title: Relationship between zolpidem concentrations and sleep parameters in pediatric burn patients.
abstract: Zolpidem is a short-acting non-benzodiazepine hypnotic that is used to improve sleep architecture in patients with burn injuries. This study evaluated the relationship between zolpidem administration and sleep parameters in a cohort of children with severe burn injuries. Standard age-based zolpidem dosing practices were employed. Polysomnography data were recorded at 30-second intervals throughout the night. Serum concentrations of zolpidem were measured at 0, 1, 2, 4, 5, 6, and 8 hours after administration of the first dose. The relationship between zolpidem concentrations and sleep parameters was evaluated using Markov mixed-effects pharmacodynamic models. Ten children received two doses of zolpidem at 22:00 and 02:00 hours. The median total amount of sleep was 361.0 (interquartile range [IQR]: 299.0-418.5) minutes; approximately 65% of the normal reference value for an 8-hour period. Slow-wave and rapid eye movement (REM) sleep were also dramatically reduced (18-37% of normal). With two doses of zolpidem, stage 2 sleep was 99% of normal levels. Higher peak zolpidem concentrations were associated with increased stage 2 sleep (r = .54; P = .04). Despite this, a median of 120.0 (IQR: 99.5-143.5) transitions between nocturnal sleep stages were recorded, with a median of 55.5 (IQR: 36-75) night-time awakenings per patient. In pediatric burn patients, higher zolpidem serum concentrations were associated with restoration of stage 2 sleep to normal levels. Nonetheless, slow-wave and REM sleep were profoundly depressed with frequent transitions between sleep stages, suggesting that alternative hypnotic agents may be required to restore normal sleep architecture in severely burned children.
authors.affiliation: From the *Division of Clinical Pharmacology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City; †The Shriners Hospitals for Children, Cincinnati, Ohio; ‡Department of Surgery, University of Cincinnati, Ohio; §Department of Pharmacy Practice and Administrative Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Ohio; and the Departments of ‖Biostatistics and ¶Nutrition Services, Cincinnati Children's Hospital Medical Center, Ohio.
authors.forename: Chris
authors.initials: C
authors.lastname: Stockmann
authors.forename: Michele M
authors.initials: MM
authors.lastname: Gottschlich
authors.forename: Daniel
authors.initials: D
authors.lastname: Healy
authors.forename: Jane C
authors.initials: JC
authors.lastname: Khoury
authors.forename: Theresa
authors.initials: T
authors.lastname: Mayes
authors.forename: Catherine M T
authors.initials: CM
authors.lastname: Sherwin
authors.forename: Michael G
authors.initials: MG
authors.lastname: Spigarelli
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kagan
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002056:Burns / Q000097:blood* / Q000150:complications* / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D017286:Polysomnography; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012892:Sleep Deprivation / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D012894:Sleep Stages / Q000187:drug effects*; D000077334:Zolpidem
chemical_list: D006993:Hypnotics and Sedatives; D011725:Pyridines; D000077334:Zolpidem