Resistance of brain glucose metabolism to thiopental‐induced CNS depression in newborn piglets

Abstract

The transition from mild sedation to deep anaesthesia is marked by the phenomenon of burst suppression (BS). FDG-PET studies show that the cerebral metabolic rate for glucose (CMRglc) declines dramatically with onset of BS in the adult brain. Global CMRglc increases substantially in the post-natal period and achieves its maximum in preadolescence. However, the impact of post-natal brain development on the vulnerability of CMRglc to the onset of BS has not been documented. Therefore, cerebral blood flow and metabolism were measured using a variant of the Kety-Schmidt method, in conjunction with quantitative regional estimation of brain glucose uptake by FDG-PET in groups of neonate and juvenile pigs, under a condition of light sedation or after induction of deep anaesthesia with thiopental. Quantification of simultaneous ECoG recordings was used to establish the correlation between anaesthesia-related changes in brain electrical activity and the observed cerebrometabolic changes. In the condition of light sedation the magnitude of CMRglc was approximately 20% higher in the older pigs, with the greatest developmental increase evident in the cerebral cortex and basal ganglia (P<0.05). Onset of BS was associated with 20-40% declines in CMRglc. Subtraction of the mean parametric maps for CMRglc showed the absolute reductions in CMRglc evoked by thiopental anaesthesia to be two-fold greater in the pre-adolescent pigs than in the neonates (P<0.05). Thus, the lesser suppression of brain energy demand of neonate brain during deep anaesthesia represents a reduced part of thiopental suppressing brain metabolism in neonates.

The effect of burst suppression on cerebral blood flow and autoregulation: a scoping review of the human and animal literature

“…Overall, there were 66 studies that were included in the final results, 41 of which examined animals ( Michenfelder, 1974 ; Harper and MacKenzie, 1977 ; Kassell et al, 1980 ; Gronert et al, 1981 ; Newberg et al, 1983 ; Milde et al, 1985 ; Maekawa et al, 1986 ; Scheller et al, 1986 ; Baughman et al, 1989 ; Warner et al, 1989 ; Lutz et al, 1990 ; Zornow et al, 1990 ; Roald et al, 1991 ; Artru et al, 1992 ; Ramani et al, 1992 ; Werner et al, 1992 ; Kochs et al, 1993 ; Golanov and Reis, 1995 ; Werner et al, 1995 ; Nemoto et al, 1996a ; Nemoto et al, 1996b ; Klementavicius et al, 1996 ; Young et al, 1997 ; Zarchin et al, 1998 ; Schmid-Elsaesser et al, 1999 ; Westermaier et al, 2000 ; Mäkiranta et al, 2002 ; Joshi et al, 2004 ; Joshi et al, 2005 ; Hungerhuber et al, 2006 ; Joshi et al, 2006 ; Liu et al, 2011 ; Liu et al, 2013a ; Liu et al, 2013b ; Walter et al, 2013 ; Sutin et al, 2014 ; Choi et al, 2016 ; Benveniste et al, 2017 ; Yang et al, 2018 ; Zhang et al, 2019 ; Berndt et al, 2021 ), 24 of which examined humans ( Bendtsen et al, 1985 ; Woodcock et al, 1987 ; Young et al, 1991 ; Matta et al, 1995a ; Matta et al, 1995b ; Lam et al, 1995 ; Matta and Lam, 1995 ; Newman et al, 1995 ; Artru et al, 1997 ; Hoffman et al, 1997 ; Doyle and Matta, 1999 ; Matta et al, 1999 ; Ludbrook et al, 2002 ; Johnston et al, 2003 ; Reinsfelt et al, 2003 ; Reinsfe...…”

“…Of the 42 studies that examined animals, six used propofol ( Artru et al, 1992 ; Ramani et al, 1992 ; Werner et al, 1992 ; Joshi et al, 2006 ; Wang et al, 2011 ; Liu et al, 2013a ), 13 used barbiturates (thiopental) ( Michenfelder, 1974 ; Kassell et al, 1980 ; Gronert et al, 1981 ; Milde et al, 1985 ; Nemoto et al, 1996a ; Nemoto et al, 1996b ; Klementavicius et al, 1996 ; Zarchin et al, 1998 ; Schmid-Elsaesser et al, 1999 ; Westermaier et al, 2000 ; Mäkiranta et al, 2002 ; Joshi et al, 2005 ; Hungerhuber et al, 2006 ), 18 used inhalational anaesthetics (isoflurane) ( Newberg et al, 1983 ; Maekawa et al, 1986 ; Scheller et al, 1986 ; Baughman et al, 1989 ; Lutz et al, 1990 ; Zornow et al, 1990 ; Roald et al, 1991 ; Kochs et al, 1993 ; Golanov and Reis, 1995 ; Liu et al, 2011 ; Walter et al, 2013 ; Sutin et al, 2014 ; Choi et al, 2016 ; Benveniste et al, 2017 ; Yang et al, 2018 ; Zhang et al, 2019 ; Berndt et al, 2021 ; Sirmpilatze et al, 2022 ), four used a combination of methods ( Harper and MacKenzie, 1977 ; Warner et al, 1989 ; Young et al, 1997 ; Joshi et al, 2004 ), and one induced BS through hypotension ( Werner et al, 1995 ).…”

“…In terms of the subjects that were used in the studies, 12 used different species of dogs (beagle, mongrel) ( Michenfelder, 1974 ; Kassell et al, 1980 ; Gronert et al, 1981 ; Newberg et al, 1983 ; Milde et al, 1985 ; Lutz et al, 1990 ; Zornow et al, 1990 ; Roald et al, 1991 ; Artru et al, 1992 ; Werner et al, 1992 ; Kochs et al, 1993 ; Werner et al, 1995 ), 18 used different species of rodents (Sprague Dawley rats, wistar rats, gerbils) ( Maekawa et al, 1986 ; Baughman et al, 1989 ; Warner et al, 1989 ; Golanov and Reis, 1995 ; Nemoto et al, 1996a ; Nemoto et al, 1996b ; Klementavicius et al, 1996 ; Young et al, 1997 ; Zarchin et al, 1998 ; Schmid-Elsaesser et al, 1999 ; Westermaier et al, 2000 ; Hungerhuber et al, 2006 ; Liu et al, 2011 ; Liu et al, 2013a ; Sutin et al, 2014 ; Choi et al, 2016 ; Benveniste et al, 2017 ; Berndt et al, 2021 ), six used different species of rabbits ( Scheller et al, 1986 ; Ramani et al, 1992 ; Joshi et al, 2004 ; Joshi et al, 2005 ; Joshi et al, 2006 ; Wang et al, 2011 ), two used different species of swine ( Mäkiranta et al, 2002 ; Walter et al, 2013 ), three used different species of non-human primates ( Harper and MacKenzie, 1977 ; Yang et al, 2018 ; Zhang et al, 2019 ), and one used both rodents and non-human primates ( Sirmpilatze et al, 2022 ).…”

“…Out of the 18 studies that used inhalational anaesthetics to induce BS, four measured blood flow in the superior sagittal sinus ( Newberg et al, 1983 ; Lutz et al, 1990 ; Zornow et al, 1990 ; Roald et al, 1991 ), two used the Laser Doppler Flowmetry Method ( Golanov and Reis, 1995 ; Berndt et al, 2021 ), two used quantitative autoradiography ( Maekawa et al, 1986 ; Baughman et al, 1989 ), three used near infrared spectroscopy ( Sutin et al, 2014 ; Choi et al, 2016 ; Yang et al, 2018 ), two used functional MRI and BOLD signal analysis ( Zhang et al, 2019 ; Sirmpilatze et al, 2022 ), two used FDG-PET ( Walter et al, 2013 ), two used hydrogen clearance method ( Scheller et al, 1986 ), one analyzed glymphatic transport and used magnetic resonance time of flight ( Liu et al, 2013b ), one used laser doppler flowmetry and fMRI ( Liu et al, 2011 ), and one used quantitative autoradiography and TCD ( Kochs et al, 1993 ).…”

“…There was more variability in the results of the isoflurane studies which may be in part be due to the variability in the techniques used. Of the studies that looked at overall CBF, four studies showed that BS led to a decrease in CBF ( Baughman et al, 1989 ; Zornow et al, 1990 ; Walter et al, 2013 ; Berndt et al, 2021 ), two showed an increase in CBF ( Ramani et al, 1992 ; Gomez et al, 2022 ), three showed no change ( Newberg et al, 1983 ; Scheller et al, 1986 ; Roald et al, 1991 ), and two showed an increase or decrease depending on the region of the brain and the concentration of anaesthetic used ( Maekawa et al, 1986 ; Lutz et al, 1990 ). In the remainder, conclusions could not be drawn on the average effect of BS on CBF but did shed light on neurovascular coupling ( Golanov and Reis, 1995 ; Liu et al, 2011 ; Sutin et al, 2014 ; Zhang et al, 2019 ; Sirmpilatze et al, 2022 ).…”