Enhancement in Tonically Active Glutamatergic Inputs to the Rostral Ventrolateral Medulla Contributes to Neuropathic Pain-Induced High Blood Pressure.

Neuropathic pain increases the risk of cardiovascular diseases including hypertension with the characteristic of sympathetic overactivity. The enhanced tonically active glutamatergic input to the rostral ventrolateral medulla (RVLM) contributes to sympathetic overactivity and blood pressure (BP) in cardiovascular diseases. We hypothesize that neuropathic pain enhances tonically active glutamatergic inputs to the RVLM, which contributes to high level of BP and sympathetic outflow. Animal model with the trigeminal neuropathic pain was induced by the infraorbital nerve-chronic constriction injury (ION-CCI). A significant increase in BP and renal sympathetic nerve activity (RSNA) was found in rats with ION-CCI (BP, n = 5, RSNA, n = 7, p < 0.05). The concentration of glutamate in the RVLM was significantly increased in the ION-CCI group (n = 4, p < 0.05). Blockade of glutamate receptors by injection of kynurenic acid into the RVLM significantly decreased BP and RSNA in the ION-CCI group (n = 5, p < 0.05). In two major sources (the paraventricular nucleus and periaqueductal gray) for glutamatergic inputs to the RVLM, the ION-CCI group (n = 5, p < 0.05) showed an increase in glutamate content and expression of glutaminase 2, vesicular glutamate transporter 2 proteins, and c-fos. Our results suggest that enhancement in tonically active glutamatergic inputs to the RVLM contributes to neuropathic pain-induced high blood pressure.

Chitosan aerosol inhalation alleviates lipopolysaccharide- induced pulmonary fibrosis in rats.

PURPOSE: Pulmonary fibrosis (PF) is an insidiously progressive scarring disorder of the alveoli and is associated with high mortality. Currently, therapies available are associated with restricted efficacy and side effects. This study aimed to investigate the effect of chitosan aerosol inhalation on lipopolysaccharide (LPS)-induced pulmonary remodeling and fibrosis in rats. METHODS: A rat model of PF was established by intratracheal injection of LPS (5 mg/kg). Chitosan was nebulized to rats from day 4 to 28 after LPS injection. We analyzed the effect of chitosan on LPS-induced pulmonary remodeling and fibrosis by hematoxylin-eosin staining (HE), Masson staining, and the determination of the hydroxyproline content. The expression intensities of matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were analyzed by western blots. RESULTS: Histological assessments showed that chitosan aerosol inhalation attenuated the fibrotic changes in LPS-induced PF in rats. Compared with the LPS group, the fibrosis parameters were significantly improved in the LPS + chitosan group (LCh group), although not as good as those of the control group. The expressions of MMP-3 and TIMP-1 in the LCh group were markedly less than that of the LPS group on the 28th day. CONCLUSIONS: Our findings show that chitosan aerosol inhalation inhibits the expression of MMP-3 and TIMP-1, and ameliorates LPS-induced pulmonary remodeling and fibrosis in rats.

Dexmedetomidine for the management of awake fibreoptic intubation.

BACKGROUND: Awake fibreoptic intubation (AFOI) frequently requires sedation, anxiolysis and relief of discomfort without impairing ventilation and depressing cardiovascular function. The goal is to allow the patient to be responsive and co-operative. Medications such as fentanyl, remifentanil, midazolam and propofol have been reported to assist AFOI; however,these agents are associated with cardiovascular or respiratory adverse effects. Dexmedetomidine has been proposed as an alternative to facilitate AFOI. OBJECTIVES: The primary objective of this review is to evaluate and compare the efficacy and safety of dexmedetomidine in the management of patients with a difficult or unstable airway undergoing awake fibreoptic intubation (AFOI). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2012, Issue 5), MEDLINE (1966 to May 2012) through Ovid, EMBASE (1980 to May 2012) and Web of Science (1945 to May 2012); we screened the reference lists of all eligible trials and reviews to look for further trials and contacted authors of trials to ask for additional information. We searched for ongoing trials at http://www.controlledtrials.com/ and http://clinicaltrials.gov/ . We reran our search of all databases listed above on 21 November 2013. SELECTION CRITERIA: We included published and unpublished randomized controlled trials, regardless of blinding or language of publication, in participants 18 years of age or older who were scheduled for an elective AFOI because of an anticipated difficult airway. Participants received dexmedetomidine or control medications. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data on study design, participants, interventions and outcomes. We assessed risk of bias using The Cochrane Collaboration's tool. We estimated risk ratios (RRs) or mean differences (MDs) with 95% confidence internals (CIs) for outcomes with sufficient data; for other outcomes, we performed a qualitative analysis. MAIN RESULTS: We identified four randomized controlled trials (RCTs), which included 211 participants. The four trials compared dexmedetomidine with midazolam, fentanyl, propofol or a sodium chloride placebo, respectively. The trials showed low or unclear risk of bias primarily because information provided on allocation concealment and other potential sources of bias was inadequate. Owing to clinical heterogeneity and potential methodological heterogeneity, it was impossible to conduct a full meta-analysis. We described findings from individual studies or presented them in tabular form. Limited evidence was available for assessment of the outcomes of interest for this review. Results of the limited included trials showed that dexmedetomidine significantly reduced participants' discomfort with no significant differences in airway obstruction, low oxygen levels or treatment-emergent cardiovascular adverse events noted during AFOI compared with control groups. When the search was rerun (from May 2012 to November 2013), it was noted that four studies are awaiting assessment. We will deal with these studies when we update the review. AUTHORS' CONCLUSIONS: Small, limited trials provide weak evidence to support dexmedetomidine as an option for patients with an anticipated difficult airway who undergo AFOI. The findings of this review should be further corroborated by additional controlled investigations.

Strategies for prevention of postoperative delirium: a systematic review and meta-analysis of randomized trials.

INTRODUCTION: The ideal measures to prevent postoperative delirium remain unestablished. We conducted this systematic review and meta-analysis to clarify the significance of potential interventions. METHODS: The PRISMA statement guidelines were followed. Two researchers searched MEDLINE, EMBASE, CINAHL and the Cochrane Library for articles published in English before August 2012. Additional sources included reference lists from reviews and related articles from 'Google Scholar'. Randomized clinical trials (RCTs) on interventions seeking to prevent postoperative delirium in adult patients were included. Data extraction and methodological quality assessment were performed using predefined data fields and scoring system. Meta-analysis was accomplished for studies that used similar strategies. The primary outcome measure was the incidence of postoperative delirium. We further tested whether interventions effective in preventing postoperative delirium shortened the length of hospital stay. RESULTS: We identified 38 RCTs with interventions ranging from perioperative managements to pharmacological, psychological or multicomponent interventions. Meta-analysis showed dexmedetomidine sedation was associated with less delirium compared to sedation produced by other drugs (two RCTs with 415 patients, pooled risk ratio (RR)=0.39; 95% confidence interval (CI)=0.16 to 0.95). Both typical (three RCTs with 965 patients, RR=0.71; 95% CI=0.54 to 0.93) and atypical antipsychotics (three RCTs with 627 patients, RR=0.36; 95% CI=0.26 to 0.50) decreased delirium occurrence when compared to placebos. Multicomponent interventions (two RCTs with 325 patients, RR=0.71; 95% CI=0.58 to 0.86) were effective in preventing delirium. No difference in the incidences of delirium was found between: neuraxial and general anesthesia (four RCTs with 511 patients, RR=0.99; 95% CI=0.65 to 1.50); epidural and intravenous analgesia (three RCTs with 167 patients, RR=0.93; 95% CI=0.61 to 1.43) or acetylcholinesterase inhibitors and placebo (four RCTs with 242 patients, RR=0.95; 95% CI=0.63 to 1.44). Effective prevention of postoperative delirium did not shorten the length of hospital stay (10 RCTs with 1,636 patients, pooled SMD (standard mean difference)=-0.06; 95% CI=-0.16 to 0.04). CONCLUSIONS: The included studies showed great inconsistencies in definition, incidence, severity and duration of postoperative delirium. Meta-analysis supported dexmedetomidine sedation, multicomponent interventions and antipsychotics were useful in preventing postoperative delirium.

Butorphanol prevents morphine-induced pruritus without increasing pain and other side effects: a systematic review of randomized controlled trials.

PURPOSE: Pruritus is a frequent adverse event after administration of morphine. Butorphanol has been used to prevent morphine-induced pruritus, but its efficacy is still controversial. The aim of this systematic review was to evaluate the efficacy of using butorphanol to prevent morphine-induced pruritus. SOURCE: We searched PubMed, Cochrane Library, EMBASE, and China's BioMedical Disc for full reports of randomized controlled trials that compared the use of butorphanol with either placebo or no treatment for preventing morphine-induced pruritus. The number of patients experiencing pruritus or other side effects was analyzed using relative risk (RR) with 95% confidence intervals (CI). PRINCIPAL FINDINGS: Sixteen trials (795 patients) were analyzed. Continuous intravenous and epidural butorphanol reduced pruritus with RR 0.22 (95% CI 0.10 to 0.45) and RR 0.24 (95% CI 0.16 to 0.36), respectively. Use of epidural butorphanol decreased the number of patients requesting rescue treatment for pruritus (RR 0.57; 95% CI 0.41 to 0.81). Butorphanol decreased postoperative pain intensity at four, eight, and 12 hr with standardized mean differences of -0.29 (95% CI -0.52 to -0.05), -0.30 (95% CI -0.56 to -0.04), and -0.23 (95% CI -0.46 to -0.01), respectively. Epidural but not intravenous butorphanol reduced postoperative nausea and vomiting (PONV) (RR 0.35; 95% CI 0.19 to 0.66). Butorphanol did not increase respiratory depression (RR 0.71; 95% CI 0.31 to 1.63), somnolence (RR 0.71; 95% CI 0.22 to 2.37), or dizziness (RR 2.45; 95% CI 0.35 to 17.14). CONCLUSION: Butorphanol administered with morphine may be an effective strategy for preventing morphine-induced pruritus as it decreases pain intensity and PONV without increasing other side effects. Thus, it can be recommended for preventing morphine-induced pruritus during the perioperative period.

Dexmedetomidine versus morphine or fentanyl in the management of children after tonsillectomy and adenoidectomy: a meta-analysis of randomized controlled trials.

OBJECTIVES: The primary objective of this review was to evaluate and compare the efficacy and safety of dexmedetomidine hydrochloride with the efficacy and safety of opioids for postoperative management of children after tonsillectomy and adenoidectomy. METHODS: We searched the Cochrane Central Register of Controlled Trials (Central) in the Cochrane Library (most recent issue), Medline (1966 to date) through Ovid, Embase (1980 to date), and Web of Science (1945 to date). The number of patients who required rescue analgesics (morphine or fentanyl) in the postanesthesia care unit, the number of patients with emergence agitation, the number of patients with postoperative nausea and vomiting, the time to eye-opening in response to verbal stimuli, and the time to extubation were analyzed. RESULTS: We included 5 trials, consisting of 482 patients in total. There were no significant differences in the number of patients who required rescue analgesics in the postanesthesia care unit, the number of patients with emergence agitation, the number of patients with postoperative nausea and vomiting, or the time to extubation between patients who received dexmedetomidine and those who received opioids. Compared with opioids, dexmedetomidine was associated with a significantly decreased time to eye-opening in response to verbal stimuli (mean difference, -2.11 minutes; 95% confidence interval, -3.32 to -0.91 minutes; p = 0.0006). CONCLUSIONS: Intraoperative use of dexmedetomidine was as effective as opioids in preventing postoperative pain and emergence agitation in children who had undergone tonsillectomy and adenoidectomy.

Autologous transplantation of peripheral blood-derived circulating endothelial progenitor cells attenuates endotoxin-induced acute lung injury in rabbits by direct endothelial repair and indirect immunomodulation.

BACKGROUND: Studies have demonstrated the role of circulating endothelial progenitor cells (EPCs) in maintaining normal endothelial function and in endothelial repairing. This study was aimed to observe the protective effects of autologous transplantation of circulating EPCs against endotoxin-induced acute lung injury in rabbits and to investigate the underlying mechanisms. METHODS: One-hundred-and-fifty rabbits were enrolled. After acute lung injury was induced by endotoxin, autologous circulating EPCs, endothelial cell, or normal saline were transfused intravenously, respectively. Pao(2)/FiO(2) ratios, concentrations of plasma nitric oxide, malonyldialdehyde, and activity of superoxide dismutase were examined. The lung wet-to-dry weight ratios were counted; polymorphonuclear cell ratios and areas of hyaline membrane formation and hemorrhage were measured. The levels of interleukin-1ß, E-selectin, intercellular adhesion molecule-1, interleukin-10, vascular endothelial growth factor protein, and inducible nitric oxide synthase protein were analyzed. RESULTS: Pao(2)/FiO(2) ratios were significantly increased with EPC transfusion. Infiltration of polymorphonuclear cells, lung wet-to-dry weight ratios, and area of hyaline membrane and hemorrhage in lung tissue were significantly decreased after EPC transplantation. Plasma level of nitric oxide and malondialdehyde were significantly inhibited, and the activity of superoxide dismutase was enhanced in the EPC-treated animals. EPC transplantation significantly increased level of interleukin-10 and vascular endothelial growth factor protein and reduced levels of interleukin-1ß, E-selectin, intercellular adhesion molecule-1, and inducible nitric oxide synthase in injury lung tissues. CONCLUSIONS: Autologous transplantation of circulating EPCs can partly restore the pulmonary endothelial function and effectively attenuate endotoxin-induced acute lung injury by direct endothelial repair and indirect immunomodulation of antioxidation and antiinflammation.

Antihypertensive effects and safety of eprosartan: a meta-analysis of randomized controlled trials.

PURPOSE: The benefits of reducing blood pressure (BP) have been well established, but uncertainty remains about the comparative effects of different BP-lowering regimens. We aimed to estimate the efficacy and the tolerability of eprosartan compared with other agents as monotherapy. METHODS: PubMed, EMBASE, and Cochrane Library were searched for relevant studies. A meta-analysis of randomized controlled trials (RCTs) meeting the criteria was performed using Review Manager and Stata/SE. RESULTS: Twenty-two articles were ultimately included out of 78 studies, involving 6,460 patients. Eprosartan had a greater systolic blood pressure (SBP) reduction than placebo [weighted mean difference (WMD): 6.55, 95% confidence interval (CI) 4.86-8.25] and losartan (WMD: 2.24, 95% CI 0.08-4.40) and a greater diastolic blood pressure (DBP) reduction than placebo (WMD 3.95, 95% CI 2.77-5.13). Therapeutic response rate of BP favored eprosartan [risk ratio (RR) 1.13, 95% CI 1.03-1.24] compared with enalapril. There were no statistical differences in SBP or DBP reductions comparing eprosartan with enalapril or telmisartan. Original RCTs included comparing eprosartan with valsartan and nitrendipine reported no differences in BP-lowering efficacy. CONCLUSIONS: Eprosartan monotherapy is equivalent to many first-line antihypertensive agents and is effective for the treatment of essential hypertension, especially for isolated systolic hypertension. The favorable efficacy and tolerability make eprosartan worthwhile to be taken into consideration by physicians.

Postreperfusion syndrome during orthotopic liver transplantation: a single-center experience.

BACKGROUND: Marked hemodynamic alteration, commonly referred to as postreperfusion syndrome (PRS), often occurs after revascularization of the donor organ during orthotopic liver transplantation (OLT) and is associated with poor outcomes. This study aimed to investigate the incidence, predictive factors and clinical outcomes of PRS in Chinese patients following OLT at a liver transplantation center in China. METHODS: Over a 5-year period, 330 consecutive patients who had undergone OLT for hepatocellular carcinoma or cirrhosis were included in this retrospective study. PRS was defined as a >30% decrease in the mean arterial pressure compared with that before revascularization for more than 1 minute during the first 5 minutes of graft reperfusion. The patients were divided into 2 groups according to the development of PRS: group 1 (patients with PRS, n=56) and group 2 (patients without PRS, n=274). The demographic characteristics, operative and postoperative courses, and outcomes of the patients were analyzed using SPSS version 18.0. RESULTS: Multivariate regression analysis showed that left ventricular diastolic dysfunction determined by echocardiography and prolonged cold ischemia time were the independent risk factors for PRS. More patients in group 1 showed postoperative renal dysfunction than those in group 2 (19.23% vs 8.4%). Moreover, patients in group 1 also had higher intraoperative (7.14% vs 0%) and postoperative mortalities (26.92% vs 12.04%). CONCLUSION: Left ventricular diastolic dysfunction and prolonged cold ischemia time contribute to a high incidence of PRS, which is associated with adverse outcomes in Chinese patients following OLT.

Hydroxyethyl starch for cardiovascular surgery: a systematic review of randomized controlled trials.

PURPOSE: The objective of this study was to appraise the safety profiles of HES preparations and to find out which HES preparation was the most acceptable in cardiovascular surgery through a comparison with control solutions. METHODS: Pertinent randomized controlled trials were selected through a search of Pubmed, Embase, and Cochrane Controlled Trials Register. Quantitative and qualitative analysis was carried out to evaluate blood loss, blood transfusion, renal function, complications, reoperation, and mortality. RESULTS: A total of 3,234 patients from 52 randomized controlled trials were included. HES preparations versus control solutions in blood loss: HES 130 kD vs. albumin (SMD -0.61, 95% CI -0.82, -0.40), HES 200 kD vs. albumin (SMD -0.01, 95% CI -0.29, 0.28), HES 450 kD vs. albumin (SMD 0.47, 95% CI 0.26, 0.68). When comparing control solutions with HES preparations, 50% (HES 450 kD), 40.9% (HES 200 kD), and 18.2% (HES 130 kD) of the comparisons showed more blood/blood products infusion with HES than with control solutions. A numerically lower mortality rate seemed to be related to HES preparations (2.68 vs 4.23%). No difference was found in terms of complications, renal failure, or reoperation. CONCLUSIONS: Perioperative administration of HES preparations is comparatively safe. The data appraising safety profiles of HES preparations are insufficient to make direct comparisons among themselves. As the third generation of HES preparations, HES 130 kD showed a trend toward lower blood loss and transfusion rates and is a suitable choice for cardiovascular surgery.

An evaluation of intrathecal bupivacaine combined with intrathecal or intravenous clonidine in children undergoing orthopedic surgery: a randomized double-blinded study.

BACKGROUND: Propofol is a popular agent for providing intraoperative sedation in pediatric population during lumbar puncture and spinal anesthesia. Adjuvant-like clonidine is used increasingly in pediatric anesthesia to provide postoperative analgesia with a local anesthetic agent. The aim of this study was to assess the effects of intrathecal and intravenous clonidine on postoperative analgesia/sedation and intraoperative requirements of propofol after intrathecal bupivacaine for orthopedic surgery in children. METHODS: Fifty-nine ASA I and II children aged 6-8 year undergoing orthopedic surgery were randomized to receive intrathecal 0.5% bupivacaine 0.2-0.4 mg·kg(-1) and intravenous 2 ml saline (Group B), intrathecal 0.5% bupivacaine 0.2-0.4 mg·kg(-1) plus 1 µg·kg(-1) clonidine and intravenous 2 ml saline (Group BCit), and 0.5% bupivacaine 0.2-0.4 mg·kg(-1) and intravenous 1 µg·kg(-1) clonidine in 2 ml of saline (Group BCiv). Intraoperative sedation was maintained with 20-50 µg·kg(-1)·min(-1) of propofol infusion. The requirements of propofol, time to first rescue analgesia, and postoperative pain or sedation scores were assessed. The duration of motor and sensory blocks and perioperative adverse events were determined. RESULTS: Clonidine significantly prolonged the time to first rescue analgesia and reduced the requirements of propofol sedation whether administered intravenously or intrathecally. The mean Children and Infants Postoperative Pain Scale scores of children were significantly lower in groups BCit and BCiv than in group B. Postoperative sedation scores were higher in groups BCit and BCiv than in group B. Intrathecal clonidine significantly prolonged the time to regression of the sensory block and recovery of motor block. There were no significant differences among the three groups regarding the incidence of perioperative adverse events. CONCLUSION: Intrathecal or intravenous clonidine similarly provided better postoperative analgesia and sedation and reduced the requirements of propofol. Only intrathecal clonidine prolonged the duration of sensory and motor blocks.

Propofol post-conditioning protects against cardiomyocyte apoptosis in hypoxia/reoxygenation injury by suppressing nuclear factor-kappa B translocation via extracellular signal-regulated kinase mitogen-activated protein kinase pathway.

BACKGROUND AND OBJECTIVE: Perioperative myocardial ischaemia leads to an exceedingly high mortality. Previous studies have indicated that propofol pre-conditioning could mimic the cardioprotective effects of ischaemic pre-conditioning. The purpose of this study was to determine whether propofol post-conditioning is cardioprotective and to explore the possible molecular mechanism of propofol post-conditioning. METHODS: Primary cultured neonatal rat cardiomyocytes were exposed to 12 h of hypoxia followed by 4 h of reoxygenation (H/R) and post-conditioned by different concentrations of propofol at the onset of reperfusion with and without a specific inhibitor of extracellular signal-regulated kinases (ERKs). Cell apoptosis and the generation of intracellular reactive oxygen species were measured using FACScalibur flow cytometric analysis. ERK1/2 phosphorylation and nuclear factor-kappa B (NF-κB) translocation were determined by western blot and immunofluorescence, respectively. RESULTS: Propofol post-conditioning enhanced cell viability (86.6 ± 6.5 versus 64.1 ± 3.4%) and reduced apoptosis (3.6 ± 0.4 versus 12.5 ± 2.1%) to protect cardiomyocytes against H/R injury. Meanwhile, propofol post-conditioning stimulated expression of phosphor-ERKs. H/R markedly induced p65 NF-κB nuclear translocation in cardiomyocytes, whereas propofol post-conditioning significantly suppressed H/R-primed NF-κB translocation. Moreover, addition of the mitogen-activated protein kinase kinase 1 inhibitor U0126 into cardiomyocytes 30 min before H/R eliminated the cardioprotection of propofol post-conditioning. CONCLUSION: Propofol exerts cardioprotection when administered at the early phase of reperfusion. The effect is mediated through decrease in cardiomyocyte apoptosis and NF-κB nucleus translocation potentially via ERK signalling pathways.

Glutamine-induced heat shock protein protects against renal ischaemia-reperfusion injury in rats.

AIM: To find out if a single dose of glutamine can relieve acute renal ischaemia-reperfusion injury in rats, to explore the role of heat shock protein in this process. METHODS: Forty-eight Sprague-Dawley rats were assigned to four groups: saline as control group; glutamine group; quercetin (heat shock protein inhibitor) plus glutamine group; and quercetin plus saline group. The renal ischaemia-reperfusion rat model was established 1 h after drug administration. Serum creatinine (CR) and blood urea nitrogen (BUN) were analyzed. The kidneys were harvested to evaluate the degree of renal injuries. Heat shock protein expression was detected by immunohistochemistry and western blot. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and apoptosis index was calculated. RESULTS: Statistical data from CR, BUN, haematoxylin-eosin (HE) dyeing and TUNEL assay results showed that ischaemia-reperfusion injury and cell apoptosis in the glutamine group were significantly milder than those in control group (P < 0.05), while ischaemia-reperfusion injury and cell apoptosis in the quercetin plus glutamine group and quercetin plus saline group were more severe than those in the control group (P < 0.05). Statistical data from immunohistochemistry and western blot results showed that heat shock protein expression was enhanced in the glutamine group compared with that in the control group (P < 0.01), while it was weaker in the quercetin plus glutamine group and quercetin plus saline group than that in the control group (P < 0.01). CONCLUSION: Our experiment suggested that a single dose of glutamine could relieve renal ischaemia-reperfusion injury in rats in 24 h, and its mechanism may be associated with enhanced heat shock protein expression. This finding may provide a new alternative for protecting against clinical renal ischaemia-reperfusion injury.

Promoting sleep and circadian health may prevent postoperative delirium: A systematic review and meta-analysis of randomized clinical trials.

This systematic review with meta-analysis and trial sequential analysis of randomized clinical trials aimed to clarify the efficacy of sleep and circadian interventions on preventing postoperative delirium. The search and screening identified 13 trials with great heterogeneity in interventions, surgery types as well as methods for evaluating delirium, sleep and circadian rhythms. Meta-analyses revealed that sleep and circadian interventions were associated with decreased incidences of postoperative delirium (pooled relative risk (RR) = 0.48, 95% confidence interval (CI) = 0.29 to 0.78) compared with control. The pooled incidences of delirium for patients receiving interventions and no intervention (control) were 8.6% and 20.7% respectively. Results of the trial sequential analysis supported the interpretation that sleep and circadian interventions significantly diminished delirium compared to control. Subgroup analysis found that interventions that showed positive efficacy on sleep and circadian outcomes (p < 0.001), but not those without improvements (p = 0.114) or without assessments (p = 0.858), were associated with decreased risk of delirium. Dexmedetomidine sedation (p < 0.001) and timed bright light exposure (p = 0.006) appeared to reduce postoperative delirium. In summary, currently only limited evidence suggests strategies targeted at sleep and circadian health as a useful way to prevent postoperative delirium.

[Changes in alpha2-adrenergic receptors gene expression after high-level spinal cord injury in Wistar rats].

OBJECTIVE: To evaluate the change in alpha(2)-adrenergic receptors (alpha(2)-ARs) gene expression after high-level injury of the spinal cord (SCI), aiming as developing a more effective perioperative anesthetic management for high-level SCI patients. METHODS: Adult male Wistar rats were anesthetized and severe spinal crush injury at T4 was produced using modified Allens device. The expression of alpha(2)-ARs mRNA at different levels of spinal cord in normal control rats (C), injured segment (I), above (A) and below (B) the site of injured segment, were measured by reverse transcription-polymerase chain reaction (RT-PCR) 1 day, 3 days, 1 week, 2 weeks, 3 weeks and 4 weeks, respectively after SCI. RESULTS: Compared with group C (sham group), in group A the expression of alpha(2)-ARs mRNA decreased 1 day after SCI (P<0.05) and dropped to the nadir 2 weeks later (P<0.01), but the expression was restored to the normal level 4 weeks later. In group I the lowering of alpha(2)-ARs mRNA expression occurred immediately after SCI and down to the lowest value 1 week later (P<0.01), and did not recover to normal level 4 weeks later (P<0.05). In group B downregulation of alpha(2)-ARs mRNA expression was detected 1 day after SCI (P<0.05), but it was upregulated 1 week later reaching the normal level, which was maintained for 4 weeks. CONCLUSION: In a chronic SCI rat model, alpha(2)-ARs gene expression is downregulated in the injured segment, but returns to the normal level above and below the injured segment. The changes in alpha(2)-ARs may be a pivotal factor contributing to a series of abnormal responses after high-level SCI.

Propofol postconditioning protects H9c2 cells from hypoxia/reoxygenation injury by inducing autophagy via the SAPK/JNK pathway.

Propofol postconditioning (P­PostC) offers cardioprotection in mice, and the upregulation of autophagy protects cardiac cells against ischemia/reperfusion injury. The present study aimed to examine the effects of P­PostC on the induction of autophagy and its potential roles in hypoxia/reoxygenation (H/R) injury. Rat heart­derived H9c2 cells were exposed to H/R, comprising 6 h of hypoxia followed by 4 h of reoxygenation, as well as postconditioning with various concentrations of propofol at the onset of reperfusion. Lactate dehydrogenase (LDH) activity and the rate of cell apoptosis were measured to evaluate the degree of cardiomyocyte H/R injury. The induction of autophagy in myocytes subjected to H/R injury and P­PostC was detected by western blotting and immunofluorescence. Furthermore, the activation of c­Jun N­terminal kinase (JNK) in cells treated with P­PostC with or without co­treatment with SP600125, an inhibitor of JNK, was also determined by western blotting. P­PostC reduced the activity of LDH in the culture medium and the percentage of apoptotic cells compared with cells in the untreated H/R group. In addition, P­PostC induced autophagy and promoted survival signaling in H9c2 cardiac myoblast cells. The inhibition of autophagy by 3­methyladenine treatment diminished the cardioprotective effects of P­PostC. These results indicated that propofol postconditioning promoted cell survival through the induction of autophagy in H9c2 cardiac cells, and that the stress­activated protein kinase/JNK survival pathway may be partly involved in P­PostC­induced autophagy.

Cardiac arrest after graft reperfusion during liver transplantation.

BACKGROUND: Cardiac arrest (CA) during orthotopic liver transplantation (OLT) is rare but it threatens the lives of patients. The cause of perioperitive CA is not fully understood. We reported the occurrence of CA in 5 patients after unclamping of the vena cava and investigated the relationship between CA and associated variables. METHODS: Five patients with CA after graft reperfusion during OLT in our unit from November 1996 to September 2003 were retrospectively reviewed. Analyzed data included donor and recipient demographic data, and recipient operative and postoperative events. RESULTS: Five (2.1%) of 240 patients undergoing OLT experienced CA 5 minutes after graft reperfusion. Two patients died of resuscitation failure. Hyperkalemia and metabolic acidosis after revascularization were observed in some patients. The five patients had hypothermia and hypocalcemia, and one had pulmonary embolism. CONCLUSIONS: CA is one of the syndromes after reperfusion. Many factors such as hyperkalemia, acidosis or pulmonary embolism combined with hypothermia and hypocalcemia during the operation seem to contribute to the occurrence of CA.

[Role of alpha-adrenergic receptors in vascular hyperreactivity in rats with high level spinal injury].

OBJECTIVE: To explore the vascular reactivity of abdominal aorta to agonists of alpha-adrenergic receptors in rat with high level transection of the spinal cord, and to quantify the expression of alpha-AR mRNA subtypes, in order to investigate relationship between alpha-AR and hyperreactivity of abdominal aorta. METHODS: Four weeks after transection of the spinal cord at the level of 4th thoracic vertebra, the rats were sacrificed, and abdominal aorta rings were adopted to assay sensitivity to phenylephrine and clonidine with isolated organ perfusion system. Alpha(1A)-AR, alpha(1B)-AR, alpha(1D)-AR, alpha(2A)-AR, alpha(2B)-AR, alpha(2C)-AR mRNA expressions were quantified by real time polymerase chain reaction (PCR). RESULTS: Compared with abdominal aorta, of rat with sham operation, reactivity of aorta of rat after transection of spinal cord to clonidine was significantly higher (P<0.05 or P<0.01), but difference of vascular reactivity to phenylephrine between them was not significant (P>0.05). Expressions of alpha(1A)-AR mRNA, alpha(1D)-AR mRNA, alpha(2A)-AR mRNA, alpha(2B)-AR mRNA, alpha(2C)-AR mRNA were significantly higher (P<0.05 or P<0.01), while the expression of alpha(1B)-AR mRNA did not vary significantly. CONCLUSION: Vascular hyperreactivity to agonist of alpha(2)-AR may be the mechanism of hyperreactivity of abdominal aorta in rat after transection of spinal cord. Although alpha(1)-AR mRNA expression is higher in aorta of rat with spinal cord injury, vascular hyperreactivity is not the result of upregulation of alpha(1)-AR sensitivity.

A non-invasive magnetic resonance imaging-based model predicts portal venous pressure.

OBJECTIVE: To establish a non-invasive model for the assessment of portal venous pressure (PVP) based on the magnetic resonance (MR) parameters. METHODS: In this prospective study, contrast-enhanced magnetic resonance imaging (MRI) scan was performed in 109 patients indicated for upper abdominal surgeries after their written consents were obtained, and intraoperative PVP measurements were completed in 92 patients. Altogether 17 patients were excluded for not undergoing surgery or unsuccessful catheterization. A linear model was constructed for estimating PVP levels in 56 patients and further validation was conducted in the other 36 patients. RESULTS: The PVP levels were significantly correlated with MR parameters, including splenic volume (SV), splenic venous diameter (SVD), liver/splenic volume ratio, portal venous diameter, hepatic diameter, portal venous cross-sectional area, ascites, varices and arterial portal shunts. A linear model was established as follows: PVP (mmHg) = 2.529 + 1.572 × SVD (mm) + 0.231 × SV/body mass index (× 10(4) cm(5) /kg) + 3.44 × aspartate aminotransferase-to-platelet ratio index. This model showed excellent accuracy in the detection of portal hypertension, with the area under the receiver operating characteristic curve (AUROC) of 0.945 (95% CI 0.867-1.000), with the sensitivity and specificity of 91.7% and 93.7%, respectively. The agreement analysis revealed that the predictive value using this formula closely reflected the patients' actual PVP level. Moreover, the validation confirmed the accuracy of this model for the assessment of portal hypertension [AUROC 0.935 (95% CI 0.856-1.000)]. CONCLUSIONS: The MRI-based formula has great potential for detecting portal hypertension. As a non-invasive measurement, it may be clinically accepted for the replacement of invasive modalities after further refinement.

[Effect of high level spinal cord injury on rat heart function].

OBJECTIVE: To study the effects of high level spinal cord injury (SCI) on rat heart, and investigate the role of endothelin-1 (ET-1) in the harmful effects on heart after SCI. METHODS: Forty-eight male SD rats were randomly divided into six groups of 8 animals each: control group; 4-hour group: 4 th hour after injury to spinal cord at cervical 7 level; 12-hour group: 12 th hour after injury to 7 spinal cord at C7 level; 24-hour group with same injury; 48-hour group and 72-hour group, all with same injury. Mean arterial pressure (MAP), heart rate (HR), left ventricle systolic pressure (LVSP), and left ventricular maximum velocities of contraction (+/-dp/dt max) were recorded in each group. Lactate dehydrogenase (LDH), creatine kinase (CK), MB isoenzyme of creatine kinase (CK-MB) and ET-1 contents in the myocardium. were also measured. Specimens of the myocardium were harvested for ultrastructure examination with transmission electron microscopy. RESULTS: Hemodynamics variables including HR, MAP, LVSP and+/-dp/dtmax were significantly decreased in all the injury groups compared with that of control group (P<0.05 or P<0.01). These variables in 12-hour group showed lowest values among all the groups (all P<0.01). But the values of cardiac enzymes were much higher in five injury groups compared with that of control group (P<0.05 or P<0.01). ET-1 contents in serum and cardiac tissue raised markedly after the injury was inflicted to the animals (P<0.05), reaching peak at 12 hours (P<0.01). Ultrastructural examination of the myocardial tissue demonstrated that there were mild dissolution of myocardial fibrils and vacuolation of mitochondria at 12 hours after injury. CONCLUSION: High level SCI could induce myocardial injuries and an excessive production of ET-1 in circulation and myocardial tissue might play a role in myocardial damage after injury of the spinal cord at a high level.