Effect of continuous measurement and adjustment of endotracheal tube cuff pressure on postoperative sore throat in patients undergoing gynecological laparoscopic surgery: a randomized controlled trial.

BACKGROUND: Postoperative sore throat (POST) is a common complication following endotracheal tube removal, and effective preventive strategies remain elusive. This trial aimed to determine whether actively regulating intraoperative cuff pressure below the tracheal capillary perfusion pressure threshold could effectively reduce POST incidence in patients undergoing gynecological laparoscopic procedures. METHODS: This single-center, randomized controlled superiority trial allocated 60 patients scheduled for elective gynecological laparoscopic procedures into two groups: one designated for cuff pressure measurement and adjustment (CPMA) group, and a control group where only cuff pressure measurement was conducted without any subsequent adjustments. The primary outcome was POST incidence at rest within 24 h post-extubation. Secondary outcomes included cough, hoarseness, postoperative nausea and vomiting (PONV) incidence, and post-extubation pain severity. RESULTS: The incidence of sore throat at rest within 24 h after extubation in the CPMA group was lower than in the control group, meeting the criteria for statistically significant superiority based on a one-sided test (3.3% vs. 26.7%, P < 0.025). No statistically significant differences were observed in cough, hoarseness, or pain scores within 24 h post-extubation between the two groups. However, the CPMA group had a higher incidence of PONV compared to the control group. Additionally, the control group reported higher sore throat severity scores within 24 h post-extubation. CONCLUSIONS: Continuous monitoring and maintenance of tracheal tube cuff pressure at 18 mmHg were superior to merely monitoring without adjustment, effectively reducing the incidence of POST during quiet within 24 h after tracheal tube removal in gynecological laparoscopic surgery patients. TRIAL REGISTRATION: The study was registered at www.chictr.org.cn (ChiCTR2200064792) on 18/10/2022.

Transforming Growth Factor ß1 Ameliorates Microglial Activation in Perioperative Neurocognitive Disorders.

Perioperative neurocognitive disorder (PND) is a common complication of surgery and anesthesia, especially among older patients. Microglial activation plays a crucial role in the occurrence and development of PND and transforming growth factor beta 1 (TGF-ß1) can regulate microglial homeostasis. In the present study, abdominal surgery was performed on 12-14 months-old C57BL/6 mice to establish a PND model. The expression of TGF-ß1, TGF-ß receptor 1, TGF-ß receptor 2, and phosphor-smad2/smad3 (psmad2/smad3) was assessed after anesthesia and surgery. Additionally, we examined changes in microglial activation, morphology, and polarization, as well as neuroinflammation and dendritic spine density in the hippocampus. Behavioral tests, including the Morris water maze and open field tests, were used to examine cognitive function, exploratory locomotion, and emotions. We observed decreased TGF-ß1 expression after surgery and anesthesia. Intranasally administered exogenous TGF-ß1 increased psmad2/smad3 colocalization with microglia positive for ionized calcium-binding adaptor molecule 1. TGF-ß1 treatment attenuated microglial activation, reduced microglial phagocytosis, and reduced surgery- and anesthesia-induced changes in microglial morphology. Compared with the surgery group, TGF-ß1 treatment decreased M1 microglial polarization and increased M2 microglial polarization. Additionally, surgery- and anesthesia-induced increase in interleukin 1 beta and tumor necrosis factor-alpha levels was ameliorated by TGF-ß1 treatment at postoperative day 3. TGF-ß1 also ameliorated cognitive function after surgery and anesthesia as well as rescue dendritic spine loss. In conclusion, surgery and anesthesia induced decrease in TGF-ß1 levels in older mice, which may contribute to PND development; however, TGF-ß1 ameliorated microglial activation and cognitive dysfunction in PND mice.

Gender differences in the prevalence and clinical correlates of thyroid dysfunction in patients with first-episode and drug-naïve major depressive disorder with comorbid suicide attempts: a large cross-sectional study.

BACKGROUND: Gender differences in patients with major depressive disorder (MDD) are commonly reported; however, gender differences in first-episode and drug-naïve (FEDN) MDD patients with comorbid suicide attempts have not been reported. This study aimed to examine potential gender differences in the prevalence and clinical correlates of comorbid abnormal thyroid function (ATF) in FEDN MDD patients with comorbid suicide attempts. METHODS: A cross-sectional study of 1718 FEDN MDD patients was conducted. The demographic and clinical data were collected. The Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA) and Positive and Negative Syndrome Scale (PANSS) were used to assess depression, anxiety and psychotic symptoms, respectively. Thyroid function parameters and blood glucose levels were measured. RESULTS: There was no gender difference in the prevalence of ATF between male (78.6%, 88/112) and female MDD patients (74.8%, 175/234) with comorbid suicide attempts. In the male and female subgroups, duration of disease, HAMD score, HAMA score, anti-thyroglobulin (TgAb), thyroid peroxidases antibody (TPOAb), diastolic blood pressure (DBP), systolic blood pressure (SBP), glucose level and the rate of psychotic symptoms were higher in patients with ATF than those without ATF in MDD with comorbid suicide attempt (all P < 0.05). There was a gender main effect only on SBP (F = 7.35, P = 0.007). Furthermore, binary logistic regression analysis showed that HAMD score, DBP and glucose levels were independently with ATF in both male and female MDD patients with comorbid suicide attempts. However, anxiety symptoms, psychotic symptoms and TPOAb levels were significantly associated with ATF only in female MDD patients with comorbid suicide attempts. CONCLUSION: Our study showed no gender differences in the prevalence of ATF in FEDN MDD patients with comorbid suicide attempts. Depression, DBP and glucose levels were associated with ATF in both male and female MDD patients with comorbid suicide attempts, whereas anxiety, psychotic symptoms and TPOAb level were correlated with ATF only in female MDD patients with suicide attempts.

Prevalence and clinical profile of abnormal glucose in first-episode and drug-naïve patients with major depressive disorder with comorbid abnormal thyroid function: a large-scale cross-sectional study.

BACKGROUND: The associated factors of abnormal glucose in patients with major depressive disorder (MDD) with comorbid abnormal thyroid function (ATF) remain unclear. To the best of our knowledge, this is the first study with a large sample size that examines the risk factors of abnormal glucose in first-episode drug-naïve (FEDN) MDD patients comorbid with ATF and includes clinical correlates and thyroid hormone levels. METHODS: A total of 1718 FEDN MDD patients were recruited. The Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) positive subscale were used to evaluate the symptoms of patients. Fasting blood glucose concentration and thyroid hormone levels were measured. RESULTS: The prevalence of abnormal glucose in MDD patients with comorbid ATF was 47.3%, which was 4.25 times higher than that in MDD patients without ATF (17.4%). Compared to those ATF patients without abnormal glucose, ATF patients with abnormal glucose scored higher on HAMD, HAMA and PANSS positive subscale, had a higher rate of suicide attempts, severe anxiety and psychotic symptoms, and had higher levels of thyroid-stimulating hormone (TSH), and thyroid peroxidases antibody (TPOAb) which were also correlated with abnormal glucose in MDD patients comorbid ATF (all P < 0.05). The combination of HAMD score and TSH could differentiate abnormal glucose from ATF. Further, TSH was independence-related with the concentration of fasting blood glucose in MDD patients with comorbid ATF. CONCLUSION: Our results demonstrate a high prevalence of abnormal glucose in MDD patients with comorbid ATF. Some clinical and thyroid function-related variables may be associated with abnormal glucose in MDD patients with comorbid ATF.

Airway management for a patient with tracheobronchomegaly undergoing lobectomy: a case report.

BACKGROUND: Tracheobronchomegaly (TBM) is a rare disorder mainly characterized by dilatation and malacia of the trachea and major bronchi with diverticularization. This will be a great challenge for airway management, especially in thoracic surgery requiring one-lung ventilation. Using a laryngeal mask airway and a modified double-lumen Foley catheter (DFC) as a "blocker" may achieve one-lung ventilation. This is the first report introducing this method in a patient with TBM. CASE PRESENTATION: We present a 64-year-old man with TBM receiving left lower lobectomy. Preoperative chest computed tomography demonstrated a prominent tracheobronchial dilation and deformation with multiple diverticularization. The most commonly used double-lumen tube or bronchial blocker could not match the distorted airways. After general anesthesia induction, a 4# laryngeal mask was inserted, through which the modified DFC was positioned in the left main bronchus with the guidance of a fiberoptic bronchoscope. The DFC balloon was inflated with 10 ml air and lung isolation was achieved without any significant air leak during one-lung or two-lung ventilation. However, the collapse of the non-dependent lung was delayed and finally achieved by low-pressure artificial pneumothorax. The surgery was successful and the patient was extubated soon after the surgery. CONCLUSIONS: Using a laryngeal mask airway with a modified double-lumen Foley catheter acted as a bronchial blocker could be an alternative method to achieve lung isolation.

Ginkgolide B improved postoperative cognitive dysfunction by inhibiting microgliosis-mediated neuroinflammation in the hippocampus of mice.

BACKGROUND: Postoperative cognitive dysfunction (POCD) are a common complication of the central nervous system following surgery and anesthesia. The specific pathogenesis and effective therapeutics of POCD need to be further studied. Ginkgolide B (GB), a platelet-activating factor receptor-specific antagonist, has been suggested to have strong anti-inflammatory effects. Here we tested the effects and mechanism of GB on POCD of aged rats. METHODS: Neurobehavioral tests were used to investigate the effect of GB pretreatment on POCD. The hippocampus were harvested to test the expression of proinflammatory cytokines by ELISA. The expression of the microglial marker ionized calcium-binding adaptor molecule-1 (Iba-1) in the hippocampus was evaluated by western blot assay and immunohistochemistry. A Nissl staining experiment was used to detect the neuronal numbers in the hippocampus. RESULTS: Surgery might result in the overexpression of platelet activating factor (PAF) in the plasma and hippocampus and might cause hippocampus-dependent memory impairment. GB pretreatment, inhibited the activation of microglia, reduced the levels of IL-1ß and TNF-α, decreased the loss of neurons after surgery, and prevented POCD in aged rats. CONCLUSION: Our findings suggested that PAF was involved in the development of POCD. Improvement of POCD by PAF antagonist GB was associated with the inhibition of microgliosis-mediated neuroinflammation and neuronal apoptosis in aged rats.

Gene Signatures Associated with Temporal Rhythm as Diagnostic Markers of Major Depressive Disorder and Their Role in Immune Infiltration.

Temporal rhythm (TR) is involved in the pathophysiology and treatment response of major depressive disorder (MDD). However, there have been few systematic studies on the relationship between TR-related genes (TRRGs) and MDD. This study aimed to develop a novel prognostic gene signature based on the TRRGs in MDD. We extracted expression information from the Gene Expression Omnibus (GEO) database and retrieved TRRGs from GeneCards. Expressed genes (TRRDEGs) were identified differentially, and their potential biological functions were analyzed. Subsequently, association analysis and receiver operating characteristic (ROC) curves were adopted for the TRRDEGs. Further, upstream transcription factor (TF)/miRNA and potential drugs targeting MDD were predicted. Finally, the CIBERSORT algorithm was used to estimate the proportions of immune cell subsets. We identified six TRRDEGs that were primarily involved in malaria, cardiac muscle contraction, and the calcium-signaling pathway. Four genes (CHGA, CCDC47, ACKR1, and FKBP11) with an AUC of >0.70 were considered TRRDEGs hub genes for ROC curve analysis. Outcomes showed that there were a higher ratio of T cells, gamma-delta T cells, monocytes, and neutrophils, and lower degrees of CD8+ T cells, and memory resting CD4+ T cells in TRRDEGs. Four new TRRDEG signatures with excellent diagnostic performance and a relationship with the immune microenvironment were identified.

Activation of CD200-CD200R1 Axis Attenuates Perioperative Neurocognitive Disorder Through Inhibition of Neuroinflammation in Mice.

Perioperative neurocognitive disorder (PND) is the mild cognitive impairment associated with surgery and anesthesia. It is a common surgical complication in the elderly. An important mechanism of PND is the surgically induced neuroinflammation. The interaction between the neuronal surface protein CD200 and its receptor in microglia, CD200R1, is an important regulatory pathway to control neuroinflammation. However, the potential role of the CD200-CD200R1 pathway in the acute period of PND has not been fully investigated. In this study, in a PND mouse model, we first measured the protein expression level of CD200, CD200R1, and the related pro- and anti-inflammatory cytokines in the hippocampus. Then, we investigated cognitive function, neuroinflammation and postsynaptic density protein 95 (PSD-95) expression after the injection of CD200-Fc (agonist), CD200R1-Fc (antagonist) or IgG1-Fc (vehicle) into lateral ventricle in PND models. Compared with the control group, the expression of CD200 was up-regulated at day 1 after surgery in PND models. The injection of the CD200-Fc into the lateral ventricle could mitigate primed neuroinflammation and cognitive decline, increase the expression of PSD-95 at day 1 after surgery in PND models. In conclusion, we have demonstrated that CD200-CD200R1 signaling was involved in the acute inflammatory process of PND, and activating CD200R1 can inhibit neuroinflammation and attenuate PND. Thus, the CD200-CD200R1 axis is a potential novel target for PND prevention and treatment.

Desflurane and Surgery Exposure During Pregnancy Decrease Synaptic Integrity and Induce Functional Deficits in Juvenile Offspring Mice.

Anesthesia in pregnant women may cause adverse effects in the hippocampus of unborn babies and fetal brain development. The mechanisms underlying pathological changes resulting from anesthetics are unclear. This study tested the hypothesis that exposure to desflurane during pregnancy may impair cognition and memory functions of juvenile offspring. Pregnant mice (at gestational day 14) were administered 10% desflurane for 3 h and compared to sham control and sciatic nerve hemi-transection surgery. Hippocampal tissues of both fetal (G14) and offspring mice (postnatal day 31) were collected and analyzed by real-time qPCR and Western blot. Functional tests were performed to assess fear and memory functions in offspring mice. Primary hippocampal neuronal cultures from postnatal day 0 (without desflurane exposure) were examined for neuronal and synaptic development under desflurane treatment in vitro. In this acute experiment, we showed that neuronal cultures exposed to desflurane significantly increased interleukin (IL)-6 expression and apoptotic gene caspase-3 activation. Desflurane exposure significantly reduced PSD-95 expression in hippocampal neurons. Similar changes were observed in hippocampal tissues from juvenile offspring mice. Inhaled desflurane impaired memory functions in offspring mice compared to sham control. These mice displayed higher sensitivity to fear conditioning. Neurons isolated from the mice exposed to desflurane exhibited significantly lower levels of synaptophysin expression. These results suggest that anesthetic exposure together with surgery during pregnancy may induce detrimental effects in juvenile offspring mice via the induction of cell death and disruption of synaptic integrity.

Electroencephalography-Guided Anesthetic Delivery for Preventing Postoperative Delirium in Adults: An Updated Meta-analysis.

BACKGROUND: Postoperative delirium is a major debilitating complication for patients and is associated with poor outcomes. Previous studies have suggested that excessive general anesthesia may lead to postoperative delirium. Electroencephalography (EEG)-based monitors have been administered in clinical practice in an attempt to deliver appropriate anesthesia. The aim of this updated meta-analysis was to evaluate the current body of research concerning the effects of EEG-based monitor on postoperative delirium. METHODS: We conducted a meta-analysis of randomized controlled trials of the effect of processed EEG monitor on postoperative delirium as the primary outcome. The search was performed in CENTRAL, MEDLINE, and EMBASE, with no language restrictions from inception until June 23, 2019. Two independent reviewers screened records and full-text articles for inclusion. Data extraction and risk-of-bias assessment were conducted by 3 independent reviewers. Random-effects models were used to calculate combined-effect estimates. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence. RESULTS: Of 5904 records screened, 5 studies met our inclusion criteria, including 3612 patients. Meta-analysis revealed no significant effect of EEG-based monitors on postoperative delirium (risk ratio [RR], 0.79; 95% confidence interval [CI], 0.60-1.05; I = 73%). The results showed a statistically significant reduction in intensive care unit (ICU) length of stay (3 studies, weight mean difference [WMD] -0.29 days; 95% CI, -0.53 to -0.05) in patients with EEG monitored. EEG-guided anesthesia did not have a statistically significant difference in all-cause mortality (3 studies, RR, 0.63; 95% CI, 0.31-1.29) and hospital length of stay (4 studies, WMD -0.61 days; 95% CI, -1.34 to 0.11). Few studies investigated the effects of EEG-guided anesthesia on perioperative major nonneurological complications and did not come up with promising results. CONCLUSIONS: The current evidence is not sufficient to support the prevention effects of EEG monitor on postoperative delirium. More robustly designed and well-conducted studies with emphasis on this matter are warranted.

The effectiveness of PC6 acupuncture in the prevention of postoperative nausea and vomiting in children: A systematic review and meta-analysis.

BACKGROUND: A growing number of studies have demonstrated the effectiveness of acupuncture in preventing and treating postoperative nausea and vomiting. Here, we used meta-analysis to confirm these benefits in children and to determine the optimal time to perform this treatment. METHODS: Four databases (MEDLINE, EMBASE, CENTRAL, and Chinese Database of Biology and Medicine) were searched from inception until January 16, 2019. We included randomized controlled trials for evaluating the effectiveness of acupuncture in the prevention and treatment of postoperative nausea and vomiting during the early stage (0-4 hours) and within 24 hours postoperatively in pediatrics. Control groups received standardized care control or standardized care combined with sham control. RESULTS: Sixteen literatures and 1773 patients undergoing general anesthesia were included in the study. The results indicated that acupuncture was effective in reducing postoperative vomiting, both during the first 4 hours (RR = 0.47, 95% CI 0.26, 0.84; low quality) and within 24 hours postoperatively (RR = 0.74, 95% CI 0.60, 0.91; low quality). Stratifying by the timing of acupuncture, acupuncture was effective in reducing the first 4 hours (RR = 0.34, 95% CI 0.18, 0.64; moderate quality), and 0-24 hours postoperative vomiting (RR = 0.81, 95% CI 0.70, 0.93; moderate quality) when performed before and during anesthesia, respectively. Further, the RR value was more robust when acupuncture was performed before anesthesia. Acupuncture was also effective in treating 0-24 hours postoperative nausea (RR = 0.73, 95% CI 0.60, 0.88; moderate quality) and in reducing the utilization of remedies during the first 4 hours (RR = 0.64, 95% CI 0.45, 0.89; moderate quality). CONCLUSION: Acupuncture reduces the incidence of postoperative nausea and vomiting as well as the utilization of antiemetic remedies, particularly during the first 4 hours following the operation. Acupuncture performed before anesthesia was demonstrated to be the most ideal intervention time for children.

Intraoperative cell salvage is associated with reduced allogeneic blood requirements and has no significant impairment on coagulation function in patients undergoing cesarean delivery: a retrospective study.

OBJECTIVE: The aim of the study is to examine the association between Intraoperative cell salvage (ICS), allogeneic blood transfusion (ABT) and coagulation function in obstetrics. METHODS: A total of 486 pregnant women undergoing cesarean delivery, of whom 157 were enrolled in this retrospective study. Patients were divided into ICS group (n = 101, ICS used during operation) and control group (n = 56, ICS not used during operation). Clinical data, including plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and thrombin time (TT) levels, were collected from all patients preoperatively (within 12-24 h) and postoperatively (within 6-12 h) and analyzed by t test, two-way repeated-measures ANOVA and Spearman's correlation. RESULTS: The use of ICS is associated with lower requirement rate for ABT (P < .001), while the blood loss was similar between the two groups (P = .990). Mean volume of ICS transfusion was 432.65 mL. Compared to preoperative values, the postoperative PT and APTT levels were significantly increased, while Fib was decreased in the two groups (all P < .01). No significant difference in coagulation function was observed between groups in preoperative and postoperative phase (P > .05). Furthermore, PT, APTT and TT after surgery were not correlated with the transfused volume of salvaged blood (P > .05) while the levels of Fib were negatively correlated with the volume (P < .01). In addition, there were no transfusion reactions in both two groups. CONCLUSIONS: Intraoperative cell salvage is correlated with reduced allogeneic blood requirements but did not impair blood coagulation significantly in patients undergoing cesarean delivery.

Variation of bispectral index in children aged 1-12 years under propofol anesthesia: an observational study.

BACKGROUND: The use of the bispectral index (BIS) is widespread in pediatric anesthesia, but few studies have attempted to perform a detailed evaluation of how BIS varies according to age in children under propofol anesthesia. This prospective study aimed to explore the exact relationship between BIS value and the age of 1- to 12-year-old children under propofol anesthesia. METHODS: This study enrolled 165 children (1 < yr. ≤ 12), scheduled for surgery under anesthesia, and divided them into 11 age groups. Of the 165 participants, 157 completed the study protocol. All patients were anesthetized with propofol for over 30 s. An observation period of 4 min followed. BIS values were recorded at 0 (immediately after propofol injection), 30, 40, 50, 60, 90, 120, 180, and 240 s after the injection. BIS values at each time point corresponding to the 11 age groups were compared using repeated measures ANOVA. RESULTS: BIS values significantly differed among the nine time points (p < 0.01) as well as among the different age groups (p < 0.01) after propofol administration. Post-hoc Bonferroni tests showed a difference in BIS values between groups 1-4 (1 < yr. ≤ 5) and groups 5-11(5 < yr. ≤ 12). BIS values were lower in the latter than in the former, from 50 to 240 s. The minimum BIS values in group 1 < yr. ≤ 5 and in group 5 < yr. ≤ 12 were recorded at 60 s as 49 ± 17 and 35 ± 14, respectively. CONCLUSIONS: During propofol anesthesia, the BIS values were closely related to age, which can be divided into two groups: 1 < yr. ≤ 5 and 5 < yr. ≤ 12. BIS values of the older age group were lower than those of the younger age group at the same time points. TRIAL REGISTRATION: Registration number: chictr-roc-16008630 . Registered on 12 June 2016. Retrospectively registered.

Complement activation contributes to perioperative neurocognitive disorders in mice.

BACKGROUND: The complement system plays an important role in many neurological disorders. Complement modulation, including C3/C3a receptor signaling, shows promising therapeutic effects on cognition and neurodegeneration. Yet, the implications for this pathway in perioperative neurocognitive disorders (PND) are not well established. Here, we evaluated the possible role for C3/C3a receptor signaling after orthopedic surgery using an established mouse model of PND. METHODS: A stabilized tibial fracture surgery was performed in adult male C57BL/6 mice under general anesthesia and analgesia to induce PND-like behavior. Complement activation was assessed in the hippocampus and choroid plexus. Changes in hippocampal neuroinflammation, synapse numbers, choroidal blood-cerebrospinal fluid barrier (BCSFB) integrity, and hippocampal-dependent memory function were evaluated after surgery and treatment with a C3a receptor blocker. RESULTS: C3 levels and C3a receptor expression were specifically increased in hippocampal astrocytes and microglia after surgery. Surgery-induced neuroinflammation and synapse loss in the hippocampus were attenuated by C3a receptor blockade. Choroidal BCSFB dysfunction occurred 1 day after surgery and was attenuated by C3a receptor blockade. Administration of exogenous C3a exacerbated cognitive decline after surgery, whereas C3a receptor blockade improved hippocampal-dependent memory function. CONCLUSIONS: Orthopedic surgery activates complement signaling. C3a receptor blockade may be therapeutically beneficial to attenuate neuroinflammation and PND.

Changes in duration of action of rocuronium following decrease in hepatic blood flow during pneumoperitoneum for laparoscopic gynaecological surgery.

BACKGROUND: A moderate insufflation pressure and deep neuromuscular blockade (NMB) have been recommended in laparoscopic surgery in consideration of the possible reduction in splanchnic perfusion due to the CO2-pneumoperitoneum. Since the liver is the major organ for rocuronium metabolism, the question of whether NMB of rocuronium would change with the variation of liver perfusion during pneumoperitoneum during laparoscopic surgery merits investigation. METHODS: In this prospective study, a total of sixty female patients scheduled for either selective laparoscopic gynaecological surgery (group laparoscopy) or laparotomy for gynaecological surgery (group control) were analyzed. Rocuronium was administered with closed-loop feedback infusion system, which was also applied to monitor NMB complied with good clinical research practice (GCRP). The onset time, clinical duration, and recovery index were measured. Hepatic blood flow was assessed by laparoscopic intraoperative ultrasonography before insufflation/after entering the abdominal cavity (T1), 5 min after insufflation in the Trendelenburg position/5 min after skin incision (T2), 15 min after insufflation in the Trendelenburg position/15 min after skin incision (T3), 30 min after insufflation in the Trendelenburg position/30 min after skin incision (T4), and 5 min after deflation/before closing the abdomen (T5) in group laparoscopy/group control respectively. The relationship between the clinical duration of rocuronium and portal venous blood flow was analyzed using linear or quadratic regression. RESULT: The clinical duration and RI of rocuronium were both prolonged significantly in group laparoscopy (36.8 ± 8.3 min; 12.8 ± 5.5 min) compared to group control (29.0 ± 5.8 min; 9.8 ± 4.0 min) (P < 0.0001; P = 0.018). A significant decrease was found in portal venous blood flow during the entire pneumoperitoneum period in group laparoscopy compared with group control (P < 0.0001). There was a significant correlation between the clinical duration of rocuronium and portal venous blood flow (Y = 51.800-0.043X + (1.86E-005) X 2; r2 = 0.491; P < 0.0001). CONCLUSION: Rocuronium-induced NMB during laparoscopic gynaecological surgery might be prolonged due to the decrease in portal venous blood flow induced by CO2-pneumoperitoneum. Less rocuronium could be required to achieve a desirable NMB in laparoscopic gynaecological surgery. TRIAL REGISTRATION: ChiCTR. Registry number: ChiCTR-OPN-15007524 . Date of registration: December 4, 2015.

Upregulation of α2δ-1 Calcium Channel Subunit in the Spinal Cord Contributes to Pelvic Organ Cross-Sensitization in a Rat Model of Experimentally-Induced Endometriosis.

Pelvic organ cross-sensitization, also termed as viscero-visceral referred hyperalgesia, is a major contributor to painful endometriosis. Its underlying mechanism is poorly understood. Clinical and basic studies have shown that gabapentin, a drug that binds to the α2δ-1 subunit of voltage-dependent calcium channels (Cavα2δ-1), is effective in treating chronic visceral pain. Accordingly, we hypothesized that pelvic organ cross-sensitization in painful endometriosis is mediated by an upregulation of Cavα2δ-1 in the spinal cord. We examined if the dysregulation of spinal Cavα2δ-1 subunit may play an important role in the development of ectopic growths-to-colon cross-sensitization in a rat model of experimentally-induced endometriosis. Our findings suggest that there was an increased Cavα2δ-1 expression in the dorsal horn and an ectopic growths-to-colon cross-sensitization in female rats with established endometriosis. Intrathecal administration of gabapentin (300 µg) remarkably reduced the ectopic growths-to-colon cross-sensitization in rats with established endometriosis. Furthermore, intrathecal injection of Cavα2δ-1 antisense oligodeoxynucleotides reversed the ectopic growths-to-colon cross-sensitization and also normalized the upregulation of spinal Cavα2δ-1 expression in endometriosis rats. The current study suggests that the upregulation of Cavα2δ-1 in the spinal cord may contribute to pelvic organ cross-sensitization in painful endometriosis. Our study may provide a biological basis for selectively targeting this pathway to relieve viscero-visceral referred hyperalgesia in patients with painful endometriosis.

2-deoxy-D-glucose enhances anesthetic effects in mice.

BACKGROUND: The mechanisms of general anesthesia by volatile drugs remain largely unknown. Mitochondrial dysfunction and reduction in energy levels have been suggested to be associated with general anesthesia status. 2-Deoxy-D-glucose (2-DG), an analog of glucose, inhibits hexokinase and reduces cellular levels of adenosine triphosphate (ATP). 3-Nitropropionic acid is another compound which can deplete ATP levels. In contrast, idebenone and L-carnitine could rescue deficits of energy. We therefore sought to determine whether 2-DG and/or 3-nitropropionic acid can enhance the anesthetic effects of isoflurane, and whether idebenone and L-carnitine can reverse the actions of 2-DG. METHODS: C57BL/6J mice (8 months old) received different concentrations of isoflurane with and without the treatments of 2-DG, 3-nitropropionic acid, idebenone, and L-carnitine. Isoflurane-induced loss of righting reflex (LORR) was determined in the mice. ATP levels in H4 human neuroglioma cells were assessed after these treatments. Finally, 31P-magnetic resonance spectroscopy was used to determine the effects of isoflurane on brain ATP levels in the mice. RESULTS: 2-DG enhanced isoflurane-induced LORR (P = 0.002, N = 15). 3-Nitropropionic acid also enhanced the anesthetic effects of isoflurane (P = 0.005, N = 15). Idebenone (idebenone + saline versus idebenone + 2-DG: P = 0.165, N = 15), but not L-carnitine (L-carnitine + saline versus L-carnitine + 2-DG: P < 0.0001, N = 15), inhibited the effects of 2-DG on enhancing isoflurane-induced LORR in the mice, as evidenced by 2-DG not enhancing isoflurane-induced LORR in the mice pretreated with idebenone. Idebenone (idebenone + saline versus idebenone + 2-DG: P = 0.177, N = 6), but not L-carnitine (L-carnitine + saline versus L-carnitine + 2-DG: P = 0.029, N = 6), also mitigated the effects of 2-DG on reducing ATP levels in cells, as evidenced by 2-DG not decreasing ATP levels in the cells pretreated with idebenone. Finally, isoflurane decreased ATP levels in both cultured cells and mouse brains (ß-ATP: P = 0.003, N = 10; ß-ATP/phosphocreatine: P = 0.006, N = 10; ß-ATP/inorganic phosphate: P = 0.001, N = 10). CONCLUSIONS: These results from our pilot studies have established a system and generated a hypothesis that 2-DG enhances anesthetic effects via reducing energy levels. These findings should promote further studies to investigate anesthesia mechanisms.

Efficacy of palonosetron for preventing postoperative nausea and vomiting: a systematic review and meta-analysis.

PURPOSE: Palonosetron, a second-generation 5-hydroxytryptamine 3 receptor antagonist (5-HT3RA), has unique characteristics relative to first-generation 5-HT3RAs such as ondansetron. Nevertheless, it remains unclear if palonosetron is better than ondansetron for the prevention of nausea and vomiting during the first 24 hr after surgery and is thus the focus of this systematic review. METHODS: We conducted a systematic search of the MEDLINE®, EMBASE™, Cochrane Central Register of Controlled Trials and Web of Science® databases to identify randomized controlled trials (RCTs) that addressed a comparison of the prophylactic antiemetic efficacy between palonosetron and ondansetron within 24 hr after surgery. The primary outcomes were the proportion of participants who experienced postoperative nausea (PON), postoperative vomiting (POV), or both, in the early (0-6 hr) or late (6-24 hr) period. The pooled relative risks (RRs) were calculated along with their corresponding 95% confidence intervals (CIs). RESULTS: We identified nine RCTs that comprised 741 participants. Palonosetron was superior to ondansetron in the reduction of early PON [RR, 0.51; 95% CI, 0.37 to 0.71], late PON (RR, 0.53; 95% CI, 0.36 to 0.77), and late POV (RR, 0.41; 95% CI, 0.28 to 0.62), but not early POV (RR, 0.77; 95% CI, 0.45 to 1.34). CONCLUSION: Palonosetron provides more effective prophylaxis of early PON, late PON, and late POV compared with ondansetron. Future studies are required to investigate the role of palonosetron during 24-72 hr following surgery.

Down-regulation of Stargazin inhibits the enhanced surface delivery of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor GluR1 subunit in rat dorsal horn and ameliorates postoperative pain.

BACKGROUND: Stargazin is the first transmembrane protein known to regulate synaptic targeting of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors. However, it is unclear whether regulation of the surface delivery of spinal AMPA receptor subunits by stargazin contributes to postoperative pain development. METHODS: Western blot analysis was used to examine changes in the surface delivery of AMPA receptor subunits, GluR1 and GluR2, in rat dorsal horn. The interaction between stargazin and GluR1 and GluR2 was examined by coimmunoprecipitation. Expression of stargazin was suppressed by intrathecal administration of small interfering RNA311. RESULTS: Membrane-bound GluR1, but not GluR2, in ipsilateral dorsal horn was increased at 3 h (1.49 ± 0.15-fold of ß-tubulin, mean ± SEM) and 1 day (1.03 ± 0.25) after incision, as compared with that in control rats (naive, 0.63 ± 0.23, P < 0.05, n = 6 per group). The amount of GluR1 coimmunoprecipitated with stargazin was greater at 3 h after incision (1.48 ± 0.31-fold of input) than that in control animals (0.45 ± 0.24, P < 0.05, n = 6 per group). Importantly, the increase in membrane GluR1 at 3 h after incision was normalized to near control level (0.72 ± 0.20-fold of ß-tubulin) by pretreatment with intrathecal stargazin small interfering RNA311 (0.87 ± 0.09), but not scrambled small interfering RNA (1.48 ± 0.24) or vehicle (1.25 ± 0.13, P < 0.05, n = 6 per group). Stargazin small interfering RNA311 pretreatment prevented the increase in stargazin-GluR1 interaction and decreased postoperative pain after incision. CONCLUSIONS: This study suggests a critical role of stargazin-mediated surface delivery of GluR1 subunit in the development of postoperative pain. A better therapeutic strategy for postoperative pain may involve selectively down-regulating spinal stargazin to inhibit synaptic targeting of GluR1 subunit.

Do fluctuations in endogenous melatonin levels predict the occurrence of postoperative cognitive dysfunction (POCD)?

Delirium is a complex neuropsychiatric disorder that has an adverse impact on CNS function. Abnormal fluctuation of melatonin secretion occurs in the postoperative delirium (POD) in elderly patients. POD is strongly associated with early postoperative cognitive dysfunction (POCD). The aim of this study is to test if significant fluctuation of melatonin secretion perioperatively might indicates POCD. A total of 97 patients, ages 65-80 years, scheduled for major orthopedic surgery or abdominal surgery which was expected to last more than 2 h, were consecutively recruited into this study. Neuropsychological evaluation was performed 1 d before and one week after surgery. Morning urine samples were collected on the day of surgery and on days 1, 2 and 7 after surgery. The 6-SMT/creatinine ratio (M/C ratio) was employed to give an objective estimate of urine 6-SMT concentration. Ultimately, 95 patients completed assessments and were included in the analysis. POCD was found in 30 patients (31.6%) at 1 week after operation. There was significant fluctuation in urinary 6-SMT in 39 of the 95 patients (as evidenced by urinary 6-SMT levels increased or decreased by more than twofold compared with their preoperative baseline). Fluctuations in 6-SMT levels occurred on different days and in some patients lasted for more than 1 d. The incidence of POCD in patients with 6-SMT fluctuation was significantly higher (p < 0.01). The results indicate that in the first week after major noncardiac surgery, POCD occurs in a significant proportion of people, and is linked to fluctuations in endogenous melatonin levels. Measurement of urinary 6-SMT during the perioperative period may assist the diagnosis of POCD.