The patient is a 34 yo female with a history of gastric bypass and recurrent kidney stones who presents with a 1-week history of body pain, lethargy and dyspnea. She reported to the ED with intractable pain for which she was taking 30 tablets of ibuprofen (200 mg) during the day and up to 20 tablets of ibuprofen/diphenhydramine (200/25 mg) at night. She denied suicidal attempts and seemed unaware of side effects of NSAID overdose. Her physical exam was unremarkable. Her labs revealed a low serum potassium (2.2 mmol/L), a low bicarbonate (10 mmol/L), and an elevated creatinine (2.27 mg/dl). Venous blood pH was low (7.14), as was her pCO2 (30 ppm). Further analysis revealed a triple mixed acid-base disturbance: an anion gap (AG) metabolic acidosis (AG = 18); a non-ion gap metabolic acidosis (D/D of 0.42:1); and a concomitant respiratory acidosis. The patient was started on IV bicarbonate and aggressive electrolyte repletion. Her acid-base disturbance gradually resolved and her acute renal insufficiency improved with NSAID avoidance.
Ibuprofen, the most frequently used OTC pain medicine, treats ailments ranging from headaches to advanced heart disease. With widespread OTC availability, the public may be unaware of ibuprofen’s deleterious side effects such as gastrointestinal pain, bleeding, weakness, and even renal impairment. Renal tubular acidosis (RTA) is an under-appreciated side effect of ibuprofen overdose, typically occurring only after extremely high doses (>100 mg/kg/day). Several subtypes of ibuprofen-induced RTA have been proposed. Type I RTA can occur through ibuprofen’s inhibitory effect on carbonic anhydrase that blocks the exchange of potassium (K) and hydrogen (H+) in the distal tubule, leading to H+ accumulation and K loss, and a resultant metabolic acidemia and hypokalemia. Ibuprofen may also cause Type II RTA by blocking carbonic anhydrase in the proximal tubule, dramatically increasing secretion of bicarbonate into the urine, causing acidemia with an extremely low serum bicarbonate level. Furthermore, ibuprofen can block prostaglandin I2‘s stimulatory effect on renin and aldosterone, thus reducing renal secretion of both acid and potassium into the urine. This Type IV RTA is characterized by a normal anion gap, mild acidemia, and sometimes a pronounced hyperkalemia. Thus, ibuprofen may produce a unique RTA through combination of all three physiologic mechanisms. Moreover, ibuprofen can directly constrict the afferent arteriole, leading to an accumulation of unmeasured anions responsible for an anion gap metabolic acidosis.
Gastrointestinal bleeding and renal failure are commonly seen complications of NSAID abuse. However, in patients who overdose on NSAID medications, one should not overlook complex acid-base disorders, involving an unique RTA, as a potentional adverse complication.
To cite this abstract:Raphael CW, Kumar D. Back Pain? Take 50 Ibuprofen and Call Me in the Morning. Abstract published at Hospital Medicine 2016, March 6-9, San Diego, Calif. Abstract 754. Journal of Hospital Medicine. 2016; 11 (suppl 1). https://www.shmabstracts.com/abstract/back-pain-take-50-ibuprofen-and-call-me-in-the-morning/. Accessed May 22, 2019.