| Popis: |
Evidence from clinical and experimental research suggests that exposure to commonly used inhaled anaesthetics during early development may lead to neurobehavioral deficit later in life: However, exposure to these drugs may be unavoidable as exposure to pain and distress may lead to worse outcome. It is possible that co-administration of xenon, a rare anaesthetic gas, with proven neuroprotective properties, may reduce exposure to inhaled anaesthetics in neonates and provide a method to avoid these long term sequelae. Research in these areas relies on neonatal rodent models which contain confounding variables; many linked to the physiological derangement caused by the dosage of inhaled anaesthetic that has been chosen. This dissertation describes a new method to measure a sub-anaesthetic potency of sevoflurane and xenon in neonatal rats on postnatal days seven and nine: The effective inhaled concentration preventing cold-stimulated vocalisation in 50% (EiC50 CSV). The method, unlike other anaesthetic dose-response studies, uses randomisation of groups of rats to a range of concentrations and three durations of exposure. Logistic regression, with absence of vocalisation as the dependent variable and concentration as the explanatory variable is then performed and concentration-response curves with confidence intervals can be plotted. Additional explanatory variables can then be inserted into the model to assess the effect on the EiC50 CSV: Adequacy of exposure duration can be assessed with this approach. Models and equipotent sub-anaesthetic concentrations of sevoflurane and xenon in normothermic neonatal rats are presented. Maintenance of cardio-respiratory function and equal suppression of single channel electroencephalogram is demonstrated with exposure to these concentrations. Finally, neonatal models of anaesthesia are proposed in rats, pigs and humans. |
