Cost-effectiveness of bispectral index monitoring.

PURPOSE OF REVIEW: In the current era of limited resources, organizations are evaluating the cost-effectiveness of their care. To analyze the cost-effectiveness of a physiologic monitor, one must first determine what negative outcome will be reduced or what positive outcome will be promoted. For example, if one was studying the cost-effectiveness of the pulse oximeter, it would be important to state whether the endpoint is prevention of hypoxic events or prevention of myocardial infarction. One would then need outcome data demonstrating the incidence of the chosen endpoint with and without the monitor. With these data, one can begin to construct a model for cost-effectiveness. Like many medical technologies, the bispectral index (BIS) monitor has recently been the subject of several articles which study its cost-effectiveness. This review examines the rationale of cost-effectiveness analyses and their application specifically to the BIS monitor. RECENT FINDINGS: The BIS monitor has been shown in multiple prospective randomized studies to positively affect several important aspects of an anesthetic. Use of the BIS monitor results in less use of hypnotic anesthetic drugs, decreased time to extubation, decreased incidence of nausea and vomiting, and decreased intraoperative awareness. These benefits are achieved for an additional cost of around five dollars per anesthetic. In addition, there is an emerging body of literature demonstrating an association between low intraoperative BIS readings and decreasing intermediate-term survival in both noncardiac and cardiac surgical patients. SUMMARY: Given the trivial cost of the BIS and the proven benefits demonstrated in prospective randomized studies, we consider its use justified in every general anesthetic.

Preserved memory function during bispectral index-guided anesthesia with sevoflurane for major orthopedic surgery.

BACKGROUND: Memory function under anesthesia is undesired but may arise from light hypnosis as well as stress-enhanced learning during surgery. The bispectral index (BIS, Aspect Medical Systems, Norwood, MA) is a monitor of hypnotic state that can help to avoid light hypnosis (i.e., BIS above 60). This study tested the hypothesis that BIS-guided anesthesia maintaining BIS 50-60 reduces the likelihood of memory function under anesthesia. METHODS: After obtaining informed consent, 128 patients scheduled for joint replacement surgery under general anesthesia with sevoflurane were randomly assigned to BIS-guided anesthesia, titrating drugs to BIS 50-60 (BIS group), or a standard practice group in which BIS was recorded but did not guide drug administration. After induction, all patients were repeatedly played a list of 15 words. After recovery from anesthesia, all were interviewed about recall and completed a recognition memory test containing the presented words (targets, 33.3%) and new words (distractors). Preoperatively, patients filled out a stress questionnaire (Spielberger State-Trait Anxiety Inventory). RESULTS: BIS values above 60 were recorded in both groups, but no patient recalled the presented words postoperatively. Only patients in the BIS group selected targets more often than distractors (37.1% vs. 31.5% hit rate, P = 0.001). Target hit rates correlated poorly to stress scores (P > 0.9), but were associated with the amount of fentanyl received preoperatively (P = 0.01) and pain management technique (P < 0.01). CONCLUSIONS: BIS titration to BIS 50-60 does not necessarily curb memory function under anesthesia when BIS values higher than 60 occur. Preoperative analgesia attenuated the likelihood of memory function under anesthesia.

Interaction of propofol and sevoflurane on loss of consciousness and movement to skin incision during general anesthesia.

BACKGROUND: Loss of consciousness (LOC) and immobility to surgical incision seem to be mediated at different levels of the central nervous system. Pharmacologic studies of hypnotic agents have previously focused on combinations of either volatile or intravenous anesthetics. This study examined the combination of inhaled sevoflurane and intravenous propofol at these two clinically relevant anesthetic end points. METHODS: Thirty-six elective surgical patients were initially enrolled. Conditions approximating steady state were obtained for sevoflurane and target-controlled propofol infusions. Patients were sequentially evaluated for LOC (loud voice plus mild prodding) and immobility to surgical incision. The study was designed using the Dixon up-down method. RESULTS: The observed propofol effect target with 50% response plus sevoflurane (0.46% end-tidal concentration) was 1.2 microg/ml (95% confidence interval, 1.1-1.3 microg/ml). It was not significantly different from that predicted (1.5 microg/ml; 95% confidence interval, 1.2-1.7 microg/ml) by simple additivity. The effective plasma concentration of propofol that suppressed movement to skin incision in 50% of patients was 5.4 microg/ml (95% confidence interval, 4.8-6.0 microg/ml) plus sevoflurane (0.86%) and was not significantly different from that predicted by additivity (5.4 microg/ml; 95% confidence interval, 4.8-5.9 microg/ml). Both analyses had adequate power (90%) to detect a significant change (+/-19 to 25%) from predicted value. Repeated-measures analysis of variance identified a Bispectral Index value of 70 as the break point between those who responded at LOC or did not. CONCLUSIONS: Propofol and sevoflurane interact in a simple additive manner to produce LOC and immobility to surgical incision, suggesting a common mechanism or a single site of action. These clinical observations are consistent with a single site of interaction at the gamma-aminobutyric acid type A receptor.

The influence of gender on loss of consciousness with sevoflurane or propofol.

UNLABELLED: Studies have suggested that hypnotic requirements for general anesthesia and emergence may be influenced by gender. In this study, we examined the effect of gender on the hypnotic requirement for loss of consciousness (LOC) using either a volatile (sevoflurane) or an IV (propofol) anesthetic. One-hundred-fifteen unpremedicated, ASA physical status I-II patients, aged 18-40 yr old, received either sevoflurane by mask to a predetermined end-tidal concentration (%ET(sevo)) or propofol by target-controlled infusion (effect site) while breathing spontaneously. After sufficient time for equilibration, LOC was assessed by lack of response to mild prodding. The up-down method of Dixon was used to determine the hypnotic target concentration at 50% response (LOC(50)). No statistically significant difference in LOC(50) was noted between men and women for sevoflurane (0.83% +/- 0.1% and 0.92% +/- 0.09% ET, respectively). Men required significantly more propofol than women (2.9 +/- 0.2 versus 2.7 +/- 0.1 microg/mL, respectively). However, there was no difference in the bispectral index (BIS) at LOC for men or women with either hypnotic anesthetic. This investigation identified a small, statistically significant difference in hypnotic requirement at LOC(50) between men and women with propofol but not with sevoflurane. As defined by BIS, men and women had equivalent hypnotic states at LOC(50), indicating that gender had no clinically significant effect on hypnotic requirements. However, BIS at a defined clinical end-point (LOC(50)) was significantly different between the sevoflurane and propofol groups, suggesting that neurophysiological effects of these anesthetics may be different. IMPLICATIONS: Gender affects the dosing requirements for, and response to, many drugs used in anesthetic practice. Loss of consciousness is an early clinical marker of hypnotic drug effect. We found no significant difference to either an inhaled (sevoflurane) or IV (propofol) anesthetic related to patient gender.

Attenuated brain response to auditory word stimulation with sevoflurane: a functional magnetic resonance imaging study in humans.

BACKGROUND: Functional magnetic resonance imaging offers a compelling, new perspective on altered brain function but is sparsely used in studies of anesthetic effect. To examine effects on verbal memory encoding, the authors imaged human brain response to auditory word stimulation using functional magnetic resonance imaging at different concentrations of an agent not previously studied, and tested memory after recovery. METHODS: Six male volunteers were studied breathing 0.0, 2.0, and 1.0% end-tidal sevoflurane (awake, deep, and light states, respectively) via laryngeal mask. In each condition, they heard 15 two-syllable English nouns via closed headphones. Each word was repeated 15 times (1/s), followed by 15 s of rest. Blood oxygenation level-dependent brain activations during blocks of stimulation versus rest were assessed with a 3-T Siemens Trio scanner and a 20-voxel spatial extent threshold. Memory was tested approximately 1.5 h after recovery with an auditory recognition task (chance performance = 33% correct). RESULTS: Scans showed widespread activations (P < 0.005, uncorrected) in the awake state, including bilateral superior temporal, frontal, and parietal cortex, right occipital cortex, bilateral thalamus, striatum, hippocampus, and cerebellum; more limited activations in the light state (bilateral superior temporal gyrus, right thalamus, bilateral parietal cortex, left frontal cortex, and right occipital cortex); and no significant auditory-related activation in the deep state. During recognition testing, subjects correctly selected 77 +/- 12% of words presented while they were awake as "old," versus 32 +/- 15 and 42 +/- 8% (P < 0.01) correct for the light and deep stages, respectively. CONCLUSIONS: Sevoflurane induces dose-dependent suppression of auditory blood oxygenation level-dependent signals, which likely limits the ability of words to be processed during anesthesia and compromises memory.

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 x 10) 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.

No evidence of memory function during anesthesia with propofol or isoflurane with close control of hypnotic state.

BACKGROUND: The authors previously demonstrated memory function during apparently adequate general anesthesia in trauma patients. Hypnotic state fluctuations, stress, and variable amnesic qualities of commonly used anesthetics could account for this effect. METHODS: The authors replicated the trauma investigation in 90 elective surgical patients to enable anesthetic titration to a bispectral index value of 50-55 during auditory presentation of word stimuli. Patients were randomly assigned to maintenance with propofol (n = 48) or isoflurane (n = 42). Before surgery, state anxiety and trait anxiety were assessed using self-report measures. Postoperative memory assessment relied on the process dissociation procedure using a word stem completion task. RESULTS: There were no differences between groups for relevant demographic, preoperative, or supplemental drug variables. Ninety-eight percent of words were presented within a bispectral index range of 40-60, with values averaging 48.8 (SD = 5.7) during word presentation. Neither the process dissociation procedure nor standard measures of conscious recall and recognition memory showed evidence of explicit or implicit memory. Preoperative stress levels did not correlate with postoperative memory test scores in either study group. CONCLUSIONS: In contrast to the results of their previous study, the authors found no evidence of memory function with close control of hypnotic state. This suggests that hypnotic state fluctuations are important to memory activation under anesthesia. Other variables may contribute to preserved memory function as well. Propofol and isoflurane block memory equally well during adequate anesthesia.

BIS monitoring: awareness and catastrophic events.

The bispectral index is an electroencephalogram-based monitoring tool to help anesthesiologists determine depth of anesthesia. The bispectral index indicates both the potential for awareness and of relative hypnotic overdose, but it does not predict movement or hemodynamic responses to stimulation, and it cannot predict the exact moment consciousness returns. The bispectral index has been assessed for its relationship to awareness, and bispectral index monitoring appears to be generally associated with a low incidence of awareness. The bispectral index has also has been noted to detect periods of cerebral ischemia. It is also being used in intensive care units to help quantify the level of sedation in patients and as an outcome predictor in patients with brain injuries. Low values of the bispectral index often occur during catastrophic, ischemic, events but the use of this technology for the routine monitoring of such events is unproven.

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.

Remifentanil dose/electroencephalogram bispectral response during combined propofol/regional anesthesia.

UNLABELLED: The effect of opioid administration on the bispectral index (BIS) during general anesthesia is controversial. Several investigators have reported BIS to be insensitive to opioid addition, whereas others have found a hypnotic response. We designed this study to examine the effect of remifentanil on BIS during combined regional/general propofol anesthesia under steady-state conditions. After Human Investigations Committee approval, 19 healthy ASA physical status I or II patients were enrolled in a prospective experimental design. Regional anesthesia was initiated and general anesthesia induced by using computer-assisted continuous infusion of propofol. Propofol was incrementally adjusted to a BIS of approximately 60. After 20 min at a stable propofol infusion rate, a remifentanil computer-assisted continuous infusion (effect-site target concentration of 0.5, 2.5, and then 10 ng/mL) was sequentially administered at stepped 15-min intervals. BIS decreased from 56 +/- 2 to 44 +/- 1, 95% spectral edge frequency from 17.9 +/- 0.5 Hz to 15.0 +/- 0.4 Hz, heart rate from 84 +/- 5 bpm to 62 +/- 4 bpm, and mean arterial blood pressure from 93 +/- 4 mm Hg to 69 +/- 3 mm Hg with increasing remifentanil concentration. A significant linear correlation between BIS, 95% spectral edge frequency, heart rate, and log (remifentanil effect-site) concentration was found. The change in baseline BIS was relatively modest but significant, suggesting that remifentanil has some sedative/hypnotic properties, or that it potentiates the hypnotic effect of propofol. IMPLICATIONS: This experiment identified a significant, dose-dependent decrease in bispectral index (BIS), 95% spectral edge frequency, heart rate, and mean arterial blood pressure with increasing remifentanil dose. The change in baseline BIS was relatively modest but significant, suggesting that remifentanil has some sedative/hypnotic properties, or that it potentiates the hypnotic effect of propofol.