Life-threatening hypokalaemia associated with ibuprofen-induced renal tubular acidosis
Authors: Colin B Page, Paul A Wilson, Aidan Foy, Michael A Downes, Ian M Whyte and Geoffrey K Isbister
Published online: 6 June 2011
To the Editor: We read with interest the article by Ng and colleagues on life-threatening hypokalaemia associated with ibuprofen-induced renal tubular acidosis,1 and wish to present our own experience of four patients presenting to our hospital over a year (Box).
The patients all presented with biochemical signs of renal tubular acidosis with severe hypokalaemia and a normal anion gap metabolic acidosis from long-standing misuse of ibuprofen taken in combination with codeine from over-the-counter (OTC) medications. Patients 1 and 2 presented acutely with deliberate misuse that included an ibuprofen–codeine combination product. Both patients subsequently admitted to long-standing misuse of ibuprofen and codeine taken in combination. Patients 3 and 4 presented with constitutional symptoms and generalised weakness with a history of taking large amounts of an ibuprofen–codeine combination product. Both these patients required intensive care unit admission for central venous access and potassium replacement.
As in the case series by Ng and colleagues, there was no history to suggest gastrointestinal loss of potassium, and medication histories were negative for drugs known to cause intracellular potassium movement or potassium wasting (eg, diuretics). Ibuprofen cessation, potassium replacement and supportive care resulted in biochemical recovery in all four patients.
Opioid addiction appears to be the common thread reported by Ng et al and in our case series. Other case reports support this.2,3 Paracetamol taken in supratherapeutic doses is known to cause hepatotoxicity, and it appears that patients with opioid addiction may now be turning to ibuprofen–codeine combination products. More evidence of the danger of these products comes from a case series reporting 27 patients with ibuprofen–codeine misuse that resulted in significant morbidity, including presentations for opioid dependence, gastrointestinal haemorrhage, hypokalaemia, anaemia and/or renal failure.4
In Australia, ibuprofen–codeine combination products are available OTC, albeit in restricted amounts due to problems related to codeine misuse.1 Further restrictions may need to be considered in light of the significant morbidity related to the ibuprofen component.
Baseline laboratory investigations and other characteristics of four patients with ibuprofen-induced renal tubular acidosis*
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RR = reference range. | |||||||||||||||
References
- Ng JL, Morgan DJR, Loh NKM, et al. Life-threatening hypokalaemia associated with ibuprofen-induced renal tubular acidosis. Med J Aust 2011; 194: 313-316.
- Ter A, Salha R, Vadamalai V, et al. Ibuprofen codeine combination precipitating severe hypokalaemia in a patient with pre-existing type 1 renal tubular acidosis. NDT Plus 2008; 1: 270-271. 0_i1096037
- Levine M, Khurana A, Ruha AM. Polyuria, acidosis, and coma following massive ibuprofen ingestion. J Med Toxicol 2010; 6: 315-317. 0_i1096039
- Frei MY, Nielsen S, Dobbin MDH, Tobin CL. Serious morbidity associated with misuse of over-the-counter codeine–ibuprofen analgesics: a series of 27 cases. Med J Aust 2010; 193: 294-296. 0_i1096043