Adequacy of maternal anesthesia depth with two sodium thiopental doses in elective caesarean section: a randomized clinical trial.

BACKGROUND: Administration of an optimal dose of anesthetic agent to ensure adequate depth of hypnosis with the lowest risk of adverse effects to the fetus is highly important in cesarean section. Sodium thiopental (STP) is still the first choice for induction of anesthesia in some countries for this obstetric surgery. We aimed to compare two doses of STP with regarding the depth of anesthesia and the condition of newborn infants. METHODS: In this clinical trial, parturient undergoing elective Caesarian section were randomized into two groups receiving either low-dose (5 mg/kg) or high-dose (7 mg/kg) STP. Muscle relaxation was provided with succinylcholine 2 mg/kg and anesthesia was maintained with O2/N2O and sevoflurane. The depth of anesthesia was evaluated using isolated forearm technique (IFT) and bispectral index (BIS) in various phases. Additionally, infants were assessed using Apgar score and neurobehavioral test. RESULTS: Forty parturient were evaluated in each group. BIS was significantly lower in high-dose group at skin incision to delivery and subcutaneous and skin closure. Also, significant differences were noticed in IFT over induction to incision and incision to delivery. Apgar score was significantly lower in high-dose group at 1 min after delivery. Newborn infants in low-dose group had significantly better outcomes in all three domains of the neurobehavioral test. CONCLUSION: 7 mg/kg STP is superior to 5 mg/kg in creating deeper hypnosis for mothers. However, it negatively impacts Apgar score and neurobehavioral test of neonates. STP seems to has dropped behind as an acceptable anesthetic in Cesarean section. TRIAL REGISTRATION: IRCT No: 2016082819470 N45 , 13/03/2019.

Monitoring Depth of Hypnosis: Mid-Latency Auditory Evoked Potentials Derived aepEX in Children Receiving Desflurane-Remifentanil Anesthesia.

BACKGROUND: The aepEXplus monitoring system, which uses mid-latency auditory evoked potentials to measure depth of hypnosis, was evaluated in pediatric patients receiving desflurane-remifentanil anesthesia. METHODS: Seventy-five patients, 1-18 years of age (stratified for age; 1-3, 3-6, 6-18 years, for subgroup analyses), were included in this prospective observational study. The aepEX and the bispectral index (BIS) were recorded simultaneously, the latter serving as a reference. The ability of the aepEX to detect different levels of consciousness, defined according to the University of Michigan Sedation Scale, investigated using prediction probability (Pk), and receiver operating characteristic (ROC) analysis, served as the primary outcome parameter. As a secondary outcome parameter, the relationship between end-tidal desflurane and the aepEX and BIS values were calculated by fitting in a nonlinear regression model. RESULTS: The Pk values for the aepEX and the BIS were, respectively, .68 (95% CI, 0.53-0.82) and .85 (95% CI, 0.73-0.96; P = .02). The aepEX and the BIS had an area under the ROC curve of, respectively, 0.89 (95% CI, 0.80-0.95) and 0.76 (95% CI, 0.68-0.84; P = .04). The maximized sensitivity and specificity were, respectively, 81% (95% CI, 61%-93%) and 86% (95% CI, 74%-94%) for the aepEX at a cutoff value of >52, and 69% (95% CI, 56%-81%) and 70% (95% CI, 57%-81%) for the BIS at a cutoff value of >65. The age-corrected end-tidal desflurane concentration associated with an index value of 50 (EC50) was 0.59 minimum alveolar concentration (interquartile range: 0.38-0.85) and 0.58 minimum alveolar concentration (interquartile range: 0.41-0.70) for, respectively, the aepEX and BIS (P = .69). Age-group analysis showed no evidence of a difference regarding the area under the ROC curve or EC50. CONCLUSIONS: The aepEX can reliably differentiate between a conscious and an unconscious state in pediatric patients receiving desflurane-remifentanil anesthesia.

Effect of magnesium sulfate on anesthesia depth, awareness incidence, and postoperative pain scores in obstetric patients. A double-blind randomized controlled trial.

OBJECTIVES: To assess the effects of magnesium on the depth of anesthesia and to determine the effects of magnesium on incidence of awareness and postoperative pain after caesarean section.  Methods: The study was designed as a double-blind, controlled, randomized study and conducted in Hacettepe University Hospital, Ankara, Turkey  between January 2015 and March 2016. A total of 100 pregnant healthy women who were between 17 and 41 years old, ASA II, and scheduled for an elective cesarean section with general anesthesia were included in the study. After induction, sevoflurane was used for maintenance in Group S and desflurane in Group D (control groups). At Group S-M and Group D-M (study groups), magnesium infusion was started with sevoflurane and desflurane anesthesia respectively. Minimum alveolar concentration of sevoflurane and desflurane were kept constant. Bispectral index scores (BIS), fentanyl consumption and postoperative visual analogue scale (VAS) values were recorded. All of the patients had been followed-up for awareness until the postoperative first year. Results: Demographic variables of the patients were similar. BIS values were significantly higher in control groups throughout the operation (p less than 0.001). No significant difference was detected for intraoperative fentanyl consumption and awareness incidence. VAS values were significantly lower in study groups (p less than 0.05). Conclusion: Magnesium infusion provided significantly lower intraoperative BIS values and lower postoperative VAS scores. We believe that magnesium can be useful as an adjuvant to general anesthesia.

Different effects of propofol and dexmedetomidine sedation on electroencephalogram patterns: Wakefulness, moderate sedation, deep sedation and recovery.

Sedation induces changes in electroencephalography (EEG) dynamics. However, the distinct EEG dynamic characteristics at comparable sedation levels have not been well studied, resulting in potential interpretation errors in EEG monitoring during sedation. We aimed to analyze the EEG dynamics of dexmedetomidine and propofol at comparable sedation levels and to explore EEG changes with increased sedation levels for each agent. We measured the Bispectral Index (BIS) and 20-channel EEG under dexmedetomidine and propofol sedation from wakefulness, moderate sedation, and deep sedation to recovery in healthy volunteers (n = 10) in a randomized, 2-day, crossover study. Observer's Assessment of Alertness and Sedation (OAA/S) score was used to assess sedation levels. Despite similar changes in increased delta oscillations, multiple differences in the EEG spatiotemporal dynamics were observed between these two agents. During moderate sedation, both dexmedetomidine and propofol induced increased spindle power; however, dexmedetomidine decreased the global alpha/beta/gamma power, whereas propofol decreased the alpha power in the occipital area and increased the global spindle/beta/gamma power. During deep sedation, dexmedetomidine was associated with increased fronto-central spindle power and decreased global alpha/beta/gamma power, but propofol was associated with increased theta/alpha/spindle/beta power, which was maximized in the frontal area. The transition of topographic alpha/spindle/beta power distribution from moderate sedation to deep sedation completely differed between these two agents. Our study demonstrated that there was a distinct hierarchy of EEG changes with increased sedation depths by propofol and dexmedetomidine. Differences in EEG dynamics at the same sedation level might account for differences in the BIS value and reflect the different sedation mechanisms. EEG-based clinical sedation monitoring should consider the effect of drug types on EEG dynamics.

Regulation of hypnosis in Propofol anesthesia administration based on non-linear control strategy.

Continuous adjustment of Propofol in manual delivery of anesthesia for conducting a surgical procedure overburdens the workload of an anesthetist who is working in a multi-tasking scenario. Going beyond manual administration and Target Controlled Infusion, closed-loop control of Propofol infusion has the potential to offer several benefits in terms of handling perturbations and reducing the effect of inter-patient variability. This paper proposes a closed-loop automated drug administration approach to control Depth Of Hypnosis in anesthesia. In contrast with most of the existing research on anesthesia control which makes use of linear control strategies or their improved variants, the novelty of the present research lies in applying robust control strategy i.e. Sliding Mode Control to accurately control drug infusion. Based on the derived patient's model, the designed controller uses measurements from EEG to regulate DOH on Bispectral Index by controlling infusion rate of Propofol. The performance of the controller is investigated and characterized with real dataset of 8 patients undergoing surgery. Results of this in silico study indicate that for all the patients, with 0% overshoot observed, the steady state error lies in between ±5. Clinically, this implies that in all the cases, without any overdose, the controller maintains the desired DOH level for smooth conduction of surgical procedures.

Intraoperative aberrant bispectral index values due to facial nerve monitoring.

Bispectral index is an accepted depth of anaesthesia monitor for guiding intraoperative hypnotic agent administration. Frontalis EMG displayed on BIS monitor may increase due to twitching of frontalis muscle. EMG increases are also known to cause artefactual increases in BIS values. We report a case of artefactual increase of EMG and subsequently BIS values, due to electrical artefact from cranial nerve stimulator being used to identify the facial nerve. An explanation of the effect of stimulator signal on BIS EMG and BIS values has been provided.

Hypnosis closed loop TCI systems in outpatient surgery. / Sistemas de TCI en circuito cerrado para la hipnosis en cirugía ambulatoria.

OBJECTIVE: Determine the influence of general anaesthesia with closed-loop systems in the results of outpatient varicose vein surgery. PATIENTS AND METHODS: Retrospective observational study including data from 270 outpatients between 2014 and 2015. The patients were divided into 2 groups according to the type of general anaesthesia used. The CL Group included patients who received propofol in closed-loop guided by BIS and remifentanil using TCI, and the C Group received non-closed-loop anaesthesia. Age, sex, surgical time, discharge time and failure of outpatient surgery were recorded. Quantitative data were checked for normal distribution by the method of Kolmogorov-Smirnov-Lilliefors. Differences between groups were analysed by a Student-t-test or Mann-Whitney-Wilcoxon test, depending on their distribution. Categorical data were analysed by a Chi-squared test. We used Kaplan-Meier estimator and the effect size (calculated by Cohen's d) to study the discharge time. Statistical analysis was performed using R 3.2.3 binary for Mac OS X 10.9. RESULTS: There were no significant differences in age, sex and surgical time and failure of outpatient surgery. Discharge time was different in both groups: 200 (100) vs. 180 (82.5) minutes, C Group and CL Group, respectively (data are median and interquartile rank); P=.005. CONCLUSION: The use of closed-loop devices for the hypnotic component of anaesthesia hastens discharge time. However, for this effect to be clinically significant, some improvements still need to be made in our outpatient surgery units.

Changes in First Postoperative Night Bispectral Index After Daytime Sedation Induced by Dexmedetomidine or Midazolam Under Regional Anesthesia: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Supplementation of spinal anesthesia with various sedatives is a standard protocol to alleviate patient anxiety associated with the surgical procedure. We hypothesized that, compared with dexmedetomidine, midazolam might have a subtle influence on sleep quality after surgery following elective transurethral prostatic resection (TURP) in elderly male patients. METHODS: A randomized, double-blind, controlled trial was conducted at the First Hospital of China Medical University from July 2014 to January 2015. One hundred eleven patients undergoing TURP were enrolled and received intravenous saline infusion (control group), dexmedetomidine (dexmedetomidine group), or midazolam (midazolam group) for sedation during the spinal anesthesia procedure. The intraoperative sedative state and postoperative sleep quality were evaluated using a Bispectral Index (BIS)-Vista monitor. The primary outcome was postoperative sleep quality, as measured by the BIS-Vista monitor on the first night after surgery. RESULTS: The intraoperative BIS area under the curve value was significantly lower in the dexmedetomidine group (54.1%) compared with those in the other 2 groups (control group, 94.1%; midazolam group, 77.2%).The postoperative BIS area under the curve value was highest in the dexmedetomidine group at 88.7%. The BIS sleep efficiency index showed a significant 33.1% increase in the midazolam group compared with the dexmedetomidine group. The duration of sleep in the midazolam group was 237.8 minutes longer than that in the dexmedetomidine group. CONCLUSIONS: We conclude that midazolam combined with spinal anesthesia might preserve the sleep quality of elderly male patients immediately after TURP.

Comparisons of Electroencephalographically Derived Measures of Hypnosis and Antinociception in Response to Standardized Stimuli During Target-Controlled Propofol-Remifentanil Anesthesia.

BACKGROUND: Current electroencephalogram (EEG)-derived measures provide information on cortical activity and hypnosis but are less accurate regarding subcortical activity, which is expected to vary with the degree of antinociception. Recently, the neurophysiologically based EEG measures of cortical input (CI) and cortical state (CS) have been shown to be prospective indicators of analgesia/antinociception and hypnosis, respectively. In this study, we compared CI and an alternate measure of CS, the composite cortical state (CCS), with the Bispectral Index (BIS) and another recently developed measure of antinociception, the composite variability index (CVI). CVI is an EEG-derived measure based on a weighted combination of BIS and estimated electromyographic activity. By assessing the relationship between these indices for equivalent levels of hypnosis (as quantified using the BIS) and the nociceptive-antinociceptive balance (as determined by the predicted effect-site concentration of remifentanil), we sought to evaluate whether combining hypnotic and analgesic measures could better predict movement in response to a noxious stimulus than when used alone. METHODS: Time series of BIS and CVI indices and the raw EEG from a previously published study were reanalyzed. In our current study, the data from 80 patients, each randomly allocated to a target hypnotic level (BIS 50 or BIS 70) and a target remifentanil level (Remi-0, -2, -4 or -6 ng/mL), were included in the analysis. CCS, CI, BIS, and CVI were calculated or quantified at baseline and at a number of intervals after the application of the Observer's Assessment of Alertness/Sedation scale and a subsequent tetanic stimulus. The dependency of the putative measures of antinociception CI and CVI on effect-site concentration of remifentanil was then quantified, together with their relationship to the hypnotic measures CCS and BIS. Finally, statistical clustering methods were used to evaluate the extent to which simple combinations of antinociceptive and hypnotic measures could better detect and predict response to stimulation. RESULTS: Before stimulation, both CI and CVI differentiated patients who received remifentanil from those who were randomly allocated to the Remi-0 group (CI: Cohen's d = 0.65, 95% confidence interval, 0.48-0.83; CVI: Cohen's d = 0.72, 95% confidence interval, 0.56-0.88). Strong correlations between BIS and CCS were found (at different periods: 0.55 < R2 < 0.68, P < 0.001). Application of the Observer's Assessment of Alertness/Sedation stimulus was associated with changes in CI and CCS, whereas, subsequent to the application of both stimuli, changes in all measures were seen. Pairwise combinations of CI and CCS showed higher sensitivity in detecting response to stimulation than CVI and BIS combined (sensitivity [99% confidence interval], 75.8% [52.7%-98.8%] vs 42% [15.4%-68.5%], P = 0.006), with specificity for CI and CCS approaching significance (52% [34.7%-69.3%] vs 24% [9.1%-38.9%], P = 0.0159). CONCLUSIONS: Combining electroencephalographically derived hypnotic and analgesic quantifiers may enable better prediction of patients who are likely to respond to tetanic stimulation.

Effects of Music Therapy on Anesthesia Requirements and Anxiety in Women Undergoing Ambulatory Breast Surgery for Cancer Diagnosis and Treatment: A Randomized Controlled Trial.

PURPOSE: To investigate the effect of live and recorded perioperative music therapy on anesthesia requirements, anxiety levels, recovery time, and patient satisfaction in women experiencing surgery for diagnosis or treatment of breast cancer. PATIENTS AND METHODS: Between 2012 and 2014, 207 female patients undergoing surgery for potential or known breast cancer were randomly assigned to receive either patient-selected live music (LM) preoperatively with therapist-selected recorded music intraoperatively (n=69), patient-selected recorded music (RM) preoperatively with therapist-selected recorded music intraoperatively (n=70), or usual care (UC) preoperatively with noise-blocking earmuffs intraoperatively (n=68). RESULTS: The LM and the RM groups did not differ significantly from the UC group in the amount of propofol required to reach moderate sedation. Compared with the UC group, both the LM and the RM groups had greater reductions (P<.001) in anxiety scores preoperatively (mean changes [and standard deviation: -30.9 [36.3], -26.8 [29.3], and 0.0 [22.7]), respectively. The LM and RM groups did not differ from the UC group with respect to recovery time; however, the LM group had a shorter recovery time compared with the RM group (a difference of 12.4 minutes; 95% CI, 2.2 to 22.5; P=.018). Satisfaction scores for the LM and RM groups did not differ from those of the UC group. CONCLUSION: Including music therapy as a complementary modality with cancer surgery may help manage preoperative anxiety in a way that is safe, effective, time-efficient, and enjoyable.

Cross-evidence for hypnotic susceptibility through nonlinear measures on EEGs of non-hypnotized subjects.

Assessment of hypnotic susceptibility is usually obtained through the application of psychological instruments. A satisfying classification obtained through quantitative measures is still missing, although it would be very useful for both diagnostic and clinical purposes. Aiming at investigating the relationship between the cortical brain activity and the hypnotic susceptibility level, we propose the combined use of two methodologies - Recurrence Quantification Analysis and Detrended Fluctuation Analysis - both inherited from nonlinear dynamics. Indicators obtained through the application of these techniques to EEG signals of individuals in their ordinary state of consciousness allowed us to obtain a clear discrimination between subjects with high and low susceptibility to hypnosis. Finally a neural network approach was used to perform classification analysis.

SNAP II index: an alternative to the COMFORT scale in assessing the level of sedation in mechanically ventilated pediatric patients.

Sedation monitoring is essential in pediatric patients on ventilatory support to achieve comfort and safety. The COMFORT scale was designed and validated to assess the level of sedation in intubated pediatric patients. However, it remains unreliable in pharmacologically paralyzed patients. The SNAP II index is calculated using an algorithm that incorporates high-frequency (80-420 Hz) electroencephalogram (EEG) components, known to be useful in discriminating between awake and unconscious states, unlike other measurements that only include low-frequency EEG segments such as the bispectral index score. Previous studies suggested that the SNAP II index is a reliable and sensitive indicator of the level of consciousness in adult patients. Despite its potential, no data are currently available in the pediatric critically ill population on ventilatory support. This is the first pilot study assessing the potential application of the SNAP II index in critically ill pediatric patients by comparing it to the commonly used COMFORT scale.

[BIS values were useful on the evaluation of consciousness recovery in acute Vegetamin-A poisoning: report of a case].

A 37-year-old man was admitted to our hospital with acute phenobarbital poisoning. On arrival, he was in deep coma with respiro-circulatory depressions. The serum concentration of the agent was elevated to 149.04 µg/mL which was consistent with a lethal concentration level. He underwent a gastric lavage, administration of activated charcoal, urinary alkalinazation and bowel irrigation. Respiro-circulatory status was recovered rapidly, while the serum concentration of phenobarbital did not decrease smoothly. Although the concentration of the agent decreased to 77.07 µg/mL that should be a comatose level, BIS values were gradually elevated, and then eventually the patient regained his consciousness. Because he was a chronic user of Vegetamin-A containing phenobarbital, the serum level might not have been correlated with symptoms. BIS values were highly reflective of the consciousness level, so it could be a useful indicator for predicting the consciousness levels of patients in deep coma with acute poisoning from hypnotic agents.

Auditory stimuli as a contributor to consciousness while under general anesthesia.

BACKGROUND: The incidence of intraoperative awareness under general anesthesia approaches 1% in high-risk patients. Anesthesiologists commonly utilize processed electroencephalograms (EEG) in order to monitor "depth" of anesthesia, the most common of which is the Bispectral Index (BIS). The B-aware and B-Unaware trials, which were designed to test the efficacy of the BIS monitor, noted an auditory component in 16 of 17 confirmed cases of intraoperative awareness. Implicit auditory memory formation has been documented under general anesthesia. Small studies have documented a significant effect of noise on BIS scores during monitored anesthesia care. METHODS: Twenty-two patients undergoing general anesthesia received earplugs after the induction of anesthesia. Every ten minutes the earplugs were reinserted or removed. Noise levels were recorded every 0.125 s and both average and maximal BIS scores were recorded every minute. Non-parametric analysis of both populations (with and without earplugs) was performed. A mixed effects model with one degree of freedom (with and without earplugs) was generated to take into account the effect of anesthetic agents on BIS scores. RESULTS: 3009 min of data were recorded. The median and range (25-75%) BIS scores were 39 (29-46) and 39 (28-44) with and without earplugs in place, respectively. Earplugs were associated with lower BIS scores (p=0.0183). The mixed effects model confirmed this relationship (p<0.001). Subgroup analysis of BIS scores in which the potential for awareness existed (maximum BIS>60 in any one minute epoch) showed a 32% reduction in the incidence of maximal BIS scores exceeding 60 (p=0.0012). There was no relationship between ambient noise level and average maximal BIS score (R(2)=0.003). CONCLUSIONS: Our study suggests that earplugs may reduce the incidence of BIS scores >60 in patients undergoing total intravenous anesthesia and that auditory stimuli may affect EEG interpretation. Because of the low cost and safety of noise reduction, as well as the catastrophic implications of intraoperative awareness, further studies to explore the effects of auditory stimuli on awareness and anesthesia are warranted.

Bispectral index dynamics during propofol hypnosis is similar in red-haired and dark-haired subjects.

BACKGROUND: We have previously shown that red hair is associated with increased desflurane requirement for immobility, compared with dark hair. The effect of red hair on IV anesthetic requirement remains unknown. We tested the hypothesis that the propofol concentration in the effect site associated with half maximal electroencephalogram response, Ce50, is at least 50% higher in subjects with red hair. METHODS: We modeled the propofol concentration versus electroencephalogram response relationship using a 2-step approach in 29 healthy dark- and red-haired volunteers receiving a propofol infusion to produce loss of consciousness. Bispectral Index (BIS) was the measure of drug effect. The parameters of a 3-compartment pharmacokinetic model were fit to measured arterial propofol concentrations. The relationship between effect-site propofol concentration (Ce) and BIS was characterized using a sigmoid Emax model. Model performance and accuracy of the estimated parameters were evaluated using accepted metrics and bootstrap resampling. The effect of hair color on the Ce50 for BIS response in the final model was assessed using a threshold of 6.63 (P<0.01) in reduction of -2 log likelihood. The influence of body weight on the model was also assessed. RESULTS: The inclusion of hair color as a model covariate did not improve either the pharmacokinetic or the pharmacodynamic model. A separate analysis for the dark- and red-haired subjects estimated a median (95% confidence interval) Ce50 BIS of 2.71 µg/mL (2.28-3.36 µg/mL) and 2.57 µg/mL (1.68-3.60 µg/mL), respectively. Body weight was a significant covariate for the CL1 and V1. CONCLUSIONS: Red hair phenotype does not affect the pharmacokinetics or pharmacodynamics of propofol.

Acupuncture on Yintang point decreases preoperative anxiety.

OBJECTIVES: The aim of this study was to investigate the effect of ear-press needle acupuncture on Yintang point for preoperative anxiety. DESIGN: This was a prospective, randomized, single-blind, controlled study. SETTINGS/LOCATION: The study setting was the Department of Anesthesiology in Ankara Training and Research Hospital of Ministry of Health, Ankara, Turkey. SUBJECTS: The study comprised 52 adult surgical patients. INTERVENTIONS: A single, 20-minute session of single-point acupuncture was applied on Yintang (acupuncture group) or sham point (sham acupuncture group). OUTCOME MEASURES: The efficacy of acupuncture was evaluated by means of the changes in bispectral index (BIS) and STAI (State-Trait Anxiety Index). RESULTS: BIS values in the acupuncture group were significantly lower than in the sham group in all time intervals (p<0.0042). BIS values were lower than baseline in the study group during the entire study period (p<0.0004) while no such effect has been observed in the sham group (p>0.0004). Mean values of state anxiety (STAI-S) decreased after acupuncture in the study group (p=0,018), while no change was observed in trait anxiety (STAI-T) (p=0.156). Patients of the sham group showed no change in both parameters (p=0.387 and p=0,116). CONCLUSIONS: Ear-press needle acupuncture on Yintang point reduces preoperative anxiety in adult surgical patients.

Awake during General Anesthesia with BispectralIndex Value of 35

Awareness of intraoperative events in patients under general anesthesia is rare, but awareness during anesthesia is a serious complication that leads to anxiety and post-traumatic stress disorder. The Bispectral Index (BIS) has generally been accepted as a measurement of hypnosis under anesthesia. It is derived from a processed electroencephalogram and computer algorithm that assigns a numerical value based on the probability of consciousness. A 46-year-old, 65-kg male without underlying disease underwent elective surgery for ventral hernia. The patient in this case was administered an anesthetic that we frequently use and then average BIS value are 35. But he experienced awake during general anesthesia. We describe the first case of intraoperation awake under BIS 40 using desflurane.