Decrease of the peak heights of EEG bicoherence indicated insufficiency of analgesia during surgery under general anesthesia.

BACKGROUND: Studies show that the two peak heights of electroencephalographic bicoherence (pBIC-high, pBIC-low) decrease after incision and are restored by fentanyl administration. We investigated whether pBICs are good indicators for adequacy of analgesia during surgery. METHODS: After local ethical committee approval, we enrolled 50 patients (27-65 years, ASA-PS I or II) who were scheduled elective surgery. Besides standard anesthesia monitors, to assess pBICs, we used a BIS monitor and freeware Bispectrum Analyzer for A2000. Fentanyl 5 µg/kg was completely administered before incision, and anesthesia was maintained with sevoflurane. After skin incision, when the peak of pBIC-high or pBIC-low decreased by 10% in absolute value (named LT10-high and LT10-low groups in order) or when either peak decreased to below 20% (BL20-high and BL20-low groups), an additional 1 g/kg of fentanyl was administered to examine its effect on the peak that showed a decrease. RESULTS: The mean values and standard deviation for pBIC-high 5 min before fentanyl administration, at the time of fentanyl administration, and 5 min after fentanyl administration for LT10-high group were 39.8% (10.9%), 26.9% (10.5%), and 35.7% (12.5%). And those for pBIC-low for LT10-low group were 39.5% (6.0%), 26.8% (6.4%) and 35.0% (7.0%). Those for pBIC-high for BL20-high group were 26.3% (5.6%), 16.5% (2.6%), and 25.7% (7.0%). And those for pBIC-low for BL20-low group were 26.7% (4.8%), 17.4% (1.8%) and 26.9% (5.7%), respectively. Meanwhile, at these trigger points, hemodynamic parameters didn't show significant changes. CONCLUSION: Superior to standard anesthesia monitoring, pBICs are better indicators of analgesia during surgery. TRIAL REGISTRY: Clinical trial Number and registry URL: UMIN ID: UMIN000042843 https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno = R000048907.

The arousal level of consciousness required for working memory performance: An anaesthesia study.

Regarding the stage of arousal level required for working memory to function properly, limited studies have been conducted on changes in working memory performance when the arousal level of consciousness decreases. This study aimed to experimentally clarify the stages of consciousness necessary for optimal working memory function. In this experiment, the sedation levels were changed step-by-step using anaesthesia, and the performance accuracy during the execution of working memory was assessed using a dual-task paradigm. Participants were required to categorize and remember words in a specific target category. Categorization performance was measured across four different sedative phases: before anaesthesia (baseline), and deep, moderate and light stages of sedation. Short-delay recognition tasks were performed under these four sedative stages, followed by long-delay recognition tasks after participants recovered from sedation. The results of the short-delay recognition task showed that the performance was lowest at the deep stage. The performance of the moderate stage was lower than the baseline. In the long-delay recognition task, the performance under moderate sedation was lower than that under baseline and light sedation. In addition, the performance under light sedation was lower than that under baseline. These results suggest that task performance becomes difficult under half sedation and that transferring information to long-term memory is difficult even under one-quarter sedation.

What are standard monitoring devices for anesthesia in future?

Monitoring the patient's physiological functions is critical in clinical anesthesia. The latest version of the Japanese Society of Anesthesiologists' Guidelines for Safe Anesthesia Monitoring, revised in 2019, covers various factors, including electroencephalogram monitoring, oxygenation, ventilation, circulation, and muscle relaxation. However, with recent advances in monitoring technologies, the information provided has become more detailed, requiring practitioners to update their knowledge. At a symposium organized by the Journal of Anesthesia in 2023, experts across five fields discussed their respective topics: anesthesiologists need to interpret not only the values displayed on processed electroencephalogram monitors but also raw electroencephalogram data in the foreseeable future. In addition to the traditional concern of preventing hypoxemia, monitoring for potential hyperoxemia and the effects of mechanical ventilation itself will become increasingly important. The importance of using AI analytics to predict hypotension, assess nociception, and evaluate microcirculation may increase. With the recent increase in the availability of neuromuscular monitoring devices in Japan, it is important for anesthesiologists to become thoroughly familiar with the features of each device to ensure its effective use. There is a growing desire to develop and introduce a well-organized, integrated "single screen" monitor.

Effect of remifentanil on three effect-site concentrations of propofol and their relationship during electroencephalography at loss of response, at maximum alpha power, and at onset of burst suppression: a prospective randomized trial.

PURPOSE: The effect-site concentration (Ce) at loss of response (Ce-LOR) to propofol closely correlates both with Ce as electroencephalographic alpha power becomes highest (Ce-alpha) and with Ce at onset of burst suppression (BS) (Ce-OBS), when no opioids are administered. Co-administration of opioids dose-dependently decreases Ce-LOR. We investigated the influence of remifentanil on the relationship between these three Ces. METHODS: After receiving approval from our local ethical committee, with written informed consent, we enrolled 90 participants (ASA-PS I or II) who were scheduled for elective surgery. Participants were randomly assigned to three groups: constant remifentanil Ce 0 ng/ml (Remi_0); 1 ng/mL (Remi_1); and 2 ng/mL (Remi_2). We recorded both raw EEG and EEG-derived parameters on a computer. After reaching remifentanil equilibrium, we administered propofol using a target-controlled infusion pump such that propofol Ce increased to about 0.3 µg/mL/min. After determining Ce-LOR, we administered 0.6 mg/kg of rocuronium and started mask ventilation. The study protocol ended after observation of BS. RESULTS: Three participants were excluded. Ce-LOR in each group (Remi_0, Remi_1, Remi_2) was 2.00 ± 0.58 µg/mL, 1.43 ± 0.49 µg/mL, and 1.37 ± 0.42 µg/mL. Ce-alpha was 2.91 ± 0.63 µg/mL, 2.30 ± 0.41 µg/mL, and 2.12 ± 0.39 µg/mL. Ce-OBS was 3.80 ± 0.69 µg/mL, 3.25 ± 0.68 µg/mL, and 2.90 ± 0.57 µg/mL. In three other instances, Ce was decreased by remifentanil. Generalized linear model analysis revealed that remifentanil had no influence on the relationship between the three Ces. CONCLUSION: During propofol anesthesia, even low concentrations of remifentanil shifted concentration-related electroencephalographic changes.

The surgical Apgar score predicts postoperative complications and the survival in lung cancer patients.

PURPOSE: The surgical Apgar score (SAS)-calculated using the intraoperative variables estimated blood loss, lowest heart rate, and lowest mean systolic pressure-is associated with mortality in cancer surgery. We investigated the utility of the SAS in patients with lung cancer undergoing surgery. METHODS: We retrospectively analyzed the data of 691 patients who underwent surgery for primary lung cancer between 2015 and 2019 in a single institute and analyzed the impact of the SAS. RESULTS: Of the 691 patients, 138 (20%), 57 (8.2%), and 7 (1.0%) had postoperative complications of all grades, grades ≥ III, and grade V, respectively, according to the Clavien-Dindo classification. The C-index for postoperative complications of grades ≥ III was 0.605. A lower score (0-5 points) (odds ratio 3.09 against 8-10 points, P = 0.04) and a lower percentage of vital capacity (odds ratio 0.97, P = 0.04) were independent negative risk factors for major postoperative complications. Patients with a lower score (0-5 points) had poor 5-year overall and cancer-specific survival rates (60.1% and 72.3%, respectively; P < 0.05 for both). CONCLUSIONS: The surgical Apgar score predicted postoperative complications and the long-term survival. Surgeons may improve surgical results using the SAS.

The pulmonary surgical Apgar score for lung cancer surgery predicts postoperative complications and long-term survival.

OBJECTIVES: The surgical Apgar score, calculated using 3 intraoperative variables (blood loss, lowest mean arterial pressure and lowest heart rate), is associated with mortality in cancer surgery. The original score has less applicability in lung cancer surgery; therefore, we innovated the modified pulmonary surgical Apgar score with additional intraoperative oxygen saturation representing pulmonary parenchymal damage and cardiopulmonary dynamics. METHODS: We retrospectively analysed the data of 691 patients who underwent surgery for primary lung cancer between 2015 and 2019 at a single institute. We analysed the utility of the pulmonary surgical Apgar score compared with the original surgical Apgar score. RESULTS: Postoperative complications were observed in 57 (8.2%) and 7 (1.0%) of the 691 patients who were stratified as grade ≥III and V, respectively, according to the Clavien-Dindo classification. We compared the fitness of the score in predicting postoperative complications; the calculated c-index (0.622) was slightly higher than the original c-index (0.604; P = 0.398). Patients were categorized into 3 groups based on their scores as follows: 0-6 points (n = 59), 7-9 points (n = 420) and 10-12 points (n = 212). Univariable and multivariable analyses demonstrated that a lower score was an independent negative risk factor for postoperative complications (odds ratio 3.53; P = 0.02). Patients with lower scores had a considerably poor 5-year overall survival (64.6%) (P = 0.07). CONCLUSIONS: The pulmonary surgical Apgar score predicts postoperative complications and long-term survival in patients with lung cancer undergoing surgery and may be utilized for postoperative management.

Equilibration rate constant, ke0, to determine effect-site concentration for the Masui remimazolam population pharmacokinetic model in general anesthesia patients.

Effect-site concentration is widely used to determine drug dosage in anesthesia practice. To obtain effect-site concentration, a pharmacokinetic model with a corresponding equilibration rate constant between plasma and effect-site, ke0, is necessary. Remimazolam, a novel short-acting benzodiazepine, has been approved as anesthetic/sedative. Recently, a remimazolam pharmacokinetic model has been published using a large dataset including wide range of subject characteristics (416 males and 246 females, age 18-93 years, total body weight 34-149 kg, height 133-204 cm, body mass index 14-61 kg m-2, ASA physical status: I-IV, and Asian, White, American African, and 2 other races). This Masui model can be applicable to various patients, but a pharmacodynamic model including ke0 was not developed simultaneously. A previous article has indicated that the time to peak effect of drug after its bolus should be used to determine ke0 for a pharmacokinetic model without simultaneous development of corresponding pharmacodynamic model. The ke0 value can be calculated using numerical analysis but not algebraic solution. We provide the detail method of the numerical analysis and a tool to have ke0 value easily for the Masui remimazolam PK model. Additionally, we provide a multiple regression model to have ke0 value for the PK model.

Bi-national survey of Korea and Japan related to the injection site for ultrasound-guided stellate ganglion blocks and anatomic comparisons using cadaver dissection.

The aims of this study were to investigate the current clinical practice of ultrasound (US)-guided stellate ganglion block (SGB) using a bi-national survey of Korea and Japan, and to clarify the anatomical relation of the cervical sympathetic trunk with the prevertebral fascia at the level of cervical vertebrae. The current clinical practice of US-guided SGB in Korea and Japan was investigated using an Internet survey, which received 206 (10.2%) replies from Korea and 97 (8.8%) replies from Japan. The survey questionnaire addressed the actual clinical practice for US-guided SGB, including where the tip of the injection needle is placed. Additionally, 16 half necks of 8 embalmed cadavers were used in an anatomical study. An in-plane needle approach technique and administering 5 ml of local anesthetic were preferred in both countries. However, the type of local anesthetic differed, being lidocaine in Korea and mepivacaine in Japan. The final position of the needle tip also clearly differed in an US image, being predominantly positioned above the prevertebral fascia in Korea (39.3%) and under the prevertebral fascia in Japan (59.8%). In all of the anatomic dissections, the cervical sympathetic trunk was over the prevertebral fascia at the level of the sixth vertebra and under the prevertebral fascia at the level of the seventh vertebra. These results are expected to improve the knowledge on the current clinical practice and to suggest future studies.

Use of Multiple EEG Features and Artificial Neural Network to Monitor the Depth of Anesthesia.

The electroencephalogram (EEG) can reflect brain activity and contains abundant information of different anesthetic states of the brain. It has been widely used for monitoring depth of anesthesia (DoA). In this study, we propose a method that combines multiple EEG-based features with artificial neural network (ANN) to assess the DoA. Multiple EEG-based features can express the states of the brain more comprehensively during anesthesia. First, four parameters including permutation entropy, 95% spectral edge frequency, BetaRatio and SynchFastSlow were extracted from the EEG signal. Then, the four parameters were set as the inputs to an ANN which used bispectral index (BIS) as the reference output. 16 patient datasets during propofol anesthesia were used to evaluate this method. The results indicated that the accuracies of detecting each state were 86.4% (awake), 73.6% (light anesthesia), 84.4% (general anesthesia), and 14% (deep anesthesia). The correlation coefficient between BIS and the index of this method was 0.892 ( p < 0.001 ). The results showed that the proposed method could well distinguish between awake and other anesthesia states. This method is promising and feasible for a monitoring system to assess the DoA.

New criteria of burst suppression on electroencephalogram in dogs anesthetized with sevoflurane.

Burst suppression on electroencephalogram (EEG) is defined as suppression periods longer than 0.5 s during which the amplitude does not exceed 5 µV in human. The aims of this study were; 1) an attempt of creating new criteria of burst suppression in dogs; and 2) a survey on accuracy of sub-parameter of Bispectral index (BIS). Using a BIS monitor, suppression ratio (SRBIS) and raw-EEG data were recorded at 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, and 5.0% end-tidal sevoflurane concentration (ETSEV) in 6 beagle dogs. The minimum ETSEV at which burst suppression was visually confirmed (ETSEVBS) was determined. By applying various duration and voltage threshold to criteria, suppression ratio was calculated (SR). Using the minimum balanced error rate (BER), new criteria consisting of the minimum duration of 0.35 s and the maximum threshold of 2.25 µV that provided SR > 0 above ETSEVBS was screened. SR was set by these criteria (SRBER) and by manual inspection (SRTRUE). The median detection rate of SRBER/SRTRUE was a statistically significant increase (p < .01) compared to that of SRBIS/SRTRUE (77% and 17% at 3.5% ETSEV, 89% and 19% at 4.0% ETSEV, and 86% and 84% at 5.0% ETSEV, respectively). In addition, between SRBER and SRTRUE evaluated by regression and Bland-Altman analyses, there was a strong correlation (r = 0.967, p < .001) and a moderate agreement (Limits of agreement: -7.14 ±â€¯13.95). The method using BER may help to establish new criteria of burst suppression to grasp the excessive deep level of anesthesia.

Severe Progressive Diffuse Alveolar Hemorrhage in a Patient with Systemic Lupus Erythematosus.

Diffuse alveolar hemorrhage (DAH) refers to the effusion of blood into the alveoli due to damaged pulmonary microvasculature. The ensuing alveolar collapse can lead to severe hypoxemia with poor prognosis. In these cases, it is crucial to provide respiratory care for hypoxemia in addition to treating the underlying disease. Here, we describe our experience with a case involving a 46-year-old woman with severe DAH-induced hypoxemia accompanying systemic lupus erythematosus (SLE). Mechanical ventilation was managed using airway pressure release ventilation (APRV) after intubation. Through APRV-based respiratory care and treatment of the underlying disease, hemoptysis was eliminated and oxygenation improved. The patient did not experience significant barotrauma and was successfully weaned from mechanical ventilation after 25 days in the intensive care unit. This case demonstrates that APRV-based control for respiratory management can inhibit the effusion of blood into the alveoli and achieve mechanical hemostasis, as well as mitigate alveolar collapse. APRV may be a useful method for respiratory care in patients with severe DAH-induced hypoxemia.

Moderate sedation induced by general anaesthetics disrupts audio-spatial feature binding with sustained P3 components in healthy humans.

Feature binding is considered to be the basis for conscious stimulus perception, while anaesthetics exert a gradient effect on the loss of consciousness (LOC). By integrating these two streams of research, the present study assessed the effect of two anaesthetic agents (i.e. propofol and midazolam) on audio-spatial feature binding. We also recorded the electrophysiological activity of the frontal channels. Using pharmacokinetic simulation, we determined the effect-site concentration (Ce) of the anaesthetics at loss of response to verbal command and eyelash reflex. We subsequently adjusted Ce to 75%, 50% and 25% of Ce-LOC to achieve deep, moderate and light sedation, respectively. Behavioural results showed that moderate sedation selectively disrupted feature binding. The frontal channels showed a P3 component (350-600 ms peristimulus period) following the presentation of audio-spatial stimuli at baseline and under moderate and light sedations. Critically, the late event-related potential component (600-1000 ms) returned to the pre-activated level (0-350 ms) at baseline and under light sedation but was sustained under moderate sedation. We propose that audio-spatial feature binding may require the presence of a P3 component and its subsequent and sufficient decline, as under anaesthetic-induced moderate sedation the P3 component was sustained and featured binding was impaired.

Effects of sedation on subjective perception of pain intensity and autonomic nervous responses to pain: A preliminary study.

Rather than relying solely on subjective pain evaluation using means such as the visual analogue scale (VAS), in clinical situations it is possible to observe evoked responses of the autonomic nervous system (ANS) as objective indicators. Few studies, however, have reported these relationships under finely controlled sedation. 16 healthy male participants were administrated in intravenous sedation with either propofol or midazolam randomly. We initially determined, using pharmacokinetic simulation, the effect-site concentration (Ce) of anaesthetic at loss of response to verbal command and eyelash reflex (Ce-LOR). Then subsequently adjusted Ce to 75%, 50%, and 25% of Ce-LOR to achieve deep, moderate, and light sedation. At awake control state and each sedation level, a noxious electrical stimulation was applied three times at the right forearm, an average pain intensity of the three stimuli was rated on a VAS (0-10). Changes in the peripheral perfusion index measured by oximetry were used as an indicator of ANS response. We analyzed the influence of sedation level on VAS and ANS responses compared to the awake control state. While ANS responses were similar in all conditions, VAS was statistically significantly lower in moderate (5.6±0.6, p <0.005) or deep (5.3±0.6, p <0.001) sedation than in the awake state (7.2±0.4). This study revealed that even when the ANS responds similarly to the same stimulation, subjective pain perception is attenuated by sedation. A cerebral mechanism other than that of the brainstem might determine subjective pain intensity.

Individual indicators of appropriate hypnotic level during propofol anesthesia: highest alpha power and effect-site concentrations of propofol at loss of response.

BACKGROUND: Electroencephalogram (EEG) waveforms vary widely among individuals, this decreases the usefulness of BIS™ monitors for assessing the effects of propofol. Practically, anesthesia is only seen as too deep when evidence of burst-suppression is seen. We designed an experiment to help towards better assessment of individual anesthetic needs. First, to mark the Ce (effect-site concentration) of propofol at loss of response to calling name and gently shaking shoulders (LOR), we defined Ce-LOR. To mark the transient power increase in the alpha range (9-14 Hz), common to all patients, when propofol concentration gradually increases, we defined Ce-alpha as the highest recorded alpha power for Ce. We also defined Ce-OBS as the Ce of propofol at initial observation of burst-suppression. Then we tried to predict Ce-LOR and Ce-alpha from Ce-OBS, vice versa, and considered the significance of these parameters. METHODS: We enrolled 26 female patients (age 33-65) who were undergoing scheduled mastectomy. During anesthesia, we recorded all raw EEG packets as well as EEG-derived parameters on a computer from BIS-XP™ monitor. Propofol was infused using a TCI pump. Target concentration was adjusted so that Ce of propofol was gradually increased. RESULTS: We obtained the following regression equation; Ce-alpha or Ce-OBS = Ce-LOR × 0.87 + 1.06 + dummy × 0.83 (for Ce-alpha dummy = 0, and for Ce-OBS = 1; adjusted r = 0.90, p < 2.2e-16) by ANCOVA. At Ce-alpha, BIS was 50.2 ± 7.7. CONCLUSION: Ce-alpha and Ce-OBS could be estimated from Ce-LOR. Based on Ce-LOR it is possible to manage the hypnotic level of individual patients.

In vitro and in vivo effects of hemodilution on kaolin-based activated clotting time predicted heparin requirement using a heparin dose-response technique.

PURPOSE: The heparin dose-response (HDR) technique is based on activated clotting time (ACT) response to a fixed-dose heparin bolus, which varies substantially among patients. It is unclear, however, whether hemodilution-associated reductions in coagulation and anticoagulation factors affect the HDR slope. METHODS: For in vitro hemodilution, aliquots of whole blood from healthy volunteers were diluted 9:1 and 8:2 v/v with normal saline. For in vivo hemodilution, a prospective observational study was performed on 46 patients who underwent elective cardiovascular surgery with or without cardiopulmonary bypass. HDR slope, antithrombin (AT) activity, complete blood count, and other coagulation parameters were compared after induction of anesthesia and after hemodilution with 500 ml of intravenous fluid. RESULTS: In vitro 10 and 20 % hemodilution significantly increased the HDR slope relative to baseline, reducing the heparin requirement. Hemodilution of heparinized samples significantly prolonged ACT, whereas there was no significant change in non-heparinized blood. The percent changes in fibrinogen and AT activity were significantly greater at 20 % than those of the other coagulation variables. In vivo, hemodilution significantly increased the HDR slope and reduced heparin requirement. The percent change in fibrinogen due to hemodilution was significantly greater than the change in AT activity. Target ACTs of 300 and 450 s were not achieved in 83.3 and 53.8 % of patients, respectively. CONCLUSION: In vitro and in vivo hemodilution significantly increased the HDR slope and reduced the requirement for heparin. In vitro, the HDR slope did not change in parallel but became steeper, depending on the degree of hemodilution.

Sensory cognitive abnormalities of pain in autism spectrum disorder: a case-control study.

BACKGROUND: The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) recently included sensory processing abnormalities in the diagnostic criteria for individuals with autism spectrum disorder (ASD). However, there is no standard method for evaluating sensory abnormalities in individuals with ASD. METHODS: Fifteen individuals with ASD and 15 age- and sex-matched controls were enrolled in this study. We compared objective pain sensitivity by measuring the pain detection threshold and pain tolerance to three different stimuli (electricity, heat, and cold). Then, we compared both subjective pain sensitivity, assessed by the visual analog scale (VAS), and quality of pain, assessed by the short-form McGill Pain Questionnaire (SF-MPQ), to determine the maximum tolerable pain intensities of each stimulation. RESULTS: The pain detection threshold and pain tolerance of individuals with ASD were not impaired, indicating that there were no differences in the somatic perception of pain between groups. However, individuals with ASD were hyposensitive to subjective pain intensity compared to controls (VAS; electrical: p = 0.044, cold: p = 0.011, heat: p = 0.042) and hyposensitive to affective aspects of pain sensitivity (SF-MPQ; electrical: p = 0.0071, cold: p = 0.042). CONCLUSIONS: Our results suggest that the cognitive pathways for pain processing are impaired in ASD and, furthermore, that our methodology can be used to assess pain sensitivity in individuals with ASD. Further investigations into sensory abnormalities in individuals with ASD are needed to clarify the pathophysiologic processes that may alter sensory processing in this disorder.

Rethinking general anesthesia for cesarean section.

In this review, we describe the current consensus surrounding general anesthetic management for cesarean section. For induction of anesthesia, rapid-sequence induction using thiopental and suxamethonium has been the recommended standard for a long time. In recent years, induction of anesthesia using propofol, rocuronium, and remifentanil have been gaining popularity. To prevent aspiration pneumonia, a prolonged preoperative fasting and an application of cricoid pressure during induction of anesthesia have been recommended, but these practices may require revision. Guidelines for difficult airway management were developed first in obstetric anesthesia, and the use of a supraglottic airway is now recognized as an effective rescue device. After the delivery of a fetus, switching from volatile anesthetics to intravenous anesthetics has been recommended to avoid uterine atony. At the same time, intraoperative awareness should be avoided. The rate of persistent wound pain is higher when only general anesthesia was used during cesarean section than with regional anesthesia, and thus it is necessary to provide a sufficient postoperative analgesia using multimodal analgesia, including intravenous patient-controlled analgesia (IV-PCA), transversus abdominis plane (TAP) block, non-steroidal inflammatory drugs, and acetaminophen.