A seizure case induced by topical application of tranexamic acid in a local incision
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Dear Editor,
Tranexamic acid (TXA), an artificially synthesized analog of lysine first introduced in 1962, achieves hemostasis by competitively inhibiting fibrinolysis through its affinity for lysine-binding sites [1]. Conversely, when TXA crosses the blood-brain barrier, it binds to γ-aminobutyric acid (GABA) receptors, amplifying neuronal excitation without opening chloride channels, which can lead to the occurrence of seizures [2].
Currently, TXA is widely applied in clinical surgical procedures, such as orthopedic joint replacement, spinal surgery, cardiac surgery, and cesarean section. Numerous studies have indicated that during the perioperative period, TXA reduces intraoperative and postoperative bleeding without increasing the risk of thrombosis. However, no uniform standards are currently available regarding the route of administration, dosage, timing, or methods to enhance the safety of TXA. Even when applied locally, it should only be used in the subcutaneous tissue and muscles around the incision site. The intrathecal injection of TXA is clearly inappropriate. Luo et al. [3] emphasized this issue by reviewing 21 case reports of accidental spinal administration of TXA from 1988 to 2018. Among these cases, seizures that were treated with a single antiepileptic drug completely resolved, and individuals with life-threatening neurological or cardiac complications requiring resuscitation and intensive care eventually died within a year.
We present the case of a 67-year-old male patient with a history of recurrent low back pain for over 20 years, exacerbated by numbness in the left lower limb for over 20 days, and a medical history of grade 2 hypertension (high-risk group). This patient took antihypertensive medications regularly and his blood pressure was generally well controlled, with no history of brain trauma or epilepsy. Preoperative laboratory tests revealed no abnormalities. Electrocardiography showed sinus rhythm with broad P waves and an intraventricular conduction block. Chest radiography revealed chronic bronchitis and emphysema. Lumbar spine magnetic resonance imaging indicated L1, 3 vertebral instability, L1, 2 vertebral compression changes, and L3/4, L4/5 disc herniation. The patient was admitted to our hospital and was diagnosed with L3/L4, L4/L5 lumbar disc herniation with radiculopathy, degenerative lumbar spine disease, lumbar spinal instability, and grade 2 hypertension (high-risk group).
On November 20, 2023, the patient underwent L3/4, L4/5 lumbar discectomy with nucleotomy and laminectomy under general anesthesia. Immediately before surgery, 1 g TXA was administered intravenously. The surgical procedure was uneventful, and vital signs remained stable throughout. At the end of skin closure, 1 g of TXA and 20 ml of 0.9% sodium chloride were injected through the surgical area drainage catheter.
At 13:03, the surgery was concluded, and approximately 10 min later, the patient became restless and reported burning pain in the lumbar back and both lower limbs, accompanied by elevated blood pressure and increased heart rate. This was soon followed by intractable spasms in both lower limbs and severe pain. Intravenous uraprilat (10 mg) was administered to reduce blood pressure, and dexamethasone (40 mg) and calcium gluconate (1 g) were administered for symptomatic treatment; however, the effects were suboptimal. At 15:01, an arterial blood gas analysis revealed no significant abnormalities. At 15:30 an emergency lumbar exploration was performed under general anesthesia through the original incision. No significant bleeding or hematoma formation was observed at the surgical site. After surgery, the patient was transferred to the intensive care unit for further treatment, where he received symptomatic treatments such as mechanical ventilation, propofol sedation, sodium valproate for seizure control, and sufentanil for analgesia. The following day, his lower limb spasms improved, vital signs stabilized, and the tracheal cannula was removed. Computed tomography (CT) of the head showed no obvious abnormalities. The patient recovered and was discharged after a week. At the 12-month follow-up, the patient showed no seizure recurrence or other neurological symptoms. The studies involving human participants were reviewed and approved by the People Hospital of Lezhi. The patients provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.
For this case, we comprehensively reviewed and analyzed the treatment process. Seizures induced by intravenous TXA, anesthetic medications, and preoperative antibiotic infusions are more likely to manifest as generalized seizures; however, this patient’s convulsions were limited to the lower limbs. He also had no convulsive symptoms prior to the surgery. Postoperative review showed that the screws did not contact the nerves, and head CT revealed no cerebrovascular abnormalities. Moreover, spasms caused by lumbar disc herniation mainly occur in specific areas of the limbs; indeed, they are more likely to occur in the left lower limb in someone with this patient’s condition. Additionally, the patient presented with unique clinical symptoms of accidental intrathecal injection of TXA (i.e., burning pain in the lower back and both lower limbs accompanied by increased blood pressure, accelerated heart rate, and development of involuntary spasms in both lower limbs accompanied by severe pain). Previous studies have shown that intraoperative rupture of the nucleus pulposus and annulus fibrosus can release inflammatory factors, leading to sterile inflammation of the local meninges, thereby increasing their permeability [4]. Alternatively, the surgeon may have injured the local meninges during surgery, resulting in TXA infiltration into the spinal cord. Therefore, we could hypothesize that, in this case, the patient may have experienced vascular dilation of the dura or local tearing during surgery, leading to TXA infiltration into the spinal cord and an epileptic seizure. The clinical manifestation of seizure, caused by the local application of TXA to the surgical incision, are consistent with those of previous reports [3].
We reviewed previous case reports of epilepsy caused by intrathecal TXA injection and found that most patients died within a short time after intrathecal TXA injection, and some survivors developed neurological complications within one year, such as seizures, bilateral peroneal nerve palsy, cognitive dysfunction, cauda equina syndrome, and paraplegia. As application at the local incision site may have resulted in a relatively small dose of TXA penetrating the sheath, this patient did not develop any neurological complications at the one-year follow-up, similar to the previous reports of TXA application in spinal surgery [3].
Currently, no standard treatment recommendations for TXA-related seizures exist. Previously reported cases were mainly treated using two approaches: management of the seizure itself and management of the cardiovascular system. For seizure-like convulsions caused by accidental intrathecal injection of TXA, in addition to management of the seizure itself and the cardiovascular system, early use of lavage with fluid or magnesium sulfate is recommended [5].
Consequently, we believe that TXA should be used with caution at the local incision site during spinal surgery and patients should be closely monitored after surgery to detect possible TXA-induced seizures. However, we acknowledge that our recommendation is based on only a few cases and its effectiveness and practicality must be fully evaluated.
Notes
Funding: None.
Conflicts of Interest: No potential conflict of interest relevant to this article was reported.
Author Contributions: Yanping Wu (Methodology; Writing – original draft); Xin Xiong (Funding acquisition; Supervision); Quan Hu (Resources); Meiling Wang (Formal analysis; Investigation); Yongbing Wu (Conceptualization; Writing – review & editing)