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There have been few studies comparing the response to asphyxia and the effectiveness of typical cardiopulmonary resuscitation (CPR) using exogenous epinephrine administration and manual closed-chest compression between total intravenous anaesthesia (TIVA) and inhalational anaesthesia.Twenty pigs were randomly assigned to two study groups anaesthetized using either 2% end-tidal isoflurane (n=10) or propofol (12 mg kg–1 h–1)–fentanyl (50 µg kg–1) (n=10). Asphyxia was induced by clamping the tracheal tube until the mean arterial pressure (MAP) decreased to 40% of the baseline value (40% MAP time). The tracheal tube was declamped at that point, and CPR was performed. Haemodynamic parameters and blood samples were obtained before the induction of asphyxia, at 1-min intervals during asphyxia, and 1, 2, 3, 5, 10, 30 and 60 min after asphyxia.TIVA maintained the MAP against hypoxia–hypercapnia stress significantly longer than isoflurane anaesthesia (mean (SD) 40% MAP time 498 (95) and 378 (104) s respectively). In all animals in the isoflurane group, spontaneous circulation returned within 1 min of the start of CPR. In six of the TIVA animals, spontaneous circulation returned for 220 (121) s; spontaneous circulation did not return within 5 min in the remaining four animals.Although TIVA is less prone than isoflurane anaesthesia to primary cardiovascular depression leading to asphyxia, TIVA is associated with reduced effectiveness of CPR in which resuscitation because of asphyxic haemodynamic depression occurs.