Q&A Report: The Use of Vascular Access Buttons in Rabbits for PK/TK Studies

Jon Ehrmann, BS, SRS, SRA, LATg answers questions regarding use of vascular access buttons in rabbits as a solution to challenges in venipuncture, enhancing blood collection, and intravenous administration for pharmacokinetic studies.

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The answers to these questions have been provided by:

Jon Ehrmann, BS, SRS, SRA, LATg
Senior Science & Technology Manager
Veterinary Sciences
Bristol Myers Squibb

For the aseptic preparation of the button prior to access, do you use an alcohol wipe following the chloraprep?

I do an alcohol wipe prior to the chloraprep to remove any debris but I want the chloraprep to stay on the button during the access to continue to kill off bacteria. Once I am done using the implant, I will wipe off the chloraprep with alcohol as it can leave behind a sticky residue.

Do you ever lose the caps? What sort of housing can you use with these rabbits?

Caps occasionally come off but are usually found in the bottom pan of the cage. We are using Techniplast caging and house our rabbits in pairs.

Do the caps ever get stuck?

Yes, especially during the immediate postoperative period. We remove the caps each day and clean the cap and implant hub with alcohol to remove the sticky exudate that can develop during the healing process. We do this for ~ 5 days post-op. That being said, as our technique has improved with multiple surgeries this has become less of an issue.

Is monthly catheter maintenance optimal? Will the patency be better with once weekly or worse with once every two/three months?

I feel monthly maintenance is optimal but others may disagree. I base this off our current success with prolonged patency. Keep in mind, each time you access an implant there is a risk of introducing bacteria and thus a potential for an infection. I do feel weekly maintenance is too frequent and not worth the time/effort.

For PK studies, are you worried about the diluting effects (or any other compound interaction effects) of the lock solution and heparin flush on the data collected?

Great question. It is important to collect a “dirty sample” prior to each study sample to avoid this potential situation. The first access of the day should be a decent volume for the “dirty sample”, say 1 ml, to clear the catheter of blood products. However, after that sample, the following dirty samples can be minimal to just clear the saline and/or lock. This will allow you to stay within the appropriate blood volume restrictions.

Once the blood withdraw patency is lost, will any clot busters restore the patency?

Yes, we use Activase with good success.

What volume of flush and lock do you use for maintenance?

We routinely flush with ~ 3 ml of sterile saline and lock with 0.30 ml TCS. We determine our lock volume by doubling the volume of the catheter and implant which in our case averages around 0.15 ml.

Do you tack the felt on the button down to the musculature?

No, the felt will promote tissue ingrowth.

What size suture material do you use to ligate the vessels?

“4-0.

Can VABs be used in other species?

Yes – mice, rats, ferrets & pigs. Check out the third webinar of the series, “Successful Modification of a Rodent Surgical Procedure and Device for Vascular Access in Minipigs (Vascular Access Button).“

Are you opposed to giving one dose of BupSR prior to surgery?

Not at all! We did some pilot work for Fidelis using BupSR in rabbits with good results regarding blood concentrations and tolerability by the rabbits. We hope to publish this study in the future.

Where can I be trained in the surgical implantation of VAB button?

We are offering this as a wet lab at the ASR conference in Clearwater, FL next year, September 25-27. We hope to see you there! Information will be provided here soon: https://surgicalresearch.org/annual-meeting/.

Can you speak to the maximum frequency of procedure sampling per time period? Is the success and patency of the VAB something that is heavily dependent on frequency of use?

Personally, I do not feel there is a maximum frequency in regards to use of the implant and that is a major advantage to the system. More importantly is your dedication to aseptic technique, flushing and locking the system, and the use of a positive pressure technique.

Have you tried silicone vessel loops to occlude the vessel instead of silk to reduce the vasoconstriction/trauma?

No. We use the same suture for isolation, occlusion, and securing the catheter in place. That way we do not have to remove any loops and then replace with the actual suture. Please note, we use 4-0 Prolene for the occluding/anchor suture and 4-0 vicryl for the cranial sutures.

What is the timeline for patency maintenance?

We used to flush every two weeks. About 10 years ago, I started pushing the limits with our dogs and NHPs because our colonies were very large and required a significant amount of work. We tested it all the way out to 6 weeks and found 4 weeks to be optimal. Thus, I applied this to our rabbits as well. Please note, we flush our rats every 2 weeks.

What is the average patency?

75% of the cohort maintained patency for over 600 days and we still have a few of those still going!

When the ligation is done, do you go through the tubing device or just around? And do you worry about it slipping off?

Just around the catheter to hold it in place for a few weeks. The vessel will ultimately fibrose around the catheter and help secure it. Additionally, the anchor suture between the fixed beads is non-absorbable and should keep it locked in place.

Have you tried using mouse caps in the post op period?

We have not, did not realize they would fit over the rat implant, I will be sure to look into it. Btw, as our technique improved we have significant less exudate and thus the caps sticking were less of an issue.