Salicylate toxicity from chronic bismuth subsalicylate use

Background

Adverse drug events are a common cause of morbidity, hospitalisation and even death in older adults.1 This includes harm from over-the-counter (OTC) medications, which are widely used for a variety of ailments and easily procured. A US cross-sectional study of 2976 older adults (age range: 57–84 years) between 2005 and 2006 identified that 42% used an OTC medication or dietary supplement.2

One substance that is often found in OTC and non-prescription medications is salicylates.3 This includes methyl salicylate (an active ingredient in muscle rubs and oils), acetylsalicylic acid (such as in low-dose aspirin and certain antacids), bismuth subsalicylate (contained in gastric relief products) and choline salicylate found in teething gels which pose a risk for paediatric ingestion.3–5 Salicylate toxicity can present either acutely in overdose or from chronic low-level exposure.3 The latter often being harder to appreciate and can be missed. Older adults with significant comorbidities such as chronic kidney disease or on medications that can impair renal function are susceptible to adverse effects of salicylates even if not taken in overdose.6

Chronic salicylate toxicity is an especially challenging diagnosis that can often be misattributed and easily missed. Here we present a case report of a nearly missed diagnosis of chronic salicylate toxicity that resolved once exposure was eliminated and appropriate supportive care provided.

Case presentation

A 79-year-old man was brought to the emergency department with a 1-week history of worsening confusion, inattention and ataxia resulting in two falls from a prior baseline of ambulating independently. His medical history included atrial fibrillation, type 2 diabetes mellitus, hypertension, chronic kidney disease secondary to diabetic nephropathy (baseline creatinine 150 µmol/L), a repaired abdominal aortic aneurysm and gastro-oesophageal reflux disease (GERD).

His medications included metoprolol, sitagliptin, metformin, amlodipine, ramipril, hydrochlorothiazide, atorvastatin, pantoprazole, ranitidine, tamsulosin, dutasteride, zopiclone, melatonin, docusate sodium and senna. In the 2 weeks prior to presentation, he used occasional acetaminophen/codeine phosphate 300 mg/15 mg tablets for pain.

On the next day, a detailed medication history discovered that he was ingesting one to two bottles of Pepto-Bismol (bismuth subsalicylate) daily for GERD for 6 months. He also reported impaired hearing in the past week and worsening confusion over 6 months.

Initially, on examination he was disoriented to place and time, he had a blood pressure of 114/65 mm Hg, heart rate of 78 beats/min, respiratory rate of 18 breaths/min and temperature of 36.9°C. His cardiovascular and respiratory examinations were normal. He did not have any focal neurological deficits on examination.

Investigations

Initial laboratory investigations revealed a normal complete blood count and an acute kidney injury with a creatinine on admission of 232 µmol/L and a peak of 313 µmol/L on day 1. His lactate was 0.6 mmol/L and liver function tests and liver enzymes were normal. Thyroid-stimulating hormone was 0.16 mIU/L, and B₁₂ was 246 pmol/L.

A urine toxicology immunoassay screen was negative aside from opiates, which was expected because the patient was known to use codeine as needed. Plasma acetaminophen concentration was only 11 µmol/L (therapeutic reference range 65–130 µmol/L), plasma ethanol concentration was undetectable (reference range <1 mmol/L) and blood cultures ultimately revealed no growth.

A CT scan of his brain was normal with no evidence of infarct or haemorrhage and an abdominal pelvis ultrasound revealed no acute process and no hydronephrosis.

On day 2, collateral history revealed Pepto-Bismol ingestion, plasma salicylate concentration was sent and returned at 2.08 mmol/L, despite no sources of salicylate in hospital.

Differential diagnosis

Part of the diagnostic criteria for an adverse drug event is to ensure alternative causes are ruled out. Structural causes such as a stroke or haemorrhage were ruled out with a CT brain, and infectious etiologies were felt unlikely given the absence of fever, meningismus, normal liver function and ultimately negative blood cultures. The acute on chronic kidney injury was felt to be predominantly a consequence from poor oral intake and ongoing nephrotoxic home medications, rather than a cause of his presentation.

The resolution of symptoms with supportive care only correlating with a resolving plasma salicylate concentration helped to establish a diagnosis of chronic salicylate toxicity secondary to daily Pepto-Bismol ingestion.

Treatment

Pepto-Bismol was discontinued, his ramipril and hydrochlorothiazide were held and he was treated with isotonic intravenous fluids in order to facilitate renal excretion of salicylate. His renal function improved to baseline with a creatinine near discharge of 162 µmol/L and the plasma salicylate concentration cleared to less than 0.36 mmol/L. Concurrently, his mental status, hearing and gait dramatically improved, and on discharge, he was ambulating independently.