Abstract

BACKGROUND Vascular surgery may be followed by internal bleeding due to inadequate surgical haemostasis, abnormal clotting, or surgical complications. Bleeding ranges from minor, with no transfusion requirement, to massive, requiring multiple blood product transfusions. There are a number of drugs, given systemically or applied locally, which may reduce the need for blood transfusion. OBJECTIVES To assess the effectiveness and safety of anti-fibrinolytic and haemostatic drugs and agents in reducing bleeding and the need for blood transfusion in people undergoing major vascular surgery or vascular procedures with a risk of moderate or severe (> 500 mL) blood loss. SEARCH METHODS We searched: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL, and Transfusion Evidence Library. We also searched the WHO ICTRP and ClinicalTrials.gov trial registries for ongoing and unpublished trials. Searches used a combination of MeSH and free text terms from database inception to 31 March 2022, without restriction on language or publication status. SELECTION CRITERIA We included randomised controlled trials (RCTs) in adults of drug treatments to reduce bleeding due to major vascular surgery or vascular procedures with a risk of moderate or severe blood loss, which used placebo, usual care or another drug regimen as control. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were units of red cells transfused and all-cause mortality. Our secondary outcomes included risk of receiving an allogeneic blood product, risk of reoperation or repeat procedure due to bleeding, risk of a thromboembolic event, risk of a serious adverse event and length of hospital stay. We used GRADE to assess certainty of evidence. MAIN RESULTS We included 22 RCTs with 3393 participants analysed, of which one RCT with 69 participants was reported only in abstract form, with no usable data. Seven RCTs evaluated systemic drug treatments (three aprotinin, two desmopressin, two tranexamic acid) and 15 RCTs evaluated topical drug treatments (drug-containing bioabsorbable dressings or glues), including fibrin, thrombin, collagen, gelatin, synthetic sealants and one investigational new agent. Most trials were conducted in high-income countries and the majority of the trials only included participants undergoing elective surgery. We also identified two ongoing RCTs. We were unable to perform the planned network meta-analysis due to the sparse reporting of outcomes relevant to this review. Systemic drug treatments We identified seven trials of three systemic drugs: aprotinin, desmopressin and tranexamic acid, all with placebo controls. The trials of aprotinin and desmopressin were small with very low-certainty evidence for all of our outcomes. Tranexamic acid versus placebo was the systemic drug comparison with the largest number of participants (2 trials; 1460 participants), both at low risk of bias. The largest of these included a total of 9535 individuals undergoing a number of different higher risk surgeries and reported limited information on the vascular subgroup (1399 participants). Neither trial reported the number of units of red cells transfused per participant up to 30 days. Three outcomes were associated with very low-certainty evidence due to the very wide confidence intervals (CIs) resulting from small study sizes and low number of events. These were: all-cause mortality up to 30 days; number of participants requiring an allogeneic blood transfusion up to 30 days; and risk of requiring a repeat procedure or operation due to bleeding. Tranexamic acid may have no effect on the risk of thromboembolic events up to 30 days (risk ratio (RR) 1.10, 95% CI 0.88 to 1.36; 1 trial, 1360 participants; low-certainty evidence due to imprecision). There is one large ongoing trial (8320 participants) comparing tranexamic acid versus placebo in people undergoing non-cardiac surgery who are at high risk of requiring a red cell transfusion. This aims to complete recruitment in April 2023. This trial has primary outcomes of proportion of participants transfused with red blood cells and incidence of venous thromboembolism (DVT or PE). Topical drug treatments Most trials of topical drug treatments were at high risk of bias due to their open-label design (compared with usual care, or liquids were compared with sponges). All of the trials were small, most were very small, and few reported clinically relevant outcomes in the postoperative period. Fibrin sealant versus usual care was the topical drug comparison with the largest number of participants (5 trials, 784 participants). The five trials that compared fibrin sealant with usual care were all at high risk of bias, due to the open-label trial design with no measures put in place to minimise reporting bias. All of the trials were funded by pharmaceutical companies. None of the five trials reported the number of red cells transfused per participant up to 30 days or the number of participants requiring an allogeneic blood transfusion up to 30 days. The other three outcomes were associated with very low-certainty evidence with wide confidence intervals due to small sample sizes and the low number of events, these were: all-cause mortality up to 30 days; risk of requiring a repeat procedure due to bleeding; and risk of thromboembolic disease up to 30 days. We identified one large trial (500 participants) comparing fibrin sealant versus usual care in participants undergoing abdominal aortic aneurysm repair, which has not yet started recruitment. This trial lists death due to arterial disease and reintervention rates as primary outcomes. AUTHORS' CONCLUSIONS Because of a lack of data, we are uncertain whether any systemic or topical treatments used to reduce bleeding due to major vascular surgery have an effect on: all-cause mortality up to 30 days; risk of requiring a repeat procedure or operation due to bleeding; number of red cells transfused per participant up to 30 days or the number of participants requiring an allogeneic blood transfusion up to 30 days. There may be no effect of tranexamic acid on the risk of thromboembolic events up to 30 days, this is important as there has been concern that this risk may be increased. Trials with sample size targets of thousands of participants and clinically relevant outcomes are needed, and we look forward to seeing the results of the ongoing trials in the future.

Abstract

Tranexamic acid (TXA) is one of the most commonly used antifibrinolytic agents for surgical patients. However, the effect of TXA on myocardial injury remains controversial. We systemically reviewed literature regarding the effectiveness of TXA on myocardial injury in patients who have undergone a cardiac surgery. We included all randomized controlled trials (RCTs) comparing TXA and control (saline) in cardiac surgical patients. Relevant studies were identified by a comprehensive electronic literature search from database inception to 15 August 2021. A standardized data extraction form was used to collect methodological and outcome variables from each eligible study. We conducted a meta-analysis to estimate the pooled effect size of TXA administration on myocardial injury. In total, eight RCTs were identified, with 292 patients in the TXA group, and 241 patients in saline or control group. The meta-analysis demonstrated that patients in the TXA group had lower levels of CK-MB and cTnI within 24 h postoperatively (CK-MB: P = 0.005; cTnI: P = 0.01), compared with the saline group. No significant difference was found with respect to AST level (P = 0.71) between TXA and saline groups within 24 h postoperatively. TXA administration was found to be associated with less myocardial injury among patients who have undergone cardiac surgery. High-quality randomized controlled trials are warranted to further examine the cardioprotective effects of TXA.

Abstract

Background: Protamine can decrease the risk of hemorrhage during carotid recanalization. However, it may cause severe side effects. There is no consensus on the safety and efficacy of protamine during surgery. Thus, we conduct a comprehensive review and meta-analysis to compare the differences between the protamine and the no-protamine group. Method: We systematically obtained literature from Medline, Google Scholar, Cochrane Library, and PubMed electronic databases. All four databases were scanned from 1937 when protamine was first adopted as a heparin antagonist until February 2021. The reference lists of identified studies were manually checked to determine other eligible studies that qualify. The articles were included in this meta-analysis as long as they met the criteria of PICOS; conference or commentary articles, letters, case report or series, and animal observation were excluded from this study. The Newcastle-Ottawa Quality Assessment Scale and Cochrane Collaboration's tool are used to assess the risk of bias of each included observational study and RCT, respectively. Stata version 12.0 statistical software (StataCorp LP, College Station, Texas) was adopted as statistical software. When I (2) < 50%, we consider that the data have no obvious heterogeneity, and we conduct a meta-analysis using the fixed-effect model. Otherwise, the random-effect model was performed. Result: A total of 11 studies, consisting of 94,618 participants, are included in this study. Our analysis found that the rate of wound hematoma had a significant difference among protamine and no-protamine patients (OR = 0.268, 95% CI = 0.093 to 0.774, p = 0.015). Furthermore, the incidence of hematoma requiring re-operation (0.7%) was significantly lower than that of patients without protamine (1.8%). However, there was no significant difference in the incidence of stroke, wound hematoma with hypertension, transient ischemic attacks (TIA), myocardial infarction (MI), and death. Conclusion: Among included participants undergoing recanalization, the use of protamine is effective in reducing hematoma without increasing the risk of having other complications. Besides, more evidence-based performance is needed to supplement this opinion due to inherent limitations.

Abstract

BACKGROUND Tranexamic acid has been increasingly used for blood conservation in cardiac surgery. However, the evidence supporting the routine use of tranexamic acid in Chinese pediatric patients undergoing cardiac surgery remains weak. This meta-analysis aimed to systematically review the efficacy of tranexamic acid when applying to Chinese pediatric patients undergoing cardiac surgery. PARTICIPANTS Chinese pediatric patients undergoing cardiac surgery. INTERVENTIONS Tranexamic acid or control drugs (saline/blank). METHODS PUBMED, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP Data till May 4, 2021, database search was updated on August 1. Primary outcomes of interest included postoperative bleeding, allogeneic transfusion, and reoperation for bleeding. Secondary outcomes of interest included postoperative recovery. For continuous/dichotomous variables, treatment effects were calculated as weighted mean difference (WMD)/odds ratio and 95% confidence interval. RESULTS A database search yielded 15 randomized controlled trials including 1641 patients, where 8 studies were allocated into non-cyanotic congenital group, 5 were allocated into cyanotic congenital group, and the other 2 were allocated into combined cyanotic/non-cyanotic group. This meta-analysis demonstrate that tranexamic acid administration can reduce the postoperative 24 hours blood loss in non-cyanotic, cyanotic, and combined cyanotic/non-cyanotic patients, the red blood cell transfusion in non-cyanotic and cyanotic patients, and the fresh frozen plasma transfusion in non-cyanotic and combined cyanotic/non-cyanotic patients. CONCLUSION This meta-analysis demonstrates that tranexamic acid is highly effective in reducing the blood loss in Chinese pediatric cardiac surgery, but it behaves poorly when it comes to the transfusion requirement. To further confirm this, more well-designed and adequately-powered randomized trials are needed.

Abstract

BACKGROUND Large bore access procedures rely on vascular closure devices to minimize access site complications. Suture-based vascular closure devices (S-VCD) such as ProGlide and ProStar XL have been readily used, but recently, newer generation collagen-based vascular closure devices (C-VCD) such as MANTA have been introduced. Data on comparisons of these devices are limited. METHODS PubMed, Scopus and Cochrane were searched for articles on vascular closure devices using keywords, ("Vascular closure devices" OR "MANTA" OR "ProStar XL" OR "ProGlide") AND ("outcomes") that resulted in a total of 875 studies. Studies were included if bleeding or vascular complications as defined by Valve Academic Research Consortium-2 were compared between the two types of VCDs. The event level data were pooled across trials to calculate the Odds Ratio (OR) with 95% CI, and analysis was done with Review Manager 5.4 using random effects model. RESULTS Pooled analyses from these nine studies resulted in a total of 3410 patients, out of which 2855 were available for analysis. A total of 1229 received C-VCD and 1626 received S- VCD. Among the patients who received C-VCD, the bleeding complications (major and minor) were similar to patients who received S-VCD ((OR: 0.70 (0.35-1.39), p = 0.31, I(2) = 55%), OR: 0.92 (0.53-1.61), p = 0.77, I(2) = 65%)). The vascular complications (major and minor) in patients who received C-VCD were also similar to patients who received S-VCD ((OR: 1.01 (0.48-2.12), p = 0.98, I(2) = 52%), (OR: 0.90 (0.62-1.30), p = 0.56, I(2) = 35%)). CONCLUSIONS Bleeding and vascular complications after large bore arteriotomy closure with collagen-based vascular closure devices are similar to suture-based vascular closure devices.

Abstract

INTRODUCTION Significant blood loss during cardiac surgery is associated with a significant increase in morbidity and mortality. Factor Eight Inhibitor Bypassing Activity (FEIBA), a hemostatic bypassing agent mainly used in hemophiliac patients, has also been used for intractable surgical bleeding during cardiac surgical procedures in non-hemophiliac patients. However, concerns exist that its use may be linked to increased incidence of perioperative adverse effects including thrombotic complications. AREAS COVERED A systematic literature search was performed on MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases for all studies that reported the administration of FEIBA for treatment of bleeding during adult cardiac surgery in non-hemophiliac patients. After selecting of title and abstracts, two authors assessed the methodological quality of the full-text articles prior to final inclusion in the manuscript. EXPERT OPINION The safety profile of FEIBA was determined through an aggregate count of adverse events. Major complications included renal failure, re-operation for unresolved bleeding, postoperative mortality, and thromboembolic events. Overall, there is insufficient robust evidence to make a definitive conclusion about the safety or efficacy of using of FEIBA as a hemostatic agent in the setting of cardiac surgery.

Abstract

OBJECTIVES Colloid oncotic pressure is an important factor in cardiac surgery, owing to its role in haemodilution. The effect of cardiopulmonary bypass prime fluids on the colloid oncotic pressure are unknown. In this study, the effect of crystalloid and colloid prime fluids, with or without retrograde autologous priming on the colloid oncotic pressure during elective cardiac surgery were evaluated. METHODS Randomized controlled trials and prospective clinical trials comparing crystalloid and colloid priming fluids or with retrograde autologous priming were selected. Primary outcome was the colloid oncotic pressure; secondary outcomes were fluid balance, fluid requirements, weight gain, blood loss, platelet count, and transfusion requirements. RESULTS From 1582 records, 29 eligible studies were identified. Colloid oncotic pressures were comparable between gelofusine and hydroxyethyl starch during bypass (mean difference [MD]: 0.69; 95% confidence interval [CI]: -2.05, 3.43; P = 0.621), after bypass (MD: -0.11; 95% CI: -2.54, 2.32; P = 0.930), and postoperative (MD: -0.61; 95% CI: -1.60, 0.38; P = 0.228). Fluid balance was lower with hydroxyethyl starch than with crystalloids. Retrograde autologous priming reduced transfusion requirements compared with crystalloids. Blood loss was comparable between groups. CONCLUSIONS Colloid oncotic pressures did not differ between crystalloids and colloids. As a result of increased transcapillary fluid movement, fluid balance was lower with hydroxyethyl starch than with crystalloids. Haematocrit and transfusion requirements were comparable between groups. However, the latter was lower when retrograde autologous priming was applied to crystalloid priming compared with crystalloids alone. Finally, no differences in blood loss were observed between the groups.

Abstract

OBJECTIVE This study aims to evaluate the anti-inflammatory effect of tranexamic acid (TXA) on adult cardiac surgical patients. METHODS PubMed, Embase, Ovid, Web of Science, CNKI, VIP, and WANFANG databases were systematically searched using the related keywords for cardiac surgical randomized controlled trials (RCTs) published from their inception to February 1, 2022. The primary outcomes were postoperative inflammatory biomarkers levels. The secondary outcomes were postoperative systemic inflammatory response syndrome and other major postoperative outcomes. The odds ratios and/or the weighted mean difference (WMD) with a 95% confidence interval (CI) were used to pool the data. RESULTS Ten RCTs with 770 adult cardiac surgical patients were included. Compared with placebo, TXA achieved statistically significant inhibition of the postoperative interleukin (IL)-6 level (postoperative 6 h: n = 6 trials; WMD -31.66; 95% CI: -45.90, -17.42; p < 0.0001; I (2 )= 93%; postoperative 24 h: n =  8 trials; WMD, -44.06; 95% CI: -69.21, -18.91; p = 0.006; I (2 )= 100%); IL-8 level postoperative 24 h, TNF-α level postoperative 24 h, NE level postoperative 6 h: n = 3 trials; WMD, -36.83; 95% CI: -68.84, -4.83; p = 0.02; I (2 )= 95%); tissue necrosis factor alpha (TNF-α) level (postoperative 6 h: n = 3 trials; WMD, -7.21; 95% CI: -12.41, -2.01; p = 0.007; I (2 )= 47%; postoperative 24 h: n = 5 trials; WMD, -10.02; 95% CI: -14.93, -5.12; p < 0.0001; I (2 )= 94%); and neutrophil elastase (NE) level (postoperative 6 h: n = 3 trials; WMD, -66.93; 95% CI: -111.94, -21.92; p = 0.004; I (2 )= 86%). However, TXA achieved no statistically significant influence on the postoperative 24 h NE level. CONCLUSIONS TXA had a significant anti-inflammatory effect in adult cardiac surgical patients, as evidenced by the reduction of multiple postoperative proinflammatory biomarkers levels, but these results should be interpreted carefully and cautiously, as only a limited number of studies were included and there was high heterogeneity between them. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42022312919.

Abstract

BACKGROUND The renoprotective effects of erythropoietin (EPO) are well-known; however, the optimal timing of EPO administration remains controversial. Red blood cell (RBC) transfusion is an independent risk factor for cardiac surgery-associated acute kidney injury (CSA-AKI). We aimed to evaluate the efficacy of EPO on CSA-AKI and RBC transfusion according to the timing of administration. METHODS We searched the Cochrane Library, EMBASE, and MEDLINE databases for randomized controlled trials. The primary outcome was the incidence of CSA-AKI following perioperative EPO administration, and the secondary outcomes were changes in serum creatinine, S-cystatin C, S-neutrophil gelatinase-associated lipocalin, urinary neutrophil gelatinase-associated lipocalin, length of hospital and intensive care unit (ICU) stay, volume of RBC transfusion, and mortality. The subgroup analysis was stratified according to the timing of EPO administration in relation to surgery. RESULTS Eight randomized controlled trials with 610 patients were included in the study. EPO administration significantly decreased the incidence of CSA-AKI (odds ratio: 0.60, 95% confidence interval [CI]: 0.43-0.85, P = .004; I2 = 52%; P for heterogeneity = .04), intra-operative RBC transfusion (standardized mean difference: -0.30, 95% CI: -0.55 to -0.05, P = .02; I2 = 15%, P for heterogeneity = .31), and hospital length of stay (mean difference: -1.54 days, 95% CI: -2.70 to -0.39, P = .009; I2 = 75%, P for heterogeneity = .001) compared with control groups. Subgroup analyses revealed that pre-operative EPO treatment significantly reduced the incidence of CSA-AKI, intra-operative RBC transfusion, serum creatinine, and length of hospital and ICU stay. CONCLUSION Pre-operative administration of EPO may reduce the incidence of CSA-AKI and RBC transfusion, but not in patients administered EPO during the intra-operative or postoperative period. Therefore, pre-operative EPO treatment can be considered to improve postoperative outcomes by decreasing the length of hospital and ICU stay in patients undergoing cardiac surgery.

Abstract

OBJECTIVES To determine the effect of intraoperative antifibrinolytics, including tranexamic acid (TXA), aminocaproic acid (EACA), or aprotinin, on bleeding in children undergoing cardiac surgery with cardiopulmonary bypass (CPB). DATA SOURCES Relevant articles were systematically searched from Ovid MEDLINE, Ovid EMBASE, CINAHL, Cochrane Library, and Web of Science to November 15, 2021. STUDY SELECTION Abstracts were screened, and full texts were reviewed using predetermined inclusion and exclusion criteria using the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. DATA EXTRACTION A standardized data extraction tool was used. DATA SYNTHESIS Sixty-eight studies including 28,735 patients were analyzed. TXA compared with placebo resulted in a mean decrease in chest tube output of 9.1 mL/kg (95% CI, 6.0-12.3 mL/kg), I2 equals to 65.2%, p value of less than 0.001, platelet requirement of 2.9 mL/kg (95% CI, 0.1-5.8 mL/kg), I2=72.5%, p value less than 0.001 and plasma requirement of 4.0 mL/kg (95% CI, 0.6-7.2 mL/kg), I2 equals to 94.5%, p value less than0.001. Aprotinin compared with placebo resulted in a mean decrease in chest tube output of 4.3 mL/kg (2.4-6.2 mL/kg), I2 equals to 66.3%, p value of less than 0.001, platelet transfusion of 4.6 mL/kg (95% CI, 0.6-8.6 mL/kg), I2 equals to 93.6%, p value of less than 0.001, and plasma transfusion of 7.7 mL/kg (95% CI, 2.1-13.2 mL/kg), I2 equals to 95.3%, p value of less than 0.001. EACA compared with placebo resulted in a mean decrease in chest tube output of 9.2 mL/kg (2.3-21.0 mL/kg), I2 equals to 96.4%, p value of less than 0.001, RBC transfusion of 7.2 mL/kg (95% CI, 2.4-12.1 mL/kg), I2 equals to 94.5%, p value equals to 0.002, and platelet transfusion of 10.7 mL/kg (95% CI, 2.9-18.5 mL/kg), I2 equals to 0%, p value of less than 0.001. No statistical difference was observed in chest tube output when TXA was compared with aprotinin. Subgroup analysis of cyanotic patients showed a significant decrease in chest tube output, platelet requirement, and plasma requirement for patients receiving aprotinin. Overall, the quality of evidence was moderate. CONCLUSIONS Antifibrinolytics are effective at decreasing blood loss and blood product requirement in children undergoing cardiac surgery with CPB although the quality of evidence is only moderate.