Intravenous Ribavirin for Parainfluenza and Respiratory Syncytial Virus in an Infant Receiving Extracorporeal Membrane Oxygenation and Continuous Renal Replacement Therapy

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.

Keywords: extracorporeal membrane oxygenation; paramyxoviridae infections; prematurity; renal dialysis; respiratory syncytial virus; ribavirin.

Figure 1.

Response of RSV and PIV viral load to IV ribavirin as reported by PCR cycle time by hospital day and treatment modality. Cycle time indicates the number of PCR cycles needed to detect the virus (less number mean high viral load and vice versa).

Figure 2.

Measured and extrapolated plasma ribavirin versus time profile for collection period 1. Time points hours 0 through 6 are observed. Time points hours 8 through 24 are extrapolated.