Comparison of the in-vivo effect of two tranexamic acid doses on fibrinolysis parameters in adults undergoing valvular cardiac surgery with cardiopulmonary bypass - a pilot investigation.

BACKGROUND: The blood saving efficacy of TXA in cardiac surgery has been proved in several studies, but TXA dosing regimens were varied in those studies. Therefore, we performed this study to investigate if there is a dose dependent in-vivo effect of TXA on fibrinolysis parameters by measurement of fibrinolysis markers in adults undergoing cardiac surgery with CPB. METHODS: A double-blind, randomized, controlled prospective trial was conducted from February 11, 2017 to May 05, 2017. Thirty patients undergoing cardiac valve surgery were identified and randomly divided into a placebo group, low-dose group and high-dose group by 1: 1: 1. Fibrinolysis parameters were measured by plasma levels of D-Dimers, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), plasmin-antiplasmin complex (PAP), tissue plasminogen activator (tPA) and thrombomodulin (TM). Those proteins were measured at five different sample times: preoperatively before the TXA injection (T1), 5 min after the TXA bolus (T2), 5 min after the initiation of CPB (T3), 5 min before the end of CPB (T4) and 5 min after the protamine administration (T5). A Thrombelastography (TEG) and standard coagulation test were also performed. RESULTS: Compared with the control group, the level of the D-Dimers decreased in the low-dose and high-dose groups when the patients arrived at the ICU and on the first postoperative morning. Over time, the concentrations of PAI-1, TAFI, and TM, but not PAP and tPA, showed significant differences between the three groups (P <  0.05). Compared with the placebo group, the plasma concentrations of PAI-1 and TAFI decreased significantly at the T3 and T4 (P <  0.05); TAFI concentrations also decreased at the T5 in low-dose group (P < 0.05). Compared with the low-dose group, the concentration of TM increased significantly at the T4 in high-dose group. CONCLUSIONS: The in-vivo effect of low dose TXA is equivalent to high dose TXA on fibrinolysis parameters in adults with a low bleeding risk undergoing valvular cardiac surgery with cardiopulmonary bypass, and a low dose TXA regimen might be equivalent to high dose TXA for those patients. TRIAL REGISTRATION: ChiCTR-IPR-17010303 , Principal investigator: Zhen-feng ZHOU, Date of registration: January 1, 2017.

Single nucleotide polymorphisms associated with postoperative inadequate analgesia after single-port VATS in Chinese population.

BACKGROUND: Postoperative inadequate analgesia following video-assisted thoracoscopic surgery (VATS) is a common and significant clinical problem. While genetic polymorphisms may play role in the variability of postoperative analgesia effect, few studies have evaluated the associations between genetic mutations and inadequate analgesia after single-port VATS. METHODS: Twenty-eight single nucleotide polymorphisms (SNPs) among 18 selected genes involved in pain perception and modulation were genotyped in 198 Chinese patients undergoing single-port VATS. The primary outcome was the occurrence of inadequate analgesia in the first night and morning after surgery which was defined by a comprehensive postoperative evaluation. Multivariable logistic regression analyses were used to identify the association between genetic variations and postoperative inadequate analgesia. RESULTS: The prevalence of postoperative inadequate analgesia was 45.5% in the present study. After controlling for age and education level, association with inadequate analgesia was observed in four SNPs among three genes encoding voltage-gated sodium channels. Patients with the minor allele of rs33985936 (SCN11A), rs6795970 (SCN10A), and 3312G > T (SCN9A) have an increased risk of suffering from inadequate analgesia. While the patients carrying the minor allele of rs11709492 (SCN11A) have lower risk experiencing inadequate analgesia. CONCLUSIONS: We identified that SNPs in SCN9A, SCN10A, and SCN11A play a role in the postoperative inadequate analgesia after single-port VATS. Although future larger and long-term follow up studies are warranted to confirm our findings, the results of the current study may be utilized as predictors for forecasting postoperative analgesic effect for patients receiving this type of surgery. TRIAL REGISTRATION: This study was retrospectively registered in the ClinicalTrials.gov Registry (NCT03916120) on April 16, 2019.

Abnormal within- and cross-networks functional connectivity in different outcomes of herpes zoster patients.

Neuroimaging studies have displayed aberrant brain activities in individual sensory- and emotional-linked regions in postherpetic neuralgia (PHN) patients. However, multi-dimensional dysfunction in chronic pain may rely on the interplay between networks. Little is known about the changes in the functional architecture of resting state networks (RSNs) in PHN. In this cross-sectional study, we recruited 31 PHN patients, 33 RHZ patients and 34 HCs; all participants underwent resting-state functional magnetic resonance imaging scans. We investigated the differences of within- and cross-network connectivities between different outcomes of HZ patients [including PHN and recuperation from herpes zoster (RHZ)] and healthy controls (HCs) so as to extract a characteristic network pattern of PHN. The abnormal network connectivities were then correlated with clinical variables in respective groups. PHN and RHZ patients could be similarly characterized by abnormal within-default mode network (DMN), DMN-salience network (SN) and SN-basal ganglia network (BGN) connectivity relative to HCs. Of note, compared with RHZ patients, PHN patients could be characterized by abnormal DMN-BGN and within-BGN connectivity. Furthermore, the within-DMN connectivity was associated with pain-induced emotional scores among PHN patients. Our study presented that network-level imbalance could account for the pain-related dysfunctions in different outcomes of herpes zoster patients. These insights are potentially useful for understanding neuromechanism of PHN and providing central therapeutic targets for PHN.

Delayed Initiation of Supplemental Pain Management is Associated with Postherpetic Neuralgia: A Retrospective Study.

BACKGROUND: Acute pain is a risk factor for developing postherpetic neuralgia (PHN), the most common complication of herpes zoster (HZ). Supplemental analgesics are frequently used in the treatment of acute herpetic pain. However, there are insufficient data regarding when to begin supplemental analgesics, and it is unknown whether the delayed use of supplemental analgesics increases the risk of PHN in high-risk patients. OBJECTIVES: This study aimed to evaluate the association between initial time of supplemental pain management and the risk of PHN in high-risk patients. STUDY DESIGN: Retrospective study. SETTING: The Department of Anesthesiology and Pain Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine. METHODS: We performed a retrospective study between May 13, 2017 and August 8, 2018 in our clinic. Multivariable logistic regression analysis was conducted to examine the independent factors associated with PHN. Supplemental pain management was defined as any use of opioids, tricyclic antidepressants, or nerve blocks. A subgroup analysis was conducted in patients who received supplemental pain management within the first 30 days of onset. According to the initial time of supplemental pain management, patients were divided into 2 groups: the early treatment group (<= 14 days), and the late treatment group (> 14 days). The clinical outcomes in these 2 groups was compared for propensity score (PS) matching. RESULTS: A total of 134 patients with HZ aged 50 years or older with moderate to severe pain were enrolled in this study. The delayed initiation of supplemental pain management (> 14 days) (odds ratio, 4.11; 95% confidence interval, 1.69-9.92; P = 0.002) and severity of rash (odds ratio, 2.93; 95% confidence interval, 1.22-7.01; P = 0.016) were independent factors associated with PHN. In the subgroup analysis, after PS matching, there were no significant differences in the baseline clinical parameters between the early and late treatment groups. The incidence of PHN was significantly lower in the early treatment group than the late treatment group (36. 4% vs. 72.7%; P = 0.015). Reduction in pain was also greater in the early treatment group. LIMITATIONS: The findings identified in the present study are specific to the patients who were relatively older and with moderate to severe pain. It is impossible to determine from our study whether younger individuals and individuals with mild acute pain will benefit from early supplemental treatments. Furthermore, because of the retrospective nature of the study, there may be some confounders that could not be controlled. Further prospective studies with larger sample sizes and longer follow-up periods are needed. CONCLUSIONS: The early use of supplemental pain management may decrease the risk of PHN. It might therefore be beneficial to consider administering supplemental pain management earlier in older patients with moderate to severe acute herpetic pain. KEY WORDS: Herpes zoster, postherpetic neuralgia, analgesia, opioid, nerve block, tricyclic antidepressant.

Identification of Candidate Genes Associated with Postherpetic Neuralgia Susceptibility.

BACKGROUND: Postherpetic neuralgia (PHN) is one of the most common complications of herpes zoster (HZ). Heritable factors have been found to play a role in various clinical pain symptoms. However, the effect of gene variability on the susceptibility of PHN remains poorly understood. OBJECTIVES: The aim of this study was to evaluate whether genetic variation in pain pathway genes was associated with PHN susceptibility in the Chinese population. STUDY DESIGN: Case-control study. SETTING: Department of Anesthesiology and Pain Medicine in a university hospital. METHODS: Seventy patients with PHN and 111 patients with HZ without developing PHN were enrolled. All patients received standardized antiviral agents and analgesics as needed during the acute phase of HZ. Twenty-four candidate genetic polymorphisms in 12 genes (IL1B, SCN9A, KCNK9, TRPV1, P2RX7, HTR1A, HTR2A, ADRB1, ADRB2, BDNF, COMT, and OPRM1) were genotyped in all patients. Multivariable logistic regression analyses were used to identify genetic variations associated with PHN susceptibility while controlling for potential confounders. RESULTS: Our results suggested that only variation in P2RX7 gene was associated with PHN susceptibility. The P2RX7 rs7958311 AG heterozygous genotype carriers had a decreased risk for PHN in the overdominant model (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.21-0.77; P = 0.005), and codominant model (OR, 0.44; 95% CI, 0.20-0.98; P = 0.045). The P2RX7 rs7958311 GG homozygote genotype was associated with an increased risk for PHN under a recessive model (OR, 2.15; 95% CI, 1.01-4.56; P = 0.046). There were no significant associations between the other 23 single-nucleotide polymorphisms and PHN susceptibility. LIMITATIONS: Lack of validation cohort to verify the findings. CONCLUSIONS: In the present study in the Chinese population, we found purinergic receptor P2X7 rs7958311 may contribute to PHN development after HZ. Future larger independent cohorts are warranted to replicate these initial findings. KEY WORDS: Herpes zoster, postherpetic neuralgia, polymorphisms.

Disrupted default mode network dynamics in recuperative patients of herpes zoster pain.

INTRODUCTION: Previous studies of herpes zoster (HZ) have focused on acute patient manifestations and the most common sequela, postherpetic neuralgia (PHN), both serving to disrupt brain dynamics. Although the majority of such patients gradually recover, without lingering severe pain, little is known about life situations of those who recuperate or the brain dynamics. Our goal was to determine whether default mode network (DMN) dynamics of the recuperative population normalize to the level of healthy individuals. METHODS: For this purpose, we conducted resting-state functional magnetic resonance imaging (fMRI) studies in 30 patients recuperating from HZ (RHZ group) and 30 healthy controls (HC group). Independent component analysis (ICA) was initially undertaken in both groups to extract DMN components. DMN spatial maps and within-DMN functional connectivity were then compared by group and then correlated with clinical variables. RESULTS: Relative to controls, DMN spatial maps of recuperating patients showed higher connectivity in middle frontal gyrus (MFG), right/left medial temporal regions of cortex (RMTC/LMTC), right parietal lobe, and parahippocampal gyrus. The RHZ (vs HC) group also demonstrated significant augmentation of within-DMN connectivity, including that of LMTC-MFG and LMTC-posterior cingulate cortex (PCC). Furthermore, the intensity of LMTC-MFG connectivity correlated significantly with scoring of pain-induced emotions and life quality. CONCLUSION: Findings of this preliminary study indicate that a disrupted dissociative pattern of DMN persists in patients recuperating from HZ, relative to healthy controls. We have thus provisionally established the brain mechanisms accounting for major outcomes of HZ, offering heuristic cues for future research on HZ transition states.

Fan Therapy for the Relief of Dyspnea in Adults with Advanced Disease and Terminal Illness: A Meta-Analysis of Randomized Controlled Trials.

Background: Dyspnea is one of the most common symptoms in patients with advanced disease and terminal illness, associated with poorer quality of life. The efficacy of fan therapy to palliate dyspnea is inconsistent and unclear. Objective: The aim of this meta-analysis was to evaluate the efficacy of fan therapy for the relief of dyspnea in adults with advanced disease and terminal illness. Design: The CENTRAL, MEDLINE, EMBASE, CINAHL, and PsycINFO were searched to retrieve all randomized controlled trials examining the benefits of fan therapy for the relief of dyspnea in patients at the advanced stages of illness. Risk of bias was assessed according to the Cochrane Collaboration standard scheme. Results: Five studies involving 198 adults were identified. Fan therapy was associated with a significant relief of breathlessness intensity immediately after intervention (mean differences [MDs], -1.01; 95% confidence interval [CI], -1.57 to -0.45; p < 0.001) and 10 minutes after intervention (MDs, -0.90; 95% CI, -1.53 to -0.27; p = 0.005). Long-term application of fan therapy for at least one month was not related to changes of dyspnea severity (MDs, 0.10; 95% CI, -1.14 to 1.35; p = 0.870). However, significant heterogeneity and low quality of the included trials limit applicability of the results in general practice. No difference was found in activity performance, respiratory rate and SpO2, changes in other symptom intensities, and adverse events. Conclusion: Current trials provided low-quality evidence for a significant short-term effect after fan therapy in the relief of dyspnea and no beneficial effect in the long-term application in adults with advanced disease and terminal illness.

Postoperative analgesic effect of hydromorphone in patients undergoing single-port video-assisted thoracoscopic surgery: a randomized controlled trial.

Objective: To study the general efficacy of hydromorphone as a systemic analgesic in postoperative pain management following single-port video-assisted thoracoscopic surgery (VATS) and to explore the optimal administration regimen. Methods: A prospective, randomized, double-blind study was designed and conducted in a tertiary hospital. In total, 157 valid patients undergoing single-port VATS were randomly allocated into three groups. A total of 53 patients received morphine bolus only for postoperative analgesia (Group Mb); 51 patients received a hydromorphone background infusion plus bolus (Group Hb + i), and 53 patients received a hydromorphone bolus only (Group Hb). The primary outcomes were patient-reported static and dynamic pain levels; the secondary outcomes included side effects, sleep quality, and recovery indexes. Results: Patients in Group Hb + i experienced lower pain intensity (approximately 10 out of 100 on the visual analog scale) in both static pain and dynamic pain in the days following surgery (P<0.01), better sleep quality during the first night only (P=0.002), and a higher satisfaction level than those in the other two groups (P=0.006). A comparison of these variables in Group Mb and Group Hb resulted in no significant differences. Lastly, side effects and recovery indexes remained the same among bolus-only groups and bolus-plus-background-infusion groups. Conclusion: There is no advantage to administering hydromorphone over morphine using bolus only mode. Within 24 h after surgery, a background infusion should be considered as a part of a standard protocol for patient-controlled intravenous analgesia. At 24 h after surgery, the background infusion should be adjusted in accordance with patient preferences and pain intensity.

The Effect of Early Use of Supplemental Therapy on Preventing Postherpetic Neuralgia: A Systematic Review and Meta-analysis.

BACKGROUND: Postherpetic neuralgia (PHN) is the most common and refractory complication of herpes zoster (HZ). Aggressive treatment of acute pain in HZ has the potential to prevent the development of PHN, but the preventive efficacy of supplemental therapy commonly used in clinical practice is controversial. OBJECTIVES: Our aim is to examine the efficacy of supplemental therapy in preventing PHN. STUDY DESIGN: A meta-analysis. SETTING: All of the selected studies are randomized controlled trials (RCTs). METHODS: A systematic and comprehensive database search was performed in CENTRAL (1976 to March 2016), MEDLINE (1977 to January 2016), and EMBASE (May 1980 to December 2016). According to the selection criteria, data of the included studies were extracted by 2 independent reviewers. RevMan 5.3 (The Nordic Cochrane Centre for The Cochrane Collaboration, Copenhagen, Denmark) was used to perform this meta-analysis. RESULTS: Nine trials, with a total of 1,757 participants (888 in the treatment group and 867 in the control group), were included in the final analysis. Of the 9 trials, 3 compared systemic adjunct therapies with the control, and 6 trials compared interventional procedures with the control. The early use of supplemental therapy was associated with a significantly less incidence of PHN in 3 months after acute rash presence (RR 0.53, 95%CI 0.34 to 0.81, P = 0.004). The systemic adjunct treatments subgroup was not found with any benefit (RR 0.76, 95%CI 0.46 to 1.26, P = 0.29). A significant decrease in visual analog scale (VAS) score was reported in all of the 9 trials when compared with baseline, but the decrease slopes of the pain scores between the treatment group and the control group were similar in 5 trials. The most common adverse events in systemic adjunct treatments group were dizziness, nausea, dyspepsia, and dry mouth. The interventional procedures group was associated with procedure-related complications such as mild hypotension, voice change, dysphagia, drowsiness, and headache. LIMITATIONS: There were only a few RCTs and most of them lacked adequate allocation concealment and blinding. Further, the English-only approach might have omitted trials published in non-English journals. Finally, some of the secondary outcomes of data were insufficient for meta-analysis, and future studies are warranted. CONCLUSION: This meta-analysis demonstrates that the early use of supplemental therapy can significantly reduce the incidence of PHN. The subgroup analysis shows that supplemental interventional procedures have a beneficial effect on preventing PHN, while supplemental systemic adjunct treatments do not. The early use of interventional procedures for acute pain may be a preferred choice for patients without contraindication, but evidence is moderate. More data from high-quality RCTs will be needed to confirm these results.Key words: Postherpetic neuralgia, systemic treatment, local anesthesia, analgesia, meta-analysis.

Intraoperative tranexamic acid is associated with postoperative stroke in patients undergoing cardiac surgery.

BACKGROUND: Stroke is a devastating and potentially preventable complication of cardiac surgery. Tranexamic acid (TXA) is a commonly antifibrinolytic agent in cardiac surgeries with cardiopulmonary bypass (CPB), however, there is concern that it might increase incidence of stroke after cardiac surgery. In this retrospective study, we investigated whether TXA usage could increase postoperative stroke in cardiac surgery. METHODS: A retrospective study was conducted from January 1, 2010, to December 31, 2015, in 2,016 patients undergoing cardiac surgery, 664 patients received intravenous TXA infusion and 1,352 patients did not receive any antifibrinolytic agent. Univariate and propensity-weighted multivariate regression analysis were applied for data analysis. RESULTS: Intraoperative TXA administration was associated with postoperative stroke (1.7% vs. 0.5%; adjusted OR, 4.11; 95% CI, 1.33 to 12.71; p = 0.014) and coma (adjusted OR, 2.77; 95% CI, 1.06 to 7.26; p = 0.038) in cardiac surgery. As subtype analysis was performed, TXA administration was still associated with postoperative stroke (1.7% vs. 0.3%; adjusted OR, 5.78; 95% CI, 1.34 to 27.89; p = 0.018) in patients undergoing valve surgery or multi-valve surgery only, but was not associated with postoperative stroke (1.7% vs. 1.3%; adjusted OR, 5.21; 95% CI, 0.27 to 101.17; p = 0.276) in patients undergoing CABG surgery only. However, TXA administration was not associated with postoperative mortality (adjusted OR, 1.31; 95% CI, 0.56 to 3.71; p = 0.451), seizure (adjusted OR, 1.13; 95% CI, 0.42 to 3.04; p = 0.816), continuous renal replacement therapy (adjusted OR, 1.36; 95% CI, 0.56 to 3.28; p = 0.495) and resternotomy for postoperative bleeding (adjusted OR, 1.55; 95% CI, 0.55 to 4.30; p = 0.405). No difference was found in postoperative ventilation time (adjusted B, -1.45; SE, 2.33; p = 0.535), length of intensive care unit stay (adjusted B, -0.12; SE, 0.25; p = 0.633) and length of hospital stay (adjusted B, 0.48; SE, 0.58; p = 0.408). CONCLUSIONS: Based on the 5-year experience of TXA administration in cardiac surgery with CPB, we found that postoperative stroke was associated with intraoperative TXA administration in patients undergoing cardiac surgery, especially in those undergoing valve surgeries only. This study may suggest that TXA should be administrated according to clear indications after evaluating the bleeding risk in patients undergoing cardiac surgery, especially in those with high stroke risk.

[Determination of gentiopicroside in different morphological types of cultivated Gentiana manshurica population].

OBJECTIVE: To study the correlation between morphological variation and gentiopicroside content in cultivated Gentiana manshurica roots and to investigate the feasibility of breeding new varieties of high effective constituent content. METHOD: Gentiopicroside was determined in 5 morphological types of cultivated G. manshurica roots by HPLC, which are normal (or wild) type, white-flowered type, thick-rooted type, broad-leaved type I and broad-leaved type II. RESULT: Among different types gentiopicroside content is the highest in the roots of thick-rooted type, the contents decrease as following order: normal type, broad-leaved type I white-flowered type and broad-leaved type II, and the gentiopicroside contents in the same type root system are a positive correlation with root ages, as 3-years-age roots > 2-years-age roots > 1-year-age varied with roots. CONCLUSION: The contents of effective constituent vary with the morphological variation in cultivated G. manshurica. It is feasible to breed a new variety with high effective constituent with the morphological character as a selecting index.