Massive Diflunisal Overdosage with Recovery

Editor's note: Amen, Nurse Ferris. We, the Editors, will join your four-point campaign. To the Editor: — In our review of the literature, we have been able to find a single case of diflunisal overdose in which a 47-year-old woman ingested 29 grams of diflunisal over 40 minutes, became comatose for 10 hours, but had no other ill effects and made a complete recovery.1 In this letter, we report a case of a patient who suffered a severe fall and subsequent accidental overdose of diflunisal. A healthy 82-year-old woman, with previously normal CBC and creatinine, fell while leaving a bus. She complained of severe right leg pain, but x-rays of the right leg and hip at an emergency room did not reveal a fracture. Diflunisal, 500 mg every 12 hours, was prescribed for pain and she was told to rest. A local pharmacist filled the prescription with instructions to take one tablet every two hours for pain, which she did over the next 40 hours. She noted drowsiness, fatigue, dizziness, tinnitus, nausea, anorexia, decreased cognition, and loose black stools. On admission to our hospital, three days after her fall, physical examination revealed a somnolent, elderly white female, with bibasilar rales on lung exam, a nontender abdomen with guaiacpositive stools, and an exquisitely tender right thigh and calf which were without warmth, swelling, or erythema. Laboratory tests revealed elevated SGOT of 519 U/L, SGPT of 134 U/L, LDH of 1696 U/L, WBC 33,900 with a left shift, hematocrit 20.8, normal platelet count and coagulation times, BUN 102, and creatinine 5.0. Urinalysis revealed rare hyaline and waxy casts and moderate granular casts but no protein and only 1-5 RBC/hpf. A 24-hour urine collection showed a creatinine clearance of 5 mL/min, total protein excretion of 0.5 g/d, and fractional extraction of sodium of 5%. Urine myoglobin and urinary eosinophils from admission were negative. A renal ultrasound revealed no urinary obstruction. During the second hospital day, pelvic films revealed a fracture of the right superior pubic ramus and she was kept on bed rest. Her course was complicated by her refusal of transfusion, a pulmonary embolus, repeated episodes of bleeding during attempts at anticoagulation, and hypotension and dysrhythmias during dialysis, which made the procedure ineffective. Over the next 21 days, she was profoundly weak with a poor mental status, and was supported with conservative measures including a Clinitron bed, physical therapy, tube feedings, and minimal phlebotomy. By hospital day 27, her hematocrit was 18.9 with a near normal WBC and the BUN was 24 with a creatinine of 1.1. She finally decided to accept blood transfusions and her hematocrit was raised to 35. An upper GI series revealed diffuse gastritis. Because of a right peroneal nerve palsy which was noted in the recovery phase of her hospital course, she was transferred to a rehabilitation center on day 42. The dose ingested was approximately 12 times that recommended for this age group (500 mg loading dose followed by 250 mg every 12 hours).2 The peak concentration would be at least an order of magnitude greater than normal and it would require a minimum of eight days to return to typical therapeutic levels.3 The drug presumably contributed to her symptoms of tinnitus, dizziness, decreased cognition, black stools and antral gastritis, and hepatitis.4,5 Although coagulation studies were normal (bleeding time not done), the episodes of bleeding with controlled anticoagulation implied a drug interference with platelet function and thrombus formation.2 With respect to the renal failure, no renal biopsy was performed; therefore, the pathology cannot be compared to previously published cases of renal failure resulting from chronic diflunisal use.6,7 Although we cannot rule out hypotension as a contributing factor, it is more likely that she suffered acute tubular necrosis secondary to the diflunisal itself. This case points out the reversibility of most of the complications brought on by diflunisal overdose in the setting of a pelvic fracture. With the exception of a mild noncholestatic hepatitis and a right peroneal nerve palsy, the patient recovered completely from the overdose.