Comparison of the negative effect of remimazolam and propofol on cardiac contractility: Analysis of a randomised parallel-group trial and a preclinical ex vivo study.

Remimazolam is a newly developed ultra-short-acting benzodiazepine that exerts sedative effects. This study aimed to clarify the effects of remimazolam on cardiac contractility. In a randomised-parallel group trial, haemodynamic parameters were compared between propofol (n = 11) and remimazolam (n = 12) groups during the induction of general anaesthesia in patients undergoing non-cardiac surgery. In a preclinical study, the direct effects of remimazolam on cardiac contractility were also evaluated using isolated rat hearts. RNA sequence data obtained from rat and human hearts were analysed to assess the expression patterns of the cardiac γ-aminobutyric acid type A (GABAA ) receptor subunits. In a clinical study, the proportional change of the maximum rate of arterial pressure rise was milder during the study period in the remimazolam group (propofol: -52.6 [10.2] (mean [standard deviation])% vs. remimazolam: -39.7% [10.5%], p = 0.007). In a preclinical study, remimazolam did not exert a negative effect on left ventricle developed pressure, whereas propofol did exert a negative effect after bolus administration of a high dose (propofol: -26.9% [3.5%] vs. remimazolam: -1.1 [6.9%], p < 0.001). Analysis of the RNA sequence revealed a lack of γ subunits, which are part of the major benzodiazepine binding site of the GABAA receptor, in rat and human hearts. These results indicate that remimazolam does not have a direct negative effect on cardiac contractility, which might contribute to its milder effect on cardiac contractility during the induction of general anaesthesia. The expression patterns of cardiac GABAA receptor subunits might be associated with the unique pharmacokinetics of benzodiazepines in the heart.

Comparing leak pressure of LMA® ProSeal™ versus i-gel® at head rotation: a randomized controlled trial.

PURPOSE: The effect of head rotation on supraglottic airway (SGA) oropharyngeal leak pressure (OPLP) has not been well elucidated. The aim of this study was to help clarify which SGA device provides higher OPLP at head-rotated position. METHODS: Patients who underwent elective surgery under general anesthesia were enrolled and randomly divided into laryngeal mask airway (LMA®) ProSeal™ and i-gel® groups. The allocated SGA device was inserted under anesthesia. The primary outcome was OPLP, and secondary outcomes were ventilation score, expiratory tidal volume, and maximum pressure under volume-controlled ventilation (VCV) with an inspiratory tidal volume of 10 mL·kg-1 ideal body weight and fibreoptic view of the vocal cords at 0°, 30°, and 60° head rotation. RESULTS: Data from 78 and 76 patients were analyzed in the LMA ProSeal and i-gel groups, respectively. The mean (standard deviation) OPLP of the LMA ProSeal was significantly higher than that of the i-gel at the 60° head-rotated position (LMA ProSeal, 20.4 [6.5] vs i-gel, 16.9 [7.8] cm H2O; difference in means, 3.6; adjusted 95% confidence interval, 0.5 to 6.6; adjusted P = 0.02, adjusted for six comparisons). The maximum pressure under VCV at 60° head rotation was significantly higher in the LMA ProSeal group than in the i-gel group. The expiratory tidal volume of the LMA ProSeal did not significantly change with head rotation and was significantly higher than that of the i-gel at 60° head rotation. Ventilation score, fibreoptic view of the vocal cords, and complications were not significantly different between the ProSeal and i-gel groups. CONCLUSIONS: The LMA ProSeal provides higher OPLP than the i-gel at a 60° head-rotated position under general anesthesia. TRIAL REGISTRATION: Japan Registry of Clinical Trials (https://jrct.niph.go.jp) (JRCT1012210043); registered 18 October 2021.

RéSUMé: OBJECTIF: L'effet de la rotation de la tête sur la pression de fuite oropharyngée (OPLP en anglais) des dispositifs supraglottiques (DSG) n'est pas encore bien élucidé. L'objectif de cette étude était d'aider à déterminer quel DSG procurait une pression de fuite oropharyngée plus élevée lorsque la tête est en rotation. MéTHODE: Les patient·es qui ont bénéficié d'une intervention chirurgicale non urgente sous anesthésie générale ont été recruté·es et aléatoirement réparti·es en deux groupes, soit masque laryngé (LMA®) ProSeal™ ou i-gel®. Le DSG alloué a été inséré sous anesthésie. Le critère d'évaluation principal était la pression de fuite oropharyngée, et les critères d'évaluation secondaires étaient le score de ventilation, le volume courant expiratoire et la pression maximale sous ventilation à volume contrôlé (VVC) avec un volume courant inspiratoire de 10 mL·kg−1 du poids corporel idéal et une visualisation fibroscopique des cordes vocales à une rotation de la tête de 0°, 30° et 60°. RéSULTATS: Les données de 78 et 76 patient·es ont été analysées dans les groupes LMA ProSeal et i-gel, respectivement. La pression de fuite oropharyngée moyenne (écart type) du LMA ProSeal était significativement plus élevée que celle de l'i-gel en position de rotation de la tête à 60° (LMA ProSeal, 20,4 [6,5] vs i-gel, 16,9 [7,8] cm H2O; différence de moyennes, 3,6; intervalle de confiance ajusté à 95 %, de 0,5 à 6,6; P = 0,02 ajusté, ajusté pour six comparaisons). La pression maximale sous VVC à une rotation de la tête de 60° était significativement plus élevée dans le groupe LMA ProSeal que dans le groupe i-gel. Le volume courant expiratoire du LMA ProSeal n'a pas changé de manière significative avec la rotation de la tête et était significativement plus élevé que celui de l'i-gel à une rotation de la tête de 60°. Le score de ventilation, la visualisation fibroscopique des cordes vocales et les complications n'étaient pas significativement différents entre les groupes ProSeal et i-gel. CONCLUSION: Le LMA ProSeal procure une pression de fuite oropharyngée plus élevée que l'i-gel dans une position de rotation de la tête à 60° sous anesthésie générale. ENREGISTREMENT DE L'éTUDE: Registre japonais des essais cliniques (https://jrct.niph.go.jp) (JRCT1012210043); enregistré le 18 octobre 2021.

Effect of a Low Concentration of Sevoflurane Combined With Propofol on Transcranial Electrical Stimulation Motor Evoked Potential: A Case Series.

Transcranial electrical motor evoked potential (TCeMEP) is used to monitor the integrity of intraoperative motor function. Total intravenous anesthesia (TIVA) is the preferred method because its effect on MEP is relatively smaller than volatile anesthetics. However, maintaining the balanced anesthesia in long-time surgery using TIVA is challenging and may sometime cause problems including body movement during microsurgery. Such problems can be avoided by intraoperative anesthesia management using a mixture of propofol and a low concentration of sevoflurane. We recorded TCeMEP under a mixture of propofol and low concentration of sevoflurane anesthesia in three cases of neurosurgery. Anesthesia was induced with a 5.0 µg/mL target-controlled infusion of propofol and 0.6 mg/kg rocuronium. General anesthesia was maintained by propofol and 0.1-0.25 µg/kg/min remifentanil infusion. After the recording of control TCeMEP, sequential inhalation of 0.2 minimum alveolar concentration (MAC) and 0.5 MAC of sevoflurane was performed. The duration of each sevoflurane inhalation was 10 minutes, and the MACs were adjusted by the patient's age. In our cases, the combination of propofol and 0.2 MAC sevoflurane suppressed the amplitude of TCeMEP to 38.0±21.7% (379.8±212.0 µV), but the amplitude was high enough for evaluation of motor function monitoring. On the other hand, the combination of 0.5 MAC sevoflurane greatly decreased the amplitude of TCeMEP to 6.3±6.0% (71.9±66.9 µV) resulting in less than 150 µV, and it was difficult to record the change in TCeMEP amplitude over time. The combination of 0.2 MAC sevoflurane with TIVA might enable TCeMEP monitoring with TIVA.

A case of safe airway management by fiber-optic nasotracheal intubation in general anesthesia in a pediatric patient with Hajdu-Cheney syndrome: a case report.

BACKGROUND: Hajdu-Cheney syndrome (HCS) is an extremely rare disorder characterized by progressive acro-osteolysis. A unique facial structure and deformity of the cervical spine are associated with a difficult airway. Although several reports describe general anesthesia with orotracheal intubation for patients with HCS, there have been no reports of nasotracheal intubation with a risk of skull base fracture. We describe nasotracheal intubation for oral surgery in a patient with HCS. CASE PRESENTATION: A 13-year-old girl with HCS was scheduled for dental surgery. Preoperative computed tomography revealed no abnormalities including fractures in the skull base or cervical spine. After confirming a lack of vocal cord paralysis by bronchofiberscopic inspection from the nose, general anesthesia was induced with sevoflurane, remifentanil, and rocuronium. Fiber-optic nasotracheal intubation was successfully performed without complications such as depletion of oxygen saturation and massive epistaxis, and the surgery was completed uneventfully. She was discharged the day after surgery with no anesthesia-related complications. CONCLUSIONS: We were able to safely manage the airway of a patient with HCS by nasotracheal intubation under general anesthesia.

Head cooling wrap could suppress the elevation of core temperature after cardiac surgery during forced-air warming in a pediatric intensive care unit: a randomized clinical trial.

PURPOSE: The main aim of the current trial was to explore our hypothesis that cooling head wraps lower the core temperature more effectively than ice packs on the head during forced-air warming after pediatric cardiac surgeries. METHODS: This study was a single-center Randomized Controlled Trial. Participants were children with a weight ≤ 10 kg and hyperthermia during forced-air warming after cardiac surgeries. When the core temperature reached 37.5 °C, ice packs on the head (group C) or a cooling head wrap (group H) were used as cooling devices to decrease the core temperature. The primary outcome was the core temperature. The secondary outcomes were the foot surface temperature and heart rate. We measured all outcomes every 30 min for 240 min after the patient developed hyperthermia. We conducted two-way ANOVA as a pre-planned analysis and also the Bonferroni test as a post hoc analysis. RESULTS: Twenty patients were randomly assigned to groups C and H. The series of core temperatures in group H were significantly lower than those in group C (p < 0.0001), and post hoc analysis showed that there was no significant difference in core temperatures at T0 between the two groups and statistically significant differences in all core temperatures at T30-240 between the two groups. There was no difference between the two groups' surface temperatures and heart rates. CONCLUSIONS: Compared to ice packs on the head, head cooling wraps more effectively suppress core temperature elevation during forced-air warming after pediatric cardiac surgery.

Mouth-Opener Technique for Ultrasound-Guided Inferior Alveolar Nerve Block: A Case Series of Extraction of Impacted Mandibular Third Molars.

Extraction of the impacted mandibular third molar (IMTM) is common in oral surgery, but its postoperative pain is severe. Ultrasound-guided inferior alveolar nerve block (UGIANB) is an analgesic technique in the mandibular nerve region. We describe UGIANB using a mouth opener and report the cases with a good postoperative course. Six patients underwent the extraction of bilateral IMTMs under general anesthesia. After surgery, we performed UGIANB and administered 5 mL of 0.375% levobupivacaine on each side. The postoperative numerical rating scale pain scores were 1 (0-2) and 2.5 (0-5) (mean (range)), postoperative day one and seven, respectively. The postoperative quality of recovery-40 scores were 188.5 (8.1) and 191.7 (7.6) (mean (SD)), postoperative day one and seven, respectively. No procedural complications were encountered. We performed UGIANB with a mouth opener on a patient with IMTM extraction and were able to provide safe and good analgesia.

A case of monosomy 21 presented with difficult tracheal intubation.

BACKGROUND: Monosomy 21 is a rare chromosomal abnormality. It is mainly associated with mental retardation, intellectual disability, growth retardation, microcephaly, and characteristic facial features. General anesthesia in adults with this disease has not been reported. We report difficult airway management of an adult patient with monosomy 21. CASE DESCRIPTION: A 30-year-old female was scheduled for laparoscopic gynecological surgery. She was diagnosed with monosomy 21 at birth and accompanied with mental retardation. Preoperative examination revealed limited mouth opening with Mallampati score of IV, but no abnormal laboratory test or chest X-P. Anesthesia was performed using general anesthesia with epidural analgesia. Although bag-mask ventilation was improved by a muscle relaxant, mouth opening was further restricted, and laryngoscope insertion was impossible. Tracheal intubation was achieved using a bronchofiberscope. The operation procedure was completed, and the patient was discharged from the hospital without any major postoperative complications. CONCLUSIONS: In this patient, mouth opening was further reduced after induction of general anesthesia with a muscle relaxant. Preoperative evaluation and adequate preparation of airway management are important for general anesthesia in an adult patient with monosomy 21.

Anesthetic management of tracheal stent extraction using a double gum elastic bougie technique.

BACKGROUND: Tracheal stenosis is a life-threatening condition, and management of a patient with a risk of tracheal stenosis is challenging for anesthesiologists. In this report, we describe a method for airway management using two gum elastic bougie method when removing a tracheal stent via a tracheostomy orifice with a risk of airway restenosis. CASE PRESENTATION: A 71-year-old man had an enlarged squamous cell carcinoma of the lung invading the upper mediastinum that had caused severe stenosis of the trachea. Two months after diagnosis, a tracheal stent had been placed to maintain tracheal patency. One month after stent placement, acute respiratory failure was induced by upper airway obstruction caused by subglottic airway edema due to mechanical stimulation of the cranial end of the stent, and the patient was rescued by oral tracheal intubation. Tracheal stent extraction was scheduled to relieve the laryngeal edema. Since there was a risk of tracheal restenosis because of the possibility of accidental evulsion of the orally tracheal tube which intubated to secure an emergency airway and tracheal stent extraction, two gum elastic bougies were inserted through the oral tracheal tube and tracheostomy orifice to facilitate re-intubation. After extraction of the tracheal stent, airway openness was maintained and tracheostomy was completed without any complication. CONCLUSION: Successful management of tracheal stent extraction was performed using a double gum elastic bougie technique.

Risk factors of cardiac arrest and failure to achieve return of spontaneous circulation during anesthesia: a 20-year retrospective observational study from a tertiary care university hospital.

PURPOSE: There is still a lack of robust data on the epidemiology of cardiac arrest during anesthesia. We investigated the frequency and risk factors of cardiac arrest during anesthesia over the past two decades at a tertiary care university hospital in Japan. METHODS: We retrospectively analyzed 111,851 anesthesia records of patients who underwent surgery under anesthesia between 2000 and 2019. Cardiac arrest cases were classified according to the patient's background, surgical status, main cause and initial rhythm of cardiac arrest, and the presence of the return of spontaneous circulation (ROSC). Univariate and multivariate logistic regression analyses were used to identify the risk factors of cardiac arrest and failure to achieve ROSC. RESULTS: Ninety cardiac arrest cases during anesthesia were identified. The incidence of cardiac arrest was 8.05 per 10,000 anesthetics (95% CI, 6.54-9.90). There were 6 anesthesia-related cardiac arrests and 9 anesthesia-contributory cardiac arrests. The most common cause of cardiac arrest was blood loss. American Society of Anesthesiologists physical status 4-5, emergency surgery, and cardiovascular surgery were identified as independent risk factors of cardiac arrest. American Society of Anesthesiologists physical status 4-5, blood loss-induced cardiac arrest, and non-shockable rhythm were independently associated with failure to achieve ROSC. CONCLUSION: Blood loss was the most common cause of cardiac arrest and blood loss-induced cardiac arrest was independently associated with failure to achieve ROSC. Further improvements in treatment strategies for bleeding may reduce the future incidence of cardiac arrest and death during anesthesia.

Effect of remimazolam on intraoperative neuromonitoring during thyroid surgery: a case series.

Intraoperative neuromonitoring is widely used to prevent accidental injury during thyroid surgery. Anesthesia should be performed without muscle relaxant or agents with high muscle-relaxant potency. Remimazolam, a novel intravenous anesthetic, became available for clinical use in 2020. Remimazolam is an ultra-short-acting benzodiazepine with a very high clearance rate. However, there are very few data regarding its effect on currently used intraoperative neurological monitoring. Five patients underwent thyroid surgery using intraoperative recurrent laryngeal neuromonitoring. In all cases, intubation was performed after the administration of rocuronium. Anesthesia was maintained by continuous administration of remimazolam at the recommended dose and remifentanil, and no additional rocuronium or sugammadex was administered. Recurrent laryngeal nerve activity could be detected at the first stimulus after surgery was started, and monitoring continued thereafter. Intraoperative monitoring was performed without problems and all surgeries were completed without any complications. Anesthesia with remimazolam at the normal dose did not prolong the time to first positive electromyogram in patients undergoing thyroid surgery, and enables intraoperative recurrent laryngeal nerve monitoring to be performed without any serious perioperative adverse events. Remimazolam may provide a comparable quality of anesthesia to that of existing drugs for neuromonitoring during thyroid surgery.

Head Rotation Reduces Oropharyngeal Leak Pressure of the i-gel and LMA® Supreme™ in Paralyzed, Anesthetized Patients: A Randomized Trial.

BACKGROUND: Second-generation supraglottic airway (SGA) devices are useful for airway management during positive pressure ventilation in general anesthesia and emergency medicine. In some clinical settings, such as the anesthetic management of awake craniotomy, SGAs are used in the head-rotated position, which is required for exposure of the surgical field, although this position sometimes worsens the efficiency of mechanical ventilation with SGAs. In this study, we investigated and compared the influence of head rotation on oropharyngeal leak pressures (OPLP) of the i-gel and LMA® Supreme™, which are second-generation SGA devices. METHODS: Patients who underwent elective surgery under general anesthesia were enrolled in this study and randomly divided into i-gel or LMA Supreme groups. After induction of anesthesia with muscle relaxation, the i-gel or LMA Supreme was inserted according to computerized randomization. The primary outcome was the OPLP at 0°, 30°, and 60° head rotation. The secondary outcomes were the maximum airway pressure and expiratory tidal volume when patients were mechanically ventilated using a volume-controlled ventilation mode with a tidal volume of 10 mL/kg (ideal body weight), ventilation score, and fiber-optic views of vocal cords. RESULTS: Thirty-four and 36 participants were included in the i-gel and LMA Supreme groups, respectively. The OPLPs of the i-gel and LMA Supreme significantly decreased as the head rotation angle increased (mean difference [95% confidence interval], P value: i-gel; 0° vs 30°: 3.5 [2.2-4.8], P < .001; 30° vs 60°: 2.0 [0.6-3.5], P = .002; 0° vs 60°: 5.5 [3.3-7.8], P < .001, LMA Supreme; 0° vs 30°: 4.1 [2.6-5.5], P < .001; 30° vs 60°: 2.4 [1.1-3.7], P < .001; 0° vs 60°: 6.5 [5.1-8.0], P < .001). There were statistically significant differences in expiratory tidal volume and ventilation score between 0° and 60° in the i-gel group and in ventilation score between 30° and 60° in the LMA Supreme group. There was no statistically significant difference between the 2 devices in all outcome measures. The incidences of adverse events, such as hoarseness or sore throat, were not significantly different between i-gel and LMA Supreme. CONCLUSIONS: Head rotation to 30° and 60° reduces OPLP with both i-gel and LMA Supreme. There is no difference in OPLP between i-gel and LMA Supreme in the 3 head rotation positions.

Lipid emulsion, but not propofol, induces skeletal muscle damage and lipid peroxidation.

PURPOSE: Prolonged propofol infusion induces skeletal muscle damage. However, it is well known that the lipid emulsion that is the solvent of propofol causes various types of tissue damage via lipid peroxidation, and that propofol, conversely, has an anti-lipid peroxidative effect. The purpose of this study was to determine whether propofol or the lipid emulsion is the cause of muscle damage following prolonged administration. METHODS: Rats were divided into four groups: NI group (no intervention), Cath group (venous catheter insertion only), Prop group (1% propofol (Maruishi) intravenous infusion at 10 mg/kg/h), and Lipid group (10% Lipofundin® intravenous infusion at 100 mg/kg/h) (n = 10, each group). 1% Propofol (Maruishi) or Lipofundin was infused at 1 mL/kg/h for 72 h. The solvent of 1% propofol (Maruishi) is a 10% lipid emulsion. Lipofundin consists of 50% long-chain triacylglycerols and 50% medium-chain triacylglycerols, similar to the propofol solvent. Plasma concentrations of creatine kinase and myoglobin, superoxide production level, and 4-hydroxynonenal and malondialdehyde expression in the gastrocnemius muscle were evaluated 72 h after the interventions. RESULTS: Plasma concentrations of creatine kinase and myoglobin in the Lipid group were significantly higher than those in the other three groups. The superoxide production level, and 4-hydroxynonenal and malondialdehyde expression in the Lipid group were also significantly higher than in the other three groups. CONCLUSION: Lipofundin induces skeletal muscle damage via lipid peroxidation, and 1% propofol (Maruishi) conversely suppresses the muscle damage via antioxidant effects.

Remifentanil prevents increases of blood glucose and lactate levels during cardiopulmonary bypass in pediatric cardiac surgery.

INTRODUCTION: Cardiopulmonary bypass (CPB) can cause stress response that increases levels of cytokine and catecholamine in plasma, resulting in hyperglycemia. In adults, it has been demonstrated that remifentanil infusion during CPB could prevent increases of cytokine, catecholamine, and blood glucose levels, but such effects of remifentanil in children have not been elucidated. AIM: In this study, we investigated the preventive effects of remifentanil on blood glucose and lactate levels during CPB in children. MATERIALS AND METHODS: This retrospective study included children who underwent ventricular septal defect or atrial septal defect closure. Data for patients who did not receive, during CPB period, remifentanil infusion (non-Remi group) and patients who received remifentanil infusion at 0.5 µg/kg/min (Remi group) during CPB were used for analysis. Primary outcomes were lactate and blood glucose levels just before and after CPB. Data are presented as medians and interquartile ranges. Data were analyzed by the Mann-Whitney U-test and Chi-square test. A P < 0.05 was considered statistically significant. RESULTS: During CPB, 13 and 11 patients were allocated into Remi and non-Remi groups, respectively. Pre-CPB lactate and blood glucose levels were not significantly different between the two groups, but post-CPB lactate and blood glucose levels in the Remi group were significantly lower than that in the non-Remi group. CONCLUSION: 0.5 µg/kg/min remifentanil infusion during CPB suppresses the increases of blood glucose and lactate levels in children.

Movements of the double-lumen endotracheal tube due to lateral position with head rotation and tube fixation: a Thiel-embalmed cadaver study.

PURPOSE: Following successful double-lumen endotracheal tube (DLT) insertion for pulmonary surgery, the body position of a patient is changed from supine to lateral. This change occasionally leads to the malposition of the DLT and difficulty in differential lung ventilation. METHODS: In this study, we investigated movements of the DLT induced by change in body position from supine to lateral, using Thiel-embalmed cadavers. Thiel-embalmed cadavers retain full flexibility of the body and preservation of natural colours, using novel preservation techniques. After the tip of the DLT was directly fixed with forceps at the appropriate position in the bronchus, the DLT depth was measured at the lip in supine and lateral positions. RESULTS: The depth of DLT insertion measured at the lip in right (25.2 ± 0.3 cm; mean ± SEM) and left (25.1 ± 0.3 cm) lateral positions was significantly increased compared to the supine position (24.7 ± 0.3 cm). CONCLUSIONS: We recommend that the depth of DLT insertion should be advanced by approximately 0.5 cm from the best position, before changing from the supine to lateral position.