Tranexamic acid (TXA) is a synthetic lysine analogue that competitively inhibits the binding of plasminogen to fibrin, thereby suppressing fibrinolysis and reducing surgical blood loss.1 Since the CRASH-2 trial established a mortality benefit for TXA in traumatic hemorrhage, its use has expanded across orthopedic, cardiac, obstetric, and spinal surgery, and — more cautiously — into cranial neurosurgery.2,3 Cranial procedures pose a distinctive risk–benefit calculus for antifibrinolytic therapy. Highly vascular tumors such as meningiomas can produce substantial intraoperative blood loss, and the resulting need for allogeneic transfusion carries recognized risks including transfusion-related acute lung injury, circulatory overload, and immunomodulation.4,5 At the same time, TXA is understood to lower the seizure threshold through an anti-GABAergic mechanism, and neurosurgical patients are theorized to carry an elevated baseline risk of venous thromboembolism (VTE), raising concern that antifibrinolytic therapy could precipitate seizures or thrombotic events in a population where either complication is poorly tolerated.6,7 Over the past decade, this question has been addressed by a series of systematic reviews and meta-analyses (SRs/MAs), most concentrated on intracranial meningioma resection, alongside separate reviews addressing skull base surgery, aneurysmal subarachnoid hemorrhage (aSAH), craniosynostosis, and traumatic brain injury (TBI).8–17 These reviews substantially overlap in the primary trials they include, yet have not, to our knowledge, been consolidated into a single synthesis spanning the full spectrum of cranial neurosurgical practice and all five outcomes of principal clinical interest: blood loss, blood transfusion, thromboembolic events, operative time, and mortality. Where multiple reviews of the same evidence base report differing conclusions — as is the case here for blood transfusion — an overview that places their findings side by side is more informative to practicing neurosurgeons and anesthesiologists than any single review considered in isolation. The objective of this overview was therefore to systematically identify existing SRs/MAs of TXA use in cranial neurosurgery and synthesize their reported findings across the five outcomes above, in order to characterize the consistency, gaps, and clinical implications of the current evidence base.

Design. This is an overview of systematic reviews (a systematic review of systematic reviews), reported following PRISMA 2020 principles as adapted for overviews.18 A prospective protocol was not registered. Eligibility criteria. Systematic reviews and/or meta-analyses evaluating the intravenous administration of TXA during cranial neurosurgical procedures — including resection of intracranial meningiomas or other neoplasms, skull base surgery, aSAH, craniosynostosis, or TBI — were eligible if they reported at least one of the five outcomes of interest (blood loss, blood transfusion, thromboembolic events, operative time, mortality) against a non-TXA or placebo comparator. One large retrospective cohort study without a formal systematic search was retained given its frequent citation as primary evidence in this literature and its comparable outcome structure.19 Reviews restricted to spinal, orthopedic, or non-neurosurgical populations, non-English-language reports, and reviews without extractable comparative outcome data were excluded. Information sources and search. PubMed and Google Scholar were searched using combinations of "tranexamic acid," "cranial neurosurgery," "meningioma," "craniosynostosis," "subarachnoid hemorrhage," and "traumatic brain injury," supplemented by manual cross-referencing of the reference lists of eligible reviews, for records published between January 2016 and September 2026. Study selection and data extraction. Screening and extraction were performed by a single reviewer; outcome estimates, study designs, and sample sizes were extracted as reported by the original review authors and were not re-derived from primary trial data. This single-reviewer process is noted as a limitation below. Quality considerations. A formal instrument-based quality appraisal (e.g., AMSTAR-2) of included reviews was not performed for this overview; instead, methodological features reported by each review — PRISMA adherence, prospective registration, and use of the JADAD scale for included-trial quality — are noted narratively where applicable. Data synthesis. Findings are synthesized narratively by outcome domain and summarized in tabular form. Because the included reviews draw on a substantially overlapping pool of primary RCTs (principally trials by Hooda et al., Siddiqui et al., Ravi et al., Rebai et al., Sutanto et al., and Khalid et al.),20–25 with only partial incorporation of the most recent trial by Li et al.,26 their effect estimates are not statistically independent. An original quantitative re-pooling across reviews was therefore not attempted, as this would double-count shared primary data; instead, this overview reports the range and direction of effect estimates as published.

Overview of included reviews Ten publications met eligibility criteria: eight meta-analyses focused specifically on intracranial meningioma resection,8–15 one broader review of TXA across cranial and spinal neuro-oncologic surgery,16 one narrative review spanning TBI, aSAH, and cranial tumor surgery,17 and one large retrospective cohort study of complex skull base neurosurgery.19 Publication years ranged from 2016 to 2025. Table 1 summarizes their scope, design, and evidence base. Review (year) Journal Scope Design / included studies Patients, n Mebel et al. (2016) Anesth Analg Complex skull base surgery Retrospective cohort 519 (245 TXA) de Faria et al. (2021) Neurosurg Rev TBI, aSAH, spinal, cranial surgery (narrative) Narrative review, 1976–2019 Not pooled Prastikarunia et al. (2021) Surg Neurol Int Brain tumor surgery Meta-analysis Not extracted Brown et al. (2022) World Neurosurg Elective intracranial neoplasm resection SR, 4 studies 682 Wijaya et al. (2023) J Neurooncol Intracranial meningioma MA, 5 RCTs 321 Clynch et al. (2023) J Clin Neurosci Meningioma surgery SR/MA Not extracted Nguyen et al. (2023) J Neurosurg Intracranial meningioma MA, 6 RCTs 381 (190 TXA) Liu et al. (2024) PLoS ONE Meningioma resection MA, PROSPERO-registered Not extracted Vychopen et al. (2024) Front Oncol Cranial meningioma surgery MA of RCTs Not extracted Khan et al. (2025) J Clin Neurosci Neuro-oncologic surgery incl. spine SR/MA, 28 studies (9 neoplasm, 10 aSAH, 9 craniosynostosis) Not pooled overall Blood loss Every review reporting this outcome favored TXA. Wijaya et al. reported a standardized mean difference (SMD) of −1.40 (95% CI −2.49 to −0.31) across five RCTs.9 Nguyen et al. reported a mean difference of −282.48 mL (95% CI −367.77 to −197.20; p<0.001) across six RCTs.11 Brown et al. reported mean total blood loss of 821.9 mL with TXA versus 1099.0 mL without, across four studies.8 Clynch et al. and Vychopen et al. similarly concluded that TXA reduces intraoperative blood loss in meningioma surgery, and Khan et al. reported a reduction in brain tumor surgery specifically (p<0.01).10,12,16 No included review reported a null or unfavorable blood-loss finding. Blood transfusion Most reviews reported a statistically significant reduction in transfusion requirement with TXA: Wijaya et al. (relative risk 0.58, 95% CI 0.34–0.99),9 Nguyen et al. (odds ratio [OR] 0.26, 95% CI 0.09–0.77),11 Brown et al. (OR 0.627, 95% CI 0.425–0.925),8 and Mebel et al., in the largest cohort in this overview, reported an adjusted OR of 0.32 (95% CI 0.15–0.65) for perioperative transfusion after adjusting for hemoglobin, tumor diameter, and procedure category.19 By contrast, Clynch et al. concluded that TXA had no significant effect on blood transfusion requirement in meningioma surgery, despite reporting a reduction in blood loss — the one clear point of discordance identified across the included reviews.12 This inconsistency likely reflects differences in included trials, transfusion thresholds, and statistical power rather than a true absence of effect, but it means transfusion-sparing cannot be regarded as an unqualified finding. Figure 1 displays the published transfusion-outcome estimates for the four reviews reporting a comparable odds/relative-risk metric, illustrating both the consistent direction of effect and the one review (Clynch et al.) whose non-significant finding fell outside this pattern. Figure 2 illustrates the magnitude of blood-loss reduction using the one review reporting pooled raw means for both arms (Brown et al., 4 studies, n=682); other reviews reported this outcome as a standardized or weighted mean difference rather than raw millilitres, and are summarized in Table 2 instead. Summary of outcome-level effect estimates Table 2 consolidates the effect estimates reported for each of the five outcomes across the included reviews, for reference alongside the narrative synthesis above. Outcome Review Effect estimate (95% CI) Direction / significance Blood loss Wijaya et al. 2023 SMD −1.40 (−2.49 to −0.31) Favors TXA, significant Nguyen et al. 2023 MD −282.48 mL (−367.77 to −197.20) Favors TXA, significant (p<0.001) Brown et al. 2022 821.9 vs 1099.0 mL (means) Favors TXA Clynch / Vychopen / Khan Not extracted (qualitative) Favors TXA (direction only) Blood transfusion Wijaya et al. 2023 RR 0.58 (0.34–0.99) Favors TXA, significant Nguyen et al. 2023 OR 0.26 (0.09–0.77) Favors TXA, significant Brown et al. 2022 OR 0.627 (0.425–0.925) Favors TXA, significant Mebel et al. 2016 adj. OR 0.32 (0.15–0.65) Favors TXA, significant Clynch et al. 2023 Not significant (NS) No effect — discordant with above Thromboembolic events Nguyen et al. 2023 0 VTE, both arms (6 RCTs) No signal Mebel et al. 2016 Similar rates, TXA vs control No signal Khan et al. 2025 p<0.01 (no increase) No signal Operative time Wijaya et al. 2023 SMD −0.36 (−0.63 to −0.09) Favors TXA (shorter), significant Nguyen et al. 2023 MD −0.92 min (−56.92 to 55.08) No significant difference (p=0.97) Mortality All reviews Not independently powered No benefit or harm reported Thromboembolic events No review identified an increased risk of VTE or seizure with TXA in cranial tumor surgery. Nguyen et al. reported zero VTE events in either arm across all six included RCTs.11 Mebel et al. found similar rates of thromboembolic events and seizure between groups in their skull base cohort.19 Khan et al. reported that TXA reduced blood loss in brain tumor surgery without predisposing patients to VTE or seizure (p<0.01), though it did not reduce rates of vasospasm in aSAH (p=0.27) and was not associated with meaningful differences in long-term neurological outcome in that subgroup.16 In the broader neurosurgical literature, de Faria et al. noted that moderate-to-high TXA doses have been associated with neurological complications (seizure, transient ischemic attack, delirium), that TXA reduces rebleeding risk in ruptured aneurysm but with only weak evidence for a mortality benefit, and that evidence for TXA in TBI and brain surgery specifically remains limited and does not show clear benefit.17 Operative time Findings for operative and anesthetic time were mixed. Wijaya et al. reported a modest reduction in anesthetic time favoring TXA (SMD −0.36, 95% CI −0.63 to −0.09).9 Nguyen et al., by contrast, found no significant difference in operative duration between groups overall (mean difference −0.92 minutes, 95% CI −56.92 to 55.08; p=0.97), although two of the six individual RCTs they pooled reported significantly shorter operative time with TXA.11 No review identified a prolongation of operative time with TXA. Mortality Mortality was inconsistently reported and was not a primary or adequately powered outcome in any included review. Where mortality-related data were reported in individual trials pooled by these reviews, event rates were low and did not differ significantly between arms; de Faria et al. specifically characterized the mortality evidence for TXA in ruptured intracranial aneurysm as weak despite a reduction in rebleeding risk.17 No included review reported a mortality benefit or harm attributable to TXA in cranial neurosurgery.

This overview consolidates ten reviews published between 2016 and 2025 and finds a consistent signal across all of them: TXA reduces intraoperative blood loss in cranial neurosurgery, most robustly demonstrated in intracranial meningioma resection, without an observed increase in thromboembolic events or seizures. This consistency is notable precisely because the reviews were conducted by different author groups using different search strategies and statistical approaches, yet converge on the same direction of effect for blood loss and safety outcomes. The evidence is markedly less consistent for blood transfusion, where the discordant finding from Clynch et al. against five other reviews reporting significant transfusion reduction illustrates a broader limitation of this literature: nearly every meta-analysis to date has pooled the same small cluster of six to seven RCTs — principally the trials by Hooda, Siddiqui, Ravi, Rebai, Sutanto, and Khalid — with only the most recent reviews beginning to incorporate the 2024 non-inferiority trial by Li et al.9–15,20–26 Repeated re-analysis of an overlapping, geographically concentrated trial base (predominantly conducted in India, Indonesia, Pakistan, and Tunisia) inflates the apparent volume of confirmatory evidence without materially increasing the underlying sample size, and may limit generalizability to other healthcare settings and dosing protocols. Evidence outside meningioma-specific resection remains comparatively sparse and heterogeneous. Skull base surgery data derive from a single large retrospective cohort rather than a randomized design;19 aSAH evidence suggests a reduction in rebleeding without a clear mortality signal;17 and TBI evidence, despite the precedent set by CRASH-2 in trauma populations broadly, does not clearly support benefit specifically in cranial neurosurgical TBI management.2,17 Craniosynostosis evidence, addressed within the broader Khan et al. review, likewise favors reduced blood loss.16 Taken together, these findings support a reasonably confident, if narrow, clinical conclusion: TXA can be considered a safe and effective adjunct specifically for reducing blood loss during intracranial meningioma resection, with transfusion benefit likely but not universally demonstrated, and no signal of increased thromboembolic or seizure risk. Evidence for skull base, aSAH, craniosynostosis, and TBI cranial surgery is comparatively limited, with fewer dedicated RCTs in each domain, variable dosing regimens, and inconsistent reporting of mortality and long-term neurological outcomes across all ten reviews synthesized here. Limitations This overview has several limitations. Screening and data extraction were performed by a single reviewer rather than in duplicate, which is a departure from standard systematic review methodology and a source of potential selection or extraction error. A formal, instrument-based quality appraisal of included reviews (e.g., AMSTAR-2) was not conducted. Because the included reviews substantially overlap in their primary RCT evidence base, this overview reports their published effect estimates narratively rather than generating a new independent pooled statistic, which limits the precision of any single combined estimate. The search was restricted to English-language publications and two databases plus citation tracking, rather than a full multi-database search with a formal PRISMA flow diagram of primary records; it is possible that additional eligible reviews were not identified. Finally, as an overview of reviews, this synthesis inherits any reporting bias, selective outcome reporting, or publication bias present in the underlying primary trials and reviews.

Across a substantially overlapping but methodologically varied set of ten reviews, tranexamic acid consistently reduces intraoperative blood loss in cranial neurosurgery — most convincingly in intracranial meningioma resection — without evidence of increased thromboembolic or seizure risk. Its effect on transfusion requirement, while favorable in most analyses, is not uniformly significant, and evidence for operative time and mortality benefit is inconsistent or underpowered. Evidence in skull base, aSAH, craniosynostosis, and TBI cranial surgery remains comparatively limited, and current conclusions remain concentrated in meningioma-focused surgery. DISCLOSURES Conflicts of interest: This overview was not prospectively registered.

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