Notwithstanding the absence of robust evidence to justify the use of antipyretic analgesics either for reducing patient discomfort or for reducing morbidity and mortality in febrile illnesses(1), it is only in recent times(2)(3) that the issue of drug-related mortality has been adressed in patients receiving either nonsteroidal anti-inflammatory drugs(NSAIDs) or paracetamol for febrile illnesses. Due to insensible losses via the skin and also via the respiratory tract, patients with pneumonia seem to be uniquely predisposed to NSAID-related nephrotoxicity, as was the case in a five year old girl who received recommended doses of ibuprofen(presumably for its antipyretic action) over a period of 4 days before she developed acute renal failure, characterised by peak serum creatinine 171 mcmol/l, and peak serum urea 23 mmol/l. Following the discontinuation of ibuprofen these parameters took 3 days to revert to the normal range(4). Both hepatitis and non-oliguric renal failure were the cardinal complications of the administration of paracetamol, followed by ibuprofen, in a 5 year old girl with febrile convulsions and vomiting. The former was prescribed as 11 mg/kg/dose, two total doses, over 5 hours. This was followed by ibuprofen 5 mg/kg/dose every 8 hours, three total doses. Both drugs were administered by mouth. Although her renal function tests and liver function tests had been within the normal range on admisssion, on day six aspartate transaminase and gammaglutamyl transaminase had increased to 144 iu/l, and 1394 iu/l, respectively. Correspondigly, serum urea and serum creatinine had increased to 67.9 mg/dl and 6.34 mg/dl, respectively. By day 60 all the abnormal parameters had reverted to the normal range(5). In the non febrile context, recommended doses of paracetamol administerd to adult patients over a period of 4-5 days, have been documented as being the cause of acute liver failure(6). Accordingly, especially in the context of febrile illnesses where insensible loss of fluid via the skin is compouded by fluid loss via the respiratory tract(as in pneumonia)(4) or compouded by fluid loss via the gastrointestinal tract as in the second case(5), there should be a high index of suspicion for subsequent development of renal failure. Where paracetamol is administered to patients with poor nutritional status, clinicians should be alert to the risk of drug-related hepatotoxicity(6) References (1) Greisman L., Mackowiak PA Fever: beneficial and detrimental effects of antipyretics Current Opinion in Infectious Diseases 2002;15:241-5 (2) Plaisance Toxicities of drugs used in the management of fever Clinical Infectious Diseases 2000;31(Suppl 5): S219-23 (3)Jefferies S., Weatherall M., Young P., Eyers S., Beasley R Ssystematic review and meta analysis of the effects of antipyretic medications on mortality in Streptococcus Pneumoniae infections Postgraduate Medical Journal 2012;88:21-27 (4)Ulinski T., Guigonis V., Dunan O., Bensman A Acute renal failure after treatment with nonsteroidal antiinflammatory drugs Eur J Pediatr 2004;163:148-150 (5) Zaffanello M., Brugnara M., Angeli S., Cuzzolin L Acute non-oliguric kidney failure and cholestatic hepatitis induced by ibuprofen and acetoaminophen: a case report Acta Paediatrica 2009;96:901-9 (6)Claridge LC., Eksteen B., Smith A., Shah T., Holt AP Acute liver failure after administration of paracetamol at the maximum recommended daily dose in adults BMJ 2010;341:1269-1271

Conflict of Interest:

None declared