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MODE OF ACTION

JCN supplement

2015,Vol 29, No 5

7

MODE OF ACTION

To date, knowledge of the mechanisms

of action of NPWT has largely been

gained from animal and laboratory

studies and there appears to be no

single mechanism responsible for the

clinical benefits seen. NPWT’s mode

of action can be summarised as:

Micro- and macromechanical

deformation of tissue

Changes in blood flow patterns

Removal of fluid and reduction

in oedema

Wound homeostasis (prevention

of desiccation, minimises

contamination).

Tissue deformation

The beneficial effects of NPWT on

wound healing are thought to depend

on the delivery of mechanical forces

(often termed macromechanical and

micromechanical forces) to the tissue.

The notable contraction of

wounds upon application of NPWT

demonstrates the macromechanical

force or tension that is being applied

to the tissue under vacuum. It is

thought that the application of tension

upon the tissue edges‘stretches’the

tissue and stimulates cells to undergo

increased proliferation and matrix

production, resulting in the growth

of new skin tissue (granulation and

epithelialisation) (Saxena et al, 2004).

Interestingly, in studies of tissue

contraction in animals where NPWT

was removed 48–72 hours after

application, wounds did not revert

back to their original size. This

demonstrates a degree of permanency

reduction of between 15–32% in

wound volume per week (Campbell

et al, 2008; Bondokji et al, 2011;

Dorafshar et al, 2012).

Blood flow changes

Despite being one of the most widely

studied effects of NPWT, tissue

perfusion remains a subject of intense

debate. Spanning almost 20 years of

research, experimental studies have

shown that NPWT results in both

an increase and decrease in tissue

perfusion, which very much depends

on the method of detection used

in the study, location and pressure

levels being applied. This area of

research has mostly been limited

to experimental studies with little

clinical evidence owing to the invasive

procedures involved in attempting to

measure local tissue perfusion.

Morykwas et al (1997) were the

first to report changes in blood flow

associated with NPWT. Using laser

Doppler flowmetry in a pig wound

model, it was shown that periwound

blood flow increased upon the

application of NPWT. Subsequent

studies have shown that NPWT

causes an immediate increase in blood

flow in the periwound area (2cm from

the wound edge); whereas blood flow

at the wound edge is reduced, creating

a‘zone of hypoperfusion’(Wackenfors

et al, 2004).

This reduction in blood flow

observed at the wound edge is most

likely due to the compression caused

by the wound filler material pressing

against the surface of the wound. It is

not known whether wounds progress

because of, or despite this zone of

hypoperfusion. One theory is that the

subsequent hypoxic environment is

a potent stimulator for angiogenesis,

which is also a key precursor to

granulation tissue formation (Malsiner

et al, 2013).

Removal of fluid and oedema

Wound exudate, particularly that

seen in chronic wounds, can contain

elevated levels of inhibitory factors

such as proteases and inflammatory

mediators that impair wound healing

and keep the wound in a stalled state

(Schultz et al, 2003). By removing

excess fluid and reducing tissue

oedema, the wound is more likely to

in the contraction effect and supports

the hypothesis that NPWT contributes

to increased cell and matrix

production (Malmsjö et al, 2012).

Perhaps the most notable of all

NPWT’s effects is the stimulation of

tissue granulation and a dramatic

improvement in the appearance

of the wound bed. This relatively

rapid phenomenon is the result of

microscopic interactions between

tissue and wound dressing

materials placed under vacuum.

The combination of both negative

and positive pressures creates

micro-deformation of tissue and the

resultant strain generates increased

responsiveness to growth factors,

cell proliferation, production of

extracellular matrix and angiogenesis

(formation of new blood vessels)

(Wilkes et al, 2009).

Numerous animal studies

have recreated the stimulation of

granulation tissue in open wounds

using a variety of wound fillers and

pressure levels (Morykwas et al,

1997; Malmsjö et al, 2012), while

histological analysis of clinical biopsies

following NPWT clearly shows a more

angiogenic environment (Malsiner et

al, 2013; Fraccalvieri et al, 2014).

It is the combination of these

macro- and microdeformations

(wound contraction and filling of

tissue defects with new granulation

tissue) that ultimately leads to the

visible reduction in wound area

and wound depth. Rate of volume

reduction varies by wound type,

but clinical studies demonstrate a

Table 1:

NPWT benefits

Wound

Promotion of granulation tissue

Improvement in blood flow

~ increased delivery of oxygen and nutrients

Control of exudate

~ decreased wound oedema and congestion

~ improved wound environment

Reduced risk of infection

Patient and carer

Greater patient comfort:

~ better management of exudate

~ reduced frequency of dressing changes

~ reduced wound odour

~ increased mobilisation

Reduction in wound area and depth

Reduced overall treatment costs