The Trigeminocardiac Reflex: An Unusual Suspect of Sudden Intraoperative Hemodynamic Alteration, Encountered during Endovascular Embolization with DMSO/Onyx

Abstract

Continuous intraoperative hemodynamic monitoring is essential during endovascular procedures. Ethylene vinyl alcohol (EVOH) embolization, using Onyx liquid embolizing agent with dimethyl sulfoxide, can trigger an unusual brainstem reflex termed the “trigeminocardiac reflex (TCR),” characterized by sudden bradycardia and hypotension. We report a case of intracranial mycotic pseudoaneurysm in a postoperative case of coronavirus disease 2019-associated rhinocerebral mucormycosis patient, treated with parent artery occlusion using Onyx and coils. Intraoperatively, TCR was promptly recognized and managed, ensuring hemodynamic recovery and favorable outcome. This case highlights the importance of early TCR detection and management during EVOH embolization for optimal patient care.

Keywords

trigeminocardiac reflex - bradycardia - Onyx/ DMSO

Introduction

Intracranial mycotic pseudoaneurysms can be treated via coiling or parent artery occlusion (PAO) using microcoils, liquid embolic agents such as Onyx, or a combination. Onyx, which is delivered with dimethyl sulfoxide (DMSO), has been implicated in triggering the trigeminocardiac reflex (TCR) due to its chemical and thermal effects. TCR is a rare brainstem reflex characterized by sudden bradycardia and hypotension, typically induced by trigeminal nerve stimulation. Although classically seen in neurosurgical and maxillofacial surgeries, its occurrence during endovascular embolization is uncommon. The cavernous sinus, traversed by the ophthalmic (V1) and maxillary (V2) trigeminal branches, is particularly sensitive. Surgical manipulations around this region have been linked to TCR episodes marked by abrupt bradycardia and hypotension.[1] We describe the clinical course of a middle-aged man who developed TCR during endovascular PAO using coils and Onyx LES, for a mycotic intracranial pseudoaneurysm arising from the cavernous segment of the internal carotid artery (ICA).

Case Report

A 40-year-old man, previously treated for coronavirus disease 2019-associated invasive rhinocerebral mucormycosis with antifungals and surgical debridement, presented to the emergency department with profuse oral bleeding. Examination revealed a pulsatile posterior pharyngeal wall. Computed tomography angiography demonstrated a 14-mm saccular pseudoaneurysm arising from the posterior genu of the left cavernous ICA with a 3.5-mm neck and inferomedial teat. Multidisciplinary consensus favored a PAO of the left ICA. Baseline left ICA diagnostic angiogram confirmed the pseudoaneurysm without active extravasation. Manual compression of the left common carotid artery with right ICA angiogram demonstrated robust cross-flow via the anterior communicating artery. Further, four detachable and two pushable coils were deployed into the parent artery across the neck of the pseudoaneurysm via an Echelon-10 microcatheter. Persistent pseudoaneurysm filling postcoiling, necessitated usage of Onyx-18 injection. During Onyx injection, the patient developed abrupt bradycardia (30 bpm) and hypotension (50/28 mm Hg), consistent with TCR. The procedure was momentarily halted, and vitals eventually normalized. Embolization was then completed. Final angiograms confirmed complete occlusion of the ICA segment and pseudoaneurysm ([Fig., 3]). On the subsequent clinical and imaging follow-up, patient had no repeat episodes of oral bleeding and the imaging did not reveal any residual opacification of the aneurysmal segment of the parent ICA, with preserved normal patent intracranial vasculature.

Discussion

Current endovascular strategies for intracranial mycotic pseudoaneurysms include PAO, or direct aneurysm embolization using either coils or liquid agents[2] such as Onyx LES (EV3 Medtronic, Irvine, California, United States) or a combination of both. Onyx comprises three components: ethylene vinyl alcohol (EVOH) copolymer (active agent), micronized tantalum powder (radio-opaque agent), and DMSO (used to flush catheters and prevent premature Onyx precipitation). DMSO can induce local toxicity, leading to vasospasm, vessel wall inflammation, or angionecrosis. It has also been infrequently linked to bradycardia or asystole, likely via the TCR.[3] TCR is a brainstem reflex marked by sudden cardiac dysrhythmia (bradycardia/asystole), hypotension, apnea, and gastric hypermotility.[4] Schaller[4] proposed the underlying neural pathway, depicted in [Figs. 1] and [2]. Both physical and chemical stimulation of trigeminal nerve branches can trigger TCR.[5] Risk factors that may increase TCR incidence include hypercapnia, hypoxemia, light anesthesia, young age, nature of stimulus, and use of narcotic agents like sufentanil or alfentanil.[6]

Fig. 1 Graphical illustration of the mechanism of occurrence of trigeminocardiac reflex (TCR) during endovascular embolization using Onyx LES.

LV et al[7] reported what may be the first documented case of TCR during embolization of an intracranial dural arteriovenous fistula (AVF) using Onyx. Bradycardia occurred but resolved upon halting the injection; subsequent episodes were prevented with atropine. They noted that temporary cessation of embolization followed by resumption could blunt the reflex. In a study by Vollherbst et al[3] involving five patients, TCR was observed during transarterial Onyx or transvenous DMSO injections for embolization of cerebral arteriovenous malformations and dural AVFs. The reflex was attributed to chemical stimulation from DMSO and Onyx cast formation. The authors suggested that a slow injection rate may allow DMSO to dissipate in the bloodstream, reducing toxicity. Potti et al[8] described TCR during percutaneous embolization of two juvenile nasopharyngeal angiofibromas, where bradycardia lasted approximately 30 seconds and resolved after pausing the procedure and administering atropine. The event occurred during injection of DMSO, before the injection of EVOH copolymer. They hypothesized that DMSO injection near the foramen ovale stimulated the mandibular trigeminal branch, triggering TCR.

Key aspects of management include: (1) recognizing the potential for TCR; (2) prophylactic peripheral nerve block (3) close interventionist–anaesthesiologist coordination; (4) continuous heart rate and blood pressure monitoring; (5) stopping the stimulus until vitals normalize; (6) atropine for severe cases; (7) epinephrine as a last resort if atropine fails.[9] Recent evidence[10] also supports the role of prophylactic intra-arterial lidocaine in preventing TCR . However, no prophylactic intra-arterial lidocaine injection was used during the embolization procedure in our case.

Conclusion

Bradycardia and hypotension due to TCR is a potential intraprocedural complication during endovascular embolization of intracranial pathologies using Onyx. Early recognition and appropriate management are essential for good clinical outcomes.

Fig. 2 Schematic flow chart depicting the afferent and efferent limbs of the TCR pathway.[4] TCR, trigeminocardiac reflex.

Fig. 3 Top row: A, B are from baseline imaging. (A) Axial TOF MRI depicting normal cavernous ICA siphons at first clinical presentation. (B) Axial postcontrast 3D-T1CUBE MRI showing enhancing soft tissue with a necrotic core involving the right greater wing of sphenoid (arrow), suggestive of osteomyelitis, with normal bilateral cavernous ICA siphons (circle); C, D are imaging at current presentation. (C) Axial MIP computed tomography angiography image demonstrating the inferomedially directed wide necked aneurysm arising from the posterior genu of the cavernous segment of the left internal carotid artery (arrow). (D) Sagittal bone window images showing bony dehiscence involving clivus and major portion of left sphenoid bone (white arrow). Bottom row: (A) Left ICA frontal angiogram depicting the cavernous ICA aneurysm. (B) Endovascular coiling of the parent cavernous ICA using multiple coils. (C) Negative roadmap guidance for Onyx injection over coils to achieve optimal parent artery occlusion (arrow). (D) Postembolization AP view angiogram showing complete left ICA parent artery occlusion with coil mass and onyx cast (circle). Also note contrast stasis within left ICA. AP, anteropostrior; ICA, internal carotid artery; MIP, maximum intensity projection; MRI, magnetic resonance imaging; TOF, time of fight.

Conflict of Interest

None declared.

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Publication History

Article published online:
09 December 2025