DOES RIBAVIRIN IMPACT ON THE HOSPITAL COURSE OF CHILDREN WITH RESPIRATORY SYNCYTIAL VIRUS (RSV) INFECTION - AN ANALYSIS USING THE PEDIATRICINVESTIGATORS COLLABORATIVE NETWORK ON INFECTIONS IN CANADA (PICNIC) RSV DATABASE

Objectives. To determine the relationship between receipt of aerosoliz ed ribavirin and the hospital course of high-risk infants and children with respiratory syncytial virus (RSV) lower respiratory infection (L RI). Methods. The 1993-1994 Pediatric Investigators Collaborative Netw ork on Infections in Canada (PICNIC) RSV database consists of prospect ively enrolled children with acute RSV LRI, admitted to nine Canadian pediatric tertiary care centers. After excluding cases with compromise d immunity and/or nosocomial infection, subsets with any congenital he art disease (CHD), chronic lung disease (CLD), age 6 weeks (INFANT), g estation 36 weeks (PREM), or severe disease within 48 hours of admissi on as shown by an oxygen saturation 90% or an FiO(2) requirement of >. 35 (EARLY HYPOXIA) were studied in two ways. First, each risk group su bset was analyzed separately to assess the association between ribavir in receipt and measures of disease severity including duration of inte nsive care, mechanical ventilation, hypoxia and RSV-attributable hospi tal stay. Secondly, ribavirin was added as an independent variable to a previously described multiple regression model for RSV-attributable length of hospital stay and two mutually exclusive subsets were analyz ed: 1) previously healthy patients with 1 of: INFANT, PREM, or EARLY H YPOXIA; 2) patients with CHD and/or CLD. Results. Between January 1993 and June 1994, 1425 community-acquired hospitalized cases of RSV LRI were entered into the RSV database. Among these 750 (52.6%) fit into o ne or more of the defined subsets including 97 CHD, 134 CLD, 213 INFAN T, 211 PREM, and 463 EARLY HYPOXIA. The proportion ventilated in each group was 20.6%, 20.9%, 15.5%, 15.2%, and 13.3%, respectively. Across the subsets ribavirin use ranged from 36% to 57% of ventilated patient s and 6% to 39% of nonventilated patients. For nonventilated patients in each subset the median RSV-attributable hospital length of stay (RS V-LOS) was 2 to 3 days longer for ribavirin recipients and the duratio n of hypoxia was significantly increased. Duration of intensive care u nit (ICU) stay was also increased for all ribavirin-treated subgroups except those with CHD. In contrast, for ventilated patients, ribavirin therapy was not significantly associated with any of the outcome meas ures regardless of risk group. In the multiple regression model, ribav irin was significantly associated with a prolonged RSV-LOS both for ch ildren with CHD and/or CLD as well as for those whose only risk factor s included INFANT, PREM, and/or EARLY HYPOXIA. Conclusions. These data raise further doubts about the clinical effectiveness of ribavirin in infants and children with risk factors for severe disease. Selection bias, with ribavirin used for sicker children, may have influenced out come. Nevertheless the long durations of hospitalization, ICU, ventila tion, and oxygen supplementation in nonventilated ribavirin recipients stress the need for further randomized trials to assess its efficacy.