High-Dose Tranexamic Acid Is Associated with Nonischemic Clinical Seizures in Cardiac Surgical Patients

Murkin, John M.; Falter, Florian; Granton, Jeff; Young, Bradley W.; Burt, Christiana; Chu, Michael

doi:10.1213/ane.0b013e3181c92b23

Cited by 310 publications

(232 citation statements)

References 24 publications

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“…Thus, the anesthetic is no longer available to provide anticonvulsant effects. Consistent with this notion that anesthetics protect against TXA‐induced seizures, many patients first develop seizures during emergence from propofol sedation 17, 24. Also, case reports indicate that propofol is effective for treating seizures in patients who inadvertently received an intrathecal injection of TXA 15, 23.…”

Section: Prevention and Treatment Of Txa‐associated Seizuresmentioning

confidence: 89%

“…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. However, several case reports indicate that TXA‐associated seizures also occur in nonsurgical patients 10, 22, 27.…”

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confidence: 99%

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Tranexamic acid–associated seizures: Causes and treatment

Lecker

Wang

Whissell

et al. 2015

Annals of Neurology

206

146

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Antifibrinolytic drugs are routinely used worldwide to reduce the bleeding that results from a wide range of hemorrhagic conditions. The most commonly used antifibrinolytic drug, tranexamic acid, is associated with an increased incidence of postoperative seizures. The reported increase in the frequency of seizures is alarming, as these events are associated with adverse neurological outcomes, longer hospital stays, and increased in‐hospital mortality. However, many clinicians are unaware that tranexamic acid causes seizures. The goal of this review is to summarize the incidence, risk factors, and clinical features of these seizures. This review also highlights several clinical and preclinical studies that offer mechanistic insights into the potential causes of and treatments for tranexamic acid–associated seizures. This review will aid the medical community by increasing awareness about tranexamic acid–associated seizures and by translating scientific findings into therapeutic interventions for patients. ANN NEUROL 2016;79:18–26

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Section: Prevention and Treatment Of Txa‐associated Seizuresmentioning

confidence: 89%

mentioning

confidence: 99%

Tranexamic acid–associated seizures: Causes and treatment

Lecker

Wang

Whissell

et al. 2015

Annals of Neurology

206

146

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show abstract

“…1 In another recent review, all cardiac surgery patients who experienced seizures associated with high-dose TXA recovered without any permanent neurological sequelae. 4 While the etiology of the seizure observed in this patient was almost certainly multifactorial, we cannot exclude the possibility that TXA may have contributed to this outcome.…”

Section: To the Editormentioning

confidence: 79%

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

Merriman

Mayson

Sawka

et al. 2013

Can J Anesth/J Can Anesth

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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...

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“…12 While no human trials have been conducted, Yamamura et al reported that 5 mg/kg of intrathecal tranexamic acid produced seizures within 45-60 seconds in felines with a ruptured intracranial aneurysm. 13 The proposed mechanisms for the cardiac and neurologic manifestations include central sympathetic discharge, GABA A inhibition, and direct cerebral ischemia.…”

Section: Discussionmentioning

confidence: 99%

Refractory status epilepticus after inadvertent intrathecal injection of tranexamic acid treated by magnesium sulfate

Hatch¹,

Atito-Narh²,

Herschmiller³

et al. 2016

International Journal of Obstetric Anesthesia

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We present a case of accidental injection of tranexamic acid during spinal anesthesia for an elective cesarean delivery. Immediately following intrathecal injection of 2 mL of solution, the patient complained of severe back pain, followed by muscle spasm and tetany. As there was no evidence of spinal block, the medications given were checked and a 'used' ampoule of tranexamic acid was found on the spinal tray. General anesthesia was induced but muscle spasm and tetany persisted despite administration of a non-depolarizing muscle relaxant. Hemodynamic instability, ventricular tachycardia, and status epilepticus developed, which were refractory to phenytoin, diazepam, and infusions of thiopental, midazolam and amiodarone. Magnesium sulfate was administered postoperatively in the intensive care unit, following which the frequency of seizures decreased, eventually stopping. Unfortunately, on postoperative day three the patient died from cardiopulmonary arrest after an oxygen supply failure that was not associated with the initial event. This report underlines the importance of double-checking medications before injection in order to avoid a drug error. As well, it suggests that magnesium sulfate may be useful in stopping seizures caused by the intrathecal injection of tranexamic acid.

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High-Dose Tranexamic Acid Is Associated with Nonischemic Clinical Seizures in Cardiac Surgical Patients

Abstract: Our results suggest that use of high-dose TXA in older patients in conjunction with cardiopulmonary bypass and open-chamber cardiac surgery is associated with clinical seizures in susceptible patients.

Cited by 310 publications

References 24 publications

Tranexamic acid–associated seizures: Causes and treatment

Tranexamic acid–associated seizures: Causes and treatment

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

Refractory status epilepticus after inadvertent intrathecal injection of tranexamic acid treated by magnesium sulfate

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