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.

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.

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.

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.

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.

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.

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.

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.

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

[This corrects the article DOI: 10.1371/journal.pone.0135412.].

Effects of long periods of pneumoperitoneum combined with the head-up position on heart rate-corrected QT interval during robotic gastrectomy: an observational study.

OBJECTIVE: Pneumoperitoneum and the head-up position reportedly stimulate the sympathetic nervous system, potentially increasing the risk of cardiac arrhythmia. We evaluated the effects of a long duration of pneumoperitoneum in the head-up position on the heart rate-corrected QT (QTc) interval during robotic gastrectomy. METHODS: This prospective observational study involved 28 patients undergoing robotic gastrectomy. The QTc interval was recorded at the following time points: before anaesthetic induction (baseline); 10 minutes after tracheal intubation; 1, 5, 30, 60, and 90 minutes after pneumoperitoneum induction in the head-up position; after pneumoperitoneum desufflation in the supine position; and at the end of surgery. The primary outcome was the QTc interval, which was measured 90 minutes after pneumoperitoneum combined with the head-up position. RESULTS: Compared with baseline, the QTc interval was significantly prolonged at 1 and 60 minutes after pneumoperitoneum, peaked at 90 minutes, and was sustained and notably prolonged until the end of surgery. However, no considerable haemodynamic changes developed. CONCLUSION: A long period of carbon dioxide pneumoperitoneum application in a head-up position significantly prolonged the QTc interval during robotic gastrectomy. Therefore, diligent care and close monitoring are required for patients who are susceptible to developing ventricular arrhythmia. Trial Registration: Registered at ClinicalTrials.gov; https://clinicaltrials.gov/ct2/show/NCT02604979 ; Registration number NCT02604979.

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.

Inhibition of Mammalian Target of Rapamycin (mTOR) Signaling in the Insular Cortex Alleviates Neuropathic Pain after Peripheral Nerve Injury.

Injury of peripheral nerves can trigger neuropathic pain, producing allodynia and hyperalgesia via peripheral and central sensitization. Recent studies have focused on the role of the insular cortex (IC) in neuropathic pain. Because the IC is thought to store pain-related memories, translational regulation in this structure may reveal novel targets for controlling chronic pain. Signaling via mammalian target of rapamycin (mTOR), which is known to control mRNA translation and influence synaptic plasticity, has been studied at the spinal level in neuropathic pain, but its role in the IC under these conditions remains elusive. Therefore, this study was conducted to determine the role of mTOR signaling in neuropathic pain and to assess the potential therapeutic effects of rapamycin, an inhibitor of mTORC1, in the IC of rats with neuropathic pain. Mechanical allodynia was assessed in adult male Sprague-Dawley rats after neuropathic surgery and following microinjections of rapamycin into the IC on postoperative days (PODs) 3 and 7. Optical recording was conducted to observe the neural responses of the IC to peripheral stimulation. Rapamycin reduced mechanical allodynia and downregulated the expression of postsynaptic density protein 95 (PSD95), decreased neural excitability in the IC, thereby inhibiting neuropathic pain-induced synaptic plasticity. These findings suggest that mTOR signaling in the IC may be a critical molecular mechanism modulating neuropathic pain.

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.

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.

In vivo voltage-sensitive dye imaging of the insular cortex in nerve-injured rats.

The insular cortex (IC) is a pain-related brain region that receives various types of sensory input and processes the emotional aspects of pain. The present study was conducted to investigate spatiotemporal patterns related to neuroplastic changes in the IC after nerve injury using voltage-sensitive dye imaging. The tibial and sural nerves of rats were injured under pentobarbital anesthesia. To observe optical signals in the IC, rats were re-anesthetized with urethane 7days after injury, and a craniectomy was performed to allow for optical imaging. Optical signals of the IC were elicited by peripheral electrical stimulation. Neuropathic rats showed a significantly higher optical intensity following 5.0mA electrical stimulation compared to sham-injured rats. A larger area of activation was observed by 1.25 and 2.5mA electrical stimulation compared to sham-injured rats. The activated areas tended to be larger, and the peak amplitudes of optical signals increased with increasing stimulation intensity in both groups. These results suggest that the elevated responsiveness of the IC to peripheral stimulation is related to neuropathic pain, and that neuroplastic changes are likely to be involved in the IC after nerve injury.

Comparing McGRATH® MAC, C-MAC®, and Macintosh Laryngoscopes Operated by Medical Students: A Randomized, Crossover, Manikin Study.

We hypothesized that the McGRATH MAC would decrease the time of intubation compared to C-MAC for novices. Thirty-nine medical students who had used the Macintosh blade to intubate a manikin fewer than 3 times were recruited. The participants performed sequential intubations on the manikin in two simulated settings that included a normal airway and a difficult airway (tongue edema). The intubation time, success rate of intubation, Cormack-Lehane grade at laryngoscopy, and difficulty using the device were recorded. Each participant was asked to identify the device that was most useful. The intubation time decreased significantly and by a similar amount to the McGRATH MAC and C-MAC compared to the Macintosh blade (P < 0.001 and P = 0.017, resp.). In the difficult airway, the intubation times were similar among the three devices. The McGRATH MAC and C-MAC significantly increased the success rate of intubation, improved the Cormack-Lehane grade, and decreased the difficulty score compared to the Macintosh blade in both airway settings. The majority of participants selected the McGRATH MAC as the most useful device. The McGRATH MAC and C-MAC may offer similar benefits for intubation compared to the Macintosh blade in normal and difficult airway situations.

Comparison of the effects of remifentanil-based general anesthesia and popliteal nerve block on postoperative pain and hemodynamic stability in diabetic patients undergoing distal foot amputation: A retrospective observational study.

Diabetic foot ulcer is the most common cause of diabetes-associated nontraumatic lower extremity amputation. Most patients who undergo lower extremity amputation for a diabetic foot have had diabetes for a long time and suffer from multiorgan disorder; thus, it can be a challenge to ensure sufficient anesthetic and analgesic effects while maintaining stable hemodynamics. Recently, peripheral nerve block has gained popularity owing to its attenuating effects of systemic concerns. This retrospective observational study aimed to compare the effects of remifentanil-based general anesthesia (GEA) and popliteal nerve block (PNB) on postoperative pain and hemodynamic stability in diabetic patients undergoing distal foot amputation.A total of 59 consecutive patients with a diabetic foot who underwent distal foot amputation between January 2012 and May 2014 were retrospectively reviewed. Patients received remifentanil-based GEA (GEA group, n = 32) or PNB (PNB group, n = 27). The primary outcomes were to evaluate postoperative analgesic effects and perioperative hemodynamics. Also, postoperative pulmonary complications and 6-month mortality were assessed as secondary outcomes.Significant differences in pain scores using numeric rating scale were observed between the groups in a linear mixed model analysis (PGroup×Time = 0.044). Even after post hoc analysis with the Bonferroni correction, the numeric rating scale scores were significantly lower in the PNB group. Furthermore, patients in the PNB group required less pethidine during the first 6 hours after surgery (27 ±â€Š28 vs 9 ±â€Š18 mg; P = 0.013). The GEA group had a lower mean blood pressure (Bonferroni-corrected P < 0.01), despite receiving more ephedrine (P < 0.001). Significantly more patients in the GEA group suffered from postoperative pneumonia and required the management in intensive care unit (P = 0.030 and 0.038, respectively). However, the groups did not differ in terms of 6-month mortality.This study demonstrated that compared with remifentanil-based GEA, PNB might be a favorable option for diabetic patients undergoing distal foot amputation, despite the lack of significant mortality benefits, as PNB was associated with improved postoperative analgesia, hemodynamic stability, and a low incidence of pulmonary complications during the immediate postoperative period, especially in high-risk patients.

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.

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.

The Effects of Oral Atenolol or Enalapril Premedication on Blood Loss and Hypotensive Anesthesia in Orthognathic Surgery.

PURPOSE: The aim of this study was to evaluate the effects of premedication with oral atenolol or enalapril, in combination with remifentanil under sevoflurane anesthesia, on intraoperative blood loss by achieving adequate deliberate hypotension (DH) during orthognathic surgery. Furthermore, we investigated the impact thereof on the amount of nitroglycerin (NTG) administered as an adjuvant agent. MATERIALS AND METHODS: Seventy-three patients undergoing orthognathic surgery were randomly allocated into one of three groups: an angiotensin converting enzyme inhibitor group (Group A, n=24) with enalapril 10 mg, a ß blocker group (Group B, n=24) with atenolol 25 mg, or a control group (Group C, n=25) with placebo. All patients were premedicated orally 1 h before the induction of anesthesia. NTG was the only adjuvant agent used to achieve DH when mean arterial blood pressure (MAP) was not controlled, despite the administration of the maximum remifentanil dose (0.3 µg kg⁻¹ min⁻¹) with sevoflurane. RESULTS: Seventy-two patients completed the study. Blood loss was significantly reduced in Group A, compared to Group C (adjusted p=0.045). Over the target range of MAP percentage during DH was significantly higher in Group C than in Groups A and B (adjusted p-values=0.007 and 0.006, respectively). The total amount of NTG administered was significantly less in Group A than Group C (adjusted p=0.015). CONCLUSION: Premedication with enalapril (10 mg) combined with remifentanil under sevoflurane anesthesia attenuated blood loss and achieved satisfactory DH during orthognathic surgery. Furthermore, the amount of NTG was reduced during the surgery.