Peter S. Sebel

bispectral Analysis Measures Sedation and Memory Effects of Propofol, Midazolam, Isoflurane, and Alfentanil in Healthy Volunteers

Background:The bispectral index (BIS), a value derived from the electroencephalograph (EEG), has been proposed as a measure of anesthetic effect. To establish its utility for this purpose, it is important to determine the relation among BIS, measured drug concentration, and increasing levels of seda

Bispectral index monitoring allows faster emergence and improved recovery from propofol, alfentanil and nitrous oxide anesthesia

Background: The bispectral index (BIS), a parameter derived from the electroencephalograph (EEG), has been shown to correlate with increasing sedation and loss of consciousness. This study determined whether addition of BIS monitoring to standard anesthetic practice results in improvements in the conduct of anesthesia or in patient outcomes. Methods: Three hundred two patients receiving a propofol‐alfentanil‐nitrous oxide anesthetic were studied at four institutions. Thirty‐four patients were initially enrolled to determine preexisting anesthetic practice and patient outcomes at each institution. Subsequent patients were randomized to either standard clinical practice (SP group), or standard practice plus BIS monitoring (BIS group). In all patients, the anesthesiologist attempted to provide a stable anesthetic with the fastest possible recovery. BIS was recorded for all patients, but viewed only in the BIS group. In the BIS group, propofol infusions were adjusted to achieve a target BIS between 45–60, increasing to 60–75 during the final 15 min of the case. In the SP group, propofol dose adjustments were made based only on standard clinical signs. Drug use, intraoperative responses, and patient recovery parameters were recorded. Results: Demographics were similar between groups. Compared with the SP group, patients in the BIS group required lower normalized propofol infusion rates (134 vs. 116 micro gram [center dot] kg sup ‐1 [center dot] min sup ‐1; P < 0.001), were extubated sooner (11.22 vs. 7.25 min; P < 0.003), had a higher percentage of patients oriented on arrival to PACU (43% vs. 23%; P < 0.02), had better postanesthesia care unit (PACU) nursing assessments (P < 0.001), and became eligible for discharge sooner (37.77 vs. 31.70 min; P < 0.04). There was no significant difference in the incidence of intraoperative responses between the groups. Conclusions: Titrating propofol with BIS monitoring during balanced anesthesia decreased propofol use and significantly improved recovery. Intraoperative course was not changed. These findings indicate that the use of BIS may be valuable in guiding the administration of propofol intraoperatively.

Development and Clinical Application of Electroencephalographic Bispectrum Monitoring

Development and Clinical Application of Electroencephalographic Bispectrum Monitoring Jay Johansen;Peter Sebel; Anesthesiology

The incidence of awareness during anesthesia: a multicenter United States study.

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.

Pharmacokinetics of Remifentanil (GI87084B) and Its Major Metabolite (GI90291) in Patients Undergoing Elective Inpatient Surgery

BackgroundRemifentanil is a highly potent opioid with a rapid onset and a short duration of action due to its rapid hydrolysis by esterases in blood and tissues. The major metabolite of remifentanil, GI90291, is much less potent than remifentanil. MethodsThe pharmacokinetics of remifentanil and its major metabolite, GI90291, were determined in 24 patients undergoing elective inpatient surgery. Remifentanil was administered as a 1-min infusion (2, 5, 15, and 30 μg/kg) after the induction of anesthesia and tracheal intubation. Serial arterial blood samples were collected over 6 h and assayed for remifentanil and GI90291. ResultsThe pharmacokinetics of remifentanil were described using a three-compartment model. Total clearance (250–300 1/h) of remifentanil was independent of dose and was approximately three to four times greater than the normal hepatic blood flow. Volume of distribution at steady state (25–40 1) also was independent of dose. The terminal half-life of remifentanil ranged from 10 to 21 min. Covariate analysis of remifentanil clearance and patient demographics showed that patient body weight, age, and gender did not influence total clearance. This suggests that remifentanil may not need to be dosed according to body weight in adult patients. A simulation was conducted to determine the time required for a 50% reduction in effect site concentration after an infusion designed to maintain a constant effect site concentration. The time required for a 50% reduction in the effect site concentration of remifentanil (3.65 min) was considerably less than that for sufentanil (33.9 min), alfentanil (58.5 min), and fentanyl (262 min). The pharmacokinetics of the major metabolite, GI90291, were independent of the dose of remifentanil. The mean terminal half-life of GI90291 ranged from 88 to 137 min. ConclusionsThe pharmacokinetics of remifentanil are consistent with its rapid elimination by blood and tissue esterases; its major metabolite is eliminated more slowly but is not likely to make any significant contribution to the total effect because of its much lower potency. The rapid onset and short duration of action of remifentanil make it well suited for titration of dose (infusion rate) to the desired degree of effect.

The effect of the interaction of propofol and alfentanil on recall, loss of consciousness, and the bispectral index

The Bispectral Index (BIS) correlates well with the level of consciousness with single anesthetic drugs.We studied the effect of the interaction of propofol with alfentanil on propofol concentration and BIS associated with 50% probability of loss of consciousness and lack of recall (Cp50 and BIS50,

Recovery of consciousness after thiopental or propofol : Bispectral index and the isolated forearm technique

Background Currently, there exists no effective monitor that can predict the probability of a patient being conscious during general anesthesia. The electroencephalogram‐derived bispectral index (BIS) is a promising new method to assess anesthetic adequacy. This study used the BIS to predict the probability of recovery of consciousness after a single bolus induction dose of propofol or thiopental. Methods Twenty unpremedicated surgical patients were anesthetized with 4 mg/kg thiopental and 20 patients with 2 mg/kg propofol. The BIS was monitored throughout the study. After induction, before administration of neuromuscular blocking agent, a tourniquet was applied to one arm and inflated above the systolic blood pressure. This allowed preservation of the ability to move the hand after neuromuscular blocking agent onset. Patients were then prompted to squeeze the investigators hand every 30 s, until they responded to the request. At the time of response, anesthesia was reinduced and the study terminated. Results The BIS at loss of consciousness and recovery of a response was not statistically different between propofol and thiopental. No patient with a BIS less than 58 was conscious. In both groups, a BIS of less than 65 signified a less than 5% probability of return of consciousness within 50 s. Conclusion The BIS can be used to predict probability of recovery of consciousness after a single injection of either thiopental or propofol.

Prediction of movement using bispectral electroencephalographic analysis during propofol/alfentanil or isoflurane/alfentanil anesthesia

Conventional electroencephalographic (EEG) analysis techniques do not use the phase information from the Fourier analysis.This study used a new technique of EEG analysis, bispectral analysis, which measures interfrequency phase relationships in the EEG. Using a reference database, and a process of multivariate discriminant analysis, we developed a univariate bispectral variable, the bispectral index (BIS). This study was designed to test the efficacy of BIS in predicting movement to incision during either an isoflurane/alfentanil anesthetic or a propofol/alfentanil anesthetic technique. Fifty consenting patients were randomized to two groups; one received isoflurane/alfentanil and the other, propofol/alfentanil for anesthesia. EEG was recorded using a microcomputer system and the data were analyzed off-line. Hemodynamic variables were also recorded. After skin incision, each patient was observed carefully for 2 min to detect purposeful movement. A significant difference was found between the BIS values for movers versus nonmovers within each of the two treatment groups (P <or=to 0.002). However, isoflurane/alfentanil nonmovers could not be distinguished from propofol/alfentanil movers (P <or=to 0.180), suggesting a treatment group effect independent of response classification. Preincision hemodynamic variables did not predict patient movement in response to skin incision. These findings suggest the possibility that different anesthetics have different effects on BIS, and thus BIS may not be independent of the anesthetic. Interfrequency phase coupling, a nonlinear feature of the EEG which is measured with bispectral analysis, may contain clinically useful information for the assessment of anesthetic adequacy. In this study, BIS was a better predictor of patient response than other currently available variables including hemodynamic status. (Anesth Analg 1995;80:780-5)

Functional connectivity changes with concentration of sevoflurane anesthesia

Low-frequency oscillations (<0.08 Hz) have been detected in functional magnetic resonance imaging studies, and appear to be synchronized between functionally related areas. The effect of anesthetic agents on cortical activity is not completely characterized. This study assessed the effect of anesthesia on the temporal relations in activity in the motor cortices. Resting-state magnetic resonance data were acquired on six volunteers under different anesthetic states (using 0.0%, 2.0% and 1.0% stable end-tidal sevoflurane). Across all volunteers, the number of significant voxels (p<2.5×10−5) in the functional connectivity maps was reduced by 78% for light anesthesia and by 98% for deep anesthesia, compared with the awake state. Additionally, significant correlations in the connectivity maps were bilateral in the awake state but unilateral in the light anesthesia state.

The Pharmacokinetics of Sufentanil in Surgical Patients

The pharmacokinetics of sufentanil, a new thienyl analogue of fentanyl, were studied in 10 surgical patients. Sufentanil, 5 μg/kg, was given intravenously as a bolus injection and plasma concentrations measured at intervals up to 8 h. Plasma sufentanil concentrations decreased rapidly after injection—98% of the administered dose having left the plasma within 30 min. In 9 of the 10 patients, a tri-exponential equation optimally described the sufentanil concentration decay curve, with average (±SEM) half-lives for the rapid (π) and slow (α) distribution phases of 1.4 ± 0.3 min and 17.7 ± 2.6 min, respectively. The average terminal elimination (β) half-life was 164 ± 22 min. The average value for Vdβ was 2.9 ± 0.2 1/kg, Vdss 1.7 ± 0.2 1/kg and total plasma clearance 12.7 ± 0.8 ml · kg-1 · min-1 (935 ± 50 ml/min). In one patient, a biexponential equation was sufficient to describe the concentration-time data, yielding a distribution half-life of 4.7 min and an elimination half-life of 117 min.