Salicylate Toxicity

Background

Salicylates are found in a myriad of prescription and over-the-counter medicinal preparations:

Toxic levels of salicylate exert a direct stimulatory effect on the respiratory center of the medulla, causing an increase in the rate and depth of respiration and the development of respiratory alkalosis.
Salicylates also uncouple oxidative phosphorylation and inhibit citric acid cycle dehydrogenases, causing a shift in metabolism to glycolysis
- compensatory increase in body catabolism and substrate breakdown is required to supply the energy needed for the increasingly inefficient production of ATP from ADP through glycolysis
- manifested by increased oxygen consumption, increased heat production (leading to hyperpyrexia, diaphoresis, and dehydration), depletion of liver glycogen, and increased metabolic production of carbon dioxide
Anion gap: accumulation of ketoacids and other organic acids accounts for the majority of the increase in the anion gap. The contribution of salicylate is minor (<5 mmol per liter)
Increased renal bicarbonate excretion in response to respiratory alkalosis decreases buffer capacity, potentially worsening the degree of acidosis as organic acids accumulate

Suicide attempt.
Inadvertent overdose in patients chronically using aspirin (often elderly with multiple medical problems).

Salicylate toxicity can easily present as several common and serious mimics:

Pneumonia (fever, pulmonary edema/rales, tachypnea, diaphoresis)
Sepsis (acidosis, lactate, tachypnea, diaphoresis, confiusion , fever, tachycardia, leukocytosis)
Intoxication (EtOH)
Encephalopathy
1. Dementia or delirium
2. Viral encephalitis

generally occurs in young adults who have a psychiatric history or who have had a previous overdose. Time of ingestion of salicylate, the plasma level, and clinical toxicity are only loosely correlated (depends on formulations, co-ingestions, multiple ingestions)
clinical manifestations occur within 1-2 hours after a single ingestion:
- >2.9-3.6 mM: tinnitus, vertigo, nausea, vomiting, hyperpnea
- >5.1 mM: severe intoxication with fever, sweating, listlessness, incoordinatioj
- >5.4 mM: hallucinations, seizures, cerebral edema, coma ARDS, CV collapse

may occur in patients who are ingesting acetylsalicylic acid therapeutically and then have an inadvertent overdose (elderly or dependent patients)
baseline tissue burden of the drug is high and pathways for salicylate elimination are nearly or fully saturated, additional intake of the drug may lead to substantial accumulation of free salicylate and extension of the normal half-life of 2 to 4 hours to as long as 20 hours.
plasma level of salicylate required to elicit symptoms tends to be lower in chronic than in acute salicylate poisoning (can be near the ULN)
classic symptoms and signs tend to be milder or absent in cases of chronic toxicity
Neurologic abnormalities, such as agitation, confusion, hallucinations, slurred speech, seizures, and coma, occur more frequently in patients with chronic salicylate poisoning than in those with acute intoxication.