Therapeutic Drug Monitoring of Guanfacine for Sedation in a Patient on Extracorporeal Membrane Oxygenation and Continuous Venovenous Hemofiltration: Grand Round/A Case Study.

BACKGROUND Guanfacine, an enteral α2-adrenergic and imidazoline receptor agonist, has occasionally been described in critical care as an adjunctive agent for the management of delirium and suspected dexmedetomidine withdrawal. However, its pharmacokinetic behavior during venovenous extracorporeal membrane oxygenation (VV ECMO) combined with continuous venovenous hemofiltration (CVVH) has not been defined.

METHODS A 64-year-old man with severe COVID-19 pneumonia developed refractory hypoxemia, requiring VV ECMO and CVVH for multiorgan support. Enteral guanfacine 7 mg/d was initiated on day 14 to transition from dexmedetomidine sedation.

RESULTS Steady-state trough plasma and ultrafiltrate guanfacine concentrations of 3.2 and 0.5 ng/mL, respectively, were obtained on day 24, yielding a sieving coefficient of 0.16 and convective clearance of 0.267 mL/min. ECMO adsorption was negligible based on expected pharmacokinetic concentrations. The patient was decannulated from ECMO on day 30, and guanfacine was successfully tapered over 7 days without withdrawal symptoms occurring.

CONCLUSIONS In this patient, high-dose guanfacine achieved predicted plasma concentrations during concurrent VV ECMO and CVVH, with minimal extracorporeal clearance or circuit sequestration. These findings suggest that standard dosing is appropriate in similar patients and support the use of guanfacine as a viable transition agent during dexmedetomidine weaning. Prospective pharmacokinetic studies in ECMO-supported patients are warranted.