“Is Rejuran injected with a needle or a cannula?”

More people are asking it at consultation: “I hear a cannula doesn't hurt and bruises less — could you use that instead?”

The first half is correct. A blunt-tipped cannula pushes vessels aside as it travels, so it does generally bruise less, and that is what we wrote in our column on bruising and swelling. The difficulty is the assumption sitting behind the sentence — the assumption that both instruments can do the same job. With Rejuran, that assumption does not hold.

This is not a piece arguing that one instrument beats the other. It sets out what each instrument actually does, and therefore why pain is not the criterion you can choose on. And at the end it sets out how far the evidence for this judgement goes — less far than you might expect.

The last two rows are the whole of this column. To cover a broad area with a cannula you have to travel a long way along one plane, and the material is laid into that plane as a line. To cover a broad area with a needle you have to puncture repeatedly, and the material ends up scattered as points.

PN (polynucleotide), the active component of Rejuran, forms a water-holding mesh in the dermis and creates conditions in which the skin can repair itself. It is not a product for filling volume; it is a product that changes the state of the dermis.

So the aim is not to concentrate it in one spot but to distribute it widely and evenly through the dermis. That is why small raised papules appear on the face immediately after treatment — physical swelling from material pooled in the dermis, which settles as it is absorbed. Each of those papules is also a marker that the material went where it was meant to go.

In a survey of 235 Korean dermatologists, most reported using a 33G needle with multiple punctures aimed at the dermis. In the same survey, fine lines under the eyes were the second most common reason for using PN.

There is research that actually imaged where each instrument puts the material: contrast-mixed material injected into cadaver foreheads and then examined by CT and MRI.

Turn the numbers into a picture and it comes out like this. A cannula lays material long and flat within a single plane. It spreads nearly twice as far horizontally as the needle, sits thinner vertically, and does not leave the plane it was aimed at. In other cadaver work, material placed by cannula likewise stayed within the deep plane, while material placed by needle was found across several planes, from periosteum up into superficial skin.

For a doctor working with fillers, that result is an argument in the cannula's favour. When you are placing volume, you want the material to stay at the depth you intended. The word attached to the titles of those studies is, in fact, ‘precision’.

There is one more thing worth pinning down here. The pain difference itself is smaller than people assume.

One trial compared needle and cannula properly: fifty faces split down the middle, hyaluronic acid filler placed into the nasolabial folds by needle on one side and by cannula on the other. Marking pain on a 100 mm scale gave 34.7 for the cannula and 41.3 for the needle. The difference was 6.6.

The authors themselves wrote in the paper that the difference was “statistically significant but difficult to regard as clinically meaningful” — because it falls below the smallest difference on a pain scale that a person actually registers as “that hurt less”.

And the figure has an item missing. Before a cannula can go in, an entry port has to be made with a larger needle. The paper contains no description at all of how that port was created, and does not say whether the pain of making it was counted in the score or left out. Which makes it a 6.6 with the cannula's own cost not yet on the ledger.

And this is not a study of Rejuran. It is a study of filler. We come back to that point below.

The main reason cannulas are recommended is not pain but vascular injury. A blunt tip is less likely to pierce a vessel, and that direction is right. It is worth knowing what kind of evidence sits behind it.

• The most frequently cited source is not a trial but a survey. 370 dermatologists were asked to answer from memory of the previous ten years. Vascular occlusion came out at 1 per 6,410 injections with a needle and 1 per 40,882 with a cannula. The gap between the numbers is large. But these are estimates that depend on recall, and mixed into them is the likelihood that cannulas were chosen for the risky areas in the first place
• In a review collecting cases of blindness (511 cases cumulatively, from 1906 to 2023), among the most recent 365 cases only 38 had the instrument recorded at all, and 16 of those were cannulas. That the instrument goes unrecorded even when something this serious happens tells you something about the state of the evidence in this field
• In one Chinese series, 16 of the 27 patients who lost vision had been treated with a cannula
• The authors who compiled the blindness cases also wrote that “vascular injury has been reported with cannulas of various gauges”, and on gauge took the view that 25G or larger is preferable and 27G or smaller is more likely to penetrate a vessel wall

So a cannula is an instrument known to move risk in the right direction, not an instrument exempt from risk. “It's fine, we're using a cannula” runs one step ahead of what is established.

We would rather this did not read as a piece running the cannula down. There are places where it is clearly the better instrument.

• Filler placing volume in a deep plane. The aim is for the material to stay at the depth intended, and the property the cadaver work demonstrated is exactly suited to that aim
• When a wide area has to be covered from a single entry point. You can fan out from one place rather than puncturing repeatedly
• Areas that bruise heavily. The cannula's advantage is greatest where the skin is thin and vessels are dense, as under the eyes

For reference, an expert paper written by clinicians who act as advisors to the PN manufacturer raises the cannula for PN treatment only around the temple, and does not recommend a cannula around the eyes. The periorbital area is described there as fine needle injection of 0.01–0.02 mL per point.

For anyone who has read this far, the most important sentence is still to come.

So our reason for using a needle with Rejuran is not “because the needle won in the research”. It is an inference from the properties of the drug and the tool — that the material has to be scattered through the dermis, and that a cannula lays material as a line within one plane. Give an inference the weight an inference deserves.

If research emerges showing a cannula is better for PN, our practice changes with it. And we will correct this column when it does.

• Rejuran is injected intradermally, point by point, with the 33G needle supplied in the box. Because the aim is for the material to be spread widely and evenly through the dermis
• The instrument is chosen by where the material needs to go, not by pain. The answer differs by treatment and by area
• Pain is reduced by other means rather than by changing the instrument. Enough time on the topical anaesthetic, formulations containing lidocaine, and control of injection speed
• If bruising is a worry, we adjust the plan. We check what medication you are taking first, and if something important is close we will suggest moving the date — set out in detail in our column on bruising and swelling

Written and reviewed by Lee Chi-Hak, MD, medical director of Miso Clinic in Daegu, South Korea. Every study cited above is given together with the conclusion of the original and its limitations, and where we could not verify something, we have said that we could not verify it.