Introduction: During total knee arthroplasty (TKA), tranexamic acid (TXA) can be used to reduce intraoperative bleeding, decreasing transfusion rates and total surgery costs. However, TXA's most effective administration protocol remains up for debate. This study used fragility index (FI), reverse fragility index (rFI), and fragility quotient (FQ) metrics to evaluate the statistical robustness of outcomes reported in RCTs evaluating dosage and administration of TXA in TKA.
Methods: PubMed, Embase, and MEDLINE were systematically searched for recent RCTs (January 1, 2014, and June 30th, 2024) assessing TXA use in TKA. The FI and rFI were calculated for all dichotomous outcomes, representing the number of outcome event reversals required to alter statistical significance for significant and non-significant outcomes, respectively. The FQ was determined by dividing the FI or rFI by the study sample size.
Results: After screening, 51 studies were included for analysis. Across 134 total outcomes, the median FI was 4 (IQR 4-5) with an associated median FQ of 0.040 (IQR 0.023-0.057), suggesting that just 4 outcome event reversals would alter significance for 50 % of outcomes. 13 outcomes were statistically significant with a median FI of 2 (IQR 1-5) and FQ of 0.014 (IQR 0.011-0.057). 121 outcomes were non-significant with a median FI of 5 (IQR 4-6) and FQ of 0.040 (IQR 0.025-0.057). Outcomes were grouped into four categories, including blood or platelet transfusions (34 outcomes), thromboembolic events (33 outcomes), wound complications such as infections (21 outcomes), and other adverse events (46 outcomes). Their median FQs were 0.040, 0.039, 0.041, and 0.043, respectively. The 51 outcomes from studies published prior to 2018 showed a median FQ of 0.034, while the 84 outcomes published in 2018 or later showed a median FQ of 0.050. Across 108 outcomes from studies only administering TXA, the median FQ was 0.038, whereas the 26 outcomes from studies administering TXA and another drug showed a median FQ of 0.050.
Conclusion: RCT outcomes describing TXA usage in TKA are statistically fragile, particularly among significant outcomes, thromboembolic events, and blood/platelet transfusion rates. Given this degree of fragility, current literature may not definitively prove a superior route of TXA administration in TKA. Further study including appropriately powered RCTs is recommended to further examine this field, along with combined reporting of p-values with FI and FQ metrics to aid in interpreting future clinical findings.