Abstract
BACKGROUND: Viral bronchiolitis remains a significant cause of hospitalization as well as morbidity and mortality during the first year of life, with treatment options beyond supportive care being limited. In cases of severe illness, ribavirin may offer therapeutic benefit. OBJECTIVE: We report the use of intravenous (IV) ribavirin in an infant requiring concomitant venovenous extracorporeal membrane oxygenation (VV-ECMO) and continuous venovenous hemofiltration (CVVH) for respiratory syncytial virus (RSV) and parainfluenza virus (PIV) coinfection. PATIENTS AND METHODS: A 5-week-old male former 33-week preterm infant was admitted with respiratory failure and subsequently tested positive for RSV and PIV-type 1 infection. Progressive clinical deterioration subsequently required the initiation of both VV-ECMO and CVVH. Although the patient received combined VV-ECMO and CVVH, IV ribavirin was administered, and serial plasma and ultrafiltrate samples were obtained for pharmacokinetic analyses after the first dose (collection period 1) and again after an estimated 5 half-lives (collection period 2). RESULTS: Pharmacokinetics for collection period 1 demonstrated a calculated C(max) of 11.99 mg/L, an AUC(0-24) of 43.32 mg·hr/L, k(e) 0.26 hr(-1), t½ 2.69 hr, Vd 10.04 L (2.92 L/kg, using patient's dosing weight 3.43 kg), CL(T) 43.47 mL/min, and CL(CVVH) 6.75 mL/min. Pharmacokinetics for collection period 2 demonstrated a calculated C(max) of 10.31 mg/L, AUC(0-6) of 52.55 mg· hr/L, k(e) 0.06 hr(-1), t½ 10.69 hr, Vd 17.5 L (5.1 L/kg), and CL(T) 17.44 mL/min. The sieving coefficient during collection period 1 was 1.17 (range, 1.07-1.37). The percent decline between prefilter and postfilter oxygenator was 19.1%. CONCLUSION: Our patient demonstrated therapeutic concentrations of ribavirin, despite drug removal via CVVH and the ECMO oxygenator. Standard ribavirin dosing used and resultant concentrations achieved were associated with viral clearance and clinical improvement.