Relationship between zolpidem concentrations and sleep parameters in pediatric burn patients

• Published in: Journal of burn care & research 2015-01, Vol.36 (1), p.137-144
• Main Authors: Stockmann, Chris, Gottschlich, Michele M, Healy, Daniel, Khoury, Jane C, Mayes, Theresa, Sherwin, Catherine M T, Spigarelli, Michael G, Kagan, Richard J
• Format: Article
• Language: English
• Subjects: Adolescent; Age Factors; Burns - blood; Burns - complications; Burns - therapy; Child; Child, Preschool; Cohort Studies; Drug Administration Schedule; Female; Humans; Hypnotics and Sedatives - administration & dosage; Hypnotics and Sedatives - pharmacokinetics; Male; Polysomnography; Pyridines - administration & dosage; Pyridines - pharmacokinetics; Sleep Deprivation - diagnosis; Sleep Deprivation - etiology; Sleep Deprivation - prevention & control; Sleep Stages - drug effects
• ISSN: 1559-047X; 1559-0488
• DOI: 10.1097/BCR.0000000000000164

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.