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.