Hyaluronidase for Enhancement of Tissue Perfusion: A Pilot Study

Traumata, pressure ulcers and oncologic treatments can cause severe tissue
defects. The plastic surgeon can restore the contour and function of tissue
defects. The success rate of a perforator flap depends on the quality of the
blood flow. In 20-30% of cases, there is skin and fat necrosis, meaning that
parts of the flap die because of insufficient blood flow. This often involves
the fragile, most distal parts. The challenge is to reduce the risk of
circulation problems during and after the procedure. We want to investigate
whether hyaluronidase could help to reduce this risk. Hyaluronidase is a drug
that has been studied several times. It is used to improve systemic effects of
injectable drugs, for local anesthesia in ophthalmic surgery, keloid scar
treatment and cosmetic facial fillers. The effect of the substance
hyaluronidase relies on the dissolution of hyaluronic acid and
monopolysaccharides in connective and epithelial tissues. The enzymatic
breakdown of hyaluronic acid occurs directly, breaking subcutaneous tissue
connections and allowing diffusion of the extravasated fluid over a 3-5 times
larger interstitial space. The dissolution of the ground substance thus changes
the viscosity and increases interstitial perfusion. In this way, hyaluronidase
may possibly contribute to improve blood flow in the perforator flap and thus
could reduce the risk of fat necrosis.

We do not currently have enough knowledge about the potentially beneficial
effect that hyaluronidase might have on skin flap angiogenesis.

The procedure will start according to the standard surgical protocol. After
preparation of the flap, the flap will be measured and a special camera system
will be set up to visualize the tracer. Next, 7.5 mg of indocyanine green (ICG)
will be administered intravenously. The NIR fluorescence intensity in the
perforator flap will be recorded for 5 minutes using the Quest Spectrum
platform. This becomes the baseline fluorescence. Then after 20 minutes, 150 IE
hyaluronidase will be injected intradermally. Immediately afterwards, another
intravenous 7.5 mg indocyanine green (ICG) will be administered and another
fluorescence measurement will follow. During the camera recording, the time to
staining and intensity of the signal will be recorded.

The procedure will start according to the standard surgical protocol. After
preparation of the flap, the flap will be measured and a special camera system
will be set up to visualize the tracer. Next, 7.5 mg of indocyanine green (ICG)
will be administered intravenously. The NIR fluorescence intensity in the
perforator flap will be recorded for 5 minutes using the Quest Spectrum
platform. This becomes the baseline fluorescence. Then after 20 minutes, where
the surgeon normally takes a break, 150 IE hyaluronidase will be injected
intradermally. Immediately afterwards, another intravenous 7.5 mg indocyanine
green (ICG) will be administered and another fluorescence measurement will
follow. During the camera recording, the time to staining and intensity of the
signal will be recorded.

Like any drug, hyaluronidase can have side effects, although not everyone
experiences them. The following side effects could occur: existing infections
may worsen, an allergic reaction and injection pain. Indocyanine green, has
been used for decades, is very safe and side effects are very rare. The only
possible side effect is a treatable allergic reaction. Moreover, this reaction
has only been seen in people who received a higher amount of indocyanine green
(about 10-15 times higher).