Effect of dexmedetomidine on preventing perioperative respiratory adverse events in children: A systematic review and meta­analysis of randomized controlled trials.

The most common critical incidents in pediatric anesthesia are perioperative respiratory adverse events (PRAEs). The present meta-analysis aimed to assess the preventive effect of dexmedetomidine on PRAEs in children. Dexmedetomidine is a highly selective α2-adrenoceptor agonist that provides sedation, anxiolysis and analgesic effects without causing respiratory depression. Dexmedetomidine can diminish airway and circulatory responses during extubation in children. Original randomized controlled trial data were analyzed to study the putative effect of dexmedetomidine on PRAEs. By searched the Cochrane Library, EMBASE and PubMed, a total of ten randomized controlled trials (1,056 patients) was identified. PRAEs included cough, breath holding, laryngospasm, bronchospasm, desaturation (percutaneous oxygen saturation <95%), body movement and pulmonary rales. Compared with placebo, dexmedetomidine resulted in a significant reduction of incidence of cough, breath holding, laryngospasm and emergence agitation. The incidence of PRAEs was significantly reduced in dexmedetomidine compared with active comparators group. Moreover, dexmedetomidine decreased heart rate and increased post-anesthesia care unit stay duration by 11.18 min. The present analysis suggested that dexmedetomidine improved the airway function and decreased risks associated with general anesthesia in children. The present data demonstrated that dexmedetomidine may be a good choice to prevent PRAEs in children.

Effect of a carbohydrate-rich beverage on rate of cesarean delivery in primigravidae with epidural labor analgesia: a multicenter randomized trial.

BACKGROUND: Labor represents a period of significant physical activity. Inefficient energy supply may delay labor process and even lead to cesarean delivery. Herein we investigated whether ingestion of a carbohydrate-rich beverage could reduce cesarean delivery in laboring women with epidural analgesia. METHODS: This multicenter randomized trial was conducted in obstetrician-led maternity units of nine tertiary hospitals in China. Primigravidae with single term cephalic pregnancy who were preparing for vaginal birth under epidural analgesia were randomized to intake a carbohydrate-rich beverage or commercially available low-carbohydrate beverages during labor. The primary outcome was the rate of cesarean delivery. Secondary outcomes included maternal feeling of hunger, assessed with an 11-point scale where 0 indicated no hunger and 10 the most severe hunger, and maternal and neonatal blood glucose after childbirth. RESULTS: Between 17 January 2018 and 20 July 2018, 2008 women were enrolled and randomized, 1953 were included in the intention-to-treat analysis. The rate of cesarean delivery did not differ between the two groups (11.3% [111/982] with carbohydrate-rich beverage vs. 10.9% [106/971] with low-carbohydrate beverages; relative risk 1.04, 95% CI 0.81 to 1.33; p = 0.79). Women in the carbohydrate-rich beverage group had lower subjective hunger score (median 3 [interquartile range 2 to 5] vs. 4 [2 to 6]; median difference - 1; 95% CI - 1 to 0; p < 0.01); their neonates had less hypoglycemia (1.0% [10/968] vs. 2.3% [22/956]; relative risk 0.45; 95% CI 0.21 to 0.94; p = 0.03) when compared with those in the low-carbohydrate beverage group. They also had higher rates of maternal hyperglycemia (6.9% [67/965] vs. 1.9% [18/953]; p < 0.01) and neonatal hyperglycemia (9.2% [89/968] vs. 5.8% [55/956]; p < 0.01), but none required special treatment. CONCLUSIONS: For laboring primigravidae with epidural analgesia, ingestion of a carbohydrate-rich beverage compared with low-carbohydrate beverages did not reduce cesarean delivery, but relieved maternal hunger and reduced neonatal hypoglycemia at the expense of increased hyperglycemia of both mothers and neonates. Optimal rate of carbohydrate supplementation remains to be determined. TRIAL REGISTRATION: www.chictr.org.cn ; identifier: ChiCTR-IOR-17011994 ; registered on 14 July 2017.

Long-term sevoflurane exposure reduces the differentiation potential and hypoxia tolerance potential of neural stem cells.

PURPOSE: To investigate the effect of prolonged sevoflurane (SEV) exposure on differentiation potential and hypoxia tolerance of neural stem cells (NSCs). MATERIALS AND METHODS: NSCs were extracted from 15-day fetal mice. After sub-culture, SEV exposure treatment was performed. Cell cycle were detected by flow cytometry. Western blot and immunofluorescence assay were used to detect the expression and spatial distribution of Nestin, NSE, GFAP, Oct4, and SOX2; CCK-8 detected cell viability. Cell growth morphology was observed under a microscope. TUNEL detected cell apoptosis; the concentration of extracel-lular lactate dehydrogenase (LDH) was determined by ELISA. RESULTS: Compared with the control group, the proportion of NSCs in the G2/M phase increased in the SEV exposure group; our results also suggested the sphere-formation rate decreased significantly, increased apoptosis and decreased cell viability. Besides, the level of LDH release increased. CONCLUSION: Long-term exposure to SEV (>8 h) promoted the premature differentiation of NSCs and reduced their pluripotency, reserves, and hypoxia tolerance. This study reveals the reasons underlying damage to the nervous system of young children induced by long-term exposure to SEV from the perspective of CNS reserve cells.

Dexmedetomidine attenuates one-lung ventilation associated lung injury by suppressing inflammatory responses: A systematic review and meta-analysis.

One-lung ventilation (OLV), a common ventilation technique, is associated with perioperative lung injury, tightly connected with inflammatory responses. Dexmedetomidine has shown positive anti-inflammatory effects in lung tissues in pre-clinical models. This study investigated the efficacy of dexmedetomidine for suppressing inflammatory responses in patients requiring OLV. We searched PubMed, MEDLINE, Embase, Scopus, Ovid, and Cochrane Library for randomized controlled trials focusing on dexmedetomidine's anti-inflammatory effects on patients requiring OLV without any limitation on the year of publication or languages. 20 clinical trials were assessed with 870 patients in the dexmedetomidine group and 844 in the control group. Our meta-analysis investigated the anti-inflammatory property of dexmedetomidine perioperatively [T1 (30-min OLV), T2 (90-min OLV), T3 (end of surgery) and T4 (postoperative day 1)], demonstrating that dexmedetomidine's intraoperative administration resulted in a significant reduction in serum concentration of interleukin-6, tumor necrosis factor-α and other inflammatory cytokines perioperatively. By calculating specific I2 index, significant heterogeneity was observed on all occasions, with I2 index ranging from 95% to 99%. For IL-6 changes, sensitivity analysis showed that the exclusion of a single study led to a significant decrease of heterogeneity (96%-0%; p < 0.00001). Besides, pulmonary oxygenation was ameliorated in the dexmedetomidine group comparing with the control group. In conclusion, perioperative administration of dexmedetomidine can attenuate OLV induced inflammation, ameliorate pulmonary oxygenation, and may be conducive to a decreased occurrence of postoperative complications and better prognosis. However, the results should be prudently interpreted due to the evidence of heterogeneity and the limited number of studies.

Effects of transcutaneous electrical acupoint stimulation on perioperative immune function and postoperative analgesia in patients undergoing radical mastectomy: A randomized controlled trial.

Radical mastectomy may lead to suppression of cellular immune function in patients with malignant tumors. Transcutaneous electrical acupoint stimulation (TEAS) is widely used in clinical practice. However, there have been relatively few studies on the effects of TEAS on postoperative analgesia and immune function. The present study aimed to evaluate the effects of TAES on postoperative pain and immune function in patients undergoing radical mastectomy. A total of 65 patients were enrolled and allocated to either receive TEAS or sham TEAS. TEAS was implemented on bilateral Hegu (LI4), Neiguan (PC6) and Zusanli (ST36) acupoints simultaneously for 30 min before induction of anesthesia at 4 and 12 h post-operation. The primary outcomes included visual analogue scale (VAS) scores at 4 h (T1), 12 h T2), 24 h (T3) and 48 h (T4) post-operation, and serum levels of IL-2, IL-4, IFN-γ and the IL-2/IL-4 ratio at 30 min before TEAS (T0), T1, T2, T3 and T4. Secondary outcomes included the cumulative time of rescue analgesia within 48 h post-surgery, as well as the incidence of postoperative nausea and vomiting (PONV) and pruritus. Compared with the sham TEAS group, postoperative VAS scores at T2 and T3, the total consumption of opioids in the patient-controlled analgesia (PCA) pump, pressing times of the PCA pump and the incidences of PONV and headache were significantly lower in the TEAS group. The serum levels of IFN-γ at T3 and T4, and the serum levels of IL-2 and the IL-2/IL-4 ratio at T2, T3 and T4 were higher in the TEAS group compared with the sham TEAS group. By contrast, the serum levels of IL-4 were lower at T2, T3 and T4 in the TEAS group compared with the sham TEAS group. The results indicated that TEAS could improve postoperative analgesia, reduce postoperative consumption of opioids and alleviate postoperative side effects. Simultaneously, TEAS was able to reverse decreased serum levels of IL-2 and IFN-γ, reduce the level of IL-4 and restore the balance of Th1/Th2, thereby partially attenuating perioperative immune function depression in patients with breast cancer. The current trial was registered prior to participant enrollment at www.chictr.org.cn (Clinical Trial no. ChiCTR1800017768).

Moderate hypothermia induces protection against hypoxia/reoxygenation injury by enhancing SUMOylation in cardiomyocytes.

Moderate hypothermia plays a major role in myocardial cell death as a result of hypoxia/reoxygenation (H/R) injury. However, few studies have investigated the molecular mechanisms of hypothermic cardioprotection. Several responses to stress and other cell functions are regulated by post­translational protein modifications controlled by small ubiquitin­like modifier (SUMO). Previous studies have established that high SUMOylation of proteins potentiates the ability of cells to withstand hypoxic­ischemic stress. The level to which moderate hypothermia affects SUMOylation is not fully understood, as the functions of SUMOylation in the heart have not been studied in depth. The aim of the present study was to investigate the effect of moderate hypothermia (33˚C) on the protective functions of SUMOylation on myocardial cells. HL­1 and H9c2 cells were treated with the hypoxia­mimetic chemical CoCl2 and complete medium to simulate H/R injury. Hypothermia intervention was then administered. A Cell Counting kit­8 assay was used to analyze cell viability. Mitochondrial membrane potential and the generation of reactive oxygen species (ROS) were used as functional indexes of mitochondria dysfunction. Bcl­2 and caspase­3 expression levels were analyzed by western blotting. The present results suggested that moderate hypothermia significantly increased SUMO1 and Bcl­2 expression levels, as well as the mitochondrial membrane potential, but significantly decreased the expression levels of caspase­3 and mitochondrial ROS. Thus, moderate hypothermia may enhance SUMOylation and attenuate myocardial H/R injury. Moreover, a combination of SUMOylation and moderate hypothermia may be a potential cardiovascular intervention.

Expression of SUMO associated proteins in the mouse endometrium is regulated by ovarian hormones throughout the estrous cycle.

The modification of proteins by small ubiquitin-like modifier (SUMO), known as SUMOylation, regulates biological function by changing protein transcription and translation. During the estrous cycle the endometrium undergoes continual change to processes including cell proliferation, secretion and exfoliation and these changes are regulated by the levels of ovarian hormones. Increasing the expression of SUMO family members has previously been shown to promote proliferation and invasion of endometrial cancer cells. However, limited research has been carried out into the expression and function of SUMO in the mammalian endometrium. In the present study, the level and localization of SUMO-associated proteins throughout the natural estrous cycle in the mouse uterus was determined using immunohistochemical staining and western blot analysis. The association between the spatiotemporal expression of these SUMO modified proteins and SENPs in endometrium and the concentration of ovarian hormones during estrous cycle was revealed. The present study clarified the role of SUMOylation in maintenance of normal estrous cycling and may have important significance in the study of hormone-dependent endometrial diseases.

Effectiveness and safety of intravenous application of dexmedetomidine for cesarean section under general anesthesia: a meta-analysis of randomized trials.

OBJECTIVE: The meta-analysis was conducted to assess the effectiveness and safety of intravenous administration of dexmedetomidine for cesarean section under general anesthesia, as well as neonatal outcomes. MATERIALS AND METHODS: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials and the China National Knowledge Infrastructure database for relevant randomized controlled trials (RCTs) about the application of intravenous dexmedetomidine under general anesthesia for cesarean section. RevMan 5.3 was used to conduct the meta-analysis of the outcomes of interest. RESULTS: Eight RCTs involved 376 participants were included in this study. The meta-analysis showed that the mean blood pressure at the time of intubation (weighted mean difference [WMD]: -15.67, 95% CI: -21.21, -10.13, P<0.00001), skin incision (WMD: -12.83, 95% CI -20.53, -5.14, P=0.001), and delivery (WMD: -11.65, 95% CI -17.18, -6.13, P<0.0001) in dexmedetomidine group were significantly lower than that in the control group. The heart rate (HR) at the time of intubation (WMD: -31.41, 95% CI -35.01, -27.81, P<0.00001), skin incision (WMD: -22.32, 95% CI -34.55, -10.10, P=0.0003), and delivery (WMD: -19.07, 95% CI -22.09, -16.04, P<0.00001) were also lower than that in control group. For neonatal parameters, no differences existed in umbilical blood gases at delivery, and Apgar scores at 1 minute (WMD: -0.12, 95% CI -0.37, 0.12, P=0.33) and 5 minutes (WMD: -0.17, 95% CI -0.13, 0.46, P=0.27) among two groups. CONCLUSION: Intravenous administration of dexmedetomidine could efficiently attenuate the maternal cardiovascular response during cesarean section, without affecting Apgar score of the neonate.

Paravertebral Block for Inguinal Herniorrhaphy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Paravertebral block (PVB) is a safe and effective anesthetic technique for thoracotomy and mastectomy. However, no systematic review or meta-analysis has focused on PVB for inguinal herniorrhaphy. Our study compares PVB with general anesthesia/systemic analgesia, neuraxial blocks, and other peripheral nerve blocks. METHODS: We analyzed 14 randomized controlled trials from PubMed, MEDLINE, CENTRAL, EMBASE, and CINAHL up to February 2015, without language restriction, comparing PVB under sedation with general anesthesia/systematic analgesia (135 vs 133 patients), neuraxial blocks (191 vs 186 patients), and other peripheral nerve blocks (119 vs 117 patients). We investigated pain scores, consumption of postoperative analgesia, incidence of postoperative nausea and vomiting (PONV), length of hospital stay, postanesthesia care unit bypassing rate, time to perform blocks, intraoperative hemodynamics, and incidence of urinary retention. Joint hypothesis testing was adopted for pain and analgesics, PONV, and hemodynamic variables. All analyses were performed with RevMan 5.2.11 (Cochrane Collaboration, Copenhagen). Hartung-Knapp-Sidik-Jonkman method was used for post hoc testing. RESULTS: PVB reduced PONV (nausea: risk ratio [RR] = 0.22; 95% confidence interval [CI], 0.05-0.93; numbers needed to treat [NNT] = 4.5; I = 15% and vomiting: RR = 0.15; 95% CI, 0.03-0.76; NNT = 8.3; I = 0%) compared with general anesthesia/systematic analgesia (quality of evidence [QoE]: high). Compared with neuraxial blocks, PVB resulted in less postoperative nausea (RR = 0.34 [95% CI, 0.13-0.91], NNT = 8.3, I = 0%) and urinary retention (RR = 0.14 [95% CI, 0.05-0.42], NNT = 7.4, I = 0%) than neuraxial blocks (QoE: high). More time was needed to perform PVB than neuraxial blocks (standardized mean difference = 1.90 [95% CI, 0.02-3.77], I = 92%; mean difference = 5.33 minutes; QoE: moderate). However, the available data could not reject the null hypothesis of noninferiority on all pain scores and analgesic requirements for both PVB versus general anesthesia/systematic analgesia and PVB versus neuraxial blocks (QoE: low), as well as on hemodynamic outcomes for PVB versus neuraxial blocks (QoE: moderate). Our systematic review showed that PVB decreased postoperative pain scores and analgesic requirement as compared with ilioinguinal block and transversus abdominis plane block. CONCLUSIONS: This meta-analysis shows that PVB provides an anesthesia with fewer undesirable effects for inguinal herniorrhaphy. The choice between general anesthesia/systematic analgesia, neuraxial blocks, PVB, and other peripheral nerve blocks should be based on time available to perform the block and a complete coverage over the relevant structures by the blocks.

Lidocaine patch for acute pain management: a meta-analysis of prospective controlled trials.

BACKGROUND: Local anesthetic is one of the cornerstones of multimodal analgesia. We investigated the efficacy of the lidocaine patch for acute pain management. METHODS: We searched MEDLINE, CINAHL, Scopus, and the Cochrane Controlled Trials Register for published prospective controlled clinical trials that evaluated the analgesic effect of the lidocaine patch for acute or postoperative pain management (1966--2014). The outcomes were postoperative opioid consumption, pain intensity and length of hospital stay. RESULTS: Five trials comparing the lidocaine patch with control (no treatment/placebo) for acute or postoperative pain treatment/management were included in this meta-analysis. Data was analyzed on 251 patients. Between the lidocaine patch group and the control group, no significant difference was found for all three outcomes (all p > 0.05). For postoperative opioid consumption, mean difference (MD) was -8.2 mg morphine equivalent (95% CI -28.68, 12.24). For postoperative pain intensity, MD was -9.1 mm visual analog scale or equivalent (95% CI -23.31, 5.20). For length of hospital stay, MD was -0.2 days (95% CI -0.80, 0.43). CONCLUSION: Application of a lidocaine patch may not be an effective adjunct for acute and postoperative pain management, in terms of pain intensity, opioid consumption and length of hospital stay. LIMITATIONS: The limitations were a small number of included studies, potential biases from some unblinded studies, clinical heterogeneity between studies, and incomplete reported data for adjunct analgesics.