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: At 1.5 minimum alveolar anesthetic concentration, dynamic autoregulation was better preserved during sevoflurane than isof lurane anesthesia in humans.
Abstract: We investigated dynamic cerebral pressure autoregulation awake and during 1.5 minimum alveolar anesthetic concentration (MAC) sevoflurane or isoflurane anesthesia in 16 patients undergoing nonintracranial neurosurgical procedures. All patients received a standardized anesthetic, and their lungs were ventilated with 1.5 MAC volatile anesthetic in 100% oxygen to normocapnia. Routine monitors included electrocardiogram, pulse oximetry, end-tidal capnography, and continuous noninvasive blood pressure. In addition, middle cerebral artery blood velocity (Vmca) was measured continuously using transcranial Doppler ultrasonography. Dynamic cerebral autoregulation was tested by inducing a rapid transient decrease in mean arterial pressure by deflation of large thigh cuffs, which were placed around both thighs and inflated to 100 mm Hg above systolic pressure. The Vmca response to the decrease in blood pressure was fitted to a series of curves to determine the rate of dynamic cerebral autoregulation (dRoR). Awake dRoR values were similar in the isoflurane and sevoflurane groups, 32 +/- 2%/s and 29 +/- 2%/s, respectively. dRoR decreased to 5 +/- 1%/s during isoflurane anesthesia but to only 24 +/- 2%/s during sevoflurane anesthesia. We conclude that dynamic cerebral autoregulation is better preserved during sevoflurane than isoflurane anesthesia in humans. Implications: We investigated the effect of sevoflurane and isoflurane on dynamic cerebral pressure autoregulation using transcranial Doppler ultrasonography. At 1.5 minimum alveolar anesthetic concentration, dynamic autoregulation was better preserved during sevoflurane than isoflurane anesthesia. (Anesth Analg 1999;88:341-5)
128 citations
TL;DR: To compare the intrinsic action of volatile anesthetics, the effect of halothane, isoflurane, and desflurane on flow velocity in the middle cerebral artery during propofol‐induced isoelectricity of the electroencephalogram was examined.
Abstract: BackgroundThe effect of volatile anesthetics on cerebral blood flow depends on the balance between the agent's direct vasodilatory action and the indirect vasoconstrictive action mediated by flow-metabolism coupling. To compare the intrinsic action of volatile anesthetics, the effect of halothane, i
124 citations
TL;DR: It was concluded that Etomidate is a potent cerebral metabolic depressant and the cerebrovascular reactivity to carbon dioxide was maintained under etomidate anaesthesia.
Abstract: The effects of etomidate on regional cerebral blood flow (rc.b.f.) and cerebral metabolic rate for oxygen (CMRo2) were studied in seven patients undergoing diagnostic carotid angiography. Following determination of baseline rc.b.f. while awake, the patients were anaesthetized with a single dose of etomidate 15 mg. Thereafter an infusion of etomidate (2 or 3 mg min–1) was administered. Etomidate decreased both rc.b.f.10 (mean decrease 34%) and CMRo2 (mean decrease 45%). It was concluded that etomidate is a potent cerebral metabolic depressant. Furthermore, the cerebrovascular reactivity to carbon dioxide was maintained under etomidate anaesthesia.
124 citations
TL;DR: The data suggest that midazolam might be a safe agent to use for the induction of anesthesia in neurosurgical patients with intracranial hypertension and the effect of this new benzodiazepine on cerebral blood flow was evaluated.
Abstract: The effects of intravenously administered midazolam on cerebral blood flow were evaluated in eight healthy volunteers using the 133Xe inhalation technique. Six minutes after an intravenous dose of 0.15 mg/kg midazolam, the cerebral blood flow decreased significantly (P less than 0.001) from a value of 40.6 +/- 3.3 to a value of 27.0 +/- 5.0 ml . 100 g-1 . min-1. Cerebrovascular resistance (CVR) increased from 2.8 +/- 0.2 to 3.9 to 0.6 mmHg/(ml . 100 g-1 . min-1)(P less than 0.001). Mean arterial blood pressure decreased significantly (P less than 0.05) from 117 +/- 8 to 109 +/- 9 mmHg and arterial carbon dioxide tension increased from 33.9 +/- 2.3 to 38.6 +/- 3.2 mmHg (P less than 0.05). Arterial oxygen tension remained stable throughout the study, 484 +/- 95 mmHg before the administration of midazolam and 453 +/- 76 mmHg after. All the subjects slept after the injection of the drug and had anterograde amnesia of 24.5 +/- 5 min. The decrease in mean arterial blood pressure was probably not important since it remained in the physiologic range for cerebral blood flow autoregulation. The increase in arterial carbon dioxide tension observed after the midazolam injection may have partially counteracted the effect of this new benzodiazepine on cerebral blood flow. Our data suggest that midazolam might be a safe agent to use for the induction of anethesia in neurosurgical patients with intracranial hypertension.
118 citations
TL;DR: Propofol-remifentanil anaesthesia induced a dose-dependent low-flow state with preserved cerebral autoregulation, whereas sevoflurane at high doses provided a certain degree of luxury perfusion.
Abstract: Background Sevoflurane or propofol–remifentanil-based anaesthetic regimens represent modern techniques for neurosurgical anaesthesia. Nevertheless, there are potential differences related to their activity on the cerebrovascular system. The magnitude of such difference is not completely known. Methods In total 40 patients, treated for spinal or maxillo-facial disorders, were randomly allocated to either i.v. propofol–remifentanil or inhalational sevoflurane anaesthesia. Transcranial Doppler was used to assess changes in cerebral blood flow velocity, carbon dioxide reactivity, cerebral autoregulation and the bispectral index to assess the depth of anaesthesia. Results Time-averaged mean flow velocity (MFV) was significantly reduced after induction of anaesthesia in both sevoflurane and propofol–remifentanil groups ( P P P 2 concentrations impaired cerebral autoregulation in the sevoflurane group but not in patients anaesthetized with propofol–remifentanil. Conclusions Propofol–remifentanil anaesthesia induced a dose-dependent low-flow state with preserved cerebral autoregulation, whereas sevoflurane at high doses provided a certain degree of luxury perfusion.
116 citations