Study Objective Dexmedetomidine is titrated to achieve sedation in the pediatric and cardiovascular intensive care units (PICU and CVICU). In adults, dexmedetomidine response has been associated with an ADRA2A polymorphism (rs1800544); CC genotype is associated with an increased sedative response compared with GC and GG. To date, this has not been studied in children. Design We conducted a pilot study to determine whether ADRA2A genotype is associated with dexmedetomidine dose in children. Measurements and Main Results Forty intubated PICU or CVICU patients who received dexmedetomidine as a continuous infusion for at least 2 days were genotyped for ADRA2A with a custom‐designed TaqMan® Assay. Ten (25%) subjects were wildtype (GG), 15 (37.5%) were heterozygous (GC), and 15 (37.5%) were homozygous (CC) variant. The maximum dexmedetomidine doses (mCg/kg/h) were not different between genotype groups CC (1, 0.3–1.2), GC (1, 0.3–1.3), and GG (0.8, 0.3–1.2), (p = 0.37); neither were mean dexmedetomidine doses for these respective genotype groups 0.68 (0.24–1.07), 0.72 (0.22–0.98), 0.58 (0.3–0.94), (p = 0.67). Conclusions These findings did not confirm the results from adult studies where ADRA2A polymorphisms correlate with dexmedetomidine response, therefore highlighting the need for pediatric studies to validate PGx findings in adults prior to implementation in pediatrics.

Background: Critically ill children in the pediatric intensive care unit (PICU) often require sedation with dexmedetomidine, an α2-adrenergic receptor (ADRA2A) agonist. In adults, evidence suggests an ADRA2A polymorphism (rs1800544) modulates the dexmedetomidine response. We hypothesize that pediatric patients with at least one wild-type allele (GG and GC) will require larger dexmedetomidine doses and a longer time to effective dose than patients with a variant genotype (CC). Methods: This study was approved by the institutional review board (IRB). Patients in the PICU, 1 week through 25 years of age, and sedated with dexmedetomidine for ≥ 2 days were approached for enrollment. Genomic DNA was extracted from blood or saliva before genotyping for rs1800544 with a custom designed TaqMan® Assay on the QuantStudio 12K Flex platform. Patient genotype was determined using TaqMan® Genotyper software. Patient data were collected from the electronic medical record. Results: Sixty-five patients were enrolled and genotyped. Twenty-six patients were homozygous variant (CC), 27 heterozygous (GC), and 12 wildtype (GG) for rs1800544. The maximum dose (mcg/kg/hr) was 0.75 ± 0.31, and 0.78 ± 0.32, in patients with and without a G allele, respectively (p=0.65). The mean doses were 0.59 ± 0.22 and 0.58 ± 0.24 in patients with and without a G allele, respectively (p=0.85). The time to effective dose (hrs) was 5.8 ± 12.0 for patients with a G allele and 4.0 ± 8.2 for patients with no G allele (p=0.74).  Conclusion:  Our hypothesis that the CC genotype would require lower doses of dexmedetomidine was not confirmed. Patients without a G allele required lower dexmedetomidine dosage and a longer time to achieve an effective dose, but these findings were not significant. This could be due to the small sample size or clinical factors that affect pediatric sedation.  An adequately powered study could determine the association of ADRA2A genotype with dexmedetomidine.