Is High-Dose Tranexamic Safe in Spine Surgery? A Systematic Review and Meta-Analysis

Abstract

Study Design Literature review and meta-analysis. Objectives Single-center series may be underpowered to detect whether high-dose (HD) tranexamic acid (TXA) confers a higher risk of complications. We sought to determine the safety and efficacy of HD TXA as compared to low-dose (LD) or placebo. Methods A systematic literature review was performed to find studies where spine surgery patients were given HD TXA (loading dose ≥30 mg/kg). Complication rates were pooled, and meta-analyses performed on outcomes of interest. Articles were evaluated for risk of bias and a strength of evidence assessment was given for each conclusion. Results Twenty three studies (n = 2331) were included. The pooled medical complication rate was 3.2% in pediatric patients, 8.2% in adults. Using lower dose TXA or placebo as the reference, meta-analysis showed no difference in medical complications (n = 1,723, OR 1.22 [95% CI, .78 to 1.22]; P = .388; I2 = 0%) or thrombotic events (n = 1158 patients, OR 1.27 [95% CI, .71 to 2.63]; P = .528; I2 = 0%). Compared to LD, HD TXA was associated with less intraoperative blood loss (823 patients, WMD = −285 [95% CI, −564 to −5.90]; P = .0454; I2 = 86%), fewer perioperative transfusions (n = 505, OR .28 [95% CI, .082 to .96]; P = .043; I2 = 76%) and lower perioperative transfusion volumes (n = 434, WMD −227.7 mL [95% CI, −377.3 to −78.02]; P = .0029; I2 = 0%). Conclusion Compared to LD TXA or placebo, there is moderate evidence that HD is not associated with an increased risk of medical complications. Compared to LD, there is moderate evidence that HD reduces transfusion requirements. High-Dose TXA can be safely utilized in healthy patients undergoing major spine surgery.

Comparative efficacy and safety of different hemostatic medications during spinal surgery: A network meta-analysis

“…There was no statistically significant difference for the occurrence of DVT and PE between these drugs. Akosman et al [70] performed a meta-analysis about the safety of high-dose TXA in spinal surgery. Results suggested that high dose of TXA is not associated with an increased risk of complications, including DVT and PE.…”

Perioperative Blindness in Spine Surgery: A Scoping Literature Review

“…Additionally, as blood loss can be significant in certain complex spine procedures, the use of hemostatic agents such as transexamic acid and other antifibrinolytic agents has become more common. These agents have the potential to become embolic and may be associated with an increased risk of vascular occlusion if they enter the systemic circulation, although no study has demonstrated a difference in thrombotic rate with tranexamic acid (TXA) [72][73][74].…”

Perioperative Management for Complex Spine Fusion Surgery

“…36,37 In most studies, administration typically entails a preincision loading dose of 10 to 30 mg/kg followed by an infusion with doses generally ranging from 1 to 3 mg · kg −1 · h −1 , although the literature also demonstrates significant outliers from these parameters. 38 “Low-dose” regimens are described in meta-analyses as less than 15-mg/kg loading dose with 1 mg · kg −1 · h −1 or lower infusion rates, and are effective at reducing blood loss and transfusion requirements. 39 Large meta-analyses have also demonstrated improved efficacy and maintenance of safety with “high-dose” tranexamic acid regimens (greater than 30-mg/kg loading dose or an initial dose in excess of 2,000 mg) without associated increased incidences of thromboembolic phenomena, seizures, or nonbleeding mortality in populations of spine surgery patients as well as general noncardiac surgery patients.…”

“…39 Large meta-analyses have also demonstrated improved efficacy and maintenance of safety with "high-dose" tranexamic acid regimens (greater than 30-mg/kg loading dose or an initial dose in excess of 2,000 mg) without associated increased incidences of thromboembolic phenomena, seizures, or nonbleeding mortality in populations of spine surgery patients as well as general noncardiac surgery patients. [38][39][40] While there is no clear consensus on the optimal dosing of tranexamic acid, one commonly employed and reported regimen for adult patients undergoing open spinal instrumentation of three or more vertebral levels is the administration of a 15-mg/kg intravenous loading dose with an intraoperative infusion of 1 mg • kg −1 • h −1 until surgical closure. 36,37 Blood product transfusion algorithms based on goal-directed therapy with conventional coagulation studies (e.g., prothrombin time, activated partial thromboplastin time, platelet count, fibrinogen concentration, and so forth) can be used to direct blood product administration, but more functional studies of whole blood hemostasis based on viscoelastography may be preferred for complex spinal deformity correction surgeries that incorporate osteotomies and severe angular corrections, and hence significant anticipated blood losses.…”

“…39 Large meta-analyses have also demonstrated improved efficacy and maintenance of safety with “high-dose” tranexamic acid regimens (greater than 30-mg/kg loading dose or an initial dose in excess of 2,000 mg) without associated increased incidences of thromboembolic phenomena, seizures, or nonbleeding mortality in populations of spine surgery patients as well as general noncardiac surgery patients. 38–40 While there is no clear consensus on the optimal dosing of tranexamic acid, one commonly employed and reported regimen for adult patients undergoing open spinal instrumentation of three or more vertebral levels is the administration of a 15-mg/kg intravenous loading dose with an intraoperative infusion of 1 mg · kg −1 · h −1 until surgical closure. 36,37…”