Three cases of difficulty in achieving definitive loss of consciousness with remimazolam

Background Remimazolam is a novel, ultra-short-acting benzodiazepine used for general anesthesia. Because remimazolam is an emerging drug, the tolerance to remimazolam in benzodiazepine-taking patients has been unclear. Also, the efficacy of remimazolam in different races is not fully elucidated so far. Case presentation Here we experienced three cases in which high dose of remimazolam was needed for attempting to achieve appropriate anesthetic depth. Two of the three cases were of preoperatively benzodiazepine-taking patients. The other was a case of a Chinese patient. In all three cases, conversion to general anesthesia with propofol was necessitated. Conclusions When signs of inadequate sedative effect of remimazolam are observed in patients of benzodiazepine users or of different races, conversion to another sedative agent such as propofol should be considered.

Recovery Profiles of Sevoflurane and Desflurane with or without M-Entropy Guidance in Obese Patients: A Randomized Controlled Trial

Obesity increases the risk of prolonged emergence from general anesthesia due to the delayed release of anesthetic agents from body fat. This trial aimed to evaluate the effects of sevoflurane and desflurane along with anesthetic depth monitoring on emergence time from anesthesia in obese patients. Adults with a body mass index ≥ 30 kg·m−2 undergoing laparoscopic sleeve gastrectomy at a medical center were randomized into four groups: sevoflurane or desflurane anesthesia with or without M-Entropy guidance on anesthetic depth in a ratio of 1:1:1:1. In the M-Entropy guidance groups, the dosage of sevoflurane and desflurane was adjusted to achieve response and state entropy values between 40 and 60 during surgery. In the non-M-Entropy guidance groups, the dosage of anesthetics was titrated according to clinical signs. Primary outcome was time to spontaneous eye opening. A total of 80 participants were randomized. Compared to sevoflurane, desflurane anesthesia significantly reduced the time to spontaneous eye opening [mean difference (MD): −129 s; 95% confidence interval (CI): −211, −46], obeying commands (−160; −243, −77), tracheal extubation (−172; −266, −78), and leaving operating room (−148; −243, −54). M-Entropy guidance further reduced time to eye opening (MD: −142 s; 99.2% CI: −276, −8), tracheal extubation (−199; −379, −19), and leaving operating room (−190; −358, −23) in the desflurane but not the sevoflurane group. M-Entropy guidance significantly reduced the risk of agitation during emergence, i.e., risk difference: −0.275 (95% CI: −0.464, −0.086); and number needed to treat: 4. Compared to sevoflurane, using desflurane to maintain general anesthesia accelerated the return of consciousness in obese patients. M-Entropy guidance further hastened awakening in patients using desflurane and prevented emergence agitation.

Effects of circadian rhythm on Narcotrend index and target-controlled infusion concentration of propofol anesthesia

Background The effects of circadian rhythms on drug metabolism and efficacy are being increasingly recognized. However, the extent to which they affect general anesthesia remains unclear. This study aims to investigate the effects of circadian rhythms on anesthetic depth and the concentrations of propofol target-controlled infusion (TCI). Methods Sixty patients undergoing laparoscopic surgeries were sequentially assigned to four groups. Group ND (n = 15): Propofol TCI with Narcotrend monitor during the day (8:00–18:00), Group NN (n = 15): Propofol TCI with Narcotrend monitor during the night (22:00–5:00), Group CLTD (n = 15): Propofol closed-loop TCI guided by bispectral index (BIS) during the day (8:00–18:00), Group CLTN (n = 15): Propofol closed-loop TCI guided by BIS during the night (22:00–5:00). The Narcotrend index, mean arterial pressure (MAP) and heart rate (HR) were compared between group ND and NN at 7 time points, from 5 min before induction to the end of operation. The propofol TCI concentrations, MAP and HR were compared between group CLTD and CLTN at 7 time points, from 5 min after induction to the end of operation. Results The Narcotrend index, MAP, and HR in group NN were lower than those in group ND from the beginning of mechanical ventilation to the end of operation (p < 0.05). The propofol TCI concentrations in group CLTN were lower than those in group CLTD from the beginning of operation to the end of operation (p < 0.05). Conclusion Circadian rhythms have a significant effect on the depth of anesthesia and drug infusion concentrations during propofol TCI. When using general anesthesia during night surgery, the propofol infusion concentration should be appropriately reduced compared to surgery during the day. Trial registration The present study was registered on the ClinicalTrials.gov website (NCT02440269) and approved by the Medical Ethics Committee of Southwest Hospital of Third Military Medical University (ethics lot number: 2016 Research No. 93). All patients provided informed written consent to participate in the study.

Dopaminergic brainstem disconnection is common to pharmacological and pathological consciousness perturbation

Clinical research into consciousness has long focused on cortical macroscopic networks and their disruption in pathological or pharmacological consciousness perturbation. Despite demonstrating diagnostic utility in disorders of consciousness (DoC) and monitoring anesthetic depth, these cortico-centric approaches have been unable to characterize which neurochemical systems may underpin consciousness alterations. Instead, preclinical experiments have long implicated the dopaminergic ventral tegmental area (VTA) in the brainstem. Despite dopaminergic agonist efficacy in DoC patients equally pointing to dopamine, the VTA has not been studied in human perturbed consciousness. To bridge this translational gap between preclinical subcortical and clinical cortico-centric perspectives, we assessed functional connectivity changes of a histologically characterized VTA using functional MRI recordings of pharmacologically (propofol sedation) and pathologically perturbed consciousness (DoC patients). Both cohorts demonstrated VTA disconnection from the precuneus and posterior cingulate (PCu/PCC), a main default mode network node widely implicated in consciousness. Strikingly, the stronger VTA–PCu/PCC connectivity was, the more the PCu/PCC functional connectome resembled its awake configuration, suggesting a possible neuromodulatory relationship. VTA-PCu/PCC connectivity increased toward healthy control levels only in DoC patients who behaviorally improved at follow-up assessment. To test whether VTA–PCu/PCC connectivity can be affected by a dopaminergic agonist, we demonstrated in a separate set of traumatic brain injury patients without DoC that methylphenidate significantly increased this connectivity. Together, our results characterize an in vivo dopaminergic connectivity deficit common to reversible and chronic consciousness perturbation. This noninvasive assessment of the dopaminergic system bridges preclinical and clinical work, associating dopaminergic VTA function with macroscopic network alterations, thereby elucidating a critical aspect of brainstem–cortical interplay for consciousness.

Age-dependent electroencephalogram characteristics during different levels of anesthetic depth

Objective The monitoring of anesthetic depth based on electroencephalogram (EEG) derivation is not currently adjusted for age. Here we analyze the influence of age factors on EEG characteristics. Methods Frontal EEG recordings were obtained from 80 adults during routine clinical anesthesia. The characteristics of EEG with age and anesthesia were observed during four kinds of anesthesia. Results Relative slow wave power, relative delta power, absolute slow wave power, BIS value and approximate entropy were statistically different in the adjacent anesthesia states (P < 0.05). Under very deep anesthesia, the relative slow wave power increases linearly with age (R2 = 0.1802; P = 0.0001), the relative delta power decreased linearly with age (R2 = 0.3587; P < 0.0001), the BIS value increased linearly with age (R2 = 0.0986; P = 0.005), and the approximate entropy increases linearly with age (R2 = 0.0565; P = 0.036). The relative slow wave power did not change in an age-dependent manner. Conclusions When using relative delta power, absolute slow wave power, BIS value and approximate entropy to monitor the depth of anesthesia, the influence of age should be considered, However, when using relative slow wave power, age should not be considered.

Studies to Evaluate the Safety of Constant Rate Infusions of Dexmedetomidine, Ketamine and Lidocaine Alone or in Combination during Isoflurane Anesthesia in Horses

Background: Horses mount a huge stress response to anesthesia when compared to other animals, hence are risky candidates for anesthesia. Inhalant anesthetic agents offer more control to anesthetic depth and facilitate rapid recovery, hence are considered to be safer than intravenous agents for surgical procedures requiring more than an hour, however, newer drug combinations are being explored to minimize the undesired consequences and dose rate of inhalant agents. The present study explored the safety of dexmedetomidine, ketamine and lidocaine constant rate infusion alone or as a combination along with Isoflurane for safer anesthesia in horses.Methods: The study was conducted on 28 horses divided into S, D, DK and DKL groups having 7 animals in each. Xylazine (1 mg/kg) and butorphanol (0.05mg/kg) were given intravenously for premedication. Ketamine (2 mg/kg) and midazolam (0.2 mg/kg) were used for induction and anesthesia was maintained with isoflurane. Normal saline (1000ml/hour), Dexmedetomidine (2µg/kg/hr), Dexmedetomidine and ketamine (2 µg/kg/hr and 2 mg/kg/hr) and Dexmedetomidine, ketamine and lidocaine (2 µg/kg/hr, 2 mg/kg/hr and 2 mg/kg/h) were given as CRI in groups S, D, DK and DKL, respectively. Thiopentone sodium (250mg bolus, 5%) was given as a fast intravenous bolus whenever required. Anesthetic efficacy was evaluated based on clinical, haemato-biochemical, hemodynamic, and endocrine variables.Result: A significant decline in mean arterial pressure was noticed in group DKL but changes in CVP and SpO2 in different groups were non-significant. Higher Blood glucose and low Insulin levels were seen in group DK during 45-60 min. Constant rate infusions of Dexmedetomidine, Ketamine and Lidocaine alone or in combination produced a significant sparing effect on Isoflurane and thiopentone while they improved peri-operative quality of anesthesia in horses.

Simultaneous comparison of depth of sedation performance between SedLine and BIS during general anesthesia using custom passive interface hardware: study protocol for a prospective, non-blinded, non-randomized trial

Background Intraoperative brain function monitoring with processed electroencephalogram (EEG) indices, such as the bispectral index (BIS) and patient state index (PSI), may improve characterization of the depth of sedation or anesthesia when compared to conventional physiologic monitors, such as heart rate and blood pressure. However, the clinical assessment of anesthetic depth may not always agree with available processed EEG indices. To concurrently compare the performance of BIS and SedLine monitors, we present a data collection system using shared individual generic sensors connected to a custom-built passive interface box. Methods This prospective, non-blinded, non-randomized study will enroll 100 adult American Society of Anesthesiologists (ASA) class I-III patients presenting for elective procedures requiring general anesthesia. BIS and SedLine electrodes will be placed preoperatively according to manufacturer recommendations and their respective indices tracked throughout anesthesia induction, maintenance and emergence. The concordance between processed EEG indices and clinical assessments of anesthesia depth will be analyzed with chi-square and kappa statistic. Discussion Prior studies comparing brain function monitoring devices have applied both sensors on the forehead of study subjects simultaneously. With limited space and common sensor locations between devices, it is not possible to place both commercial sensor arrays according to the manufacturer’s recommendations, thus compromising the validity of these comparisons. This trial utilizes a custom interface allowing signals from sensors to be shared between BIS and SedLine monitors to provide an accurate comparison. Our results will also characterize the degree of agreement between processed EEG indices and clinical assessments of anesthetic depth as determined by the anesthesiologists’ interpretations of acute changes in blood pressure and heart rate as well as the administration, or change to the continuous delivery, of medications at these timepoints. Patient factors (such as burst suppression state or low power EEG conditions from aging brain), surgical conditions (such as use of electrocautery), artifacts (such as electromyography), and anesthesia medications and doses (such as end-tidal concentration of volatile anesthetic or hypnotic infusion dose) that lead to lack of agreement will be explored as well. Trial registration Clinical Trials (ClinicalTrials.gov), NCT03865316. Registered on 4 February 2019 – retrospectively registered. Sponsor: Masimo Corporation.

The influence of moderate or deep neuromuscular block status on anesthetic depth monitoring system during total intravenous anesthesia using propofol and remifentanil: A randomized trial

The neuromuscular block state may affect the electroencephalogram-derived index representing the anesthetic depth. We applied an Anesthetic Depth Monitoring for Sedation (ADMS) to patients undergoing laparoscopic cholecystectomy under total intravenous anesthesia, and evaluated the requirement of propofol according to the different neuromuscular block state. Adult patients scheduled to undergo laparoscopic cholecystectomy were enrolled and randomly assigned to either the moderate (MB) or deep neuromuscular block (DB) group. The UniCon sensor of ADMS was applied to monitor anesthetic depth and the unicon value was maintained between 40 and 50 during the operation. According to the group assignment, intraoperative rocuronium was administered to maintain proper neuromuscular block state, moderate or deep block state. The unicon value, electromyography (EMG) index, and total dose of propofol and rocuronium were analyzed. At similar anesthetic depth, less propofol was used in the DB group compared to the MB group (6.19 ± 1.36 in the MB mg/kg/h group vs 4.93 ± 3.02 mg/kg/h in the DM group, p = 0.042). As expected, more rocuronium were used in the DB group than in the MB group (0.8 ± 0.2 mg/kg in the MB group vs 1.2 ± 0.2 mg/kg in the DB group, p = 0.023) and the EMG indices were lower in the DB group than in the MB group, at several time points as follows: at starting operation ( p < 0.001); at 15 ( p = 0.019), 45 ( p = 0.011), and 60 min ( p < 0.001) after the initiation of the operation; at the end of operation ( p = 0.003); and at 5 min after the administration of sugammadex ( p < 0.001). At similar anesthetic depth, patients under the deep neuromuscular block state required less propofol with lower intraoperative EMG indices compared to those under the moderate neuromuscular block state during general anesthesia.