A systematic review and narrative synthesis on the histological and neurobehavioral long‐term effects of dexmedetomidine

• Published in: Pediatric anesthesia 2019-02, Vol.29 (2), p.125-136
• Main Authors: Hoorn, Camille E., Hoeks, Sanne E., Essink, Heleen, Tibboel, Dick, Graaff, Jurgen C., Vutskits, Laszlo
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-2 Receptor Agonists - pharmacology; anesthesia; animal experimentation; Animals; brain/growth & development; child development/drug effects; Child, Preschool; Cognition - drug effects; dexmedetomidine; Dexmedetomidine - pharmacology; Humans; Hypnotics and Sedatives - pharmacology; Infant; Infant, Newborn; Mental Status and Dementia Tests; neurotoxicity; Neurotoxicity Syndromes - etiology; newborn; Randomized Controlled Trials as Topic; sedation; Systematic Review
• ISSN: 1155-5645; 1460-9592
• DOI: 10.1111/pan.13553

Summary Background Recent experimental studies suggest that currently used anesthetics have neurotoxic effects on young animals. Clinical studies are increasingly publishing about the effects of anesthesia on the long‐term outcome, providing contradictory results. The selective alpha‐2 adrenergic receptor agonist dexmedetomidine has been suggested as an alternative nontoxic sedative agent. Aims The aim of this systematic review was to assess the potential neuroprotective and neurobehavioral effects of dexmedetomidine in young animals and children. Methods Systematic searches separately for preclinical and clinical studies were performed in Medline Ovid and Embase on February 14, 2018. Results The initial search found preclinical (n = 661) and clinical (n = 240) studies. A total of 20 preclinical studies were included. None of the clinical studies met the predefined eligibility criteria. Histologic injury by dexmedetomidine was evaluated in 11 studies, and was confirmed in three of these studies (caspase‐3 activation or apoptosis). Decrease of injury caused by another anesthetic was evaluated in 16 studies and confirmed in 13 of these. Neurobehavioral tests were performed in seven out of the 20 studies. Of these seven rodent studies, three studies tested the effects of dexmedetomidine alone on neurobehavioral outcome in animals (younger than P21). All three studies found no negative effect of dexmedetomidine on the outcome. In six studies, outcome was evaluated when dexmedetomidine was administered following another anesthetic. Dexmedetomidine was found to lessen the negative effects of the anesthetic. Conclusion In animals, dexmedetomidine was found not to induce histologic injury and to show a beneficial effect when administered with another anesthetic. No clinical results on the long‐term effects in children have been identified yet.