Effective bolus dose of remimazolam for i-gel® insertion in nonparalyzed patients: a dose-finding study.

PURPOSE: Remimazolam is a recently developed ultra-short-acting benzodiazepine used for anesthesia induction and maintenance. Nevertheless, the effective bolus dose of remimazolam for i-gel® (Intersurgical Ltd., Wokingham, Berkshire, UK) insertion without the use of neuromuscular blocking agents (NMBAs) has not been well established. METHODS: This study included 25 adult patients scheduled for surgery under general anesthesia who were eligible for i-gel use. Anesthesia was induced with predetermined bolus doses of remimazolam, starting at 0.3 mg·kg-1 for the first patient, without the use of NMBAs. All patients concurrently received remifentanil using target-controlled infusion (TCI) at a fixed effect-site concentration (Ce) of 3.0 ng·mL-1. Insertion of the i-gel was attempted 90 sec after remimazolam administration, and insertion conditions were assessed. Subsequent doses of remimazolam were decreased or increased by 0.05 mg·kg-1, depending on the success or failure of i-gel insertion. RESULTS: The mean (standard deviation) 50% effective dose (ED50) of a remimazolam bolus for successful i-gel insertion as determined by the modified Dixon's up-and-down method was 0.100 (0.027) mg·kg-1. The ED50 and ED95 estimated by isotonic regression were 0.111 (83% confidence interval [CI], 0.096 to 0.131) mg·kg-1 and 0.182 (95% CI, 0.144 to 0.195) mg·kg-1, respectively. None of the patients required treatment for hypotension or bradycardia during anesthesia induction. CONCLUSION: Based on the ED95 of remimazolam bolus dose determined in our study, we recommend using 0.182 mg·kg-1 of remimazolam in combination with remifentanil TCI at a Ce of 3.0 ng·mL-1 for successful i-gel insertion without NMBAs in adult patients. This regimen seems effective with a low risk of hemodynamic instability during anesthesia induction. STUDY REGISTRATION: ClinicalTrials.gov ( NCT05298228 ); first submitted 6 March 2022.

RéSUMé: OBJECTIF: Le remimazolam est une benzodiazépine à action ultra-courte récemment mise au point et utilisée pour l'induction et le maintien de l'anesthésie. Toutefois, la dose efficace en bolus de remimazolam pour l'insertion de l'i-gel® (Intersurgical Ltd., Wokingham, Berkshire, Royaume-Uni) sans utiliser de bloqueurs neuromusculaires (BNM) n'a pas été bien établie. MéTHODE: Cette étude a inclus 25 adultes devant bénéficier d'une intervention chirurgicale sous anesthésie générale qui étaient éligibles à l'utilisation d'un i-gel. L'anesthésie a été induite avec des doses prédéterminées en bolus de remimazolam, à partir de 0,3 mg·kg−1 pour la première personne, sans utiliser de BNM. Toutes les personnes anesthésiées ont reçu en parallèle du rémifentanil en perfusion à objectif de concentration à une concentration au site effecteur (Ce) de 3,0 ng·mL−1. L'insertion de l'i-gel a été tentée 90 secondes après l'administration de remimazolam, et les conditions d'insertion ont été évaluées. Les doses subséquentes de remimazolam ont été diminuées ou augmentées de 0,05 mg·kg−1, en fonction du succès ou de l'échec de l'insertion de l'i-gel. RéSULTATS: La dose efficace moyenne (écart type) de 50 % (DE50) d'un bolus de remimazolam pour une insertion réussie de l'i-gel, telle que déterminée par la méthode « up-and-down ¼ de Dixon modifiée, était de 0,100 (0,027) mg·kg−1. Les DE50 et DE95 estimées par régression isotonique étaient de 0,111 (intervalle de confiance [IC] à 83 %, 0,096 à 0,131) mg·kg−1 et 0,182 (IC 95 %, 0,144 à 0,195) mg·kg−1, respectivement. Aucun·e patient·e n'a eu besoin de traitement pour une hypotension ou une bradycardie pendant l'induction de l'anesthésie. CONCLUSION: D'après la DE95 de la dose de remimazolam en bolus déterminée dans notre étude, nous recommandons d'utiliser 0,182 mg·kg−1 de remimazolam en association avec une perfusion à objectif de concentration de rémifentanil à une Ce de 3,0 ng·mL−1 pour réussir l'insertion de l'i-gel sans BNM chez la patientèle adulte. Ce schéma semble efficace avec un faible risque d'instabilité hémodynamique lors de l'induction de l'anesthésie. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT05298228); première soumission le 6 mars 2022.

An explainable machine learning model to predict early and late acute kidney injury after major hepatectomy.

BACKGROUND: Risk assessment models for acute kidney injury (AKI) after major hepatectomy that differentiate between early and late AKI are lacking. This retrospective study aimed to create a model predicting AKI through machine learning and identify features that contribute to the development of early and late AKI. METHODS: Patients that underwent major hepatectomy were categorized into the No-AKI, Early-AKI (within 48 h) or Late-AKI group (between 48 h and 7 days). Modeling was done with 20 perioperative features and the performance of prediction models were measured by the area under the receiver operating characteristic curve (AUROCC). Shapley Additive Explanation (SHAP) values were utilized to explain the outcome of the prediction model. RESULTS: Of the 1383 patients included in this study, 1229, 110 and 44 patients were categorized into the No-AKI, Early-AKI and Late-AKI group, respectively. The CatBoost classifier exhibited the greatest AUROCC of 0.758 (95% CI: 0.671-0.847) and was found to differentiate well between Early and Late-AKI. We identified different perioperative features for predicting each outcome and found 1-year mortality to be greater for Early-AKI. CONCLUSIONS: Our results suggest that risk factors are different for Early and Late-AKI after major hepatectomy, and 1-year mortality is greater for Early-AKI.

Propofol intravenous anaesthesia with desflurane compared with desflurane alone on postoperative liver function after living-donor liver transplantation: A randomised controlled trial.

BACKGROUND: Propofol is an anaesthetic that resembles α-tocopherol and it has been suggested that it protects against ischaemia-reperfusion injury in liver transplantation. Living-donor liver transplantation (LDLT) presents an opportunity to test this hypothesis in both donors and recipients. OBJECTIVES: We compared clinical outcomes after LDLT following anaesthesia with propofol and desflurane against desflurane alone. DESIGN: A randomised, parallel study. SETTING: Single-centre trial, study period June 2014 and May 2017. PATIENTS: Sixty-two pairs of adult donors and recipients who underwent LDLT. INTERVENTION: Patients were randomised to receive either desflurane balanced anaesthesia or propofol total intravenous anaesthesia combined with desflurane anaesthesia. MAIN OUTCOME MEASURES: The primary outcome was peak liver transaminase levels during the first 7 days after surgery. Liver function was assessed at 10 different time-points (before surgery, 1 h after reperfusion, upon arrival in the ICU, and daily until postoperative day 7). Creatinine was measured to evaluate the incidence of acute kidney injury. TNF-α, IL-1ß, IL-6 and TGF-ß1 were assessed in 31 donors after induction, at hepatectomy and at the end of surgery and in 52 recipients after induction, and 1, 3 and 24 h after reperfusion. RESULTS: Peak liver transaminase levels were not significantly different between the two groups. Liver function tests and creatinine were also similar between groups at all time-points. There was no difference in the incidence of postoperative complications, including acute kidney injury. With the exception of higher TNF-α in donors of the Propofol group at hepatectomy (0.60 ±â€Š0.29 vs. 1.03 ±â€Š0.53, P = 0.01) cytokine results were comparable between the two groups. CONCLUSION: Despite the simultaneous administration of propofol infusion in both donors and recipients, no improvement in laboratory or surgical outcome was observed after LDLT compared with patients who received desflurane anaesthesia alone. TRIAL REGISTRATION: NCT02504138 at clinicaltrials.gov.

Efficacy of Palonosetron-Dexamethasone Combination Versus Palonosetron Alone for Preventing Nausea and Vomiting Related to Opioid-Based Analgesia: A Prospective, Randomized, Double-blind Trial.

Background: The efficacy of dexamethasone plus palonosetron for postoperative nausea and vomiting (PONV) prophylaxis is not firmly established. This randomized, double-blind, controlled study evaluated whether the combination was superior to palonosetron alone in preventing PONV in patients receiving intravenous patient-controlled analgesia (IV-PCA) after upper extremity surgery. Methods: A total of 202 patients undergoing upper extremity surgery were randomly assigned to group P (palonosetron alone) or group PD (palonosetron plus dexamethasone). Group P patients received palonosetron 0.075 mg and normal saline 1.6 mL; group PD patients received palonosetron 0.075 mg and dexamethasone 8 mg. In both groups, palonosetron was added to the IV-PCA opioid infusion, which was continued for 48 h postoperatively. Incidence and severity of nausea, incidence of vomiting, rescue antiemetic requirements, pain intensity, and rescue analgesic requirements were evaluated for 72 h postoperatively. Quality of recovery was assessed using the quality of recovery-15 (QoR-15) questionnaire. Results: The incidence of PONV was significantly lower in group PD than in group P at 0-48 h postoperatively (61.5% vs 77.1%; p = 0.019). Severity of nausea at 0-6 h postoperatively was significantly less in group PD compared with group P (none/mild/moderate/severe: 49/22/15/10 vs. 36/16/25/19, p = 0.008). The incidence of vomiting and rescue antiemetic requirements were similar between groups. Pain intensity was significantly less in group PD than in group P at 0-48 h and 48-72 h postoperatively. Global QoR-15 was similar 24 h postoperatively between groups. Conclusions: Dexamethasone-palonosetron combination therapy reduced PONV incidence and postoperative pain in patients receiving opioid-based analgesia after upper extremity surgery.

Comparison of the laryngeal mask airway supreme and the i-gel in paralysed elderly patients: A randomised controlled trial.

BACKGROUND: The laryngeal mask airway supreme (LMA-S) and i-gel are both popular second-generation supraglottic airway devices that have been widely studied in surgical patients, but their differences in clinical performance in the elderly are not clear. OBJECTIVE: We compared the efficacy and safety of the LMA-S and i-gel in anaesthetised and paralysed elderly patients. DESIGN: A randomised study. SETTING: Single-centre trial, study period January 2014 from to October 2016. PATIENTS: One hundred and six elderly patients who underwent urological or orthopaedic surgery with an expected duration less than 2 h. INTERVENTION: Patients were allocated to either the LMA-S (n = 53) or i-gel (n = 53) group. All insertions were performed in a standardised manner according to the manufacturers' instructions. MAIN OUTCOME MEASURES: Our primary endpoint was the rate of successful insertion at the first attempt. The adequacy of positive pressure ventilation and airway sealing, fibreoptic laryngoscopy grades and stability of airway maintenance during anaesthesia were also assessed. RESULTS: Although the rate of successful insertion at the first attempt was similar between the two groups (94.3 vs. 82.7%, P = 0.072), more patients required device manipulation during insertion with the LMA-S than the i-gel (42.3 vs. 18.9%, P = 0.011). Good fibreoptic laryngoscopy grades were significantly more common with the i-gel than the LMA-S (79.3 vs. 55.8%, P = 0.042), and peak inspiratory pressures were lower in the i-gel group both immediately after insertion and at the end of surgery. Leak pressures were significantly higher in the i-gel group than the LMA-S group, both immediately after insertion and at the end of surgery (25.8 vs. 23.0, P = 0.036; and 28.1 vs. 23.7, P < 0.001, respectively). CONCLUSION: Both the LMA-S and i-gel were used successfully and safely in elderly patients. However, the i-gel demonstrated better airway sealing than the LMA-S at insertion and during maintenance of anaesthesia. TRIAL REGISTRATION: NCT02026791 at clinicaltrial.gov.

Patient satisfaction after endoscopic submucosal dissection under propofol-based sedation: a small premedication makes all the difference.

BACKGROUND: Ideal sedation for endoscopic submucosal dissection (ESD) aims to satisfy both the endoscopist and patient. However, previous studies show that a satisfactory procedure for the endoscopist does not equal higher patient satisfaction. This study attempted to find a sedation protocol that is able to increase patient satisfaction during propofol-based sedation by adding low-dose midazolam as premedication. METHODS: Seventy-two adult patients were randomly allocated to receive either 0.02 mg/kg midazolam (Midazolam Group) or placebo (Control Group) as premedication before ESD. Sedation was done by targeting Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale of 3 or 4 with continuous propofol infusion and bolus doses of fentanyl. Satisfaction scores of the endoscopists and patients, and whether the patient was willing to receive the same sedation method in the future was assessed. Interim analysis was done after enrollment of 50 % of patients. RESULTS: This study was prematurely terminated when interim analysis showed that patients willing to receive the same sedation method in the future were significantly lower in the Control Group compared to the Midazolam Group (P = 0.001). There was no difference in sedation time, procedure and recovery time, drug requirements and adverse events between the two groups. Endoscopist and overall patient satisfaction scores, patient pain scores and degree of recall were also similar between groups. CONCLUSIONS: A small dose of midazolam given as premedication before propofol-based sedation is able to reduce patient reluctance to repeat the same procedure in the future, without affecting procedural performance, recovery time or endoscopist satisfaction.

Effects of Dexmedetomidine on Changes in Heart Rate Variability and Hemodynamics During Tracheal Intubation.

Sympathetic hyperactivation during tracheal intubation prolongs the QT interval and increases the risk of arrhythmias. We investigated if dexmedetomidine pretreatment affected autonomic nervous system balance and QT intervals during intubation. Sixty-six patients were randomized to receive 1.0 µg/kg fentanyl (group F, n = 22), 0.5 µg/kg dexmedetomidine (group D0.5, n = 22), or 1.0 µg/kg dexmedetomidine (group D1.0, n = 22) before induction. Autonomic nervous system balance was assessed by the ratio of low-frequency/high-frequency (LF/HF) power for heart rate variability at baseline (T0), before intubation (T1), and after intubation (T2). QT intervals were corrected by the Bazett's formula (QTc) and compared at baseline, before intubation, and 1, 2, and 3 minutes after intubation. The LF/HF ratio was higher after intubation compared with that at T0 in group F (P < 0.001). There were no significant changes in groups D0.5 and D1.0. The LF/HF ratio was significantly higher in group F compared with those in groups D0.5 and D1.0 after intubation (7.9 vs. 2.1 and 2.5; P < 0.001). The heart rate was increased for 3 minutes after intubation in group F, whereas only for 1 minute after intubation in groups D0.5 and D1.0, compared with that at baseline. More patients in group F had QTc greater than 440 ms compared with that in group D0.5 or D1.0 (8 vs. 1 and 2; P = 0.005) at 1 minute after intubation. In contrast to 1.0 µg/kg fentanyl, pretreatment with 0.5 or 1.0 µg/kg dexmedetomidine suppressed sympathetic hyperactivity and attenuated QTc prolongation during intubation.

Prediction of fluid responsiveness in the beach chair position using dynamic preload indices.

Hemodynamic instability in the beach chair position (BCP) may lead to adverse outcomes. Cardiac preload optimization is a prerequisite to improve hemodynamics. We evaluated the clinical usefulness of dynamic indices for the prediction of fluid responsiveness in BCP patients under general anesthesia. Forty-two patients in the BCP under mechanical ventilation received colloids at 6 ml/kg for 10 min. Stroke volume variation (SVV), pulse pressure variation (PPV), pleth variability index (PVI), and hemodynamic data were measured before and after the fluid challenge. Patients were considered responders to volume expansion if the stroke volume index increased by ≥15 %. The areas under receiver operating characteristic curves for SVV, PPV and PVI were 0.83, 0.81 and 0.74, respectively (p < 0.05), with the corresponding optimal cut-off values of 12, 15 and 10 %. SVV, PPV and PVI can be used to predict fluid responsiveness in the BCP under mechanical ventilation.

Comparison of three sedation regimens for drug-induced sleep endoscopy.

PURPOSE: Drug-induced sleep endoscopy (DISE) allows for direct airway observation in patients with obstructive sleep apnea. This study compared the safety profiles and efficacies of three regimens for DISE. METHODS: Sixty-six patients were randomly assigned to receive propofol alone (n = 22), a propofol-remifentanil combination (n = 22), or a dexmedetomidine-remifentanil combination (n = 22). Remifentanil was infused at a concentration of 1.5 ng·ml(-1) in the propofol-remifentanil and dexmedetomidine-remifentanil groups, whereas saline was infused in the propofol group. The propofol and propofol-remifentanil groups received propofol at a starting concentration of 1.0 µg·ml(-1), then 0.1 µg·ml(-1) increments at 5 min intervals. The dexmedetomidine-remifentanil group received 1.0 µg·kg(-1) loading dose of dexmedetomidine for 10 min and then 0.2 µg·kg(-1)·h(-1) increments at 5 min intervals. RESULTS: The incidence of oxygen desaturation was significantly higher in the propofol-remifentanil group compared with that of the dexmedetomidine-remifentanil group (77 vs. 45%, respectively, P = 0.024). Even with a maximum dose of dexmedetomidine (1.4 µg·kg(-1)·h(-1)), 50% of the dexmedetomidine-remifentanil group did not reach sufficient sedation and required additional propofol. Cough reflex occurred in five patients of propofol group and in neither of the other groups (P = 0.004). CONCLUSIONS: The propofol-remifentanil combination was associated with a higher incidence of desaturation. The dexmedetomidine-remifentanil combination was associated with inadequate sedation in one half of the patients, even though it produced less respiratory depression. Addition of remifentanil reduced the cough reflex.

Sedation for interventional gastrointestinal endoscopic procedures: are we overlooking the "pain"?

BACKGROUND: Although interventional gastrointestinal (GI) endoscopic procedures are known to cause greater pain and discomfort than diagnostic procedures, the efficacy of adequate pain control or the difference in pain and amount of analgesic required according to type of intervention is not well known. This study was done to investigate the safety and efficacy of combining fentanyl with propofol for interventional GI endoscopic procedures and determine whether this method is superior to propofol monosedation. METHODS: The data of 810 patients that underwent interventional GI endoscopic procedures under sedation with either propofol alone (Group P, n = 499) or propofol/fentanyl (Group PF, n = 311) at a single tertiary-care hospital between May 2012 and December 2012 were retrospectively reviewed. Rates of respiratory and cardiovascular events, propofol and fentanyl requirements, and risk factors of respiratory events of the two groups were analyzed. RESULTS: The incidence of respiratory events (P = 0.001), number of cases in which the procedure had to be interrupted for assisted mask bagging (P = 0.044), and propofol infusion rates were significantly lower in Group PF compared to Group P (P < 0.0001). The amount of fentanyl required for diagnostic procedures was significantly lower than that for interventional procedures (P < 0.001). Patients of Group PF showed a lower risk of developing respiratory events compared to Group P (OR 0.224, 95 % CI 0.069­0.724). CONCLUSIONS: Combining fentanyl with propofol seems to reduce the risk of respiratory events compared with propofol monosedation during GI endoscopic procedures by providing effective analgesia.

Increase in intraocular pressure is less with propofol than with sevoflurane during laparoscopic surgery in the steep Trendelenburg position.

BACKGROUND: Intraocular pressure is increased during laparoscopic surgeries performed in a steep Trendelenburg position. This study compared the effects of propofol with those of sevoflurane on intraocular pressure in patients undergoing robot-assisted laparoscopic radical prostatectomy in a 30° Trendelenburg position. METHODS: Sixty-six patients were randomly allocated to a maintenance anesthetic consisting of remifentanil and sevoflurane (Sevoflurane Group) or remifentanil and propofol (Propofol Group). Intraocular pressure (IOP) was measured at nine predefined time points, including baseline (T0), five minutes after establishing pneumoperitoneum (T2), 30 min after establishing the Trendelenburg position with pneumoperitoneum (T3), five minutes after returning to the horizontal position (T4), and immediately after tracheal extubation (T6). The primary outcome was the change in intraocular pressure from T0 to T3. RESULTS: The results of linear mixed model analysis showed that intraocular pressure differed between the two groups (P = 0.0039). At T3, the mean (SD) IOP was greater in the Sevoflurane Group [23.5 (4.3) mmHg] than in the Propofol Group [19.9 (3.8) mmHg] (P = 0.0019). At T2 and T6, IOP was also greater in the Sevoflurane Group than in the Propofol Group (P = 0.038 and P = 0.009, respectively). There was a statistically significant increase in intraocular pressure from baseline to T3 (pneumoperitoneum and steep Trendelenberg) in the Sevoflurane Group [6.0 (5.0) mmHg; P < 0.001] but not in the Propofol Group [2.1 (5.1) mmHg; P = 0.136]. None of the patients experienced ocular complications. CONCLUSIONS: Intraocular pressure increases after pneumoperitoneum and the steep Trendelenburg position are established. This increase is less with propofol than with sevoflurane anesthesia. This trial was registered at ClinicalTrials.gov: NCT01744262.

Positioning of double-lumen tubes based on the minimum peak inspiratory pressure difference between the right and left lungs in short patients: a prospective observational study.

BACKGROUND: Peak inspiratory pressures (PIPs) during one-lung ventilation (OLV) have served as a clinical marker that could indirectly verify the proper positioning of double-lumen tubes (DLTs). Patients of short stature are highly susceptible to initial DLT malpositioning. OBJECTIVES: We investigated the usefulness of positioning left-sided DLTs using minimum PIP differences between the right and left lungs by comparing with the previously used method of auscultation without fibreoptic bronchoscopy (FOB). We also evaluated the difference in PIPs between the two lungs during OLV after the DLT was ideally positioned with FOB examination. DESIGN: Prospective, observational study. SETTING: A university hospital. PATIENTS: One hundred and two female patients of short stature (≤160  cm). INTERVENTIONS: Verification of DLT position was conducted by three sequential steps: auscultation; minimising the difference in PIP during each OLV; and verifying the resulting position by FOB. MAIN OUTCOME MEASUREMENTS: Fibreoptic bronchoscopic view results of DLT position followed by the position adjustment using the minimum PIP difference method. RESULTS: Repositioning the DLT using the minimum PIP difference led to clinically successful positioning of the DLT in 88% of patients and a more ideal placement of the tube than auscultation alone (69.6 vs. 11.8%, P <0.001). Additionally, the ideal position of DLTs verified by FOB showed that PIP differences were zero or ±1  mmHg in 93% of patients. CONCLUSION: Positioning the DLT based on the minimum PIP difference between the right and left lungs as a supplementation to routine auscultation serves as an easy and reliable method for DLT positioning and may improve the accuracy of DLT positioning as an adjuvant to FOB in short patients. TRIAL REGISTRATION: Clinicaltrial.gov identifier: NCT01533012.

Anti-Proliferative Effects of Lidocaine as an Autophagy Inducer in Bladder Cancer via Intravesical Instillation: In Vitro and Xenograft Mouse Model Experiments.

Lidocaine exerts potential anti-tumor effects on various cancer cell lines, and its intravesical instillation is considered safer than intravenous administration for bladder cancer. However, the mechanisms underlying its anti-tumor effects have not been fully elucidated. Here, we aimed to elucidate the anti-tumor molecular mechanisms of lidocaine in bladder cancer cells and a xenograft model to substantiate the efficacy of its intravesical administration. We investigated the anti-proliferative and autophagyinducing activities of lidocaine in Nara Bladder Tumor No. 2 (NBT-II) rat bladder carcinoma cells using cell viability, flow cytometry, a wound healing assay, and western blotting. We also established a xenograft mouse model of bladder cancer, and cancer growth was examined using in vivo bioluminescence imaging. Lidocaine decreased cell viability, induced G0/G1 phase cell cycle arrest, and inhibited cell migration partially via glycogen synthase kinase (GSK) 3ß phosphorylation. Moreover, a combination of lidocaine and SB216763 (a GSK3ß inhibitor) suppressed autophagy-related protein expression. Bafilomycin-A1 with lidocaine significantly enhanced microtubule-associated protein 1A/1B-light chain (LC3B) expression; however, it decreased LC3B expression in combination with 3-methyladenine compared to lidocaine alone. In the xenograft mouse model, the bladder cancer volume was reduced by lidocaine. Overall, lidocaine exerts anti-proliferative effects on bladder cancer via an autophagy-inducing mechanism.

The effects of combined epidural and general anesthesia on the autonomic nervous system and bioavailability of nitric oxide in patients undergoing laparoscopic pelvic surgery.

BACKGROUND: Pneumoperitoneum during laparoscopic surgery is known to affect visceral blood flow and result in oxidative stress. Whether epidural anesthesia will effectively reduce visceral ischemia and oxidative stress by blocking the sympathetic nervous system (SNS) during laparoscopic surgery has not been proven. METHODS: Forty-five patients who were to undergo robot-assisted laparoscopic prostatectomy were randomly assigned to the combined general-epidural anesthesia group (group GE, n = 22) or to the general anesthesia group (group G, n = 23). Blood pressure, heart rate, and the balance between sympathetic and parasympathetic nervous system activity as measured by heart rate variability were recorded at 10 min after induction of anesthesia (T1), 60 (T2) and 120 (T3) min after intra-abdominal CO(2) insufflation, and 10 min after returning the patient to the supine position following CO(2) exsufflation (T4). Arterial blood gas analysis and blood sampling for measurements of nitrite (NO(2-)) and malondialdehyde (MDA) were performed at all time points. RESULTS: Intraoperative mean blood pressure was significantly lower in group GE compared with group G. The low-frequency to high-frequency ratio was significantly increased after induction of pneumoperitoneum in group G but was unchanged in group GE. Plasma levels of nitrite decreased after pneumoperitoneum induction in group G while there was no change in group GE. A significant increase in MDA levels was seen in group G after pneumoperitoneum induction and were higher than group GE at T3 and T4. The 24-h urine output was higher in group GE than in group G on POD 1. The 24-h CrCl was higher in group GE on POD 1 but was not different between groups on POD 2. CONCLUSIONS: Combined epidural and general anesthesia effectively blocks SNS stimulation during laparoscopic surgery and reduces NO inactivation and oxidative stress.

Analgesic efficacy of bilateral superficial cervical plexus block in robot-assisted endoscopic thyroidectomy using a transaxillary approach.

BACKGROUND: Nerve blocks and infiltration with local anesthetics are commonly employed methods for postoperative pain control. This prospective, randomized trial was conducted to determine whether bilateral superficial cervical plexus block (BSCPB) is effective for reducing acute postoperative pain after robot-assisted endoscopic thyroidectomy (RAET) and to compare its effects with that of local wound infiltration (LWI). METHODS: Ninety-seven patients who were to undergo RAET were randomly assigned to one of three groups to receive BSCPB with either 20 mL of 0.525% ropivacaine (BSCPB group, n=32) or 20 mL of isotonic sodium chloride solution (Control group, n=32) or LWI with 20 mL of 0.525% ropivacaine (LWI group, n=33). Postoperative pain scores were assessed at the postoperative anesthesia care unit (PACU) and at 6, 24, and 48 h postoperatively using a visual analog scale (VAS). Patients with VAS scores of ≥40 were administered rescue analgesics according to a standardized protocol. The main outcome variables were pain scores during the first postoperative 24 h and the number of patients requiring postoperative analgesic rescue. RESULTS: The BSCBP and LWI groups showed lower pain scores compared with the Control group at the PACU. The BSCPB group continued to show significantly lower pain scores compared with the LWI and Control groups at postoperative 6 and 24 h. The number of patients requiring analgesic rescue at the PACU was lower in the BSCPB and LWI groups than in the Control group. The number of patients requiring additional rescue analgesics after discharge from the PACU until the first 24 postoperative h was lower in the BSCPB group than in the LWI group. CONCLUSIONS: BSCPB and LWI are effective for reducing pain scores and analgesic requirements during the immediate postoperative period in patients who undergo RAET, with BSCPB being superior to LWI at postoperative 6-24 h.

Identification of the correct cervical level by palpation of spinous processes.

BACKGROUND: The ability to identify the correct vertebral level through examination is an important skill for clinicians who are performing nerve blocks without fluoroscopy. The conventional palpation method, which identifies the most prominent cervical spinous process as the seventh cervical (C7) spinous process is unreliable in many cases. We compared the accuracy of 2 different palpation methods used for identifying C7. METHODS: Ninety-six patients scheduled for cervical spine procedures under fluoroscopy guidance were randomized into either the control group or the flexion-extension group. The control group was examined with the conventional method, and the flexion-extension group was examined through assisted flexion and extension of the patient's cervical spine and identifying the lowest freely moving spinous process as C6 and the following stationary cervical spinous process as C7. A single anesthesiologist attempted to identify the C7 spinous process by using either the conventional method or the flexion-extension method and marked the presumed C7 spinous process with a radiopaque indicator. The actual vertebral level was then confirmed by fluoroscopy. The accuracy of the 2 different palpation techniques was compared, and the influence of patients' age, gender, and body mass index (BMI) was also examined. RESULTS: The C7 spinous process was correctly identified in 77.1% of patients in the flexion-extension group, compared with 37.5% in the control group (P<0.001). The C6 spinous process was identified as the most prominent cervical spinous process instead of C7 in 47.9% of patients in the control group, showing that errors are more common in the cephalad direction with the conventional method. The accuracy of the flexion-extension method was significantly higher than the conventional method regardless of the patient's age, gender, and BMI. Particularly, this difference in accuracy was seen not only in patients with a BMI <25 kg/m(2), but also in those with a BMI ≥25 kg/m(2) (BMI <25 kg/m(2), P=0.006 vs BMI ≥25 kg/m(2), P=0.008). CONCLUSIONS: The flexion-extension method is more accurate than the conventional method when identifying cervical vertebral level.

Effect of the mitochondrial unfolded protein response on hypoxic death and mitochondrial protein aggregation.

Mitochondria are the main oxygen consumers in cells and as such are the primary organelle affected by hypoxia. All hypoxia pathology presumably derives from the initial mitochondrial dysfunction. An early event in hypoxic pathology in C. elegans is disruption of mitochondrial proteostasis with induction of the mitochondrial unfolded protein response (UPRmt) and mitochondrial protein aggregation. Here in C. elegans, we screen through RNAis and mutants that confer either strong resistance to hypoxic cell death or strong induction of the UPRmt to determine the relationship between hypoxic cell death, UPRmt activation, and hypoxia-induced mitochondrial protein aggregation (HIMPA). We find that resistance to hypoxic cell death invariantly mitigated HIMPA. We also find that UPRmt activation invariantly mitigated HIMPA. However, UPRmt activation was neither necessary nor sufficient for resistance to hypoxic death and vice versa. We conclude that UPRmt is not necessarily hypoxia protective against cell death but does protect from mitochondrial protein aggregation, one of the early hypoxic pathologies in C. elegans.

Inhalational versus intravenous maintenance of anesthesia for quality of recovery in patients undergoing corrective lower limb osteotomy: A randomized controlled trial.

BACKGROUND: Inhalational anesthesia and propofol-based total intravenous anesthesia (TIVA) are the two most popular methods of general anesthesia with distinct characteristics that may affect quality of recovery (QOR) differently. This study compared QOR after corrective lower limb osteotomy between desflurane-based inhalational anesthesia and propofol-based TIVA. METHODS: Sixty-eight patients, ASA class I or II who underwent corrective lower limb osteotomy were randomized to receive either desflurane anesthesia or propofol TIVA. The primary outcome was quality of recovery 40 (QoR-40) questionnaire scores on postoperative day (POD) 1 and 2. Postoperative nausea scores, antiemetic requirements, and amount of opioid consumption via intravenous patient-controlled analgesia (IV PCA) were assessed as secondary outcomes. RESULTS: Global QoR-40 scores on POD 1 (153.5 (140.3, 171.3) vs. 140.0 (120.0, 173.0), P = 0.056, 95% CI; -22.5, 0.2) and POD 2 (155.5 (146.8, 175.5) vs. 152.0 (134.0, 179.0), P = 0.209, 95% CI; -17.5, 3.9) were comparable between the two groups. Among the five dimensions of QoR-40, physical independence scores were significantly higher in the TIVA group compared to the Desflurane group on POD both 1 and 2. Nausea scores (0.0 (0.0, 0.0) vs. 1.0 (0.0, 3.5), P < 0.001) and number of patients requiring rescue antiemetics (0% vs. 15.2%, P = 0.017) were significantly lower in the TIVA group at the post anesthesia care unit (PACU). Although the number of bolus attempts between 0-24 h and the morphine equivalent dose of analgesics administered via IV PCA between 12-24 h were significantly less in the TIVA group compared to the Desflurane group, there was no significant difference between groups for the overall 48 h postoperative period. CONCLUSIONS: Propofol-based TIVA did not improve global QoR-40 scores compared with desflurane-based inhalational anesthesia. However, considering the better QoR-40 scores in the domain of physical independence and less nausea in the early postoperative period, propofol TIVA should be considered as a useful option in patients undergoing corrective lower limb osteotomy.

Immunomodulatory Effects of Perioperative Dexmedetomidine in Ovarian Cancer: An In Vitro and Xenograft Mouse Model Study.

BACKGROUND: The surgical stress response (SSR) causes immunosuppression which may cause residual tumor growth and micrometastasis after cancer surgery. We investigated whether dexmedetomidine affects cancer cell behavior and immune function in an ovarian cancer xenograft mouse model. METHODS: The effect of dexmedetomidine on cell viability and cell cycle was assessed using SK-OV-3 cells at drug concentrations of 0.5, 0.1, 5, and 10 µg mL-1. BALB/c nude mice were used for the ovarian cancer model with the Dexmedetomidine group (n=6) undergoing surgery with dexmedetomidine infusion and the Control group (n=6) with saline infusion for 4 weeks. Natural killer (NK) cell activity, serum proinflammatory cytokines, and cortisol were measured at predetermined time points and tumor burden was assessed 4 weeks after surgery. RESULTS: Dexmedetomidine had no effect on cell viability or cell cycle. Following a sharp decrease on postoperative day (POD) 1, NK cell activity recovered faster in the Dexmedetomidine group with significant difference vs. the Control group on POD 3 (P=0.028). In the Dexmedetomidine group, cortisol levels were lower on POD 3 (P=0.004) and TNF-α levels were lower at 4 weeks after surgery (P<0.001) compared to the Control group. The Dexmedetomidine group showed lower tumor burden at 4 weeks vs. the Control group as observed by both tumor weight (P<0.001) and the in vivo imaging system (P=0.03). CONCLUSIONS: Dexmedetomidine infusion may improve ovarian cancer surgery outcome by suppressing the SSR and stress mediator release. Further studies are needed to elucidate the mechanisms by which dexmedetomidine acts on cancer and immune cells.

Perioperative Intravenous Lidocaine Infusion on Postoperative Recovery in Patients Undergoing Arthroscopic Rotator Cuff Repair Under General Anesthesia: A Randomized Controlled Trial.

OBJECTIVE: Arthroscopic rotator cuff repair (ARCR) is known to cause severe postoperative pain that may interfere with recovery. Intravenous (IV) lidocaine has analgesic, anti-inflammatory, and antihyperalgesic effects, and is being used in various types of surgeries. However, the effect of IV lidocaine in ARCR is not well-known. MATERIALS AND METHODS: Ninety patients undergoing ARCR were randomly allocated to receive IV lidocaine (1.5 mg/kg bolus of 1% lidocaine after anesthesia induction followed by a continuous infusion of 2 mg/kg/h up to 1 h after surgery) or an equal volume of saline. In both groups, an IV patient-controlled analgesia (PCA) device was used that contained fentanyl 10 µg/mL, infused at 1 mL/h with a 1 mL bolus dose. The primary outcome was fentanyl requirements given via IV PCA during the first 24 hours after surgery. Perioperative pain scores and functional recovery were assessed as secondary outcomes. RESULTS: The amount of fentanyl administered via IV PCA up to 24 hours after surgery was significantly lower in the lidocaine group compared with the control group (329 [256.2 to 428.3] vs. 394.5 [287.0 to 473.0], P=0.037). The number of PCA bolus attempts were lower in the lidocaine group without statistical significance. There were no differences in postoperative pain scores or functional shoulder scores between the 2 groups. DISCUSSION: IV lidocaine appears to be helpful in reducing opioid requirements during the acute postoperative period in patients undergoing ARCR. IV lidocaine may be a viable option as a component of multimodal analgesia in ARCR when regional analgesia is not possible.