Role of VVZ-149, a Novel Analgesic Molecule, in the Affective Component of Pain: Results from an Exploratory Proof-of-Concept Study of Postoperative Pain following Laparoscopic and Robotic-Laparoscopic Gastrectomy.

OBJECTIVE: VVZ-149 is a small molecule that both inhibits the glycine transporter type 2 and the serotonin receptor 5 hydroxytryptamine 2 A. In a randomized, parallel-group, and double-blind trial (NCT02844725), we investigated the analgesic efficacy and safety of VVZ-149 Injections, which is under clinical development as a single-use injectable product for treating moderate to severe postoperative pain. METHODS: Sixty patients undergoing laparoscopic and robotic-laparoscopic gastrectomy were randomly assigned to receive a 10-hour intravenous infusion of VVZ-149 Injections or placebo, initiated approximately 1 hour before completion of surgical suturing. Major outcomes included pain intensity and opioid consumption via patient-controlled analgesia and rescue analgesia provided "as needed." The treatment efficacy of VVZ-149 was further examined in a subpopulation requiring early rescue medication, previously associated with the presence of high levels of preoperative negative affect in a prior Phase 2 study (NCT02489526). RESULTS: Pain intensity was lower in the VVZ-149 (n = 30) than the placebo group (n = 29), reaching statistical significance at 4 hours post-emergence (P < .05), with a 29.5% reduction in opioid consumption for 24 hours and fewer demands for patient-controlled analgesia. In the rescued subgroup, VVZ-149 further reduced pain intensity (P < .05) with 32.6% less opioid consumption for 24 hours compared to placebo patients. CONCLUSIONS: VVZ-149 demonstrated effective analgesia with reduced postoperative pain and opioid requirements. Consistent with the results from the previous Phase 2 study, patients with early rescue requirement had greater benefit from VVZ-149, supporting the hypothesis that VVZ-149 may alleviate the affective component of pain and mitigate excessive use of opioids postoperatively.

Comparison of the effects of patient-controlled epidural and intravenous analgesia on postoperative bowel function after laparoscopic gastrectomy: a prospective randomized study.

BACKGROUND: Although laparoscopic surgery significantly reduces surgical trauma compared to open surgery, postoperative ileus is a frequent and significant complication after abdominal surgery. Unlike laparoscopic colorectal surgery, the effects of epidural analgesia on postoperative recovery after laparoscopic gastrectomy are not well established. We compared the effects of epidural analgesia to those of conventional intravenous (IV) analgesia on the recovery of bowel function after laparoscopic gastrectomy. METHOD: Eighty-six patients undergoing laparoscopic gastrectomy randomly received either patient-controlled epidural analgesia with ropivacaine and fentanyl (Epi PCA group) or patient-controlled IV analgesia with fentanyl (IV PCA group), beginning immediately before incision and continuing for 48 h thereafter. The primary endpoint was recovery of bowel function, evaluated by the time to first flatus. The balance of the autonomic nervous system, pain scores, duration of postoperative hospital stay, and complications were assessed. RESULTS: The time to first flatus was shorter in the epidural PCA group compared with the IV PCA group (61.3 ± 11.1 vs. 70.0 ± 12.3 h, P = 0.001). Low-frequency/high-frequency power ratios during surgery were significantly higher in the IV PCA group, compared with baseline and those in the epidural PCA group. The epidural PCA group had lower pain scores during the first 1 h postoperatively and required less analgesics during the first 6 h postoperatively. CONCLUSIONS: Compared with IV PCA, epidural PCA facilitated postoperative recovery of bowel function after laparoscopic gastrectomy without increasing the length of hospital stay or PCA-related complications. This beneficial effect of epidural analgesia might be attributed to attenuation of sympathetic hyperactivation, improved analgesia, and reduced opioid use.

Effects of dexmedetomidine in combination with fentanyl-based intravenous patient-controlled analgesia on pain attenuation after open gastrectomy in comparison with conventional thoracic epidural and fentanyl-based intravenous patient-controlled analgesia.

Background: This study was investigated the effects of dexmedetomidine in combination with fentanyl-based intravenous patient-controlled analgesia (IV-PCA) on pain attenuation in patients undergoing open gastrectomy in comparison with conventional thoracic epidural patient-controlled analgesia (E-PCA) and IV-PCA. Methods: One hundred seventy-one patients who planned open gastrectomy were randomly distributed into one of the 3 groups: conventional thoracic E-PCA (E-PCA group, n = 57), dexmedetomidine in combination with fentanyl-based IV-PCA (dIV-PCA group, n = 57), or fentanyl-based IV-PCA only (IV-PCA group, n = 57). The primary outcome was the postoperative pain intensity (numerical rating scale) at 3 hours after surgery, and the secondary outcomes were the number of bolus deliveries and bolus attempts, and the number of patients who required additional rescue analgesics. Mean blood pressure, heart rate, and adverse effects were evaluated as well. Results: One hundred fifty-three patients were finally completed the study. The postoperative pain intensity was significantly lower in the dIV-PCA and E-PCA groups than in the IV-PCA group, but comparable between the dIV-PCA group and the E-PCA group. Patients in the dIV-PCA and E-PCA groups needed significantly fewer additional analgesic rescues between 6 and 24 hours after surgery, and had a significantly lower number of bolus attempts and bolus deliveries during the first 24 hours after surgery than those in the IV-PCA group. Conclusions: Dexmedetomidine in combination with fentanyl-based IV-PCA significantly improved postoperative analgesia in patients undergoing open gastrectomy without hemodynamic instability, which was comparable to thoracic E-PCA. Furthermore, this approach could be clinically more meaningful owing to its noninvasive nature.

Spatiotemporal changes of optical signals in the somatosensory cortex of neuropathic rats after electroacupuncture stimulation.

BACKGROUND: Peripheral nerve injury causes physiological changes in primary afferent neurons. Neuropathic pain associated with peripheral nerve injuries may reflect changes in the excitability of the nervous system, including the spinothalamic tract. Current alternative medical research indicates that acupuncture stimulation has analgesic effects in various pain symptoms. However, activation changes in the somatosensory cortex of the brain by acupuncture stimulation remain poorly understood. The present study was conducted to monitor the changes in cortical excitability, using optical imaging with voltage-sensitive dye (VSD) in neuropathic rats after electroacupuncture (EA) stimulation. METHODS: Male Sprague-Dawley rats were divided into three groups: control (intact), sham injury, and neuropathic pain rats. Under pentobarbital anesthesia, rats were subjected to nerve injury with tight ligation and incision of the tibial and sural nerves in the left hind paw. For optical imaging, the rats were re-anesthetized with urethane, and followed by craniotomy. The exposed primary somatosensory cortex (S1) was stained with VSD for one hour. Optical signals were recorded from the S1 cortex, before and after EA stimulation on Zusanli (ST36) and Yinlingquan (SP9). RESULTS: After peripheral stimulation, control and sham injury rats did not show significant signal changes in the S1 cortex. However, inflamed and amplified neural activities were observed in the S1 cortex of nerve-injured rats. Furthermore, the optical signals and region of activation in the S1 cortex were reduced substantially after EA stimulation, and recovered in a time-dependent manner. The peak fluorescence intensity was significantly reduced until 90 min after EA stimulation (Pre-EA: 0.25 ± 0.04 and Post-EA 0 min: 0.01 ± 0.01), and maximum activated area was also significantly attenuated until 60 min after EA stimulation (Pre-EA: 37.2 ± 1.79 and Post-EA 0 min: 0.01 ± 0.10). CONCLUSION: Our results indicate that EA stimulation has inhibitory effects on excitatory neuronal signaling in the S1 cortex, caused by noxious stimulation in neuropathic pain. These findings suggest that EA stimulation warrants further study as a potential adjuvant modulation of neuropathic pain.

The impact of two different inspiratory to expiratory ratios (1:1 and 1:2) on respiratory mechanics and oxygenation during volume-controlled ventilation in robot-assisted laparoscopic radical prostatectomy: a randomized controlled trial.

BACKGROUND: Volume-controlled ventilation with a prolonged inspiratory to expiratory ratio (I:E ratio) has been used to optimize gas exchange and respiratory mechanics in various surgical settings. We hypothesized that, when compared with an I:E ratio of 1:2, a prolonged I:E ratio of 1:1 would improve respiratory mechanics without reducing cardiac output (CO) during pneumoperitoneum and steep Trendelenburg positioning, both of which can impair respiratory function in robot-assisted laparoscopic radical prostatectomy. Furthermore, we evaluated its effect on oxygenation during robot-assisted laparoscopic radical prostatectomy. METHODS: Eighty patients undergoing robot-assisted laparoscopic radical prostatectomy were randomly allocated to receive an I:E ratio of either 1:1 (group 1:1) or 1:2 (group 1:2). The primary endpoint, peak airway pressure (Ppeak), as well as hemodynamic data, including cardiac output (CO) and arterial oxygen tension (PaO2), were compared between groups at four time points: ten minutes after anesthesia induction (T1), 30 and 60 min after pneumoperitoneum with steep Trendelenburg positioning (T2 and T3), and ten minutes after supine positioning (T4). Overall comparisons were made between groups using linear mixed model analysis with post hoc testing of individual time points adjusted using a Bonferroni correction. RESULTS: Linear mixed model analysis showed a significant overall difference in Ppeak between the two groups (P < 0.001). Post hoc analysis showed a significantly lower mean (SD) Ppeak in group 1:1 than in group 1:2 at T2 [28.4 (4.0) cm H2O vs 32.8 (5.2) cm H2O, respectively; mean difference, 4.3 cm H2O; 95% confidence interval (CI), 2.3 to 6.4; P < 0.001] and T3 [27.8 (3.9) cm H2O vs 32.6 (5.0) cm H2O, respectively; mean difference, 4.7 cm H2O; 95% CI, 2.7 to 6.7; P < 0.001]. The CO assessed over these time points was comparable in both groups (P = 0.784). In addition, there were no significant differences in PaO2 between the two groups (P = 0.521). CONCLUSIONS: Compared with an I:E ratio of 1:2, a ratio of 1:1 lowered Ppeak without reducing CO during pneumoperitoneum and steep Trendelenburg positioning. Nevertheless, our results did not support its use solely for improving oxygenation. This trial was registered at http://clinicaltrials.gov/ (NCT01892449).

Plasticity-Related PKMζ Signaling in the Insular Cortex Is Involved in the Modulation of Neuropathic Pain after Nerve Injury.

The insular cortex (IC) is associated with important functions linked with pain and emotions. According to recent reports, neural plasticity in the brain including the IC can be induced by nerve injury and may contribute to chronic pain. Continuous active kinase, protein kinase Mζ (PKMζ), has been known to maintain the long-term potentiation. This study was conducted to determine the role of PKMζ in the IC, which may be involved in the modulation of neuropathic pain. Mechanical allodynia test and immunohistochemistry (IHC) of zif268, an activity-dependent transcription factor required for neuronal plasticity, were performed after nerve injury. After ζ-pseudosubstrate inhibitory peptide (ZIP, a selective inhibitor of PKMζ) injection, mechanical allodynia test and immunoblotting of PKMζ, phospho-PKMζ (p-PKMζ), and GluR1 and GluR2 were observed. IHC demonstrated that zif268 expression significantly increased in the IC after nerve injury. Mechanical allodynia was significantly decreased by ZIP microinjection into the IC. The analgesic effect lasted for 12 hours. Moreover, the levels of GluR1, GluR2, and p-PKMζ were decreased after ZIP microinjection. These results suggest that peripheral nerve injury induces neural plasticity related to PKMζ and that ZIP has potential applications for relieving chronic pain.

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.

Effects of acupuncture stimulation at different acupoints on formalin-induced pain in rats.

Acupuncture is the process of stimulating skin regions called meridians or acupoints and has been used to treat pain-related symptoms. However, the pain-relieving effects of acupuncture may be different depending on acupoints. In the present study, the effects of acupuncture on behavioral responses and c-Fos expression were evaluated using a formalin test in male Sprague-Dawley rats in order to clarify the analgesic effects of three different acupoints. Each rat received manual acupuncture at the ST36 (Zusanli), SP9 (Yinlingquan) or BL60 (Kunlun) acupoint before formalin injection. Flinching and licking behaviors were counted by two blinded investigators. Fos-like immunoreactivity was examined by immunohistochemistry in the rat spinal cord. Manual acupuncture treatment at BL60 acupoint showed significant inhibition in flinching behavior but not in licking. Manual acupuncture at ST36 or SP9 tended to inhibit flinching and licking behaviors but the effects were not statistically significant. The acupuncture at ST36, SP9, or BL60 reduced c-Fos expression as compared with the control group. These results suggest that acupuncture especially at the BL60 acupoint is more effective in relieving inflammatory pain than other acupoints.

Quadriceps recovery and pain relief in knee osteoarthritis rats by cog polydioxanone filament insertion.

Quadriceps muscles play a pivotal role in knee osteoarthritis (OA) progression and symptom manifestation, particularly pain. This research investigates the therapeutic effectiveness of muscle enhancement and support therapy (MEST), a recently developed device intended for intramuscular insertion of cog polydioxanone filaments, in quadriceps restoration to alleviate OA pain. Knee OA was induced in Sprague Dawley rats via monoiodoacetate injections. MEST or sham treatment was performed in OA or Naive rat quadriceps. Pain was assessed using paw withdrawal threshold and weight bearing. Quadriceps injury and recovery via MEST were evaluated using biomarkers, tissue morphology, muscle mass, contractile force and hindlimb torque. Satellite cell and macrophage activation, along with their activators, were also assessed. Data were compared at 1- and 3-weeks post-MEST treatment (M-W1 and M-W3). MEST treatment in OA rats caused muscle injury, indicated by elevated serum aspartate transferase and creatinine kinase levels, and local ß-actin changes at M-W1. This injury triggered pro-inflammatory macrophage and satellite cell activation, accompanied by heightened interleukin-6 and insulin-like growth factor-1 levels. However, by M-W3, these processes gradually shifted toward inflammation resolution and muscle restoration. This was seen in anti-inflammatory macrophage phenotypes, sustained satellite cell activation and injury markers regressing to baseline. Quadriceps recovery in mass and strength from atrophy correlated with substantial OA pain reduction at M-W3. This study suggests that MEST-induced minor muscle injury triggers macrophage and satellite cell activation, leading to recovery of atrophied quadriceps and pain relief in OA rats.

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.

Comparison of 2 cuff inflation methods before insertion of laryngeal mask airway for safe use without cuff manometer in children.

PURPOSE: This prospective, randomized trial was conducted to establish whether the pediatric laryngeal mask airway (LMA) could be used without any concerns for abnormally high intra-cuff pressure when a cuff of the LMA was inflated with half the maximum recommended inflation volume or the resting volume before insertion. BASIC PROCEDURES: Eighty children 0 to 9 years of age and weighing of 5 to 30 kg scheduled for general anesthesia were included. Before insertion, the cuff of the LMA was filled with half the maximum recommended inflation volume in the Half volume group, or the resting volume by opening the pilot balloon valve to atmospheric pressure in the Resting volume group. After insertion of the LMA, intra-cuff pressure, oropharyngeal leak pressure, and leakage volume were investigated. MAJOR FINDINGS: The Half volume group showed lower mean intra-cuff pressure than the Resting volume group (49.6 ± 12.1 cm H(2)O vs 58.1 ± 13.8 cm H(2)O, P = .005). There was no difference in oropharyngeal leak pressure (22.1 ± 5.8 vs 21.7 ± 5.1 cm H(2)O, P = .757) or leakage volume between the Half volume group and the Resting volume group (0.13 ± 0.13 ml/kg vs 0.11 ± 0.12 ml/kg, P = .494) under spontaneous respiration. CONCLUSIONS: Both methods of the LMA cuff inflation before insertion provided an acceptable range of intra-cuff pressure with adequate pharyngeal sealing without any intervention after insertion.

Modulation of Neuropathic Pain by Glial Regulation in the Insular Cortex of Rats.

The insular cortex (IC) is known to process pain information. However, analgesic effects of glial inhibition in the IC have not yet been explored. The aim of this study was to investigate pain alleviation effects after neuroglia inhibition in the IC during the early or late phase of pain development. The effects of glial inhibitors in early or late phase inhibition in neuropathic pain were characterized in astrocytes and microglia expressions in the IC of an animal model of neuropathic pain. Changes in withdrawal responses during different stages of inhibition were compared, and morphological changes in glial cells with purinergic receptor expressions were analyzed. Inhibition of glial cells had an analgesic effect that persisted even after drug withdrawal. Both GFAP and CD11b/c expressions were decreased after injection of glial inhibitors. Morphological alterations of astrocytes and microglia were observed with expression changes of purinergic receptors. These findings indicate that inhibition of neuroglia activity in the IC alleviates chronic pain, and that purinergic receptors in glial cells are closely related to chronic pain development.

Analgesic Efficacies of Intraoperative Pectoralis Nerve II Block under Direct Vision in Patients Undergoing Robotic Nipple-Sparing Mastectomy with Immediate Breast Reconstruction: A Prospective, Randomized Controlled Study.

This prospective, randomized study aimed to evaluate the efficacy of an intraoperative pectoralis nerve II block (PECS II block) under direct vision in the reduction of fentanyl consumption during postoperative 24 h in patients undergoing robotic nipple-sparing mastectomy (RNSM) with immediate breast reconstruction (IBR) using direct-to-implant (DTI) or tissue expander (TE). Thirty patients scheduled for RNSM with IBR were randomly allocated to the PECS (n = 15) or control (n = 15) groups. The PECS II block was applied under direct vision after RNSM. The primary outcome was the cumulative dose of fentanyl consumption. The secondary outcomes were pain intensity using a numerical rating scale (NRS) at rest and acting during the postoperative 24 h. The cumulative dose of fentanyl at 24 h was significantly lower in the PECS group than in the control group (p = 0.011). Patients in the PECS group showed significantly lower NRS scores during the first postoperative 2 h compared to those in the control group in both resting and acting pain (p < 0.05). An intraoperative PECS II block under direct vision can reduce opioid consumption during the postoperative 24 h and provide effective analgesia in patients undergoing RNSM with IBR using DTI or TE.

Physiologic and hemodynamic changes in patients undergoing open abdominal cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

OBJECTIVE: We aimed to determine the physiological and hemodynamic changes in patients who were undergoing hyperthermic intraperitoneal chemotherapy (HIPEC) cytoreductive surgeries. METHODS: This prospective, observational study enrolled 21 patients who were undergoing elective cytoreductive surgery with HIPEC at our hospital over 2 years. We collected vital signs, hemodynamic parameters including global end-diastolic volume index (GEVI) and extravascular lung water index (ELWI) using the VolumeView™ system, and arterial blood gas analysis from all patients. Data were recorded before skin incision (T1); 30 minutes before HIPEC initiation (T2); 30 (T3), 60 (T4), and 90 (T5) minutes after HIPEC initiation; 30 minutes after HIPEC completion (T6); and 10 minutes before surgery completion (T7). RESULTS: Patients showed an increase in body temperature and cardiac index and a decrease in the systemic vascular resistance index. GEDI was 715.4 (T1) to 809.7 (T6), and ELWI was 6.9 (T1) to 7.3 (T5). CONCLUSIONS: HIPEC increased patients' body temperature and cardiac output and decreased systemic vascular resistance. Although parameters that were extracted from the VolumeView™ system were within their normal ranges, transpulmonary thermodilution approach is helpful in intraoperative hemodynamic management during open abdominal cytoreductive surgery with HIPEC.Trial registry name: ClinicalTrials.govTrial registration number: NCT02325648URL: https://clinicaltrials.gov/ct2/results?cond=NCT02325648&term.

Influence of Deep Neuromuscular Blockade on Perioperative Stress Response in Patients Undergoing Robot-Assisted Gastrectomy: A Prospective Double-Blinded Randomized-Controlled Trial.

Attenuating the intraoperative stress response is crucial; however, the effect of neuromuscular blockade (NMB) on surgical stress is not completely understood. We aimed to investigate the effects of NMB on the perioperative stress response during robot-assisted gastrectomy. Patients were assigned to the deep or moderate NMB group. Serum cortisol, prolactin, and interleukin-6 (IL-6) levels and natural killer (NK) cell percentage were measured before anesthesia induction, 90 min after pneumoperitoneum, operation end (OPEnd), and postoperative day 1. Additionally, C-reactive protein (CRP) and albumin levels were estimated. Additionally, intraoperative heart rate variability was evaluated. The deep NMB group showed significantly lower levels of low-frequency/high-frequency (HF) ratio at OPEnd compared to the moderate NMB group (1.4 ± 0.2 vs. 2.2 ± 0.3, respectively; Bonferroni corrected p = 0.039). Furthermore, HF power in the deep NMB group was significantly higher at OPEnd than that in the moderate NMB group (45.2 ± 3.6 vs. 33.8 ± 4.0, respectively; Bonferroni corrected p = 0.044). However, no significant differences in cortisol, prolactin, IL-6, CRP, and albumin levels and NK cell percentage were found between the two groups. The degree of NMB may have similar effects on stress-related biological markers in patients undergoing robot-assisted gastrectomy.

The usefulness of the laryngeal mask airway Fastrach for laryngeal surgery.

BACKGROUND AND OBJECTIVE: Suspension laryngoscopy under general anaesthesia with a tracheal tube has been widely used for laryngeal microsurgery, but it has some limitations such as intense cardiovascular stimulation during anaesthesia of short duration, occasionally a poor surgical field, and the possibility of a mass being hampered by the tracheal tube. The aim of this study was to compare the usefulness of the laryngeal mask airway (LMA) Fastrach and fibreoptic bronchoscope with a conventional suspension laryngoscope in laryngeal microsurgery. METHODS: Forty patients scheduled for laryngeal microsurgery were enrolled in this prospective randomized study consecutively. After general anaesthesia was induced, laryngeal microsurgery was performed with a fibreoptic bronchoscope through the LMA Fastrach or conventional suspension laryngoscope. The best view of the surgical field, evaluated by percentage of glottic opening score, was obtained by the up-down manipulations of the LMA Fastrach or repositioning the suspension laryngoscope. Blood pressure and heart rate changes at the baseline, preinsertion, and postinsertion were recorded. RESULTS: Percentage of glottic opening score of the LMA Fastrach group was 100 and that of the suspension laryngoscope group was 80 (P < 0.05). The LMA Fastrach insertion was performed without remarkable systolic or diastolic blood pressure or heart rate changes, but systolic, diastolic blood pressure or heart rate were increased after intubation in the suspension laryngoscope group. CONCLUSION: The LMA Fastrach during fibreoptic bronchoscope-guided laryngeal surgery provided a good surgical field and haemodynamic stability without additional risk compared with the conventional suspension laryngoscope.

Comparison of Analgesic and Adverse Effects of Oxycodone- and Fentanyl-Based Patient-Controlled Analgesia in Patients Undergoing Robot-Assisted Laparoscopic Gastrectomy Using a 55:1 Potency Ratio of Oxycodone to Fentanyl: A Retrospective Study.

PURPOSE: Oxycodone has affinities for both kappa- and mu-opioid receptors. Therefore, it has been used for postoperative analgesia of surgeries in which visceral pain is expected to be the main cause of pain. However, there are few studies of the 55:1 potency ratio of oxycodone to fentanyl when using it as intravenous patient-controlled analgesia (IV-PCA). Thus, we compared the analgesic and adverse effects of IV-PCA using the 55:1 potency ratio of oxycodone to fentanyl in patients who underwent robot-assisted laparoscopic gastrectomy. PATIENTS AND METHODS: This retrospective study included 100 patients using an automatic PCA pump with oxycodone or fentanyl who underwent robot-assisted laparoscopic gastrectomy between January and November 2017. All patients were provided with an IV-PCA consisting of 20 µg/kg of fentanyl or 1.1 mg/kg of oxycodone mixed with 0.9% normal saline solution to a total volume of 250 mL, which was infused basally at a rate of 0.1 mL/h with a bolus dose of 1 mL and lockout time of 6 min. The primary and secondary endpoints were to evaluate the efficacies of IV-PCA using the 55:1 potency ratio of oxycodone to fentanyl on analgesic and adverse effects. RESULTS: Pain intensity on arrival at the post-anesthesia care unit (PACU; 3.6±1.4 vs 4.4±2.0, P=0.031) and additional analgesic requirement within an hour after surgery (including the PACU period) (12% vs 37%; P=0.005) were significantly lower in the oxycodone group (n=49) than in the fentanyl group (n=51). Regarding adverse effects, the rate of postoperative nausea within 1 h after surgery (2% vs 16%; P=0.031) was also significantly lower in the oxycodone group than that in the fentanyl group. CONCLUSION: Oxycodone-based IV-PCA by dose calculations with a 55:1 potency ratio may achieve better analgesia without any significant adverse effects, when using IV-PCA in patients undergoing robot-assisted laparoscopic gastrectomy.

Pain-Relieving Effects of mTOR Inhibitor in the Anterior Cingulate Cortex of Neuropathic Rats.

The anterior cingulate cortex (ACC) is a well-known brain area that is associated with pain perception. Previous studies reported that the ACC has a specific role in the emotional processing of pain. Chronic pain is characterized by long-term potentiation that is induced in pain pathways and contributes to hyperalgesia caused by peripheral nerve injury. The mammalian target of rapamycin (mTOR) signaling, which is involved in synaptic protein synthesis, could be a key factor controlling long-term potentiation in neuropathic pain conditions. Until now, there have been no reports that studied the role of mTOR signaling in the ACC involved in neuropathic pain. Therefore, this study was conducted to determine the relationship of mTOR signaling in the ACC and neuropathic pain. Male Sprague-Dawley rats were subjected to cannula implantation and nerve injury under pentobarbital anesthesia. Microinjection with rapamycin into the ACC was conducted under isoflurane anesthesia on postoperative day (POD) 7. A behavioral test was performed to evaluate mechanical allodynia, and optical imaging was conducted to observe the neuronal responses of the ACC to peripheral stimulation. Inhibition of mTOR by rapamycin reduced mechanical allodynia, down-regulated mTOR signaling in the ACC, and diminished the expressions of synaptic proteins which are involved in excitatory signaling, thereby reducing neuropathic pain-induced synaptic plasticity. These results suggest that inhibiting mTOR activity by rapamycin in the ACC could serve as a new strategy for treating or managing neuropathic pain before it develops into chronic pain.

Influence of reversal of neuromuscular blockade with sugammadex or neostigmine on postoperative quality of recovery following a single bolus dose of rocuronium: A prospective, randomized, double-blinded, controlled study.

STUDY OBJECTIVE: To evaluate the influence of reversal of neuromuscular blockade with sugammadex or neostigmine on postoperative quality of recovery following a single bolus dose of rocuronium after pars plana vitrectomy (PPV) under general anesthesia. DESIGN: Prospective, double-blind, randomized controlled trial. SETTING: This study was conducted in a University Teaching Hospital from February to July 2017. PATIENTS: A total of 84 patients with an American Society of Anesthesiologists physical status of I or II who were scheduled to undergo PPV under general anesthesia. INTERVENTIONS: The patients were randomly assigned to the neostigmine (Group N, n = 44) or sugammadex (Group S, n = 40) groups; 3 ml of study drug was prepared for the patients. For patients in Group N, a solution of neostigmine methylsulfate (1 mg) and glycopyrrolate (0.2 mg) was prepared, while a solution of sugammadex sodium (2 mg/kg) and normal saline was prepared for patients in Group S. MEASUREMENTS: The primary endpoint was the effect of sugammadex, compared with neostigmine, on the recovery rate in the physiological domain in patients who underwent PPV with general anesthesia. The quality of recovery was assessed using the Postoperative Quality Recovery Scale at 15 min and 40 min after surgery, and on postoperative day 1. MAIN RESULTS: The recovery rate in the physiological domain was higher in Group S at 15 min after surgery (P = 0.020). Though there were no significant differences in the overall cognitive recovery domain, patients in Group S could recall more numbers in reverse order. However, there were no significant differences between the groups in the other domains of the scale. CONCLUSIONS: The use of sugammadex may increase the quality of physiological recovery at early postoperative periods, compared with that of neostigmine, following a single bolus dose of rocuronium in patients undergoing PPV with general anesthesia. TRIAL REGISTRATION: Registered at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT03108989). Registration number: NCT03108989.

The duration of intrathecal bupivacaine mixed with lidocaine.

BACKGROUND: Although spinal bupivacaine may have too long duration to be useful in the ambulatory setting, recent animal data suggest that lidocaine added to spinal bupivacaine may reduce the duration of bupivacaine spinal anesthesia. We explored whether lidocaine added to spinal bupivacaine could shorten the duration of bupivacaine spinal anesthesia in humans similarly to what has been reported in animals. METHODS: Ninety patients presenting for transurethral resection of bladder tumor or prostate were assigned to one of three groups by double blind randomization to receive intrathecal 1.5 mL of hyperbaric 0.5% bupivacaine, plus 0.6 mL of one of three solutions: saline (Group I, n = 30, control), 1% lidocaine (Group II, n = 30), and 2% lidocaine (Group III, n = 30). Peak sensory block level, time to peak sensory block, times to two-segment, L1, and S2 regressions from peak sensory block, motor blocks at peak sensory block, L1, and S2 regressions, and postanesthesia care unit stay time (PACU time) were measured. RESULTS: Times to peak sensory block were similar in all three groups. Times to two-segment, L1, and S2 regressions from peak sensory block, and PACU time were significantly reduced in Group II compared to Group I. Times to L1, S2 regressions, and PACU times in Group III were significantly prolonged. CONCLUSIONS: We conclude that lidocaine (6 mg) mixed to spinal bupivacaine (7.5 mg) can shorten the duration of bupivacaine spinal anesthesia, therefore provide more rapid recovery from the spinal anesthesia compared to the same dose of bupivacaine (7.5 mg) alone.