Professor, Surgery Population Health Research Institute Hamilton, Ontario, Canada
Background: Intravenous tranexamic acid (TxA) is widely recommended for use as a blood-conservation strategy during cardiac surgery. However, post-operative seizures remain a concern, generating an avoidance of high doses and leading to different practices in Canada. It has been previously demonstrated that oxygen bubbles activated by focused ultrasound could “pop” and temporarily disrupt the blood brain barrier (BBB), allowing complex molecules to enter the BBB despite being normally impervious to these molecules. We hypothesize that open-chamber surgeries with air bubbles to the brain could facilitate the entry of tranexamic acid by disturbing the BBB and increase the risk of seizures. Therefore, we aimed to investigate seizures in patients undergoing open-chamber versus closed-chamber cardiac surgery, using pooled data from the large DEPOSITION and OPTIMAL trials.
METHODS AND RESULTS: We conducted a meta-analysis of the 2 largest randomized controlled trials of tranexamic acid use that documented post-operative seizures in patients undergoing cardiac surgery with cardiopulmonary bypass. Of the 6,191 patients included in the meta-analysis, 3,458 (56%) underwent open-chamber surgery and 2,733 (44%) underwent closed-chamber surgery. The primary outcome was post-operative seizure within 30 days. Summary statistics from each trial were pooled using an inverse variance-weighted random effects model. Open-chamber compared with closed-chamber cardiac surgery increased the risk of seizures within 30 days based on high quality evidence (risk ratio, 3.13; 95% CI, 1.35-7.25; P=0.008). Heterogeneity across included studies was minimal (I2 = 0%). The dose of intravenous TxA used was left to the discretion of the anesthesiologist in DEPOSITION, whereas a fixed dose of either 1.0 mg/kg or 10.0 mg/kg was used according to the randomization in OPTIMAL. The risk of seizure was not different between doses of TxA received in these 2 trials (P=0.35).
Conclusion: In this meta-analysis of 6,191 patients from the DEPOSITION and OPTIMAL trials, we found evidence that open-chamber surgery is associated with an increased risk of seizures after cardiac surgery. These findings suggest that TxA dosing could be tailored to the type of surgery.
