus if the patient is hypoglycemic. Consider administering concentrated glucose boluses to those patients exhibiting altered mental status or seizures, despite normal blood glucose concentrations.
Maintenance
Give maintenance fluids of 2 to 3 mL/kg/h. Give potassium replacement
as necessary. (See below.)
Hyperthemia
Body temperature can rise to levels seen in malignant hyperthermia.
External cooling measures should begin with cooling blankets, cold
compresses, sprayed water with fans, and other standard therapies. Note
that shivering may occur with rapid external cooling, thus generating
more heat.
Iced gastric or colonic lavage or even ice-water immersion may lower core temperature. Rapidly gain control of seizures and agitation.
Seizures
Use benzodiazepines to treat seizures
Diazepam Adult: 2 to 5 mg IV, repeat every 5 min prn (PEDS: 0.2 to 0.5
mg/kg)
Lorazepam Adult: 2 to 4 mg IV, repeat every 5 min prn (PEDS: 0.05 to
0.1 mg/kg). Do not exceed 2 mg/minute
Check to make sure acidosis, electrolytes, and hypoglycemia are corrected.
Enhanced Elimination
Urinary Alkalinization (may increase salicylate excretion 10-fold)
- Indications for alkalinization: tinnitus, hyperventilation, altered CNS, acidosis, salicylate level > 40 mg/dL or a level that is rising. Begin even if dialysis is planned.
- The goal is urine pH 7.5 or 8. Test urine pH by bedside dipstick urinalysis each time patient voids. Monitor arterial pH and electrolytes at least every 4 hours. Infuse D5W with 3 amps (132 mEq) sodium bicarbonate per liter at 2 to 3 mL/kg/h. Unless renal failure is present, add potassium, 20 to 40 mEq to each L of IV fluids. (Potassium depletion inhibits alkalinization.)
- Alkalemia is not a contraindication to bicarbonate therapy considering that patients often have a significant base deficit in spite of the elevated blood pH.
- Fluid and bicarbonate administration is potentially dangerous for patients at high risk for pulmonary edema
Hemodialysis
Hemodialysis is the most effective means of removing salicylate from
the body. Hemodialysis is also effective in correcting acid-base and
fluid abnormalities caused by salicylate intoxication.
Indications for Hemodialysis
- In general, patients with an acute salicylate level > 80 to 100 mg/dL with severe acidosis and other manifestations of intoxication.
- Patients with chronic salicylate levels> 40 to 60 mg/dL accompanied by acidosis, confusion, or lethargy, especially if the patient is geriatric or debilitated.
- Any patient with severe manifestation of salicylate intoxication or renal insufficiency
Summary
Patients with severe acidosis (which is difficult to correct with
fluids and sodium bicarbonate), severe hypokalemia, and seizures or
coma are candidates for hemodialysis. Transfer patients to a health
care facility capable of hemodialysis.