Caffeine Citrate: An Alternative to Theophylline for Apnea in Prematurity

TOTHEEDITOR: Pentamidine isethionate is now available commercially for the treatment of Pneumocystis carinii pneumonia. The use of pentamidine has risen sharply with increasing incidence of acquired immunodeficiency syndrome (AIDS) patients presenting with Pneumocystis infection.' The drug has been associated with many adverse effects. Hypotension, azotemia, leukopenia, nausea, vomiting, and hypoglycemia are reported frequently.'> When given intramuscularly, pain, swelling, and sterile abscesses at the injection site have been known to occur." We report the case history of a patient who sustained significant sciatic nerve damage after repeated intramuscular injections of pentamidine. A 36-year-old, previously healthy, homosexual male was admitted with a two-week history of shortness of breath, fever, diarrhea, and significant weight loss. On physical examination, he appeared thin and in respiratory distress, with a blood pressure of 118/64 mm Hg, pulse 108/min and regular, and respiratory rate 36/min. His oral temperature was 104.8°F. An examination of his mouth revealed a white exudate over the entire mucosa. The remainder of the physical examination, including the lungs, was unremarkable. Laboratory tests revealed: hemoglobin 14.5 g/dL; white cell count 8.5 x 1(}'/mm with 54070 segmented neutrophils, 4070 banded neutrophils, 27070 lymphocytes, 4070 atypical lymphocytes, 7070 monocytes, 3070 eosinophils, and 1070 basophils. Arterial blood gases on room air showed: pH 7.46, Paco, 33 mm Hg, Pao, 42 mm Hg, and HCOi 23 mEq/L. Other laboratory values were within normal limits. A Gram-stain of the oral mucosal exudate showed yeast and hyphal forms suggestive of candida. The patient's chest X-ray revealed diffuse bilateral interstitial infiltrates and hilar lymphadenopathy. The patient was admitted to the intensive care unit where he was intubated and trirnethoprimsulfamethoxazole (TMP/SMX) was begun empirically. Fiberoptic bronchoscopy with brushings and transbronchial biopsy were negative. A silver-stain of an open-lung biopsy specimen demonstrated P. carinii. After II days of TMP/SMX, the patient developed a maculopapular rash on his face, which progressed to involve his trunk, back, and extremities. TMP/SMX was discontinued and pentamidine isethionate was substituted. Pentamidine 250 mg (4 mg/kg) was reconstituted in 3 ml sterile water and given as a single, intramuscular injection in the gluteal region once daily. All intramuscular injections were given into the left buttock, as the patient preferred to lie on his right side following left-lung biopsy. With treatment, the patient became afebrile and his respiratory status gradually improved. He was discharged after 14days of pentamidine therapy. Four days after discharge, the patient noted a dull ache in the left buttock radiating down the posterior side of his thigh. The pain increased with walking or lying on the affected side. As of six weeks after discharge the patient had not returned to work because of persistent pain. His entire left lower extremity showed marked wasting with decreased sensation over the buttock. However, no redness, warmth, or mass was noted over the site of pentamidine injections, but his knee and ankle reflexes on the left side had diminished considerably. Further follow-up four months after discharge revealed a lessening of pain in the last few weeks and a return of muscle strength in the left lower extremity. This suggests that the neurologic damage is transient, although the follow-up is not sufficient to detect permanent sequelae. Due to an increased incidence of serious allergic reactions to TMP/SMX in AIDS patients,' the use of pentamidine as an alternative agent has increased in recent years. Intramuscular administration of pentamidine is recommended by the Centers for Disease Control (CDC), unless otherwise contraindicated. Recently, however, the CDC analyzed information from practitioners who gave pentamidine by the intravenous route." Hypotension, noted in the past with slow intravenous injections," was not encountered when pentamidine was diluted in 5070 dextrose 50-100 ml and given over at least 60 minutes. Moreover, adverse reactions occurred with similar frequency for both administration routes. Many hospitals continue to administer pentamidine by the intramuscular route. Although not unique to pentamidine, sciatic nerve damage, particularly in cachectic patients with little muscle mass, should be added to the list of possible adverse effects following the intramuscular route. According to the manufacturer, the dose should be dissolved in no more than 3 ml of sterile water to minimize the volume for injection. The potential for neurologic damage from pentamidine may be lessened considerably by dividing each dose into two injections and by using alternate sites. L. MARIA GUTSCHI, Pharm.D. Clinical Pharmacist Department of Pharmacy Services PRANATHARTHI H. CHANDRASEKAR, M.D. Assistant Professor of Internal Medicine Division of Infectious Diseases Detroit Receiving Hospital and University Health Center 4201 St. Antoine Detroit, Michigan 48202