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Tranexamic acid for percutaneous nephrolithotomy
Cleveland, B., Norling, B., Wang, H., Gandhi, V., Price, C. L., Borofsky, M. S., Pais, V., Dahm, P.
The Cochrane database of systematic reviews. 2023;10(10):Cd015122
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Editor's Choice
Abstract
BACKGROUND Percutaneous nephrolithotomy (PCNL) is the gold standard for the treatment of large kidney stones but comes with an increased risk of bleeding compared to other treatments, such as ureteroscopy and shock wave lithotripsy. Tranexamic acid (TXA) is an antifibrinolytic agent that has been used to reduce bleeding complications in other settings. OBJECTIVES To assess the effects of TXA in individuals with kidney stones undergoing PCNL. SEARCH METHODS We performed a comprehensive literature search of the Cochrane Library, PubMed (including MEDLINE), Embase, Scopus, Global Index Medicus, trials registries, other sources of the grey literature, and conference proceedings. We applied no restrictions on the language of publication nor publication status. The latest search date was 11 May 2023. SELECTION CRITERIA We included randomized controlled trials (RCTs) that compared treatment with PCNL with administration of TXA to placebo (or no TXA) for patients ≥ 18 years old. DATA COLLECTION AND ANALYSIS Two review authors independently classified studies and abstracted data. Primary outcomes were: blood transfusion, stone-free rate (SFR), and thromboembolic events (TEEs). Secondary outcomes were: adverse events (AEs), secondary interventions, major surgical complications, minor surgical complications, unplanned hospitalizations or readmissions, and hospital length of stay (LOS). We performed statistical analyzes using a random-effects model. We rated the certainty of evidence (CoE) according to the GRADE approach using a minimally contextualized approach with predefined thresholds for minimally clinically important differences (MCIDs). MAIN RESULTS We analyzed 10 RCTs assessing the effect of systemic TXA in PCNL versus placebo (or no TXA) with 1883 randomized participants. Eight studies were published as full text. One was published in abstract proceedings, but it was separated into two separate studies for the purpose of our analyzes. Average stone surface area ranged 3.45 to 6.62 cm(2). We also found a single RCT published in full text assessing the effects of topical TXA in PCNL versus placebo (or no TXA) with 400 randomized participants, the results of which are further described in the review. Here we focus only on the results of TXA used systemically. Blood transfusion - Based on a representative baseline risk of 5.7% for blood transfusions taken from a large presentative observational studies, systemic TXA may reduce blood transfusions (risk ratio (RR) 0.45, 95% confidence interval (CI) 0.27 to 0.76; I(2) = 28%; 9 studies, 1353 participants; low CoE). We assumed an MCID of ≥ 2%. Based on 57 participants per 1000 with placebo (or no TXA) being transfused, this corresponds to 31 fewer (from 42 fewer to 14 fewer) participants being transfused per 1000. Stone-free rate - Based on a representative baseline risk of 75.7% for SFR, systemic TXA may increase SFRs (RR 1.11, 95% CI 0.98 to 1.27; I(2) = 62%; 4 studies, 603 participants; low CoE). We assumed an MCID of ≥ 5%. Based on 757 participants per 1000 being stone free with placebo (or no TXA), this corresponds to 83 more (from 15 fewer to 204 more) stone-free participants per 1000. Thromboembolic events - There is probably no difference in TEEs (risk difference (RD) 0.00, 95% CI -0.01 to 0.01; I(2) = 0%; 6 studies, 841 participants; moderate CoE). We assumed an MCID of ≥ 2%. Since there were no thromboembolic events in intervention and/or control groups in 5 out of6 studies, we opted to assess a risk difference with systemic TXA for this outcome. Adverse events - Systemic TXA may increase AEs (RR 5.22, 95% CI 0.52 to 52.72; I(2) = 75%; 4 studies, 602 participants; low CoE). We assumed an MCID of ≥ 5%. Based on 23 participants per 1000 with placebo (or no TXA) having an adverse event, this corresponds to 98 more (from 11 fewer to 1000 more) participants with adverse events per 1000. Secondary interventions - Systemic TXA may have little to no effect on secondary interventions (RR 1.15, 95% CI 0.84 to 1.57; I(2) = 0%; 2 studies, 319 participants; low CoE). We assumed an MCID of ≥ 5%. Based on 278 participants per 1000 with placebo (or no TXA) having a secondary intervention, this corresponds to 42 more (from 44 fewer to 158 more) participants with secondary interventions per 1000. Major surgical complications - Based on a representative baseline risk for major surgical complications of 4.1%, systemic TXA may reduce major surgical complications (RR 0.36, 95% CI 0.21 to 0.62; I(2) = 0%; 5 studies, 733 participants; moderate CoE). We assumed an MCID of ≥ 2%. Based on 41 participants per 1000 with placebo (or no TXA) having a major surgical complication, this corresponds to 26 fewer (from 32 fewer to 16 fewer) participants with major surgical complications per 1000. Minor surgical complications - Systemic TXA may reduce minor surgical complications (RR 0.71, 95% CI 0.45 to 1.10; I(2) = 76%; 5 studies, 733 participants; low CoE). We assumed an MCID of ≥ 5%. Based on 396 participants per 1000 with placebo (or no TXA) having a minor surgical complication, this corresponds to 115 fewer (from 218 fewer to 40 more) participants with minor surgical complications per 1000. Unplanned hospitalizations or readmissions - We are very uncertain how unplanned hospitalizations or readmissions are affected (RR 1.55, 95% CI 0.45 to 5.31; I(2) = not applicable; 1 study, 189 participants; very low CoE). We assumed an MCID of ≥ 2%. Hospital length of stay - Systemic TXA may reduce hospital LOS (mean difference 0.52 days lower, 95% CI 0.93 lower to 0.11 lower; I(2) = 98%; 7 studies, 1151 participants; low CoE). We assumed an MCID of ≥ 0.5 days. AUTHORS' CONCLUSIONS Based on 10 RCTs with substantial methodological limitations that lowered all CoE of effect, we found that systemic TXA in PCNL may reduce blood transfusions, major and minor surgical complications, and hospital LOS, as well as improve SFRs; however, it may increase AEs. We are uncertain about the effects of systemic TXA on other outcomes. Findings of this review should assist urologists and their patients in making informed decisions about the use of TXA in the setting of PCNL.
PICO Summary
Population
Patients with kidney stones undergoing percutaneous nephrolithotomy (PCNL), (10 randomised controlled trials (RCTs), n= 1,883).
Intervention
Tranexamic acid.
Comparison
Placebo or no tranexamic acid.
Outcome
The primary outcomes were: blood transfusion, stone-free rate, and thromboembolic events. Based on 10 RCTs with substantial methodological limitations that lowered all certainty of evidence of effect, the authors found that systemic tranexamic acid in PCNL may reduce blood transfusions, major and minor surgical complications, and hospital length of stay, as well as improve stone-free rates; however, it may increase adverse events. The authors were uncertain about the effects of systemic TXA on other outcomes.
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Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial
Lancet. 2020;395(10241):1927-1936
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Editor's Choice
Abstract
BACKGROUND Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. METHODS We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0.9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0.9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and http://clinicaltrials.gov/ ClinicalTrials.gov, NCT01658124. FINDINGS Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49.9%) or matching placebo (6015, 50.1%), of whom 11 952 (99.5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0.99, 95% CI 0.82-1.18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0.7%] of 5952 vs 46 [0.8%] of 5977; 0.92; 0.60 to 1.39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0.8%] of 5952 vs 26 [0.4%] of 5977; RR 1.85; 95% CI 1.15 to 2.98). INTERPRETATION We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial. FUNDING UK National Institute for Health Research Health Technology Assessment Programme.
PICO Summary
Population
Patients with gastrointestinal bleeding enrolled in the HALT-IT trial (n= 12009).
Intervention
Loading dose of tranexamic acid followed by a maintenance dose of tranexamic acid (n= 5994).
Comparison
Placebo: sodium chloride (n= 6015).
Outcome
Death due to bleeding within 5 days of randomisation occurred in (4%) of patients in the tranexamic acid group and in (4%) of patients in the placebo group. Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (0.7%) vs. (0.8%). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (0.8%) vs. (0.4%).
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A randomized controlled trial of the effects of local tranexamic acid on mortality, rebleeding, and recurrent endoscopy need in patients with upper gastrointestinal hemorrhage
Karadas A, Dogan NO, Pinar SG, Yesil O, Pekdemir M, Yilmaz S, Yaka E
European journal of gastroenterology & hepatology. 2019
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Editor's Choice
Abstract
OBJECTIVE Tranexamic acid (TXA) is an antifibrinolytic agent used to control bleeding in different circumstances. We conducted a randomized controlled trial to assess the efficacy and safety of locally administered TXA in upper gastrointestinal hemorrhage. METHODS This single-center, double-blind, randomized controlled trial was performed in a tertiary emergency department (ED) in patients presenting with upper gastrointestinal bleeding symptoms between 2016 and 2018. The patients received either 2000 mg of 5% TXA in 100 mL of isotonic saline solution or 100 mL isotonic saline (control group) via the nasogastric route. As a composite outcome, recurrent endoscopy need, rebleeding, surgery need, recurrent admission to the ED, and mortality parameters were evaluated at the end of a one-month period. RESULTS During the study period, 78 patients were randomized into the TXA group, and 79 patients were randomized into the isotonic saline group. The majority of the bleedings (61%) were in Forrest class 3, and the most frequent cause was peptic ulcer disease. The composite outcome occurred in 25 of the TXA patients (32.1%) and 23 of the isotonic saline patients (29.1%); no statistically significant difference was found between the groups (P = 0.690). In addition, no statistically significant differences were observed between the TXA and control groups regarding mortality (10.3 vs 12.7%; P = 0.637), recurrent ED admission (17.9 vs 12.7%; P = 0.357), or thromboembolic complications (3.8 vs 1.3%; P = 0.367). CONCLUSION Locally administered TXA confers no additional benefit over standard care in patients with upper gastrointestinal hemorrhage.
PICO Summary
Population
Patients presenting with upper gastrointestinal bleeding symptoms in a tertiary emergency department.
Intervention
TXA group: 2000 mg of 5% TXA in 100 mL of isotonic saline solution (n=78).
Comparison
Control group: 100 mL isotonic saline (n=79).
Outcome
The composite outcome occurred in 25 of the TXA patients (32.1%) and 23 of the isotonic saline patients (29.1%); no statistically significant difference was found between the groups. No statistically significant differences were observed between the TXA and control groups regarding mortality (10.3 vs 12.7%), recurrent ED admission (17.9 vs 12.7%), or thromboembolic complications (3.8 vs 1.3%).