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Optimal administration strategies of tranexamic acid to minimize blood loss during spinal surgery: results of a Bayesian network meta-analysis
Cao Z, Li Q, Guo J, Li Y, Wu J
Annals of medicine. 2022;54(1):2053-2063
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Abstract
BACKGROUND Tranexamic acid (TXA) has been widely used for bleeding reduction in spinal surgery. Available evidence is insufficient to inform clinical decisions making and there remains a lack of comprehensive comparisons of dose regimens and delivery routes. This study is aimed to assess and compare different strategies regarding the involvement of TXA in spinal surgery for the optimal pathway of efficacy and safety. MATERIALS AND METHODS Cochrane Library, PubMed, Embase, Scopus and CNKI were searched for the period from January 1990 to October 2021. A random-effect model was built in the Bayesian network meta-analysis. The surface under the cumulative ranking analysis (SUCRA) and clustering rank analysis was performed for ranking the effects. RESULTS The current network meta-analysis incorporated data from 33 studies with 3302 patients. Combination administration showed superior effects on reducing intraoperative bleeding (SUCRA 78.78%, MD -129.67, 95% CI [(-222.33, -40.58)]) than placebo, and was ranked as top in reducing postoperative bleeding (SUCRA 86.91%, MD -169.92, 95% CI [(-262.71, -83.52)]), changes in haemoglobin (SUCRA 97.21%, MD -1.28, 95% CI [(-1.84, -0.73)]), and perioperative blood transfusion (SUCRA 93.23%, RR 0.10, 95% CI [(0.03, 0.25)]) simultaneously, and was shown as the best effectiveness and safety (cluster-rank value for IBL and VTE: 4057.99 and for TRF and VTE: 4802.26). CONCLUSIONS Intravenous (IV) plus topical administration of TXA appears optimal in the reduction of perioperative bleeding and blood transfusion, while the local infiltration administration is not effective for blood conservation. Further studies are required to verify the current findings.
PICO Summary
Population
Patients undergoing spinal surgery (33 studies, n= 3,302).
Intervention
Tranexamic acid (TXA).
Comparison
Various comparators: low-dose intravenous (IV), high-dose IV, low-dose topical, high-dose topical, combined use (IV plus topical), oral, local infiltration, multiple IV use before and after surgery, and placebo.
Outcome
The surface under the cumulative ranking analysis (SUCRA) and clustering rank analysis was performed for ranking the effects. Combination administration showed superior effects on reducing intraoperative bleeding (SUCRA 78.78%, weighted mean difference (MD) -129.67) than placebo, and was ranked as top in reducing postoperative bleeding (SUCRA 86.91%, MD -169.92), changes in haemoglobin (SUCRA 97.21%, MD -1.28), and perioperative blood transfusion (SUCRA 93.23%) simultaneously, and was shown as the best effectiveness and safety.
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An alternative method for personalized tourniquet pressure in total knee arthroplasty: a prospective randomized and controlled study
Wu J, Fu Q, Li H, Han Y, Deng J, Chen Y, Qian Q
Scientific reports. 2022;12(1):9652
Abstract
Tourniquet use always carries potential risks, which can range from mild transient functional impairments of thigh pain, skin blisters to severe permanent dysfunction of limb paralysis, nerve injuries or compartment syndrome. The ideal method for minimizing intraoperative tourniquet pressure (TP) for reducing postoperative complications remains controversial. In this prospective, randomized and controlled study, we reinvestigated an estimation formula for TP based on thigh circumferences and systolic blood pressure (SBP) with two traditional methods for TP determination in total knee arthroplasty (TKA): SBP plus 100 mmHg and a fixed value of 300 mmHg. TP values and postoperative thigh pain scores were compared among three groups. The intraoperative TP value of the formula-calculated group was lower than that of the traditional groups (14.7 mmHg, P = 0.3475 and 94.7 mmHg, P < 0.0001, respectively), while no differences of hemostatic effect at the surgical fields and wound complications were detected among groups. The thigh pain scores at the tourniquet site decreased gradually over time and the estimation group had the lowest scores at each timepoint after surgery. Estimation method for TP was easy and rapid, without relying on specific equipment. It could provide a practical low TP and comparable hemostatic effect in TKA using an inflating tourniquet.
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Endoscopic Cyanoacrylate Injection vs BRTO for Prevention of Gastric Variceal Bleeding: A Randomized Controlled Trial
Luo X, Xiang T, Wu J, Wang X, Zhu Y, Xi X, Yan Y, Yang J, García-Pagán JC, Yang L
Hepatology (Baltimore, Md.). 2021
Abstract
The optimal treatment for gastric varices (GVs) has not yet been fully determined. This study compared the efficacy and safety of endoscopic cyanoacrylate injection and balloon-occluded retrograde transvenous obliteration (BRTO) to prevent rebleeding in patients with cirrhosis and GVs after primary hemostasis. Patients with cirrhosis and history of bleeding from gastroesophageal varices type 2 or isolated gastric varices type 1 were randomized to cyanoacrylate injection (n = 32) or BRTO treatment (n = 32). The primary outcomes were gastric variceal rebleeding or all-cause rebleeding. The patient characteristics were well-balanced between two groups. The mean follow-up time was 27.1 ± 12 months in a cyanoacrylate injection group and 27.6 ± 14.3 months in a BRTO group. The probability of gastric variceal rebleeding was higher in the cyanoacrylate injection group than in the BRTO group (p = 0.024). The probability of remaining free of all-cause rebleeding at 1 and 2 years for cyanoacrylate injection vs BRTO was 77% vs 96.3% and 65.2% vs 92.6% (p = 0.004). The survival rates, frequency of complications, and worsening of EVs were similar in both groups. BRTO resulted in fewer hospitalizations, inpatient stays, and lower medical costs. CONCLUSIONS BRTO is more effective than cyanoacrylate injection in preventing rebleeding from GVs, with similar frequencies of complications and mortalities.
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Comparison of efficacy and safety of different tourniquet applications in total knee arthroplasty: a network meta-analysis of randomized controlled trials
Cao Z, Guo J, Li Q, Wu J, Li Y
Annals of medicine. 2021;53(1):1816-1826
Abstract
OBJECTIVE Total knee replacement (TKA) is an effective way to treat teratogenic and disabling knee diseases such as advanced osteoarthritis. Tourniquets are often used in TKA to reduce bleeding and to get a better visualization of the surgical field, while it is related to safety concerns. We did this network meta-analysis to comprehensively compare the efficacy and safety of various tourniquet application strategies. METHOD PubMed, Embase, Cochrane Library, CNKI, and WanFang Database were systematically searched from January 1990 to May 2020. A network meta-analysis with a frequentist framework was done to assess the relative efficacy and safety by comparing seven clinical important endpoints. RESULTS 38 eligible studies that assessed 3007 participants who underwent TKA were included in this network meta-analysis. Tourniquet inflation before osteotomy then deflation after wound closure effectively reduce perioperative bleeding (WMD compared with control group -234.66, 95% CI [-409.19 to -60.13]), while shortening the operation time (WMD -8.98, 95%CI [-14.07 to -3.88]) and reducing postoperative complications, including DVT (OR -0.58, 95%CI [-1.19 to 0.03]) and minor wound complications (OR -1.38, 95%CI [-3.00 to 0.25]). No difference was found in the late postoperative knee pain and function outcomes. CONCLUSIONS Using tourniquets during the entire operation can effectively reduce blood loss, but it also can cause many safety problems, including DVTs, wound oozing, delayed healing, and serious wound complications. Tourniquet inflation before osteotomy then deflation after wound closure effectively can reduce perioperative bleeding while shortening the operation time and reducing postoperative complications, so it could be the ideal tourniquet application strategy in TKA.Key messagesThis is the first study that comprehensively compared different tourniquet application strategies to evaluate their impact on postoperative recovery following TKA, and five clinically important endpoints were assessed in this study: perioperative blood loss, operation time, postoperative pain and function, and complications.We conclude that tourniquet inflation before osteotomy then deflation after wound closure could be the ideal tourniquet application strategy in TKA.
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Comparative Efficacy and Safety of Thrombopoietin Receptor Agonists in Adults With Thrombocytopenia: A Systematic Review and Network Meta-analysis of Randomized Controlled Trial
Deng J, Hu H, Huang F, Huang C, Huang Q, Wang L, Wu A, Yang J, Qin D, Zou W, et al
Frontiers in pharmacology. 2021;12:704093
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Editor's Choice
Abstract
Thrombopoietin receptor agonists (TPO-RAs) play a crucial role in stimulating thrombopoiesis. However, conventional meta-analyses have shown inconsistent results regarding the efficacy of thrombopoietin receptor agonists versus placebo. Therefore, we performed a network meta-analysis to assess the effects of five TPO-RAs via indirect comparison. For this network meta-analysis, we considered randomized trials that included any of the following interventions: avatrombopag, lusutrombopag, eltrombopag, romiplostim, recombinant human thrombopoietin (rhTPO). We searched the Medline, PubMed, Embase, the Cochrane Library, and Web of Science databases for randomized controlled clinical trials from inception to January 31, 2021. We use randomized controlled clinical trials of TPO-RAs for treatment of immune thrombocytopenia in adults. The primary outcome was the number of patients achieving platelet response which was defined as the achievement of a platelet count of more than 30 or 50 cells × 10(9)/L in the absence of rescue therapy, and the secondary outcome was the therapy-related serious adverse events and incidence of bleeding episodes. To obtain the estimates of efficacy and safety outcomes, we performed a random-effects network meta-analysis. These estimates were presented as odds ratios with 95% confidence intervals. We use surface under the cumulative ranking probabilities to rank the comparative effects and safety of all drugs against the placebo. In total, 2,207 patients were analyzed in 20 clinical trials. All preparations improved the point estimates of platelet response when compared with the placebo. Avatrombopag and lusutrombopag had the best platelet response compared to the placebo, the former had a non-significant advantage compared to the latter [odds ratio (OR) = 1.91 (95% confidence interval: 0.52, 7.05)]. The treatments were better than eltrombopag, romiplostim, rituximab, and rhTPO + rituximab, with corresponding ORs of 3.10 (1.01, 9.51), 9.96 (2.29, 43.29), 33.09 (8.76, 125.02), and 21.31 (3.78, 119.98) for avatrombopag and 1.62 (0.63, 4.17), 5.21 (1.54, 17.62), 17.34 (5.15, 58.36), and 11.16 (2.16, 57.62) for lusutrombopag. Regarding bleeding, the placebo group had the highest probability of bleeding, whereas lusutrombopag had the lowest risk of bleeding when compared to the placebo. Adverse events were slightly higher in patients receiving rituximab than in those receiving placebo or other treatments. Overall, this meta-analysis showed that avatrombopag may yield the highest efficacy because it has the most favorable balance of benefits and acceptability.
PICO Summary
Population
Adults with thrombocytopenia (20 studies, n= 2,207).
Intervention
Thrombopoietin receptor agonists: avatrombopag, lusutrombopag, eltrombopag, romiplostim, recombinant human thrombopoietin.
Comparison
Placebo.
Outcome
All preparations improved the point estimates of platelet response when compared with the placebo. Avatrombopag and lusutrombopag had the best platelet response compared to the placebo, the former had a non-significant advantage compared to the latter [odds ratio (OR)= 1.91 (95% confidence interval: 0.52, 7.05)]. The treatments were better than eltrombopag, romiplostim, rituximab, and rhTPO + rituximab, with corresponding ORs of 3.10 (1.01, 9.51), 9.96 (2.29, 43.29), 33.09 (8.76, 125.02), and 21.31 (3.78, 119.98) for avatrombopag and 1.62 (0.63, 4.17), 5.21 (1.54, 17.62), 17.34 (5.15, 58.36), and 11.16 (2.16, 57.62) for lusutrombopag. Regarding bleeding, the placebo group had the highest probability of bleeding, whereas lusutrombopag had the lowest risk of bleeding when compared to the placebo. Adverse events were slightly higher in patients receiving rituximab than in those receiving placebo or other treatments.
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The effects of acute hypervolemic hemodilution and conventional infusion in laparoscopic radical prostatectomy patients
Wu J, Zhang Z
American journal of translational research. 2021;13(7):7866-7873
Abstract
OBJECTIVE To compare the effect of acute hypervolemic hemodilution and conventional infusion in prostate cancer patients undergoing laparoscopic radical prostatectomies. METHODS A total of 87 patients with prostate cancer who underwent laparoscopic radical prostatectomies in our hospital were retrospectively analyzed. The patients were randomly divided into a control group (the CNG, n=43, conventional infusion) and an observation group (the OG, n=44, acute hypervolemic hemodilution). Blood gas analyses were performed at different time points, and the patients' cognitive dysfunction was evaluated. RESULTS The intraoperative blood transfusion rates of the OG and the CNG were 11.36% and 30.23%. The average intraoperative blood transfusions in the OG and the CNG were (315.46±24.49) ml and (486.95±42.17) ml (P < 0.05). The CVP and JVP levels in the OG and the CNG at T2 and T3 were significantly higher than the levels at T0 (P < 0.05). The Hb levels of the CNG at T3 and T4 were lower than they were at T0 (P < 0.05), and the Hb level in the OG at T4 was lower than it was at T1 (P < 0.05). The Hb levels in the CNG at T3 and T4 were lower than they were at T1 (P < 0.05), and the Hb levels in the OG at T1 and T2 were lower than they were in the CNG (P < 0.05). The MMSE cognitive function scores were lower than the scores recorded on the day before the operations (P < 0.05). CONCLUSION Acute hypervolemic hemodilution in laparoscopic radical prostatectomy patients can maintain their hemodynamics in a stable state, help reduce blood transfusion, improve the oxygen supply to the brain tissue to maintain the supply and demand balance, and reduce the impact on the patients' cognitive function.
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Safety and Efficacy of Tranexamic Acid in Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis of Randomized Controlled Trials
Ren J, Qian D, Wu J, Ni L, Qian W, Zhao G, Huang C, Liu X, Zou Y, Xing W
Frontiers in neurology. 2021;12:710495
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Editor's Choice
Abstract
BACKGROUND In recent decades, tranexamic acid (TXA) antifibrinolytic therapy before aneurysm clipping or embolization has been widely reported, but its safety and efficacy remain controversial. This meta-analysis evaluated the efficacy and safety of TXA therapy in aneurysmal subarachnoid hemorrhage (aSAH) patients, aiming to improve the evidence-based medical knowledge of treatment options for such patients. METHODS Pubmed, Web of Science, and Cochrane Library databases were searched up to 1 March 2021 for randomized controlled trials (RCTs). We extracted safety and efficacy outcomes and performed a meta-analysis using the Review Manager software. We performed two group analyses of TXA duration and daily dose. RESULTS Ten RCT studies, enrolling a total of 2,810 participants (1,410 with and 1,400 without TXA therapy), matched the selection criteria. In the TXA duration group: TXA did not reduce overall mortality during the follow-up period [RR 1.00 (95% CI 0.81-1.22)]. The overall rebleeding rate in the TXA group was 0.53 times that of the control group, which was statistically significant [RR 0.53 (95% CI 0.39-0.71)]. However, an RR of 0.43 was not statistically significant in the subgroup analysis of short-term therapy [RR 0.43 (95% CI 0.13-1.39)]. The overall incidence of hydrocephalus was significantly higher in the TXA group than in the control group [RR 1.13 (95% CI 1.02-1.24)]. However, the trend was not statistically significant in the subgroup analysis [short-term: RR 1.10 (95% CI 0.99-1.23); long-term: RR 1.22 (95% CI 0.99-1.50)]. Treatment with TXA did not cause significant delayed cerebral ischemia [RR 1.18 (95% CI 0.89-1.56)], and its subgroup analysis showed an opposite and insignificant effect [short-term: RR 0.99 (95% CI 0.79-1.25); long-term: RR 1.38 (95% CI 0.86-2.21)]. Results in the daily dose group were consistent with those in the TXA duration group. CONCLUSIONS Tranexamic acid does not reduce overall mortality in patients with aSAH, nor does it increase the incidence of delayed cerebral ischemia. Tranexamic acid in treating aSAH can reduce the incidence of rebleeding. However, there is no statisticalsignificance in the ultra-early short-term and low daily dose TXA therapy, which may be due to the lack of relevant studies, and more RCT experiments are needed for further study. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/PROSPERO/display_record.asp? PROSPERO, identifier: 244079.
PICO Summary
Population
Aneurysmal subarachnoid haemorrhage patients (10 studies, n= 2,810).
Intervention
Tranexamic acid (TXA), (n= 1,410).
Comparison
Conventional treatment without TXA (n= 1,400).
Outcome
The overall re-bleeding rate in the TXA group was 0.53 times that of the control group. The overall incidence of hydrocephalus was significantly higher in the TXA group than in the control group. Treatment with TXA did not cause significant delayed cerebral ischemia.
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Two Doses of Tranexamic Acid Reduce Blood Loss in Primary Posterior Lumbar Fusion Surgery: A Randomized-controlled Trial
Zhu X, Shi Q, Li D, Wu J, Guo K, Zheng X, Li H
Clin Spine Surg. 2020
Abstract
PURPOSE Tranexamic acid (TXA) has been widely used in hip and knee arthroplasty to reduce perioperative blood loss and blood transfusion, but the dosage and efficacy of TXA in posterior lumbar spinal surgery are not fully clear. The aim of this study was to investigate the efficacy and safety of TXA and to determine whether 2 doses of TXA could reduce the blood loss in primary single-segment or double-segment posterior lumbar fusion surgery. MATERIALS AND METHODS A total of 150 patients with lumbar degenerative disease undergoing posterior lumbar interbody fusion surgery between October 2017 and February 2019 were randomized to 3 groups. Group A was treated with 0.9% normal saline solution without TXA, group B was treated with a 15 mg/kg loading dose intravenous infusion 30 minutes before surgery, and group C was treated with a 15 mg/kg loading dose intravenous infusion 30 minutes before surgery; then, the same dose was administered again 3 hours later. The assessed outcomes were the operation time, the total blood loss, the hidden blood loss, postoperative drainage, blood transfusions, incidence of venous thromboembolism, and incision infection. RESULTS The total blood loss, the hidden blood loss, and postoperative drainage were the lowest in group C. The amount of intraoperative blood loss was similar among the 3 groups. The hemoglobin and hematocrit values of the third postoperative day were the highest in group C. No significant differences in the incidence of complications and adverse events from TXA use were observed among the 3 groups. The use of TXA, the operation time, and the number of fusion segments were identified as risk factors related to total blood loss. CONCLUSION Two doses of TXA significantly reduced the total blood loss, the hidden blood loss and postoperative drainage, and decreased hemoglobin and hematocrit drop in patients undergoing posterior lumbar fusion without increasing the risk of complications.
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9.
Timing of plasma exchange for neuromyelitis optica spectrum disorders: A meta-analysis
Huang X, Wu J, Xiao Y, Zhang Y
Multiple sclerosis and related disorders. 2020;48:102709
Abstract
BACKGROUND Neuromyelitis optica spectrum disorders (NMOSDs) are autoimmune astrocytopathies with predominant involvement of the optic nerves and spinal cord. The current management is high-dose intravenous methylprednisolone, followed by apheresis therapy if it fails. We aimed to investigate plasma exchange (PE) benefits in corticosteroid-refractory NMOSDs. METHODS From Embase, PubMed, Cochrane, Web of Science, and Clinical Trials, we identified PE-based studies published between Jan 2007 and Dec 2019. We pooled the information of these studies in a binomial meta-analysis. We investigated the factors affecting the efficacy of PE and its adverse events. The effectiveness of PE was assessed using the Expanded Disability Status Scale (EDSS). The timing of PE initiation was assessed using Spearman correlation analysis. RESULTS We included 561 records and identified 8 observational studies, including 228 NMOSD patients. The mean time to the initiation of PE was 11 days, and the average volume of each exchange was 1.5-2 L. PE treatment reduced the mean EDSS score by -1.04 (95% CI, -1.44 to -0.64). The initiation time of PE significantly affected the outcome (EDSS reduction) (P = 0.01; 95% CI, -1.30 to 0.28). In the ≤ 7-day and 8-23-day groups, the mean EDSS decreased by 0.64 (95% CI, -0.93 to -0.34) and 1.41 (95% CI, -1.79 to -1.02), respectively. In addition, PE showed the same efficacy for alleviating the symptoms of NMOSDs, regardless of the day between 8 to 23 days on which it was performed (P = 0.29). Thirty-five (20.8%) of the 168 patients had adverse events. CONCLUSION PE can ameliorate severe NMOSDs. PE effectiveness was associated with the duration between disease and the initiation of PE, and the optimal timing for PE initiation is 8 to 23 days after the onset of the disease.
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10.
Ideal intraarticular application dose of tranexamic acid in primary total knee arthroplasty: a prospective, randomized and controlled study
Wu J, Zhou YQ, Deng JH, Han YG, Zhu YC, Qian QR
Annals of translational medicine. 2020;8(21):1353
Abstract
BACKGROUND Combined use of tranexamic acid (TXA) via intravenous (IV) and intraarticular (IA) routes is more effective in reducing blood loss than any single route in primary total knee arthroplasty (TKA), but the optimal dose of topical administration remains controversial. The aim of this study was to evaluate the efficacy and safety of different combined administration strategies and to determine an ideal IA application dose of TXA. METHODS A total of 180 patients who underwent primary TKA were randomized to four groups (groups A/B/C/D) with the same single IV dose of 1 g TXA preoperatively and four different IA doses after wound closure: group A (0 g), group B (1 g), group C (2 g), and group D (4 g). The primary outcome measures included wound blood drainage, hemoglobin (Hb) concentration, and blood transfusion. The secondary outcome measures included wound complications, deep vein thrombosis (DVT) and symptomatic pulmonary embolism (PE). RESULTS A total of 165 patients finished at least 3 months of follow-up visits. The amount of 48-hour blood drainage and calculated total blood loss in four groups decreased with the increased dose of TXA injected via IA route, and no difference was observed between groups C and D (P=0.6237 and P=0.9923, respectively). Hb was significantly higher in groups C and D than in groups A and B at postoperative day 1, 3 and 7, respectively (P<0.0001). Hb in group A was significantly lower than that in groups C and D at 1 month after surgery, whereas no intergroup difference was found in other groups. No intergroup difference was observed regarding DVT, PE or wound complications. CONCLUSIONS The topical injection of 2 g TXA may have reached the "ceiling effect" of local use. A preoperative IV dose of 1 g TXA combined with an IA dose of 2 g TXA could be an optimal combination regimen.