Negative Pressure Wound Therapy: Supra-Physiological or Just Physical Effects of Positive Pressure?

Dear Sir,

Negative pressure wound therapy (NPWT), also known as vacuum-assisted wound closure or VAC, has become an established wound management approach in various clinical situations. Yet, the physiological basis of this valuable method remains elusive.

A recent article indicates that NPWT can act as a “surgical leach” and quicken healing time in failing fingertip replantation, but may not improve the survival rate. ¹ The latter finding is in line with another recent study that found no survival enhancement of congested rabbit ear flaps managed by NPWT. ² It is therefore worth further discussing NPWT mechanisms that may be beneficial to compromised healing.

Use of NPWT in failing replantation and free tissue transfer seems to be primarily driven by studies that have shown enhancement of neovascularization by NPWT. It has been suggested that NPWT-induced neovascularization may be due to increase in expression of angiogenic factors, and in particular of vascular endothelial growth factor (VEGF). However, VEGF level elevation has not always been observed. ³ It has also been shown that VEGF receptor expression significantly increases at only 14 days after application of NPWT, ⁴ which cannot support the significance of the VEGF's role in early angiogenesis. Furthermore, although statistically significant increase in vascular density was observed as early as three days after NPWT application,^5,6 this significance may fade with time.^6,7

These discrepancies could be explained by combined effects of mechanical events during NPWT (as well as of differences in clinical and experimental situations). NPWT is in fact positive pressure wound therapy ⁸ with active drainage, which greatly improves contact between wound surfaces and thus conditions for naturally occurring revascularization. Within exudate-free tight tissue-to-tissue interfaces one may find higher than normal vascular densities. Also, the draining and extracellular edema-reducing action of NPWT may be responsible for increased concentrations of angiogenic factors. On the other hand, effects of natural fluid resorption with time may become comparable to those of draining by NPWT, which may influence experimental results.

Relevantly, compression by bandage has been used to reduce flap edema without compromising flap survival, ⁹ which echoes similar results achieved with NPWT.^10–15 However, excessive positive pressure can jeopardize circulation. ¹⁶ Furthermore, the magnitude of NPWT-generated positive pressure may depend not only on suction pressure but also on the size of the occlusive filler dressing. ⁸ Salvaging effect of NPWT may also depend on the relative size of the surface-to-surface contact area, which is mostly smaller in finger replantation than in flap surgery.

Numerous research has shown angiogenic effects of physiological drop in shear stress, in particular during reduction of blood flow. ¹⁷ There are also studies that imply that increased mechanical load in pathophysiological conditions may either block or promote angiogenesis depending on the magnitude of the load. ¹⁸ However, it is unlikely that the latter phenomenon, if at all inducible by NPWT, could be sufficient to salvage flaps of considerable size because of quick detrimental effects of ischemia. Notably, significant drop in tissue oxygenation due to application of standard NPWT has been shown in healthy voluteers. ¹⁹ As suggested by the authors of the latter article, while physiologic ischemia may stimulate neovascularization, this may not be the case in conditions with compromised perfusion. This notion may be particularly true in failing microvascular transplantation and replantation.

The fairly know physiological time sequence of neovascularization may indicate limits of wound healing enhancement. Revascularization of skin grafts by inosculation occurs within 48 h. ²⁰ Spontaneous by-pass bridging angiogenesis between vein stumps via minuscule neo-vessels of about 100 microns in diameter has been observed as early as three days after vein transection. ²¹ Similar findings have been reported by another study, which also found that larger vessels (300–400 microns in diameter) reanastomose at three weeks. ²²

Thus, the early beneficial effects of NPWT may not be due to new phenomena, but rather due to improvement of conditions for physiological wound healing. This supposition could stimulate relevant experimental and clinical research.