Onyx (Ethylene Vinyl Alcohol Copolymer + DMSO + Tantalum)

(2005 for AVM; 2007 for Onyx HD-500 for aneurysm), CE | Evidence Level: Level 1 (BRAVO multicenter trial; prospective Onyx vs. n-BCA RCT; EMBOLISE RCT for cSDH 2024)

8.1.1 Chemistry and Physical Behavior Onyx (Medtronic) is a non-adhesive liquid embolic agent composed of an ethylene vinyl alcohol (EVOH) copolymer dissolved in dimethyl sulfoxide (DMSO). Onyx is explicitly designed for use in interventional neuroradiological procedures. Onyx’s unique formulation allows controlled delivery and solidification within the target vessel, providing durable occlusion of abnormal vascular structures such as arteriovenous malformations and dural arteriovenous fistulas. The precipitation mechanism is progressive. Onyx precipitates into a solid on contact with blood fluids, due to rapid diffusion of the DMSO solvent. It immediately forms a skin as the polymeric embolus solidifies from the outside to the inside, while traveling further into the vascular network — a process that creates the characteristic “lava flow” angiographic appearance during injection. The “skin-first” polymerization is the key to the plug-and-push technique: an outer skin forms rapidly at the leading edge while the interior remains liquid, allowing the operator to alternately pause (allowing the skin to consolidate) and resume injection (driving fresh material through the skin into deeper vasculature). The hydrophilic properties of the agent facilitate its smooth delivery through microcatheters, ensuring precise navigation and deposition within vasculature.

8.1.2 Product Family: Onyx 18, Onyx 34, Onyx HD-500

Onyx is available in two product formulations, Onyx 18 (6% EVOH) and Onyx 34 (8% EVOH). Onyx 18 will travel more distally and penetrate deeper into the nidus due to its lower viscosity compared to Onyx 34. Onyx 18 LD (6% EVOH + 94% DMSO) was used for small vessels with low flow, Onyx 20 LD (6.5% EVOH + 93.5% DMSO) for small-medium vessels with medium/high flow, and Onyx 34 LD (8% EVOH + 92% DMSO) for medium/large vessels with high flow and for aneurysms. Onyx HD-500 (Wide-Neck Aneurysm): Onyx HD-500 (20% EVOH) is a device for the treatment of intracranial, saccular, sidewall aneurysms that present with a wide neck (≥4 mm) or with a dome-to-neck ratio less than 2 that are not amenable to treatment with surgical clipping. Once the liquid embolic composition is injected into the aneurysm, the DMSO solvent dissipates as it comes into contact with the ionic contents of the blood stream, causing the polymer to progressively solidify by means of precipitation. The largest US case series using Onyx HD-500 reported successful treatment of 21 patients with wide-neck intracranial aneurysms (mean size 4.5 mm). All aneurysms were located in the anterior circulation, and three aneurysms presented as acute subarachnoid hemorrhages. Complete aneurysm occlusion was present in 19 of 21 patients (90%). Aneurysm recanalization was not detected in any patients on mean follow-up of 8.9 months in 11 patients. Onyx Product Comparison Table: Product

EVOH Concentration

Viscosity

Primary Use

Onyx 18

6%

Low

Small feeders, distal nidal penetration, dAVF

Onyx 34

8%

Medium-High

Large feeders, high-flow fistulas, bifurcation AVMs

Onyx HD-500

20%

Very High

Wide-neck sidewall aneurysms

8.1.3 The Mandatory Agitation Requirement: Tantalum Settling A critical and operationally unique aspect of Onyx preparation is the requirement for continuous mechanical agitation before and during injection. The micronized tantalum

powder that provides fluoroscopic radiopacity is a suspension, not a true solution — it sediments under gravity over time. If not adequately resuspended, the leading edge of the injection becomes poorly radio-opaque, creating a dangerous “invisible” Onyx front that cannot be tracked fluoroscopically. Protocol: Shake the Onyx vial vigorously for a minimum of 20 minutes before use on the roller mixer. During a prolonged injection, re-agitate the syringe every 5 minutes. This stands in contrast to PHIL, which requires no agitation due to its covalently bonded iodine radiopacifier (see Section 8.3).

8.1.4 Initial AVM Experience: AJNR 2007 Landmark Series Between May 2000 and December 2005, 44 patients with brain AVMs were embolized with Onyx. There were 18 women and 26 men with a mean age of 42.4 years. In 44 patients, 52 embolization procedures were performed with 138 feeding pedicles embolized. Average estimated size reduction was 75% (median 80%, range 40%–100%). This established the benchmark for Onyx as the preferred pre-surgical AVM embolization agent.

8.1.5 Comparative Evidence: Onyx vs. n-BCA for AVM Compared with NBCA, Onyx has slower cast formation, flow-independent delivery, cohesiveness, and smaller minimum diameter of embolized vessel. These features enable the usage of the plug-and-push method and penetration into smaller microvasculature, leading to nidus occlusion. A prospective multicenter randomized trial focused on the effectiveness of embolization, defined as a size reduction of AVM by more than 50%. The results did not differ significantly (96% for Onyx vs 85% for NBCA). Onyx is superior to NBCA in injection times (longer) and possibility of halting injections with intermittent angiographic control, though NBCA is still preferred by some institutions.

8.1.6 Preoperative Embolization: Onyx vs. NBCA in AVM Surgery In Japan, N-butyl cyanoacrylate (NBCA) had been widely used for pre-operative embolization of AVMs, but after the approval of the Onyx liquid embolic system by the Japanese Ministry of Health, Labor and Welfare in 2008, this embolic material has been increasingly used in the treatment of AVMs. According to a review of 1,042 AVM cases from Japan that underwent embolization, coils were used in 165 embolization procedures (15.8%); NBCA in 627 (60.2%); and Onyx in 432 (41.5%).

8.1.7 Dural AVF Treatment: Transarterial and Transvenous Approaches Transvenous embolization is the treatment of choice for cavernous sinus dural arteriovenous fistulas (csDAVFs) despite occasional difficulty in transvenous

catheterization. In cases where transvenous embolization of the cavernous sinus is difficult, transarterial embolization of the fistulas with Onyx offers a safe and effective alternative. Transvenous Onyx embolization of dural arteriovenous fistulas with combined transvenous balloon protection of the venous sinus is safe and effective in achieving high occlusion rate, low embolization-related complications, and satisfactory clinical outcomes.

8.1.8 The Diluted Onyx Technique For cases where nidal penetration is limited by premature proximal plugging, diluted Onyx provides a lower-viscosity alternative that extends the working time and penetration depth without switching agents. The diluted Onyx technique consists of initial embolization with routine Onyx-18, followed by the diluted Onyx (1.5 mL of Onyx-18 diluted with 0.5 mL of DMSO) through the same microcatheter. When the length of reflux reached 2 cm (or close to the determined limit) and the embolic material could not move distally any more despite rounds of “injection-refluxwaiting,” regular Onyx 18 was changed to diluted Onyx. This technique extends the reflux limit while maintaining forward flow.

8.1.9 MMA Embolization and the EMBOLISE Trial (2024) Results from the first pivotal, multicenter, randomized controlled trials of MMA embolization in patients with cSDH were published in 2024. Studies evaluating the Onyx Liquid Embolic System showed a reduction in reoperation rate in surgical patients (EMBOLISE study, United States) and a similar symptomatic recurrence or progression in surgical or medically treated patients compared with usual care, but with fewer serious adverse events (MAGICMT study, China) compared with conventional treatment alone. The EMBOLISE trial was a multicenter, open-label, adaptive-design RCT conducted in the United States. It included 400 patients with symptomatic, thick, or midline-shifting subacute or chronic SDH with an indication for surgery. Patients were randomized to MMAE plus surgery or surgery alone groups, utilizing the Onyx liquid embolic system as the embolic agent. A statistically significant 64% relative reduction in hematoma recurrence or progression requiring repeat surgery within 90 days was observed. There is a growing evidence base that supports the use of liquid embolic agents such as Onyx and N-butyl cyanoacrylate in specific patient populations and clinical scenarios versus particle embolic agents, the most commonly used embolic materials in prior studies. ──────────────────────────────────────────────────