Clinical study
Topical tranexamic acid in spinal surgery: A systematic review and meta-analysis

https://doi.org/10.1016/j.jocn.2018.10.121Get rights and content

Highlights

  • Topical TXA reduced postoperative blood loss in spine surgery.

  • Patients receiving topical TXA exhibited a lower hospitalization duration.

  • Minimal complications suggest the safety of topical TXA in spine surgery.

Abstract

Tranexamic acid (TXA) is a commonly used antifibrinolytic agent for perioperative blood conservation in several surgical specialties. Although historically administered intravenously, such systemic administration may be accompanied by severe side effects. Thus, the topical usage of TXA has been established in several fields but remains poorly evaluated in spine surgery. In this study, the authors aimed to review the medical literature on topical TXA usage in spine surgery to evaluate its safety and efficacy. We reviewed manuscripts and clinical trials exploring topical TXA usage in spine surgery published by April 1st, 2018. Postoperative blood loss volumes and hospitalization lengths of stay were evaluated with separate meta-analyses. We identified five articles and one unpublished clinical trial that were placebo-controlled and comprised 218 patients receiving topical TXA in spine surgery. Patients receiving topical TXA demonstrated significantly lower postoperative blood loss as compared to the placebo group (Standardized Mean Difference [SMD] 2.21, 95% CI 0.79–3.62, p < 0.001) and had a lower hospitalization duration (MD 0.99, 95% CI 0.49–1.49, p < 0.001). Overall, topical TXA favorably reduced postoperative blood loss and hospitalization duration in patients undergoing spinal surgery. However, further randomized controlled trials will be needed to definitively establish the optimal therapeutic doses needed for hemorrhage management, and the pharmacodynamics of tTXA in spinal surgery.

Introduction

Excessive perioperative blood loss is associated with increased surgical morbidity and mortality in patients undergoing spinal surgeries [1]. This is especially relevant in the setting of spinal deformity surgery, where the potential for significant blood loss is high [2], [3]. Several strategies have been utilized by spine surgeons to minimize perioperative blood loss, including meticulous intraoperative hemostasis technique, hypotensive anesthesia, and intravenous administration of various antifibrinolytic agents such as aminocaproic acid and tranexamic acid (TXA) [4], [5].

TXA is an antifibrinolytic lysine analogue that competitively inhibits plasminogen, plasmin, and tissue plasminogen activator at lysine binding sites [6]. TXA is typically administered intravenously as a bolus before incision and then maintained as continuous infusion throughout the surgery [7], [8]. It has been shown to significantly reduce perioperative hemorrhage in several procedures, including in cardiac, orthopedic, and spinal surgery [9], [10], [11], [12], [13], [14], [15]. However, systemic administration of TXA can have potential adverse effects on patients including deep vein thrombosis (DVT), pulmonary embolism (PE), and myocardial infarction (MI) [10], [16]. In patients with prior history of MI, stroke, DVT/PE and seizure disorders, intravenous TXA is generally avoided [17], [18], [19]. This has prompted several groups to explore the efficacy of applying TXA topically in the surgical wound to reduce perioperative blood loss [20]. Topical TXA (tTXA) provides a direct and local high concentration of the agent at the surgical bleeding site, and it avoids systemic exposure of TXA [21]. Topical TXA has been widely and successfully used to reduce blood loss in orthopedic, thoracic, and cardiac surgery [22], [23], [24], [25], [26]. However, few groups have studied the efficacy and safety of tTXA in spinal surgeries.

We aim to determine the efficacy and safety profile of tTXA in spine surgery by performing a systematic review and meta-analysis of published literature and completed clinical trials to assess the current evidence on this topic.

Section snippets

Article selection and data extraction

We comprehensively searched PubMed, EMBASE, EBSCO, and Springer for articles published before April 1st, 2018. In addition, we searched clinical trials using the U.S National Institutes of Health database (www.clinicaltrials.gov), the World Health Organization International Clinical Trials Registry Platform (http://www.who.int/ictrp/en/), and the International Standard Randomized Controlled Trial Number ISRCTN registry (https://www.isrctn.com). The following search keywords were used in all

Results

Our search strategy initially yielded 1323 articles and 25 registered clinical trials that matched our search criteria (Fig. 1). After applying our exclusion criteria, a total of six articles and one clinical trial remained. Of these, one article was excluded because it described a combinatorial administration of both intravenous and topical TXA. Thus, six studies were included in our overall review (Table 1). There were two randomized controlled trials, two prospective studies, and two

Discussion

Tranexamic acid is a hemostatic agent that has been in use since the 1960s [17]. Historically, TXA has been administered intravenously and reaches peak plasma concentrations quickly, with a half-time of approximately three hours [32]. Of concern, systemically administered TXA can penetrate the blood brain barrier, therefore dispersing throughout the central nervous system [33]. Although well-tolerated – with adverse events being quite rare – high doses of intravenous TXA has been found to

Conclusion

This systematic review and meta-analysis indicates that topical TXA is effective in reducing postoperative blood loss and hospital length of stay in patients undergoing spinal surgery. Future randomized controlled trials will be needed to definitively establish the optimal therapeutic doses needed for hemorrhage management, along with the pharmacodynamics of tTXA and its associated complications in spinal surgery.

Previous presentations

This work has not been previously presented elsewhere.

Role of the funding source

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Patient consent

Patient consent was not required; this is a systematic review of the existing literature.

Availability of data and material

Not applicable.

Author contributions

(1) Conception and Design: LA Tan, K Yerneni. (2) Administrative Support: K Yerneni. (3) Provision of study materials or patients: N/A. (4). Collection and Assembly of data: K Yerneni, LA Tan, JF Burke. (5) Data analysis and interpretation: All authors. (6) Manuscript writing: All authors. (7). Final approval of manuscript: All authors

Acknowledgements

The authors thank Dr. Arian Pourmehdi Lahiji for his assistance with translating Saberi and Miri (2010) from Farsi to English.

Disclosures/conflict of interest

Dr. Lenke is a consultant for and a patent holder with Medtronic. Dr. Lehman is a consultant for Medtronic. The other authors report no conflict of interesting concerning the materials or methods used in this study or the findings specified in this paper.

References (42)

  • J.B. Gill et al.

    The use of antifibrinolytic agents in spine surgery. a meta-analysis

    J Bone Joint Surg Am

    (2008)
  • B.J. Hunt

    The current place of tranexamic acid in the management of bleeding

    Anaesthesia

    (2015)
  • H. Hourlier et al.

    Single dose intravenous tranexamic acid as effective as continuous infusion in primary total knee arthroplasty: a randomised clinical trial

    Arch Orthop Trauma Surg

    (2015)
  • N. Ohashi et al.

    Administration of tranexamic acid to patients undergoing surgery for adolescent idiopathic scoliosis evokes pain and increases the infusion rate of remifentanil during the surgery

    PLoS One

    (2017;12.)
  • P.S. Myles et al.

    Tranexamic acid in patients undergoing coronary-artery surgery

    N Engl J Med

    (2017)
  • T. Danninger et al.

    Tranexamic acid and orthopedic surgery—the search for the holy grail of blood conservation

    Ann Transl Med

    (2015)
  • B. Yang et al.

    Systematic review and meta-analysis of perioperative intravenous tranexamic acid use in spinal surgery

    PLoS One

    (2013)
  • Z.-J. Li et al.

    Is tranexamic acid effective and safe in spinal surgery? A meta-analysis of randomized controlled trials

    Eur Spine J

    (2013)
  • F. Zhang et al.

    Effectiveness of tranexamic acid in reducing blood loss in spinal surgery: a meta-analysis

    BMC Musculoskelet Disord

    (2014;15.)
  • S. Wang et al.

    Topical versus intravenous tranexamic acid in total knee arthroplasty: a meta-analysis of randomized controlled trials

    Int Orthop

    (2017)
  • S.F. Winter et al.

    Systemic and topical use of tranexamic acid in spinal surgery: a systematic review

    Glob Spine J

    (2016)
  • Cited by (31)

    • Tranexamic acid dosing strategies and blood loss reduction in multilevel spine surgery: A systematic review and network meta-analysis: Tranexamic acid for multilevel spine surgery

      2021, North American Spine Society Journal
      Citation Excerpt :

      For example, in their randomized controlled trial (RCT) of patients undergoing posterior lumbar interbody fusion, Zhang et al. administered TXA topically and intravenously. [8] Meanwhile, other studies have investigated the effect of topical TXA administration alone. [43] Investigating alternative routes of TXA administration are valuable additions to the literature and innovations that should continue to be explored; however, when reviews of TXA in spine surgery include both IV and topical TXA in their meta-analysis, [9] care should be taken in interpreting these results.

    • Interventions to minimize blood loss and transfusion risk in spine surgery: A narrative review

      2020, Clinical Neurology and Neurosurgery
      Citation Excerpt :

      Additionally, TXA administration may provide superior hemostasis to topical fibrin-based agents at lower overall costs [124]. Multiple studies have also investigated its use in the spine population, in intravenous, oral, and topical formulations [125–131]. Though most have been retrospective, several small RCTs have been conducted, including three double-blind, level I RCTs [132–134] and the single-blind, level II RCT of Wang et al. [133] On the whole they find intravenous tranexamic acid to reduce both intraoperative and total blood loss.

    View all citing articles on Scopus
    View full text