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.
Citations
More filters
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]....
[...]
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
More filters
TL;DR: Unlike other inhalation anesthetics, N2O at comparable anesthetic concentrations does not inhibit mitochondrial electron transport or ATP formation coupled to it (oxidative phosphorylation), but N1O does inhibit one or more other processes, as yet unidentified, which are energetically coupled to electron transport.
Abstract: The influence of N2O on O2 consumption by mitochondria isolated from the cerebral cortex of goats was examined in incubations preequilibrated with N2O-O2 or N2-O2. Rates of O2 consumption were measured polarographically in a closed system while adenosine triphosphate (ATP) formation was maximal (after addition of excess adenosine diphosphate (ADP), state 3 respiration) and then when it was at zero (after addition of excess oligomycin, state 4 respiration). Compared with 90% N2, 90% N2O produced no change in the rate of state 3 respiration; but an observed 9% decrease in the state 4 rate and an 11% increase in the state 3: state 4 ratio were statistically significant (P less than 0.05). These differences were not seen with N2 and N2O at 70% rather than at 90%, or when succinate rather than pyruvate-malate was used as the respiratory substrate. We conclude the following: Unlike other inhalation anesthetics, N2O at comparable anesthetic concentrations does not inhibit mitochondrial electron transport or ATP formation coupled to it (oxidative phosphorylation). N2O does inhibit one or more other processes, as yet unidentified, which are energetically coupled to electron transport. The increased cerebral O2 consumption that accompanies N2O anesthesia cannot be attributed to a direct effectmore » of N2O on mitochondrial respiration.« less
11 citations
TL;DR: CCO2R is preserved during hypocapnia in children anesthetized with 1.0 and 1.5 MAC desflurane, and the lack of further increase in Vmca at higher EtCO2 concentrations implies that des flurane may cause significant cerebral vasodilatation in children.
Abstract: Purpose
Maintenance of cerebrovascular reactivity to CO2 (CCO2R) is important during neurosurgical anesthesia. This study was designed to determine the effect of different desflurane concentrations on CCC2R in children.
10 citations
TL;DR: Desflurane is associated with an increase in cerebral blood flow velocity when used to facilitate rapid emergence following a propofol infusion in children.
Abstract: Desflurane may be used to replace propofol at the end of anesthesia to facilitate rapid emergence This study determined the effect of administering desflurane during emergence of anesthesia on middle cerebral artery blood flow velocity (Vmca) in children anesthetized with propofol Thirty healthy chilren aged one to six years scheduled for orchidopexy or hypospadias repair under general anesthesia were enrolled Anesthesia was maintained with a propofol infusion targeting an estimated serum level of 3 μg·mL−1, remifentanil 02 μg·kg−1·min−1 and a caudal epidural block Transcranial Doppler sonography was used to measure Vmca at five-minute intervals In half the patients, propofol was substituted with desflurane 1 MAC, 30 min prior to the end of the surgical procedure Once steady-state had been achieved recordings of Vmca, heart rate, and mean arterial pressure were resumed Upon termination of the surgical procedure, the maintenance agent was discontinued and recordings continued at one-minute intervals during emergence of anesthesia There were no demographic differences between the two groups Vmca increased from 372 ± 31 cm·sec−1 to 577 ± 41 cm·sec−1 when propofol was changed to desflurane (P < 001 ) Upon emergence of anesthesia, Vmca decreased from 578 ± 42 cm·sec−1 to 378 ± 32 cm·sec−1 in the desflurane group (P < 001) but remained unchanged in the propofol group Desflurane is associated with an increase in cerebral blood flow velocity when used to facilitate rapid emergence following a propofol infusion in children This may be of clinical significance in patients with intracranial pathology
10 citations
TL;DR: The neuroprotective effects of etomidate do not seem to be through the augmentation of collateral or global CBF, and CBF was significantly reduced in all regions of the brain, including CDT, when Etomidate was infused.
Abstract: OBJECTIVE: Augmentation of blood flow to collateral-dependent tissue (CDT) as a result of selective vasodilation of collateral vessels has been shown to occur with various stimuli after middle cerebral artery occlusion. Etomidate, a carboxylated imidazole derivative, is a nonbarbiturate anesthetic that is used clinically both as an anesthetic and as a neuroprotective agent. The effect etomidate has on collateral cerebral vessels is unknown. The purpose of our studies was to test whether etomidate selectively augmented cerebral blood flow (CBF) to CDT during ischemia as an additional mechanism of neuroprotection. METHODS: A left craniotomy was performed in each of 14 dogs, with the animals under halothane anesthesia. A branch of the middle cerebral artery was occluded and cannulated distally for determination of CDT using a shadow flow technique. CBF and vascular pressures were measured and used to calculate vascular resistance. An etomidate infusion (0.1 mg/kg of body weight/min administered intravenously) was started, and CBF and vascular pressures were measured at 10 and 40 minutes. Hypotension was then induced, and CBF and pressures were again measured. RESULTS: CBF was significantly reduced in all regions of the brain, including CDT, when etomidate was infused. CDT showed a 53.7% reduction in flow, whereas normal CBF was reduced by at least 63.4%. During hypotension, blood flow to CDT was reduced by an additional 42.7%, whereas normal cerebrum was reduced by at least 22.7%. Vascular resistance was increased in all vessels during etomidate infusion. CONCLUSION: The neuroprotective effects of etomidate do not seem to be through the augmentation of collateral or global CBF.
8 citations
TL;DR: Propofol and N2O, when one is added to the other, produce similar dynamic FVMCA responses to sudden changes in Petco2, which slows the dynamic response and produces the response whose magnitude is proportional to the baseline FVM CA.
Abstract: Background: Nitrous oxide (N 2 O) and propofol exhibit directionally opposite effects on the cerebral circulation, vasodilation and vasoconstriction, respectively. The authors investigated an interaction between the two anesthetic agents on the dynamic cerebrovascular response to step changes in end-tidal pressure of carbon dioxide (PETCO 2 ) in humans. Methods: Participants with no systemic diseases were allocated into two groups, each of which was anesthetized sequentially with two protocols. Patients in group 1 were anesthetized with 30% O 2 + 70% N 2 O. A continuous intravenous infusion of propofol (7-10 mg . kg -1 . h -1 ) was then added to the N 2 O. Patients in group 2 were anesthetized first with continuous infusion of propofol (10 mg . kg -1 . h -1 ), and then 30% O 2 + 70% N 2 O was added to the propofol anesthesia. Using transcranial Doppler ultrasonography, blood flow velocity at the middle cerebral artery (FV MCA ) was measured during a step increase (on-response) followed by a step decrease (off-response) in PETCO 2 , with PETCO 2 ranging between approximately 28 and 50 mmHg. The dynamic FV MCA -PETCO 2 relationship was analyzed using a mathematical model that was characterized with a pure time delay, and a time constant and a gain each for the on-or off-response. Results: The addition of propofol to the N 2 O anesthesia increased the on-response time constant (P < 0.01), whereas the addition of N 2 O to the propofol anesthesia increased the time constants for on- (P < 0.01) and off-responses (P < 0.05). However, the addition of either anesthetic did not affect the gains. Conclusions: Propofol and N 2 O, when one is added to the other, produce similar dynamic FV MCA responses to sudden changes in PETCO 2 . Addition of each anesthetic slows the dynamic response and produces the response whose magnitude is proportional to the baseline FV MCA .
8 citations