Constantinos Chrysostomou1, Scott R Schulman2, Mario Herrera Castellanos3, Benton E Cofer4, Sanjay Mitra5, Marcelo Garcia da Rocha6, Wayne A Wisemandle6, Lisa Gramlich7. 1. Department of Pediatric Critical Care Medicine, Cardiac Intensive Care Unit, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA. Electronic address: chrycx@chp.edu. 2. Department of Anesthesiology, Duke Children's Hospital, Durham, NC. 3. Department of Pediatrics, Hospital Roosevelt, Guatemala City, Guatemala. 4. Neonatology, Greenville Hospital System, Greenville, SC. 5. Department of Pediatrics, West Virginia University Hospitals and Clinics, Ruby Memorial Hospital, Morgantown, WV. 6. Global Clinical R & D and Medical Affairs, Hospira Inc, Lake Forest, IL. 7. Department of Anesthesiology, Loyola University Medical Center, Maywood, IL.
Abstract
OBJECTIVE: To investigate the safety, efficacy, and pharmacokinetic profile of dexmedetomidine in preterm and full-term neonates ≥ 28 to ≤ 44 weeks gestational age. STUDY DESIGN:Forty-two intubated, mechanically ventilated patients (n = 42) were grouped by gestational age into group I (n = 18), ≥ 28 to <36 weeks, and group II (n = 24), ≥ 36 to ≤ 44 weeks. Within each age group, there were 3 escalating dose levels, including a loading dose (LD, μg/kg) followed by a maintenance dose (MD, μg · kg(-1) · h(-1)) for 6-24 hours: level 1, 0.05 LD/MD; level 2, 0.1 LD/MD; and level 3, 0.2 LD/MD. The primary endpoint was the number of patients requiring sedation as determined by the Neonatal Pain, Agitation, Sedation Scale. RESULTS: During dexmedetomidine infusion, 5% of Neonatal Pain, Agitation, Sedation Scale scores were >3, indicating agitation/pain, with 4 patients (10%) requiring more sedation and 17 (40%) requiring more analgesia. Though there was significant variability in pharmacokinetic variables, group I appeared to have lower weight-adjusted plasma clearance (0.3 vs 0.9 L · h(-1) · kg(-1)) and increased elimination half-life (7.6 vs 3.2 hours) compared with group II. Fifty-six adverse events (AEs) were reported in 26 patients (62%); only 3 AEs (5%) were related to dexmedetomidine. There were no serious AEs and no AEs or hemodynamic changes requiring dexmedetomidine discontinuation. CONCLUSION:Dexmedetomidine is effective for sedating preterm and full-term neonates and is well-tolerated without significant AEs. Preterm neonates had decreased plasma clearance and longer elimination half-life.
RCT Entities:
OBJECTIVE: To investigate the safety, efficacy, and pharmacokinetic profile of dexmedetomidine in preterm and full-term neonates ≥ 28 to ≤ 44 weeks gestational age. STUDY DESIGN: Forty-two intubated, mechanically ventilated patients (n = 42) were grouped by gestational age into group I (n = 18), ≥ 28 to <36 weeks, and group II (n = 24), ≥ 36 to ≤ 44 weeks. Within each age group, there were 3 escalating dose levels, including a loading dose (LD, μg/kg) followed by a maintenance dose (MD, μg · kg(-1) · h(-1)) for 6-24 hours: level 1, 0.05 LD/MD; level 2, 0.1 LD/MD; and level 3, 0.2 LD/MD. The primary endpoint was the number of patients requiring sedation as determined by the Neonatal Pain, Agitation, Sedation Scale. RESULTS: During dexmedetomidine infusion, 5% of Neonatal Pain, Agitation, Sedation Scale scores were >3, indicating agitation/pain, with 4 patients (10%) requiring more sedation and 17 (40%) requiring more analgesia. Though there was significant variability in pharmacokinetic variables, group I appeared to have lower weight-adjusted plasma clearance (0.3 vs 0.9 L · h(-1) · kg(-1)) and increased elimination half-life (7.6 vs 3.2 hours) compared with group II. Fifty-six adverse events (AEs) were reported in 26 patients (62%); only 3 AEs (5%) were related to dexmedetomidine. There were no serious AEs and no AEs or hemodynamic changes requiring dexmedetomidine discontinuation. CONCLUSION:Dexmedetomidine is effective for sedating preterm and full-term neonates and is well-tolerated without significant AEs. Preterm neonates had decreased plasma clearance and longer elimination half-life.
Authors: Teeda Pinyavat; David O Warner; Randall P Flick; Mary Ellen McCann; Dean B Andropoulos; Danquig Hu; Jeffrey W Sall; Marisa N Spann; Caleb Ing Journal: J Neurosurg Anesthesiol Date: 2016-10 Impact factor: 3.956
Authors: Rachel G Greenberg; Huali Wu; Matthew Laughon; Edmund Capparelli; Stevie Rowe; Kanecia O Zimmerman; P Brian Smith; Michael Cohen-Wolkowiez Journal: J Clin Pharmacol Date: 2017-04-25 Impact factor: 2.860