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: The distribution of compliance and outflow resistance between cerebral and spinal compartments was measured in anesthetized, ventilated cats by analysis of the cerebrospinal fluid (CSF) pressure response to changes in CSF volume.
Abstract: ✓ The distribution of compliance and outflow resistance between cerebral and spinal compartments was measured in anesthetized, ventilated cats by analysis of the cerebrospinal fluid (CSF) pressure response to changes in CSF volume. Cerebral and spinal compartments were isolated by inflating a balloon positioned epidurally at the level of C-6. The change of CSF volume per unit change in pressure (compliance) and change of CSF volume per unit of time (absorption) were evaluated by inserting pressure data from the experimental responses into a series of equations developed from a mathematical model. It was found that 68% of total compliance is contributed by the cerebral compartment while the remaining 32% is contained within the spinal axis. The cerebral compartment accounted for 84% of total CSF absorption. The mechanism for spinal absorption appears to be similar in that no differences were obvious on the basis of pressure dynamics.
687 citations
TL;DR: Cerebral blood flow was measured, using the 133Xe clearance technique, a few hours after birth in 19 infants with varying degrees of respiratory distress syndrome, showing a linear relationship that was identical in infants with asphyxia at birth and infants with RDS only.
631 citations
TL;DR: Physicians should be aware that etomidate inhibits adrenal steroidogenesis, and they should consider treating selected patients with corticosteroids if etamidate is used.
Abstract: The use of the intravenous anesthetic etomidate for prolonged sedation has been associated with low levels of plasma cortisol and increased mortality. We measured the cortisol and aldosterone responses to ACTH stimulation in five patients receiving etomidate, and we also studied the direct effects of etomidate on enzymes in the rat steroidogenic pathway. One patient who was receiving a 20-hour infusion of etomidate (1.3 to 1.5 mg per kilogram of body weight per hour) had marked adrenocortical suppression that was still evident four days after etomidate was discontinued. Four surgical patients receiving etomidate during their operations were all found to have adrenal suppression four hours after the operation; mean (+/- S.D.) increases in cortisol and aldosterone after ACTH stimulation were only 1.8 +/- 0.5 micrograms per deciliter and 0.5 +/- 1.1 ng per deciliter, respectively. In rat adrenal cells, etomidate produced a concentration-dependent blockade of the two mitochondrial cytochrome P-450-dependent enzymes, cholesterol-side-chain cleavage enzyme, and 11 beta-hydroxylase, without evident inhibition of the microsomal enzymes in the glucocorticoid pathway. Physicians should be aware that etomidate inhibits adrenal steroidogenesis, and they should consider treating selected patients with corticosteroids if etomidate is used.
476 citations
453 citations
TL;DR: The effects of sevoflurane and propofol as sole anesthetics and in combination with N2O on regional cerebral blood flow, metabolic rate of oxygen (rCMRO2), and blood volume (rCBV) in the living human brain using positron emission tomography are quantified.
Abstract: Background: Anesthetic agents, especially volatile anesthetics and nitrous oxide (N2O), are suspected to perturb cerebral homeostasis and vascular reactivity. The authors quantified the effects of sevoflurane and propofol as sole anesthetics and in combination with N2O on regional cerebral blood flow (rCBF), metabolic rate of oxygen (rCMRO2), and blood volume (rCBV) in the living human brain using positron emission tomography. Methods: 15 O-labeled water, oxygen, and carbon monoxide were used as positron emission tomography tracers to determine rCBF, rCMRO2 and rCBV, respectively, in eight healthy male subjects during the awake state (baseline) and at four different anesthetic regimens: (1) sevoflurane alone, (2) sevoflurane plus 70% N2 O( SN), (3) propofol alone, and (4) propofol plus 70% N2 O( PN). Sevoflurane and propofol were titrated to keep a constant hypnotic depth (Bispectral Index 40) throughout anesthesia. End-tidal carbon dioxide was strictly kept at preinduction level. Results: The mean SD end-tidal concentration of sevoflurane was 1.5 0.3% during sevoflurane alone and 1.2 0.3% during S N( P < 0.001). The measured propofol concentration was 3.7 0.7 g/ml during propofol alone and 3.5 0.7 g/ml during PN (not significant). Sevoflurane alone decreased rCBF in some (to 73‐ 80% of baseline, P < 0.01), and propofol in all brain structures (to 53‐70%, P < 0.001). Only propofol reduced also rCBV (in the cortex and cerebellum to 83‐ 86% of baseline, P < 0.05). Both sevoflurane and propofol similarly reduced rCMRO2 in all brain areas to 56 ‐70% and 50 ‐ 68% of baseline, respectively (P < 0.05). The adjunct N2O counteracted some of the rCMRO2 and rCBF reductions caused by drugs alone, and especially during SN, a widespread reduction (P < 0.05 for all cortex and cerebellum vs. awake) in the oxygen extraction fraction was seen. Adding of N2O did not alter the rCBV effects of sevoflurane and propofol alone. Conclusions: Propofol reduced rCBF and rCMRO2 comparably. Sevoflurane reduced rCBF less than propofol but rCMRO2 to an extent similar to propofol. These reductions in flow and metabolism were partly attenuated by adjunct N2O. SN especially reduced the oxygen extraction fraction, suggesting disturbed flow‐activity coupling in humans at a moderate depth of anesthesia. KNOWLEDGE about the effects of different anesthetics and anesthetic regimens on cerebral circulation and brain metabolism is of vital clinical importance. Improper use of anesthetic techniques may have deleterious effects on the compromised brain. The current understanding of the effects of general anesthetics on cerebral blood flow (CBF) and metabolism is largely based on laboratory data using a variety of different animal species and methods. In spite of partly
407 citations