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: Extrapolation of cerebral ZFP from instantaneous AP-V(MCA) relationships enables detection of severely elevated ICP and may be a useful and less invasive method for CPP monitoring than other methods.
Abstract: Background Cerebral perfusion pressure (CPP) is commonly calculated from the difference between arterial blood pressure (AP) and intracranial pressure (ICP). ICP can be considered the effective downstream pressure of the cerebral circulation. Consequently, cerebral circulatory arrest would occur when AP equals ICP. Estimation of AP for zero-flow pressure (ZFP) may thus allow estimation of ICP. We estimated ZFP from cerebral pressure–flow velocity relationships so that ICP could be measured by transcranial Doppler sonography. Methods We studied 20 mechanically ventilated patients with severe head injury, in whom ICP was monitored by epidural pressure transducers. AP was measured with a radial artery cannula. Blood flow velocity in the middle cerebral artery (VMCA) ipsilateral to the site of ICP measurement was measured with a 2 MHz transcranial Doppler probe. All data were recorded by a microcomputer from analogue–digital converters. ZFP was extrapolated by regression analysis of AP–VMCA plots and compared with simultaneous measurements of ICP. Results ZFP estimated from AP–VMCA plots was linearly related to ICP over a wide range of values (r=0.93). There was no systematic difference between ZFP and ICP. Limit of agreement (2 sd) was 15.2 mm Hg. Short-term variations in ICP were closely followed by changes in ZFP. Conclusion Extrapolation of cerebral ZFP from instantaneous AP–VMCA relationships enables detection of severely elevated ICP and may be a useful and less invasive method for CPP monitoring than other methods.
35 citations
TL;DR: To determine the effects of sevoflurane on middle cerebral artery blood flow velocity (Vmca) in neurologically normal children, Vmca was measured both at different MAC values and at one MAC over a specified time period, using transcranial Doppler sonography.
Abstract: Background: Sevoflurane is a suitable agent for neuroanesthesia in adult patients. In children, cerebrovascular carbon dioxide reactivity is maintained during hypo- and normocapnia under sevoflurane anesthesia. To determine the effects of sevoflurane on middle cerebral artery blood flow velocity (Vmca) in neurologically normal children, Vmca was measured both at different MAC values and at one MAC over a specified time period, using transcranial Doppler sonography.
Methods: Twenty-six healthy children undergoing elective urological surgery were enrolled (16 patients in part I and 10 in part II). In part I of the study anesthesia comprised sevoflurane 0.5, 1.0 and 1.5 MAC in 30% oxygen and a caudal epidural block. Once steady state had been reached at each sevoflurane MAC level, three measurements of Vmca, mean arterial pressure (MAP) and heart rate (HR) were recorded. In part II of the study patients received sevoflurane 1.0 MAC over a 90-min period, with the same variables being recorded at 15-min intervals.
Results: Vmca did not vary significantly at 0.5, 1.0 and 1.5 MAC sevoflurane. There was a significant decrease in MAP between 0.5 MAC and 1.0 MAC sevoflurane (P < 0.005) and also between 1.0 MAC and 1.5 MAC (P < 0.01). There was no significant change in Vmca over 90 min at 1.0 MAC sevoflurane.
Conclusion: Sevoflurane does not significantly affect cerebral blood flow velocity in healthy children at working concentrations.
35 citations
TL;DR: High-dose remifentanil decreases rCBF and mean CBFv without impairing cerebrovascular carbon dioxide reactivity, which makes remifENTanil a useful agent in the intensive care unit when sedation that can be titrated rapidly is required.
Abstract: BACKGROUND Cerebrovascular carbon dioxide reactivity during high-dose remifentanil infusion was investigated in volunteers by measurement of regional cerebral blood flow (rCBF) and mean CBF velocity (CBFv). METHODS Ten healthy male volunteers with a laryngeal mask for artificial ventilation received remifentanil at an infusion rate of 2 and 4 microg x kg-1 x min-1 under normocapnia, hypocapnia, and hypercapnia. Stable xenon-enhanced computed tomography and transcranial Doppler ultrasonography of the left middle cerebral artery were used to assess rCBF and mean CBFv, respectively. If required, blood pressure was maintained within baseline values with intravenous phenylephrine to avoid confounding effects of altered hemodynamics. RESULTS Hemodynamic parameters were maintained constant over time. Remifentanil infusion at 2 and 4 microg x kg-1 x min-1 significantly decreased rCBF and mean CBFv. Both rCBF and mean CBFv increased as the arterial carbon dioxide tension increased from hypocapnia to hypercapnia, indicating that cerebrovascular reactivity remained intact. The average slopes of rCBF reactivity were 0.56 +/- 0.27 and 0.49 +/- 0.28 ml. 100 g-1 x min-1 x mmHg-1 for 2 and 4 microg x kg-1 x min-1 remifentanil, respectively (relative change in percent/mmHg: 1.9 +/- 0.8 and 1.6 +/- 0.5, respectively). The average slopes for mean CBFv reactivity were 1.61 +/- 0.95 and 1.54 +/- 0.83 cm x s-1 x mmHg-1 for 2 and 4 microg x kg-1 x min-1 remifentanil, respectively (relative change in percent/mmHg: 1.86 +/- 0.59 and 1.79 +/- 0.59, respectively). Preanesthesia and postanesthesia values of rCBF and mean CBFv did not differ. CONCLUSION High-dose remifentanil decreases rCBF and mean CBFv without impairing cerebrovascular carbon dioxide reactivity. This, together with its known short duration of action, makes remifentanil a useful agent in the intensive care unit when sedation that can be titrated rapidly is required.
34 citations
TL;DR: The data suggest that etomidate produces an adverse effect on mitochondrial function early in the course of focal cerebral ischemia, in part, by inhibition of NOS.
Abstract: We evaluated the effect of N(G)-nitro-L-arginine-methyl-ester (l-NAME, a nitric oxide synthase [NOS] inhibitor) and L-arginine (nitric oxide substrate) on cerebral mitochondrial dysfunction (hereafter referred to as "injury") after temporary middle cerebral artery occlusion (MCAo) during halothane or etomidate anesthesia in spontaneously hypertensive rats. Sixty minutes before MCAo, rats were randomized to 1 of 5 regimens (n = 8 per group): h/control, 1.2 minimum alveolar anesthetic concentration of halothane; h/L-NAME, 1.2 minimum alveolar anesthetic concentration of halothane and L-NAME (30 mg/kg); etomidate, an electroencephalographic (EEG) burst suppression dose of etomidate; e/L-NAME, an EEG burst suppression dose of etomidate and L-NAME (30 mg/kg); or e/L-NAME/arg, an EEG burst suppression dose of etomidate, L-NAME (30 mg/kg), and L-arginine (bolus of 300 mg/kg with an infusion at 35 mg x kg(-1) x min(-1)). After 180 min of MCAo and 120 min of reperfusion, volume of injury was determined using 2,3,5-triphenytetrazolium stain. Injury volume (mm(3), mean +/- sd) was larger in the etomidate group (153 +/- 17) than the halothane anesthetized h/control group (93 +/- 16) (P < 0.05) but did not differ between the e/L-NAME (162 +/- 17) and h/L-NAME groups (155 +/- 26). Injury volume in the e/L-NAME/arg group (88 +/- 15) was not different from the h/control group (93 +/- 16) and was less than that in either the etomidate or the e/L-NAME groups (P < 0.05). The data reproduce our previous observation that, relative to a halothane-anesthetized control state, etomidate has an adverse effect on ischemic injury in the setting of temporary focal cerebral ischemia. Prior inhibition of NOS with L-NAME resulted in no difference in the volume of injury between groups receiving etomidate or halothane (162 +/- 17 versus 155 +/- 26). Administration of a large dose of L-arginine prevented the adverse effect of etomidate. The data were obtained after only 2 h of reperfusion and therefore cannot be construed as representative of final neurologic outcome. They nonetheless suggest that etomidate produces an adverse effect on mitochondrial function early in the course of focal cerebral ischemia, in part, by inhibition of NOS.
33 citations
TL;DR: Nitrous oxide inhalation had no effect either on CBV or on the normal CBV–CO2 response in humans during normocapnia and hypocapnia.
Abstract: BACKGROUND: It is generally argued that variations in cerebral blood flow create concomitant changes in the cerebral blood volume (CBV). Because nitrous oxide (N(2)O) inhalation both increases cerebral blood flow and may increase intracranial pressure, it is reasonable to assume that N(2)O acts as a general vasodilatator in cerebral vessels both on the arterial and on the venous side. The aim of the current study was to evaluate the effect of N(2)O on three-dimensional regional and global CBV in humans during normocapnia and hypocapnia. METHODS: Nine volunteers were studied under each of four conditions: normocapnia, hypocapnia, normocapnia + 40-50% N(2)O, and hypocapnia + 40-50% N(2)O. CBV was measured after (99m)Tc-labeling of blood with radioactive quantitative registration via single photon emission computer-aided tomography scanning. RESULTS: Global CBV during normocapnia and inhalation of 50% O(2) was 4.25 +/- 0.57% of the brain volume (4.17 +/- 0.56 ml/100 g, mean +/- SD) with no change during inhalation of 40-50% N(2)O in O(2). Decreasing carbon dioxide (CO(2)) by 1.5 kPa (11 mmHg) without N(2)O inhalation and by 1.4 kPa (11 mmHg) with N(2)O inhalation reduced CBV significantly (F = 57, P < 0.0001), by 0.27 +/- 0.10% of the brain volume per kilopascal (0.26 +/- 0.10 ml x 100 g(-1) x kPa(-1)) without N(2)O inhalation and by 0.35 +/- 0.22% of the brain volume per kilopascal (0.34 +/- 0.22 ml x 100 g(-1) x kPa(-1)) during N(2)O inhalation (no significant difference). The amount of carbon dioxide significantly altered the regional distribution of CBV (F = 47, P < 0.0001), corresponding to a regional difference in Delta CBV when CO(2) is changed. N(2)O inhalation did not significantly change the distribution of regional CBV (F = 2.4, P = 0.051) or Delta CBV/Delta CO(2) in these nine subjects. CONCLUSIONS: Nitrous oxide inhalation had no effect either on CBV or on the normal CBV-CO(2) response in humans. (Less)
33 citations