Cerebral Complication of Antifibrinolytic Therapy in the Treatment of Ruptured Intracranial Aneurysm

Abstract

Among the reported complications of the antifibrinolytic therapy in the treatment of ruptured intracranial aneurysms, nausea and vomiting, cerebral arteriopathy and secondary hydrocephalus would be a matter of concern in its possible CNS involvement. However, little is known about the possibility of direct cerebral effect in synthetic antifibrinolytics. A simply designed animal experiment disclosed remarkable effects on electroencephalography, blood flow of the cerebral cortex and intracranial pressure. Such antifibrinolytics should not be given intrathecally in any situation even if the accumulation of the agents in cerebrospinal fluid is essential to prevent recurrent hemorrhage.

Tranexamic Acid, a Widely Used Antifibrinolytic Agent, Causes Convulsions by a γ-Aminobutyric AcidA Receptor Antagonistic Effect

“…This is further supported by the observation that spinal application of the GABA A receptor antagonist bicuculline can evoke allodynia as well as strong generalized seizures depending on its dose (Beitz and Larson, 1985;Ishikawa et al, 2000). Squires et al (1988) and Chang and Gao (1995) Yamaura et al (1980) that i.v. application of high amounts of ⑀-amino caproic acid elicits epileptic brain activity in cats.…”

“…TAMCA was initially also considered as an adjunct in the treatment of subarachnoid hemorrhages. However, experimental studies in the early 1980s showed that cortical application of TAMCA elicits epileptic seizures in cats (Yamaura et al, 1980;Pellegrini et al, 1982). Moreover, clinical studies demonstrated that patients treated with TAMCA had a higher incidence of ischemic events than untreated patients (Guidetti and Spallone, 1981;Tsementzis et al, 1992).…”

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

“…Several cases resulted in neurologic recovery with patients safely discharged. 5,7,8,10,11,13 In other cases, ours included, the patient died. 6,9 Our case presented an interesting dilemma in that, despite treatment with benzodiazepines, barbiturates and phenytoin, our patient remained in refractory status epilepticus until magnesium was added.…”

“…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. [6][7][8][9][10][11]14 In a report similar to ours, a patient was inadvertently given 500 mg intrathecal tranexamic acid and developed convulsions followed by a pulseless electrical activity arrest treated with diazepam, multiple defibrillation attempts, epinephrine, and amiodarone.…”

Effects of 7-ethoxycarbonyl-6,8-dimethyl-4-hydroxymethyl-1(2H)-phthalazinone (EG626) on the spinal trigeminal nucleus, ventral posteromedial nucleus, and sensory cortex.

“…A needle type element (NT-100, Unique Medical) was inserted into the VPM of the cat fixed in the stereotaxic apparatus. Blood flow was measured using a UM-meter (UM-2000, Unique Medical) according to the method described by Yamaura et al (10). The value of blood flow was expressed as a percent of the level obtained in the untreated condition (100%) and that of death was 0%.…”