Safety of antifibrinolytics in 6583 pediatric patients having craniosynostosis surgery: A decade of data reported from the multicenter Pediatric Craniofacial Collaborative Group

Abstract

Background: Antifibrinolytics such as tranexamic acid and epsilon-aminocaproic acid are effective at reducing blood loss and transfusion in pediatric patients having craniofacial surgery. The Pediatric Craniofacial Collaborative Group has previously reported low rates of seizures and thromboembolic events (equal to no antifibrinolytic given) in open craniofacial surgery. Aims: To query the Pediatric Craniofacial Collaborative Group database to provide an updated antifibrinolytic safety profile in children given that antifibrinolytics have become recommended standard of care in this surgical population. Additionally, we include the population of younger infants having minimally invasive procedures. Methods: Patients in the Pediatric Craniofacial Collaborative Group registry between June 2012 and March 2021 having open craniofacial surgery (fronto-orbital advancement, mid and posterior vault, total cranial vault remodeling, intracranial LeFort III monobloc), endoscopic cranial suture release, and spring mediated cranioplasty were included. The primary outcome is the rate of postoperative complications possibly attributable to antifibrinolytic use (seizures, seizure-like activity, and thromboembolic events) in infants and children undergoing craniosynostosis surgery who did or did not receive antifibrinolytics.Results: Forty-five institutions reporting 6583 patients were included. The overall seizure rate was 0.24% (95% CI: 0.14, 0.39%), with 0.20% in the no Antifibrinolytic group and 0.26% in the combined Antifibrinolytic group, with no statistically reported difference. Comparing seizure rates between tranexamic acid (0.22%) and epsilon-aminocaproic acid (0.44%), there was no statistically significant difference (odds ratio = 2.0; 95% CI: 0.6, 6.7; p = .257). Seizure rate was higher in patients greater than 6 months (0.30% vs. 0.18%; p = .327), patients undergoing open procedures (0.30% vs. 0.06%; p = .141), and syndromic patients (0.70% vs. 0.19%; p = .009).

Epsilon aminocaproic acid is associated with acute kidney injury after life‐threatening hemorrhage in children

“…A last limitation of this study is inability to report number of thrombotic events and seizures, other potentially important adverse outcomes associated with antifibrinolytic therapy, as this information was not collected. However, reported rates of these complications in pediatric patients receiving anti‐fibrinolytics are low 43 . Given the limitations of this observational study, we intend these results to be hypothesis‐generating rather than lead to changes in clinical practice on their own.…”

Epilepsy in Patients with Craniosynostosis: A Systematic Review

“…They also reported post-operative complications of hypotension, hypothermia, metabolic acidosis, blood loss, fever of unknown origin, and hyperglycemia [20]. The evaluation of incidents in the reported cohort showed clinically significant metabolic or hemodynamic events, despite the wide range of problems described in the literature [11,12,14,17,19,21,22]. These findings imply that those children require close monitoring for at least 24 hours following surgery.…”

“…A total of 11 studies were included in this review, with 21456 patients diagnosed with craniosynostosis, and more than half of them were males. Eight studies were conducted in the United States (USA) [10][11][12][13][14][15][16][17], one in Brazil [18], one in India [19], and one in Turkey [20]. We found that the nonsyndromic craniosynostosis weighed much more than the syndromic incidence.…”

“…Three studies reported preoperative/history of epileptic seizures; the highest rate (12.2%) was reported by Ongun et al [20], followed by Agochukwu et al (12%) [14], and the lowest rate (2.5%) was reported by Stanbouly et al, [15]. Post-operative epilepsy was reported in seven studies; the highest rate (12.2%) [20] and the lowest (0.24%) [11]. Seven studies [10, 12-14, 17, 18, 20] found a high risk of bias, while four studies reported a moderate risk [11,15,16,19].…”

“…Post-operative epilepsy was reported in seven studies; the highest rate (12.2%) [20] and the lowest (0.24%) [11]. Seven studies [10, 12-14, 17, 18, 20] found a high risk of bias, while four studies reported a moderate risk [11,15,16,19].…”