Inspine surgery, perioperative tranexamic acid (TXA) administration is an accepted method for decreasing blood loss and risk of transfusion.1–3A synthetic lysine analog, TXA competitively binds to the lysine-binding site on plasminogen molecules, thereby blocking conversion to plasmin and preventing plasmin from converting fibrinogen to fibrin.4Via this mechanism, TXA acts as a clot stabilizer and can reduce visible blood loss (VBL), hidden blood loss (HBL), and postoperative blood loss (PBL).5,6VBL is bleeding recorded during surgery. HBL is the difference between total blood loss and the sum of VBL and transfusion volume.7PBL is traditionally measured on the basis of drainage output and may include HBL, which is not readily observed. TXA can effectively reduce blood loss when administered orally, intravenously, topically, or as a combination of the latter two routes.6,8,9
In neurosurgery, intravenous (IV) TXA is the most studied TXA administration route.6,8,9Nonetheless, there remain concerns regarding postoperative seizures and thromboembolic events after IV TXA administration, with the highest reported incidence of seizure being 3.5%.10,11Topical TXA limits systemic exposure, expanding the clinical indications of TXA.12Although recent reviews have emphasized the efficacy of topical TXA for reducing blood loss, the literature on topical TXA, including randomized controlled trials (RCTs), is not as robust compared with that on IV TXA.13–16的re have been limited investigations into the safety and efficacy of topical TXA in the wider clinical context of spinal oncology, cervical spine disorders, and thoracolumbar trauma.
Applying the keywords "topical tranexamic acid and spine surgery" within Cochrane Library, Embase, Web of Science, and PubMed, we noted that approximately 70% of the search items were published between 2019 and 2023. Prior meta-analyses have focused on articles published before 2019; hence, an update on topical TXA may be timely.15,17–19Here, we used RCTs, cohort studies, and cross-sectional studies from 2016 through 2022 to conduct a quantitative review of the safety and efficacy of topical TXA for various spinal procedures. To the best of our knowledge, this review includes the most recent articles regarding topical TXA.
开云体育世界杯赔率
Literature Search
We followed the PRISMA guidelines to optimize reporting quality.20An expansive search of electronic databases was conducted, including PubMed, Embase, Cochrane Library, and Web of Science, for studies published from January 1, 2016, to January 1, 2023. The following keywords were used in the database search: "local infiltration/topical tranexamic acid" AND "neurosurgery," "spine surgery," "interbody fusion," "spinal fusion," "spinal tumor," "trauma," and "thoracolumbar fracture."
Study Selection and Quality Assessment
Two researchers independently assessed the studies, reaching a consensus on their relevance. Disagreements were resolved via a third party (A.K.C.). The full texts of the RCTs and cross-sectional, cohort, and case-control studies were read and included if they met at least three of the following criteria: 1) inclusion of adult patients (age ≥18 years) who underwent spinal surgery; 2) comparison of combined or topical TXA versus controls or IV TXA; 3) published in English; and 4) evaluation of dosage, safety, and efficacy of topical TXA using at least 1 of the following variables of PBL, VBL, postoperative hemoglobin, length of hospital stay (LOS), or complications (including infections and thrombosis). Studies regarding topical TXA that did not meet these criteria were evaluated and included in theDiscussiononly.
的research quality of the nonrandomized studies was assessed independently by two trained researchers using the Newcastle-Ottawa Scale, with studies scoring 7–9 considered to have low bias.21Studies with scores less than 7 were excluded. For RCTs, the Cochrane risk of bias tool for randomized trials was used to assess the risks of bias in randomization, intended interventions, missing outcome data, measurement outcomes, and reporting of results.22
Data Extraction and Analysis
Extracted data included the study and treatment groups, sample size, and mean ± standard deviation (SD) PBL, VBL, hemoglobin level, transfusion rates, and LOS. Mean differences without standard deviations were considered in the systematic review, not the pooled analysis. Hemoglobin values obtained immediately after the procedure were used. Meta-analysis was performed using the meta package in RStudio version 4.3.0. The metacont function was used to perform a random-effects model meta-analysis. Hedges’ g method was applied to calculate standardized mean difference (SMD), the Hartung and Knapp method was used to estimate variance, and the restricted maximum likelihood method was used to assess heterogeneity. Forest plots were generated using the forest.meta function.
Results
Database searches in Embase, Web of Science, Cochrane, and PubMed between January 1, 2016, and January 1, 2023, yielded 264, 267, 80, and 110 papers, respectively (Fig. 1）.After removal of duplicates, 128 papers remained, with 78 involving topical TXA in adult spine surgery. After exclusion of meta-analyses, reviews, letters to the editor, and cohort studies scoring less than 7 on the Newcastle-Ottawa Scale, 18 studies remained.Table 1lists the PBL, VBL, hemoglobin level, and LOS, complications, and dosages for each of the 18 papers. Complications were reported in half the included studies, with no significant differences reported between TXA and controls. Transfusion rates were not reported with standard deviations, preventing pooled analyses.
PRISMA model used for the systematic review of the literature. Data added to the PRISMA template (from Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.BMJ. 2021;372:n71) under the terms of the Creative Commons Attribution (CC BY 4.0) License (https://creativecommons.org/licenses/by/4.0/）.
Systematic review of studies published between January 1, 2016, and January 1, 2023, and evaluated on the basis of the PRISMA method
| Authors & Year | Study Size | Study Design | Type of Surgery | Interventions | Outcomes | Complications |
|---|---|---|---|---|---|---|
| Arain et al., 202128 | 125 | Prospective RCT at a single tertiary academic center | Elective decompressive lumbar laminectomy of 1–4 levels | Group 1: Surgical site bathed in saline immediately prior to wound closure Group 2: Initiation dose of 10 mg/kg IV TXA prior to incision and 2nd dose after 3 hrs Group 3: Topical TXA (3 g TXA diluted in 250 ml saline) immediately prior to wound closure |
Group 1: PBL 172 ± 98.2 ml; VBL 211.2 ± 152.5 ml; HGB NA; LOS* Group 2: PBL 72.8 ± 52.9 ml†; VBL 157.1 ± 119.2 ml; HGB NA; LOS* Group 3: PBL 52.0 ± 50.0 ml†; VBL 175.6 ± 153 ml; HGB NA; LOS* |
No statistically significant differences in postop complications btwn groups |
| Arun-Kumar & Naresh-Babu, 202126 | 78 | Single-center RCT | Degenerative grade 1 or 2 spondylolisthesis treated w/ single-level interbody fusion | Group 1: 10 ml 2% lidocaine w/ adrenaline prior to incision Group 2: IV TXA (single dose of 1 g) prior to incision Group 3: Topical TXA (1 g in 100 ml saline) immediately prior to wound closure |
Group 1: PBL 316.3 ± 110.1 ml; VBL 344.0 ± 88.4 ml; HGB 9.05 ± 0.48 g/dl; LOS 4.4 ± 1.6 days Group 2: PBL 190 ± 112.7 ml†; VBL 223.6 ± 40.1 ml†; HGB 11.04 ± 0.33 g/dl†; LOS 3.1 ± 0.5 days† Group 3: PBL 67.3 ± 32.6 ml†‡; VBL 311.3 ± 84.7 ml†‡; HGB 9.09 ± 0.73 g/dl‡; LOS 3.0 ± 0.6 days† |
No complications reported |
| Chen et al., 202231 | 133 | Single-center RCT | Cervical expansive open-door laminoplasty | Group 1: No intervention Group 2: TXA administered through Gelfoam soaked w/ 1 g in 20 ml saline prior to wound closure Group 3: 1 g TXA in 20 ml saline administered through retrograde injection in the wound drain postop & clamped for 1 hr |
Group 1: PBL 275.45 ± 75.27 ml; VBL 125.20 ± 45.44 ml; HGB 11.28 ± 1.76 g/dl; LOS 7.50 ± 1.25 days Group 2: PBL 156.60 ± 38.63 ml†; VBL 138.60 ± 52.76 ml; HGB 12.14 ± 1.53 g/dl†; LOS 5.64 ± 0.96 days† Group 3: PBL 126.60 ± 31.27 ml†‡; VBL 123.30 ± 35.83 ml; HGB 12.58 ± 1.67 g/dl†‡; LOS 5.31 ± 1.18 days† |
No complications reported |
| Emrah et al., 202132 | 60 | Single-center cross-sectional study | Thoracolumbar fusion surgery | Group 1: No intervention Group 2: Topical TXA (1 g) immediately prior to wound closure |
Group 1: PBL 241.6 ± 51.8 ml; VBL 650.0 (487.5–812.5) ml; HGB NA; LOS 5.53 days Group 2: PBL 136.0 ± 53.5 ml†; VBL 650.0 (400.0–1000.0) ml; HGB NA; LOS 2.93 days† |
No complications reported |
| Erdogan et al., 202238 | 112 | Retrospective observational study | Posterior thoracic/lumbar instrumented spinal fusion surgery | Group 1: Saline Group 2: 10 mg/kg IV TXA prior to incision, w/ 10 mg/kg/hr of isotonic solution during surgery & 1–2 g local administration of TXA immediately prior to wound closure |
组1:PBL 588.4±232.2毫升;轮式侦察车的813.4±451.9 ml; HGB 12.16 ± 1.55 g/dl; LOS NA Group 2: PBL 383.0 ± 166.9 ml†; VBL 581.3 ± 294.4 ml†; HGB 12.77 ± 1.61 g/dl; LOS NA |
1 patient in the TXA group had pulmonary embolism; another patient in the TXA group had paraparesis due to spinal epidural hematoma |
| Farzanegan et al., 202224 | 104 | Single-center RCT | Posterior lumbar spine surgery w/ diagnosis of disc herniation, spinal canal stenosis, or both | Group 1: Saline Group 2: Topical TXA (3 g in 100 ml saline) immediately prior to wound closure |
Group 1: PBL NA; VBL 407.20 ± 165.77 ml; HGB NA; LOS 1.34 ± 0.59 days Group 2: PBL NA; VBL 230 ± 323.58 ml†; HGB NA; LOS 1.24 ± 0.55 days |
Nonsignificant difference in complications: group 1 (13/50 patients) vs group 2 (9/54 patients) |
| Khadivi et al., 202325 | 88 | Single-center retrospective study | Posterior cervical laminectomy & fusion surgery | Group 1: No intervention Group 2: Irrigation of surgical field w/ topical TXA (3 g in 100 ml saline) throughout procedure |
Group 1: PBL 113.7 ± 75.4 ml; VBL 292.2 ± 155.8 ml; HGB NA; LOS 1.45 ± 0.55 days Group 2: PBL 70.8 ± 64.9 ml†; VBL 215.9 ± 167.2 ml†; HGB NA; LOS 1.5 ± 0.65 days |
No complications reported |
| Li et al., 202029 | 280 | Single-center RCT | 2-level posterior lumbar fusion | Group 1: 100 ml IV saline Group 2: Single-dose of 15 mg/kg IV TXA administered 1 hr prior to incision Group 3: Topical TXA (2 g in 20 ml saline) administered w/ retrograde injection through wound drain postop & clamped for 6 hrs Group 4: IV TXA prior to incision plus retrograde injection of topical TXA postop & clamped for 6 hrs |
Group 1: PBL 180.42 ± 42.54 ml; VBL 270.15 ± 90.64 ml; HGB 7.84 ± 1.44 g/dl; LOS* Group 2: PBL 124.63 ± 31.12 ml†; VBL 226.60 ± 50.53 ml†; HGB 8.80 ± 1.01 g/dl†; LOS* 第三组:PBL 134.48±40.45毫升*; VBL 259.40 ± 40.34 ml‡; HGB 8.74 ± 1.17 g/dl†; LOS* Group 4: PBL 87.24 ± 13.28 ml†‡; VBL 150.10 ± 30.90 ml†‡; HGB 9.74 ± 1.13 g/dl†‡; LOS* |
No statistically significant differences in postop complications btwn groups |
| Liang et al., 201634 | 90 | RCT | Lumbar spondylosis w/ or w/o disc herniation undergoing posterior lumbar decompression & fusion of ≥2 levels | Group 1: No TXA or Gelfoam Group 2: TXA administered through Gelfoam soaked with 2 g in 20 ml saline prior to wound closure |
Group 1: PBL 96.08 ± 34.59 ml; VBL 320.33 ± 184.21 ml; HGB 11.50 ± 1.91 g/dl; LOS 6.90 ± 3.45 days Group 2: PBL 30.03 ± 23.99 ml†; VBL 376.67 ± 249.39 ml; HGB 12.03 ± 1.69 g/dl; LOS 5.00 ± 2.26 days* |
Group 1: 2 complications w/ wound oozing & 1 complication w/ dressing reinforcement 30 days postop Group 2: 2 complications w/ wound oozing & 2 complications w/ dressing reinforcement 30 days postop No DVT or PE observed |
| Liang et al., 202027 | 40 | Retrospective observational study | Degenerative lumbar scoliosis undergoing posterior lumbar decompression & fusion of ≥3 levels | Group 1: No TXA Group 2: TXA retrograde injection (10% Transamin [10 ml, 1000 mg], Daiichi Sankyo) postop & clamped for 1 hr |
Group 1: PBL 605.50 ± 184.70 ml; VBL 516.50 ± 241.25 ml; HGB 10.57 ± 1.45 g/dl; LOS 9.80 ± 2.44 days Group 2: PBL 322.20 ± 187.32 ml†; VBL 456.00 ± 210.10 ml; HGB 11.24 ± 1.43 g/dl; LOS 7.50 ± 0.95 days† |
Group 1: 1 complication w/ wound oozing 1 wk postop Group 2: 1 complication w/ dressing reinforcement 1 wk postop No DVT or PE observed |
| Maethungkul et al., 202239 | 65 | Single-center RCT | Palliative decompressive thoracolumbar spinal metastasis | Group 1: 1 g IV TXA prior to incision followed by saline-soaked gelatin sponge immediately prior to wound closure Group 2: Preop IV TXA + gelatin sponge soaked in 1 g of TXA in 20 ml saline immediately prior to wound closure |
Group 1: PBL 670 ± 527 ml; VBL 648 ± 465 ml; HGB NA; LOS NA Group 2: PBL 790 ± 493 ml; VBL 589 ± 381 ml; HGB NA; LOS NA |
No complications reported |
| Mallepally et al., 202023 | 250 | Prospective case-controlled study | Single-level transforaminal lumbar interbody fusion | Group 1: Wound surface soaked w/ 100 ml saline solution for 3 mins throughout the procedure Group 2: Wound surfaced soaked w/ 1 g topical TXA for 3 mins throughout the procedure |
Group 1: PBL 167.10 ± 53.83 ml; VBL 783.33 ± 332.71 ml; HGB NA; LOS 7.0 ± 2.3 days Group 2: PBL 99.33 ± 37.5 ml†; VBL 410.57 ± 189.72 ml†; HGB NA; LOS 4.8 ± 1.1 days† |
No statistically significant differences in postop complications btwn groups |
| Mu et al., 20196 | 126 | Single-center randomized placebo-controlled trial | PLIF腰椎退行性疾病 | Group 1: Gelatin sponge soaked in 100 ml saline administered immediately prior to wound closure Group 2: IV TXA (15 mg/kg in 100 ml saline) prior to incision & maintained at a dose of 1mg/kg 第三组:局部酸(1 g 50毫升的酸盐)& gelatin sponge soaked for 5 mins immediately prior to wound closure |
Group 1: PBL 291.78 ± 42.91 ml; VBL 476.31 ± 77.23 ml; HGB 9.302 ± 1.375 g/dl; LOS: 8.00 ± 1.13 days Group 2: PBL 187.89 ± 42.61 ml†; VBL 301.78 ± 34.66 ml†; HGB 10.716 ± 1.477 g/dl†; LOS 6.27 ± 1.76 days† Group 3: PBL 193.59 ± 28.72 ml†; VBL 461.03 ± 65.36 ml‡; HGB 10.077 ± 1.185 g/dl†‡; LOS 6.67 ± 1.03 days† |
Group 1: 2 postop wound infections Group 2: 1 postop wound infection Group 3: 2 postop wound infections |
| Shen et al., 202135 | 76 | Singe-center RCT | Acute thoracolumbar burst fracture requiring early decompression | Group 1: Saline administration after sacrospinous muscle was stripped Group 2: Topical TXA (1 g in 100 ml saline) soaked for 5 mins after sacrospinous muscle exposure |
Group 1: PBL 144.05 ± 30.04 ml; VBL NA; HGB 10.600 ± 0.864 g/dl; LOS 9.78 ± 2.03 days Group 2: PBL 101.28 ± 14.45 ml†; VBL NA; HGB 11.546 ± 0.808 g/dl†; LOS 6.08 ± 0.77 days† |
No complications reported |
| Shi et al., 202112 | 120 | Single-center retrospective cohort study | Previous history of embolism diagnosed w/ lumbar degenerative disease & received a single-level PLIF surgery | Group 1: 100 ml saline immediately prior to wound closure Group 2: Topical TXA (1 g in 100 ml saline) immediately prior to wound closure |
Group 1: PBL 385.17 ± 184.86 ml; VBL 213.83 ± 111.399 ml; HGB*; LOS 8.00 ± 1.54 days Group 2: PBL 238.83 ± 140.49 ml†; VBL 218.00 ± 79.67 ml; HGB*; LOS 7.17 ± 1.22 days† |
Group 1: 5% DVT, 3.3% infection Group 2: 3.3% DVT, 3.3% infection |
| Sudprasert et al., 201933 | 57 | Prospective RCT | Thoracolumbar spine trauma treated w/ long-segment instrumented posterior spinal fusion | Group 1: 20 ml normal saline administered through retrograde injection in wound drain postop & clamped for 2 hrs Group 2: 1 g TXA in 20 ml saline administered through retrograde injection in wound drain postop & clamped for 2 hrs |
Group 1: PBL 488.8 ± 223.5 ml; VBL 260.3 ± 166.0 ml; HGB NA; LOS 17.3 ± 6.5 days Group 2: PBL 279 ± 135.2 ml†; VBL 265.0 ± 146.6 ml; HGB NA; LOS 12.9 ± 5.1 days† |
No adverse events or complications were recorded in any patient during treatment over a mean follow-up period of 27.5 mos |
| Wang et al., 20195 | 181 | Single-center RCT | Thoracolumbar fracture treated w/ percutaneous pedicle screw fixation | Group 1: 15 mg/kg IV TXA administered 30 mins before op & saline before wound closure Group 2: Preop IV saline and 3 g topical TXA immediately prior to wound closure Group 3: 15 mg/kg IV TXA administration prior to incision followed by 3 g topical TXA immediately prior to wound closure |
Group 1: PBL 354.13 ± 117.46 ml; VBL 103.44 ± 71.92 ml; HGB NA; LOS NA Group 2: PBL 453.56 ± 223.77 ml†; VBL 139.34 ± 63.32 ml†; HGB NA; LOS NA Group 3: PBL 302.03 ± 154.88 ml; VBL 92.03 ± 60.74 ml; HGB NA; LOS NA |
No complications reported |
| Xu et al., 202030 | 60 | Single-center RCT | PLIF | Group 1: Wound soaked in normal saline for 5 mins immediately prior to wound closure Group 2: Wound soaked in 1 g TXA in 100 ml saline immediately prior to wound closure |
Group 1: PBL 249.0 ± 103.4 ml; VBL 324.5 ± 184.6 ml; HGB NA; LOS 6.9 ± 1.8 days Group 2: PBL 183.6 ± 102.6 ml†; VBL 314.9 ± 203.6 ml; HGB NA; LOS 5.1 ± 2.3 days† |
No complications reported |
DVT = deep venous thrombosis; HGB = hemoglobin; NA = not available; PE = pulmonary embolism; PLIF = posterior lumbar interbody fusion.
Values are shown as mean ± SD or median (interquartile range) unless indicated otherwise.
Exact value was not recorded, but no significant difference was noted between groups.
Significant difference compared with group 1 (p < 0.05).
Significant difference compared with group 2 (p < 0.05).
Topical TXA Compared With No TXA
Visual Blood Loss
Mallepally et al. found significantly lower VBL (410.57 ± 189.72 ml vs 783.33 ± 332.71 ml) in the topical TXA group compared with the saline control group during single-level open transforaminal lumbar interbody fusion (p < 0.001).23Farzanegan et al. (lumbar laminectomy and discectomy) and Khadivi et al. (cervical laminectomy and fusion) also reported significantly reduced VBL with topical TXA (p < 0.05).24,25Other studies showed no significant difference in VBL between groups.6,12,26–34This discrepancy may be because topical TXA was applied throughout the procedure in two of the studies that displayed significance rather than immediately before closure, as was the case in many of the other studies.23–25Pooled analysis showed a significant decrease in VBL (SMD −0.22, 95% CI −0.45 to −0.00001) (Fig. 2A）.
A:Forest plot diagram showing the effect of topical TXA on VBL compared with non-TXA controls.B:Forest plot diagram showing the effect of topical TXA on PBL compared with non-TXA controls.C:Forest plot diagram showing the effect of topical TXA on postoperative hemoglobin level compared with non-TXA controls.D:Forest plot diagram showing the effect of topical TXA on LOS compared with non-TXA controls. HGB = hemoglobin.
Postoperative Blood Loss
All studies demonstrated a significant reduction in PBL with topical TXA compared with no TXA.6,12,23,25–35例如,1研究(包括患者degenerative grade 1 or 2 spondylolisthesis treated with single-level interbody fusion) reported PBL of 67.3 ± 32.6 ml with topical TXA compared with 316.3 ± 110.1 ml in the non-TXA group (p < 0.00001).26Pooled analysis demonstrated a significant decrease in PBL (SMD −1.63, 95% CI −2.03 to −1.22) (Fig. 2B）.
Postoperative Hemoglobin
Most papers that reported hemoglobin levels also reported reduced blood loss and higher hemoglobin levels with topical TXA.6,29,31,35For example, Shen et al. showed hemoglobin levels of 11.546 ± 0.808 g/dl with topical TXA compared with 10.600 ± 0.864 g/dl with saline for the treatment of thoracolumbar trauma (p < 0.001).35Few studies showed no significant difference in hemoglobin levels.26,27,34Pooled analysis showed a significant difference in hemoglobin levels with topical TXA compared with no TXA (SMD 0.59, 95% CI 0.34–0.83) (Fig. 2C）.
Length of Stay
LOS was reduced in nearly all studies.6,12,23,26,27,30,31,33–35Shen et al. reported the greatest decrease in LOS (6.08 ± 0.77 days) with topical TXA compared with no TXA (9.78 ± 2.03 days) (p < 0.001).35Two studies that did not report significant differences in LOS investigated procedures traditionally associated with shorter LOS (cervical surgery, lumbar laminectomy).24,25,36,37Pooled analysis showed a significant decrease in LOS after topical TXA (SMD −1.02, 95% CI −1.42 to −0.61) (Fig. 2D）.
Topical TXA Compared With IV TXA
Visual Blood Loss
Four of five studies demonstrated a significant increase in VBL with topical TXA compared with IV TXA.5,6,26,29For example, Mu et al. found decreased VBL with IV versus topical TXA in posterior lumbar interbody fusion for lumbar degenerative disease (301.78 ± 34.66 vs 461.03 ± 65.36 ml, p < 0.001).6Similarly, Li et al. found decreased VBL with IV versus topical TXA in posterior 2-level lumbar spine fusion (226.60 ± 50.53 vs 259.40 ± 40.34 ml, p = 0.01).29Arain et al. (1- to 4-level lumbar laminectomy) found no significant difference in VBL when comparing IV to topical TXA (157.1 ± 119.2 vs 175.6 ± 153.0 ml, p = 0.207).28的large variation in operated levels may have contributed to the lack of significance. Given the heterogeneity of these studies (I2= 94%), pooled analysis demonstrated no significant difference between IV and topical TXA regarding VBL (Fig. 3A）.
A:Forest plot diagram showing the effect of topical TXA on VBL compared with IV TXA.B:Forest plot diagram showing the effect of topical TXA on PBL compared with IV TXA.C:Forest plot diagram showing the effect of topical TXA on postoperative hemoglobin level compared with IV TXA.D:Forest plot diagram showing the effect of topical TXA on LOS compared with IV TXA.
Postoperative Blood Loss
Arun-Kumar and Naresh-Babu found that topical TXA significantly reduced PBL compared with IV TXA in patients with degenerative spondylolisthesis undergoing single-level interbody fusion (67.3 ± 32.6 ml vs 190 ± 112.7 ml, p = 0.0001).26Conversely, Wang et al. reported significantly higher PBL with topical compared with IV TXA in patients with thoracolumbar fracture undergoing percutaneous pedicle screw fixation (453.56 ± 223.77 ml vs 354.13 ± 117.46 ml, p<0.001).5This discrepancy may be attributed to the use of topical TXA in a percutaneous procedure, which may diminish the effect of topical agents due to reduced exposed surface area. Pooled analysis showed no statistical difference in PBL between topical and IV TXA groups (Fig. 3B）.
Postoperative Hemoglobin
Arun-Kumar and Naresh-Babu were the only authors to show a statistically significant reduction in hemoglobin level with topical compared with IV TXA (9.09 ± 0.73 vs 11.04 ± 0.33 g/dl, p < 0.01) (Fig. 3C）.26
Length of Stay
的re were no notable differences in the LOS between groups (Fig. 3D）.
Combined TXA Compared With No TXA
Two studies compared combined TXA administration with no TXA, and both reported significant improvements in VBL, PBL, and postoperative hemoglobin level.29,38的lack of significance in the pooled analyses of VBL and PBL was likely due to the large variation in the outcomes of the two studies and the limited number of studies in this analysis.
Visual Blood Loss
Li et al. found a decrease in VBL with combined TXA versus no TXA (150.10 ± 30.90 ml vs 270.15 ± 90.64 ml, p = 0.01), and Erdogan et al. also reported a decrease in VBL between groups (581.3 ± 294.4 ml vs 813.4 ± 451.9 ml, p < 0.0002).29,38Pooled analysis showed no significant difference in VBL between groups (Fig. 4A）.
A:Forest plot diagram showing the effect of combined TXA on VBL compared with non-TXA controls.B:Forest plot diagram showing the effect of combined TXA on PBL compared with non-TXA controls.C:Forest plot diagram showing the effect of combined TXA on hemoglobin compared with non-TXA controls.
Postoperative Blood Loss
Li et al. reported a decrease in PBL with combined TXA versus no TXA (87.24 ± 13.28 ml vs 180.42 ± 42.54 ml, p = 0.02), and Erdogan et al. also reported a decrease in PBL (383.0 ± 166.9 ml vs 588.4 ± 232.2 ml, p < 0.0001).29,38Pooled analysis showed no significant difference in PBL between groups (Fig. 4B）.
Postoperative Hemoglobin
Li et al. found a significantly higher hemoglobin level with combined TXA versus no TXA (9.74 ± 1.13 g/dl vs 7.84 ± 1.44 g/dl, p = 0.03).29However, Erdogan et al. did not find this association.38Pooled analysis showed no statistically significant change between groups (Fig. 4C）.
Combined TXA Compared With IV TXA
Three studies compared combined TXA with IV TXA.5,29,39
Visual Blood Loss
Li et al. found a decrease in VBL with combined TXA versus IV TXA (150.10 ± 30.90 ml vs 226.60 ± 50.53 ml, p = 0.01).29Other studies did not report significant differences.5,39Pooled analysis showed no significant difference in VBL between the groups (Fig. 5A）.
A:Forest plot diagram showing the effect of combined TXA on VBL compared with IV TXA.B:Forest plot diagram showing the effect of combined TXA on PBL compared with IV TXA.
Postoperative Blood Loss
Li et al. found a decrease in PBL with combined TXA versus IV TXA (87.24 ± 13.28 vs 124.63 ± 31.12 ml, p = 0.02), while the remaining studies found no significant differences.5,29,39Pooled analysis showed no statistically significant difference in PBL between groups (Fig. 5B）.
Discussion
Many individual studies and meta-analyses have highlighted the antifibrinolytic and hemostatic properties of TXA in spine surgery patients.40–43TXA has generally been linked to decreases in intraoperative and postoperative blood loss and may even reduce transfusion requirements.6,39,40,44–47However, these studies largely focused solely on IV TXA.48,49A growing body of literature has reported on the use of topical TXA.6,12,23,25–32,35In this comprehensive review and meta-analysis, we have summarized and compared the findings of recent studies (2016–2022), exploring the effects of topical TXA on perioperative blood loss in spine surgery.
Safety and Adverse Events After Topical TXA
酸已被吹捧为一个低风险的治疗limited complication profile.40However, the reported adverse effects—especially with systemic absorption—include potentially increased incidence of epileptic seizures and risk of clotting events such as venous thromboembolism or pulmonary embolism.40,50的epileptogenic activity of TXA has been hypothesized to be associated with high central nervous system penetrance and potential interference with the inhibitory pathways of GABA and glycine.40,50,51Also, the prothrombotic nature of TXA makes concerns for clotting events reasonable. However, the evidence has been inconclusive regarding such adverse events. Many studies found no link between TXA and epileptic seizures or thrombotic events.51–53的studies that reported such associations typically administered high TXA doses (total dose 61–259 mg/kg) and were largely conducted using IV TXA.50,54,55的refore, topical TXA may mitigate such risks, given the reduced systemic concentrations in comparison with IV application.
Our systematic review adds to the existing body of literature that supports the overall safety profile of TXA, regardless of administration route. While some of our reviewed studies reported rare events such as venous thromboembolism, infection, and pulmonary embolism, there were no significant differences in the rates of complications among groups treated with topical TXA, IV TXA, or combined administration of TXA (Table 1）.6,12,38In fact, most studies reported no complications at all after TXA administration. Furthermore, there were no cases of post-TXA seizure in any studies reviewed (Table 1）.
Although we found no association between topical TXA and adverse events, there remain concerns for its use in high-risk patients with a history of thromboembolic complications and patients in the prothrombotic, hypercoagulable states of trauma and malignancy. The individual studies included in our review may provide some insight. Shi et al. found no differences in adverse events between patients with a history of thromboembolism treated with TXA and those treated without topical TXA.12Similarly, both Wang et al. and Maethungkul et al., studying topical TXA in patients with thoracolumbar fracture/trauma and spinal metastasis, respectively, reported no complications.5,39Furthermore, Sudprasert et al. (studying topical TXA during thoracolumbar trauma surgery) reported no cases of seizure, deep vein thrombosis, or pulmonary embolism.33Although these results are promising, further adequately powered studies investigating TXA treatment for high-risk patients are warranted.
Cytotoxicity and Potential Wound-Healing Complications After Topical TXA
Although topical TXA may reduce blood loss in spine surgery, the cellular effects on the exposed chondrocytes, fibroblasts, and myocytes must be investigated. Specifically, some studies have reported mixed results regarding the cytotoxicity of topical TXA. Ambra et al. noted that topical TXA did not affect the viability of Yucatan pig chondrocytes (physiologically similar to human chondrocytes) when treated at low doses of 1–4 mg/ml.57Marmotti et al. similarly found that human chondrocytes and synoviocytes exposed to low-dose topical TXA (7 mg/ml) conserved their structure and growth ability.58However, increasing evidence has shown that human fibroblasts chronically exposed (> 4 hours) to > 20 mg/ml topical TXA experience a reduction in cell adhesion, motility, and viability, and an increase in apoptosis. At higher doses (> 50 mg/kg) of topical TXA, cytotoxicity is apparent after 10 minutes of exposure.59,60的se results suggest that the cytotoxicity of topical TXA may be dose and time dependent.
Application of topical TXA may expose the spinal wound environment to local excesses of TXA. Unfortunately, few studies—primarily in cardiac and orthopedic joint surgery—have quantified absorption and local concentrations after topical TXA administration (and only at a single point in time).60–63Given the risk of cytotoxicity and impaired healing, future research is needed to study the cytotoxic and pharmacokinetic properties of topical TXA.
Efficacy of Topical TXA Versus No TXA and IV TXA
Although TXA has been widely reported to reduce blood loss during and after surgery, studies assessing the efficacy of topical TXA are limited. Although a few studies have yielded inconsistent results, our pooled analyses comparing topical TXA to no TXA demonstrated that topical TXA yields statistically significant benefits, including decreases in VBL, PBL, and overall hospitalization length, as well as higher postoperative hemoglobin levels (Fig. 2A–D）.这些研究结果表明,局部酸推广应用es hemostasis and may be a useful tool for limiting surgical blood loss. This is a novel pooled finding that contrasts those of prior topical TXA metanalyses, which are limited by the inclusion of fewer RCTs and nonrandomized controlled trials, that have not clearly shown the impact of topical TXA on reducing intraoperative blood loss.15,48However, more research into topical TXA is warranted.
Like topical TXA, IV TXA demonstrated reductions in VBL, PBL, and LOS compared with placebo (Fig. 6A, B, and D）.However, because IV TXA is more extensively studied and used, it is important to compare these different administrations of TXA.6,8,9集中分析了没有统计significant differences in the measured outcomes between patients treated with topical and those treated with IV TXA (Fig. 3A–D）.This lack of significance may be due to the large standard deviations reported by several of the studies (Table 1,Fig. 3A）.26,28
A:Forest plot diagram showing the effect of IV TXA on VBL compared with non-TXA controls.B:Forest plot diagram showing the effect of IV TXA on PBL compared with non-TXA controls.C:Forest plot diagram showing the effect of IV TXA on postoperative hemoglobin level compared with non-TXA controls.D:Forest plot diagram showing the effect of IV TXA on LOS compared with non-TXA controls.
Combined Topical and IV TXA Administration
Topical TXA appears to be safe, even for high-risk patients. In addition, topical TXA (compared with placebo) may improve intraoperative and postoperative blood loss, resulting in higher postoperative hemoglobin levels and shorter hospitalization lengths (Fig. 2A–D）.Thus, an interesting clinical question is if the combined administration of topical TXA with IV TXA would result in an additive effect for blood loss. However, our pooled analysis showed that combined topical TXA and IV TXA was not associated with significantly synergistic effects in reducing blood loss both during and after surgery (Fig. 5A and B）.This is in contrast to a subset of studies that analyzed combined IV and topical TXA.5,29,38,39Li et al. and Erdogan et al. demonstrated statistically superior VBL, PBL, and hemoglobin levels after combined TXA compared with no TXA.29,38此外,当比较结合局部和我V TXA administration to IV TXA alone in a large RCT with 280 patients, Li et al. demonstrated statistically significant improvements in intraoperative blood loss (VBL), PBL, postoperative hemoglobin levels, and transfusion rates in the combined group compared with the IV TXA group.5Our statistically insignificant pooled analysis results could be due to high heterogeneity (I2≥ 94%), and our comparison may have been underpowered due to limited research that has compared combined topical and IV TXA with no TXA or IV TXA (Figs. 4A–C,5A, and 5B）.5,6,26,29Further studies are required to establish if combined topical and IV TXA is superior to IV TXA alone.
Impact of TXA Administration Route on Transfusion Rates
Though the transfusion rates were not accompanied by standard deviations and therefore excluded from the pooled analysis, reductions in transfusion rates were reported in topical TXA and combined TXA groups when compared with non-TXA and IV TXA groups. Of 12 studies that compared topical TXA and non-TXA controls, 6 studies reported reduced transfusion rates after topical TXA. Further, 1 study, of 4 that compared transfusion rates between topical and IV TXA groups, found reduced transfusions in the topical TXA group.26Two studies demonstrated that the transfusion rate was reduced in the combined TXA group compared with the non-TXA control.29,38Three studies compared combined TXA with IV TXA, of which 1 demonstrated that the transfusion rate was reduced in the combined TXA group compared with that of the IV TXA group.29In the other 2 studies, 1 reported no blood transfusions in any of the patients, and the other found no significant difference in the blood transfusion rates between the combined and IV TXA groups.5,39的se findings may be clinically significant, given the transfusion-associated risks.26
Limitations
Some key limitations affected this systematic review and pooled analysis. One limitation was the diversity of studies included, with variations in prospective versus retrospective nature, patient characteristics (e.g., age, comorbidities), spine surgery types, and TXA doses. Although our pooled analyses provided promising results, most comparisons (excluding those shown in Figs. 2C, 3D, and 6D) exhibited high heterogeneity (I2> 50%). Another limitation is that similar meta-analyses were conducted previously, but they primarily focused on articles published before 2019. However, as approximately 70% of the literature on the topical administration of TXA was published after 2019, an updated analysis is warranted.15,17–19此外,从2016年到2021年以前的荟萃分析included fewer RCTs and nonrandomized controlled trials, concentrated on the use of topical TXA for the treatment of lumbar degenerative disease, and lacked analysis of its intraoperative effects and combined administration with IV TXA. The most recent meta-analyses have discussed topical TXA, including those by Cao et al. and Xiao et al., and included more studies.48,64However, Cao et al. included only 9 articles, compared with 18 in this study, that investigated topical TXA specifically. Unlike Cao et al., we solely investigated topical TXA and its combined use with IV TXA in various contexts, including posterior cervical surgery, spinal oncology, and in patients with increased risk of thromboembolism. We also investigated a wider range of topical TXA administration methods, including Gelfoam, irrigation solutions, and retrograde injection via drains. The largest TXA meta-analysis to date by Xiao et al. included 21 studies published in Chinese and English. The authors conducted an analysis on several forms of TXA administration (including topical) but focused on posterior lumbar fusion surgery only.64Here, we conducted a focused study on the use of topical TXA—in a variety of clinical contexts—providing novel insight into its effects on intraoperative blood loss (VBL), HGB, and LOS.
Conclusions
As an invasive procedure, spine surgery may be associated with blood loss. Topical TXA is a promising strategy to reduce overall and perioperative blood loss. Importantly, our review appreciated no cases of seizure and only rare occurrences of adverse events, such as deep vein thrombosis and pulmonary embolism, after topical TXA administration. In pooled analyses, topical TXA was associated with less intraoperative and postoperative blood loss, higher postoperative hemoglobin levels, and shorter hospitalization length compared with controls.
Disclosures
Dr. Chou reported personal fees from Globus and personal fees from Orthofix outside the submitted work.
Author Contributions
Conception and design: Chan, Izima, Chou. Acquisition of data: Izima, Sampath. Analysis and interpretation of data: Izima, Sampath, Tang, Ambati. Drafting the article: Chan, Izima, Sampath, Tang, Ambati. Critically revising the article: all authors. Reviewed submitted version of manuscript: Chan, Izima, Sampath, Tang, Ambati. Approved the final version of the manuscript on behalf of all authors: Chan. Statistical analysis: Izima, Tang. Study supervision: Chan.
References
-
1 ↑
BednarDA,BednarVA,ChaudharyA,FarrokhyarF.Tranexamic acid for hemostasis in the surgical treatment of metastatic tumors of the spine.Spine (Phila Pa 1976).2006;31(8):954–957.
-
2 ↑
BibleJE,MirzaM,KnaubMA.Blood-loss management in spine surgery.J Am Acad Orthop Surg.2018;26(2):35–44.
-
3 ↑
SahuS,Hemlata,VermaA.Adverse events related to blood transfusion.Indian J Anaesth.2014;58(5):543–551.
-
4 ↑
RobertsI,Prieto-MerinoD,MannoD.Mechanism of action of tranexamic acid in bleeding trauma patients: an exploratory analysis of data from the CRASH-2 trial.Crit Care.2014;18(6):685.
-
5 ↑
WangX,YangR,SunH,ZhangY.Different effects of intravenous, topical, and combined application of tranexamic acid on patients with thoracolumbar fracture.World Neurosurg.2019;127:e1185–e1189.
-
6 ↑
MuX,WeiJ,WangC,et al.Intravenous administration of tranexamic acid significantly reduces visible and hidden blood loss compared with its topical administration for double-segment posterior lumbar interbody fusion: a single-center,.placebo-controlled, randomized trial. World Neurosurg. 2019;122:e821-e827.
-
7 ↑
CuiH,ChenK,LvS,YuanC,WangY.An analysis of perioperative hidden blood loss in femoral intertrochanteric fractures: bone density is an important influencing factor.BMC Musculoskelet Disord.2021;22(1):6.
-
8 ↑
YuCC,FidaiM,WashingtonT,BartolS,GrazianoG.Oral is as effective as intravenous tranexamic acid at reducing blood loss in thoracolumbar spinal fusions: a prospective randomized trial.Spine (Phila Pa 1976).2022;47(2):91–98.
-
9 ↑
ViraniSR,DahaputeAA,PandaI,BavaSS.Role of local infiltration of tranexamic acid in reducing blood loss in peritrochanteric fracture surgery in the elderly population.Malays Orthop J.2016;10(3):26–30.
-
10 ↑
GoobieSM,FaraoniD.Tranexamic acid and perioperative bleeding in children: what do we still need to know?Curr Opin Anaesthesiol.2019;32(3):343–352.
-
11 ↑
LeckerI,WangDS,WhissellPD,AvramescuS,MazerCD,OrserBA.Tranexamic acid-associated seizures: causes and treatment.Ann Neurol.2016;79(1):18–26.
-
12 ↑
ShiP,WangJ,CaiT,et al.Safety and efficacy of topical administration of tranexamic acid in high-risk patients undergoing posterior lumbar interbody fusion surgery.World Neurosurg.2021;151:e621–e629.
-
13 ↑
LinGX,ChenCM,ZhuMT,ZhengL.的safety and effectiveness of tranexamic acid in lumbar interbody fusion surgery: an updated meta-analysis of randomized controlled trials.World Neurosurg.2022;166:198–211.
-
14
GuoT,XuanW,FengH,WangJ,MaX.的efficacy and safety of topical tranexamic acid for spinal surgery.Curr Pharm Des.2021;27(44):4496–4503.
-
15 ↑
FatimaN,BarraME,RobertsRJ,et al.Advances in surgical hemostasis: a comprehensive review and meta-analysis on topical tranexamic acid in spinal deformity surgery.Neurosurg Rev.2021;44(1):163–175.
-
16 ↑
HuiS,PengY,TaoL,et al.Tranexamic acid given into wound reduces postoperative drainage, blood loss, and hospital stay in spinal surgeries: a meta-analysis.J Orthop Surg Res.2021;16(1):401.
-
17 ↑
XiongZ,LiuJ,YiP,WangH,TanM.Comparison of intravenous versus topical tranexamic acid in nondeformity spine surgery: a meta-analysis.BioMed Res Int.2020;2020:7403034.
-
18
YerneniK,BurkeJF,TuchmanA,et al.Topical tranexamic acid in spinal surgery: a systematic review and meta-analysis.J Clin Neurosci.2019;61:114–119.
-
19 ↑
LuoW,SunRX,JiangH,MaXL.的efficacy and safety of topical administration of tranexamic acid in spine surgery: a meta-analysis.J Orthop Surg Res.2018;13(1):96.
-
20 ↑
PageMJ,McKenzieJE,BossuytPM,et al.的PRISMA 2020 statement: an updated guideline for reporting systematic reviews.Int J Surg.2021;88:105906.
-
21 ↑
LoCK,MertzD,LoebM.Newcastle-Ottawa Scale: comparing reviewers’ to authors’ assessments.BMC Med Res Methodol.2014;14:45.
-
22 ↑
SterneJAC,SavovićJ,PageMJ,et al.RoB 2: a revised tool for assessing risk of bias in randomised trials.BMJ.2019;366:l4898.
-
23 ↑
MallepallyAR,MahajanR,RustagiT,GoelSA,DasK,ChhabraHS.Use of topical tranexamic acid to reduce blood loss in single-level transforaminal lumbar interbody fusion.Asian Spine J.2020;14(5):593–600.
-
24 ↑
FarzaneganG,AhmadpourF,KhoshmohabbatH,KhadiviM,RasouliHR,EslamianM.的effect of topical tranexamic acid on intraoperative blood loss in patients undergoing posterior lumbar laminectomy and discectomy: a randomized, double-blind, controlled trial study.Asian Spine J.2022;16(6):857–864.
-
25 ↑
KhadiviM,SaghebdoustS,MoghadamN,et al.Effect of topical administration of tranexamic acid on intraoperative and postoperative blood loss during posterior cervical laminectomy and fusion surgery: a retrospective study.Turk Neurosurg.2023;33(1):94–100.
-
26 ↑
Arun-KumarV,Naresh-BabuJ.Is there a role for preoperative local infiltration of tranexamic acid in elective spine surgery? A prospective randomized controlled trial analyzing the efficacy of intravenous, local infiltration, and topical administration of tranexamic acid.Glob Spine J.2021;11(1):21–27.
-
27 ↑
LiangJQ,RongTH,LiuHZ,et al.Topical injection of tranexamic acid via a drain plus drain-clamping to reduce blood loss in degenerative lumbar scoliosis surgery.Orthop Surg.2020;12(1):67–73.
-
28 ↑
ArainA,PosnerA,VigKS,et al.201. Prospective randomized controlled trial of tranexamic acid use during elective lumbar spine surgery, preliminary results.Spine J.2021;21(9)(suppl):S102–S103.
-
29 ↑
LiJ,WangL,BaiT,LiuY,HuangY.Combined use of intravenous and topical tranexamic acid efficiently reduces blood loss in patients aged over 60 operated with a 2-level lumbar fusion.J Orthop Surg Res.2020;15(1):339.
-
30 ↑
XuD,ChenX,LiZ,RenZ,ZhuangQ,LiS.Tranexamic acid reduce hidden blood loss in posterior lumbar interbody fusion (PLIF) surgery.Medicine (Baltimore).2020;99(11):e19552.
-
31 ↑
ChenC,YeYY,ChenYF,et al.比较氨甲环acid-s之间的失血oaked absorbable Gelfoam and topical retrograde injection via drainage catheter plus clamping in cervical laminoplasty surgery.BMC Musculoskelet Disord.2022;23(1):668.
-
32 ↑
EmrahK,AliAH,UtkuO,MuratK,KenanS,DenizB.Efficacy of tranexamic acid on blood loss in thoracolumbar spinal fusion surgery.J Coll Physicians Surg Pak.2021;31(12):1449–1454.
-
33 ↑
SudprasertW,TanaviriyachaiT,ChoovongkomolK,JongkittanakulS,PiyapromdeeU.A randomized controlled trial of topical application of tranexamic acid in patients with thoracolumbar spine trauma undergoing long-segment instrumented posterior spinal fusion.Asian Spine J.2019;13(1):146–154.
-
34 ↑
LiangJ,LiuH,HuangX,et al.使用氨甲环酸浸泡可吸收明胶sponge following complex posterior lumbar spine surgery: a randomized control trial.Clin Neurol Neurosurg.2016;147:110–114.
-
35 ↑
ShenJ,YangZ,FuM,HaoJ,JiangW.的influence of topical use of tranexamic acid in reducing blood loss on early operation for thoracolumbar burst fracture: a randomized double-blinded controlled study.Eur Spine J.2021;30(10):3074–3080.
-
36 ↑
FjeldOR,GrøvleL,HelgelandJ,et al.Complications, reoperations, readmissions, and length of hospital stay in 34 639 surgical cases of lumbar disc herniation.Bone Joint J.2019;101-B(4):470-477.
-
37 ↑
BasquesBA,VarthiAG,GolinvauxNS,BohlDD,GrauerJN.Patient characteristics associated with increased postoperative length of stay and readmission after elective laminectomy for lumbar spinal stenosis.Spine (Phila Pa 1976).2014;39(10):833–840.
-
38 ↑
ErdoganU,SariS,AkbasA.的efficiency of simultaneous systemic and topical use of tranexamic acid in spinal fusion surgery.J Neurol Surg A Cent Eur Neurosurg.2022;83(1):46–51.
-
39 ↑
MaethungkulR,AtthakomolP,PhinyoP,PhanphaisarnA,MurakamiH,SangsinA.Adjunctive topical tranexamic acid for blood salvage does not reduce postoperative blood loss compared with placebo in patients who undergo palliative decompressive spinal metastasis surgery: a randomized controlled trial.Spine (Phila Pa 1976).2022;47(3):187–194.
-
40 ↑
YooJS,AhnJ,KarmarkarSS,LamoutteEH,SinghK.的use of tranexamic acid in spine surgery.Ann Transl Med.2019;7(suppl 5):S172.
-
41
WongJ,El BeheiryH,RampersaudYR,et al.氨甲环酸减少围手术期血液loss in adult patients having spinal fusion surgery.Anesth Analg.2008;107(5):1479–1486.
-
42
VermaK,ErricoT,DiefenbachC,et al.的relative efficacy of antifibrinolytics in adolescent idiopathic scoliosis: a prospective randomized trial.J Bone Joint Surg Am.2014;96(10):e80.
-
43 ↑
LykissasMG,CrawfordAH,ChanG,AronsonLA,Al-SayyadMJ.的effect of tranexamic acid in blood loss and transfusion volume in adolescent idiopathic scoliosis surgery: a single-surgeon experience.J Child Orthop.2013;7(3):245–249.
-
44 ↑
PetersA,VermaK,SlobodyanyukK,et al.Antifibrinolytics reduce blood loss in adult spinal deformity surgery: a prospective, randomized controlled trial.Spine (Phila Pa 1976).2015;40(8):E443–E449.
-
45
DunnLK,ChenCJ,TaylorDG,et al.Postoperative low-dose tranexamic acid after major spine surgery: a matched cohort analysis.Neurospine.2020;17(4):888–895.
-
46
RaviGK,PandaN,AhluwaliaJ,ChauhanR,SinglaN,MahajanS.Effect of tranexamic acid on blood loss, coagulation profile, and quality of surgical field in intracranial meningioma resection: a prospective randomized, double-blind, placebo-controlled study.Surg Neurol Int. 2021;12:272.
-
47 ↑
ShakeriM,SalehpourF,ShokouhiG,et al.Minimal dose of tranexamic acid is effective in reducing blood loss in complex spine surgeries: a randomized double-blind placebo controlled study.Asian Spine J.2018;12(3):484–489.
-
48 ↑
CaoZ,LiQ,GuoJ,LiY,WuJ.Optimal administration strategies of tranexamic acid to minimize blood loss during spinal surgery: results of a Bayesian network meta-analysis.Ann Med.2022;54(1):2053–2063.
-
49 ↑
TodeschiniAB,UribeAA,Echeverria-VillalobosM,et al.Efficacy of intravenous tranexamic acid in reducing perioperative blood loss and blood product transfusion requirements in patients undergoing multilevel thoracic and lumbar spinal surgeries: a retrospective study.Front Pharmacol.2020;11:566956.
-
50 ↑
MurkinJM,FalterF,GrantonJ,YoungB,BurtC,ChuM.High-dose tranexamic acid is associated with nonischemic clinical seizures in cardiac surgical patients.Anesth Analg.2010;110(2):350–353.
-
51 ↑
McCormackPL.Tranexamic acid: a review of its use in the treatment of hyperfibrinolysis.Drugs.2012;72(5):585–617.
-
52
CRASH-3 trial collaborators.Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial.Lancet.2019;394(10210):1713–1723.
-
53 ↑
ChenC,LiuJ,DuL.Tranexamic acid after cardiopulmonary bypass does not increase risk of postoperative seizures: a retrospective study.Gen Thorac Cardiovasc Surg.2022;70(4):337–346.
-
54 ↑
OckermanA,VanasscheT,GaripM,et al.Tranexamic acid for the prevention and treatment of bleeding in surgery, trauma and bleeding disorders: a narrative review.Thromb J.2021;19(1):54.
-
56
HodgsonS,LarvinJT,DearmanC.What dose of tranexamic acid is most effective and safe for adult patients undergoing cardiac surgery?Interact Cardiovasc Thorac Surg.2015;21(3):384–388.
-
57 ↑
AmbraLF,de GirolamoL,NiuW,PhanA,SpectorM,GomollAH.No effect of topical application of tranexamic acid on articular cartilage.Knee Surg Sports Traumatol Arthrosc.2019;27(3):931–935.
-
58 ↑
MarmottiA,MattiaS,MangiaviniL,et al.Tranexamic acid effects on cartilage and synovial tissue: an in vitro study for a possible safe intra-articular use.J Biol Regul Homeost Agents.2016;30(4)(suppl 1):33–40.
-
59 ↑
GkiatasI,KontokostopoulosAP,TsirigkakisSE,et al.Topical use of tranexamic acid: are there concerns for cytotoxicity?World J Orthop.2022;13(6):555–563.
-
60 ↑
De BonisM,CavaliereF,AlessandriniF,et al.Topical use of tranexamic acid in coronary artery bypass operations: a double-blind, prospective, randomized, placebo-controlled study.J Thorac Cardiovasc Surg.2000;119(3):575–580.
-
61
AusenK,PleymH,LiuJ,et al.Serum concentrations and pharmacokinetics of tranexamic acid after two means of topical administration in massive weight loss skin-reducing surgery.Plast Reconstr Surg.2019;143(6):1169e–1178e.
-
62
KrohnCD,SørensenR,LangeJE,RiiseR,BjørnsenS,BrosstadF.Tranexamic acid given into the wound reduces postoperative blood loss by half in major orthopaedic surgery.Eur JSurg Suppl. 2003;(588):57-61.
-
63 ↑
WongJ,AbrishamiA,El BeheiryH,et al.Topical application of tranexamic acid reduces postoperative blood loss in total knee arthroplasty: a randomized, controlled trial.J Bone Joint Surg Am.2010;92(15):2503–2513.
-
64 ↑
XiaoK,ZhuoX,PengX,WuZ,LiB.的efficacy and safety of tranexamic acid in lumbar surgery: A meta-analysis of randomized-controlled trials.Jt Dis Relat Surg.2022;33(1):57–85.
