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Background Perioperative hypothermia has been reported to increase the occurrence of cardiovascular complications. By increasing the activity of sympathetic nervous system, perioperative hypothermia also has the potential to increase cardiac injury and dysfunction associated with subarachnoid hemorrhage. Methods The Intraoperative Hypothermia for Aneurysm Surgery Trial randomized patients undergoing cerebral aneurysm surgery to intraoperative hypothermia (n = 499, 33.3 degrees +/- 0.8 degrees C) or normothermia (n = 501, 36.7 degrees +/- 0.5 degrees C). Cardiovascular events (hypotension, arrhythmias, vasopressor use, myocardial infarction, and others) were prospectively followed until 3-month follow-up and were compared in hypothermic and normothermic patients. A subset of 62 patients (hypothermia, n = 33; normothermia, n = 29) also had preoperative and postoperative (within 24 h) measurement of cardiac troponin-I and echocardiography to explore the association between perioperative hypothermia and subarachnoid hemorrhage-associated myocardial injury and left ventricular function. Results There was no difference between hypothermic and normothermic patients in the occurrence of any single cardiovascular event or in composite cardiovascular events. There was no difference in mortality (6%) between groups, and there was only a single primary cardiovascular death (normothermia). There was no difference between hypothermic and normothermic patients in postoperative versus preoperative left ventricular regional wall motion or ejection fraction. Compared with preoperative values, hypothermic patients had no postoperative increase in cardiac troponin-I (median change 0.00 microg/l), whereas normothermic patients had a small postoperative increase (median change + 0.01 microg/l, P = 0.038). Conclusion In patients undergoing cerebral aneurysm surgery, perioperative hypothermia was not associated with an increased occurrence of cardiovascular events.

Background Although hypothermia and barbiturates improve neurologic outcomes in animal temporary focal ischemia models, the clinical efficacy of these interventions during temporary occlusion of the cerebral vasculature during intracranial aneurysm surgery (temporary clipping) is not established. Methods A post hoc analysis of patients from the Intraoperative Hypothermia for Aneurysm Surgery Trial who underwent temporary clipping was performed. Univariate and multivariate logistic regression methods were used to test for associations between hypothermia, supplemental protective drug, and short- (24-h) and long-term (3-month) neurologic outcomes. An odds ratio more than 1 denotes better outcome. Results Patients undergoing temporary clipping (n = 441) were assigned to intraoperative hypothermia (33.3 degrees +/- 0.8 degrees C, n = 208) or normothermia (36.7 degrees +/- 0.5 degrees C, n = 233), with 178 patients also receiving supplemental protective drug (thiopental or etomidate) during temporary clipping. Three months after surgery, 278 patients (63%) had good outcome (Glasgow Outcome Score = 1). Neither hypothermia (P = 0.847; odds ratio = 1.043, 95% CI = 0.678-1.606) nor supplemental protective drug (P = 0.835; odds ratio = 1.048, 95% CI = 0.674-1.631) were associated with 3-month Glasgow Outcome Score. The effect of supplemental protective drug did not significantly vary with temperature. The effects of hypothermia and protective drug did not significantly vary with temporary clip duration. Similar findings were made for 24-h neurologic status and 3-month Neuropsychological Composite Score. Conclusion In the Intraoperative Hypothermia for Aneurysm Surgery Trial, neither systemic hypothermia nor supplemental protective drug affected short- or long-term neurologic outcomes of patients undergoing temporary clipping.

Background Cardiac protection afforded by ischemic preconditioning (IPC) and anesthetic preconditioning (APC) are significantly reduced in the senescent myocardium. The authors hypothesized that age would differentially modulate gene expression induced by IPC and APC in vivo. Methods Affymetrix RAT EXON ST 1.0 gene chips (Affymetrix, Santa Clara, CA) were used to explore the transcriptional response to IPC and APC in Fisher 344 male rats (young, 3-5 months, and old, 20-24 months, respectively). Both cohorts, young and old, were divided into three groups: (1) sham control, (2) IPC, and (3) APC. After a total of 90 min, the heart was removed, and the total RNA and protein were extracted. Results Thirty-one transcripts were increased in the young animals subjected to IPC, particularly transcriptional regulators (Atf3, Egr-1, Btg2, Egr2), cytokines (interleukin 6, CSF1, Myd88), chemokines (Cxcl10, Ccl2, Ccl7), regulators of growth and inflammation (Reg3g, Hamp), remodeling and cell adhesion migration (Cyr61, Tfpi2, Timp1), regulators of apoptosis/cell death (Birc3, Arntl, Hamp, Phlda1), and cell cycle control/DNA repairs (Rrad, Gadd45b, Gadd45g). In contrast, only one transcript increased (Atf3) in the old animals subjected to IPC. No changes in gene expression were found in the young or the old animals subjected to APC. Conclusions Early-phase IPC and APC induced different genomic responses. The absence of detectable changes associated with early-phase APC suggests a posttranscriptional or posttranslational mechanism. The absence of a genomic response in the senescent myocardium (except for IPC-induced Atf3) could underlie the failure of IPC to provide any cardiac protective benefit to older animals.

General anesthesia, at a minimum, provides amnesia and unresponsiveness. Although anesthetics have many modulatory effects on neuronal ionophore protein complexes, it is not clear that the resulting electrophysiologic changes are the sole mechanisms of clinical anesthetic action. Cells respond to environmental changes in several ways, including alterations in DNA transcription leading to changes in the cell's proteins. We sought to expose the changes in global genomic expression, seeking potential targets involved in the processes of anesthetic-induced amnesia, and persistent long-term side effects of general anesthesia, including nausea and postoperative cognitive decline. Using Affymetrix GeneChips, we surveyed changes in expression across the entire expressed genome of Sprague-Dawley rat (n = 10 baseline, n = 6 isoflurane) basolateral amygdala 6 h after exposure to 15 min of 2% (1.4 MAC) isoflurane. Isoflurane administration was associated with altered expression in 269 unique genes possessing functional annotation. Affected genes were related to DNA transcription, protein synthesis, metabolism, signaling cascades, cytoskeletal structural proteins, and neural-specific proteins, among others. Even brief exposure to isoflurane leads to widespread changes in the genetic control in the amygdala 6 h after exposure. Gene expression is a dynamic process that may explain some long-term effects of anesthesia and that has the potential to modulate some of those effects using specific molecular therapeutics.

Awareness with recall after general anesthesia is an infrequent, but well described, phenomenon that may result in posttraumatic stress disorder. There are no recent data on the incidence of this complication in the United States. We, therefore, undertook a prospective study to determine the incidence of awareness with recall during general anesthesia in the United States. This is a prospective, nonrandomized descriptive cohort study that was conducted at seven academic medical centers in the United States. Patients scheduled for surgery under general anesthesia were interviewed in the postoperative recovery room and at least a week after anesthesia and surgery by using a structured interview. Data from 19,575 patients are presented. A total of 25 awareness cases were identified (0.13% incidence). These occurred at a rate of 1-2 cases per 1000 patients at each site. Awareness was associated with increased ASA physical status (odds ratio, 2.41; 95% confidence interval, 1.04-5.60 for ASA status III-V compared with ASA status I-II). Age and sex did not influence the incidence of awareness. There were 46 additional cases (0.24%) of possible awareness and 1183 cases (6.04%) of possible intraoperative dreaming. The incidence of awareness during general anesthesia with recall in the United States is comparable to that described in other countries. Assuming that approximately 20 million anesthetics are administered in the United States annually, we can expect approximately 26,000 cases to occur each year.

Devices which monitor some aspect of anesthetic drug effects have evolved in the past few years into imperfect, but very useful, clinical tools. With appropriate respect for their limitations these monitors can be used to reduce anesthetic drug utilization and turnover time. The intriguing hypothesis that such monitors will reduce the risk of intraoperative awareness is currently under test.

Background Nitrous oxide (N2O) is a commonly used sedative for painful diagnostic procedures and dental work. The authors sought to characterize the effects of N2O on quantitative electroencephalographic (EEG) variables including the bispectral index (BIS), a quantitative parameter developed to correlate with the level of sedation induced by a variety of agents. Methods Healthy young adult volunteers (n = 13) were given a randomized sequence of N2O/O2 combinations via face mask. Five concentrations of N2O (10, 20, 30, 40, and 50% atm) were administered for 15 min (20 min for the first step). EEG was recorded from bilateral frontal poles continuously. At the end of each exposure, level of sedation was assessed using primarily the Observer Assessment of Alertness/Sedation (OAA/S) scale. Results One subject withdrew from the study because of emesis at 50% N2O. N2O (50%) increased theta, beta, 40-50 Hz, and 70-110 Hz band powers. BIS and spectral edge frequency during 50% N2O/O2 did not differ significantly from baseline values. Abrupt decreases from higher to lower concentrations frequently evoked a profound, transient slowing of activity. No significant change in OAA/S was detected during the study. Conclusions Although the spectral content of the EEG changed during N2O administration, reflecting some pharmacologic effect, the subjects remained cooperative and responsive throughout, and therefore N2O can only be considered a weak sedative at the tested concentrations. Despite changes in the lower and higher frequency ranges of EEG activity, the BIS did not change, which is consistent with its design objective as a specific measure of hypnosis.

Background Evoked, recurrent electromyographic activity (F waves) reflect alpha-motor neuron excitability. Based on observations that other inhaled anesthetics do so, we hypothesized that nitrous oxide, alone or in combination with isoflurane, would depress F-wave activity and correlate with depression of movement response to tail clamp or electric stimulation. Methods In study 1, the authors examined the effect of nitrous oxide in combination with isoflurane in 13 normocapnic Sprague-Dawley rats anesthetized with 1.0% isoflurane (0.7 minimum alveolar concentration) in oxygen. The tibial nerve was stimulated at the popliteal fossa, and evoked electromyographic activity [M (direct neuromuscular junctional response) and F waves] were recorded from ipsilateral foot muscles. The effect of the addition of 30% or 70% nitrous oxide was measured. F-wave amplitude/M-wave amplitude ratio (F/M) was determined from each stimulus-electromyographic response pair. F/M vs. movement response to 60-s tail clamp was assessed after each recording session. F-wave amplitude/M-wave amplitude ratio at adjacent doses that permitted and prevented movement were compared. In study 2, the authors examined the effect of (hyperbaric) nitrous oxide as the sole anesthetic agent on F waves. In 11 rats anesthetized with isoflurane, stimulation and recording electrodes were placed as described above, with additional electrodes for stimulation placed in the tail. Rats were placed in a pressure chamber pressurized with nitrous oxide/oxygen to 3.4 atm. Thirty m were allowed for isoflurane washout. Electromyographic activity was evoked and recorded at 1.0, 1.6, 2.2 and 2.7 atm N2O (random order). Movement in response to 60 s of 15 V, 50-Hz tail stimulation was evaluated after each recording session. Results Nitrous oxide with or without isoflurane produced a dose-dependent decrease in F/M. By interpolation of this data, the authors found that 2 atm N2O alone, or 44% N2O added to 1.0% isoflurane at 1.0 atm, produced 1.0 minimum alveolar concentration anesthesia. At the deepest level of isoflurane/ nitrous oxide that permitted movement, mean F/M was 20.6 +/- 17.5%; at the lowest concentration that blocked movement, rats had a mean F/M of 13.7 +/- 13.9% (P = 0.01). At the minimal hyperbaric nitrous oxide blocking movement, rats had a mean F/M of 3.7 +/- 2.9%, whereas the F/M at the highest nitrous oxide dose that permitted movement was 4.4 +/- 2.7% (P < 0.04). Conclusions Because nitrous oxide depressed F-wave but not M-wave activity, the data suggest a central (spinal) rather than neuromuscular junctional site of action of this agent. The direct correlation between nitrous oxide dose, F-wave amplitude depression, and surgical immobility suggests the possibility of using F-wave activity to predict the likelihood of anesthetic-induced immobility. However, the mechanism of action of nitrous oxide may differ from that of the potent inhaled agents.

Summary: Surgical treatment is increasingly used for patients with medically refractory seizures. Valproate (VPA) is an effective, widely used anticonvulsant in this patient population, but believed by some researchers to increase surgical bleeding because of quantitative thrombocytopenia and functional defects in platelet aggregation. Because we have observed no clinical evidence that perioperative administration of VPA increases blood loss or complications related to postoperative bleeding in patients undergoing temporal lobectomy at our institution, we sought to test this hypothesis. We made a retrospective review of the medical records of all patients who underwent epilepsy surgery at the University of California, San Francisco Medical Center, from September 1986 through January 1993. Patients who had a temporal lobectomy and whose medical records documented preoperative platelet counts and pre- and postoperative hematocrit and hemoglobin values were included. We excluded patients who had cranial surgery before temporal lobectomy and those with intracranial neoplasms or vascular malformations. Patients were divided into two groups: those who received VPA in the immediate preoperative period and those who had not received VPA recently. We compared the estimated surgical blood loss and the estimated change in red blood cell (RBC) volume between groups by unpaired t tests. The charts of 87 consecutive patients qualified for inclusion in the study. Patients in the VPA group had relative (but not absolute) thrombocytopenia preoperatively (235 ± 64 vs. 277 ± 69 k in the No-VPA group). There were no differences in the estimated blood loss, RBC volume, or in the incidence of postoperative transfusion. VPA apparently does not increase complications of hemostasis during therapeutic surgical resections for epilepsy. Therefore, we do not recommend routinely discontinuing VPA before craniotomy.

Background In vitro studies demonstrate that halothane, but not isoflurane, inhibits bradykinin-induced calcium currents and prostacyclin release in cultured endothelial cells. Because bradykinin is an important endogenous mediator of inflammation, we assessed the effects of halothane, isoflurane, and pentobarbital on plasma extravasation, a component of tissue inflammation induced by bradykinin, in rats. Methods We anesthetized 23 rats with halothane (0.8 or 1.3 minimum alveolar concentration [MAC]), isoflurane (1.3 MAC), or pentobarbital (total of 85 mg/kg intraperitoneally). Their tracheas were intubated and their lungs mechanically ventilated. After intravenous administration of Evans blue dye, we perfused normal saline followed by bradykinin or platelet-activating factor, another inflammatory mediator, intraarticularly via needles placed in the knee joint. We collected perfusate and estimated extravasation by measuring dye in the perfusate using spectrophotometry. Results Bradykinin increased plasma extravasation eight- to ninefold above baseline in both pentobarbital- and isoflurane-anesthetized rats. In contrast, bradykinin-induced plasma extravasation at 0.8 MAC and 1.3 MAC of halothane was approximately 40% (P < 0.01) and 15% (P < 0.001), respectively, of that in pentobarbital- and isoflurane-anesthetized rats. Baseline plasma extravasation was lower in rats anesthetized with either concentration of halothane compared with pentobarbital or isoflurane (all P < 0.001). Platelet-activating factor-induced plasma extravasation was similar for all anesthetics. Conclusion Halothane, but not isoflurane or pentobarbital, inhibits both baseline and bradykinin-induced peripheral plasma extravasation, demonstrating that volatile anesthetics differentially modulate this important component of inflammation.

BACKGROUND: The power spectrum of the electroencephalogram (EEG) may be analyzed to provide quantitative measures of EEG activity (e.g., spectral edge, which defines the highest EEG frequency at which significant activity is found). The current study tested the hypothesis that spectral edge and similar measures distinguish different functional depths of anesthesia in humans. METHODS: Three groups were studied. Group 1 consisted of 34 surgical patients (ASA physical status 1 or 2) who received 0.6, 1.0 and 1.4 MAC isoflurane anesthesia. A subgroup (group 2) of group 1 was tested during 1.0 MAC isoflurane anesthesia at surgical incision. Group 3 consisted of 16 volunteers who listened to an audiotape while receiving 0.15, 0.3, and 0.45 MAC isoflurane or 0.3, 0.45, and 0.6 MAC nitrous oxide in oxygen. The audiotape contained information designed to test implicit and explicit memory formation. We tested the ability of six EEG parameters (spectral-edge, 95th percentile power frequency, median power, and zero crossing frequencies and total power in the alpha- [8-13 Hz] and delta- [< 4 Hz] power ranges) to predict movement after surgical incision, purposeful response to command, or memory of information presented during anesthetic administration. RESULTS: Isoflurane decreased EEG activity in group 1 in a dose-related fashion. The 55% of group 2 who made purposeful movements in response to incision did not differ in their EEG from nonresponders (e.g., spectral edge 19.8 +/- 3.1 vs. 19.3 +/- 2.6 Hz, mean +/- SD). In group 3, memory of the information presented did not correlate with values of any EEG parameter. Response to verbal command was associated with lower anesthetic concentrations and with smaller alpha- and delta-band power (298 +/- 66 vs. 401 +/- 80 watts; and 75 +/- 20 vs. 121 +/- 49 watts, mean +/- SD), but there was no difference in values for other parameters. CONCLUSIONS: We conclude that our EEG measures do not predict depth of anesthesia as defined by the response to surgical incision, the response to verbal command or the development of memory.

In essence, the clinical goal of general anesthesia is to produce a state of unresponsiveness and amnesia. These endpoints are commonly achieved with drugs like isoflurane, but the sites and mechanisms by which these specific endpoints are achieved remain unknown. Blocking the somatic motor response to painful stimuli is widely used as an indicator of anesthetic adequacy, and the concentration of anesthetic agent (minimum alveolar concentration [MAC]) required to achieve this unresponsiveness is the benchmark of anesthetic potency. Recent work has demonstrated that precollicular decerebration does not alter MAC in rats, suggesting that the forebrain is not a major site of action of isoflurane in blocking motor responses. The brain stem contains systems that modulate pain processing in the spinal cord. The current study was undertaken to assess the relative roles of the brain stem and spinal cord as sites of anesthetic action in blocking somatic responsiveness.In seven rats, anesthesia was induced and maintained with isoflurane in oxygen. MAC was determined by observing the response to tail clamp and fore- and hind limb toe pinch at three times: after intubation, after cervical laminectomy, and after staged hypothermic spinal cord transection.MAC determined by tail clamp did not change during the protocol (1.28 +/- 0.08% [mean +/- standard deviation] baseline vs. 1.25 +/- 0.18% postlaminectomy vs. 1.03 +/- 0.40% posttransection). In one animal, the MAC value decreased from a prelesion value of 1.2% to 0.25%, accounting for most of the variance in the postlesion mean; the MAC value as determined by withdrawal to rear paw pinch was unchanged from its prelesion value in this animal. The MAC values as determined by toe pinch in all animals remained unchanged after spinal transection of the lesion both rostrally and caudally.Somatic motor responsiveness and its sensitivity to isoflurane appeared to be unaltered despite acute loss of descending cortical and bulbar controls. This observation suggests that the site of anesthetic inhibition of motor response may be in the spinal cord.

When given for a sufficient time and dose intravenously, neuromuscular blocking drugs eventually can enter the cerebrospinal fluid (CSF). To study the potential pharmacologic consequences of neuromuscular blocking drugs in the CSF, a model was developed in the rat by using an intrathecal infusion of these drugs. A cannula was stereotaxically implanted in a lateral cerebral ventricle of anesthetized male Sprague-Dawley rats (250-300 g). Several days later, the effects of an intraventricular infusion (5 microL/min) of atracurium (0.804 mumol/mL), pancuronium (0.172 mumol/mL), and vecuronium (21.978 mumol/mL) were studied in unanesthetized rats. These rats (n = 6 in each group) exhibited dose-dependent hyperexcitability, during drug infusion, with seizures occurring at threshold doses of (mean), 0.12, 0.26, and 0.065 +/- 0.010 and 3.32 mumol/kg of atracurium, pancuronium, and vecuronium, respectively. The neuromuscular ED50 (intravenous dose required to produce a 50% depression of twitch tension) in rats determined by other investigators are 0.408, 0.115, and 0.352 mumol/kg for atracurium, pancuronium, and vecuronium, respectively. Therefore, seizure threshold doses were not related to the potencies of these drugs as neuromuscular blocking drugs. Based on these data, central nervous system effects were studied over the subseizure dose range approximating 1/100, 1/10, and 1/5 of the cumulative dose causing seizures for each drug (n = 5 for each dose). At 1/100 of seizure dose, decreased locomotor activity and piloerection occurred. At 1/10 to 1/5 of seizure dose, agitation, shivering, splayed limbs, and whole body shaking resulted.(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVE: We examined the incidence of perioperative fever and its relationship to outcome among patients enrolled in the Intraoperative Hypothermia for Aneurysm Surgery Trial. METHODS: One thousand patients with initial World Federation of Neurological Surgeons grades of I to III undergoing clipping of intracranial aneurysms after subarachnoid hemorrhage were randomized to intraoperative normothermia (36 degrees C-37 degrees C) or hypothermia (32.5 degrees C-33.5 degrees C). Fever (> or =38.5 degrees C) and other complications (including infections) occurring between admission and discharge (or death) were recorded. Functional and neuropsychologic outcomes were assessed 3 months postoperatively. The primary outcome variable for the trial was dichotomized Glasgow Outcome Scale (good outcome versus all others). RESULTS: Fever was reported in 41% of patients. In 97% of these, fever occurred in the postoperative period. The median time from surgery to first fever was 3 days. All measures of outcome were worse in patients who developed fever, even in those without infections or who were World Federation of Neurological Surgeons grade I. Logistic regression analyses were performed to adjust for differences in preoperative factors (e.g., age, Fisher grade, initial neurological status). This demonstrated that fever continued to be significantly associated with most outcome measures, even when infection was added to the model. An alternative stepwise model selection process including all fever-related measures from the preoperative and intraoperative period (e.g., hydrocephalus, duration of surgery, intraoperative blood loss) resulted in the loss of significance for dichotomized Glasgow Outcome Scale, but significant associations between fever and several other outcome measures remained. After adding postoperative delayed ischemic neurological deficits to the model, only worsened National Institutes of Health Stroke Scale score, Barthel Activities of Daily Living index, and discharge destination (home versus other) remained independently associated with fever. CONCLUSION: These findings suggest that fever is associated with worsened outcome in surgical subarachnoid hemorrhage patients, although, because the association between fever and the primary outcome measure for the trial is dependent on the covariates used in the analysis (particularly operative events and delayed ischemic neurological deficits), we cannot rule out the possibility that fever is a marker for other events. Only a formal trial of fever treatment or prevention can address this issue.

Desflurane is a potent inhaled anesthetic associated with a dose-dependent depression of cortical electrical activity. Recently, it has been suggested that the burst suppression pattern seen in dogs given moderately high doses (2.0 MAC) of desflurane may spontaneously subside. This observation suggests the development of acute tolerance to at least some of the anesthetic effects of this drug. No other volatile anesthetic has been found to produce acute tolerance. We attempted to replicate these findings in domestic swine. Five juvenile swine (25-30 kg) were anesthetized with desflurane in oxygen and during normocapnia were exposed to two doses of desflurane sufficient to induce burst suppression (1.5 and 1.7 MAC) for 35 min at each dose, with a period of EEG recovery (0.6 MAC) before, between (in 3 of 5 animals), and after the high doses. Frontoparietal EEG was continuously recorded and the burst suppression ratio continuously calculated. Suppression was more complete at 1.7 MAC than at 1.5 MAC (98.24 +/- 1.75 vs. 90.80 +/- 3.05%, respectively, mean +/- standard deviation). The degree of burst suppression activity did not change over time at either 1.5 (P greater than 0.33) or 1.7 MAC desflurane (P greater than 0.41). There was no EEG evidence of tolerance to desflurane anesthesia in swine.

Desflurane (formerly I-653) is a new inhalaticnal anesthetic with a promising pharmacokinetic profile that includes low solubility in blood and tissue, including fat. Since its lipid solubility is less than that of other volatile agents, it may have lower potency. Low solubility would be expected to increase the rate at which alveolar concentration approaches inspired concentration during induction as well as to increase the rate of elimination of desflurane from blood at emergence. We determined the minimum alveolar concentration (MAC) of desflurane in 44 unpremedicated ASA physical status 1 or 2 patients undergoing elective surgery. We prospectively studied four patient groups distinguished by age and anesthetic regimen: 18-30 versus 31-65 yr and desflurane in 60% N2O/40% O2 versus desflurane in O2. Anesthesia was induced with desflurane or desflurane in 60% N2O/40% O2. MAC was determined by a modification of Dixon's up-and-down method with increments of 0.5% desflurane. The MAC of desflurane in O2 was 7.25 +/- 0.0 (mean +/- SD) in the 18-30-yr age group, and 6.0 +/- 0.29 in the 31-65-yr group; the addition of 60% N2O reduced the MAC to 4.0 +/- 0.29 and 2.83 +/- 0.58, respectively. The median time from discontinuation of desflurane to an appropriate response to commands was 5.25 min. Desflurane appears to be a mild airway irritant but was well tolerated by all patients.

The electroencephalographic (EEG) effects of a new inhaled anesthetic are of interest because of the potential of such agents to produce excitatory (convulsant) activity and because of the potential usefulness of the EEG as an indicator of anesthetic depth and cerebral activity. Accordingly, we examined the EEG in 12 healthy, young male volunteers during desflurane anesthesia. Each subject had a baseline recording and then steady-state exposure to 6, 9, and 12% (0.83, 1.24, and 1.66 MAC) desflurane in O2 alone, and to 3, 6, and 9% desflurane in O2 with 60% N2O. The sequence of doses and the presence of N2O were randomized. We used mechanical ventilation to maintain normocapnia at each dose level. We also tested the effects of hypercapnia secondary to spontaneous ventilation. Additionally, at 1.24 MAC, subjects' lungs were hyperventilated to a PCO2 of 25.8 +/- 0.7 mmHg and exposed to rhythmic, loud clapping to attempt to provoke excitatory phenomena. Finally, after at least 6 h exposure to desflurane, we repeated measurements at 0.83 and 1.66 MAC to assess possible tolerance. Four channels of EEG were monitored visually, and at each dose, a quantitative EEG analysis was performed. Desflurane produced EEG changes comparable to those observed with equipotent levels of isoflurane. No epileptiform activity was seen. Desflurane significantly suppressed EEG activity; prominent burst suppression was seen at 1.24 MAC and higher. Substitution of N2O for 0.42 MAC desflurane reduced the degree of EEG suppression relative to the equipotent administration of desflurane and O2. Quantitative EEG measures for the early doses and for the later, repeated exposures did not differ.

Background From a patient's perspective, intraoperative amnesia is an essential component of general anesthesia. Without specific strategies to reduce recall, its incidence is approximately 0.2% in the general surgical population and may be higher in certain subpopulations. We sought to test the validity for predicting recall of a new spectral entropy-based clinical electroencephalogram monitor. Methods We studied 16 volunteers in an unblinded crossover design to assess the correlation of entropy values with behavioral end points during sedation with either propofol or sevoflurane. The end points we considered included word recall, and motor response to verbal command. We also examined the stimulatory effect of verbal commands on electroencephalogram entropy. Logistic regression, receiver operating characteristics, and prediction probability were used to analyze the data. Results Both State Entropy and Response Entropy were closely correlated with both behavioral end points. The prediction probability of these parameters under a variety of conditions ranged from 0.85 to 0.96. Verbal command to move increased entropy in a dose and drug-dependent fashion. Conclusions Entropy parameters in this group of young, healthy volunteers appear to be reliable predictors of recall. These results justify extending these studies to additional anesthetics and to surgical patients.

Background Depression of spinal alpha-motor neurons apparently plays a role in the surgical immobility induced by isoflurane. Using the noninvasive technique of F-wave analysis, the authors tested the hypothesis that depressed motor neuron excitability is an effect common to other clinically relevant inhaled anesthetics. Methods The authors measured F-wave amplitude in rats anesthetized with desflurane, enflurane, halothane, or sevoflurane. Each animal received one anesthetic at five equipotent anesthetic concentrations (0.6, 0.8, 1.2, and 1.6 minimum alveolar concentration [MAC] and 0.8 MAC with 65% N2O). F waves were detected as late potentials in electromyographic responses evoked in the intrinsic muscles of the hind paw after monopolar stimulation of the ipsilateral posterior tibial nerve. Results All tested inhaled anesthetics depressed F-wave amplitude but not M-wave (orthodromic, early muscle activation) amplitude, and increased M-F latency in a dose-dependent manner. At 1.0 MAC, the estimated F/M ratio was 70 +/- 13% SD of that at baseline (0.6 MAC). Nitrous oxide added to 0.8 MAC of the potent vapors depressed F/M ratio by 63 +/- 17%. Conclusions All anesthetics tested appeared to depress the excitability of spinal motor neurons. This effect may contribute to surgical immobility, and its magnitude is comparable at equipotent concentrations of agents. The authors hypothesize that this effect is due to hyperpolarization, although, currently, there is insufficient information to discriminate between pre- and postsynaptic mechanisms.

Background The ability of general anesthetics to suppress somatomotor responses to surgical incision and other noxious stimuli is of particular clinical relevance. When the blockade is due to inhaled agents, this effect can be quantified as the minimum alveolar concentration (MAC), i.e., that concentration that blocks movement evoked by a noxious stimulus (ED50). Methods To identify the neural structures that subtend this somatomotor response, we anesthetized 14 rats with isoflurane in oxygen and performed bilateral parietal-temporal craniotomles. In each rat, MAC was repeatedly tested using tail-clamping and Dixon's up-down concentration technique. After determination of baseline MAC, seven rats underwent aspiration decerebration, after which MAC was repeatedly measured. Results In the control group (N = 7), MAC (mean ± SD) remained constant at 1.30 ± 0.25% for more than 6 h. In the seven rats that underwent aspiration decerebration, baseline MAC was 1.26 ± 0.14%. These seven rats with histologically validated precollicular decerebration demonstrated no change in MAC relative to control rats, as much as 11 h after decerebration (P = 0.14). Conclusions These findings suggest that the anesthetic-induced unresponsiveness to noxious stimuli measured by MAC testing does not depend on cortical or forebrain structures in the rat.

BACKGROUND: Sufentanil has been reported to increase cerebral blood flow in comparison with fentanyl. However, because of the use of animal models, supraclinical doses and/or background anesthetic agents, the clinical applicability of these studies remains difficult to assess. Therefore, transcranial Doppler ultrasonography was used to determine the cerebral hemodynamic effects of equianesthetic doses of fentanyl and sufentanil on middle cerebral artery (MCA) blood flow velocity in patients without intracranial pathologic conditions. METHODS: Twenty-four unpremedicated American Society of Anesthesiologists physical status 1 and 2 patients undergoing elective nonintracranial neurosurgery were assigned randomly to receive equipotent blinded infusions of either sufentanil (15 micrograms/min) or fentanyl (150 micrograms/min) for anesthetic induction during spontaneous ventilation of 100% oxygen. Normocapnia, as measured by infrared capnography, was maintained by manually assisting ventilation, as necessary. The cerebral opioid effect was quantified using the spectral edge frequency parameter. The infusion was continued until either 1) spectral edge frequency decreased below 10 Hz or 2) 150 micrograms of sufentanil or 1,500 micrograms of fentanyl was infused, whichever occurred first. On average, the patients received 1.7 +/- 0.55 micrograms/kg or 16 +/- 4 micrograms/kg of sufentanil or fentanyl, respectively. The right MCA mean, peak systolic, and peak diastolic velocities and pulsatility index were measured continuously by transcranial Doppler ultrasonography. RESULTS: The mean arterial pressure decreased slightly in both groups, but only in the fentanyl group were the changes significant. The MCA velocity increased by approximately 25% in both groups. However, the relative changes in MCA velocity were not different between groups. The pulsatility indexes were unchanged in both groups. CONCLUSIONS: These data suggest that, at clinically relevant doses in the absence of other drugs, cerebral blood flow velocity is increased by both fentanyl and sufentanil. Furthermore, there appears to be no significant differences in the cerebral hemodynamic profiles of the two drugs, as assessed by transcranial Doppler ultrasonography.

A meaningful use of the electroencephalogram (EEG) for monitoring depth of anesthesia has proven elusive. Although changes in the EEG with changing anesthetic dose or concentration have been noted for 60 yr, it has been difficult to demonstrate reliable, quantitative correlation between the EEG and other physiologic measures of anesthetic depth. We attempted to correlate several quantitative EEG measurements in rats, including average amplitude, spectral edge frequency, and burst suppression ratio, with the movement response to supramaximal noxious stimulation. We anesthetized 21 Sprague-Dawley rats with isoflurane 1.5% and allowed them to breathe spontaneously. After equilibration, EEG was recorded for off-line analysis; then a noxious stimulation was delivered with a tail clamp and the somatic response noted. Isoflurane concentration was adjusted up and down, and the EEG and movement response to tail clamp were assessed at each level until the minimum alveolar concentration was determined in each rat. We found no EEG dose response to increasing inspired concentrations of isoflurane, except for an increasing degree of burst suppression. We found no difference in any parameter between rats that responded and those that did not respond to stimuli at a given concentration of isoflurane. Finally, we found that the presence of burst suppression did not predict lack of response.

Current forms of brain monitoring, such as electroencephalography (EEG), have had limited clinical utility. The EEG records spontaneous cerebrocortical activity and thus is an indirect indicator of metabolic demand and, to a lesser extent, an indicator of mismatch of supply versus demand. Ischemia modulates EEG activity in ways that can usually be detected, but EEG patterns can be similarly modulated by many other factors, including temperature and pharmacologic manipulation. This in vivo study in physiologically monitored animals evaluated the use of correlated optical spectroscopy, performed with an instrument having a fiberoptic light-guide bundle in contact with the cerebral cortex, for the simultaneous monitoring of cerebrovascular oxygen availability and intracellular oxygen delivery. A highly specific monitor of cerebral intracellular oxygen supply, the cerebrocortical intramitochondrial NADH redox state, was monitored in vivo with a fluorescence technique. Absorption spectroscopy was used concurrently to monitor hemoglobin content (blood volume) and oxygen saturation in the microcirculation. Correlated changes in optical signals from cerebrocortical NADH and hemoglobin were studied in a swine model (n = 7) of nitrogen hypoxia. Measurements were made at four wavelengths with a time-division, multiplexed fluorometer/reflectometer. Because the NADH fluorescence signal at 450 nm is affected by local changes in blood volume, a "corrected" fluorescence signal is usually calculated. In previous studies, where only two wave lengths have been measured, attempts at correction were based on reflectance at the excitation wavelength (366 nm). We compared estimators of changes in microcirculatory blood volume using reflection at two wavelengths: 366 nm and 585 nm, the wavelengths for maximum and isobestic absorption. The results of the studies were as follows: (1) during transient hypoxia, NADH and local hemoglobin saturation signals changed in concert with arterial pulse oximetry, with changes in NADH lagging behind changes in saturation by an average of 5.3 seconds; (2) after hypocapnic ventilation to a mean PaCO2 of 20.2 +/- 0.8 mm Hg, NADH increased by 11.5 +/- 8.7% (as compared with maximal change during anoxia), local hemoglobin saturation decreased by 7.7 +/- 6.4%, and local blood volume decreased by 12.5 +/- 13%, while arterial SpO2 was unchanged; (3) our two measures of local blood volume were closely correlated during carbon dioxide perturbations, but poorly correlated during hypoxic perturbation; and (4) NADH fluorescence provided a more rapid, sensitive indicator of oxygen deprivation than did the EEG. During transient hypoxia, EEG changes occurred 57.4 +/- 10.4 seconds after the onset of decline in local hemoglobin saturation, after NADH had completed 50% of its maximal increase.

Laser is an acronym for Light Amplification by Stimulated Emission of Radiation. This article will review relevant highlights of the physics of lasers and laser light, rationales for the variety of lasers in clinical use, and important anesthesia-related concerns during laser surgery.

Percutaneous loss of inhaled anesthetics is small relative to their uptake. The minor nature of this loss results in part from the substantial barrier to diffusion posed by the skin. Pleural and peritoneal surfaces pose less effective barriers because diffusion distances are smaller than in the skin. Accordingly, we measured visceral loss to air of desflurane, isoflurane, and halothane from pleural and peritoneal surfaces in five juvenile swine. Pleural and peritoneal losses per percent end-tidal anesthetic correlated directly with the solubility of the anesthetic in blood or tissues. The total pleural losses for the first 30 min of anesthetic administration were desflurane, 1.22 +/- 0.22 mL (mean +/- standard deviation for the 30-min period); isoflurane, 2.34 +/- 0.52 mL; and halothane, 4.69 +/- 0.98 mL; respective peritoneal losses were 0.64 +/- 0.12 mL, 1.23 +/- 0.25 mL, and 2.69 +/- 0.57 mL. Pleural loss per unit time did not change with increasing duration of anesthesia, whereas peritoneal loss increased for all anesthetics. These visceral losses are greater than total percutaneous losses in humans given these anesthetics for the same period of time, but the loss of anesthetic by either route is too small to affect measurements of anesthetic kinetics or recovery.

We examined the metabolism of desflurane in 13 healthy volunteers given 7.35 +/- 0.81 MAC-hours (mean +/- SD) of desflurane and 26 surgical patients given 3.08 +/- 1.84 MAC-hours (mean +/- SD). Markers of desflurane metabolism included fluoride ion measured via an ion-specific electrode, nonvolatile organic fluoride measured after sodium fusion of urine samples, and trifluoroacetic acid determined by a gas chromatographic-mass spectrometric method. In both volunteer and patient groups, postanesthesia serum fluoride ion concentrations did not differ from background fluoride ion concentrations. Similarly, postanesthesia urinary excretion of fluoride ion and organic fluoride in volunteers was comparable to preanesthesia excretion rates. However, small but significant levels of trifluoroacetic acid were found in both serum and urine from volunteers after exposure to desflurane. A peak serum concentration of 0.38 +/- 0.17 mumol/L of trifluoroacetic acid and a peak urinary excretion rate of 0.169 +/- 0.107 mumol/h were detected in volunteers at 24 h after desflurane exposure. Although these increases in trifluoroacetic acid after exposure to desflurane were statistically significant, they are approximately 10-fold less than levels seen after exposure to isoflurane. Thus, desflurane strongly resists biodegradation, but a small amount is metabolized in humans.

We studied the ventilatory effects of desflurane (formerly I-653) with and without N2O in healthy male volunteers. After insertion of venous and arterial (radial and pulmonary) catheters, baseline measurements of tidal volume (VT), respiratory rate (RR), ventilatory response to CO2, and arterial and mixed venous blood gases were made. Subjects were randomly assigned to receive either desflurane with O2 (n = 6) or with O2 and 60% N2O (n = 6). Anesthesia was induced by inhalation of desflurane followed by tracheal intubation without muscle relaxants. In each volunteer, at end-tidal concentrations totaling 0.83, 1.24, and 1.66 MAC, we repeated measurements of VT, RR, response to CO2, and arterial and mixed venous blood gases. As depth of anesthesia increased, VT significantly (P less than 0.05) decreased from 363 +/- 22 ml awake to 76 +/- 22 ml at 1.66 MAC without N2O and from 473 +/- 70 ml awake to 128 +/- 6 ml at 1.66 MAC with N2O (mean +/- SE). Similarly, RR increased from 15 +/- 0.5 breaths per min awake to 32 +/- 2 breaths per min at 1.66 MAC without N2O and from 14 +/- 0.5 breaths per min awake to 40 +/- 3 breaths per min at 1.66 MAC with N2O. Desflurane without N2O depressed the ventilatory response to CO2 to 45 +/- 9, 31 +/- 5, and 11 +/- 4% of the awake values at 0.83, 1.24, and 1.66 MAC, respectively. With N2O, values were 52 +/- 14, 23 +/- 5, and 26 +/- 9% of the awake value at 0.83, 1.24, and 1.66 MAC, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)