Salicylates Toxicity


Article Author:
Tyler Runde


Article Editor:
Thomas Nappe


Editors In Chief:
Chaddie Doerr


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes


Updated:
7/30/2019 4:14:20 PM

Introduction

Salicylate toxicity is a medical emergency. Intentional ingestion or accidental overdose can cause severe metabolic derangements making treatment difficult. Co-ingestion of other medications can further complicate management. [1][2]

Etiology

Salicylates are widely available over the counter medications. They are commonly used for their analgesic, antipyretic, and anti-thrombotic properties. Toxicity can occur due to acute ingestion or from chronic ingestions that result in an increased serum concentration. Salicylates can be compounded into formulations with other classes of medications including narcotics, antihistamines, and anticholinergic medications. This can complicate management.[3][4]

Epidemiology

In 2011 there were 30,000 cases of salicylate toxicity in the United States with 39 deaths. Overall the mortality was less than 0.01%; however, this increased to 15% for patients with severe toxicity. Complications increased when the diagnosis was not made upon initial evaluation.[5][6]

Pathophysiology

Salicylate poisoning causes a variety of metabolic disorders. Direct stimulation of the cerebral medulla causes hyperventilation and respiratory alkalosis. As it is metabolized, it causes an uncoupling of oxidative phosphorylation in the mitochondria. Lactate levels then increase due to the increase in anaerobic metabolism. The lactic acid along with a slight contribution from the salicylate metabolites result in metabolic acidosis. Hyperventilation worsens in an attempt to compensate for the metabolic acidosis. Eventually, the patient fatigues and is no longer able to compensate via hyperventilation, and metabolic acidosis prevails. This results in hemodynamic instability and end-organ damage.[7]

Toxicokinetics

The ionization constant of aspirin is 3, which makes it is more readily absorbed in acidic environments such as the stomach. A variety of factors can affect absorption. The formulation of the salicylate (extended vs. immediate release) being one. Food in the stomach at the time of ingestion can delay absorption. Aspirin has the propensity to form bezoars which will delay absorption. Aspirin can cause pyloric sphincter spasms, which increases the amount of time in the stomach allowing for more absorption.  Absorption continues in the small intestine.

The liver metabolizes salicylates by first-order elimination, and the inactive metabolites are then excreted in the urine. With increased salicylate levels, these pathways become saturated resulting in zero order elimination. Elimination is further delayed in patients with underlying renal and liver disease.

Dermal salicylate preparations have been shown to reach the bloodstream. However, the serum concentrations do not reach toxic levels. Theoretically, this may occur in children or patients with compromised skin, such as due to burns or psoriasis.

History and Physical

If the patient can provide history, there are several important pieces of information to obtain. These include time of ingestion, amount ingested, as well as formulation. The later is important as it may affect the rate of absorption. It is also critical to determine if there were any other substances ingested as this may complicate treatment and increase mortality. Finally, determine whether this was accidental or intentional. This information should be corroborated by family, friends, or EMS personnel.

In an acute salicylate overdose, the onset of symptoms will occur within 3 to 8 hours. The severity of symptoms is dependent on the amount ingested. For mild ingestions (salicylate levels 40 to 80 mg/dL) nausea, vomiting, and generalized abdominal pain are common. Tachypnea is usually present. Headaches and dizziness may also occur. The classic finding of tinnitus may also be present. However, this can occur at lower, non-toxic levels.

Patients with moderate salicylate toxicity (80 to 100 mg/dL) will experience more severe neurological symptoms. These can include confusion, slurred speech, and hallucinations. Tachypnea is more pronounced and is accompanied by tachycardia and orthostatic hypotension. Expect these symptoms 6 to 18 hours after ingestion.

Salicylate levels greater than 100 mg/dL are considered severe toxicity and occur 12 to 24 hours after ingestion. Damage to the basement membranes will cause cerebral and pulmonary edema. Patients may become obtunded and develop seizures. Hypoventilation may replace hyperventilation, which is concerning for impending respiratory failure. Endotracheal intubation, while not ideal for the metabolic disorders, may be necessary for airway protection. Hypotension due to acidosis and hypovolemia is possible. Cardiac dysrhythmias may occur. Sinus tachycardia is the most common. Cardiac arrest may also occur with asystole being the most common rhythm.

Patients suffering from chronic salicylate toxicity will experience similar symptoms as acute toxicity but at lower levels. Pediatric patients will progress from mild symptoms to severe symptoms more quickly than adults.

Evaluation

A salicylate level should be checked on all patients with a concern for salicylate toxicity. Serial levels are recommended as absorption is widely variable and will impact treatment. Acetaminophen levels should also be checked as confusion about what substance was ingested may occur. Electrolytes, including calcium and magnesium, ABG, LFTs, CBC, lactate, and coagulation studies should be obtained. An ECG to evaluate for dysrhythmias should be obtained. Consider a CT head if the patient has altered mental status. Serial ABGs and salicylate levels should be obtained until levels clearly begin to downtrend and pH stabilizes.

Lab results may be normal or reveal slight electrolyte abnormalities at mild salicylate levels. PA pure respiratory alkalosis may be noted due to tachypnea. At moderate levels, metabolic acidosis with respiratory alkalosis will be present. Leukocytosis and thrombocytopenia may be noted. Hypokalemia and hypercalcemia as well as an increased BUN, creatinine, and lactate levels can occur. Worsening of the metabolic acidosis with an anion gap occurs at severe toxicity.[4]

Treatment / Management

Patients with salicylate toxicity are volume depleted due to hyperventilation, fever, and increased metabolic activity. Fluid resuscitation should utilize D5 with 3 amps of sodium bicarbonate. The dextrose will treat the central nervous system (CNS) hypoglycemia. The sodium bicarb will help correct the metabolic acidosis. Potassium may be supplemented if hypokalemia is present. Goal urine output is 2 to 3 mL/kg per hour.[8][9]

Patients with severe toxicity will eventually fatigue and be unable to maintain respiratory compensation for the metabolic acidosis. Mechanical ventilation, while not ideal, may be required. Consider a bolus of 1 to 2 mEq/kg of sodium bicarbonate at the time of intubation to temporize the patient’s pH until hyperventilation can be resumed on the ventilator. Mechanical ventilation will not be able to compensate for the metabolic acidosis as well. Arrangements for emergent hemodialysis should be arranged following intubation. Patients may also experience respiratory distress secondary to pulmonary edema following fluid resuscitation.

Following initial stabilization, attempts should be made to decrease the serum salicylate levels. Activated charcoal has been shown to decrease salicylate levels. However, no morbidity or mortality benefit has been shown. Gastric lavage may be considered if the patient presents after acute ingestion of enteric-coated aspirin. If there is any concern for aspiration, these options should be avoided. Whole bowel irrigation has shown no benefit and may increase absorption.

Fluid resuscitation and serum alkalization will increase salicylate elimination. Hemodialysis can also accomplish this. Indications for hemodialysis include severe acidosis or hypotension despite fluid resuscitation; salicylate levels are greater than 100 mg/dL, mechanical ventilation, or end-organ damage. Common signs of end-organ damage in salicylate toxicity include seizures, rhabdomyolysis, pulmonary edema, cerebral edema, and renal failure. Hemodialysis removes salicylates and lactate, which should improve the patient’s metabolic acidosis.

Seizures should be treated with benzodiazepines. Glucose should also be administered as CNS hypoglycemia may be present. Expect the patient’s metabolic acidosis to be worse following a seizure and consider administering a bicarbonate bolus.

Patients with minor ingestions and minimal symptoms may be discharged home if their salicylate levels are down trending and no metabolic derangements are present. Patients with rising salicylate levels and worsening serum pH require admission to the intensive care unit for further monitoring.[10]

Differential Diagnosis

  • Caffeine toxicity
  • Ethylene glycol overdose
  • Hydrocarbon toxicity
  • Sepsis
  • Drug withdrawal symptoms
  • Iron toxicity
  • Schizophrenia

Complications

  • Respiratory Arrest
  • Apnea
  • Dyspnea
  • Aspiration pneumonitis
  • Deafness
  • Tinnitus
  • Asystole
  • Hypotension
  • Encephalopathy
  • Seizures
  • Coma

Consultations

Patients with salicylate toxicity should be discussed with medical toxicologists. Nephrology should be consulted for patients requiring hemodialysis. Patients with increasing salicylate levels and worsening metabolic disorders should be admitted to an intensive care unit for close monitoring.

Enhancing Healthcare Team Outcomes

Salicylate toxicity in children can be decreased by educating parents. While the management of the acute toxicity is usually done with an interdisciplinary team of healthcare professionals, the nurse and the pharmacist play an important role in prevention. At the time of discharge, the parents must be told of the harm of all over the counter medications. Overuse of these medications should be avoided. Parents need to know that just because aspirin is readily available does not mean it is safe. At home, all medications should be stored away from the reach of children, preferably in a locked cabinet. Parents should be told the signs and symptoms of aspirin toxicity and the need to bring the child into the emergency room as soon as possible. Finally, if the aspirin toxicity was intentional, the nurse should recommend that the patient see a mental health counselor prior to discharge. [9][11] (Level V)

Outcomes

Salicylate toxicity has a high morbidity and mortality. At least 1-2% of patients die from this agent. Data from the poison control centers reveal that at least 1/4 of the medication-related deaths are related to aspirin alone or in combination with other medications. The important fact is that salicylate toxicity can be treated if the diagnosis and treatment are done promptly. For the survivors, some residual neurological deficit may persist for a few years.[12][13] (Level V)


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Salicylates Toxicity - Questions

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A female with a bruised wrist took some pain pills. Twelve hours later, she presents with tinnitus, nausea, hypoglycemia, metabolic acidosis and elevated BUN and creatinine. Which of the following would not benefit her acidosis?



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A 12-year-old girl inadvertently takes 12 pills of aspirin. What is she at high risk for developing?



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A mother witnessed her 4-year-old child ingest pills from an aspirin bottle left on the kitchen table. There were 10 (325 mg) tablets in the bottle at the time. She brings him directly to the emergency department where he is found to be diaphoretic and has vomited twice since he arrived. He complains of nausea and a ringing sound in his ears. Which of the following therapies is not appropriate in the early care of this child?



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A 17-year-old accidentally consumes 12 aspirin tablets and comes to the emergency department immediately. She is hyperventilating and has normal mental status. Supportive care with hydration is started. What is the appropriate next step in treatment?



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A child ingests an analgesic and develops respiratory alkalosis followed by metabolic acidosis. Which of the following is most likely responsible?



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A patient is seen in the emergency department with a low-grade fever, vomiting and, lethargy. He is tachypneic and tachycardic. His blood work including glucose levels are normal and there is no pathology visible on chest x-ray. A urine dipstick reveals proteinuria and acidosis. What is the most likely diagnosis?



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A female with a bruised wrist took some pain pills. Six hours later, she presented with tinnitus, nausea, hypoglycemia, metabolic acidosis, and elevated BUN / creatinine ratio. Which of the following would not benefit her acidosis?



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A patient presents with acute salicylate overdose. She has altered mental status and a pH of 7.3 with a wide anion gap. What is the appropriate next step in management?



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Which of the following may potentiate salicylate toxicity?



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Which of the following is used in the treatment of aspirin overdose?



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What type of acid base disorder is common in the terminal stage of salicylate poisoning?



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Which is the least likely presentation of a patient with aspirin toxicity?



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Chronic use of aspirin can cause which of the following?



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Which clinical feature is not a sign of salicylate toxicity?



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Early aspirin overdose will cause what type of arterial blood gas finding?



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Urine alkalization is helpful to enhance elimination of which of the following?



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Which of the following has enhanced elimination in the presence of sodium bicarbonate?



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Which of the following types of acid-base imbalance is seen in late stages of salicylate poisoning?



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A patient with acute salicylate overdose was diagnosed by a salicylate level of 95 mg/dL. She has altered mental status and pH 7.32 with wide anion gap. All tests occurred six hours after a witnessed ingestion. What is the appropriate next step in management?



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A 17-year-old patient arrives at the emergency department within 30 minutes of swallowing 30 tablets of aspirin, 325 mg each. Which of the following is the best antidote for initial treatment.



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A 17-year-old comes to the emergency department after swallowing pills. She is complaining of dyspnea and tinnitus but refuses to identify the pills she ingested. Laboratory values reveal arterial blood gas levels as follows: pH at 7.43; PCO2 at 13 mm of mercury; and P02 at 122 mm of mercury. Serum electrolytes show as follows: sodium at 135 mEq/L, potassium at 4.5 mEq/L, chloride at 103 mEq/L, and bicarbonate at 7 mEq/L. On which of the following drugs may this patient have overdosed?



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Which is not a treatment for aspirin toxicity?



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Which of the following can cause respiratory alkalosis?



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Salicylate toxicity can cause:



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What is a priority treatment for a patient with salicylate toxicity?



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A 3 year old patient has ingested a large amount of salicylates and you are concerned about toxicity. Which of the following is least likely to occur in cases of salicylate ingestion?



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Which of the following is not an indication for hemodialysis in acute salicylate toxicity?



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Which of the following is not true of salicylate overdosage?



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A patient takes it upon himself to excessively dose aspirin over a period of several weeks. He suffers from headaches and also heard it can prevent heart attacks. He begins to experience low-grade aspirin toxicity. Which of the following is a sign of high salicylate levels?



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Which of the following topicals do not contain methyl salicylate?



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Which of the following is a symptom typically associated with salicylate toxicity?



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A nurse is working in the emergency department when a mother brings in her teenage daughter for a possible drug overdose. The mother found an empty pill bottle in her room without a label and is unsure of the ingested substance. The healthcare provider suspects a salicylate overdose after conducting a history and physical assessment. Which findings support this probable diagnosis? Select all that apply.



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Salicylates Toxicity - References

References

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Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Nurse-Child Health PN. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Nurse-Child Health PN, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Nurse-Child Health PN, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Nurse-Child Health PN. When it is time for the Nurse-Child Health PN board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Nurse-Child Health PN.