Ibuprofen-Associated Hypokalemia and Metabolic Acidosis: Systematic Literature Review

Abstract

Objective: Ibuprofen is a widely used nonsteroidal anti-inflammatory drug, which has been occasionally associated with hypokalemia and metabolic acidosis. The objective of this report is to analyze the literature on this issue and to address the underlying pathophysiology. Data Sources: Excerpta Medica, the National Library of Medicine, and Web of Science were searched from inception to July 16, 2021. Study Selection and Data Extraction: Papers reporting individually documented humans on ibuprofen with hypokalemia, acidosis, or both were retained. Data were extracted using a checklist. Data synthesis: For the final analysis, we evaluated 41 reports describing 50 cases (26 males and 24 females; 36 adults and 14 children) with often profound hypokalemia, acidosis, or both after ingestion of ibuprofen. Twenty-six cases were acute and 24 long term. Hypokalemia and acidosis occurred not only after ingestion of very high doses but also after ingestion of moderately high or even normal doses of ibuprofen. Laboratory values consistent with an excessive urinary potassium excretion or an altered urinary acidification were often disclosed in most cases. Discontinuation of ibuprofen resulted in a resolution of hypokalemia and acidosis within days in 47 cases. The course was lethal in 3 cases. Relevance to Patient Care and Clinical Practice: This review highlights potentially fatal side effects of ibuprofen and can help doctors who are confronted with such a situation. Conclusions: These data highlight the potential of ibuprofen to occasionally induce hypokalemia and acidosis of renal origin. Discontinuation of ibuprofen results in a resolution within days.

Transient tunnel vision and altered consciousness after a single dose of ibuprofen

“… 8 A recent review discussing ibuprofen-induced hypokalemia and metabolic acidosis showed that in the case of acute ingestion, an altered state of consciousness is a major feature, even in patients with intake of a normal dosage. 9 A further argument for ibuprofen as the causative agent in the present case is that visual impairment has been previously described in cases of ibuprofen overdose. 10 Furthermore, visually-evoked potentials may show prolonged latencies and reduced amplitudes in patients with ibuprofen overdose.…”

“… 12 Disregarding these severe side effects, discontinuation of ibuprofen usually results in complete resolution of the conditions described above. 9 …”

“… 14 Whether hypokalemia and renal tubular acidosis caused by distal tubular dysfunction were involved in the pathophysiology of the described side effects remains speculative, but an inability to decrease the urine pH to less than 6, as has been found in several cases, argues in favor of this speculation. 9 …”

Ibuprofen-Induced Renal Tubular Acidosis: Case Report on a Not-So-Basic Clinical Conundrum

“…Ibuprofen has been previously linked to hypokalemia and RTA. [10][11][12][13][14][15] A recent systematic review 12 found 50 reported cases of patients with profound hypokalemia and/ or acidosis after ibuprofen use and most cases had evidence of impaired urinary acidification or renal potassium wasting. Notably, this review found 3 lethal cases and that hypokalemia and acidemia were also seen at doses generally regarded as safe (<40 mg/kg of body weight).…”

Evaluating NSAIDs in SARS-CoV-2: Immunomodulatory mechanisms and future therapeutic strategies

“…Acquired distal renal tubular acidosis (RTA) is associated with the use of NSAIDs, characterized by impaired distal acidification of urine due to a reduction in net hydrogen ion secretion in the distal nephron. The primary mechanism by which NSAIDs like ibuprofen induce metabolic acidosis is linked to their impact on renal function, specifically affecting renal tubular processes [ 111 ]. It has been observed that ibuprofen, a commonly utilized NSAID, is associated with the development of hypokalemia and metabolic acidosis.…”