Abstract

OBJECTIVES Bicuspid aortic valves have been excluded from randomized trials comparing transcatheter aortic valve replacement with surgical aortic valve replacement. We aimed to evaluate the outcomes of transcatheter aortic valve replacement versus surgical aortic valve replacement in patients with severe bicuspid aortic valve stenosis using a meta-analysis. METHODS MEDLINE and EMBASE were searched through March 2022 to identify observational studies comparing transcatheter aortic valve replacement and surgical aortic valve replacement for severe bicuspid aortic valve stenosis. Outcomes of interest were in-hospital outcomes, including all-cause mortality, stroke, vascular complication, permanent pacemaker implantation, acute kidney injury, blood transfusion, paravalvular leak, and all-cause mortality during follow-up. RESULTS Four propensity score-matched studies and 54,047 patients (transcatheter aortic valve replacement, n = 3841; surgical aortic valve replacement, n = 50,206) yielding 3142 pairs using propensity score were included. Median follow-up periods were 21 to 24 months. There were no significant differences in in-hospital mortality (risk ratio, 0.69; 95% confidence interval, 0.40-1.20; P = .19) or stroke (risk ratio, 0.86; 95% confidence interval, 0.64-1.14; P = .29). Although transcatheter aortic valve replacement was associated with higher risks of permanent pacemaker implantation rate (risk ratio, 1.87; 95% confidence interval, 1.23-2.84; P = .0003), transcatheter aortic valve replacement was associated with lower risks of acute kidney injury (risk ratio, 0.58; 95% confidence interval, 0.38-0.88; P = .01) and transfusion (risk ratio, 0.25; 95% confidence interval, 0.21-0.29; P = .0001). There were no significant differences in in-hospital vascular complication, paravalvular leak, and all-cause mortality during follow-up. CONCLUSIONS In selected patients with severe bicuspid aortic valve stenosis, no significant differences in in-hospital mortality or stroke were observed between transcatheter aortic valve replacement and surgical aortic valve replacement. Further investigations with long-term follow-up and morphological features are warranted.

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

Background: Ultrafiltration is used with cardiopulmonary bypass to reduce the effects of hemodilution and restore electrolyte balance. We performed a systematic review and meta-analysis to analyze the effect of conventional and modified ultrafiltration on intraoperative blood transfusion.Methods: Utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement, we systematically searched MEDLINE, EMBASE, Web of Science, and Cochrane Library to perform a meta-analysis of studies of randomized controlled trials (RCTs) and observational studies evaluating conventional ultrafiltration (CUF) and modified ultrafiltration (MUF) on the primary outcome of intraoperative red cell transfusions.Results: A total of 7 RCTs (n = 928) were included, comparing modified ultrafiltration (n = 473 patients) to controls (n = 455 patients) and 2 observational studies (n = 47,007), comparing conventional ultrafiltration (n = 21,748) to controls (n = 25,427). Overall, MUF was associated with transfusion of fewer intraoperative red cell units per patient (n = 7); MD -0.73 units; 95% CI -1.12 to -0.35 p = 0.04; p for heterogeneity = 0.0001, I(2) = 55%) compared to controls. CUF was no difference in intraoperative red cell transfusions compared to controls (n = 2); OR 3.09; 95% CI 0.26-36.59; p = 0.37; p for heterogeneity = 0.94, I(2) = 0%. Review of the included observational studies revealed an association between larger volumes (>2.2 L in a 70 kg patient) of CUF and risk of acute kidney injury (AKI).Conclusion: The results of this systematic review and meta-analysis suggest that MUF is associated with fewer intraoperative red cell transfusions. Based on limited studies, CUF does not appear to be associated with a difference in intraoperative red cell transfusion.

Abstract

OBJECTIVES Cardiac surgical procedures are associated with a high incidence of periprocedural blood loss and blood transfusion. Although both may be associated with a range of postoperative complications there is disagreement on the impact of blood transfusion on long-term mortality. This study aims to provide a comprehensive review of the published outcomes of perioperative blood transfusion, examined as a whole and by index procedure. METHODS A systematic review of perioperative blood transfusion cardiac surgical patients was conducted. Outcomes related to blood transfusion were analysed in a meta-analysis and aggregate survival data were derived to examine long-term survival. RESULTS Thirty-nine studies with 180,074 patients were identified, the majority (61.2%) undergoing coronary artery bypass surgery. Perioperative blood transfusions were noted in 42.2% of patients and was associated with significantly higher early mortality (OR 3.87, p < 0.001). After a median of 6.4 years (range 1-15), mortality remained significantly higher for those who received a perioperative transfusion (OR 2.01, p < 0.001). Pooled hazard ratio for long-term mortality similar for patients who underwent coronary surgery compared to isolated valve surgery. Differences in long-term mortality for all comers remained true when corrected for early mortality and when only including propensity matched studies. CONCLUSIONS Perioperative red blood transfusion appears to be associated with a significant reduction in long-term survival for patients after cardiac surgery. Strategies such as preoperative optimisation, intraoperative blood conservation, judicious use of postoperative transfusions, and professional development into minimally invasive techniques should be utilised where appropriate to minimise the need for perioperative transfusions.

Abstract

BACKGROUND Preoperative anemia is common in patients undergoing cardiac surgery with various etiologies, among which iron deficiency is the leading cause. However, the benefit of intravenous (IV) iron for the treatment of anemia before cardiac surgery is uncertain. This updated meta-analysis aimed to evaluate the efficacy of IV iron in adult cardiac surgery patients with preoperative anemia. METHODS This review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched Embase, PubMed and the Cochrane Central Register of Controlled Trials to identify eligible randomized controlled trials (RCTs) and observational studies. Quality was assessed using the Cochrane Collaboration risk of bias tool and Newcastle-Ottawa scale, and the strength of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria. Trial sequential analysis was performed on the primary outcome (transfusion rate) to confirm whether firm evidence was reached. RESULTS Six RCTs (936 patients) and 5 observational studies (1350 patients) were included in this meta-analysis. The IV iron group and the control group were comparable in terms of transfusion rate [55.1% vs 60.9%, risk ratio (RR) = 0.91, 95% confidence interval (CI) 0.81-1.03, P = 0.13, low quality]. There were no significant differences in units transfused per patient, ICU stay and hospital length of stay between the two groups. And pooled data showed a benefit of IV iron compared to the control group on mortality (2.76% vs 3.75%, RR = 0.58, 95% CI 0.36-0.95, P = 0.03, moderate quality) and no mortality reduction existed when including only RCTs. CONCLUSIONS This meta-analysis suggested that IV iron treatment for patients with anemia before cardiac surgery did not reduce the transfusion requirement (low quality), but it was associated with decreased mortality (moderate quality). More large-scale, high-quality randomized clinical trials are warranted to confirm or refute our findings. PROSPERO registry reference: CRD42022331875.

Abstract

Hemorrhoidectomy is one of the most common surgical interventions to remove the third and fourth degrees of prolapse hemorrhoid. We carried out this systematic review and meta-analysis of the randomized controlled trials (RCTs) to comprehensively evaluate the efficacy of harmonic scalpel (HS) versus bipolar diathermy (BD) methods in terms of decreasing intraoperative and postoperative morbidities among patients undergoing hemorrhoidectomy. Suitable citations were found utilizing digital medical sources, including the CENTRAL, Web of Science, PubMed, Scopus, and Google Scholar, from inception until December 2022. Only RCTs that matched the inclusion requirements were selected. We used the updated Cochrane risk of bias (ROB) tool (version 2) to assess the quality of the involved citations. The Review Manager (version 5.4 for Windows) was used to perform the pooled analysis. Data were pooled and reported as mean difference (MD) or risk ratio (RR) with a 95% confidence interval (CI) in random-effects models. Overall, there was no significant difference between HS and BD in terms of decreasing intraoperative morbidities like operative time, intraoperative blood loss, mean duration of hospital stay, and mean duration of first bowel movement (P>0.05). Similarly, the rate of postoperative complications like pain, bleeding, urinary retention, anal stenosis, flatus incontinence, and wound edema; was similar in both groups with no significant difference (P>0.05). In conclusion, our pooled analysis revealed there was no substantial difference between HS and BD in terms of intraoperative and postoperative endpoints. Additional RCTs with larger sample sizes are needed to consolidate the power and quality of the presented evidence.

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.

Abstract

BACKGROUND In some randomized controlled trials (RCTs), transradial (TRA) compared with transfemoral access (TFA) was associated with lower mortality in coronary artery disease patients undergoing invasive management. We analyzed the effects of TRA versus TFA across multicenter RCTs and whether these associations are modified by patient or operator characteristics. METHODS We performed an individual patient data meta-analysis of multicenter RCTs comparing TRA versus TFA among patients undergoing coronary angiography with or without percutaneous coronary intervention (PCI) (PROSPERO; CRD42018109664). The primary outcome was all-cause mortality and the co-primary outcome was major bleeding at 30 days. The primary analysis was conducted by one-stage mixed-effects models based on the intention-to-treat cohort. The impact of access-site on mortality and major bleeding was further assessed by multivariable analysis. The relationship among access-site, bleeding, and mortality was investigated by natural effect model mediation analysis with multivariable adjustment. RESULTS A total of 21,600 patients (TRA=10,775 vs. TFA=10,825) from 7 RCTs were included. Median age was 63.9 years, 31.9% were female, 95% presented with acute coronary syndrome (ACS), and 75.2% underwent PCI. All-cause mortality (1.6% vs. 2.1%; HR 0.77, 95% CI 0.63-0.95, p=0.012) and major bleeding (1.5% vs. 2.7%; OR 0.55, 95% CI 0.45- 0.67, p<0.001) were lower with TRA. Subgroup analyses for mortality showed consistent results, except for baseline hemoglobin ((pinteraction)=0.033), indicating that the benefit of TRA was substantial in patients with significant anemia, while it was not significant in patients with milder or no baseline anemia. After adjustment, TRA remained associated with 24% and 51% relative risk reduction of all-cause mortality and major bleeding. A mediation analysis showed that the benefit of TRA on mortality was only partially driven by major bleeding prevention, and ancillary mechanisms are required to fully explain the causal association. CONCLUSIONS TRA is associated with lower all-cause mortality and major bleeding at 30 days, compared with TFA. The effect on mortality was driven by patients with anemia. The reduction in major bleeding only partially explains the mortality benefit.

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: 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.