INTRODUCTION
Salicylate-containing products are one of the most commonly used over-the-counter pharmaceuticals in the US. Acetylsalicylate and methyl salicylate are two preparations of salicylate available on the market. For many years, acetylsalicylate (aspirin) has been used as analgesic, antipyretic, and antiplatelet agents, while methyl salicylate can be found in topical ointment, herbal oil, lotions, solutions used in hot vapor and topical analgesia.1 Due to its widespread use and easy accesability, salicylates have been implicated in accidental and intentional overdose. Moreover, some salicylate containing topical preparations including herbal oils, lotions, and ointments are gaining popularity, and can potentially increase incidence of salicylate toxicity. Some of these products may contain 98-100% of methyl salicylate. Consequently, 1 ml of solution containing approximately 5,000 mg of methyl salicylate can potentially cause severe toxicity when ingested.1In 2018, approximately 27,000 toxic exposures to salicylates were reported by the American Association of Poison Control Center, with mortality rate of 0.4%.2 Among these reported cases, approximately half was due to intentional ingestion as an attempt to commit suicide.
Salicylates are absorbed in the stomach and small intestine. Most salicylates are metabolized in the liver and then excreted by the kidneys as salicyluric acid, gentisic acid, acylglucuronides, and salicylic phenolic glucuronides, while approximately 10-30% of salicylates are excreted by kidney as free salicylic acid. Salicylate intoxication can manifest by several presentations, including hyperpnea, nausea, vomiting, dizziness, tinnitus, fever, sweating, altered mental status, coma, and organ failures.1 Acid-base abnormality is common in a setting of salicylate intoxication. Salicylates are able to directly stimulate the respiratory center resulting in hyperventilation and subsequent respiratory alkalosis. Concurrently, by interfering with aerobic metabolism salicylates cause anion-gap metabolic acidosis due to an increase of ketone bodies, lactate, and pyruvate. In addition, normal anion-gap metabolic acidosis may concomitantly occur, and is attributed to renal bicarbonate loss and chloride retention, compensating for respiratory alkalosis.3
Salicylate toxicity has been reported to affect kidneys. Several mechanisms have been proposed to be responsible for acute kidney injury (AKI). Insensible fluid loss due to increase in body temperature along with gastrointestinal losses from emesis have a potential to results in severe volume depletion, up to 6 L in some cases, causing renal hypoperfusion.4 In addition, salicylate-induced nephrotoxicity can manifest through acute tubular necrosis, acute interstitial nephritis, papillary necrosis, and proximal tubular dysfunction.5-7 Although AKI has been reported as a complication of salicylate intoxication, the epidemiology and impact of AKI on outcomes has been limited. Therefore, we conducted this study aiming to assess the risk factors and the association of AKI with outcomes of salicylate toxicity, and resource utilization in patients hospitalized with salicylate intoxication in the US.