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.

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.

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.

Preoperative Carbohydrate Drinks Do Not Decrease Postoperative Nausea and Vomiting in Type 2 Diabetic Patients Undergoing Total Knee Arthroplasty-A Randomized Controlled Trial.

INTRODUCTION: We evaluated whether preoperative carbohydrate drink would be able to decrease postoperative nausea and vomiting (PONV) and improve the quality of recovery (QoR) in diabetic patients undergoing total knee arthroplasty (TKA). METHODS: Eighty-two patients were randomized to either the intravenous (IV) Dextrose group (n = 41) or Oral carbohydrate (CHO) group (n = 41). The IV Dextrose group received dextrose solution mixed with insulin while fasting, and the Oral CHO group received carbohydrate drinks preoperatively. PONV was assessed up to postoperative 36 hours, and QoR was assessed before surgery and on postoperative day (POD) 1. Blood glucose was measured from the morning of surgery until POD 1. RESULTS: PONV scores were not different between the groups. Postoperative QoR scores were significantly higher in the Oral CHO group (median [interquartile range]; 160 [153 to 167]) than the IV Dextrose group (155 [147 to 159]) (P = 0.009), but the difference did not meet the minimal clinically important difference. Blood glucose was comparable between the groups. DISCUSSION: Preoperative CHO drink did not reduce PONV in diabetic patients after total knee arthroplasty. A statistically significant but clinically questionable improvement in the QoR was seen in the Oral CHO group. However, preoperative CHO drink did not increase hyperglycemia, which suggests that it may be a safe component of perioperative care in diabetic patients.

Effects of Anesthesia Techniques on Outcomes after Hip Fracture Surgery in Elderly Patients: A Prospective, Randomized, Controlled Trial.

The superiority of distinct anesthesia methods for geriatric hip fracture surgery remains unclear. We evaluated high mobility group box-1 (HMGB1) and interleukin-6 (IL-6) with three different anesthesia methods in elderly patients undergoing hip fracture surgery. Routine blood test findings, postoperative morbidity, and mortality were assessed as secondary outcome. In total, 176 patients were randomized into desflurane (n = 60), propofol (n = 58), or spinal groups (n = 58) that received desflurane-based balanced anesthesia, propofol-based total intravenous anesthesia (TIVA), or spinal anesthesia, respectively. The spinal group required less intraoperative vasopressors (p < 0.001) and fluids (p = 0.006). No significant differences in HMGB1 (pgroup×time = 0.863) or IL-6 (pgroup×time = 0.575) levels were noted at baseline, postoperative day (POD) 1, or POD2. Hemoglobin, albumin, creatinine, total lymphocyte count, potassium, troponin T, and C-reactive protein were comparable among groups at all time-points. No significant differences in postoperative hospital stay, intensive care unit (ICU) stay, and ventilator use among groups were observed. Postoperative pulmonary, cardiac, and neurologic complications; and in-hospital, 30-day, and 90-day mortality were not significantly different among groups (p = 0.974). In conclusion, HMGB1 and IL-6, and all secondary outcomes, were not significantly different between desflurane anesthesia, propofol TIVA, and spinal anesthesia.

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.

Effects of dexmedetomidine on inflammatory mediators after tourniquet-induced ischemia-reperfusion injury: a randomized, double-blinded, controlled study.

BACKGROUND: Tourniquet use during total knee arthroplasty (TKA) produces ischemia-reperfusion injury (IRI), with systemic release of inflammatory cytokines and reactive oxygen species upon tourniquet release. We conducted a randomized, placebo-controlled, double-blind trial to examine whether dexmedetomidine (DEX) as an adjunct during general anesthesia in patients undergoing unilateral TKA could attenuate the rise in inflammatory cytokines and oxidative stress. METHODS: Sixty-eight patients were randomized to either the control or DEX group. DEX was administered at a loading dose of 0.5 µg/kg, followed by an infusion of 0.4 µg/kg/h. We measured serum levels of malondialdehyde (biomarker of oxidative stress) and proinflammatory cytokines (interleukin-6 [IL-6] and tumour necrosis factor-α [TNF-α]) preinduction (baseline), 60 and 90 min post-tourniquet release. We also assessed hemodynamics, intraoperative remifentanil consumption, and postoperative pain scores and analgesic consumption. RESULTS: Malondialdehyde was higher than baseline after tourniquet release in both groups (P≤0.001), but the levels were similar between groups at all times. TNF-α was significantly higher than baseline at 60 min post-tourniquet release only in the control group (P=0.009). Serum IL-6 increased significantly above baseline at 60 and 90 min post-tourniquet release in both groups (P<0.001). At 90 min, IL-6 was significantly lower in the dexmedetomidine group than in the control group (P=0.049). Remifentanil consumption, heart rate, and pain scores were significantly lower in the dexmedetomidine group. CONCLUSIONS: Our results suggest that dexmedetomidine as an adjunct to general anesthesia attenuated the rise in proinflammatory cytokines, providing protective effects in tourniquet-induced IRI.

Pulse pressure variation and pleth variability index as predictors of fluid responsiveness in patients undergoing spinal surgery in the prone position.

BACKGROUND: This study investigated the ability of pulse pressure variation (PPV) and pleth variability index (PVI) to predict fluid responsiveness of patients undergoing spinal surgery in the prone position. PATIENTS AND METHODS: A total of 53 patients undergoing posterior lumbar spinal fusion in the prone position on a Jackson table were studied. PPV, PVI, and hemodynamic and respiratory variables were measured both before and after the administration of 6 mL/kg colloid in both the supine and prone positions. Fluid responsiveness was defined as a 15% or greater increase in stroke volume index, as assessed by esophageal Doppler monitor after fluid loading. RESULTS: In the supine position, 40 patients were responders. The areas under the receiver operating characteristic (ROC) curves for PPV and PVI were 0.783 [95% CI 0.648-0.884, P<0.001] and 0.814 (95% CI 0.684-0.908, P<0.001), respectively. The optimal cut-off values of PPV and PVI were 10% (sensitivity 75%, specificity 62%) and 8% (sensitivity 78%, specificity 77%), respectively. In the prone position, 27 patients were responders. The areas under the ROC curves for PPV and PVI were 0.781 (95% CI 0.646-0.883, P<0.001) and 0.756 (95% CI 0.618-0.863, P<0.001), respectively. The optimal cut-off values of PPV and PVI were 7% (sensitivity 82%, specificity 62%) and 8% (sensitivity 67%, specificity 69%), respectively. CONCLUSION: Both PPV and PVI were able to predict fluid responsiveness; their predictive abilities were maintained in the prone position.

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.

Effect of postoperative analgesia technique on the prognosis of gastric cancer: a retrospective analysis.

BACKGROUND: Whether regional analgesia techniques have favorable impact on prognosis after cancer surgery is unclear, and existing reports show controversial results. The aim of the present study was to evaluate and compare recurrence and mortality between patients that received either intravenous (IV) or epidural patient controlled analgesia (PCA) for pain control after curative surgery for gastric cancer. MATERIALS AND METHODS: Medical records of patients that underwent curative gastrectomy for gastric cancer between November 2005 and December 2010 were reviewed. Identified patients were categorized according to the use of IV or epidural PCA for postoperative analgesia. Demographic and perioperative variables including type of PCA were analyzed by univariate and multiple regression analysis to investigate any association with recurrence and mortality after surgery. Propensity score matching was done to adjust for selection bias. RESULTS: Of the 3,799 patients included in this analysis, 374 and 3, 425 patients received IV and epidural PCAs, respectively. No difference in recurrence (HR, 1.092; 95% CI 0.859 to 1.388; P = 0.471) or mortality (HR, 0.695; 95% CI 0.429 to 1.125; P = 0.138) was identified between the use of IV and epidural PCA. Propensity score matching also showed no difference in recurrence (HR, 1.098; 95% CI 0.756 to 1.596; P = 0.623) or mortality (HR, 0.855; 95% CI 0.391 to 1.869; P = 0.695) between the two groups. CONCLUSIONS: Postoperative use of epidural analgesia was not found to be associated with reduced recurrence or mortality after curative surgery in gastric cancer patients. This finding needs to be confirmed with prospective studies in the future.

Efficacy of Palonosetron vs. Ramosetron for the Prevention of Postoperative Nausea and Vomiting: A Meta-Analysis of Randomized Controlled Trials.

PURPOSE: This study was designed as a meta-analysis of randomized controlled trials (RCTs) that included the comparison of palonosetron and ramosetron for postoperative nausea and vomiting (PONV) prophylaxis. MATERIALS AND METHODS: A systematic search was conducted for the PubMed, EMBASE, Web of Science, CENTRAL, KoreaMed, and Google Scholar databases (PROSPERO protocol number CRD42015026009). Primary outcomes were the incidences of postoperative nausea (PON) and postoperative vomiting (POV) during the first 48 hrs after surgery. The total 48-hr period was further analyzed in time epochs of 0-6 hrs (early), 6-24 hrs (late), and 24-48 hrs (delayed). Subgroup analyses according to number of risk factors, sex, and type of surgery were also performed. RESULTS: Eleven studies including 1373 patients were analyzed. There was no difference in PON or POV between the two drugs for the total 48-hr period after surgery. However, palonosetron was more effective in preventing POV during the delayed period overall [relative risk (RR), 0.59; 95% confidence interval (CI), 0.39 to 0.89; p=0.013], as well as after subgroup analyses for females and laparoscopies (RR, 0.56; 95% CI, 0.36 to 0.86; p=0.009 and RR, 0.46; 95% CI, 0.23 to 0.94; p=0.033). Subgroup analysis for spine surgery showed that ramosetron was more effective in reducing POV during the total 48-hr (RR, 3.34; 95% CI, 1.46 to 7.63; p=0.004) and early periods (RR, 8.47; 95% CI, 1.57 to 45.72; p=0.013). CONCLUSION: This meta-analysis discovered no definite difference in PONV prevention between the two drugs. The significant findings that were seen in different time epochs and subgroup analyses should be confirmed in future RCTs.

Comparison of Dexmedetomidine and Fentanyl as an Adjuvant to Ropivacaine for Postoperative Epidural Analgesia in Pediatric Orthopedic Surgery.

PURPOSE: Opioids are commonly used as an epidural adjuvant to local anesthetics, but are associated with potentially serious side effects, such as respiratory depression. The aim of this study was to compare the efficacy and safety of dexmedetomidine with that of fentanyl as an adjuvant to epidural ropivacaine in pediatric orthopedic surgery. MATERIALS AND METHODS: This study enrolled 60 children (3-12 years old) scheduled for orthopedic surgery of the lower extremities and lumbar epidural patient-controlled analgesia (PCA). Children received either dexmedetomidine (1 µg/kg) or fentanyl (1 µg/kg) along with 0.2% ropivacaine (0.2 mL/kg) via an epidural catheter at 30 minutes before the end of surgery. Postoperatively, the children were observed for ropivacaine consumption via epidural PCA, postoperative pain intensity, need for rescue analgesics, emergence agitation, and other adverse effects. RESULTS: The mean dose of bolus epidural ropivacaine was significantly lower within the first 6 h after surgery in the dexmedetomidine group, compared with the fentanyl group (0.029±0.030 mg/kg/h vs. 0.053±0.039 mg/kg/h, p=0.012). The median pain score at postoperative 6 h was also lower in the dexmedetomidine group, compared to the fentanyl group [0 (0-1.0) vs. 1.0 (0-3.0), p=0.039]. However, there was no difference in the need for rescue analgesia throughout the study period between groups. CONCLUSION: The use of dexmedetomidine as an epidural adjuvant had a significantly greater analgesic and local anesthetic-sparing effect, compared to fentanyl, in the early postoperative period in children undergoing major orthopedic lower extremity surgery.

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.

Effect of the Prolonged Inspiratory to Expiratory Ratio on Oxygenation and Respiratory Mechanics During Surgical Procedures.

Prolonged inspiratory to expiratory (I:E) ratio ventilation has been researched to reduce lung injury and improve oxygenation in surgical patients with one-lung ventilation (OLV) or carbon dioxide (CO2) pneumoperitoneum. We aimed to confirm the efficacy of the 1:1 equal ratio ventilation (ERV) compared with the 1:2 conventional ratio ventilation (CRV) during surgical procedures. Electronic databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Google Scholar were searched.Prospective interventional trials that assessed the effects of prolonged I:E ratio of 1:1 during surgical procedures. Adult patients undergoing OLV or CO2 pneumoperitoneum as specific interventions depending on surgical procedures. The included studies were examined with the Cochrane Collaboration's tool. The data regarding intraoperative oxygenation and respiratory mechanics were extracted, and then pooled with standardized mean difference (SMD) using the method of Hedges. Seven trials (498 total patients, 274 with ERV) were included. From overall analysis, ERV did not improve oxygenation at 20 or 30 minutes after specific interventions (SMD 0.193, 95% confidence interval (CI): -0.094 to 0.481, P = 0.188). From subgroup analyses, ERV provided significantly improved oxygenation only with laparoscopy (SMD 0.425, 95% CI: 0.167-0.682, P = 0.001). At 60 minutes after the specific interventions, ERV improved oxygenation significantly in the overall analysis (SMD 0.447, 95% CI: 0.209-0.685, P < 0.001) as well as in the subgroup analyses with OLV (SMD 0.328, 95% CI: 0.011-0.644, P = 0.042) and laparoscopy (SMD 0.668, 95% CI: 0.052-1.285, P = 0.034). ERV provided lower peak airway pressure (Ppeak) and plateau airway pressure (Pplat) than CRV, regardless of the type of intervention. The relatively small number of the included articles and their heterogeneity could be the main limitations. ERV improved oxygenation at all of the assessment points during laparoscopy. In OLV, oxygenation improvement with ERV was observed 1 hour after application. ERV could be beneficial to reduce the Ppeak and Pplat.

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.

Elderly Patients Require Higher Doses of Sugammadex for Rapid Recovery from Deep Neuromuscular Block.

This study compared the doses of sugammadex needed for rapid recovery from deep neuromuscular blockade (NMB) between young and elderly adults. Twenty-two young (20-40 yrs) and 22 elderly (≥70 yrs) adults were enrolled, and deep NMB of 1-2 post-tetanic counts was maintained with rocuronium intraoperatively. Predetermined doses of sugammadex were given at the end of surgery starting at 4.0 mg/kg for the first patient of each group. Doses were decreased or increased in following patients by 0.5 mg/kg, depending on the 'success' or 'failure' of rapid recovery in the preceding patient. 'Success' was defined as adequate recovery (train-of-four ratio 0.9) within 2 min. after sugammadex administration. The median (range) of ages was 29 (20-40) and 73 (70-84) yrs for the young and elderly adults, respectively. Doses of sugammadex facilitating adequate recovery from deep NMB within 2 min. in each patient population with 50% and 95% probability were defined as ED50 and ED95 , respectively. The ED50 estimated by the Dixon's method was significantly higher in the elderly compared to young adults [4.2 ± 0.4 mg/kg versus 3.3 ± 0.3 mg/kg, p < 0.001]. The ED50 (83% CI) estimated by isotonic regression was 4.5 (4.2-5.0) mg/kg in elderly adults and 3.3 (3.2-3.4) mg/kg in young adults. The ED95 (95% CI) estimated by isotonic regression was 5.4 (4.9-5.5) mg/kg and 4.4 (3.9-4.5) mg/kg in the elderly and young adults, respectively. In conclusion, dose adjustments of sugammadex should be considered when rapid recovery from deep NMB is needed in elderly adults.

Effect of Pneumoperitoneum on Oxidative Stress and Inflammation via the Arginase Pathway in Rats.

PURPOSE: Oxidative stress during CO2 pneumoperitoneum is reported to be associated with decreased bioactivity of nitric oxide (NO). However, the changes in endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and arginase during CO2 pneumoperitoneum have not been elucidated. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were randomized into three groups. After anesthesia induction, the abdominal cavities of the rats of groups intra-abdominal pressure (IAP)-10 and IAP-20 were insufflated with CO2 at pressures of 10 mm Hg and 20 mm Hg, respectively, for 2 hours. The rats of group IAP-0 were not insufflated. After deflation, plasma NO was measured, while protein expression levels and activity of eNOS, iNOS, arginase (Arg) I, and Arg II were analyzed with aorta and lung tissue samples. RESULTS: Plasma nitrite concentration and eNOS expression were significantly suppressed in groups IAP-10 and IAP-20 compared to IAP-0. While expression of iNOS and Arg I were comparable between the three groups, Arg II expression was significantly greater in group IAP-20 than in group IAP-0. Activity of eNOS was significantly lower in groups IAP-10 and IAP-20 than in group IAP-0, while iNOS activity was significantly greater in group IAP-20 than in groups IAP-0 and IAP-10. Arginase activity was significantly greater in group IAP-20 than in groups IAP-0 and IAP-10. CONCLUSION: The activity of eNOS decreases during CO2 pneumoperitoneum, while iNOS activity is significantly increased, a change that contributes to increased oxidative stress and inflammation. Moreover, arginase expression and activity is increased during CO2 pneumoperitoneum, which seems to act inversely to the NO system.

The Intraocular Pressure under Deep versus Moderate Neuromuscular Blockade during Low-Pressure Robot Assisted Laparoscopic Radical Prostatectomy in a Randomized Trial.

BACKGROUND: This study aimed to determine whether continuous deep neuromuscular blockade (NMB) improves the surgical conditions and facilitates robotic-assisted laparoscopic radical prostatectomy (RALRP) under low intra-abdominal pressure (IAP) to attenuate the increase in intraocular pressure (IOP) during CO2 pneumoperitoneum in the steep Trendelenburg (ST) position. METHODS: Sixty-seven patients undergoing RALRP were randomly assigned to a moderate NMB group (Group M), including patients who received atracurium infusion until the end of the ST position, maintaining a train of four count of 1-2; and the deep NMB group (Group D), including patients who received rocuronium infusion, maintaining a post-tetanic count of 1-2. IOP was measured in all patients at nine separate time points. All RALRPs were performed by one surgeon, who rated the overall and worst surgical conditions at the end of the ST position. RESULTS: The highest IOP value was observed at T4 (60 min after the ST position) in both Group M (23.3 ± 2.7 mmHg) and Group D (19.8 ± 2.1 mmHg). RALRP was accomplished at an IAP of 8 mmHg in 88% Group D patients and 25% Group M patients. The overall surgical condition grade was 4.0 (3.0-5.0) in Group D and 3.0 (2.0-5.0) in Group M (P < 0.001). CONCLUSION: The current study demonstrated that continuous deep NMB may improve surgical conditions and facilitate RALRP at a low IAP, resulting in significant attenuation of the increase on IOP. Moreover, low-pressure pneumoperitoneum, facilitated by deep NMB still provided acceptable surgical conditions. TRIAL REGISTRATION: ClinicalTrials.gov NCT02109133.