Impact of anesthetic agents on cerebrovascular physiology in children.
TL;DR: The understanding of the effects of anesthetic agents on the physiology of cerebral vasculature in the pediatric population has significantly increased in the past decade allowing a more rationale decision making in anesthesia management.
Abstract: care to children with neurologic pathologies. The cerebral physiology is influenced by the developmental stage of the child. The understanding of the effects of anesthetic agents on the physiology of cerebral vasculature in the pediatric population has significantly increased in the past decade allowing a more rationale decision making in anesthesia management. Although no single anesthetic technique can be recommended, sound knowledge of the principles of cerebral physiology and anesthetic neuropharmacology will facilitate the care of pediatric neurosurgical patients.
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TL;DR: There is no direct evidence in humans for propofol-induced neurotoxicity to the infant brain; however, current concerns of neuroapoptosis in developing brains induced by prop ofol persist and continue to be a focus of research.
Abstract: Propofol is an intravenous agent used commonly for the induction and maintenance of anesthesia, procedural, and critical care sedation in children. The mechanisms of action on the central nervous system involve interactions at various neurotransmitter receptors, especially the gamma-aminobutyric acid A receptor. Approved for use in the USA by the Food and Drug Administration in 1989, its use for induction of anesthesia in children less than 3 years of age still remains off-label. Despite its wide use in pediatric anesthesia, there is conflicting literature about its safety and serious adverse effects in particular subsets of children. Particularly as children are not “little adults”, in this review, we emphasize
the maturational aspects of propofol pharmacokinetics. Despite the myriad of propofol pharmacokinetic-pharmacodynamic studies and the ability to use allometrical scaling to smooth out differences due to size and age, there is no optimal model that can be used in target controlled infusion pumps for providing closed loop total intravenous anesthesia in children. As the commercial formulation of propofol is a nutrient-rich emulsion, the risk for bacterial contamination exists despite the Food and Drug Administration mandating addition of antimicrobial preservative, calling for manufacturers’ directions to discard open vials after 6 h. While propofol has advantages over inhalation anesthesia such as less postoperative nausea and emergence delirium in children, pain on injection remains a problem even with newer formulations. Propofol is known to depress mitochondrial function by its action as an uncoupling agent in oxidative phosphorylation. This has implications for children with mitochondrial diseases and the occurrence of propofol-related infusion syndrome, a rare but seriously life-threatening complication of propofol. At the time of this review, there is no direct evidence in humans for propofol-induced neurotoxicity to the infant brain; however, current concerns of neuroapoptosis in developing brains induced by propofol persist and continue to be a focus of research.
256 citations
Cites background from "Impact of anesthetic agents on cere..."
...This is associated with a fall in cerebral blood flow, metabolic demand for oxygen, and any pre-existing cerebral edema [88, 89]....
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Journal Article•
06 Oct 1950-La semaine des hôpitaux : organe fondé par l'Association d'enseignement médical des hôpitaux de Paris
147 citations
TL;DR: Near‐infrared spectroscopy provides noninvasive continuous access to the venous side of regional circulations that can approximate organ‐specific and global measures to facilitate the detection of circulatory abnormalities and drive goal‐directed interventions to reduce end‐organ ischemic injury.
Abstract: The safety of anesthesia has improved greatly in the past three decades. Standard perioperative monitoring, including pulse oximetry, has practically eliminated unrecognized arterial hypoxia as a cause for perioperative injury. However, most anesthesia-related cardiac arrests in children are now cardiovascular in origin, and standard monitoring is unable to detect many circulatory abnormalities. Near-infrared spectroscopy provides noninvasive continuous access to the venous side of regional circulations that can approximate organ-specific and global measures to facilitate the detection of circulatory abnormalities and drive goal-directed interventions to reduce end-organ ischemic injury.
96 citations
TL;DR: The advantages of total intravenous anesthesia (TIVA) have emerged and driven change in practice as mentioned in this paper, and these advantages will justify why TIVA will supercede inhalational anesthesia in future pediatric anesthetic practice.
Abstract: Inhalational anesthesia has dominated the practice of pediatric anesthesia. However, as the introduction of agents such as propofol, short-acting opioids, midazolam, and dexmedetomidine a monumental change has occurred. With increasing use, the overwhelming advantages of total intravenous anesthesia (TIVA) have emerged and driven change in practice. These advantages, outlined in this review, will justify why TIVA will supercede inhalational anesthesia in future pediatric anesthetic practice.
72 citations
01 Jan 1995
TL;DR: In this paper, the effects of a high affinity gamma-aminobutyric acid (GABA)-benzodiazepine-receptor agonist (lorazepam) and an antagonist (flumazenil) in humans, using H2(15)O positron-emission tomography were studied.
Abstract: We studied the effects of a high-affinity gamma-aminobutyric acid (GABA)-benzodiazepine-receptor agonist (lorazepam) and an antagonist (flumazenil) in humans, using H2(15)O positron-emission tomography. Administration of lorazepam to healthy volunteers caused time- and dose-dependent reductions in regional cerebral blood flow and self-reported alterations in behavioral/mood parameters. Flumazenil administration reversed these changes. These observations indicated that benzodiazepine-induced effects on regional cerebral blood flow and mood/behavior are mediated at some level through GABA-benzodiazepine receptors, although the specific mechanism remains unclear. The approach described here provides a method for quantifying GABA-benzodiazepine-receptor-mediated neurotransmission in the living human brain and may be useful for studying the role of these receptors in a variety of neuropsychiatric disorders.
53 citations
References
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TL;DR: It is concluded that the decrease in cerebral blood flow in response to O2 administration is greater than previously described and appears to be greater in young adults.
Abstract: A small decrease in cerebral blood flow (approximately 10%) in response to 100% oxygen (O2) administration is well recognized. This observation was based on human volunteer studies, which employed a nitrous oxide washout method for the measurement of cerebral blood flow. Because this method is now appreciated to be subject to potential errors we have examined the cerebral blood flow response to 100% oxygen using a magnetic resonance imaging technique to quantify changes in carotid and basilar artery flow. The study, was performed in 12 normal male subjects aged 23-42 years. We report decreases in cerebral blood flow ranging from 9 to 31% with a mean value of over 20%. The decrease in cerebral blood flow was greater in seven young subjects (aged 23-26 years) with decreases in cerebral blood flow of 19.3-31.4% (mean 26.8%). In five older subjects (aged 32-42 years), decreases in CBF were smaller (mean 16. 2%). The administration of 100% O2 was accompanied by a small decrease in end-tidal CO2 (3.7-7.1%), insufficient to explain the changes in cerebral blood flow. We conclude that the decrease in cerebral blood flow in response to O2 administration is greater than previously described and appears to be greater in young adults.
196 citations
TL;DR: Cerebral blood flow, cerebral oxygen consumption, lactate and glucose metabolism, and the electroencephalograph were measured in 13 patients during anaesthesia and after 30 minutes infusion of propofol.
Abstract: Cerebral blood flow, cerebral oxygen consumption, lactate and glucose metabolism were measured in 13 patients during anaesthesia with nitrous oxide, oxygen and enflurane 0.5% and after 30 minutes infusion of propofol. The mean blood concentration of propofol was 4.06 micrograms/ml. Cerebral blood flow decreased by 27.6% and cerebral vascular resistance by 51%. There were no changes in lactate and glucose metabolism. Cerebral oxygen consumption decreased by 18.25%. Changes in the electro-encephalograph were related to the blood levels of propofol.
195 citations
Journal Article•
TL;DR: The dynamic changes of rCBF and rCMRO2 observed in children probably reflect the physiologic developmental state within anatomic areas of the brain.
Abstract: BACKGROUND AND PURPOSE: Normal values for cerebral blood flow (CBF) and metabolism in adults are well established, but not for children. Our goal, therefore, was to clarify functional developmental changes of the brain in children in relation to CBF and oxygen metabolism. METHODS: We measured regional CBF (rCBF), regional cerebral metabolic rate for oxygen (rCMRO2), and regional oxygen extraction fraction (rOEF), using positron emission tomography (PET). We performed 30 PET studies in 24 children ages 10 days to 16 years (nine boys, 15 girls), using a steady inhalation method with C15O2, 15O2, and 15CO in order to measure rCBF, rCMRO2, and rOEF, respectively. Regions of interest were set in the primary cerebral areas (sensorimotor, visual, temporal, and parietal cortex), cerebral association areas (frontal and visual association), basal ganglia (lenticular and thalamus), and posterior fossa (brain stem and cerebellar cortex). Subjects were grouped by age ( RESULTS: rCBF and rCMRO2 were lower in the neonatal period than in older children and adults, and increased significantly during early childhood. rCBF was higher as compared with adults, peaking around age 7, whereas rCMRO2 was relatively high, with the last area to increase being the frontal association cortex. Both rCBF and rCMRO2 reached adult values during adolescence. No difference in rCBF was observed between the basal ganglia and the primary cerebral cortex; however, it was prominent in the occipital lobe in every age bracket. No significant changes in rOEF were found during childhood. CONCLUSION: The dynamic changes of rCBF and rCMRO2 observed in children probably reflect the physiologic developmental state within anatomic areas of the brain.
189 citations
TL;DR: Etomidate may be effective in protecting the cerebral circulation without the detrimental cardiotoxicity observed with protective doses of barbiturates in patients whose disease processes have destroyed autoregulatory function or who have inadequate sources of anatomical collateral supply.
Abstract: ✓ The operative management of large and giant aneurysms is complicated by their typically atheromatous and thick walls, frequent intramural thrombosis with calcification, and broad-based necks that often incorporate perforating and other vital vessels. Not infrequently, it is necessary to at least focally arrest the intracranial circulation and open or excise these aneurysms to facilitate vascular reconstruction. This maneuver, in patients whose disease processes have destroyed autoregulatory function or who have inadequate sources of anatomical collateral supply, may cause the threshold for permanent ischemic injury to be exceeded. The authors have recently treated 14 such patients while under electroencephalographic monitoring to document electrical burst suppression induced by the administration of etomidate, followed by temporary clipping to permit vascular repair and intraoperative angiography to document patency of parent arteries. Up to 60 minutes of internal carotid artery occlusion, 35 minutes of...
184 citations
TL;DR: This study compared the use of remifentanil or fentanyl during elective supratentorial craniotomy for space-occupying lesions and found that the former was more beneficial than the latter.
Abstract: BackgroundRemifentanil hydrochloride is an ultra-short-acting, esterase-metabolized micro-opioid receptor agonist. This study compared the use of remifentanil or fentanyl during elective supratentorial craniotomy for space-occupying lesions.MethodsSixty-three adults gave written informed consent for
183 citations