Pediatric cardiovascular drug dosing in critically ill children and extracorporeal membrane oxygenation.

Cardiovascular disease in children is common and results in significant morbidity and mortality. The sickest children with cardiovascular disease may require support with extracorporeal membrane oxygenation (ECMO), which provides life-saving assistance for children with refractory cardiorespiratory failure. Many classes of cardiovascular drugs are used in children, but very few of these agents have been well studied in children. The knowledge gap is even more pronounced in children supported by ECMO. Pharmacokinetic (PK) data collected to date (primarily from antibiotics and sedatives) suggest that the ECMO circuit has the potential to significantly alter the PK of drugs including changes in clearance and volume of distribution. Of all cardiovascular drugs administered to children supported by ECMO, only 11 have been partially studied and reported in the medical literature. Esmolol, amiodarone, nesiritide, bumetanide, sildenafil, and prostaglandin E1 seem to require dosing modifications in children supported by ECMO, whereas it seems that hydralazine, nicardipine, furosemide, epinephrine, and dopamine can be dosed similarly to children not supported by ECMO. However, trials evaluating the PK of these drugs in patients supported by ECMO are extremely limited (ie, case reports), and therefore, definitive dosing recommendations are not plausible. Research efforts should focus on evaluating the PK of drugs in patients on ECMO to avoid therapeutic failures or unnecessary toxicities.