Onyx Liquid Embolic System

Physician Orientation Review

International

FD159D

Materials and Indications

This presentation is intended for the purpose of
didactic review with physicians regarding the use
of the Onyx LD Embolic System
Model #s 105-7000-060, 065, 080 (Onyx 18, 20, 34)

Indications for Use: Embolization of lesions in

the peripheral and neurovasculature, including
arteriovenous malformations and hypervascular
tumors.

FD159D

Onyx Development
Ongoing research since 1993
Human clinical studies commenced 1997
Name change 1999: Embolyx to Onyx (LES)
CE Mark received for AVM indication, July
1999
Regularly used since then in Europe

Estimated worldwide procedures: 15,000+

FD159D

Onyx Liquid Embolic System

Ethylene-vinyl alcohol copolymer

EVOH

Dimethyl Sulfoxide Solvent

DMSO

Micronized tantalum powder

Ta

FD159D

Onyx Embolization Process

Onyx is a pre-mixed, radiopaque, injectable embolic

fluid.

Polymer precipitation occurs upon contact with

aqueous solution.

Contact with blood = Precipitation

Solvent diffuses away

Forms a spongy polymeric cast

Forms a skin - solidifies from the outside in

Liquid center continues to flow

FD159D

Characteristics
Onyx delivers in a cohesive manner
Analogy of lava demonstrates characteristics of
behavior).

Onyx Precipitate
External Surface

Onyx Precipitate
Internal Surface
FD159D

Device Components

1.5 ml vial of Onyx

Onyx 18, 105-7000-060
Onyx 20, 105-7000-065
Onyx 34, 105-7000-080
1.5 ml vial of DMSO
MTI 1 ml luer-lock delivery syringes

2 white for Onyx,

1 yellow for DMSO

FD159D

Onyx Relative Viscosity

Onyx LD - AVM Formulations
40
35

VS.

Scale = centistokes

30

Onyx HD - Aneurysm Therapy

25
20

600

15

500

10

400

300

Water

Human
Blood

25%
nBCA

6%

6.5

Viscosity doubles between

Onyx 18 (6%) to Onyx 34 (8%)

8%

200
100
0
6%

6.50%

8%

20%

Onyx AVM v. HD for Aneurysms

Entirely Different Viscosity

FD159D

DMSO
(Dimethyl Sulfoxide Solvent)

FD159D

DMSO Study Review

In 90 - 91 Taki and Terada successfully described embolization

with EVAL dissolved in DMSO

Safety concerns emerged

Chaloupka and Viuela conducted early UCLA study - showed

severe vasospasm and angionecrosis

Subsequent studies show safety of the Onyx delivery protocol

Dr. Chaloupka (1999)
UCLA (1998)

FD159D

Chaloupka et, al., UCLA,

AJNR, June 1994

1st study: DMSO intra-arterial injections in volumes

0.5 mL and 0.8 mL
Injected over a timeframe of 15 seconds or less

Rete mirabile of 29 swine

When injected over relatively rapid timeframes
DMSO was reported to cause moderate to severe
vasospasm
Sub arachnoid hemorrhage (SAH), stroke or death

FD159D

Murayama, (et al) UCLA,

Neurosurgery, November 1998

Embolyx E (now Onyx) and its solvent DMSO

44 rete mirabile in 22 swine

Study showed two important factors influencing

vascular toxicity:
Contact time with arterial wall
Volume of DMSO

Fast delivery (0.5 mL in 5-15 seconds)

Caused severe vasospasm and histological endothelial
necrosis

Slow delivery (0.5 mL in 30-120 seconds)

Showed no vasospasm, minimal inflammation and no
complications
FD159D

Chaloupka, (et al) AJNR,

March 1999

At MTIs request, Dr. Chaloupka agreed to conduct a

2nd study reexamination DMSO angiotoxicity
Purpose was to evaluate the effects of intra-arterial
DMSO injections at slower rates of 30, 60 and 90
seconds
Rete of 26 swine
No acute hemodynamic alterations
No infarction or SAH

FD159D

Chaloupka, (et al)

AJNR,

March 1999

No significant changes in arterial blood pressure

No alterations in heart rate or ECG
Conclusion:
Found that lower dose rates of superselectively infused DMSO
are associated with a more acceptable safety and histotoxicity
profile than previously reported
Chaloupka confirmed Murayamas results

FD159D

DMSO Overview

Enters the bloodstream and is absorbed into tissues

Metabolized to dimethyl sulfone (DMSO2) and
dimethyl sulfide (DMS)
80% of these metabolites are eliminated via the kidneys in
urine within a week
Also eliminated via the skin or lungs which causes a garlic
odor to the breath

Complete elimination: 13-18 days

FD159D

Procedure Guidelines
Please refer to the Instructions for Use for
full prescribing details

FD159D

Onyx Animation

Onyx AVM Animation available

FD159D

Shake Onyx Vials

Place vials on mixer

Set mixer to maximum
setting
Shake for a minimum of 20
minutes
Maintain shaking of vials
until ready to use
FD159D

Superselective
Contrast Injection

Confirm micro
catheter placement
Contrast agent per
institutional
procedure

FD159D

Flush Microcatheter

Flush contrast from

micro catheter
IFU state 10ml of
saline

FD159D

Prime Catheter with DMSO

Aspirate 0.8 mL DMSO into the

yellow MTI DMSO 1 mL syringe

Inject DMSO to sufficiently fill

dead space of delivery catheter
Marathon = 0.23mL
UltraFlow HPC = 0.26mL

FD159D

Prepare Onyx Delivery Syringe

Remove prepared vial

from shaker
Aspirate 1 mL Onyx into
the white MTI Onyx 1 mL
syringe
Using an 18 or 20 gauge
needle

Clear any air bubbles

within the syringe and hub
FD159D

Overfill Hub with DMSO

When ready to deliver

Onyx, remove DMSO
syringe
Hold the micro catheter
hub in a vertical position
Overfill hub of the
catheter with the balance
of DMSO

FD159D

Onyx Delivery Syringe

Connect Onyx syringe to the

hub.

For optimal fluoroscopic

visualization, quickly point
vertically to create an interface
between DMSO and Onyx.

While holding the syringe

vertically, begin injection Onyx
to displace DMSO.

Inject Onyx at the

recommended slow, steady
rate of:
0.25ml over 90 seconds,
(approx. 0.1 mL/min)
IFU states: Do not exceed a
0.3 mL/min
FD159D

Continue Injecting Onyx

Continue holding the syringe

vertically until Onyx passes
through the hub

Once Onyx passes through the

hub, the syringe may be held in a
comfortable (horizontal) position

Begin fluoroscopic imaging just

prior to delivering catheter dead
space:
Marathon = 0.23mL
UltraFlow HPC = 0.26mL

FD159D

Detachment of Catheter
After completion of Onyx
injection, slightly aspirate
syringe: Only 0.1ml is needed
Gently, slowly and
incrementally pull the
catheter a few centimeters at
a time.
Tension will increase in
catheter
Hold when sufficient tension is
reached
Gradually increase

Catheter will release

FD159D

Onyx Preparation

1.

Shake Vials
20 minutes

5. Connect Onyx
Syringe vertically

2. Flush Catheter

3. Load dead space

with DMSO

6. Displace DMSO
0.25ml / 90 secs

4. Overwash
catheter hub

7. Fluoro just
prior to filling
deadspace

FD159D

Onyx AVM
Technique

FD159D

Plug and Push Technique

Create a plug around catheter tip

Allow use of Flow Arrest to promote distal movement
Use a waiting technique to create change in pressure
Can help improve penetration
Must balance with cautions and risks

FD159D

Hints for Plug and Push

Technique

Re- road map after each injection cycle (wait time)

This will help monitor deposition and movement of new material

May be necessary to repeat cycle multiple times during an injection

When material first begins to reflux
wait :30 seconds to break the motion
upon re-injection again the material should move distally
As a full circumferential plug forms
wait up to 2:00min to solidify flow arrest

When beginning injection SLOW gentle injection will help control

new deposition

FD159D

Technique Decision Tree

Begin Slow Onyx
Injection
Reflux (laminar/plug) ?

Forward Penetration

Pause

Continue
Constant Slow Rate

:30 Seconds
Momentum Break

2:00 Minutes
Solidify Plug

Re-Inject
Repeat Process
FD159D

Potential Risks

Using Plug and Push can create conditions that should

be monitored closely.
Waiting time
Catheter occlusion/pressure build up

Possible reflux
Catheter Removal

FD159D

Fundamentals of AVM Embolization

Imaging/Working
Projection
Pedicle Selection Size

Microcatheter Retrieval

Contribution / Flow

Onyx Technique
Waiting Time /
Pressures

Microcatheter Position

Injection Speed
Delivery Rate

Are Critical to Onyx Performance

FD159D

Imaging/Working Projection

Always work with Reference Image and Working Projection

A reference image becomes very useful during long Onyx

injections
Catheter distal shaft
Nidal Angioarchitecture
Primary venous drainage

Optimize working projection:

Separation of catheter tip, minimal foreshortening of catheter

Allows to recognize, measure and manage reflux
Instructions for Use recommends a maximum of 1cm reflux
Modifications based on anatomy
Distal turn or bend in catheter tip
Select a point on catheter (a turn or bend) to use as a reference and
reflux limit
FD159D

Reference Images

FD159D

Feeder Selection

Larger contributing feeders seem to

promote penetration:
Generally easier to reach nidal position
Generally provide a greater pressure
gradient
Therefore can capitalize on Onyx
characteristics for better penetration.
FD159D

Feeder Selection

Small pedicles can have limited penetration

Especially if proximal because of change in pressure as feeder
fills can cause limited nidal penetration.
Must inject very slowly, control reflux, and expect possibly limited
nidal delivery from small feeders.
Risk of delayed catheter retrieval can occur because of
potential spasm / reflux build up quickly.

FD159D

Microcatheter Position

Intra-nidal (or wedged) position seems optimal

Or as close as possible to nidus
Especially because Onyx performs best when pushed into the
lesion

Proximal positions:
May result in minimal nidal deposition and a feeder injection
As Onyx is delivered into feeder, the pressure gradient changes.
As feeder closes, the path of least resistance becomes retrograde
reflux occurs.
Plug and Push may not achieve same results as nidal position

FD159D

Injection Rate
The Slower The Better
Better Control and Better
penetration overall
More penetration before
reflux and more control
when reflux occurs

Rate must be constant

and slow

Using the DMSO

Displacement rate as a
reference
0.25ml over 90 seconds
= 0.16ml / minute
Continue this rate (or
slower)
Case examples: 0.10 0.15 ml / minute

Any change in injection rate

will create reflux
If rate is too fast, reflux will
occur quickly
FD159D

Catheter Retrieval
Consider all the
factors that can
affect difficult
catheter removal:

Tortuosity

Length of Reflux

Size of Feeder

Difficult Catheter
Retrieval

Distal 2cm
(loop, hook)

Time of Injection

Potential
for Spasm

Evaluating these parameters prior to injection can determine how much reflux will be accepted
FD159D

Retrieval Techniques:
Two Paths

Two Techniques Provide

Versatile, Effective Use

Slow Traction
Technique

Quick Wrist Snap

Technique

FD159D

Slow Traction Technique

Slowly, and incrementally (cm by cm), withdraw the catheter

Tension will slowly increase creating retrieval force directly to
the catheter tip
Sustain moderate tension (hold for a moment)
Catheter tip will release from Onyx cast
Completely withdrawal catheter

FD159D

Quick Wrist Snap Technique

Remove all slack from catheter. Withdraw catheter 3 5 cm.

This will create a slight tension throughout the catheter

Quickly move wrist from left to right (about 10 20cm)

No need to move the entire arm
This is NOT like a glue technique

This provides a spark of energy through the catheter

Without stretching the catheter too much and risking breakage

FD159D

Catheter Retrieval Management

Step #1: Apply gentle, incremental traction to catheter
(cm by cm)

Is the vasculature
straightening ?

Step #2: Assess risk of

spasm or vessel
damage

Is the Onyx cast

retracting?

Is the catheter tip

beginning to release
from Onyx cast?``

Step #2a: Sustain Traction and

Monitor Tip Release

Step #3: Release Traction and Repeat Decision Tree

Applying Intermittent Traction As Necessary

FD159D

Quick Wrist Snap - Steps

Remove all slack from the

catheter
By pulling a few cm.

Create slight tension

FD159D

Quick Wrist Snap - Steps

Quickly move wrist 10 15cm
to the right
Making a wrist snap motion

0cm

20cm

Quick but Short

Wrist Motion

NOTE: It is not necessary to move the entire arm (such as a glue technique). This
technique can risk catheter separation.
FD159D

Onyx Delivery Microcatheters

FD159D

Onyx Delivery Systems

Rebar

Marathon & Ultraflow

Echelon 10 and 14

Mirage
X-pedion, SilverSpeed
Guidewires

FD159D

Onyx Catheters
Onyx Delivery Catheter
Over The Wire
Benefits
Reinforced
High Tensile Strength
Burst Profile
Uses
Coils
Liquid Embolics
Particles

Soft Supple Tip

Superior Navigation
High Tensile Strength
Burst Pressure

UltraFlow

Flow Directed Catheter

Benefits
Soft Supple Tip
No Guidewire
Superior Navigation
Uses
AVM embo (nBCA)

Marathon
Apollo, 2009
FD159D

Embolic Injection Pressure v. Burst

psi

400
350

18x tolerance

300
250
200
150
100
50
0

0.1 ml / min

Onyx 18
Injection

UltraFlow

Marathon

Onyx injection requires very low pressure of approximately 20psi injected at a

rate of (0.1 ml / min)

Marathon provides a robust tolerance between Onyx injection pressure and

Onyx burst pressure and is more than 2x in UltraFlow

Source: TR 03-106, UltraFlow TR01-116

Test Method: TM0090, Onyx Plug & Push: 1 hour Onyx injections, repeated pressurization to intentional failure.
Engineering Note: Test results show that when catheter is intentionally ruptured, the UltraFlow fails between the fuse joint and distal tip, while Marathon fails in the distal
7cm.

FD159D

Pressure to Re-inject v. Wait Time

PSI
160
140
120
100
80
60
40
20
0

Wait Time

30 secs 1min

1.5min 2min

3min

5min

Recommendation: Limit Wait time less than 2 min.

Onyx mass can precipitate in 3 - 5 minutes.

The increased injection pressure (after a long wait) can approach this limit.

FD159D

Summary:
Burst Performance

Recognize occluded catheter if Onyx is not exiting catheter tip

Occlusion may occur after extended wait period during Onyx injection

Do not interrupt Onyx injection more than 2 minutes

If Onyx is not exiting tip, do not inject more than 0.05 ml into a potentially
occluded catheter.

Static Pressure to burst the UltraFlow or Marathon should be recognizable

to identify resistance.
If resistance is felt, stop Onyx injection.

FD159D

Detachment Force from Onyx Cast

Marathon design requires 25% less force to retrieve from a

cast of Onyx (see test method) than UltraFlow
Source:, Marathon TR 03-106, UltraFlow TR01-116
Test Method: TM 0090: Flow model, 3cm Onyx reflux, 1 hour dwell time, at body temperature, slow pull technique

70

Retrieval Force

60

Grams

50
40
30
20
10
0

UltraFlow

Marathon

FD159D

Distal Tensile Strength

600

400

Grams

500

Distal Tensile Strength

300

71%
200

130%

130%

100

Magic 1.2

Magic 1.5

Spinnaker

UltraFlow

Marathon 1.3

Marathon braiding provides significant tensile strength for excellent

catheter retrieval

Source: UltraFlow TR01-116, Marathon TR 03-106, Other Catheters: TR02-088

Test Method: TM0080 test a 1 distal segment gauge length, stretch to break at 20 / min

FD159D

FD Catheter Stretch Profile

600
500

Recommended
Traction Limit < 20cm

400

Stretch Point
to Breakage

300
200
100
0

1cm

3cm

5cm

10cm

15cm

20cm

43cm

Distance of catheter traction (cm)

Recommended Traction Limit should be < 20cm

Note: If catheter is trapped at distal tip - recommendation offers safety
margin to minimize risk of catheter separation.
FD159D

Access Summary

Tip shaping:
It is not necessary to overshape

Guidewire technique:
Some clinicians recommend keeping the guidewire placed just past the
distal tip marker during navigation. This helps maintain a patent lumen
and minimize risk of catheter prolapse

Angiographic technique
Some physicians suggest using a gentle, low volume puff of contrast to
confirm catheter patency.

Less Magnification / Larger Field of View

Prior to embolic delivery, it is suggested to deliver a small volume contrast
injection
While viewing the entire distal catheter segment to verify catheter integrity.

FD159D

Onyx Liquid Embolic System

Physician Orientation Review

International

CAUTION: Federal (USA) law restricts this device to sale by or on the order of a physician. A complete statement of indications, contraindications, warnings and
instructions can be found in the product labeling supplied with each device. WARNINGS: Serious, including fatal, consequences could result with the use of the Onyx LES
without adequate training. Contact your ev3 Sales Representative for information on training courses. Onyx is a registered trademark of ev3.

FD159D