Adjunctive Middle Meningeal Artery Embolization for Subdural Hematoma

Disclosure:

The use described in this publication has not been approved by FDA and the safety and effectiveness of the off-label use has not been established.

The FDA-approved use for the Onyx™ liquid embolic system is pre-surgical embolization of brain arteriovenous malformations (bAVMs).

This article studied the results of embolization with Onyx™ liquid embolic system to treat subacute and chronic subdural hematoma with the original primary outcome that assessed the need for re-operation. Towards the completion of the Surgery Cohort, the primary outcome was changed at the request of the FDA, and this will be subject of a future analysis.

Note that the FDA-required labeling contains the following restrictions, cautions and warnings associated with this off-label use of the Onyx™ liquid embolic system:

CAUTIONS:

This product is for the exclusive use by medical specialists experienced in angiographic and percutaneous neurointerventional procedures.

WARNINGS:

The safety and effectiveness of the Onyx™ LES as a long term implant has not been established. Not for use with premature infants (<1,500 g) or individuals with significant liver and kidney function impairment.

Performing embolization to occlude blood vessels is a high risk procedure. This device should be used only by physicians with neurointerventional training and a thorough knowledge of the pathology to be treated, angiographic techniques, and superselective embolization.

AVM embolization may influence blood flow patterns, thereby subjecting arteries supplying the AVM or the brain proximal to the AVM to increased pressures. Increased arterial pressures could result in hemorrhagic complications.

Animal experimentation has shown that when the Onyx™ LES escapes outside the vascular space, as might occur if the vessel wall is compromised, a subacute inflammatory response to the material may occur. Increased intracranial pressure due to unresorbed Onyx™ LES material in this space may cause tissue damage.

Dimethyl sulfoxide (DMSO) can initiate the liberation of histamine and there has been an occasional hypersensitivity reaction with topical administration of dimethyl sulfoxide. This hypersensitivity has been reported in one patient being treated for interstitial cystitis. If anaphylactoid symptoms develop, appropriate therapy should be instituted. DMSO may interact with other embolic agents, such as polymer coated coils, e.g., gel coatings and suture material coated coils.

Therapeutic embolization should not be performed when high blood flow precludes safe infusion of the embolic agent.

Failure to continuously mix the Onyx™ LES for the required time may result in inadequate suspension of the tantalum, resulting in inadequate fluoroscopic visualization during delivery (see instructions for use). Inject the Onyx™ LES immediately after mixing. If the Onyx™ LES injection is delayed, tantalum settling can occur within the syringe resulting in poor visualization of the Onyx™ LES during injection.

Adequate fluoroscopic visualization must be maintained during the Onyx™ LES delivery or non-target vessel embolization may result. If visualization is lost at any time during the embolization procedure, HALT the Onyx™ LES delivery until adequate visualization is reestablished. Premature solidification of the Onyx™ LES may occur if micro catheter luer contacts any amount of saline, blood or contrast.

Use only ev3 approved, Onyx™ LES/DMSO compatible micro catheters indicated for use in the neurovasculature and ev3 syringes. Other micro catheters or syringes may not be compatible with DMSO and their use can result in thromboembolic events due to catheter degradation.

Use only thumb pressure to inject the recommended rate of 0.16 mL/ min. Do not exceed 0.3 ml/min injection rate. Animal studies have shown that rapid injection of DMSO into the vasculature may lead to vasospasm and/or angionecrosis. Using palm of hand to advance plunger may result in catheter rupture due to overpressurization in the event of catheter occlusion.

Do not allow more than 1 cm of the Onyx™ LES to reflux back over catheter tip. Angioarchitecture, vasospasm, excessive Onyx™ LES reflux, or prolonged injection time may result in difficult catheter removal and potential entrapment. Excessive force to remove an entrapped catheter may cause serious intracranial hemorrhage. The long-term effects of an entrapped catheter that is left in a patient are unknown, but potentially could include clot formation, infection, or catheter migration.

After using a micro catheter with the Onyx™ LES, do not attempt to clear or inject any material through it. Such attempts may lead to embolus or embolization of an unintended area.

STOP injection if the Onyx™ LES is not visualized exiting catheter tip. If the catheter becomes occluded, over-pressurization can occur. During the Onyx™ LES injection, continuously verify that the Onyx™ LES is exiting the catheter tip. Testing has shown that overpressurization and rupture can occur if only a volume of 0.05 ml of the Onyx™ LES is injected and is not visualized exiting the catheter tip.

STOP injection if increased resistance to the Onyx™ LES injection is observed. If increased resistance occurs, determine the cause (e.g., Onyx™ LES occlusion in catheter lumen) and replace the catheter. Do not attempt to clear or overcome resistance by applying increased injection pressure, as use of excessive pressure may result in catheter rupture and embolization of unintended areas.

DO NOT interrupt the Onyx™ LES injection for longer than two minutes prior to re-injection. Solidification of the Onyx™ LES may occur at the catheter tip resulting in catheter occlusion, and use of excessive pressure to clear the catheter

 may result in catheter rupture. Complete indications, Contraindications, warnings and instructions for use can be found in the product labeling supplied with each device.

PRECAUTIONS:

Some data indicate that dimethyl sulfoxide potentiates other concomitantly administered medications.

A garlic-like taste may be noted by the patient with use of the Onyx™ LES due to the DMSO component. This taste may last several hours. An odor on the breath and skin may be present. Inspect product packaging prior to use. Do not use if sterile barrier is open or damaged.

Use prior to expiration date.

Warnings and Directions for Use sections.

Wait a few seconds following completion of the Onyx™ LES injection before attempting catheter retrieval. Failure to wait a few seconds to retrieve the micro catheter after the Onyx™ LES injection may result in fragmentation of the Onyx™ LES into non-target vessels.

Difficult catheter removal or catheter entrapment may be caused by any of the following: Angioarchitecture: very distal bAVM fed by afferent, lengthened, small, or tortuous pedicles, Vasospasm, Reflux, Injection time

To reduce the risk of catheter entrapment, carefully select catheter placement and manage reflux to minimize the factors listed above.

Should catheter removal become difficult, the following will assist in catheter retrieval:

• Carefully pull the catheter to assess any resistance to removal.
• If resistance is felt, remove any “slack” in the catheter.
• Gently apply traction to the catheter (approximately 3-4 cm of stretch to the catheter).
• Hold this traction for a few seconds and release. Assess traction on vasculature to minimize risk of hemorrhage. This process can be repeated intermittently until catheter is retrieved.

Alternate Technique for Difficult to Remove Catheters:

• Remove all slack from the catheter by putting a few centimeters of traction on the catheter to create a slight tension in the catheter system.
• Firmly hold the catheter and then pull it using a quick wrist snap motion (from left to right) 10 – 15 centimeters to remove the catheter from the Onyx™ LES cast.
• Note: Do not apply more than 20 cm of traction to catheter, to minimize risk of catheter separation.

For entrapped catheters:

• Under some difficult clinical situations, rather than risk rupturing the malformation and consequent hemorrhagic complications by applying too much traction on an entrapped catheter, it may be safer to leave the micro catheter in the vascular system.
• This is accomplished by stretching the catheter and cutting the shaft near the entry point of vascular access allowing the catheter to remain in the artery.
• If the catheter breaks during removal, distal migration or coiling of the catheter may occur. Same day surgical resection should be considered to minimize the risk of thrombosis.

Note that the labeling for the Onyx™ liquid embolic system includes the following contraindications when any of the following conditions exist:

• When optimal catheter placement is not possible.
• When provocative testing indicates intolerance to the occlusion procedure.
• When vasospasm stops blood flow.

A copy of the FDA-required labeling is available here.

Drs.  Jason Davies, Jared Knopman, Maxim Mokin, Ameer Hassan, Robert Harbaugh, Alexander Khalessi, Jens Fiehler, Bradley Gross, Ramesh Grandhi, Jason Tarpley, Mark Bain, Webster Crowley, Thomas Link, Justin Fraser, Michael Levitt, Peng Roc Chen, Ricardo Hanel, Joe Bernard, Mouhammad Jumaa, Alexandra Paul, William Mack, Joshua Osbun, Kathleen Dlouhy, Christopher Kellner, Daniel Sahlein, Clemens Schirmer, Justin Singer and Adnan Siddiqui were consultants who received compensation from Medtronic while contributing to this publication.

"Embolization of the Middle Meningeal Artery With Onyx™ Liquid Embolic System in the Treatment of Subacute or Chronic Subdural Hematoma” (EMBOLISE) was published on November 21, 2024 .