Limited data exists regarding antivirals and extracorporeal membrane oxygenation (ECMO). We present a case of pharmacokinetics (PK) of ganciclovir in an immunocompromised patient with respiratory failure requiring veno-venous ECMO support without continuous renal replacement therapy (CRRT). A 6 year old with a stage IV rhabdoid tumor s/p autologous bone marrow transplant rescue after chemotherapy 80 days prior to illness, developed acute respiratory failure. Patient was started on cefepime, vancomycin, trimethoprim/sulfamethoxazole, ganciclovir and micafungin. On day (D) 7 of ICU stay, ECMO initiated due to concerns for air leak syndrome. Bronchoalveolar lavage on D8 resulted positive for Pneumocystis and CMV by PCR. Prior to ECMO initiation, CMV levels were <500 IU/mL. After the initiation of ECMO, patient had up-trending CMV PCR that peaked at 139,000 IU/mL with concerns for antiviral resistance or ganciclovir underdosing (5mg/kg/dose) on ECMO.
Peak and random plasma levels to calculate AUC24 were drawn after concerns for under dosing on ICU D16/ECMO D9. Ganciclovir concentrations were determined by HPLC in the Special Chemistry Department at Cincinnati Children’s Hospital Medical Center. After dose adjustments on ICU D17/ECMO D10, repeat peak/random levels were obtained on ICU D19 after steady state was achieved.
Ganciclovir dosing of 5mg/kg every 12 hours was subtherapeutic, both clinically and based upon PK analysis. 0.5 and 5 hour post infusion levels were 5.47 mcg/ml and 0.76 mcg/ml respectively with a calculated AUC24 to be 26 mg hr/L. After increasing the dose to 10 mg/kg every 12 hour, repeat levels at 1 and 5 hours were 4.53 mcg/ml and 1.48 mcg/ml respectively, achieving the AUC24 goal of 50 mg hr/L.
This is the first case report of ganciclovir PK in either pediatric or adult ECMO populations. Standard recommended dosing of 5mg/kg every 12 hours provided a low, subtherapeutic AUC24 with increased CMV viral load. With dose increase to 10 mg/kg, targeted AUC24 of 50 for ganciclovir was achieved; clinically, CMV viral loads decreased and remained suppressed. Higher doses of ganciclovir may be required in ECMO patients, especially without concurrent CRRT, although further pharmacokinetic/pharmacodynamic studies are needed in these critically-ill patients.
A. Chamberlain, None