Ketone supplementation abolished isoflurane anesthesia-induced elevation in blood glucose level and increased recovery time from anesthesia in Wistar Albino Glaxo Rijswijk rats.

Background: It has been suggested that administration of exogenous ketone supplements (EKSs) not only increases blood ketone body levels but also decreases blood glucose level and modulates isoflurane-induced anesthesia in different rodents, such as Wistar Albino Glaxo Rijswijk (WAG/Rij) rats. Thus, we investigated whether administration of EKSs can modulate the isoflurane anesthesia-generated increase in blood glucose level and the time required to recover from isoflurane-induced anesthesia.
Methods: To investigate the effect of EKSs on isoflurane anesthesia-induced changes in blood glucose and R-β-hydroxybutyrate (R-βHB) level as well as recovery time from anesthesia, we used KEMCT (mix of ketone ester/KE and medium chain triglyceride/MCT oil in a 1:1 ratio) in WAG/Rij rats. First, to accustom the animals to the method, water gavage was carried out for 5 days (adaptation period). After adaptation period, rats of first group (group 1) were gavaged by water (3 g/kg), whereas, in the case of second group (group 2), the diet of animals was supplemented by KEMCT (3 g/kg, gavage) once per day for 7 days. One hour after the last gavage, isoflurane (3%) anesthesia was induced for 20 min (group 1 and group 2) and the time required for recovery from anesthesia was measured by using righting reflex. Subsequently, blood levels of both R-βHB and glucose were also evaluated. Changes in blood glucose and R-βHB levels were compared to control, which control glucose and R-βHB levels were measured on the last day of the adaptation period (group 1 and group 2). Time required for recovery from isoflurane anesthesia, which was detected after 7 ^th KEMCT gavage (group 2), was compared to recovery time measured after 7 ^th water gavage (group 1).
Results: The KEMCT maintained the normal glucose level under isoflurane anesthesia-evoked circumstances preventing the glucose level elevating effect of isoflurane. Thus, we demonstrated that administration of KEMCT not only increased blood level of R-βHB but also abolished the isoflurane anesthesia-generated increase in blood glucose level. Moreover, the time required for recovery from isoflurane-evoked anesthesia increased significantly in KEMCT treated animals.
Conclusions: Putative influence of elevated blood ketone body level on isoflurane-evoked effects, such as modulation of blood glucose level and recovery time from anesthesia, should be considered by anesthesiologists.
(© 2023. The Author(s).)