Purpose: To characterize the pharmacogenomic response of low-dose haloperidol for delirium treatment in critically ill adults. Materials and methods: Single-center, pilot study of a convenience sample of ICU adults with delirium treated with low-dose IV haloperidol. Patients were evaluated for delirium with the ICDSC every 8 h. Serum haloperidol concentrations were collected on ICU days 2–6, CYP2D6 and CYP3A4 genotypes were characterized and patients were categorized as extensive (EM), intermediate (IM) or poor metabolizers (PM). Results: The 22 patients (median age 67 [IQR 48,77] years; median APACHE III 81[IQR 54,181]; CYP2D6 [EM = 12, IM = 7, PM = 3], CYP3A [EM = 18, IM = 4]) received a median [IQR] daily haloperidol dose of 3.0 [2.4, 4.5] mg. After adjusting for age, SOFA, and ICU day, neither an association between CYP2D6 (IM p = .67/PM p = .25) or CYP3A4 (IM p = .44) metabolizer status and serum haloperidol concentrations was found. After adjusting for age, SOFA, and ICU day, neither an association between daily haloperidol dose (p = .77) or ICDSC score (p = .13) and serum haloperidol concentrations was found. No patient experienced QTc interval prolongation (≥500 ms). Conclusions: This pilot study, the first to evaluate the pharmacogenomic response of low-dose haloperidol when used to treat delirium in the ICU, suggests CYP2D6/CYP3A4 metabolizer status does not affect the serum haloperidol concentrations.

Delirium, Haloperidol, Intensive care, Pharmacodynamics, Pharmacogenetics, Pharmacokinetics
dx.doi.org/10.1016/j.jcrc.2020.03.001, hdl.handle.net/1765/125718
Journal of Critical Care: improving patient care by integrating critical care systems knowledge into practice behavior
Department of Intensive Care

Trogrlić, Z, van der Jagt, M, Osse, R.J, Devlin, J.W. (John W.), Nieboer, D, Koch, B.C.P, … Hunfeld, N.G.M. (2020). Pharmacogenomic response of low dose haloperidol in critically ill adults with delirium. Journal of Critical Care: improving patient care by integrating critical care systems knowledge into practice behavior, 57, 203–207. doi:10.1016/j.jcrc.2020.03.001