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.

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.