Comparative evaluation of Narcotrend, Bispectral Index, and classical electroencephalographic variables during induction, maintenance, and emergence of a propofol/remifentanil anesthesia

In the present study, we sought to compare the abilities of Narcotrend (NT) with the Bispectral Index (BIS) electroencephalographic system to monitor depth of consciousness immediately before induction of anesthesia until extubation during a standardized anesthetic. We investigated 26 patients undergoing laminectomy. Investigated states of anesthesia were: awake, loss of response, loss of eyelash reflex, steady-state anesthesia, first reaction, and extubation during emergence. NT, BIS, spectral edge frequency, median frequency, relative power in delta, theta, alpha, beta, and hemodynamics were recorded simultaneously. The ability of all variables to distinguish between awake versus loss of response, awake versus loss of eyelash reflex, awake versus steady-state anesthesia, steady-state anesthesia versus first reaction and extubation were analyzed with the prediction probability. Effects of remifentanil during propofol infusion were investigated with Friedman's and post hoc with Wilcoxon's test. Only NT and BIS were able to distinguish all investigated states accurately with a prediction probability >0.95. After start of remifentanil infusion, only hemodynamics changed statistically significantly (P < 0.05). NT and BIS are more reliable indicators for the assessment of anesthetic states than classical electroencephalographic variables and hemodynamics, whereas the analgesic potency of depth of anesthesia could not be detected by NT and BIS. IMPLICATIONS: The modern electroencephalographic monitoring systems Narcotrend and Bispectral Index are more reliable indicators for the assessment of anesthetic states than classical electroencephalographic and hemodynamic variables to predict anesthetic conditions from before induction of anesthesia until extubation during a standardized anesthetic regime with propofol and remifentanil. The analgesic potency of depth of anesthesia could not be detected by Narcotrend and Bispectral Index.     

ARX-derived auditory evoked potential index and bispectral index during the induction of anesthesia with propofol and remifentanil

A new commercial auditory evoked potential (AEP) monitor (A-line AEP monitor) was developed to calculate an index (ARX AEP index; AAI) by automatically using the amplitudes and latencies of the AEP. We investigated 30 patients before spine surgery. AAI; bispectral index (BIS); relative (%) delta, theta, alpha, and beta; spectral edge frequency; median frequency; mean arterial blood pressure; heart rate; and oxygen saturation were obtained simultaneously during stepwise (1.0 micro g/mL) induction of target-controlled propofol concentration until 5.0 micro g/mL, followed by an infusion of 0.3 micro g. kg(-1). min(-1) of remifentanil. Every minute, the patients were asked to squeeze the observer's hand. Prediction probability (Pk), receiver operating characteristic, and logistic regression were used to calculate the probability to predict the conditions AWAKE, UNCONSCIOUSNESS (first loss of hand squeeze), and steady-state ANESTHESIA (5.0 micro g/mL of propofol and 0.3 micro g. kg(-1). min(-1) of remifentanil). Although a statistically significant difference among the conditions was observed for AAI, BIS, mean arterial blood pressure, median frequency, and %alpha, only AAI and BIS were able to distinguish UNCONSCIOUSNESS versus AWAKE and ANESTHESIA versus AWAKE with better than Pk = 0.90. The modern electroencephalographic variables AAI and BIS were superior to the classic electroencephalographic and hemodynamic variables to distinguish the observed anesthetic conditions. IMPLICATIONS: The modern electroencephalographic ARX-derived auditory evoked potential index and the bispectral index were superior to the classic electroencephalographic and hemodynamic variables for predicting anesthetic conditions. Variables derived from the auditory evoked potential did not provide an advantage over variables derived from spontaneous electroencephalogram.     

Einfluss des Geschlechts auf Propofolverbrauch und Aufwachzeiten bei standardisierter Anästhesietiefe

INTRODUCTION: We investigated gender differences of drug consumption and recovery times for propofol-remifentanil anaesthesia. METHODS: Adult patients scheduled for minor orthopaedic surgery were randomised to receive a propofol-remifentanil anaesthesia controlled either by EEG monitoring (Narcotrend or BIS) or solely by clinical parameters. Anaesthesia was induced with remifentanil 0.4 microg/kg/min and a propofol target-controlled infusion (TCI) at 3.5 microg/ml. After intubation remifentanil was reduced to 0.2 microg/kg/min whereas propofol TCI was adjusted according to clinical parameters or to the following EEG target values: during maintenance to "D(0)" (Narcotrend) or "50" (BIS), 15 min before the end of surgery to "C(1)" (Narcotrend) or "60" (BIS). Recovery times were recorded and average normalised propofol consumption was calculated from induction and maintenance doses. RESULTS: A total of 60 male and 60 female patients completed the study. Gender differences were observed for recovery times (with standard practice) and for propofol consumption (with BIS monitoring). In the standard protocol group, propofol consumption was nearly identical for male and female patients whereas recovery times were significantly longer in the male group. In both EEG-guided groups propofol consumption was less for male patients while recovery times were slightly longer. In the group of female patients higher propofol TCI concentrations had to be used to reach the same BIS or Narcotrend values. CONCLUSION: With propofol-remifentanil anaesthesia, gender has impact on recovery times and propofol consumption. If the same amounts of propofol are applied, males awake later, with BIS or Narcotrend monitoring males receive less propofol for comparable EEG effects.     

Narcotrend monitoring allows faster emergence and a reduction of drug consumption in propofol-remifentanil anesthesia

BACKGROUND: The Narcotrend is a new electroencephalographic monitor designed to measure depth of anesthesia, based on a six-letter classification from A (awake) to F (increasing burst suppression) including 14 substages. This study was designed to investigate the impact of Narcotrend monitoring on recovery times and propofol consumption in comparison to Bispectral Index (BIS) monitoring or standard anesthetic practice. METHODS: With institutional review board approval and written informed consent, 120 adult patients scheduled to undergo minor orthopedic surgery were randomized to receive a propofol-remifentanil anesthetic controlled by Narcotrend, by BIS(R), or solely by clinical parameters. Anesthesia was induced with 0.4 micro x kg-1 x min-1 remifentanil and a propofol target-controlled infusion at 3.5 microg/ml. After intubation, remifentanil was reduced to 0.2 micro x kg-1 x min-1, whereas the propofol infusion was adjusted according to clinical parameters or to the following target values: during maintenance to D(0) (Narcotrend) or 50 (BIS); 15 min before the end of surgery to C(1) (Narcotrend) or 60 (BIS). Recovery times were recorded by a blinded investigator, and average normalized propofol consumption was calculated from induction and maintenance doses. RESULTS: The groups were comparable for demographic data, duration of anesthesia, and mean remifentanil dosages. Compared with standard practice, patients with Narcotrend or BIS monitoring needed significantly less propofol (standard practice, 6.8 +/- 1.2 mg x kg-1 x h-1 vs. Narcotrend, 4.5 +/- 1.1 mg x kg-1 x h-1 or BIS(R), 4.8 +/- 1.0 mg x kg-1 x h-1; P < 0.001), opened their eyes earlier (9.3 +/- 5.2 vs. 3.4 +/- 2.2 or 3.5 +/- 2.9 min), and were extubated sooner (9.7 +/- 5.3 vs. 3.7 +/- 2.2 or 4.1 +/- 2.9 min). CONCLUSIONS: The results indicate that Narcotrend and BIS monitoring are equally effective to facilitate a significant reduction of recovery times and propofol consumption when used for guidance of propofol titration during a propofol-remifentanil anesthetic.     

Variation of bispectral index under TIVA with propofol in a paediatric population

BACKGROUND: In this prospective observational study, we aim to explore the relationship between age and bispectral index (BIS) values at different plasma concentrations of propofol. METHODS: Fifty children aged from 3 to 15 yr were included. Anaesthesia was induced using a target-controlled infusion of propofol with the Kataria pharmacokinetic model together with a bolus of remifentanil followed by a continuous infusion rate at 0.2 microg kg(-1) min(-1). Target plasma propofol concentration was initially stabilized to 6 microg ml(-1) and continued for 6 min. The target was then decreased and stabilized to 4 microg ml(-1) and then to 2 microg ml(-1). BIS values, plasma propofol concentration, and EEG were continuously recorded. In order to explore the relationship between variations in propofol concentration and the EEG bispectrum, we used a multiple correspondence analysis (MCA). Results are shown in median (range). RESULTS: We found no statistical difference between BIS values with propofol 6 microg ml(-1) [23 (12-40)] and 4 microg ml(-1) [28 (9-67)]. At 2 microg ml(-1), BIS was significantly different [52 (24-71)], but a significant correlation between the age of children and BIS values was found (r2=0.66; P<0.01). There was little change in children's position between 6 and 4 microg ml(-1) in the structure model of the MCA. From 4 to 2 microg ml(-1), the position of children moved only on axis 2. CONCLUSIONS: These results showed the difficulty to interpret BIS values because of the absence of significant change for higher plasma propofol concentration variation or because of the link with age for the lower plasma concentration.     

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. 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.     

腹腔镜结直肠手术中滴定靶控输注麻醉的应用

目的探讨以脑电双频指数（B1S）和收缩压为滴定目标、以丙泊酚复合瑞芬太尼滴定靶控输注静脉麻醉对腹腔镜结直肠手术中麻醉用药量和麻醉深度的影响。方法选择60例择期腹腔镜结直肠手术患者为研究对象,采用丙泊酚复合瑞芬太尼滴定靶控输注静脉麻醉,以BIS维持40～60、收缩压波动不超过基础值的20％为目标,滴定调节两种药物的血浆靶浓度,当BIS与收缩压的变化趋势出现矛盾时首先调节SBP。记录不同时间点的BIS、血压及麻醉药血浆靶控浓度等。结果麻醉诱导后血压基本平稳,BIS维持在60以内,其中在人工气腹建立后和Trendelenburg体位期间,BIS低至35。40之间：整个麻醉过程中患者均无术中知晓。麻醉期间存在手术刺激时,丙泊酚和瑞芬太尼血浆靶浓度的95％C1分别为2．55～2．65mg／L和4．09～4．26μg／L,其中丙泊酚的血浆靶浓度所推荐剂量。结论在腹腔镜结直肠手术中,以BIS结合收缩压为目标进行丙泊酚复合瑞芬太尼滴定靶控输注静脉麻醉,可维持有的麻醉深度,并减少麻醉药的用量。     

Assessment of depth of anesthesia and postoperative respiratory recovery after remifentanil- versus alfentanil-based total intravenous anesthesia in patients undergoing ear-nose-throat surgery

BACKGROUND: The authors investigated whether total intravenous anesthesia (TIVA) with precalculated equipotent infusion schemes for remifentanil and alfentanil would ensure appropriate analgesia and that remifentanil would result in better recovery characteristics. METHODS: Forty consenting patients (classified as American Society of Anesthesiologists physical status I-III) scheduled for microlaryngoscopy were randomized to receive, in a double-blind manner, either remifentanil (loading dose 1 microg/kg; maintenance infusion, 0.25 microg x kg(-1) x min-1) or alfentanil (loading dose, 50 microg/kg; maintenance infusion, 1 microg x kg(-1) x min-1) as the analgesic component of TIVA. They were combined with propofol (loading dose, 2 mg/kg; maintenance infusion, 100 microg x kg(-1) min(-1)). To insure an equal state of anesthesia, the opioids were titrated to maintain heart rate and mean arterial pressure within 20% of baseline, and propofol was titrated to keep the bispectral index (BIS) less than 60. Neuromuscular blockade was achieved with succinylcholine. Drug dosages and the times from cessation of anesthesia to extubation, verbal response, recovery of ventilation, and neuropsychological testing, orientation, and discharge readiness were recorded. RESULTS: Demographics, duration of surgery, and anesthesia were similar between the two groups. Both groups received similar propofol doses. There were no difference in BIS values preoperatively (mean, 96), intraoperatively (mean, 55), and postoperatively (mean, 96). Recovery of BIS and times for verbal response did not differ. At 20, 30, and 40 min after terminating the opioid infusion, the peripheral oxygen saturation and respiratory rate were significantly higher in the remifentanil group compared with the alfentanil group. CONCLUSIONS: When both the hypnotic and analgesic components of a TIVA-based anesthetic are administered in equipotent doses, remifentanil provides a more rapid respiratory recovery, even after brief surgical procedures, compared with alfentanil.     

Clinical variables related to propofol effect-site concentrations at recovery of consciousness after neurosurgical procedures

Target controlled infusion (TCI) systems and computer data acquisition software are increasingly used in anesthesia. It was hypothesized that the use of such systems might allow retrieval of information useful to anticipate the effect-site concentrations of propofol at which patients would recover from anesthesia. The goal of the study was to identify variables related to propofol effect-site concentrations at recovery of consciousness (ROC). Sixteen patients with a Glasgow of 15, ASA 1 or 2, subjected to neurosurgical procedures, received TIVA with TCI propofol and remifentanil. Data were collected every 5 seconds from Datex AS3 and Aspect A200XP (BIS). Effect-site TCI was used for propofol (initial effect target 5.0 microg/ml) and for remifentanil (initial plasma target 2.5 ng/ml). All clinical events were noted. Variables possibly related to propofol effect-site concentration at ROC were selected. Data are expressed as mean +/- SD. Effect-site propofol concentration at ROC was 1.3 +/- 0.5 microg/ml. A positive correlation was found between propofol effect-site concentration at ROC and: age (49.3 +/- 17 years) (P = 0.003); mean remifentanil dose during surgery (0.11 +/- 0.05 microg/kg/min) (P = 0.003); mean propofol dose during surgery (0.12 +/- 0.03 mg/kg/min) (P = 0.046); and remifentanil effect-site concentration at ROC (2.85 +/- 2.06 ng/ml) (P = 0.002). Propofol effect-site concentrations were not correlated with: weight, height, LBM, duration of anesthesia, minimum BIS at induction (30.4 +/- 6.8), time till minimum BIS (4.7 +/- 2.2 min), mean and median BIS during surgery (38.2 +/- 4.5 and 37.8 +/- 5.3). BIS-related variables were not useful as ROC predictors. Only drug variables and age correlated with propofol effect-site concentrations at ROC.     

Effect site concentrations of remifentanil maintaining cardiovascular homeostasis in response to surgical stimuli during bispectral index guided propofol anestesia in seriously obese patients

AIM: The aim of this prospective study was to determine the effect site concentrations of remifentanil maintaining cardiovascular homeostasis in response to surgical stimuli during bispectral index (BIS) guided propofol anesthesia in seriously obese patients. METHODS: Twenty-two patients, female/male 15/7, ASA physical status II - III, aged 29-69 years, body mass index (BMI) 54.5+/-12, undergoing major open bariatric surgery, were enrolled to receive a propofol-remifentanil total intravenous anesthesia. All patients were intubated by using a flexible fiberoptic bronchoscopic technique facilitated by a target controlled effect site concentration of remifentanil set at 2.5 ng/mL. After endotracheal intubation, anesthesia was started with a target controlled infusion of propofol initially set at 6 microg/mL, then adjusted to maintain a BIS value between 40 and 50. The mean effect site concentration of remifentanil was recorded at different intervals time during surgery: skin incision-opening of peritoneum (T1), bowel resection (T2), cholecystojejunal anastomosis (T3), ileojejunal anastomosis (T4), closing of peritoneum (T5). RESULTS: The mean plasma concentrations of propofol required to maintain a BIS value between 40 and 50 were 4+/-0.55, 3.8+/-0.64, 3.8+/- 0.63, 3.8+/-0.65 and 3.8+/-0.63 microg/mL at T1, T2, T3, T4 and T5 interval time, respectively. The mean values of remifentanil target effect site concentration were 5.2+/-1.3, 7.7+/-1.7, 9.1+/-1.8, 9.7+/- 2.2 and 9.9+/-2.5 ng/mL at T1, T2, T3, T4 and T5 interval time. CONCLUSIONS: This study suggests that tolerance to remifentanil infusion is profound and develops very rapidly in morbidly obese patients submitted to open bariatric surgery during BIS guided propofol anesthesia. The administration of opiates during anesthesia based on target-controlled infusion should include corrections for the development of tolerance.     

Randomized placebo-controlled trial to assess the effect of remifentanil and propofol on bispectral index and sedation

The effect of the combination of opiates and hypnotics on bispectral index (BIS) is unclear. This double-blind placebo-controlled trial investigated the effect on BIS and sedation of different infusion doses of remifentanil combined with a steady infusion of propofol. Forty patients initially received a target-controlled infusion of propofol 2 micrograms ml-1 for 15 min. They were then randomized to receive either placebo, 0.01, 0.05 or 0.1 microgram kg-1 min-1 remifentanil for a further 15 min. We found a significant correlation between the dose of remifentanil and the change of BIS after 15 min of infusion. The correlation between all the sedation scores and their corresponding BIS was also significant. We concluded that remifentanil, in combination with propofol, reduces BIS when used for sedation.      

Pharmacodynamic Interaction between Propofol and Remifentanil Regarding Hypnosis, Tolerance of Laryngoscopy, Bispectral Index, and Electroencephalographic Approximate Entropy

Background: The purpose of this investigation was to describe the pharmacodynamic interaction between propofol and remifentanil for probability of no response to shaking and shouting, probability of no response to laryngoscopy, Bispectral Index (BIS), and electroencephalographic approximate entropy (AE).

Methods: Twenty healthy volunteers received either propofol or remifentanil alone and then concurrently with a fixed concentration of remifentanil or propofol, respectively, via a target-controlled infusion. Responses to shaking and shouting and to laryngoscopy were assessed multiple times after allowing for plasma effect site equilibration. The raw electroencephalogram and BIS were recorded throughout the study, and AE was calculated off-line. Response surfaces were fit to the clinical response data using logistic regression or hierarchical response models. Response surfaces were also estimated for BIS and AE. Surfaces were visualized using three-dimensional rotations. Model parameters were estimated with NONMEM.

Results: Remifentanil alone had no appreciable effect on response to shaking and shouting or response to laryngoscopy. Propofol could ablate both responses. Modest remifentanil concentrations dramatically reduced the concentrations of propofol required to ablate both responses. The hierarchical response surface described the data better than empirical logistic regression. BIS and AE are more sensitive to propofol than to remifentanil.     

Pharmacodynamic interaction between propofol and remifentanil regarding hypnosis, tolerance of laryngoscopy, bispectral index, and electroencephalographic approximate entropy

BACKGROUND: The purpose of this investigation was to describe the pharmacodynamic interaction between propofol and remifentanil for probability of no response to shaking and shouting, probability of no response to laryngoscopy, Bispectral Index (BIS), and electroencephalographic approximate entropy (AE). METHODS: Twenty healthy volunteers received either propofol or remifentanil alone and then concurrently with a fixed concentration of remifentanil or propofol, respectively, via a target-controlled infusion. Responses to shaking and shouting and to laryngoscopy were assessed multiple times after allowing for plasma effect site equilibration. The raw electroencephalogram and BIS were recorded throughout the study, and AE was calculated off-line. Response surfaces were fit to the clinical response data using logistic regression or hierarchical response models. Response surfaces were also estimated for BIS and AE. Surfaces were visualized using three-dimensional rotations. Model parameters were estimated with NONMEM. RESULTS: Remifentanil alone had no appreciable effect on response to shaking and shouting or response to laryngoscopy. Propofol could ablate both responses. Modest remifentanil concentrations dramatically reduced the concentrations of propofol required to ablate both responses. The hierarchical response surface described the data better than empirical logistic regression. BIS and AE are more sensitive to propofol than to remifentanil. CONCLUSIONS: Remifentanil alone is ineffective at ablating response to stimuli but demonstrates potent synergy with propofol. BIS and AE values corresponding to 95% probability of ablating response are influenced by the combination of propofol and remifentanil to achieve this endpoint, with higher propofol concentrations producing lower values for BIS and AE.     

Comparison of spontaneous frontal EMG, EEG power spectrum and bispectral index to monitor propofol drug effect and emergence

Background: The aim of this study was to investigate the accuracy of frontal spontaneous electromyography (SEMG) and EEG spectral edge frequency (SEF 95%), median frequency (MF), relative delta power (RDELTA) and bispectral index (BIS) in monitoring loss of and return of consciousness and hypnotic drug effect during propofol administration at different calculated plasma target concentrations.
Methods: Propofol was administered by using a target-controlled infusion at different propofol steady-state concentrations. All variables were measured simultaneously at specific calculated concentrations and endpoints.
Results: Loss of consciousness was accurately monitored by BIS, SEMG and SEF 95%, and propofol drug effect by BIS only. Return of consciousness was predicted by BIS, MF and SEF 95%. Due to the biphasic EEG pattern of propofol and the lack of reproducible data at specific propofol concentrations, the clinical usefulness of SEF 95%, MF and RDELTA was very limited. SEMG was useful to detect loss and return of consciousness, but without predictive value.
Conclusions: The BIS might be an accurate measure to monitor depth of anaesthesia and hypnotic drug effect. Other neurophysiologic measures have limited value to monitor depth of anaesthesia and hypnotic drug effect.     

Absence of implicit and explicit memory during propofol/remifentanil anaesthesia

BACKGROUND AND OBJECTIVE: High doses of opioid associated with low doses of hypnotic is a popular anaesthetic technique since the use of remifentanil has become widespread. This type of anaesthesia could result in a higher incidence of implicit memory. METHODS: Ten patients were anaesthetised with a target-controlled infusion of remifentanil (target concentration of 8 ng mL(-1)) combined with a target-controlled infusion of propofol with progressive stepwise increases until loss of consciousness was reached. A tape containing 20 words was then played to the patients. Bispectral index (BIS, Aspect Medical Systems, Newton, MA, USA) was continuously monitored during the whole study period. Implicit and explicit memories were tested between 2 and 4 h after recovery. RESULTS: Loss of consciousness was obtained with a mean calculated propofol plasma concentration of 1.3 +/- 0.4 microg mL(-1). At this low hypnotic concentration no implicit or explicit memory was found in the three postoperative memory tests. Median (range) BIS value during word presentation was 93 (80-98). CONCLUSIONS: In our group of young American Society of Anesthesiologists (ASA) I/II patients, no explicit or implicit memory was found when the calculated concentration of propofol combined with a high concentration of remifentanil was maintained at the level associated with loss of consciousness with high BIS values.     

Narcotrend Monitoring Allows Faster Emergence and a Reduction of Drug Consumption in Propofol-Remifentanil Anesthesia

Background: The Narcotrend is a new electroencephalographic monitor designed to measure depth of anesthesia, based on a six-letter classification from A (awake) to F (increasing burst suppression) including 14 substages. This study was designed to investigate the impact of Narcotrend monitoring on recovery times and propofol consumption in comparison to Bispectral Index(R) (BIS(R)) monitoring or standard anesthetic practice.

Methods: With institutional review board approval and written informed consent, 120 adult patients scheduled to undergo minor orthopedic surgery were randomized to receive a propofol-remifentanil anesthetic controlled by Narcotrend, by BIS(R), or solely by clinical parameters. Anesthesia was induced with 0.4 [mu]g [middle dot] kg-1 [middle dot] min-1 remifentanil and a propofol target-controlled infusion at 3.5 [mu]g/ml. After intubation, remifentanil was reduced to 0.2 [mu]g [middle dot] kg-1 [middle dot] min-1, whereas the propofol infusion was adjusted according to clinical parameters or to the following target values: during maintenance to D0 (Narcotrend) or 50 (BIS(R)); 15 min before the end of surgery to C1 (Narcotrend) or 60 (BIS(R)). Recovery times were recorded by a blinded investigator, and average normalized propofol consumption was calculated from induction and maintenance doses.

Results: The groups were comparable for demographic data, duration of anesthesia, and mean remifentanil dosages. Compared with standard practice, patients with Narcotrend or BIS(R) monitoring needed significantly less propofol (standard practice, 6.8 +/- 1.2 mg [middle dot] kg-1 [middle dot] h-1vs. Narcotrend, 4.5 +/- 1.1 mg [middle dot] kg-1 [middle dot] h-1 or BIS(R), 4.8 +/- 1.0 mg [middle dot] kg-1 [middle dot] h-1;P < 0.001), opened their eyes earlier (9.3 +/- 5.2 vs. 3.4 +/- 2.2 or 3.5 +/- 2.9 min), and were extubated sooner (9.7 +/- 5.3 vs. 3.7 +/- 2.2 or 4.1 +/- 2.9 min).     

Intrathecal fentanyl reduces the dose of propofol required for sedation during spinal anesthesia

OBJECTIVES: To assess the effects of 2 dosages of intrathecal fentanyl on the requirement for propofol infused intravenously for the sedation of patients under spinal anesthesia. MATERIAL AND METHODS: We conducted a prospective controlled clinical trial enrolling patients in ASA physical status class 1 randomly assigned to 3 groups. Group 1 received 12.5 mg of 0.75% hyperbaric bupivacaine; group 2, 12.5 mg of bupivacaine plus 15 microg of fentanyl; group 3, 12.5 mg of bupivacaine plus 25 microg of fentanyl. After initiation of spinal anesthesia, monitoring of the bispectral (BIS) index (BIS XP A-2000) was begun, and sedation was maintained with a propofol infusion through a target-controlled infusion device (Orchestra Base Primea) for an initial effect-site concentration of 2.5 microg mL(-1), which was adjusted to maintain the BIS index between 60 and 75. We recorded BIS indices, noninvasive blood pressure, electrocardiogram, oxygen saturation, nasal end-tidal carbon dioxide pressure, mean infusion dose of propofol, total infusion dose of propofol, time until awakening, propofol consumption, and adverse effects. RESULTS: Seventy-five patients (25 in each group) were enrolled. Patient characteristics and BIS indices were similar in all groups. Propofol doses were significantly lower and times until awakening were significantly shorter in groups 2 and 3 than in group 1 (P < .01). The incidences of pruritus were significantly higher in groups 2 and 3. CONCLUSIONS: Adding 15 or 25 microg of fentanyl to hyperbaric bupivacaine lowers the dose of intravenous propofol required for sedation of patients under spinal anesthesia.     

Determination of the pharmacodynamic interaction of propofol and remifentanil during esophagogastroduodenoscopy in children

BACKGROUND: Propofol is commonly used to anesthetize children undergoing esophagogastroduodenoscopy. Opioids are often used in combination with propofol to provide total intravenous anesthesia. Because both propofol and remifentanil are associated with rapid onset and offset, the combination of these two drugs may be particularly useful for procedures of short duration, including esophagogastroduodenoscopy. The authors previously demonstrated that the median effective concentration (C50) of propofol during esophagogastroduodenoscopy in children is 3.55 microg/ml. The purpose of this study was to describe the pharmacodynamic interaction of remifentanil and propofol when used in combination for esophagogastroduodenoscopy in pediatric patients. METHODS: The authors studied 32 children aged between 3 and 10 yr who were scheduled to undergo esophagogastroduodenoscopy. Propofol was administered via a target-controlled infusion system using the STANPUMP software based on a pediatric pharmacokinetic model. Remifentanil was administered as a constant rate infusion of 25, 50, and 100 ng.kg(-1).min(-1) to each of three study groups, respectively. A sigmoid Emax model was developed to describe the interaction of remifentanil and propofol. RESULTS: There was a positive interaction between remifentanil and propofol when used in combination. The concentration of propofol alone associated with 50% probability of no response was 3.7 microg/ml (SE, 0.4 microg/ml), and this was decreased to 2.8 microg/ml (SE, 0.1 microg/ml) when used in combination with remifentanil. CONCLUSION: A remifentanil infusion of 25 ng.kg(-1).min(-1) reduces the concentration of propofol required for adequate anesthesia for esophagogastroduodenoscopy from 3.7 to 2.8 microg/ml. Increasing the remifentanil infusion yields minimal additional decrease in propofol concentration and may increase the risk of side effects.     

Propofol and remifentanil pharmacodynamic interaction during orthopedic surgical procedures as measured by effects on bispectral index

STUDY OBJECTIVE: To identify and quantify the interaction between propofol and remifentanil during surgical procedures with a bispectral index (BIS) of 50 that was chosen as a continuous surrogate measure for "adequate depth" of anesthesia. DESIGN: Prospective, open-label study. SETTING: Department of orthopedics of a university hospital. PATIENTS: 20 patients undergoing orthopedic surgery. INTERVENTIONS: Anesthesia was induced and maintained with propofol and remifentanil, both administered by target-controlled infusion (TCI). Initial target concentrations of propofol (1.5-8 microg/mL) and remifentanil (2-15 ng/mL) were chosen and alternated in order to maintain the BIS between 45 and 55. If constant target concentrations had been maintained for 20 minutes and the BIS did not depart from the desired range, blood samples were taken to determine propofol concentrations, and the BIS value was recorded. Isobolographic interaction models were fitted to the infusion rates of remifentanil and propofol, predicted target concentrations of both drugs, and measured propofol concentrations versus predicted remifentanil concentrations. MAIN RESULTS: The isobole for the interaction of propofol and remifentanil in the concentration range investigated (propofol 1.5-8 microg/mL and remifentanil 1-30 ng/mL) is a concave up hyperbola ((0.15. C(prop))(3.13). C(rem) = 1) with C(prop) = propofol plasma concentration [microg/mL] and C(rem) = remifentanil blood concentration [ng/mL]). Use of predicted (=TCI target) concentrations or the respective infusion rates did not alter the general shape of the interaction isobole.Conclusions: The interaction between propofol and remifentanil for maintenance of a BIS value between 45 and 55 during surgery is synergistic. This finding applies regardless of whether measured concentrations (for propofol), predicted concentrations of the infusion device, or infusion rates are used as model input. Notably, the interaction isobole of the (clinically readily available) infusion rates provides a useful dosing recommendation for the coadministration of propofol and remifentanil during maintenance of anesthesia.     

Bispectral index in patients with target-controlled or manually-controlled infusion of propofol

In this prospective, randomized study we compared bispectral index (BIS), hemodynamics, time to extubation, and the costs of target-controlled infusion (TCI) and manually-controlled infusion (MCI) of propofol. Forty patients undergoing first-time implantation of a cardioverter-defibrillator were included. Anesthesia was performed with remifentanil (0.2-0.3 micro g. kg(-1). min(-1)) and propofol. Propofol was used as TCI (plasma target concentration, 2.5-3.5 micro g/mL; n = 20) or MCI (3.0-4.0 mg. kg(-1). h(-1); n = 20). BIS, heart rate, and arterial blood pressure were measured at six data points: T1, before anesthesia; T2, after intubation; T3, after skin incision; T4, after first defibrillation; T5, after third defibrillation; and T6, after extubation. There were no significant hemodynamic differences between the two groups. BIS was significantly lower at T3 and T4 in the TCI group than in the MCI group. The mean dose of propofol was larger in TCI patients (5.8 +/- 1.4 mg. kg(-1). h(-1)) than in the MCI patients (3.7 +/- 0.6 mg. kg(-1). h(-1)) (P < 0.05), whereas doses of remifentanil did not differ. Time to extubation did not differ between the two groups (TCI, 13.7 +/- 5.3 min; MCI, 12.3 +/- 3.5 min). One patient in the MCI group had signs of intraoperative awareness without explicit memory after first defibrillation (BIS before shock, 49; after shock, 83). Costs were significantly less in the MCI group (34.83 US dollars) than in the TCI group (39.73 US dollars). BIS failed to predict the adequacy of anesthesia for the next painful stimulus. IMPLICATIONS: In this prospective, randomized study, bispectral index (BIS), hemodynamics, time to extubation, and costs of target-controlled infusion (TCI) and manually-controlled infusion of propofol were compared. TCI increased the amount of propofol used. BIS failed to predict the adequacy of anesthesia for the next painful stimulus.