Seizures following cardiac surgery: the impact of tranexamic acid and other risk factors

Manji, Rizwan A.; Grocott, Hilary P.; J, Leake; Ariano, Robert E.; Manji, Jacqueline S.; Menkis, Alan H.; Jacobsohn, Eric

doi:10.1007/s12630-011-9618-z

Cited by 144 publications

(155 citation statements)

References 24 publications

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“…Thus, a lower dose of TXA is less likely to cause seizures, as lower concentrations would be “outcompeted” by endogenous neurotransmitters at the agonist‐binding sites of glycine and GABA A receptors. The notion that higher doses of TXA increase the risk of seizures is supported by animal45 and human studies 16, 20, 26. Specifically, in cardiac surgery patients, the use of higher doses of TXA drastically increased the incidence of seizures 16, 20, 26…”

Section: Prevention and Treatment Of Txa‐associated Seizuresmentioning

confidence: 99%

“…Other important risk factors for TXA‐associated seizures include the type and duration of surgery. Most seizures are reported in patients undergoing “open chamber surgery” (eg, aortic valve replacement) 16, 17, 18, 20. The risk is also increased in patients with deep hypothermic circulatory arrest, long cardiopulmonary bypass time, or prolonged aortic cross‐clamp time 16, 18, 20, 26…”

Section: Clinical Indications Incidence and Risk Factorsmentioning

confidence: 99%

“…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

229

158

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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: 99%

Section: Clinical Indications Incidence and Risk Factorsmentioning

confidence: 99%

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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

229

158

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“…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.…”

Section: To the Editormentioning

confidence: 99%

“…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.…”

Section: To the Editormentioning

confidence: 99%

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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Effect of High- vs Low-Dose Tranexamic Acid Infusion on Need for Red Blood Cell Transfusion and Adverse Events in Patients Undergoing Cardiac Surgery

Shi

Zhou

Pan

et al. 2022

JAMA

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ImportanceTranexamic acid is recommended for reducing blood loss and transfusion in cardiac surgery. However, it remains unknown whether a high dose of tranexamic acid provides better blood-sparing effect than a low dose without increasing the risk of thrombotic complications or seizures in cardiac surgery.ObjectiveTo compare the efficacy and adverse events of high-dose vs low-dose tranexamic acid in patients undergoing cardiac surgery with cardiopulmonary bypass.Design, Setting, and ParticipantsMulticenter, double-blind, randomized clinical trial among adult patients undergoing cardiac surgery with cardiopulmonary bypass. The study enrolled 3079 patients at 4 hospitals in China from December 26, 2018, to April 21, 2021; final follow-up was on May 21, 2021.InterventionsParticipants received either a high-dose tranexamic acid regimen comprising a 30-mg/kg bolus, a 16-mg/kg/h maintenance dose, and a 2-mg/kg prime (n = 1525) or a low-dose regimen comprising a 10-mg/kg bolus, a 2-mg/kg/h maintenance dose, and a 1-mg/kg prime (n = 1506).Main Outcomes and MeasuresThe primary efficacy end point was the rate of allogeneic red blood cell transfusion after start of operation (superiority hypothesis), and the primary safety end point was a composite of the 30-day postoperative rate of mortality, seizure, kidney dysfunction (stage 2 or 3 Kidney Disease: Improving Global Outcomes [KDIGO] criteria), and thrombotic events (myocardial infarction, ischemic stroke, deep vein thrombosis, and pulmonary embolism) (noninferiority hypothesis with a margin of 5%). There were 15 secondary end points, including the individual components of the primary safety end point.ResultsAmong 3079 patients who were randomized to treatment groups (mean age, 52.8 years; 38.1% women), 3031 (98.4%) completed the trial. Allogeneic red blood cell transfusion occurred in 333 of 1525 patients (21.8%) in the high-dose group and 391 of 1506 patients (26.0%) in the low-dose group (risk difference [RD], −4.1% [1-sided 97.55% CI, −∞ to −1.1%]; relative risk, 0.84 [1-sided 97.55% CI, −∞ to 0.96; P = .004]). The composite of postoperative seizure, thrombotic events, kidney dysfunction, and death occurred in 265 patients in the high-dose group (17.6%) and 249 patients in the low-dose group (16.8%) (RD, 0.8%; 1-sided 97.55% CI, −∞ to 3.9%; P = .003 for noninferiority). Fourteen of the 15 prespecified secondary end points were not significantly different between groups, including seizure, which occurred in 15 patients (1.0%) in the high-dose group and 6 patients (0.4%) in the low-dose group (RD, 0.6%; 95% CI, −0.0% to 1.2%; P = .05).Conclusions and RelevanceAmong patients who underwent cardiac surgery with cardiopulmonary bypass, high-dose compared with low-dose tranexamic acid infusion resulted in a modest statistically significant reduction in the proportion of patients who received allogeneic red blood cell transfusion and met criteria for noninferiority with respect to a composite primary safety end point consisting of 30-day mortality, seizure, kidney dysfunction, and thrombotic events.Trial RegistrationClinicalTrials.gov Identifier: NCT03782350

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Seizures following cardiac surgery: the impact of tranexamic acid and other risk factors

Cited by 144 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?

Effect of High- vs Low-Dose Tranexamic Acid Infusion on Need for Red Blood Cell Transfusion and Adverse Events in Patients Undergoing Cardiac Surgery

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