Furosemide-associated fever

EDITORIAL CORRESPONDENCE

Hemolysis after treatment with ceftriaxone To the Editor: We read with interest the reports of acute, fatal hemolysis after administration of ceftriaxone. We have also seen an unexplained, fatal cardiovascular collapse in a young child immediately after the administration of the drug. As with the cases recently reported, our patient also had a chronic hematologic disorder and had been previously treated with cephalosporin antibiotics without apparent reaction. A 3-year-old girl with hypereosinophilic syndrome was evaluated for dian'hea and dehydration. Her course had been complicated by interstitial pneumonitis that improved after treatment with vincrisfine and corticosteroids. An intestinal perforation developed, which required surgical repair, at which time cefotetan was administered without adverse effect. A diagnosis of otitis media was subsequently made; the girl was treated with amoxicillin and may have had an urticarial rash during the course of this treatment. She subsequently had acute onset of diarrhea, poor oral intake, clinical dehydration, acidosis, and listlessness. The whole blood cell count was 45.5 x 109/L (45,500/mm3) with 41% polymorphs, 16% bands, 10% lymphocytes, 2% monocytes, and 30% eosinophils. The hematocrit was 0.29; the hemoglobin level was 90 gn~_~ with reticulocytes of 2.6%; the platelet count was 312 x 109/1, (312,000/ ram3). Rehydration was begun intravenously. Because of a temperature of 39 ° C and her clinical condition, concern was raised about possible sepsis and cefiriaxone (75 mg/kg) was administered after appropriate cultures were obtained. After 5 minutes, extreme pallor with hypotension developed and the girl became unresponsive with no respk, atory distress, stridor, apparent bronchospasm, or rash. She was resuscitated, treated with intravenous fluids, vasopressor agents, and received 200 ml of packed e~2cthrocytes. After this treatment the hematocrit was 0.19 and the lactate dehydrogenase concentration was 901 U/L, increasing to 3690 U/L after 5 hours. The serum and urine were pink in color, but testing for hemoglobin was not done. The results of direct and indirect Coombs tests were negative and blood was unavailable for further antibody identification. Amikacin and clindamycin were substituted but no pathogens were identified. Oliguria soon developed along with clinical and laboratm~ evidence of consumptive coagulopathy, and the child died. Our patient had an uncommon, premalignant, chronic condition with superimposed clinical dehydration necessitating intravenous rehydration. She was examined by several physicians who did not perceive her to be acutely ill, yet she had a complete cardiovascular collapse within minutes of receiving intravenously administered ceftriaxone. We did not uncover any evidence to support a diagnosis of sepsis or anaphylaxis, and it is possible that our patient had acute, severe hemolysis as a result of the ceftriaxone administration.

The Journal of Pediatrics

The rapid onset of pallor with moderately severe anemia despite transfusion, along with oliguria, consumptive coagulopathy, and biochemical evidence consistent with massive hemolysis support this possibility. Our recent practice is to substitute other effective antibiotics whenever possible for our patients. Until further information becomes available, we believe that clinicians should carefully reconsider the use of ceftriaxone for patients with chronic hematologic disorders; this adverse effect has so far been reported only in this patient population.

Philip G. Scimeca, MD Mark E. Weinblatt, MD Robert Boxer, MD Department of Pediatrics North Shore University Hospital Manhasset, NY 11040 9/35/68308

REFERENCES l. Bemini JC, Mustafa MM, Sutor LJ, Buchanan GR. Fatal hemolysis induced by ceftriaxone in a child with sickle cell anemia. J PEDLA.TP.1995; 126:813-5. 2. Lascari AD, Amyot K. Fatal hemolysis caused by ceftriaxone. J P~DIATR 1995;126:816-7.

Furosemide-associated fever To the Editor: Clegg and Riopel 1 described a case of prolonged fever associated with furosemide treatment in an 11-week-old i~ffant. During the last 10 years, we have seen at least three similar cases of prolonged fever associated with fnrosemide treatment that resolved only after the discontinuation of the drug. All three patients had some common clinical features that may help in recognizing these unusual reactions. All affected patients were infants in the first year of life and had congestive heart failure as a result of congenital anomalies or cardiomyopathy. The fever was usually high, ranging from 38.5 ° C to 40 ° C, and resembled "septic fever." All three infants also were treated with digoxin. Results of physical examination for the source of the fever, chest x-ray studies, blood cell counts, and blood cultures were all normal. Discontinuation of the farosemide was followed by disappearance of the fever within 1 to 2 days. Our first two patients had the same exhaustive evaluation as described by Clegg and Riopel; only in the third case did we assume that the fnrosemide was the cause; as soon as the diuretic treatment was changed to hydrochlorothiazide and spironolactone, the fever disappeared within 24 hours.

January 1996

163

164

Editorial correspondence

Reintroduction of the furosemide in the third patient 2 weeks later resulted in the recurrence of the"septic fever" after 3 days. No allergic manifestations such as skin rash, edema, respiratory symptoms, arthritis, or eosinophilia in the blood count were observed. Use of furosemide in lower doses and on alternate days was tried, and there was no fever. The mechanism of the fever associated with furosemide in this group of infants is unclear but seems to be dose related. Consideration of this possibility may save unnecessary laboratory studies, and in mm will lead to the early resolution of the patient's problem. Jacob Amir, MD Itzhak Varsano, MD Department of Pediatrics ' 'C" Schneider Children's Medical Center of Israel Sackler School of Medicine, Tel Aviv University Petah Tiqva, Israel 9/35/69309

REFERENCE 1. Clegg HW, Riopel DA, Furosemide-associated fever. J PEDIATR 1995;126:817-8.

Nutrition via gastrostomy tube in children with cancer To the Editor: I read with interest the article by Aquino et aL 1 describing gastrostomy tube (GT) feedings for children with cancer. In their cost analysis they did not include the cost of placing the GT, which includes a hospital cost, anesthesia cost, surgeon and/or gastroenterologist cost, and cost of GT/percutaneous endoscopic gastrostomy kit. The argument that this is comparable to placement of a central venous line is not justified; most cancer patients have placement of a central venous line regardless of whether a GT is placed. One could make the argument that using a central venous line for total parenteral nutrition increases the risk of infection and occlusion, resulting in more frequent changes and therefore increased cost. Patients receiving chemotherapy are at an increased risk of problems with chronic vomiting, esophagitis, and even Barrett esophagus.2 To increase that risk even more by altering the anatomy of the stomach with a GT is a bit concerning. Finally, cancer patients go through enough body image changes as a result of chemotherapy and radiation. To add one more insult may be too much for parents and children. With all that said, it is well established that a functional gastrointestinal tract should be the preferred route of nutrition. Barry Z. Hirsch, AID Pediatric Gastroenterology Baystate Medical Center Springfield, MA 01107 9/35/68985

The Journal of Pediatrics January 1996 REFERENCES 1. Aquino VM, Smyrl CB, Hagg R, McHard KM, Prestridge L, Sandier ES. Enteral nutrition support by gastrostomy tube in children with cancer. J PED~TR 1995;127:58-62. 2. Dahms BB, Greco MA, Strandjord E, Rothstein FC. Barrett's esophagus in three children after antileukemia chemotherapy. Cancer 1987;60:2896-2900.

Reply To the Editor: The cost of placement of the gastrostomy tube was not included in our cost analysis because this was an analysis of monthly charges for totalparenteral nutrition versus enteral feedings. However, as we state in the discussion on page 61 " . . . most patients already have a central venous line, and this additional charge would not be encountered in those patients receiving TPN." This additional charge is approximately $5000. If we divide this cost over the average time that patients had gastrostomy tubes (10 months), the difference in cost would be $0.01/kcal of nutrition delivered. The difference in the average monthly cost of gastrostomy feedings and total parenteral nutrition (0.04 vs 0.35/kcal) still remains significant at the p