Postoperative seizure in a neurosurgical patient: Should tranexamic acid be on the differential?

Abstract

To the Editor,We read with interest the recent article by Manji et al. showing the association of tranexamic acid (TXA) with postoperative seizures following cardiac surgery. 1 These data raise important questions about the potential adverse effects of TXA on the central nervous system. The relationship between TXA and seizure activity in populations other than cardiac surgery is undefined. We present a case of postoperative seizure of unclear etiology in a neurosurgical patient who received TXA intraoperatively. The patient provided written consent for publication of this report.A 71-yr-old 122-kg patient with a medical history significant for a congenital solitary kidney (creatinine 133 lmolÁL -1 ) presented to our hospital for an elective right frontotemporal craniotomy and superior orbital osteotomy for resection of a sphenoid wing meningioma. The patient had no history of seizures or raised intracranial pressure preoperatively. Given the risk of significant intraoperative bleeding, he was given 1 g (8 mgÁkg -1 iv) of TXA intraoperatively as a loading dose followed by an infusion of 0.5 gÁhr -1 (4 mgÁkg -1 Áhr -1 ) for the remainder of the case. The estimated blood loss was 1,000 mL. Successful tracheal extubation was performed in the operating room after nine hours of uneventful surgery. Five minutes after arrival in the postanesthesia recovery room, the patient's SpO 2 was observed to be 92%. He then sustained a brief loss of consciousness and a grand mal seizure that progressed to asystolic arrest and five minutes of cardiopulmonary resuscitation, re-intubation, and the administration of epinephrine, sodium bicarbonate, calcium, atropine, and vasopressin before return of spontaneous circulation. Laboratory investigations were significant for lactic acidosis and elevated creatinine (196 lmolÁL -1 ). He was transferred to the intensive care unit for further management, including antiepileptic treatment with propofol and phenytoin. Computed tomography of the patient's head showed no new hemorrhages or infarctions, and electroencephalography performed the following day showed no seizure activity. The patient was successfully weaned from his propofol infusion on the third postoperative day. His postoperative course was complicated by aspiration, prolonged respiratory failure, and deep vein thrombosis. He was transitioned to levetiracetam for the remainder of his hospitalization given the favourable safety and toxicity profile seen with this antiepileptic agent. He was discharged home in satisfactory condition 54 days following surgery.High-dose TXA has recently been associated with an increased incidence of postoperative seizures following cardiac surgery. 1 Potential mechanisms include direct inhibition of glycine and gamma-aminobutyric acid A (GABAa) receptors as well as direct central nervous system toxicity. 2,3 A recent study showed that TXA inhibits glycine receptors to a greater extent than GABAa receptors and that this effect is attenuated by isoflurane and propofol in vitro. 2 Although these data sugg...

Tranexamic acid–associated seizures: Causes and treatment

“…In support of this hypothesis, glycine receptor antagonists, such as strychnine, cause myoclonic movements and twitching, particularly in the lower limbs, as well as muscle spasms and convulsions 55, 56, 63, 64. Interestingly, the pattern of twitching, myoclonus, and seizures observed in patients treated with TXA is similar to the pattern of the proconvulsant effects of strychnine 11, 22, 27. We found that TXA acts as a competitive antagonist of glycine receptors, with an IC 50 of 1mM (see Fig 2B) 47.…”

“…27 None of these patients had a history of seizure disorders and no abnormalities were detected on subsequent electroencephalography (EEG) or computed tomographic scans. 10,22,27 Collectively, these case studies indicate that a wide range of patients may be vulnerable to TXA-associated seizures. Increasing global "off-label" use of TXA may further increase the incidence of TXA-associated seizures.…”

“…10 Another patient who underwent a craniotomy for meningioma had tonic-clonic convulsions after the administration of TXA. 22 A third patient who was admitted for hemoptysis had a focal seizure after TXA treatment, which progressed to a generalized seizure. 27 None of these patients had a history of seizure disorders and no abnormalities were detected on subsequent electroencephalography (EEG) or computed tomographic scans.…”

“…However, observational clinical trials and case reports have shown that TXA, and to a lesser extent EACA, but not aprotinin, are associated with seizures 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34. Most TXA‐associated seizures occur in patients who have undergone cardiac procedures 16, 17, 18, 20, 21, 24, 25, 26, 30, 31, 32, 34.…”

“…[16][17][18]20,21,[24][25][26][30][31][32]34 However, sev-eral case reports indicate that TXA-associated seizures also occur in nonsurgical patients. 10,22,27 Seizures in postoperative cardiac surgery patients have been reported to be associated with a 2-fold increase in hospital length of stay and a 2.5-fold higher mortality rate. 26 An increase in the incidence of delirium and stroke, and a reduced quality of life have also been reported.…”