What happens to your body after an overdose of aspirin? A medical EMERGENCY!

Acetylsalicylic acid, or aspirin, is a nonsteroidal anti-inflammatory drug (NSAID) and pain reliever and one of the over-the-counter drugs.

It is widely used to relieve mild to moderate pain (e.g., headache, toothache, menstrual pain) and fever and swelling and can be used in small doses to reduce the risk of blood clot formation in some conditions (e.g., stroke, ischemic heart diseases), especially in high-risk patients. It may be used in autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus. 

Side effects of aspirin include bleeding up to kidney failure or death. Administration of aspirin at a young age, mainly to children under 16, is associated with a high risk of Reye syndrome, especially for those recovering from viral infections such as flu or chickenpox. This condition is rare; however, it causes severe damage to the brain and liver.

The standard dose of aspirin depends on the type of aspirin and the cause of administration. Forms of aspirin include regular tablets, chewable tablets, delayed-release tablets, extended-release tablets, and rectal suppositories. The lowest dose of aspirin available over-the-counter is 75 mg tablets, which is known as “baby aspirin” or “low-dose aspirin.”

Overdose of aspirin and similar drugs (salicylates) may be acute (single large dose), which may be accidental or intentional, or chronic (gradually developing after lower doses over time). Chronic poisoning is common but often undiagnosed. The toxic dose of aspirin for an adult is considered 200 to 300 milligrams per kilogram of body weight. A dose of 500 milligrams per kilogram of body weight (34,000 mg for a 68 kg person) is considered fatal and may lead to death.

Dehydration or hot weather can increase the risk of chronic toxicity in older adults or patients with kidney dysfunction administering regular medium- to high-dose aspirin (325-650 mg every 4 to 6 hours). The low dose of aspirin used in patients at high risk of stroke or ischemic heart disease (like heart attack), which is 1 baby aspirin or ½ of an adult aspirin, cannot cause toxicity or poisoning even for a long time. In children, toxic doses are much lower. Due to the risk of Reye syndrome in children and the risk of poisoning, aspirin is usually not prescribed; instead, acetaminophen or ibuprofen is used.

Other salicylates include oil of wintergreen (methyl salicylate), which is a very concentrated salicylate and is part of many commercial products like liniments and solutions used in hot vaporizers. Regarding the toxicity of oil of wintergreen, one teaspoon (5 mL) of this product is equal to about 7000 milligrams (22 adult tablets) of aspirin, which can be fatal to young children. Bismuth subsalicylate (8.7 mg salicylate/mL) is used to treat gastrointestinal tract (GIT) infections and can cause toxicity after several doses.

Salicylate toxicity is considered a medical emergency, and if administered with other drugs, it results in further complications.

Aspirin and other salicylates act through uncoupling oxidative phosphorylation, leading to impaired cellular respiration. They cause stimulation of respiratory centers in the medulla, resulting in primary respiratory alkalosis. They simultaneously lead to primary metabolic acidosis. After entering the cells and affecting mitochondria, metabolic acidosis becomes the primary acid-base abnormality. Salicylate toxicity causes fever, ketosis, low brain glucose levels, and dehydration due to hyperventilation (respiratory water loss) and renal sodium, potassium, and water loss. Salicylates are more toxic when blood pH is low, as they are weak acids capable of crossing the cell membrane relatively easily. Increasing urine pH increases the excretion of salicylates.

-In 2010, according to the American Association of Poison Control Centers' National Poison Data System, about 4686 cases of exposure to acetylsalicylic, whether alone or in combination with other drugs, were reported. About 2172 of these cases were intentional exposure. Serious outcomes were found in more than 140 cases, with 14 reported fatal cases.

-In 2011, about 30,000 cases of salicylate toxicity were reported in the United States; 39 deaths were reported.

-About 20,000 cases of salicylate exposure are reported every year in the U.S., and about 148 cases per 1,000,000 admissions reported being salicylate intoxication.

-Mortality rate is less than 0.01% and is increased up to 15% in severe cases of toxicity.

-Complications and mortality rates are increased if the diagnosis is delayed for any reason.

-The toxicity is more severe in infants and the elderly, in addition to people with coexisting diseases or chronic intoxication.

-The age of patients and the severity of salicylate toxicity affect the presentation with acid-base disturbances. Pure respiratory alkalosis rarely occurs in infants. In infants, the most common presentation is metabolic acidosis.

-The incidence of salicylate intoxication in children and infants decreased due to increased use of acetaminophen and ibuprofen and child-resistant packaging.

In case of acute aspirin toxicity, the symptoms occur within 3 to 8 hours and are usually the following:

-Nausea and vomiting, diarrhea, heartburn

-Sweating

- Tinnitus (ringing in the ears)

-Deep or rapid breathing (tachypnea)

-Headache

-Unsteadiness

-Fever

-Rash on the skin

-Light-headedness

-Drowsiness, confusion, blurry vision, agitation, seizures

-First respiratory alkalosis, and then mixed respiratory and metabolic acidosis 

-Renal failure, rhabdomyolysis, and respiratory failure may occur.

-Collapse and coma

These symptoms vary according to the amount of salicylate ingested:

1-In mild salicylate toxicity (salicylate levels 40 to 80 mg/dL): Nausea, vomiting, generalized abdominal pain, tachypnea, headaches, dizziness, and tinnitus.

2-In moderate salicylate toxicity (80 to 100 mg/dL): Severe neurological symptoms (confusion, slurred speech, hallucinations), tachypnea, tachycardia, and orthostatic hypotension.

Symptoms occur 6 to 18 hours after ingestion.

3-In severe salicylate toxicity (greater than 100 mg/dL): Cerebral and pulmonary edema (due to damage to the basement membranes), seizures, hypoventilation, respiratory failure, hypotension, acidosis, hypovolemia, cardiac dysrhythmias (sinus tachycardia is the most common), and cardiac arrest (asystole is the most common rhythm).

Symptoms develop 12 to 24 hours after ingestion.

Symptoms develop more rapidly in children than in adults.

In case of chronic aspirin poisoning, symptoms are non-specific, occur gradually, and may be similar to sepsis:

-Hypotension (low blood pressure)

- Tachycardia (rapid heart rate)

-Dehydration

-Fever, fatigue, dyspnea (shortness of breath), wheezes

-Drowsiness or lightheadedness, subtle confusion, hallucinations, seizures, and cerebral edema may develop.

-Pulmonary edema

-Hypoxia (low oxygen level in the blood) and lactic acidosis

Diagnosis depends on history, symptoms, blood tests (serum salicylate level, arterial blood gases [ABGs]), urine pH, serum creatinine, serum electrolytes, plasma glucose, and blood urea nitrogen (BUN). Electrocardiogram (ECG) may be used. Serum creatine kinase (CK) and urine myoglobin are measured if rhabdomyolysis is suspected.

Salicylate poisoning is suspected in case of:

-Repeated ingestion of therapeutic doses

-History of a single acute overdose

-Unexplained fever and confusion or any changes in mental status, especially in older patients

-Unexplained metabolic acidosis

-Findings suggesting sepsis, such as dehydration, fever, hypoxia, hypotension, and non-cardiogenic pulmonary edema

1-History:

Includes important information that should be obtained, such as the amount of salicylate ingested, time of ingestion, accidental or intentional, any other substance ingested, and the formulation. Moreover, the presence of other medical conditions (e.g., cardiac and renal diseases) should be questioned.

Patients of long-term ingestion of salicylates present with anxiety, diaphoresis, tachypnea, agitation, delirium, difficulty concentrating, and hallucinations. If there is an underlying psychiatric illness, patients present with symptoms of exacerbation of their underlying psychiatric illness, such as mania and psychosis.

2-Symptoms of Salicylate Poisoning as mentioned before.

3-Blood tests:

Used to measure serum aspirin level, blood pH, and the level of carbon dioxide or bicarbonate, help in the determination of the severity of toxicity, and are repeated to detect recovery of patients.

-Serum salicylate level:

Salicylate poisoning is suggested if a serum salicylate level greater than the therapeutic level (therapeutic range, 10 to 20 mg/dL [0.725 to 1.45 mmol/L]) is found 6 hours after ingestion, when the absorption is almost complete. When the serum salicylate level becomes greater than 30 mg/dL, tinnitus occurs as a symptom suggesting salicylate poisoning.

Serum salicylate level is used to confirm the diagnosis and for follow-up after management to detect recovery. Serial salicylate levels may help determine if the absorption of salicylate is continuing. However, serum salicylate levels may be misleading, and diagnosis should be confirmed clinically and by other tests.

-Arterial blood gases (ABGs):

During the first few hours after ingestion, ABGs show primary respiratory alkalosis. Then, ABGs show compensated metabolic acidosis or mixed metabolic acidosis/respiratory alkalosis. As salicylate levels decrease, ABGs show poorly compensated or uncompensated metabolic acidosis. ABGs show combined metabolic and respiratory acidosis in case of respiratory failure in addition to a chest x-ray that shows diffuse pulmonary infiltrates.

-Serum electrolytes:

Signs of salicylate poisoning include hypercalcemia, hypokalemia, acidemia, dehydration, and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hypokalemia may occur as a result of treating patients with urinary alkalization without appropriate potassium supplementation.

-Plasma glucose level:

Levels of plasma glucose may be normal, low, or high, so they are not reliable.

-Leukocytosis and thrombocytopenia may be found. Prolonged prothrombin time suggests hematologic effects of salicylate poisoning, including coagulopathy and major bleeding.

4-Electrocardiogram (ECG):

ECG is used to detect dysrhythmias and may show abnormalities such as QT prolongation due to hypokalemia, U waves, and flattened T waves.

5-Imaging:

Computerized tomography (CT) of the head if patients present with altered mental status. Chest X-ray to detect pulmonary infiltrate.

Other conditions may cause the same clinical presentation of salicylate toxicity, such as:

-Iron toxicity

-Hydrocarbon toxicity

-Chlorine gas toxicity

-Ethylene glycol toxicity

-Theophylline toxicity

-Organophosphate and carbamate toxicity

-Caffeine toxicity

-Drug withdrawal symptoms

-Acute respiratory distress syndrome

-Schizophrenia

-Sepsis and septic shock

-Pulmonary embolism

Management and treatment of salicylate poisoning includes activated charcoal by mouth or stomach tube, intravenous (IV) fluids, IV potassium salt and sodium bicarbonate, airway support, symptomatic treatment, laxatives, and hemodialysis in case of severe poisoning. No specific antidote is available for salicylates. Early management and treatment can prevent organ damage and death.

Measuring a patient’s vital signs (pulse, blood pressure, breathing rate, and temperature) is done in the emergency room.

1-Activated charcoal:

Activated charcoal reduces aspirin absorption and should be given as soon as possible. It may be repeated every 4 hours until charcoal appears in the stool if bowel sounds are detected. Activated charcoal may be contraindicated, such as in patients presenting with altered mental status.

Activated charcoal and gastric lavage are useful in acute poisoning but not chronic cases of salicylate toxicity.

2- Alkaline diuresis:

 Alkaline diuresis is used after correction of volume and electrolyte abnormalities.  Alkaline diuresis is used to elevate urine pH up to ≥ 8. It is indicated and should not be delayed in patients of salicylate poisoning with any symptoms. Alkaline diuresis acts by increasing excretion of salicylate. A solution consisting of 1 L of 5% D/W, 3 50-mEq (50-mmol) ampules of sodium bicarbonate, and 40 mEq (40 mmol) of potassium chloride at 1.5 to 2 times the maintenance IV fluid rate is given to patients, as hypokalemia may interfere with alkaline diuresis. Serum potassium and fluid are monitored. Fluid overload may lead to pulmonary edema.

3-Drugs, such as acetazolamide, that increase urinary bicarbonate should be avoided, as they may worsen metabolic acidosis and decrease blood pH.

4-Drugs that decrease respiratory function should be avoided, as they may decrease blood pH through impairment of hyperventilation and respiratory alkalosis.

5-Symptomatic treatment:

-Treatment of fever through physical measures such as external cooling.

-Treatment of seizures with benzodiazepines.

6-Management of rhabdomyolysis:

Adequate hydration and urine output are essential, in addition to alkaline diuresis, to prevent renal failure.

7-Hemodialysis:

Hemodialysis may be used to increase salicylate elimination in case of renal or respiratory insufficiency, severe neurologic deterioration, acidemia in spite of other measures, and very high serum salicylate levels (>100 mg/dL [> 7.25 mmol/L] with acute overdose or > 60 mg/dL [> 4.35 mmol/L] with chronic overdose).

8-Airway support:

Endotracheal intubation and mechanical ventilation for airway protection or oxygenation.

9-Glucose boluses:

In euglycemic patients with salicylate-induced delirium, glucose boluses may improve mental status, so glucose should be given to any patient with salicylate poisoning and alteration in mental status despite the level of serum glucose.

10-Follow-up:

Accidental ingestion of less than 150 mg/kg without signs of toxicity can be discharged 6 hours after administration. Follow-up in these cases is done in 24 hours. Follow-up is necessary. A 17-year-old female had ingested 126 mg/kg of non-enteric coated aspirin 3.9 hours post-ingestion without toxic salicylate concentration, developed tinnitus and vomiting nearly 8 hours post-ingestion, and had a toxic salicylate concentration 22.7 hours post-ingestion.

Patients with intentional ingestion of salicylate should be referred to psychiatric consultation before discharge.

A toxic aspirin dose is 200 to 300 mg/kg (milligrams per kilogram of body weight); ingestion of 500 mg/kg may be fatal. A lower level of aspirin can lead to serious results in chronic poisoning. In children, much lower levels can lead to significant effects.

If treatment is delayed, the condition will get worse. Prognosis also depends on the amount of aspirin absorbed.

Mortality rate is almost 1% and morbidity rate 16% in acute aspirin poisoning. In chronic poisoning, the morbidity rate is about 30% and the mortality rate is 25%. About 33% of analgesic-related deaths are a result of aspirin alone or aspirin in combination with other drugs, according to the American Association of Poison Control Centers. Early management is lifesaving.

Categories of toxicity are used to determine the potential severity and morbidity of an acute, single-event, non–enteric-coated salicylate ingestion:

-Less than 150 mg/kg ingested >> Ranges from no toxicity to mild toxicity

-From 150-300 mg/kg ingested >> Mild-to-moderate toxicity

-From 301-500 mg/kg ingested >> Serious toxicity

-Greater than 500 mg/kg ingested >> Potentially fatal toxicity

Complications: 

-Aspiration pneumonitis

-Respiratory Arrest

-Asystole and dysrhythmias

-Seizures, Encephalopathy

-Coma

At the end, if you take aspirin for any medical reason, you have to be careful with the doses and should not take an extra dose except after consulting your doctor. If you feel any of the previously mentioned symptoms, consult your doctor as soon as possible. If you have any medical disorder and are prescribed several drugs, it is better to seek psychiatric consultation to relieve the stress that may be caused by the disease and the drugs. Remember that your health matters. 

(1) Aspirin Overdose: Symptoms, Diagnosis, Emergency Treatment. Drugs.com

(2) Aspirin overdose, National Institutes of Health National Library of Medicine (NIH).

(3) Gerald F. O’Malley, DO, Grand Strand Regional Medical Center; Rika O’Malley, MD, Grand Strand Medical Center, Aspirin and Other Salicylate Poisoning, Merck Sharp & Dohme (New Zealand) Limited (MSD).

(4) Muhammad Waseem, MBBS, MS, FAAP, FACEP, FAHA, Salicylate Toxicity, Medscape.

(5) Runde TJ, Nappe TM. Salicylate Toxicity. [Updated 2022 Jul 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.