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British Journal of Oral and Maxillofacial Surgery 60 (2022) 1005–1011

Systematic review
Effectiveness and safety of immediate application of negative
pressure wound therapy in head and neck free flap
reconstruction: a systematic review
Azmi Marouf a,⇑, Hatan Mortada b, Banan Khedr c, Lamis Halawani d, Subhi M.K. Zino Alarki e,
Hisham Alghamdi e
a
Department of Otolaryngology-Head & Neck Surgery, School of Medicine, Case Western Reserve University and University Hospital Cleveland Medical
Center, Cleveland, OH 44106, United States
b
Division of Plastic Surgery, Department of Surgery, King Saud University Medical City, King Saud University and Department of Plastic Surgery & Burn
unit, King Saud Medical City, Riyadh, Saudi Arabia
c
Division of Plastic Surgery, King Abdullah Bin Abdulaziz University Hospital, Princess Nora Bint Abdulrahman University, Riyadh, Saudi Arabia
d
Division of Otorhinolaryngology - Head and Neck Surgery, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
e
Division of Plastic Surgery, Department of Surgery, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia

Received 28 January 2022; revised 21 March 2022; accepted in revised form 9 April 2022
Available online 18 April 2022

Abstract

To our knowledge this is the first systematic review of the immediate application of negative pressure wound therapy (NPWT) to the head
and neck in free flap reconstruction. We conducted a systematic search of the PubMed and Cochrane databases in October 2021 using the
MeSH terms ‘negative pressure wound therapy’, ‘free flaps’, ‘microsurgery’, and ‘vacuum-assisted closure’. Included studies evaluated the
use of immediate NPWT in head and neck free flap reconstruction. Outcomes, indications, monitoring, and reported complications were
retrieved. Of the 908 articles searched, nine published between 2000 and 2021 were included: four retrospective studies and five case series.
NPWT was applied to 56 free flaps, and 54 had successful outcomes. The most common reported indication for flap reconstruction was
malignancy. NPWT has the potential to be a valuable tool for complicated wounds, and further studies are needed to quantify functional
and aesthetic outcomes.
Ó 2022 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Keywords: Free flap; Head and neck; Negative pressure wound therapy; VAC

Introduction to apply the repair to complex 3-dimensional (3D) structures

Seidenberg et al introduced head and neck free flap recon-
struction in 1959 using the jejunal free flap.1 Since then, free
flaps have become the most reliable and efficient method for
reconstruction of the head and neck after surgery for cancer
or trauma, particularly with the development of microvascu-
lar surgery,2–5 and they have several benefits. A variety of
flap options are available, and surgeons have the capacity
⇑ Corresponding author.
E-mail address: axm1676@case.edu (A. Marouf).
https://doi.org/10.1016/j.bjoms.2022.04.003
0266-4356/Ó 2022 The British Association of Oral and Maxillofacial
Surgeons. Published by Elsevier Ltd. All rights reserved.
such as the tongue.6 Nonetheless, complications may occur
in 5% - 25% of cases.7 In addition, patients who undergo free
flap reconstruction may need surgical exploration of the
flap,8 circulatory compromise being the most common rea-
son for reoperation and exploration.9
Negative pressure wound therapy (NPWT) in postopera-
tive care is increasingly being investigated to manage such
complications. It is known to improve circulatory perfusion,
reduce oedema, enhance tissue granulation, and minimise the
risk of soft tissue infection.10 It is also being used conven-
tionally to close and heal intractable open wounds.11 Multi-
ple previous studies have reported positive outcomes in
patients following free flap transfer where it has improved
and resolved tissue oedema and venous insufficiency,
avoided further flap necrosis, and promoted granulation,
which might be expected in areas where a free flap is
1006 A. Marouf et al. / British Journal of Oral and Maxillofacial Surgery 60 (2022) 1005–1011
placed.11,12 A retrospective study was conducted in individ-
uals who were treated by NPWT to help resolve free flap
congestion.11
Numerous studies have focused on the effectiveness of
NPWT on free flap viability, with a focus on reconstruction
of the lower extremities.13 In 2019, a systematic review was
published of 10 articles and 211 free flap procedures in
which the application time of NPWT ranged from five to
seven days postoperatively. The authors concluded that the
immediate application of NPWT did not appear to enhance
the likelihood of flap failure.14 Nonetheless, several concerns
have been raised about its immediate use on free flaps. Dif-
ficulties cited include the monitoring of flap visibility and the
potential for NPWT to obstruct recently anastomosed arter-
ies, resulting in ischaemic insult to the flap and flap
failure.15,16
This systematic review is, to our knowledge, the first to
provide a comprehensive overview of the literature on the
effectiveness and safety of the immediate application of
NPWT in head and neck free flap reconstruction. The authors
also aimed to investigate the most common indications for
immediate NPWT in head and neck free flap reconstruction.
Material and methods
Literature search
Cochrane review methods were used to design this study,
and the Preferred Reporting Items for Systematic Reviews
and Meta-Analyses (PRISMA) guidelines were followed to
conduct the systematic review.17 In October 2021, investiga-
tors systematically searched the PubMed and Cochrane data-
bases according to PRISMA guidelines for articles that
examined the role and effectiveness of the immediate appli-
cation of NPWT in head and neck free flap reconstruction.
The terms used in the search in the title, abstract, headings,
or keyword fields included various combinations, as follows:
(“Negative pressure wound therapy” OR “Negative pressure
therapy” OR “Negative pressure” OR “NPWT” OR
“Vacuum-assisted closure” OR “Vacuum-assisted closure
therapy” OR “VAC” OR “Vacuum-assisted dressing”)
AND (“free flap” OR “microsurgical free flap” OR “flaps”
OR “microvascular free flap” OR “free tissue transfer”).
Only papers published between January 2000 and October
2021 were included. Reference lists in the included papers
were hand searched for additional potential articles.
For this study, the authors used the International Prospec-
tive Register of Systematic Reviews (PROSPERO) (ID:
CRD42021251199). This research adheres to the principles
of the Helsinki Declaration. There was no need to obtain
ethics approval because of the nature of the study.
Study selection
Two reviewers (HM, SA) independently assessed the
retrieved articles by title and abstract, and relevant studies
were selected for complete review. The full text was
reviewed if the title and abstract did not provide enough
information. The inclusion criteria of this systematic review
were as follows: (1) Patients were male and female adults
(>18 years old), (2) studies appraised the application of
NPWT and immediate outcome after free flap reconstruction
of the head and neck, (3) complications and outcomes were
clearly stated, and (4) studies were in English. Studies were
excluded if they met any of the following criteria: (1)
included duplicate studies of the same patients that should
have been counted as one study, (2) were cadaver studies
or animal trials, or (3) were review articles, systematic
reviews and meta-analyses, letters, experimental studies, or
scientific conference abstracts.
Data extraction
Three authors (LH, AM, SA) independently extracted the
following information: author, country, design, sample size,
age of patients, year of publication, indications of flap trans-
fer and immediate use of NPWT, flap monitoring, reported
complications, and length of stay (LOS). If necessary, a
fourth investigator reviewed any issues that could not be
resolved.
Methodological quality assessment
Using the methodological index for non-randomised studies
(MINORS) checklist, two reviewers (SA, LH) independently
assessed the methodological quality of each of the retrospec-
tive studies.18 According to the MINORS criteria the maxi-
mum score for non-comparative studies is 16; for
comparative studies it is 24. An additional tool, the Joanna
Briggs Institute (JBI) score, was used to assess the quality
and risk of bias for the case series.19 Score disagreements
were addressed by discussion between the two reviewers.
Results
Literature findings
A total of 908 articles were found, including 874 from the
PubMed database and 82 from the Cochrane Library. The
study authors initially retrieved 36 full-text articles, but after
applying the exclusion criteria, only nine papers published
between 2000 and 2021 were included (Fig. 1). Searches
of the reference lists of the nine included articles found no
additional papers that met the criteria for inclusion and scope
of this review. Table 1, 12,15,20–26 summarises the features
and outcomes of all the included articles. There were four ret-
rospective studies and five case series; none of the studies
was controlled.
Risk of bias in studies
The first reviewer assessed (LH) the risk of bias using the
MINORS criteria while the second (SA) checked the assess-
ment. The average score of the two comparative studies was
 A. Marouf et al. / British Journal of Oral and Maxillofacial Surgery 60 (2022) 1005–1011
Fig. 1. PRISMA flow chart for the systematic review.
17.5 (range 17–18) (Table 2), and the average score of the
two non-comparative studies was 12.5 (range 12–13)
(Table 2). The remaining studies were case series. The JBI
scores ranged from five to eight (out of 10). Details of the
JBI appraisal items are shown in Table 3.
Results of individual studies
Table 1 summarises the findings from each study. Only data
for head and neck-related articles were retrieved, yielding a
total of 56 flaps (56 patients) that had undergone early flap
compression. All the articles reported NPWT beginning on
day one postoperatively. All free flaps were reported to be
successful with no flap failure or necrosis, except for one
patient in a case series by Henry et al15 who developed fail-
ure of graft uptake by 20% due to haematoma, and one (out
of 31 cases) reported by Lin et al12 who developed flap
necrosis.
In the nine articles, the most common indicator for flap
reconstruction was malignancy. Due to variations in the
reporting of complications, it was not possible to perform a
1007
meta-analysis to compare the differences in complications
between immediate NPWT and standard wound care
(SWC) groups, but all reported complications in each study
are included in Table 1. Studies that reported no complica-
tions clearly mentioned that their patients had developed
none during the follow-up period.
More than two-thirds of the cases included had NPWT
placed immediately to investigate the outcomes of this
method of wound care. It was also placed immediately after
reconstruction to manage a dead space, optimise the repair,
or because covering with a skin graft was not possible
(Table 4).
Discussion
NPWT has a well-established role in wound care. Nonethe-
less, its immediate use as part of the treatment plan for
patients undergoing flap transfer in head and neck surgery
has barely been addressed in the literature. In this systematic
review, we shed light on the efficacy of NPWT after free flap
transfer to the head and neck. Of the reviewed articles, only
1008 A. Marouf et al. / British Journal of Oral and Maxillofacial Surgery 60 (2022) 1005–1011

Table 1
Included studies reporting immediate application of negative pressure wound therapy (NPWT) in primary head and neck free flap reconstruction.
First author, No. of Method Indication of flap transfer Flap Doppler Outcomes
year, and patients monitoring
reference
Chang 202120 4 Retrospective Malignancy (n = 4) Not Complications: three patients had anastomotic leaks that were
mentioned managed conservatively
O’Malley 2020 2 Case series Malignancy (n = 2) Not No complications or flap failure
21
mentioned
12
Lin 2018 31 Retrospective Malignancy (n = 31) Not Complication: two patients (one developed chylothorax and the
mentioned other thromboembolic event).
Failure: one patient had flap necrosis
Bi 2018 22
5 Retrospective Unspecified (include Not No complications or flap failure
trauma, burn and mentioned
malignancy)
23
Asher 2014 5 Retrospective Malignancy (n = 5) Not Complications: two patients developed complications (one had
mentioned infection and one a leak, both had good overall outcomes)
Henry 2011 15, 1 Case series NA Yes Failure: failure of graft uptake by 20% due to haematoma
Kakarala 2011 24 2 Case report Malignancy (n = 2) Not No complications or flap failure
mentioned
Hanasono 2007 5 Case series Malignancy (n = 5) Yes No complications or flap failure
25

Rosenthal 2005 1 Case series Malignancy (n = 1) Not No complications or flap failure

26
mentioned

Table 2
MINORS instrument assessment for non-randomised studies (n = 4).
Item Chang et al20 Lin et al 12
Bi et al 22
Asher et al 23

A clearly stated aim 2 2 2 2

Inclusion of consecutive patients 1 1 2 2
Prospective collection of data 1 1 1 2
Endpoints appropriate to the aim of the study 2 2 2 2
Unbiased assessment of the study endpoint 0 0 0 0
Follow-up period appropriate to the aim of the study 2 2 2 2
Loss to follow up less than 5% 1 1 2 2
Prospective calculation of the study size 1 1 1 1
An adequate control group 2 2 - -
Contemporary groups 2 2 - -
Baseline equivalence of groups 2 2 - -
Adequate statistical analyses 2 1 - -
Total score 18/24 17/24 12/16 13/16

Table 3
Joanna Briggs Institute critical appraisal checklist for case series (n = 5).
Item O’Malley Henry et al Rosenthal Hanasono and Kakarala
et al 21 15
et al26 Skoracki 25 et al 24
Were there clear criteria for inclusion in the case series? Yes Yes Yes Yes No
Was the condition measured in a standard, reliable way for all Yes Yes Yes Yes Yes
participants included in the case series?
Were valid methods used for identification of the condition for all Yes Yes Yes Yes Yes
participants included in the case series?
Did the case series have consecutive inclusion of participants? Unclear Unclear Unclear Unclear Unclear
Did the case series have complete inclusion of participants? Unclear Unclear Unclear Unclear Unclear
Was there clear reporting of the demographics of the participants in Yes Yes Yes Yes Yes
the study?
Was there clear reporting of clinical information of the participants? Yes No Yes Yes Yes
Were the outcomes or follow-up results of cases clearly reported? Yes No Yes Yes Yes
Was there clear reporting of the presenting site(s)/clinic(s) No No Yes Yes No
demographic information?
Was statistical analysis appropriate? NA Yes Yes NA NA
Total “Yes” 6 5 8 7 5
NA: not applicable.
 A. Marouf et al. / British Journal of Oral and Maxillofacial Surgery 60 (2022) 1005–1011
Table 4
Reported indications for use of negative pressure wound therapy (NPWT) immediately postoperatively.
Indication
Cover exposed muscle that could not be covered with skin graft
Manage dead space
Secure graft firmly to the underlying bed and minimise mobility
Optimise pharyngocutaneous fistula flap repair
Assess reduction in length of stay and other outcomes
two reported failure or necrosis, one case in each, and others
reported none. All the studies included initiation of NPWT
on day one postoperatively.
Negative wound therapy was introduced by Morykwas
et al to expedite healing,27 and its use has been expanded
to include all types of wounds.28 Adjustable negative pres-
sure promotes wound healing by removing exudate and
decreasing interstitial oedema and bacterial load at the
wound site, and this increases tissue perfusion and promotes
the formation of a well-granulated wound bed.27,29 A study
by Eisenhardt et al revealed that NPWT reduced inflamma-
tory cell infiltration compared with controls, which then
reduced tissue oedema and damage.30
In this systematic review, we searched the literature for
studies that assessed the use of flaps in head and neck sur-
gery. Interestingly, with adequate follow-up periods reported
in most studies, only two of 56 flaps failed. One was in a 38-
year-old patient who had a latissimus flap applied to a large
scalp defect. The patient developed a haematoma and partial
graft loss after the application of NPWT, but his flap eventu-
ally survived.15 Many patients included in this review were
undergoing or had recently undergone chemotherapy and
radiation therapy, and many others had chronic diseases such
as diabetes and hypertension.12,23,25 Despite these comor-
bidities their flaps succeeded. Failure rates with NPWT in
upper and lower limb flaps are also low and similar to our
findings.14 Although we were not able to compare NPWT
and SWC in terms of complications and failure rates, those
reported with the immediate use of NPWT in this study do
not appear to be more than those in the control group in
the study by Lin et al,12 and in what is generally reported
in the literature.31,32
Flap Doppler monitoring, which was reported in a few
studies, has been shown to possibly improve salvage
rates.33,34 However, several difficulties associated with this
type of monitoring have been cited, especially when NPWT
is applied.16,34–36 To minimise the problems associated with
application of the Doppler probe, several authors have uti-
lised the implantable probe with minimal difficulties and a
high level of safety and efficacy.33,34 One report described
a method in which a small space was created within the foam
to allow monitoring.15 Another issue described was high
false positive rates associated with Doppler monitoring, but
most of the studies showing high false positive rates were
older, and more recent work has suggested much lower rates,
indicating that a learning curve is responsible for the
change.33
1009
No. of cases References
2 [24]
2 [21]
6 [15,25]
6 [23,26]
40 [12,20,22]
Current literature suggests that NPWT is applied only
when flaps fail or in complicated wounds.36,37 From our find-
ings, and in the absence of contraindications, the investiga-
tors can generally advise the use of NPWT immediately
after flap transfer to the head and neck. NPWT exerts pres-
sure on the muscle flap without injuring the anastomosis.30
It should not be applied, however, if it is in direct contact
with a nerve or a vessel, if cancer resection is incomplete,
or in cases of necrosis.36,37
To our knowledge, this is the first systematic review to
examine the safety and failure rates of NPWT in flap transfer
to the head and neck. Although the findings are promising, it
is important to mention several limitations. None of the
included studies were randomised, and meta-analysis was
not possible due to the limited number of studies and infor-
mation presented. Although the findings are encouraging,
and there are some reports indicating that NPWT may lower
the workload and overall costs, the cost of incorporating
NPWT into the patient’s treatment plan compared with that
of SWC was difficult to assess and is a matter to consider
before it is applied.12,38 The finding of no complications in
some studies should be viewed with caution, as some were
case reports or case series.
For head and neck wounds, NPWT appears to be gener-
ally safe and has a variety of uses.37 This systematic review
focused on its use with flap transfer to the head and neck. It
indicated promising results, even in large defects and previ-
ously irradiated wounds.
Conclusion
Immediate NPWT application appears to be effective and rel-
atively safe. However, to confirm these findings and assess
its safety on flaps with vascular impairment, randomised con-
trolled trials would help to quantify functional and aesthetic
outcomes.
Ethics statement/confirmation of patients' permission
Due to the nature of this study, the need for an ethical
approval was waived. Patients’ permission not applicable.
Funding acknowledgements
This research did not receive any specific grant from funding
agencies.
1010 A. Marouf et al. / British Journal of Oral and Maxillofacial Surgery 60 (2022) 1005–1011
Conflict of interest
We have no conflicts of interest.
Acknowledgement
The authors would like to thank Barbara Every of
BioMedical Editor for her help in editing the language of
this manuscript.
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