Results from the American Society for Gastrointestinal Endoscopy/U.S. Food and Drug Administration collaborative study on complication rates and drug use during gastrointestinal endoscopy.

We used data from the American Society for Gastrointestinal Endoscopy's computer-based management system to compare the rates of serious cardiorespiratory complications and death associated with the use of midazolam and diazepam. Data were analyzed from 21,011 procedures. Midazolam was used in 15,061 of these procedures, diazepam in 4,302, and neither in 1,648. We assessed benzodiazepine dose, concomitant drug administration, type of procedure, and selected patient characteristics in each of these three groups. No significant difference between these three groups were noted other than the fact that certain clinical centers tended to exclusively use midazolam, whereas others used both benzodiazepines. Reports of serious cardiorespiratory complications and death were uncommon, occurring in 5.4 and 0.3 per thousand procedures, respectively. Midazolam did not seem to place patients in this sample at greater risk for cardiorespiratory complications than diazepam. Concomitant use of narcotics and urgent and emergent procedures, however, did increase the risk of serious cardiorespiratory events.

Morbidity and mortality among low birth weight infants exposed to an intravenous vitamin E product, E-Ferol.

In April 1984, the US FDA was notified of an unusual clinical syndrome consisting of ascites, liver and renal failure, thrombocytopenia, and death among low birth weight infants exposed to an intravenous vitamin E preparation, E-Ferol. The product, which had not been tested for safety prior to marketing, was voluntarily withdrawn from the market in early April. To further investigate the reported associations, the FDA conducted a retrospective cohort study among seven neonatal intensive care units where the product had been used. Standardized abstraction forms were completed for infants admitted to a unit between Nov 1, 1983, and April 30, 1984. Included in the study were 379 infants weighing 2,000 g or less and surviving at least two days; 148 (39%) had been exposed to E-Ferol. Compared with the unexposed infants, the exposed infants were more likely to die and to have ascites, hepatomegaly, thrombocytopenia, and a combination of clinical events similar to the syndrome initially reported. We conclude that the use of E-Ferol in these neonatal intensive care units was associated with increased morbidity and mortality among exposed infants.

Monooctanoin-associated pulmonary edema.

Monooctanoin is a cholesterol solvent indicated for dissolution of retained biliary stones. We summarize four reports--one from the U.S. Food and Drug Administration's Spontaneous Reporting System for Adverse Drug Reactions and three from published medical literature--of noncardiogenic pulmonary edema during intrabiliary monooctanoin in the United States. Based on these data, we show that pulmonary edema during intrabiliary monooctanoin infusion may occur in approximately one per 1000 patients treated.

Severe soft-tissue injury following intravenous infusion of phenytoin. Patient and drug administration risk factors.

From April 8, 1982, through June 1984, 11 patients in a single hospital experienced 17 episodes of limb edema and discoloration after the intravenous (IV) administration of phenytoin sodium (Dilantin). One patient required a below-the-elbow amputation; all other patients recovered. No single drug lot was implicated. A case-control study was performed using three controls for each case; controls received IV infusions of phenytoin and were hospitalized close in time to the case patients. Compared with controls, patients with reactions were more often female and elderly and had underlying cardiovascular disease. Affected patients also received phenytoin through an IV catheter smaller than 20 gauge (50% vs 6%), at a rate greater than 25 mg/min (63% vs 19%), and in two or more IV infusions of phenytoin given "IV push" at the same site (81% vs 24%). High-risk patients require careful monitoring and stricter guidelines for the IV administration of phenytoin.

National patterns of aspirin use and Reye syndrome reporting, United States, 1980 to 1985.

The number of cases of Reye syndrome reported annually to the Centers for Disease Control declined markedly between 1980 and 1985. In this article, we present pharmaceutical marketing research data that suggest sharp decreases in the use and purchase of children's aspirin between 1980 and 1985. These trends appear to correspond to the decrease in reporting of Reye syndrome cases. Additionally, analysis of physician mentions of aspiring and acetaminophen for treating flu and chickenpox showed statistically significant trends toward decreasing recommendations for the use of aspirin and significant trends toward increasing recommendations for use of acetaminophen. Trends in wholesale purchases of aspirin and acetaminophen by drug stores from 1979 through 1985 demonstrated a significant decline for the 81-mg children's aspirin tablet and an increase in purchases of children's acetaminophen products. Many factors may influence physician and parents' choice of analgesic/antipyretic medication, including information about Reye syndrome. Data suggest that a continuing decline in the use of aspirin for children may be accompanied by a continuing decline in the reported number of Reye syndrome cases.

Adverse respiratory and cardiovascular events attributed to timolol ophthalmic solution, 1978-1985.

Between September 1978 and December 1985, 450 case reports of serious respiratory and cardiovascular events and 32 case reports of death attributed to ophthalmic timolol were received by the United States Food and Drug Administration and the National Registry of Drug-Induced Ocular Side Effects. Two hundred sixty-seven patients (55%) experienced a cardiac arrhythmia or a bronchospasm-related event. The median age was 68 years (n = 365). Fifty-five percent of the patients were women and 45% were men (n = 41). Of the 212 persons for whom medical history was provided, 129 (61%) had respiratory disease, 65 (31%) had cardiovascular disease, 13 (6%) had other illnesses, and five (2%) had no underlying illness. Of the 318 patients for whom data on duration of drug use were available 106 (33%) experienced their adverse event within one week of beginning timolol therapy: 73 (23%) had their events on the first day of therapy. Of 192 patients for whom information was available 177 (92%) improved after the drug was discontinued.