Hemostatic spray (TC-325) vs. standard endoscopic therapy for non-variceal gastrointestinal bleeding: A meta-analysis of randomized controlled trials
Endoscopy international open. 2023;11(3):E288-e295
Background and study aims Hemospray (TC-325) is a mineral powder with adsorptive properties designed for use in various gastrointestinal bleeding (GIB) scenarios. We conducted a systematic review & meta-analysis of randomized controlled trials (RCTs) comparing TC-325 to standard endoscopic therapy (SET) for non-variceal GIB (NVGIB). Methods Multiple databases were searched through October 2022. Meta-analysis was performed using a random-effects model to determine pooled relative risk (RR) and proportions with 95 % confidence intervals (CI) for primary hemostasis, hemostasis failure, 30-day rebleeding, length of stay (LOS), and need for rescue interventions. Heterogeneity was assessed using I (2) %. Results Five RCTs with 362 patients (TC-325 178, SET 184) - 123 females and 239 males with a mean age 65 ± 16 years). The most common etiologies were peptic ulcer disease (48 %), malignancies (35 %), and others (17 %). Bleeding was characterized as Forrest IA (7 %), IB (73 %), IIA (3 %), and IIB (1 %). SET included epinephrine injection, electrocautery, hemoclips, or a combination. No statistical difference in primary hemostasis between TC-325 compared to SET, RR 1.09 (CI 0.95-1.25; I (2) 43), P = 0.2, including patients with oozing/spurting hemorrhage, RR 1.13 (CI 0.98-1.3; I (2) 35), P = 0.08. Failure to achieve hemostasis was higher in SET compared to TC-325, RR 0.30 (CI 0.12-0.77, I (2) 0), P = 0.01, including patients with oozing/spurting hemorrhage, RR 0.24 (CI 0.09 - 0.63, I (2) 0), P = 0.004. We found no difference between the two interventions in terms of rebleeding, RR 1.13 (CI 0.62-2.07, I (2) 26), P = 0.8 and LOS, standardized mean difference (SMD) 0.27 (CI, -0.20-0.74; I (2) 62), P = 0.3. Finally, pooled rate of rescue interventions (angiography) was statistically higher in SET compared to TC-325, RR 0.68 (CI 0.5-0.94; I (2) 0), P = 0.02. Conclusions Our analysis shows that for acute NV GIB, including oozing/spurting hemorrhage, TC-325 does not result in higher rates of primary hemostasis compared to SET. However, lower rates of failures were seen with TC-325 than SET. In addition, there was no difference in the two modalities when comparing rates of rebleeding and LOS.
Peroperative administration of tranexamic acid in sleeve gastrectomy to reduce hemorrhage: a double-blind randomized controlled trial
Surgical endoscopy. 2023;37(10):7455-7463
INTRODUCTION In metabolic surgery, hemorrhage is the most common major complication. This study investigated whether peroperative administration of tranexamic acid (TXA) reduced the risk of hemorrhage in patients undergoing laparoscopic sleeve gastrectomy (SG). METHODS In this double-blind randomized controlled trial, patients undergoing primary SG in a high-volume bariatric hospital were randomized (1:1) to receive 1500-mg TXA or placebo peroperatively. Primary outcome measure was peroperative staple line reinforcement using hemostatic clips. Secondary outcome measures were peroperative fibrin sealant use and blood loss, postoperative hemoglobin, heart rate, pain, major and minor complications, length of hospital stay (LOS), side effects of TXA (i.e., venous thrombotic event (VTE)) and mortality. RESULTS In total, 101 patients were analyzed and received TXA (n = 49) or placebo (n = 52). There was no statistically significant difference in hemostatic clip devices used in both groups (69% versus 83%, p = 0.161). TXA administration showed significant positive changes in hemoglobin levels (millimoles per Liter; 0.55 versus 0.80, p = 0.013), in heart rate (beats per minute; -4.6 versus 2.5; p = 0.013), in minor complications (Clavien-Dindo ≤ 2, 2.0% versus 17.3%, p = 0.016), and in mean LOS (hours; 30.8 versus 36.7, p = 0.013). One patient in the placebo-group underwent radiological intervention for postoperative hemorrhage. No VTE or mortality was reported. CONCLUSION This study did not demonstrate a statistically significant difference in use of hemostatic clip devices and major complications after peroperative administration of TXA. However, TXA seems to have positive effects on clinical parameters, minor complications, and LOS in patients undergoing SG, without increasing the risk of VTE. Larger studies are needed to investigate the effect of TXA on postoperative major complications.
Effect of Intravenous Ferric Carboxymaltose on Exercise Capacity After Kidney Transplantation (EFFECT-KTx): rationale and study protocol for a double-blind, randomised, placebo-controlled trial
BMJ open. 2023;13(3):e065423
INTRODUCTION Iron deficiency (ID) is common and has been associated with an excess mortality risk in kidney transplant recipients (KTRs). In patients with chronic heart failure and ID, intravenous iron improves exercise capacity and quality of life. Whether these beneficial effects also occur in KTRs is unknown. The main objective of this trial is to address whether intravenous iron improves exercise tolerance in iron-deficient KTRs. METHODS AND ANALYSIS The Effect of Ferric Carboxymaltose on Exercise Capacity after Kidney Transplantation study is a multicentre, double-blind, randomised, placebo-controlled clinical trial that will include 158 iron-deficient KTRs. ID is defined as plasma ferritin <100 µg/L or plasma ferritin 100-299 µg/L with transferrin saturation <20%. Patients are randomised to receive 10 mL of ferric carboxymaltose (50 mg Fe(3+)/mL, intravenously) or placebo (0.9% sodium chloride solution) every 6 weeks, four dosages in total. The primary endpoint is change in exercise capacity, as quantified by the 6 min walk test, between the first study visit and the end of follow-up, 24 weeks later. Secondary endpoints include changes in haemoglobin levels and iron status, quality of life, systolic and diastolic heart function, skeletal muscle strength, bone and mineral parameters, neurocognitive function and safety endpoints. Tertiary (explorative) outcomes are changes in gut microbiota and lymphocyte proliferation and function. ETHICS AND DISSEMINATION The protocol of this study has been approved by the medical ethical committee of the University Medical Centre Groningen (METc 2018/482;) and is being conducted in accordance with the principles of the Declaration of Helsinki, the Standard Protocol Items: Recommendations for Interventional Trials checklist and the Good Clinical Practice guidelines provided by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. Study results will be disseminated through publications in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER NCT03769441.
Small-Diameter Transjugular Intrahepatic Portosystemic Shunt versus Endoscopic Variceal Ligation Plus Propranolol for Variceal Rebleeding in Advanced Cirrhosis
Background Some studies have shown that transjugular intrahepatic portosystemic shunt (TIPS) placement within 72 hours of admission improves survival in patients at high risk who present with acute variceal bleeding. However, the role of small-diameter covered TIPS in the secondary prophylaxis of variceal bleeding is still debatable. Purpose To compare the efficacy of 8-mm TIPS and endoscopic variceal ligation (EVL) plus propranolol in the prevention of variceal rebleeding among participants with advanced cirrhosis. Materials and Methods Between June 2015 and December 2018, participants admitted to the hospital for variceal bleeding were considered for enrollment in this randomized controlled trial (ClinicalTrials.gov). Participants with Child-Pugh class B or C cirrhosis were randomly assigned to receive an 8-mm covered TIPS or EVL and propranolol. The primary end point was recurrent variceal bleeding assessed using Kaplan-Meier curve analysis. Secondary end points included survival and overt hepatic encephalopathy (HE) assessed using Kaplan-Meier curve analysis. Results A total of 100 participants were enrolled, with 50 randomly assigned to the EVL plus propranolol group (median age, 54 years; IQR, 45-60 years; 29 male, 21 female) and 50 randomly assigned to the TIPS group (median age, 49 years; IQR, 43-56 years; 32 male, 18 female). The median follow-up period was 43.4 months. In the TIPS group, variceal rebleeding risk was reduced compared with variceal rebleeding risk in the EVL plus propranolol group (hazard ratio [HR], 0.31; 95% CI: 0.14, 0.69; P = .008), but the incidence of overt HE was higher in the TIPS group (30.0% vs 16.0%, P = .03). No differences in survival were observed between the two groups (1-year survival: TIPS, 98.0%; EVL plus propranolol, 92.0%; 3-year survival: TIPS, 94.0%; EVL plus propranolol, 85.7%; HR, 0.52; 95% CI: 0.19, 1.42; P = .22). Conclusion When compared with EVL plus propranolol, 8-mm TIPS led to reduced variceal rebleeding but did not impact overall survival in participants with Child-Pugh class B or C cirrhosis. Clinical trial registration no. NCT02477384 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Barth in this issue.
Argipressin for prevention of blood loss during liver resection: a study protocol for a randomised, placebo-controlled, double-blinded trial (ARG-01)
BMJ open. 2023;13(8):e073270
INTRODUCTION Liver resection carries a high risk for extensive bleeding and need for blood transfusions, which is associated with significant negative impact on outcome. In malignant disease, the most common indication for surgery, it also includes increased risk for recurrence of cancer. Argipressin decreases liver and portal blood flow and may have the potential to reduce bleeding during liver surgery, although this has not been explored. METHOD AND ANALYSIS ARG-01 is a prospective, randomised, placebo-controlled, double-blinded study on 248 patients undergoing liver resection at Sahlgrenska University Hospital, Sweden. Patients will be randomised to one of two parallel groups, infusion of argipressin or normal saline administered peroperatively. The primary endpoint is peroperative blood loss. Secondary outcomes include need for blood transfusion, perioperative variables, length of hospital stay, the inflammatory response, organ damage markers and complications at 30 days. ETHICS AND DISSEMINATION The study is enrolling patients since March 2022. The trial is approved by the Swedish Ethical Review Authority (Dnr 2021-03557) and the Swedish Medical Product Agency (Dnr 5.1-2021-90115). Results will be announced at scientific meetings and in international peer-reviewed journals. TRIAL REGISTRATION NUMBER ClinicalTrials.gov, NCT05293041 and EudraCT, 2021-001806-32.
Application of cardiovascular interventions to decrease blood loss during hepatectomy: a systematic review and meta-analysis
BMC anesthesiology. 2023;23(1):89
BACKGROUND Perioperative bleeding and allogeneic blood transfusion are generally thought to affect the outcomes of patients. This meta-analysis aimed to determine the benefits and risks of several cardiovascular interventions in patients undergoing hepatectomy. METHODS In this systematic review and meta-analysis, randomised controlled trials (RCTs) were searched in the Cochrane Library, Medline, Embase, and Web of Science to February 02, 2023. RCTs focused on cardiovascular interventions aimed at reducing blood loss or blood transfusion requirements during hepatectomy were included. The primary outcomes were perioperative blood loss amount, number of patients requiring allogeneic blood transfusion and overall occurrence of postoperative complications. The secondary outcomes were operating time, perioperative mortality rate, postoperative liver and kidney function and length of hospital stay. RESULTS Seventeen RCTs were included in the analysis. A total of 841 patients who underwent hepatectomy in 10 trials were included in the comparative analysis between low central venous pressure (CVP) and control groups. The forest plots showed a low operative bleeding volume [(mean difference (MD): -409.75 mL, 95% confidence intervals (CI) -616.56 to -202.94, P < 0.001], reduced blood transfusion rate [risk ratio (RR): 0.47, 95% CI 0.34 to 0.65, P < 0.001], shortened operating time (MD: -13.42 min, 95% CI -22.59 to -4.26, P = 0.004), and fewer postoperative complications (RR: 0.76, 95% CI 0.58 to 0.99, P = 0.04) in the low CVP group than in the control group. Five and two trials compared the following interventions, respectively: 'acute normovolaemic haemodilution (ANH) vs control' and 'autologous blood donation vs control'. ANH and autologous blood donation could not reduce the blood loss amount but greatly decreased the number of patients requiring allogeneic blood transfusion. No benefits were found in the rate of mortality and length of postoperative hospital stay in any of the comparisons. CONCLUSION Lowering the CVP seems to be effective and safe in adult patients undergoing hepatectomy. ANH and autologous blood donation should be used as a part of blood management for suitable patients in certain circumstances. TRIAL REGISTRATION PROSPERO, CRD42022314061.
Are hemostatic agents for selective cases of tubeless percutaneous nephrolithotomy necessary for access tract control? A randomized control trial
International urology and nephrology. 2023
PURPOSE To evaluate the efficacy of percutaneous nephrolithotomy (PCNL) access tract sealing agent. Fibrin glue and Tachosil(®) were used for sealing the access tract and compared to the control. Post operative computed tomography (CT) scan was used to evaluate those efficacies. METHODS A total of 108 patients were randomized to three groups: In group 1, the access tract was sutured, and compressive dressing was done. In group 2, the fibrin glue was injected into the access tract with a tip applicator at the end of operation. And group 3, Tachosil(®) was rolled on its longitudinal axis and plugged into the access tract. Non-contrast CT at POD 1 was taken and perirenal hematoma thickness was measured and graded. Hemoglobin, hematocrit, VAS score, stone-free status, and hospital stay were analyzed. RESULTS Preoperative demographic differences were not significant in all three arms. Postoperative CT scans in all groups demonstrated mostly minimal grade access tract hematomas. Mean perirenal hematoma thickness showed no significant differences (2.66 ± 3.74, 2.73 ± 3.85, 2.54 ± 4.37 mm, p = 0.981), respectively. Postoperative hemoglobin drop (0.75 ± 0.58, 0.84 ± 0.47, 0.91 ± 0.60 g/dl, p = 0.74), stone-free rate (93.75, 87.87, 87.87%, p = 0.121), VAS (p = 0.499) and hospital stay (1.81 ± 0.84, 1.48 ± 0.71, 1.59 ± 0.75 day, p = 0.127) were not significantly different between the groups. CONCLUSION Fibrin glue and Tachosil(®) in tubeless PCNL were not necessary for postoperative access tract control.
Proton pump inhibitor has no effect in the prevention of post-endoscopic sphincterotomy delayed bleeding: a prospective randomized controlled trial
Frontiers in medicine. 2023;10:1179512
BACKGROUND AND AIMS Bleeding is one of the common adverse events of endoscopic retrograde cholangiopancreatography (ERCP), which is mainly caused by endoscopic sphincterotomy (EST). At present, it remains unclear whether proton pump inhibitor (PPI) should be used to prevent post-EST bleeding. Therefore, we performed a randomized controlled trial to investigate whether PPI is effective in the prevention of post-EST delayed bleeding. METHODS Consecutive eligible patients were randomly assigned (1:1) to experimental group (PPI group) or control group (normal saline, NS group). The patients in PPI group received intravenous esomeprazole 40 mg and normal saline 100 mL every 12 h for 2 days after ERCP immediately, and followed by oral esomeprazole (Nexium) 20 mg once a day for 7 days. Correspondingly, patients in the control group received intravenous normal saline 100 mL and did not take PPIs or any acid-suppressing drugs during hospitalization and after discharge. All patients were followed up for 30 days after ERCP. The primary endpoint was the incidence and severity of post-EST delayed bleeding. RESULTS Between July 2020 and July 2022, 290 patients were randomly assigned to PPI group (n = 146) or NS group (n = 144). 5 patients from each group were excluded from the final analysis. There were 6 patients with post-EST delayed bleeding, with an incidence rate of 2.14%. The median time of delayed bleeding was 2.5 days after ERCP. 3 cases (2.12%, 3/141) occurred in the PPI group, with 1 case of mild and 2 cases of moderate bleeding. 3 cases (2.16%, 3/139) occurred in the NS group, with 2 cases of mild and 1 case of moderate bleeding. There was no significant difference in the incidence and the severity of post-EST delayed bleeding between the two groups (p = 1.000). CONCLUSION Prophylactic use of PPI after EST does not reduce the incidence and severity of post-EST delayed bleeding in patients. CLINICAL TRIAL REGISTRATION https://www.chictr.org.cn/searchproj.aspx, identifier ChiCTR2000034697.
Clinical efficacy of anastomotic reinforcement suture in preventing anastomotic leakage after rectal cancer surgery: a systematic review and meta-analysis
Langenbeck's archives of surgery. 2023;408(1):322
PURPOSE Anastomotic leakage (AL) is a common postoperative complication of rectal cancer, with an incidence of about 10%, and the efficacy of reinforced sutures for preventing AL remains contentious. This study investigated the safety and effectiveness of reinforcement sutures for preventing AL after rectal cancer surgery. METHODS The present authors conducted a systematic search in the PubMed, Embase, Cochrane Library, Sinomed, Web of Science, Wanfang, VIP, and CNKI databases for randomized controlled trials (RCTs) and nonrandomized studies up to June 2023. We performed a meta-analysis to evaluate the efficacy of anastomotic reinforcement sutures after rectal cancer surgery. The primary outcome measures were AL, anastomotic bleeding, and infection rates. RESULTS Eleven articles (1921 subjects) were analyzed, with 912 and 1009 cases in the reinforced and unreinforced suture groups, respectively. The reinforced suture group showed a lower AL incidence (odds ratio [OR]=0.25, 95% CI 0.17-0.37, P< 0.00001), lower infection rate (OR=0.41, 95%CI 0.19-0.89, P<0.05), shorter hospital stay (mean difference [MD]=-0.57, 95%CI -1.15-0.00, P≤0.05), and earlier anal exhaust (MD=-0.12, 95%CI -0.23-0.00, P<0.05). However, the operative time (MD=18.25, 95% CI 12.20-24.30, P<0.00001) was longer for reinforced sutures than for unreinforced sutures. There were no significant differences between the suture techniques in intraoperative blood loss MD=2.74, 95% CI -4.50-9.97, P>0.05), incidence of anastomotic bleeding (OR=0.49, 95%CI 0.12-1.97, P>0.05), and incidence of intestinal obstruction (OR=0.65, 95%CI 0.27-1.61, P>0.05). CONCLUSION Existing articles indicate that anastomotic reinforcement sutures can significantly reduce AL incidence. However, this conclusion still requires confirmation based on multicentre, high-quality RCTs with large sample sizes.
Bleeding After Endoscopic Resection of Colonic Adenomatous Polyps Sized 4-10 mm
Prilozi (Makedonska akademija na naukite i umetnostite. Oddelenie za medicinski nauki). 2023;44(2):157-164
Introduction: Colonoscopy with polypectomy is an efficacious procedure in reducing the risk of colorectal cancer development, the precursor are adenomatous polyps. The most common method for resection of polyps measuring 4-10 mm are cold (CSP) and hot snare polypectomy (HSP). CSP has a lower incidence of adverse events, especially delayed post-polypectomy bleeding. Aim: To evaluate the presence of immediate and delayed bleeding in the cold snare polypectomy of sub-centimeter polyps of the colon compared with hot snare polypectomy. Materials and Methods: This prospective clinical study is comprised all patients who were incidentally detected to have adenomatous colonic polyps measuring 4-10 mm during a colonoscopy screening. Polypectomy was done with (hot snare) or without electrocautery (cold snare). After removal of polyps, immediate bleeding, delayed bleeding, and methods for were analyzed. Results: The CSP and HSP groups included 116 patients, 113 (54.4%) polyps in 61 (52.6%) patients with CSP while 95 (45.6%) polyps in 55 (47.4%) patients with HSP. 25 (22.1%) polyps after CSP had immediate bleeding. In 5 patients (20.0%), five hemostatic clips were inserted after CSP for bleeding longer than 150 sek. The average percentage difference between immediate bleeding versus total number of resected polyps using the cold snare method is not statistically significant (p<0.05) (Difference test, p=0.0000). Delayed bleeding was not registered using this method. In the second investigated group (HSP), one patient had delayed bleeding. This was stopped with 2 clips. Immediate bleeding was not registered. Conclusion: CSP is safer than HSP in resecting colon polyps sized 4-10 mm, without risk of delayed bleeding.