Correspondence
Transient Renal Failure Due to Simultaneous Ibuprofen and Aminoglycoside Therapy in Children with Cystic Fibrosis
N Engl J Med 1998; 338:65-66January 1, 1998
- Article
To the Editor:
Ibuprofen can retard the decline in pulmonary function in children with cystic fibrosis.1 Aminoglycosides are often given to treat pulmonary infections in children with cystic fibrosis. Both ibuprofen and aminoglycosides are nephrotoxic. We have seen four children with cystic fibrosis who had transient renal failure during exacerbations of their lung disease that we believe was caused by the intravenous administration of an aminoglycoside while maintenance treatment with ibuprofen was continued.
The first patient was a 16-year-old girl with severe lung disease in whom nausea and vomiting developed six days after admission and the commencement of therapy with intravenous tobramycin for exacerbation of her lung disease. She received furosemide for peripheral edema, and oliguria developed the next day. Her serum creatinine concentration rose from 0.5 mg per deciliter (48 μmol per liter) at the time of admission to 2.8 mg per deciliter (249 μmol per liter) six days later. The ibuprofen and tobramycin were discontinued, and the serum creatinine concentration was 0.8 mg per deciliter (74 μmol per liter) two days later. The maximal serum tobramycin concentration was 27 mg per milliliter. The patient died nine days later of lung disease; minimal tubulointerstitial nephritis was seen at autopsy.
The second patient was a 10-year-old girl with moderately severe lung disease in whom nausea, vomiting, and abdominal cramps developed two days after admission and the initiation of therapy with intravenous gentamicin for exacerbation of her chronic lung disease. She was found to have a supratherapeutic peak serum gentamicin concentration of 16 mg per milliliter, and her serum creatinine concentration had increased from 0.7 mg per deciliter (64 μmol per liter) at the time of admission to 2.4 mg per deciliter (211 μmol per liter). The ibuprofen and gentamicin were discontinued, and her serum creatinine concentration was 0.9 mg per deciliter (82 μmol per liter) five days later.
The other two patients were twin 23-month-old brothers who were hospitalized simultaneously for exacerbations of chronic lung disease. Both patients were treated with intravenous gentamicin. The ibuprofen they were taking before admission was inadvertently continued, despite the existence of a policy of stopping ibuprofen during hospitalization if aminoglycoside therapy was given. This policy was instituted as a result of the first two cases. One twin began vomiting four days after admission. Ibuprofen was discontinued nine days later, but lethargy, increased vomiting, and periorbital edema occurred the next day, followed by generalized edema and oliguria. The child's serum creatinine concentration rose from 0.2 mg per deciliter (20 μmol per liter; measured 3 months earlier) to 5.2 mg per deciliter (460 μmol per liter) 16 days after admission. He received peritoneal dialysis for eight days, by which time urine output was normal and his serum creatinine concentration was 0.4 mg per deciliter (32 μmol per liter). The other brother had a transient asymptomatic increase in the serum creatinine concentration, from 0.6 mg per deciliter (49 μmol per liter) at admission to 1.5 mg per deciliter (134 μmol per liter) 18 days later. In both cases, subsequent audiologic testing had normal results, although the more severely affected brother had transient ataxia.
Our observations suggest that the combination of intravenous aminoglycoside and ibuprofen can cause acute renal insufficiency. We have not seen this complication with ibuprofen alone or with ibuprofen and nebulized tobramycin.2 Aminoglycoside-induced toxicity is potentiated by extracellular volume depletion,3 and ibuprofen and other nonsteroidal antiinflammatory drugs interfere with the intrarenal production of prostaglandin E2 and prostacyclin, which cause renal vasodilatation in the presence of reduced circulating volume.4 Our findings suggest that ibuprofen should be stopped during intravenous aminoglycoside therapy.
4 ReferencesThomas A. Kovesi, M.D.
Ronald Swartz, B.Sc.Phm.
Noni MacDonald, M.D.
Children's Hospital of Eastern Ontario, Ottawa, ON K1H 8L1, Canada1
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