Y Nyman1, A Fredriksson2, P-A Lönnqvist1, H Viberg3. 1. Department of Paediatric Anaesthesia and Intensive Care, Astrid Lindgrens Children's Hospital/Karolinska University Hospital, Stockholm, Sweden. 2. Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden. 3. Department of Environmental Toxicology, Uppsala University, Uppsala, Sweden.
Abstract
BACKGROUND: Numerous animal studies have shown that all commonly used intravenous anaesthetic drugs and volatile agents may cause neuronal apoptosis following exposure in early life. Most studies have focussed on detecting increased apoptosis but their methods are not always readily transferrable to humans. The lipid formulation of etomidate represents an alternative to the currently established intravenous anaesthetic agents but there is no animal or human data on apoptosis or long-term behavioural changes. The aim of our study was to investigate the effects of etomidate on cerebral neuronal apoptosis and long-term behavioural effects using an established mouse model that represents the clinically relevant period of anaesthesia during early infancy in humans. METHODS: Six groups of 10 day old mice (P10) were injected with either etomidate 0.3, 3 or 10 mg/kg, propofol 60 mg/kg, ketamine 50 mg/kg or placebo only. Apoptosis in the cerebral cortex and hippocampus was assessed 24 h after treatment (activated caspase-3). Late behavioural effects were tested at 2 months of age (spontaneous activity in a new environment). RESULTS: No evidence was found of differences in activated caspase 3-concentrations among the study groups. Significant late behavioural changes were only observed in the ketamine group. CONCLUSION: A single dose of etomidate in early infant mice at P10 did not produce evidence of cerebral apoptosis or impaired adult motor behaviour.
BACKGROUND: Numerous animal studies have shown that all commonly used intravenous anaesthetic drugs and volatile agents may cause neuronal apoptosis following exposure in early life. Most studies have focussed on detecting increased apoptosis but their methods are not always readily transferrable to humans. The lipid formulation of etomidate represents an alternative to the currently established intravenous anaesthetic agents but there is no animal or human data on apoptosis or long-term behavioural changes. The aim of our study was to investigate the effects of etomidate on cerebral neuronal apoptosis and long-term behavioural effects using an established mouse model that represents the clinically relevant period of anaesthesia during early infancy in humans. METHODS: Six groups of 10 day old mice (P10) were injected with either etomidate 0.3, 3 or 10 mg/kg, propofol 60 mg/kg, ketamine 50 mg/kg or placebo only. Apoptosis in the cerebral cortex and hippocampus was assessed 24 h after treatment (activated caspase-3). Late behavioural effects were tested at 2 months of age (spontaneous activity in a new environment). RESULTS: No evidence was found of differences in activated caspase 3-concentrations among the study groups. Significant late behavioural changes were only observed in the ketamine group. CONCLUSION: A single dose of etomidate in early infantmice at P10 did not produce evidence of cerebral apoptosis or impaired adult motor behaviour.
Authors: Yang Li; Weiguang Li; Zeguo Feng; Jie Song; Chenggang Zhang; Lianjun Huang; Yanping Song Journal: Zhejiang Da Xue Xue Bao Yi Xue Ban Date: 2021-06-25
Authors: William M Jackson; Christy D B Gray; Danye Jiang; Michele L Schaefer; Caroline Connor; Cyrus D Mintz Journal: J Neurosurg Anesthesiol Date: 2016-10 Impact factor: 3.956