Jay W. Johansen

Development and Clinical Application of Electroencephalographic Bispectrum Monitoring

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

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

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.

Esmolol Reduces Anesthetic Requirement for Skin Incision during Propofol/Nitrous Oxide/Morphine Anesthesia

Background Although beta blockers have been used primarily to decrease unwanted perioperative hemodynamic responses, the sedative properties of these compounds might decrease anesthetic requirements. This study was designed to determine whether esmolol, a short‐acting beta1 ‐receptor antagonist, could reduce the propofol concentration required to prevent movement at skin incision. Methods Sixty consenting patients were premedicated with morphine, and then propofol was delivered by computer‐assisted continuous infusion along with 60% nitrous oxide. Patients were randomly divided into three groups, propofol alone, propofol plus low‐dose esmolol (bolus of 0.5 mg/kg, then 50 micro gram [center dot] kg‐1 min‐1), and propofol plus high‐dose esmolol (bolus of 1 mg/kg, then 250 micro gram [center dot] kg (‐1) min‐1). Two venous blood samples were drawn at equilibrium. The serum propofol concentration that prevented movement to incision in 50% of patients (Cp50) was calculated by logistic regression. Results The propofol Cp50 with nitrous oxide was 3.85 micro gram/ml. High‐dose esmolol infusion was associated with a significant reduction in the Cp50 to 2.80 micro gram/ml (P < 0.04). Propofol computer‐assisted continuous infusion produced stable serum concentrations with a slight positive bias. Esmolol did not alter the serum propofol concentration. No intergroup differences in heart rate or blood pressure response to intubation or incision were found. Conclusions Esmolol significantly decreased the anesthetic requirement for skin incision. The components and mechanism of this interaction remain unclear. A simple pharmacokinetic interaction between esmolol and propofol does not explain the Cp50 reduction. These results demonstrate an anesthetic‐sparing effect of a beta‐adrenergic antagonist in humans under clinically relevant conditions.

Esmolol potentiates reduction of minimum alveolar isoflurane concentration by alfentanil

Esmolol, a short-acting beta1-receptor antagonist, decreases anesthetic requirements during propofol/N2 O/morphine anesthesia. This study was designed to determine whether esmolol affects the volatile anesthetic (isoflurane) required to prevent movement to skin incision in 50% patients (minimum alveolar anesthetic concentration [MAC]) with or without an additional opioid (alfentanil). One hundred consenting adult patients were randomly divided into five treatment groups: isoflurane alone (I), I with continuous large-dose (250 [micro sign]g [center dot] kg-1 [center dot] min-1) esmolol (E), I with alfentanil (effect site target of 50 ng/mL) via a continuous computer-controlled infusion (A), A plus continuous small-dose (50 [micro sign]g [center dot] kg-1 [center dot] min-1) esmolol (A1), or A plus large-dose esmolol (A2). Anesthesia was induced via a face mask, and steady-state target end-tidal isoflurane concentrations were maintained before incision. The MAC of isoflurane alone was 1.28% +/- 0.13%. Large-dose esmolol did not significantly alter the isoflurane MAC (1.23% +/- 0.14%). Alfentanil alone significantly decreased isoflurane MAC by 25% (0.96% +/- 0.09%). Adding small-dose esmolol did not further decrease MAC with alfentanil (0.96% +/- 0.13%). However, large-dose esmolol significantly decreased isoflurane MAC with alfentanil (0.74% +/- 0.09%). Esmolol and alfentanil both significantly reduced the increases in heart rate and mean arterial pressure associated with endotracheal intubation and incision. The mechanism of this effect is unknown. Implications: Most anesthetic techniques rely on a balance of several highly selective medications. The current results define a new anesthetic-sparing effect when volatile anesthetic, analgesic, and beta-adrenergic blocking drugs are combined. (Anesth Analg 1998;87:671-6)

Esmolol Promotes Electroencephalographic Burst Suppression During Propofol/alfentanil Anesthesia

This study examined the effects of an esmolol infusion on the electroencephalogram during propofol/alfentanil IV anesthesia. After informed consent, 20 patients were randomly assigned into four groups on the basis of two target alfentanil concentrations (alfentanil 50 or 150 ng/mL) and of a saline or esmolol infusion. Bispectral index (BIS), burst suppression ratio (SR), and physiologic variables were continuously monitored. A 30-min blinded infusion of saline or esmolol was started after establishing a stable baseline and followed by a washout period. The electroencephalogram was significantly suppressed by esmolol (BIS, 37 ± 6 to 22 ± 6, 40% decrease [mean ± sd]; SR, 5 ± 7 to 67 ± 23, 13.4-fold increase) compared with baseline in the small-dose alfentanil groups. Discontinuation of esmolol reversed the response. BIS and SR were unaffected by placebo infusion. Twelve-minute to 16-min hysteresis between esmolol administration and the onset of half-maximal cortical suppression was observed. Physiologic variables and serum propofol and alfentanil concentrations were not significantly altered by esmolol. Although the mechanism remains unclear, significant cortical depression and the onset of burst suppression during a stable, computer-controlled propofol/alfentanil anesthetic was associated with esmolol infusion.

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 &mgr;g/ml (95% confidence interval, 1.1–1.3 &mgr;g/ml). It was not significantly different from that predicted (1.5 &mgr;g/ml; 95% confidence interval, 1.2–1.7 &mgr;g/ml) by simple additivity. The effective plasma concentration of propofol that suppressed movement to skin incision in 50% of patients was 5.4 &mgr;g/ml (95% confidence interval, 4.8–6.0 &mgr;g/ml) plus sevoflurane (0.86%) and was not significantly different from that predicted by additivity (5.4 &mgr;g/ml; 95% confidence interval, 4.8–5.9 &mgr;g/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 &ggr;-aminobutyric acid type A receptor.

Increases in electroencephalogram and electromyogram variability are associated with an increased incidence of intraoperative somatic response.

BACKGROUND: sBIS, the variability of the Bispectral Index (BIS), sEMG, the variability of facial electromyogram power (EMG), and the Composite Variability Index (CVI) are 3 new measures of electroencephalogram and EMG variability. CVI is a single measure of the combined variability in BIS and EMG. We investigated whether increases in these variables are associated with intraoperative somatic responses. METHODS: This multicenter study included 120 patients undergoing elective, noncardiac surgery from 4 different sites. General anesthesia was maintained using propofol and remifentanil at 2 of the sites and sevoflurane and remifentanil at the 2 other sites. Propofol or sevoflurane was adjusted to maintain BIS between 45 and 60. Clinicians were blinded to CVI (v2.0) at all times, and remifentanil infusions were adjusted at the discretion of the clinician. The times of all intraoperative somatic events, defined as movement, grimacing, or eye opening, were recorded. Offline, the maintenance phase of each case was divided into consecutive, nonoverlapping, 10-minute segments. Segments were identified as containing a somatic event or containing no events. For each segment, mean sBIS, sEMG, and CVI and the heart rate (HR) range and mean arterial blood pressure range were calculated. To quantify how effectively each variable discriminated between somatic event segments and nonevent segments, we computed the area under the receiver operating characteristic (ROC) curve for each variable. Finally, we observed the time course of sBIS, sEMG, CVI, and the HR range before each somatic event and characterized the earliest time before the somatic event at which each variable was able to discriminate between the somatic events and a specified set of nonevents. RESULTS: The analysis included 33 somatic event segments and 829 nonevent segments from 105 surgical cases. The areas under the ROC curve (±SE) for sBIS, sEMG, and CVI were 0.83 ± 0.04, 0.92 ± 0.02, and 0.89 ± 0.03, respectively. The areas under the ROC curve for HR range and mean arterial blood pressure range were 0.77 ± 0.03 and 0.68 ± 0.05, respectively. CVI, sBIS, and sEMG all demonstrated higher average values before upcoming somatic events when compared with nonevents. HR range only showed a difference within a few seconds before the somatic event. CONCLUSION: sBIS, sEMG, and CVI, measures of electroencephalogram and EMG variability, increased when intraoperative somatic events occurred. sBIS, sEMG, and CVI discriminated between 10-minute segments that contained a somatic event and those segments that did not contain an event better than changes in HR and mean arterial blood pressure. Furthermore, CVI increases before somatic events began earlier than HR changes and may provide caregivers with an early warning of potentially inadequate antinociception.

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

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 (%ETsevo) 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 (LOC50). No statistically significant difference in LOC50 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 &mgr;g/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 LOC50 between men and women with propofol but not with sevoflurane. As defined by BIS, men and women had equivalent hypnotic states at LOC50, indicating that gender had no clinically significant effect on hypnotic requirements. However, BIS at a defined clinical end-point (LOC50) was significantly different between the sevoflurane and propofol groups, suggesting that neurophysiological effects of these anesthetics may be different.