MED-NERD
Salicylate Poisoning (Aspirin Toxicity)
Outline:
- Introduction
- Pathophysiology of Salicylate Poisoning
- Epidemiology
- Symptoms
- Diagnosis
- Differential diagnosis
- Management and treatment
- Prognosis
- Complications
- References
Introduction:
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), fever, 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 in young age mainly children under 16 is associated with high risk of Reye syndrome especially those recovering from viral infection 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, Rectal suppositories. The lowest dose of aspirin available over-the-counter is 81 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. Aspirin toxic dose for an adult is considered 200 to 300 milligrams per kilogram of body weight. A dose of 500 milligrams per kilogram of body weight (34,000mg for a 68kg 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 administrating regular medium to high-dose aspirin (325-650mg 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 are used.
Other salicylates such as 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 the 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 administrated with other drugs results in further complications.
Pathophysiology of Salicylate Poisoning:
Aspirin and other salicylates act through uncoupling oxidative phosphorylation leading to impaired cellular respiration. They cause stimulation of respiratory centres 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.Epidemiology:
-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.
-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 elderly in addition to people with coexisting disease 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.
Symptoms:
In case of acute aspirin toxicity, the symptoms occur within 3 to 8 hours and are usually the following:-Nausea and vomiting, Diarrhoea, 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
-Difficulty breathing
-First respiratory alkalosis, and then mixed respiratory and metabolic acidosis occur
-Renal failure, Rhabdomyolysis, 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), cardiac arrest (Asystole is the most common rhythm).
Symptoms develop 12 to 24 hours after ingestion
Symptoms develop more rapid 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 light headedness, Subtle confusion, Hallucinations, Seizures, Cerebral edema may develop
-Pulmonary edema
-Hypoxia (Low oxygen level in the blood) and lactic acidosis
References:
(1) Aspirin Overdose: Symptoms, Diagnosis, Emergency Treatment.Drugs.com
https://www.drugs.com/medical-answers/aspirin-overdose-symptoms-diagnosis-emergency-3558001/
(2) Aspirin overdose, National Institutes of HealthNational Library of Medicine (NIH).
https://medlineplus.gov/ency/article/002542.htm
(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.
https://emedicine.medscape.com/article/1009987-overview
(5) Runde TJ, Nappe TM. Salicylates Toxicity. [Updated 2022 Jul 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499879/
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