Effects of dexmedetomidine on depression-like behaviour in chronic restraint stress mice: Involvement of specific brain regions.

It is crucial to develop novel antidepressants. Dexmedetomidine (DEX) can exert antidepressant effects, but its underlying mechanism remains unclear. We used chronic restraint stress (CRS) to induce depression-like behaviour in mice and administered low-dose DEX (2 µg/kg per day) during CRS modelling or one injection of high-dose DEX (20 µg/kg) after CRS. The results of the behavioural tests revealed that both methods ameliorated CRS-induced depression. The brain slices of the mice were subjected to immunohistochemical staining for c-fos and phosphorylated ERK (pERK). Results showed that the continuous low-dose DEX-treated group, but not the single high-dose DEX-treated group expressed less c-fos in the nucleus locus coeruleus (LC) with a mean optical density (MOD) of 0.06. Other brain regions, including the dentate gyrus (DG), pyriform cortex (Pir), anterior part of paraventricular thalamic nucleus (PVA), arcuate nucleus (Arc), and core or shell of accumbens nucleus (Acbc or Acbs), presented differences in c-fos expression. In contrast, the low-dose DEX-treated group exhibited three-fold greater pERK expression in the LC of the CRS mice, with a MOD of 0.15. Pir, cingulate cortex (Cg) and, anterior and posterior part of paraventricular thalamic nucleus (PVA and PVP) exhibited pERK expression differences due to distinct reagent treatments. These changes indicate that the responses of brain regions to different DEX administration methods and doses vary. This study confirmed the ability of DEX to ameliorate CRS-induced depression and identified candidate target brain regions, thus providing new information for the antidepressant mechanism of DEX.

Correction: Single-cell in vivo imaging of cellular circadian oscillators in zebrafish.

[This corrects the article DOI: 10.1371/journal.pbio.3000435.].

Single-cell in vivo imaging of cellular circadian oscillators in zebrafish.

The circadian clock is a cell-autonomous time-keeping mechanism established gradually during embryonic development. Here, we generated a transgenic zebrafish line carrying a destabilized fluorescent protein driven by the promoter of a core clock gene, nr1d1, to report in vivo circadian rhythm at the single-cell level. By time-lapse imaging of this fish line and 3D reconstruction, we observed the sequential initiation of the reporter expression starting at photoreceptors in the pineal gland, then spreading to the cells in other brain regions at the single-cell level. Even within the pineal gland, we found heterogeneous onset of nr1d1 expression, in which each cell undergoes circadian oscillation superimposed over a cell type-specific developmental trajectory. Furthermore, we found that single-cell expression of nr1d1 showed synchronous circadian oscillation under a light-dark (LD) cycle. Remarkably, single-cell oscillations were dramatically dampened rather than desynchronized in animals raised under constant darkness, while the developmental trend still persists. It suggests that light exposure in early zebrafish embryos has significant effect on cellular circadian oscillations.

Application of opioid-free general anesthesia for gynecological laparoscopic surgery under ERAS protocol: a non-inferiority randomized controlled trial.

BACKGROUND: Enhanced recovery after surgery (ERAS) is now widely used in various surgical fields including gynecological laparoscopic surgery, but the advantages of opioid-free anesthesia (OFA) in gynecological laparoscopic surgery under ERAS protocol are inexact. AIMS: This study aims to assess the effectiveness and feasibility of OFA technique versus traditional opioid-based anesthesia (OA) technique in gynecological laparoscopic surgery under ERAS. METHODS: Adult female patients aged 18 ~ 65 years old undergoing gynecological laparoscopic surgery were randomly divided into OFA group (Group OFA, n = 39) with esketamine and dexmedetomidine or OA group (Group OA, n = 38) with sufentanil and remifentanil. All patients adopted ERAS protocol. The primary outcome was the area under the curve (AUC) of Visual Analogue Scale (VAS) scores (AUCVAS) postoperatively. Secondary outcomes included intraoperative hemodynamic variables, awakening and orientation recovery times, number of postoperative rescue analgesia required, incidence of postoperative nausea and vomiting (PONV) and Pittsburgh Sleep Quality Index (PSQI) perioperatively. RESULTS: AUCVAS was (Group OFA, 16.72 ± 2.50) vs (Group OA, 15.99 ± 2.72) (p = 0.223). No difference was found in the number of rescue analgesia required (p = 0.352). There were no between-group differences in mean arterial pressure (MAP) and heart rate (HR) (p = 0.211 and 0.659, respectively) except MAP at time of surgical incision immediately [(Group OFA, 84.38 ± 11.08) vs. (Group OA, 79.00 ± 8.92), p = 0.022]. Times of awakening and orientation recovery in group OFA (14.54 ± 4.22 and 20.69 ± 4.92, respectively) were both longer than which in group OA (12.63 ± 3.59 and 18.45 ± 4.08, respectively) (p = 0.036 and 0.033, respectively). The incidence of PONV in group OFA (10.1%) was lower than that in group OA (28.9%) significantly (p = 0.027). The postoperative PSQI was lower than the preoperative one in group OFA (p = 0.013). CONCLUSION: In gynecological laparoscopic surgery under ERAS protocol, OFA technique is non-inferior to OA technique in analgesic effect and intraoperative anesthesia stability. Although awakening and orientation recovery times were prolonged compared to OA, OFA had lower incidence of PONV and improved postoperative sleep quality. TRIAL REGISTRATION: ChiCTR2100052761, 05/11/2021.

Dexmedetomidine alleviates hepatic ischaemia-reperfusion injury via the PI3K/AKT/Nrf2-NLRP3 pathway.

Hepatic ischaemia-reperfusion (I/R) injury constitutes a tough difficulty in liver surgery. Dexmedetomidine (Dex) plays a protective role in I/R injury. This study investigated protective mechanism of Dex in hepatic I/R injury. The human hepatocyte line L02 received hypoxia/reoxygenation (H/R) treatment to stimulate cell model of hepatic I/R. The levels of pyroptosis proteins and inflammatory factors were detected. Functional rescue experiments were performed to confirm the effects of miR-494 and JUND on hepatic I/R injury. The levels of JUND, PI3K/p-PI3K, AKT/p-AKT, Nrf2, and NLRP3 activation were detected. The rat model of hepatic I/R injury was established to confirm the effect of Dex in vivo. Dex reduced pyroptosis and inflammation in H/R cells. Dex increased miR-494 expression, and miR-494 targeted JUND. miR-494 inhibition or JUND upregulation reversed the protective effect of Dex. Dex repressed NLRP3 inflammasome by activating the PI3K/AKT/Nrf2 pathway. In vivo experiments confirmed the protective effect of Dex on hepatic I/R injury. Overall, Dex repressed NLRP3 inflammasome and alleviated hepatic I/R injury via the miR-494/JUND/PI3K/AKT/Nrf2 axis.

Effects of lidocaine, dexmedetomidine, and their combination infusion on postoperative nausea and vomiting following laparoscopic hysterectomy: a randomized controlled trial.

BACKGROUND: A few studies have reported that administration of lidocaine and dexmedetomidine relieves the incidence of postoperative nausea and vomiting (PONV). We explored whether combined infusion of lidocaine plus dexmedetomidine had lower occurrence of PONV undergoing laparoscopic hysterectomy with general anesthesia. METHODS: A total of 248 women undergoing elective laparoscopic hysterectomy were allocated into the following four groups: the control group (group C, n = 62) received an equal volume of saline, the lidocaine group (group L, n = 62) received intravenous lidocaine (bolus infusion of 1.5 mg/kg over 10 min, 1.5 mg/kg/h continuous infusion), the dexmedetomidine group (group D, n = 62) received dexmedetomidine administration (bolus infusion of 0.5 µg/kg over 10 min, 0.4 µg/kg/h continuous infusion), and the lidocaine plus dexmedetomidine group (group LD, n = 62) received combination of lidocaine (bolus infusion of 1.5 mg/kg over 10 min, 1.5 mg/kg/h continuous infusion) and dexmedetomidine administration (bolus infusion of 0.5 µg/kg over 10 min, 0.4 µg/kg/h continuous infusion). The primary outcome was the incidence of nausea, vomiting, and PONV during the first 48 h after surgery. The secondary outcomes included the incidence of total 24 h PONV after surgery, intraoperative remifentanil requirement, postoperative pain visual analogue scale (VAS) scores and fentanyl consumption, the incidence of bradycardia, agitation, shivering, and mouth dry during post-anesthesia care unit (PACU) stay period. RESULTS: The occurrence of nausea and PONV in group LD (5.0 and 8.3%) at 0-2 h after operation was lower than group C (21.7 and 28.3%) (P < 0.05). There was no statistically significant difference with respect to occurrence of nausea and PONV in groups L (13.3 and 20.0%) and D (8.3 and 13.3%) at 0-2 h after operation compared to group C (21.7 and 28.3%). The incidence of nausea, vomiting, and PONV at 2-24 and 24-48 h after surgery in all four groups was not statistically significant. The incidence of total 24 h PONV in group LD (33.3%) was significantly decreased compared to group C (60.0%) (P < 0.05). The cumulative consumption of fentanyl at 6 and 12 h after surgery was significantly reduced in group LD compared to other three groups (P < 0.05). The pain VAS scores were significantly decreased at 2, 6, and 12 h after operation in group LD compared to other three groups (P < 0.05). Remifentanil dose in the intraoperative period was significantly lower in groups LD and D compared with groups C and L (P < 0.05). The number of mouth dry, bradycardia, and over sedation during the PACU stay period was markedly increased in group LD (28.3, 30.0, and 35.0%, respectively) compared with groups C (1.7, 1.7, and 3.3%, respectively) and L (3.3, 5.0, and 6.7%, respectively) (P < 0.05). CONCLUSIONS: Lidocaine combined with dexmedetomidine infusion markedly decreased the occurrence of nausea and PONV at 0-2 h as well as the total 24 h PONV. However, it significantly increased the incidence of mouth dry, bradycardia, and over sedation during the PACU stay period after laparoscopic hysterectomy with general anesthesia. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT03809923 ), registered on January 18, 2019.

Effects of intravenous lidocaine, dexmedetomidine, and their combination on IL-1, IL-6 and TNF-α in patients undergoing laparoscopic hysterectomy: a prospective, randomized controlled trial.

BACKGROUND: Surgical-related inflammatory responses have negative effects on postoperative recovery. Intravenous (IV) lidocaine and dexmedetomidine inhibits the inflammatory response. We investigated whether the co-administration of lidocaine and dexmedetomidine could further alleviate inflammatory responses compared with lidocaine or dexmedetomidine alone during laparoscopic hysterectomy. METHODS: A total of 160 patients were randomly allocated into four groups following laparoscopic hysterectomy: the control group (group C) received normal saline, the lidocaine group (group L) received lidocaine (bolus infusion of 1.5 mg/kg over 10 min, 1.5 mg/kg/h continuous infusion), the dexmedetomidine group (group D) received dexmedetomidine (bolus infusion of 0.5 µg/kg over 10 min, 0.4 µg/kg/h continuous infusion), and the lidocaine plus dexmedetomidine group (group LD) received a combination of lidocaine (bolus infusion of 1.5 mg/kg over 10 min, 1.5 mg/kg/h continuous infusion) and dexmedetomidine (bolus infusion of 0.5 µg/kg over 10 min, 0.4 µg/kg/h continuous infusion). The levels of plasma interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) at different time points were the primary outcomes. Secondary outcomes included hemodynamic variables, postoperative visual analogue scale (VAS) scores, time to first flatus, and incidence of nausea and vomiting after surgery. RESULTS: The levels of plasma IL-1, IL-6, and TNF-α were lower in groups D and LD than in group C and were lowest in group LD at the end of the procedure and 2 h after the operation (P < 0.05). The VAS scores were decreased in groups D and LD compared with group C (P < 0.05). The heart rate (HR) was decreased at the end of the procedure and 2 h after the operation in groups D and LD compared to groups C and L (P < 0.001). The mean blood pressure (MBP) was lower at 2 h after the operation in groups L, D, and LD than in group C (P < 0.001). There was a lower incidence of postoperative nausea and vomiting (PONV) in group LD than in group C (P < 0.05). CONCLUSIONS: The combination of lidocaine and dexmedetomidine significantly alleviated the inflammatory responses, decreased postoperative pain, and led to fewer PONV in patients undergoing laparoscopic hysterectomy. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT03276533 ), registered on August 23, 2017.

Quality Evaluation of Rock Mass Using RMR14 Based on Multi-Source Data Fusion.

The uncertainties in quality evaluations of rock mass are embedded in the underlying multi-source data composed by a variety of testing methods and some specialized sensors. To mitigate this issue, a proper method of data-driven computing for quality evaluation of rock mass based on the theory of multi-source data fusion is required. As the theory of multi-source data fusion, Dempster-Shafer (D-S) evidence theory is applied to the quality evaluation of rock mass. As the correlation between different rock mass indices is too large to be ignored, belief reinforcement and Murphy's average belief theory are introduced to process the multi-source data of rock mass. The proposed method is designed based on RMR14, one of the most widely used quality-evaluating methods for rock mass in the world. To validate the proposed method, the data of rock mass is generated randomly to realize the data fusion based on the proposed method and the conventional D-S theory. The fusion results based on these two methods are compared. The result of the comparison shows the proposed method amplifies the distance between the possibilities at different ratings from 0.0666 to 0.5882, which makes the exact decision more accurate than the other. A case study is carried out in Daxiagu tunnel in China to prove the practical value of the proposed method. The result shows the rock mass rating of the studied section of the tunnel is in level III with the maximum possibility of 0.9838, which agrees with the geological survey report.

[Effects of low-dose dexmedetomidine combined with hydromorphone in postoperative analgesia and on the serum IL-6 and CRP levels of prostate cancer patients].

OBJECTIVE: To explore the effects of low-dose dexmedetomidine (DM) combined with hydromorphone (HM) in postoperative analgesia and on levels of serum interleukin-6 (IL-6) and C-reactive protein (CRP) in PCa patients. METHODS: Using the random number table, we divided 102 PCa patients undergoing radical prostatectomy from January 2019 to November 2020 into a trial group (n = 51) and a control group (n = 51), the former given HM and the latter low-dose DM + HM for postoperative analgesia. We recorded the postoperative resuscitation time, extubation time and pain, perioperative cognitive function, IL-6 and CRP levels, and drug-related adverse reactions of the patients, and compared them between the two groups. RESULTS: There was no statistically significant difference in postoperative resuscitation time and extubation time between the two groups of patients (P > 0.05). The frequency of patient-controlled epidural analgesia (PCEA) compressions was lower in the trial than in the control group within 24 hours after surgery (P < 0.05). The Visual Analogue Scale (VAS) scores were higher in both of the groups at 24 hours than at 4, 12, and 48 hours after surgery (P < 0.05), at 12 hours than at 4 and 48 hours (P < 0.05) and at 4 hours than at 48 hours (P < 0.05), but lower in the trial than in the control group at 4, 12 and 24 hours postoperatively (P < 0.05). No statistically significant difference was observed in the scores of the Mini Mental State Evaluation Scale between the two groups of patients (P > 0.05). The levels of IL-6 and CRP were higher in both of the groups at 24 hours after than before and at 4, 12 and 48 hours after surgery (P < 0.05), at 48 hours after than before and at 4 and 12 hours after surgery (P < 0.05), at 12 hours after than before and at 4 hours after surgery (P <0.05), and at 4 hours after than before surgery (P < 0.05), but lower in the trial than in the control group at 4, 12, 24 and 48 hours postoperatively (P < 0.05). There was no statistically significant difference in the total incidence rate of adverse reactions between the two groups (P > 0.05). CONCLUSIONS: Low-dose dexmedetomidine combined with hydromorphone is a safe and effective option for postoperative analgesia in PCa patients, and it can inhibit the expression of inflammatory factors.

Dexmedetomidine Activation of Dopamine Neurons in the Ventral Tegmental Area Attenuates the Depth of Sedation in Mice.

BACKGROUND: Dexmedetomidine induces a sedative response that is associated with rapid arousal. To elucidate the underlying mechanisms, the authors hypothesized that dexmedetomidine increases the activity of dopaminergic neurons in the ventral tegmental area, and that this action contributes to the unique sedative properties of dexmedetomidine. METHODS: Only male mice were used. The activity of ventral tegmental area dopamine neurons was measured by a genetically encoded Ca indicator and patch-clamp recording. Dopamine neurotransmitter dynamics in the medial prefrontal cortex and nucleus accumbens were measured by a genetically encoded dopamine sensor. Ventral tegmental area dopamine neurons were inhibited or activated by a chemogenetic approach, and the depth of sedation was estimated by electroencephalography. RESULTS: Ca signals in dopamine neurons in the ventral tegmental area increased after intraperitoneal injection of dexmedetomidine (40 µg/kg; dexmedetomidine, 16.917 [14.882; 21.748], median [25%; 75%], vs. saline, -0.745 [-1.547; 0.359], normalized data, P = 0.001; n = 6 mice). Dopamine transmission increased in the medial prefrontal cortex after intraperitoneal injection of dexmedetomidine (40 µg/kg; dexmedetomidine, 10.812 [9.713; 15.104], median [25%; 75%], vs. saline, -0.498 [-0.664; -0.355], normalized data, P = 0.001; n = 6 mice) and in the nucleus accumbens (dexmedetomidine, 8.543 [7.135; 11.828], median [25%; 75%], vs. saline, -0.329 [-1.220; -0.047], normalized data, P = 0.001; n = 6 mice). Chemogenetic inhibition or activation of ventral tegmental area dopamine neurons increased or decreased slow waves, respectively, after intraperitoneal injection of dexmedetomidine (40 µg/kg; delta wave: two-way repeated measures ANOVA, F[2, 33] = 8.016, P = 0.002; n = 12 mice; theta wave: two-way repeated measures ANOVA, F[2, 33] = 22.800, P < 0.0001; n = 12 mice). CONCLUSIONS: Dexmedetomidine activates dopamine neurons in the ventral tegmental area and increases dopamine concentrations in the related forebrain projection areas. This mechanism may explain rapid arousability upon dexmedetomidine sedation.

A Mouse Model of Hepatic Ischemia-Reperfusion Injury Demonstrates Potentially Reversible Effects on Hippocampal Neurons and Postoperative Cognitive Function.

BACKGROUND This study aimed to investigate cognitive function, hippocampal neuronal changes, and the expression of inflammatory cytokines in a mouse model of hepatic ischemia-reperfusion injury. MATERIAL AND METHODS Sixty mice were divided into the sham group, which underwent surgery without vascular occlusion; the I/R1 group, with occlusion of the left hepatic artery and portal vein for 20 min, and reperfusion for 30 min; and the I/R2 group, with occlusion of the left hepatic artery and portal vein for 40 min, and reperfusion for 30 min. At postoperative day 4 and 11, ten mice from each group underwent the Morris water maze (MWM) task. Hippocampal tissues were stained for Nissl bodies. Expression of nuclear factor-κB (NF-κB) and choline acetyltransferase (ChAT) were quantified by immunohistochemistry. Serum tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS Groups I/R1 and I/R2 showed a significantly increased latency in the MWM test between days 5-9, compared with the sham group (P<0.05), with no difference by day 11; the I/R2 group had an initial lower crossing frequency (P<0.05), with no difference by day 18. The I/R2 group showed reduced numbers of Nissl bodies in hippocampal neurons. The I/R1 and I/R2 groups had increased expression of NF-κB, TNF-α, and IL-1ß and decreased ChAT. No differences between the groups were found in levels of NF-κB, TNF-α, IL-1ß, or ChAT by day 18. CONCLUSIONS A mouse model of hepatic ischemia-reperfusion injury showed transient and reversible cognitive dysfunction, changes in hippocampal neurons, and expression of inflammatory cytokines.

Effects of intravenous infusion of lidocaine and dexmedetomidine on inhibiting cough during the tracheal extubation period after thyroid surgery.

BACKGROUND: Intravenous lidocaine and dexmedetomidine treatments have been proposed as methods for inhibiting cough. We compared the efficacy of intravenous lidocaine and dexmedetomidine treatments on inhibiting cough during the tracheal extubation period after thyroid surgery. METHODS: One hundred eighty patients undergoing thyroid surgeries were randomly allocated to the LIDO group (received lidocaine 1.5 mg/kg loading, 1.5 mg/kg/h infusion), the DEX group (received dexmedetomidine 0.5 µg/kg loading, 0.4 µg/kg/h infusion) and the CON group (received saline), with 60 cases in each group. The primary outcomes of cough were recorded. Secondary outcomes included hemodynamic variables, awareness time, volume of drainage, the postoperative visual analogue scale and adverse effects were recorded. RESULTS: The incidence of cough were significantly lower in the LIDO group (28.3%) and the DEX group (31.7%) than that in the CON group (66.7%) (P = 0.000). Additionally, both moderate and severe cough were significantly lower in the LIDO group (13.3%) and the DEX group (13.4%) than these in the CON group (43.4%) (P < 0.05). Compared with the two treatment groups, both mean arterial blood pressure and heart rate were significantly increased in the CON group during tracheal extubation (P < 0.05). Compared with the CON group, the volume of drainage was significantly reduced in the two treatment groups within 48 h after surgery (P < 0.05). compared with the CON group, the postoperative visual analogue scale was significantly lower in groups LIDO and DEX after surgery(P < 0.05). Compared with the LIDO group and the CON group, the time to awareness was longer in the DEX group (P < 0.05). In the DEX group, bradycardia was noted in 35 patients, while no bradycardia was noted in LIDO group and CON group. CONCLUSION: Compared with intravenous infusions of normal saline, both lidocaine and dexmedetomidine had equal effectiveness in attenuating cough and hemodynamic changes during the tracheal extubation period after thyroid surgery, and both of these treatments were able to reduce the volume of postoperative bleeding and provide better analgesic effect after surgery. But intravenous infusions of dexmedetomidine resulted in bradycardia and delayed the time to awareness when compared with lidocaine and normal saline. TRIAL REGISTRATION: ChiCTR1800017482 . (Prospective registered). Initial registration date was 01/08/2018.

Impact of perioperative blood transfusion on gene expression biomarkers in patients with gastrointestinal cancer.

OBJECTIVES: To explore the impacts of perioperative blood transfusion on specific pattern of inflammatory gene expression and nosocomial infections in gastrointestinal cancer patients. METHODS: A total of 60 gastrointestinal cancer patients aged over 27 years were recruited, blood transfusion was administered to 30 patients. The peripheral venous blood was drawn from the 30 patients undergoing transfusions and messenger RNA (mRNA) was extracted from PAXGene tubes collected before surgery and at 48 h following the operation. T-helper cell subtype transcription factors were quantified using quantitative real-time polymerase chain reaction. These genes were selected based on their ability to represent specific immune pathways and their expression level of Th1, Th2 and Th17 and the major Treg-specific TFs T-bet, GATA-3, RORγt and FOXP3 were measured. Postoperative infections were documented using predefined criteria. RESULTS: There were significantly lower in Th1-specific TF T-bet (P < 0.001) mRNA levels and significantly higher in Th2-specifc TF, GATA-3 (P < 0.001) mRNA levels assayed at 48 h. There was significantly lower in T-bet mRNA/GATA-3 (P < 0.001) mRNA ratio assayed at 48 h. There were significantly higher in Th17-specific TF RORγt (P < 0.001) and Treg-specific TF Foxp3 (P < 0.001) mRNA levels assayed at 48 h. Patients receiving a blood transfusion were more likely to develop postoperative infections (P = 0.02). CONCLUSION: There is an association between an immunosuppressive pattern of gene expressions and blood transfusion. This gene expression profile includes a reduction in the activity of T helper cell type 1 (Th1) pathways in those patients receiving a blood transfusion. Furthermore, blood transfusion was associated with an increased susceptibility to nosocomial infections.

Bispectral Index Monitoring During Anesthesia Promotes Early Postoperative Recovery of Cognitive Function and Reduces Acute Delirium in Elderly Patients with Colon Carcinoma: A Prospective Controlled Study using the Attention Network Test.

BACKGROUND Bispectral index (BIS) monitoring can reduce the duration of anesthesia. This study aimed to evaluate the effects of BIS monitoring during surgery for resection of colon carcinoma in elderly patients using the Attention Network Test (ANT) to study alerting, orienting, and executive functions, and the Confusion Assessment Method (CAM). MATERIAL AND METHODS Eighty-one patients (65-75 years) underwent radical surgery for colon carcinoma with general intravenous anesthesia, propofol (6-8 mg/kg/h), vecuronium (0.03-0.05 mg/kg/min), and remifentanil (0.1-0.2 µg/kg/min). The BIS group (n=41) underwent adjustment of anesthesia to maintain a BIS value between 40-60; the non-BIS group (N=40) underwent standard intraoperative hemodynamic monitoring. Primary endpoints were alerting, orienting, and executive functions assessed pre-operatively and on postoperative days 1 and 5 using the ANT; the secondary endpoint was delirium during the first five postoperative days, assessed using the CAM. RESULTS Propofol and remifentanil doses were significantly lower in the BIS group compared with the non-BIS group (P<0.001). Alerting, orienting, and executive functions showed no differences between the two groups pre-operatively but were impaired in both groups on postoperative day 1 compared with pre-operative levels (P<0.001). On postoperative day 5, alerting (P=0.607) and orienting (P=0.851) functions recovered in the BIS group but remained impaired in the non-BIS group (P<0.001). Delirium was significantly lower in the BIS group compared with the non-BIS group (17.5% vs. 27.5%) (P<0.001). CONCLUSIONS BIS-guided anesthesia was associated with reduced anesthetic exposure, early postoperative recovery of alerting and orienting functions, and reduced postoperative delirium.

Can Mandibular Condylar Mobility Sonography Measurements Predict Difficult Laryngoscopy?

BACKGROUND: Limited mandibular condylar mobility plays an important role in difficult laryngoscopy. Indirect assessment methods, such as mouth opening, have been proven to be useful predictors of difficult laryngoscopy. Sonography is a new direct assessment method for the limited mandibular condylar mobility. However, whether this method could be used in predicting difficult laryngoscopy still remains unknown. This study aimed to observe its ability to predict difficult laryngoscopy. METHODS: Adult patients who were administered tracheal intubations for elective surgery under general anesthesia were enrolled in the study. Mandibular condylar mobility was assessed by sonography through condylar translation measurements. Beside mouth opening, other indirect variables that correlated with temporomandibular joint mobility, such as mandibular protrusion distance, upper lip bite test, and whether the condyle-tragus distance was <1 finger breadth, were also evaluated before anesthesia. The primary outcome was difficult laryngoscopy defined as the Cormack-Lehane level 3 or 4. RESULTS: A total of 484 patients were prospectively included, and difficult laryngoscopy was reported in 41 patients. The condylar translation prediction criterion for difficult laryngoscopy was ≤10 mm. The condylar translation was correlated with Cormack-Lehane level (Spearman correlation coefficient, -0.46; 99% confidence interval [CI], -0.55 to -0.36) and owned the highest area under the receiver operating characteristic curve (0.93; 99% CI, 0.90 to 0.96, compared with that of the other predictors, P < .001) with difficult laryngoscopy. The condylar translation ≤10 mm was with a considerable κ value (κ = 0.52; 99% CI, 0.37 to 0.67) to difficult laryngoscopy and proved to be an independent predictor by a multivariate logistic regression. CONCLUSIONS: Compared with indirect assessments, such as mouth opening and other parameters, mandibular condylar mobility, as assessed directly using sonography, was correlated with difficult laryngoscopy and demonstrated an independent and notably predictive property.

Tramadol differentially regulates M1 and M2 macrophages from human umbilical cord blood.

Tramadol is an analgesic drug and relieves pain through activating µ-opioid receptors and inhibiting serotonin and noradrenaline reuptake. Emerging evidence shows that it also stimulates immune cells, including NK cells, splenocytes, and lymphocytes, and elevates IL-2 production. However, it remains unknown whether and how tramadol directly affects macrophages. To answer these questions, we collected human umbilical cord blood, isolated macrophages, and examined their responses to tramadol. Although tramadol did not alter resting macrophages and the antigen-presenting function in lipopolysaccharide-activated macrophages, it regulated M1 and M2 macrophages, which are, respectively, transformed by IFN-γ and IL-4. Interestingly, tramadol inhibits production and secretion of cytokines in M1 macrophages, but facilitates the production of inflammation-responding molecules, synthesized in M2 macrophages. We also found that STAT6 cascade pathway in M2 macrophages was significantly enhanced by tramadol. Therefore, this study reveals that tramadol regulates inflammation by inhibiting M1 macrophages (killing process), but promoting the function of M2 macrophages (healing process).

Effects of dexmedetomidine on emergence delirium in pediatric cardiac surgery.

BACKGROUND: The present study aimed to investigate the effects of dexmedetomidine on emergence delirium (ED) in pediatric patients undergoing cardiac surgery. METHODS: Fifty children of both sexes aged 1-6 years weighing 10-25 kilograms, with American Society of Anesthesiologists (ASA) physical status grade II, undergoing sevoflurane-based general anesthesia for elective cardiac surgery, were randomly assigned to two groups. The dexmedetomidine group (group D, N.=25) received 0.5 µg/kg of dexmedetomidine over 10 minutes, followed by an infusion at 0.5 µg/kg/h until the end of the surgery, whereas the saline group (group S, N.=25) received volume-matched normal saline immediately after the induction of anesthesia. Blood samples were taken preoperatively (T0), at different time points during surgery (T1-T5), and during the postoperative period (T6-T7) to determine serum melatonin, cortisol, norepinephrine, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and blood glucose levels. In the cardiac intensive care unit (CICU), the incidence of ED was assessed with a 5-point scale, and the severity of ED was assessed with the Pediatric Anesthesia Emergence Delirium scale (PAED) every two hours for the first 24 hours after surgery. ED was considered when the 5-point scale score was ≥4 for more than 5 minutes, or the PAED score was ≥10. RESULTS: Based on comparable demographic profiles, the scores of the 5-point scale and PAED Scale were significantly lower in group D compared with group S (P=0.028 and P=0.009, respectively). In addition, the fluctuation in the level of melatonin was significantly less in group D. Serum cortisol, norepinephrine, IL-6, TNF-α and glucose levels were increased in the two groups, but these increases were significantly less in group D than in group S. The consumption of sevoflurane during anesthesia was significantly less in group D (P=0.0002). The postoperative consumption of fentanyl was less in group D (P=0.04), whereas the pain scores were not significantly different (P=0.502). Extubation time was significantly delayed in group D compared with group S (P=0.032), whereas CICU and hospital stay were comparable between the two groups. CONCLUSIONS: Continuous intraoperative infusions of dexmedetomidine in pediatric patients undergoing cardiac surgery reduce sevoflurane requirements and decrease the incidence of ED, which is associated with decreasing plasma melatonin levels and surgical stress.

Clinical efficacy of dexmedetomidine in the diminution of fentanyl dosage in pediatric cardiac surgery.

BACKGROUND: This study aims to explore the clinical efficacy of dexmedetomidine (DEX) in the diminution of fentanyl dosage in pediatric cardiac surgery based on some clinical and biochemical parameters. METHODS: Fifty pediatric patients (American Society of Anesthesiologists II), 1-6 years old, were randomly allocated into two groups: group F (control group), in which patients received normal saline and high dosage of fentanyl (30 µg/kg), and group D, in which patients were given DEX and low dosage of fentanyl (15 µg/kg). Some hemodynamic and clinical parameters of the two groups were recorded. Furthermore, stress hormone (serum cortisol, norepinephrine, blood glucose) levels and cytokine (interleukin 6, tumor necrosis factor alpha) levels in the two groups were compared with each other. RESULTS: Stress hormone levels, cytokine levels, hemodynamic parameters and the consumption of sevoflurane did not differ between the two groups. Meanwhile, the extubation time was significantly shorter in Group D than F (P<0.05). CONCLUSIONS: The results indicated that low dosage of fentanyl supplemented with DEX almost had the same anesthesia effects and inflammation extent compared with high dose of fentanyl, which suggested that infusion DEX might decrease fentanyl consumption in pediatric cardiac surgery.

Determination of the median effective dose (ED50) of bupivacaine and ropivacaine unilateral spinal anesthesia : Prospective, double blinded, randomized dose-response trial.

BACKGROUND: Unilateral spinal anesthesia (USpA) has been reported to potentiate spinal anaesthesia and is used in geriatric patients. The purpose of this study was to determine the median effective dose (ED50) of 0.5% hypobaric bupivacaine and 0.5% hypobaric ropivacaine USpA for geriatric patients (age ≥ 70 years) undergoing elective hip replacement surgery. METHODS: A total of 60 geriatric patients (age ≥ 70 years) undergoing elective hip replacement surgery were enrolled in this study. The patients were randomized into 2 groups to receive either intrathecal 0.5% hypobaric bupivacaine USpA (group B) or 0.5% hypobaric ropivacaine USpA (group R). Effective anesthesia was defined as a T10 sensory blockade level maintained for more than 60 min, and a Bromage score of 3 on the operation side within 10 min after injection with no additional epidural anesthetic required during surgery. The ED50 of 0.5% hypobaric bupivacaine and 0.5% hypobaric ropivacaine was calculated using the Dixon and Massey formula. RESULTS: No significant differences were found between the two groups in terms of demographic data. The ED50 of 0.5% hypobaric bupivacaine USpA was 4.66 mg (95% confidence interval CI 4.69-4.63 mg) mg and that of 0.5% hypobaric ropivacaine USpA was 6.43 mg (95% CI 6.47-6.39 mg) for geriatric patients undergoing hip replacement surgery. CONCLUSION: We find the ED50 were lower, and the ED50 of 0.5% hypobaric bupivacaine and ropivacaine was 4.66 mg (95% CI 4.69-4.63 mg) and 6.43 mg (95% CI 6.47-6.39 mg), respectively, for USpA in geriatric patients (age ≥ 70 years) undergoing elective hip replacement surgery.

Identification of miRNAs Involved in the Protective Effect of Sevoflurane Preconditioning Against Hypoxic Injury in PC12 Cells.

The mechanism of sevoflurane preconditioning-induced neuroprotection is poorly understood. This study was aimed at identifying microRNAs (miRNAs) involved in the protective effect of sevoflurane preconditioning against hypoxic injury using the miRCURYTM LNA Array. The screened differentially expressed miRNAs were further validated using qRT-PCR. Finally, after transfection of miRNA (miR-101a or miR-34b) mimics or inhibitor, MTT and flow cytometry assays were used to evaluate cell survival and apoptosis in sevoflurane preconditioning. qRT-PCR confirmed the changes in expression of differentially expressed miRNAs that were screened by the microarray: down-regulation of rno-miR-101a, rno-miR-106b, and rno-miR-294 and up-regulation of rno-miR-883, rno-miR-16, and rno-miR-34b. MiR-101a and miR-34b were the most differentially expressed miRNAs. Sevoflurane preconditioning-inhibited apoptosis and preconditioning-enhanced cell viability of PC12 cells were significantly attenuated by transfection of miR-101a mimetic or miR-34b inhibitors, but were significantly enhanced by transfection of miR-34b mimetic. Therefore, a number of miRNAs, including miR-101a and miR-34b, might play important roles in the neuroprotection induced by sevoflurane preconditioning. Such miRNAs might provide novel targets for preventive and therapeutic strategies against cerebral ischemia-reperfusion injury.