The volatile anesthetic sevoflurane exhibits neuroprotective properties when assessed for motor function and histopathology after cerebral ischemia in rats. Damage of hippocampal neurons after ischemia relates to a number of cognitive deficits that are not revealed by testing animals for motor function. Therefore, the present study evaluates cognitive and behavioral function as well as hippocampal damage in rats subjected to cerebral ischemia under sevoflurane compared with fentanyl/nitrous oxide (N(2)O)/O(2) anesthesia.Thirty-four rats were trained for 10 days using a hole-board test to detect changes in cognitive and behavioral function. Rats were randomly assigned to the following groups: (A) sham/fentanyl/N(2)O/O(2) (n=7); (B) ischemia/fentanyl/N(2)O/O(2) (n=10); (C) sham/2.0 vol% sevoflurane in O(2)/air (n=7); and (D) ischemia/2.0 vol% sevoflurane in O(2)/air (n=10). Cerebral ischemia was produced by unilateral common carotid artery occlusion combined with hemorrhagic hypotension (mean arterial blood pressure 40 mmHg for 45 min). Temperature, arterial blood gases, and pH were maintained constant. Cerebral blood flow was measured using laser-Doppler flowmetry. After surgery, cognitive and behavioral function was re-evaluated for 10 days. On day 11, the brains were removed for histopathologic evaluation (hematoxylin/eosin-staining).Cognitive testing revealed deficits in declarative and working memory in ischemic rats anesthetized with fentanyl/N(2)O. Rats anesthetized with sevoflurane during ischemia showed a significantly better outcome. Hippocampal damage was significantly worse with fentanyl/N(2)O.The present data add to previous investigations showing that sevoflurane prevents a deficit in cognitive function and histopathological damage induced by cerebral ischemia in rats.

We evaluated cardiac vagal activity during sevoflurane anesthesia in neurosurgical patients. Heart rate variability was determined by power spectral analysis and entropy with the patient awake and during sevoflurane anesthesia. High frequency power (0.15-0.50 Hz) and heart rate entropy decreased during sevoflurane and these effects were significantly correlated (r = 0.71 +/- 0.12, P < 0.05). The results confirm that cardiac vagal activity was the primary determinant of heart rate variability, which was attenuated by sevoflurane.

INTRODUCTION:Reports indicate that brain regulation of oxygenation is inhibited in patients with low baseline oxyhemoglobin concentrations and that brain oxyhemoglobin concentrations are decreased with aging. The purpose of this study was to determine if regulation of brain oxygenation to changes in blood pressure is inhibited by normal aging. METHODS:Brain oxyhemoglobin (OHb) and deoxyhemoglobin (HHb) concentrations were determined from the forehead using a frequency domain near infrared spectroscopy in 27 healthy volunteers. Subjects were separated into two groups by age (20-39, n=16; 40-60, n=11). Brain hemoglobin and non-invasive blood pressure were measured in (1) supine, (2) sitting, (3) supine and (4) sitting positions with 10-min equilibration intervals between each determination. Statistical differences were determined by two way repeated measures analysis of variance. RESULTS:Young subjects were 28+/-5 years (mean+/-S.D.) and older subjects were 48+/-6 years. In supine position, OHb and HHb were 28.4+/-8.3 and 15.4+/-2.4micromol/L, respectively, in young; 22.4+/-5.7 and 13.4+/-2.9micromol/L, respectively, in older subjects, both P<0.05 between groups. Changing position from supine to sitting decreased OHb 5% and increased HHb 5% with no difference between groups. CONCLUSIONS:There was a small but significant decrease in OHb and an increase in HHb from supine to sitting position, and this effect was similar between young and older subjects. Regulation of brain oxygenation during modest decreases in blood pressure did not change in normal aging to 60 years compared to young adults.

OBJECTIVE:Although intracranial tumors may affect autonomic function, there are few reports of autonomic changes during anesthesia. The purpose of this study was to evaluate autonomic effects of anesthesia in patients with brain tumors compared to neurosurgical controls.METHODS:Two groups were evaluated: group 1 = 10 neurosurgical patients undergoing spinal cord surgery, group 2 = 10 patients with intracranial tumors. After placement of electrocardiogram and Response Entropy electroencephalogram (EEG) electrodes, 10 min baseline measures were made. Heart periods were transformed into a percentage index and heart rate entropy determined as a measure of variance of autonomic activity. Tone was evaluated as the balance between accelerator and inhibitory activity. Tone-entropy was measured during propofol anesthetic induction and the first 60 min of desflurane anesthesia before the start of surgery.RESULTS:Blood pressure and heart rate were similar between the groups. Starting at awake levels, vagal heart tone was observed. Anesthesia decreased vagal dominance to near zero in both groups. Heart rate entropy and EEG activity decreased during anesthesia with no significant difference between the groups. Desflurane concentrations required to maintain anesthesia were significantly lower in patients in brain tumors.CONCLUSION:Tone-entropy analysis of heart rate indicates anesthetic related depression of autonomic activity with no difference between groups. Normal titration of desflurane concentrations to maintain adequate blood pressure produced desflurane requirements that were lower in patients with brain tumors, while autonomic and EEG activity were similar.

Study Objective: To evaluate autonomic activity with dexmedetomidine or fentanyl infusion and desflurane anesthesia during laparoscopic gastric banding.Study Design: Randomized, single-blinded, open-label study.Setting: Operating rooms at a university hospital.Subjects: 40 patients scheduled for laparoscopic gastric banding with a mean body mass index of 50 kg/m(2).Interventions: Patients received either dexmedetomidine (0.5 mu g/kg given intravenously over 10 minutes, 0.4 mu g . kg(-1) . h(-1), n = 20) or fentanyl (0.5 pg . kg (-1) bolus, 1 mu g . kg(-1) . h(-1), n = 20) during anesthesia. Response entropy of the electroencephalogram was maintained at 45 +/- 5 by adjusting end-tidal desflurane concentration.Measurements: In the operating room, blood pressure, heart rate (HR), response entropy, end-tidal desflurane concentration, tone entropy, and power-spectral analysis of HR were measured with the patient awake; 20, 40, and 60 minutes from intubation and the start of drug infusion; and at extubation.Main Results: The mean end-tidal desflurane concentration during anesthesia was 4.0% +/- 0.6% with dexmedetomidine and 4.1% +/- 0.7% with fentanyl, indicating a similar anesthetic requirement in both groups. Autonomic activity, determined by tone entropy and spectral analysis of HR, decreased by 50% during anesthesia in both groups. The dexmedetomidine group showed a greater decrease in sympathovagal balance during anesthesia.Conclusion: Both dexmedetomidine and fentanyl facilitated anesthesia and attenuated autonomic activity. Dexmedetomidine produced a greater decrease in sympathovagal balance than fentanyl. (C) 2007 Elsevier Inc. All rights reserved.

Previous studies showed that the cerebrovasodilation response to hypercapnia is attenuated with aging. The purpose of this study was to determine if normal aging attenuates increases in brain oxygenation during hypercapnia. Prefrontal cortex oxyhemoglobin (OHb) and deoxyhemoglobin (HHb) concentrations were measured in 13 healthy subjects ages 26 to 59 years using a frequency domain tissue oximeter. Measurements were obtained under the following conditions: (1) subject awake breathing spontaneously, (2) during mask ventilation with 21% oxygen, (3) mask ventilation with 100% oxygen, (4) 100% oxygen in a rebreathing circuit to increase end-tidal CO(2). Under baseline conditions breathing room air, there was a negative correlation between baseline OHb and age (r=-0.60, P<0.05). Ventilation with 100% oxygen increased OHb without a change in total hemoglobin and no affect of age. During mask rebreathing, end-tidal CO(2) increased from 39.5+/-5.0 mm Hg (millimeters of mercury) to 56.5+/-5.7 mm Hg, which produced significant increases in OHb and total blood volume that were negatively correlated with age (r=-0.67, P<0.05) and positively correlated to baseline OHb (r=0.60, P<0.05). These results indicate that OHb concentrations decreased with age, consistent with attenuated cerebral vasodilation during hypercapnia.

BACKGROUND AND OBJECTIVES:The purpose of this study was to determine whether brain oxyhaemoglobin-deoxyhaemoglobin coupling was altered by anaesthesia or intubation-induced stress. METHODS:This was a prospective observational study in the operating room. Thirteen patients (ASA I and II) undergoing spinal or peripheral nerve procedures were recruited. They were stabilized before surgery with mask ventilation of 100% oxygen. Anaesthesia was induced with 2 microg kg(-1) fentanyl and 3 mg kg(-1) thiopental. Laryngoscopy and intubation were performed 4 min later. After intubation, desflurane anaesthesia (FiO2=1.0) was adjusted to maintain response entropy of the electroencephalogram at 40-45 for 20 min. Prefrontal cortex oxyhaemoglobin and deoxyhaemoglobin were determined every 2 s using frequency domain near-infrared spectroscopy. Blood pressure, heart rate and response entropy were collected every 10 s. RESULTS:Awake oxyhaemoglobin and deoxyhaemoglobin were 18.9 +/- 2.3 micromol (mean +/- SD) and 12.7 +/- 0.8 micromol, respectively, and neither changed significantly during induction. Intubation increased oxyhaemoglobin by 37% (P < 0.05) and decreased deoxyhaemoglobin by 16% (P < 0.05), and both measures returned to baseline within 20 min of desflurane anaesthesia. Blood pressure, heart rate and electroencephalogram response entropy increased during intubation, and the increase in heart rate correlated with the increase in brain oxygen saturation (r = 0.48, P < 0.05). CONCLUSIONS:Intubation-related stress increased oxyhaemoglobin related to electroencephalogram and autonomic activation. Stress-induced brain stimulation may be monitored during anaesthesia using frequency domain near-infrared spectroscopy.

Purpose: Pediatric patients who receive both intramuscular (IM) sedation and general anesthesia (GA) for oral rehabilitation occasionally experience prolonged sedation and delayed discharge. The Bispectral Index System (BIS) is an EEG monitor that measures the level of sedation. The authors compared discharge times of patients who had BIS monitoring to those who did not to determine if the use of BIS speeded discharge.Methods: After IRB approval, 20 children were enrolled. BIS was monitored continuously from admission until discharge. Each child received ketamine, midazolam, and glycopyrrolate IM. Once sedated, the patient was transferred to the operating room, monitored, and IV access was established. GA proceeded with sevoflurane, rocuronium, and fentanyl. Randomly, in half the patients, the anesthesiologist knew and maintained the BIS at GA level of sedation by adjusting sevoflurane. In the rest, the anesthesiologist did not know BIS. Time from turning of sevoflurane to discharge was noted and compared.Results: Patients where the BIS was known and used were discharged 60 13 minutes after the end of GA. Patients where BIS was unknown were discharged 90 +/- 11 minutes after the end of GA (P < .001).Conclusions: Based on the data, the authors recommend the use of BIS to facilitate faster discharge of pediatric patients who require IM sedation and GA for oral rehabilitation.

Objective. There is a potential use for spectral entropy or bispectral index (BIS) for controlling level of anesthesia, but it is not known how these EEG monitors relate during steady state anesthesia. We compared Response Entropy (RE) and BIS during anesthesia for laparoscopic gastric banding with RE targeted to 45. Methods. Forty patients undergoing laparoscopic gastric banding were randomly assigned to receive either fentanyl or dexmedetomidine infusion, with desflurane concentration adjusted to maintain RE at 45. During anesthesia the average RE and BIS was determined in each patient and the RE-BIS difference plotted as a function of RE every 10 seconds. Fifteen of 40 patients showed activation of RE above 60 during surgery. In these patients RE, BIS and the electromyogram (EMG) were evaluated for the period 10 minutes before and including the peak change in RE. Results. In fentanyl and dexmedetomidine treated patients the average RE was 44–47 with no statistical difference between anesthesia groups or between RE and BIS. In each patient there was a linear relationship between the RE-BIS difference and RE during anesthesia. RE and BIS were similar at a level of 41–44 and RE showed a greater range at higher and lower values compared to BIS. When RE activation was identified during surgery in 15 patients, it was associated with an increase in BIS and EMG. Conclusion. Within the range of 41–44, RE and BIS are equal but the gain of RE is 0.5 greater than BIS with deeper or lighter anesthesia. This is not likely due to increased smoothing with BIS. Identifying periods of RE activation show that BIS, EMG and RE increase together.

Dexmedetomidine (DEX) is a selective alpha2-adrenergic agonist that produces cerebral vasoconstriction. We used frequency domain near infrared spectroscopy (FD-NIRS) to study brain oxygenation during DEX intravenous bolus injection. Oxyhemoglobin (OHb), deoxyhemoglobin (HHb), brain oxygen saturation (SO2) and total hemoglobin (tHb) were acquired on the frontal right and left side in 4 neurosurgery patients without cerebral pathology. Measurements were performed using a portable brain oxymeter, Oxiplex TS (ISS, Champaign, IL). Dexmedetomidine 0.2 mcg/kg was given to attenuate hypertension during the initial stages of desflurane anesthesia. During DEX administration, regional cerebral OHb decreased from 17.7 ± 6.9 Mol/L to 16.1 ± 6.3 Mol/L (p < 0.05) and SO2 from 61 ± 12 % to 58 ± 12 % (p < 0.05). HHb did not change from 10.5 ± 2.8 Mol to 10.5 ± 2.7 Mol/L. Recovery of brain oxygenation to pre-DEX levels occurred within 5 minutes. After administration of DEX, a small but consistent decrease in OHb was observed, probably mediated by a local vasoconstrictor effect. Brain oxygenation decreased transiently with DEX treatment without an increase in HHb production.

Vavilala, MS; Muangman, S; Waitayawinyu, P; Fisk, D; Jaffe, K; Mitchell, P; Kirkness, C; Zimmerman, JJ; Ellenbogen, R; Lam, AM Author Information

Background: Studies with continuous wave near infrared spectroscopy (CW-NIRS) have shown little difference in brain oxygenation of dead compared to live subjects. We determined brain oxyhemoglobin (OHb) and deoxyhemoglobin (HHb) concentrations in healthy volunteers and cadavers using frequency domain near infrared spectroscopy (FD-NIRS).Methods: Regional OHb and HHb, brain oxygen saturation (SO2), and total hemoglobin (tHb) were determined. Nine patients who died in the hospital were evaluated by FD-NIRS in the morgue 7-96 h after death was confirmed. Ten volunteers served as a control group.Results: Absolute concentrations of brain tissue OHb and HHb were 24.9 +/- 19.1 uM and 13.8 +/- 32 uM, respectively, in live subjects. In dead subjects, OHb was 1.3 +/- 2.1 uM and HHb was 30.8 +/- 14.4 uM (both P < 0.05 compared to live). OHb showed a 90% decrease within 7 h of death. There was a significant trend for a continued decrease in OHb from 7 to 96 h.Conclusion: OHb decreased and HHb increased in dead patients compared to live volunteers. Depletion of OHb primarily occurred within 7 h of death but continued gradually over 96 h. FD-NIRS was a novel technique for determining OHb and HHb changes following death. (c) 2006 Elsevier B.V. All rights reserved.

Objective. It is reported that the electromyogram is an indicator of patient arousal during pain stimulation if anesthesia is inadequate. This may not be true during recovery from succinylcholine induced paralysis. We evaluated State entropy of the electroencephalogram (EEG, 0.8–32 Hz) and Response entropy, a combined measure of the electromyogram (EMG) and EEG (0.8–47 Hz), during recovery from paralysis with succinylcholine. Methods. Twenty patients were randomized to receive either 0.8% (n = 10) or 1.4% isoflurane (n = 10), with 2 mg/kg succinylcholine administered for paralysis in all patients. State entropy and Response entropy were evaluated using a Datex-Ohmeda Entropy module. Frontal EMG was measured separately by an EEG module. State entropy, Response entropy, and EMG were measured in awake patients, during isoflurane anesthesia and paralysis, and after 100% recovery to train of four stimulation. Results. Response entropy and State entropy decreased from awake levels in a dose related manner during 0.8% or 1.4% isoflurane and succinylcholine. Recovery from succinylcholine significantly increased Response entropy and EMG in 5 of 10 patients with 0.8% isoflurane and 8 of 10 with 1.4% isoflurane without a change in State entropy. Conclusion. Although RE and EMG increased during recovery from paralysis with succinylcholine, SE, an indicator of EEG, was not stimulated. EMG activity may not be an indicator of patient arousal after succinylcholine treatment.

OBJECT:Balloon occlusion tests (BOTs) are performed to identify patients who are at risk for ischemia and stroke following permanent internal carotid artery (ICA) occlusion. The object of this work was to determine whether patient-specific blood flow modeling can be used to identify patients in whom the BOT would not be tolerated. METHODS:The test was performed in 16 patients who underwent BOT with continuous neurological and electroencephalographic monitoring, followed by a hypotensive challenge. During hypotension a tracer was injected so that single-photon emission tomography (SPECT) scans could be obtained. Each individual brain circulation was modeled using information gained from phase-contrast magnetic resonance (MR) angiography and digital subtraction (DS) angiography, and the predicted effect of the BOT was evaluated. Six patients did not tolerate the BOT; in these patients, decreases in middle cerebral artery (M1 segment) blood flow of 41 +/- 27% (mean +/- standard deviation), anterior cerebral artery (A3 segment) flow of 56 +/- 33%, and posterior cerebral artery (P2 segment) flow of 4 +/- 13% ipsilateral to the site of occlusion were found with modeling; these changes were significantly greater than the percentage of changes measured in the contralateral hemisphere (p < 0.05). Ten patients who tolerated the BOT well had calculated decreases in ipsilateral flows of only 9 +/- 6% for the M1 segment, 12 +/- 40% for the A3 segment, and 17 +/- 21% for the P2 segment during BOT modeling. CONCLUSIONS:A decrease in blood flow in both the ipsilateral M1 and A3 segments that was greater than 20%, calculated by flow modeling of the BOT, was 100% sensitive and 100% specific in identifying patients who could not tolerate the BOT. Blood flow modeling, coupled with DS angiography and noninvasive phase-contrast MR angiography measurements to make calculations patient specific, can be used to identify patients who have an elevated risk of ischemia during the BOT.

Several non-opioid drugs have been shown to provide analgesia during and after surgery. We compared sevoflurane anesthesia with fentanyl analgesia to sevoflurane and non-opioid drug treatment for gastric bypass surgery and recovery.

UNLABELLED:Sevoflurane and propofol are neuroprotective possibly by attenuating central or peripheral catecholamines. We evaluated the effect of these anesthetics on circulating catecholamines and brain neurotransmitters during ischemia in rats. Forty male Sprague-Dawley rats were randomly assigned to one of the following treatment groups: fentanyl and N(2)O/O(2) (control), 2.0% sevoflurane, 0.8-1.2 mg x kg(-1) x min(-1) of propofol, and sham-operated rats with fentanyl and N(2)O/O(2). Ischemia (30 min) was produced by unilateral common carotid artery occlusion plus hemorrhagic hypotension to a mean arterial blood pressure of 32 +/- 2 mm Hg. Pericranial temperature, arterial blood gases, and pH value were maintained constant. Cerebral catecholamine and glutamate concentrations, sampled by microdialysis, and plasma catecholamine concentrations were analyzed using high-pressure liquid chromatography. During ischemia, circulating catecholamines were almost completely suppressed by propofol but only modestly decreased with sevoflurane. Sevoflurane and propofol suppressed brain norepinephrine concentration increases by 75% and 58%, respectively, compared with controls. Intra-ischemia cerebral glutamate concentration was decreased by 60% with both sevoflurane and propofol. These results question a role of circulating catecholamines as a common mechanism for cerebral protection during sevoflurane and propofol. A role of brain tissue catecholamines in mediating ischemic injury is consistent with our results. IMPLICATIONS:During incomplete cerebral ischemia, the neuroprotective anesthetics sevoflurane and propofol suppressed cerebral increases in norepinephrine and glutamate concentrations. In contrast, propofol, but not sevoflurane, suppressed the ischemia-induced increase in circulating catecholamines to baseline levels. The results question a role for plasma catecholamines in cerebral ischemic injury.

A 54-year-old woman with a past medical history of asthma and depression presented with right side hearing loss and ataxia. She was scheduled for a sitting craniotomy for cerebellopontine angle tumor resection. Somatosensory evoked potential, brainstem auditory evoked response, and facial nerve EMG were monitored intraoperatively. Approximately 30 minutes into the case, there was an episode of air embolism, which resolved after the source was identified and treated. Near the conclusion of the case, there was an abrupt loss of the right cortical somatosensory evoked potential signal, which never returned to baseline. A postoperative CT scan showed a substantial amount of subarachnoid air and intraventricular air in the frontal and temporal regions. The patient awakened in the ICU with no new neurologic deficit besides preoperative hearing loss on the right side. Despite the high specificity of somatosensory evoked potential change associated with postoperative neurodeficit when the change never returns to the baseline, there was no postoperative neurologic deficit in this patient. This case indicates the false-positive somatosensory evoked potentials caused by pneumocephalus in the sitting position.

BACKGROUND:Sodium nitroprusside (SNP) may decrease myocardial tissue oxygenation in dogs with normal coronary arteries. We compared SNP- with desflurane-induced hypotension on myocardial tissue oxygen and pH in dogs with left anterior descending artery constriction.METHODS:Twenty-four dogs were anesthetized with 8% desflurane for baseline anesthesia. Catheters were inserted into the femoral artery and vein and the coronary sinus. A flow probe and flow restriction device was placed on the left anterior descending (LAD) artery. A probe that measured myocardial oxygen pressure was inserted into the middle myocardium in the LAD region. Baseline measures were made of LAD artery flow, arterial and coronary sinus blood gases, and myocardial tissue gases. A 30% decrease in blood pressure was induced with SNP with unrestricted LAD flow (n=6) or when LAD artery flow was restricted by 30% from baseline (n=6). In separate dogs, a 30% decrease in blood pressure was produced with 14 +/- 1% desflurane with unrestricted LAD flow (n=6) or with baseline LAD artery flow restricted by 30% (n=6).RESULTS:During SNP-induced hypotension with no LAD constriction, LAD artery flow and coronary sinus oxygen tension increased but myocardial tissue oxygen tension (PmO2) decreased by 40%. When baseline artery flow was decreased by 30% by LAD constriction, SNP-induced hypotension decreased tissue oxygen pressure by 80%, and ischemic acidosis was produced. During unrestricted LAD artery flow or with a 30% flow restriction, desflurane-induced hypotension produced no significant change from baseline myocardial tissue oxygen tension or pH.CONCLUSION:During coronary artery constriction, desflurane-induced hypotension maintained myocardial tissue oxygenation and pH better than did SNP-induced hypotension. The divergence between tissue and coronary sinus oxygen tension during SNP suggests that arteriovenous shunting may occur.