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ORIGINAL ARTICLE
Limb salvage procedure in immunocompromised patients
with therapy-resistant leg ulcers—The value of ultra-radical
debridement and instillation negative-pressure wound
therapy
Alexander Geierlehner | Raymund E. Horch | Wibke Müller-Seubert |
Andreas Arkudas | Ingo Ludolph
Department of Plastic and Hand Surgery,
Laboratory for Tissue Engineering and
Regenerative Medicine, University
Hospital Erlangen, Friedrich Alexander
University Erlangen-Nuernberg (FAU),
Erlangen, Germany
Correspondence
Dr. Alexander Geierlehner, MSc,
Department of Plastic and Hand Surgery,
Laboratory for Tissue Engineering and
Regenerative Medicine, University
Hospital Erlangen, Friedrich Alexander
University Erlangen-Nuernberg (FAU),
Krankenhausstrasse 12, Erlangen 91054,
Germany.
Email: alexander.geierlehner@uk-
erlangen.de
Abstract
The purpose of this study was to analyse the outcome of our established triple
treatment strategy in therapy-resistant deep-thickness chronic lower leg ulcers.
This limb salvage approach consists of ultra-radical surgical debridement, neg-
ative-pressure wound therapy (NPWT) with or without instillation, and split-
thickness skin grafting. Between March 2003 and December 2019, a total of 16
patients and 24 severe cases of lower leg ulcers were eligible for inclusion in
this highly selective population. A total of seven patients received immunosup-
pressive medication. Complete wound closure was achieved in 25% and almost
90% of included lower leg ulcer cases after 3 and 24 months of our triple treat-
ment strategy, respectively. The overall limb salvage rate was 100%. Bacterial
colonisation of these wounds was significantly reduced after multiple surgical
debridements and NPWT. Fasciotomy and radical removal of devitalised tissue
such as deep fascia, tendons, and muscles combined with NPWT showed
promising results in terms of the overall graft take rate. This treatment strategy
was considered as last resort for limb salvage in such a critically ill and immu-
nocompromised patient population. Surgeons should be aware of its efficacy
and consider the triple treatment strategy especially if no other limb salvage
option remains.
KEYWORDS
chronic leg ulcer, negative-pressure wound therapy, skin transplantation, ultra-radical
debridement
Received: 18 April 2020 Revised: 21 May 2020 Accepted: 25 May 2020
DOI: 10.1111/iwj.13428
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any
medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
© 2020 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.
Int Wound J. 2020;1–12. wileyonlinelibrary.com/journal/iwj 1
1|INTRODUCTION
Chronic leg ulcers (CLUs) can be defined as wounds that
persist longer than 6 weeks and show no healing ten-
dency after 3 months of treatment usually affecting lower
legs, ankles, and feet.
1
The most commonly affected pop-
ulation are multimorbid elderly with 0.6% to 3% of people
over 60 years and up to 5% of those aged over 80 years.
2,3
In order to predict the probability of lower limb amputa-
tion, Knighton et al classified chronic wounds according
to its severity, which depends on the depth of the defect.
4
Venous insufficiency as the dominating cause accounts
for approximately 50% of CLU cases. Wounds of mixed
venous-arterial aetiology account for 18% and wounds
related to arterial diseases such as arteriosclerotic occlu-
sion for about 15%. Other diseases such as vasculitis (5%),
exogenous factors (4%), and pyoderma gangrenosum (3%)
are less common causes.
5
Typical symptoms of CLU are
an increase in pain and a foul wound odour.
6
Commonly
known adverse sequelae such as a negative body image,
social distress, loss of productivity, health care, and per-
sonal costs result in an impaired quality of life.
7
The ultimate goal of CLU treatment is to hinder its
persistence, attain complete wound closure, and ulti-
mately prevent lower extremity amputation. This does
not only reduce socioeconomic burden but also helps to
improve patient's quality of life.
8
The complex pathophys-
iology of CLUs and its underlying cause usually requires
a detailed medical history, meticulous physical examina-
tion, clinical assessment, and further diagnostic evalua-
tion such as laboratory screenings, venography, and
duplex imaging.
6,9,10
Besides local therapy approaches
such as compression therapy, wound dressings, antisep-
tics, and topical drug application, the establishment of an
appropriate systemic therapy based on the underlying
disease remains crucial for its treatment success.
11
Sev-
eral local treatment modalities have evolved and been
successfully used in the course of the last few years.
12-19
A detailed description of emerging treatment strategies,
however, lies beyond the scope of this study.
Especially, patients suffering from deep-thickness
CLUs large in size and refractory to conservative treat-
ment have shown to benefit from surgical intervention.
20
This usually involves the debridement of devitalised,
necrotic tissue within the wound bed followed by wound
coverage using skin grafts or tissue transfer.
20,21
Negative-pressure wound therapy (NPWT), an inven-
tion of the late 20th century, has nowadays been broadly
used as temporary wound coverage acting as a successful
tool for wound bed preparation of many different
wound types. This includes but is not limited to acute,
chronic, infectious, and burn wounds.
22,23
The additional
application of intermittent fluid instillation such as nor-
mal saline, polyhexanide, povidone-iodine, or octenidine
dihydrochloride to the wound bed for a pre-defined time
period (dwell time) can have a sufficient micro-debride-
ment effect especially to infectious or contaminated
wounds.
24-26
Irrigation of the wound bed and the removal
of debris and pathogenic bacteria showed to reduce the
microbial film at the wound surface.
27,28
NPWT com-
bined with surgical debridement can help to reduce the
complexity of surgical wound coverage procedures ulti-
mately acting as salvage procedure for limbs at high risk
of amputation.
20,29
This retrospective study aims to analyse the success of
a surgical treatment approach as limb salvage procedure
of chronic lower leg ulcers in critically ill and immuno-
compromised patients. This includes ultra-radical surgi-
cal debridement of devitalized tissue, NPWT, and split-
thickness skin graft coverage of lower leg defects. The
triple treatment concept is believed to improve the
wound healing outcome of this highly selected patient
collective ultimately preventing the amputation of the
affected limb.
Key Messages
•the combination of ultra-radical debridement,
instillation negative-pressure wound therapy
(NPWT), and split-thickness skin graft (STSG)
showed promising results in terms of wound
healing and limb salvage
•the aim of this study was to assess wound
healing outcomes of our triple treatment strat-
egy in critically ill and immunocompromised
patients suffering from chronic therapy-resis-
tant lower leg ulcers at high risk of limb ampu-
tation. In addition, comparative evaluation of
wound colonisation before and after multiple
debridements and NPWT with or without
instillation was performed
•almost 90% of recurrent leg ulcerations resis-
tant to any previous therapy completely healed
2 years after our triple treatment strategy. The
limb salvage rate was 100% in patients with leg
ulcers classified as high risk for limb
amputation
•multiple ultra-radical surgical debridements
and instillation NPWT significantly reduced
bacterial wound colonisation
2GEIERLEHNER ET AL.
2|METHODS
In a retrospective mono-centre study, data including hos-
pital, operative, general practitioner (GP), and postopera-
tive wound management records were extracted and
documented from critically ill and immunocompromised
patients suffering from therapy-resistant CLUs. GPs and
wound managers were contacted by telephone if neces-
sary. Patients at high risk of lower limb amputation
receiving our triple treatment (ultra-radical surgical
debridement, NPWT with or without instillation [NPWT
(i-d)]), and split-thickness skin grafting (STSG)) were
included. Our hospital database was searched from
March 2003 to December 2019. All surgical procedures
were performed by experienced plastic surgeons. CLUs
persisting at least 3 months before hospital admission
with no healing tendency irrespective of its previous
treatment attempts were included. Wound severity was
determined by its soft tissue defect (grade 3 or higher,
according to Knighton et al
4
) extending over 75% of the
lower limb circumference. Ultra-radical surgical debride-
ment was defined as complete excision of devitalized,
infectious tissue with more than 75% of the lower limb
circumference. In addition, fasciotomy of affected com-
partments and fasciectomy of the deep fascial layer of the
lower limb was performed until only clean and vital tis-
sue remained. Devitalised tendons and muscles were
resected if necessary. Resection was extended into adja-
cent soft tissue with the aim to remove any calcified and
chronically indurated pathological tissue. At least three
surgical debridements prior to wound closure attempt
were required for study inclusion. The reticulated open-
pore polyurethane foam-surface negative-pressure wound
dressing (KCI—an Acelity company, San Antonio, Texas)
was changed during each surgical debridement. Wounds
treated with NPWT with or without instillation and dwell
time were included in this study. The nature of this long-
term study and the fact that our high-volume centre
started using NPWT with instillation and dwell time
(NPWT(i-d)) in 2014 made it inevitable to also include
immunocompromised patients solely treated with NPWT.
Polyhexanide (0.4 mg/1 mL) (Lavasept, B. Braun Medical
AG, Germany) was the antiseptic solution used for instil-
lation. All patients received standardised postoperative
care during and after hospital admission. NPWT(i-d) was
applied in a standardised fashion and was performed
until the fifth day after STSG. The negative pressure was
set to −125 mm Hg. However, in cases of pain during
NPWT(i-d), the pressure was reduced to −100 or
−75 mm Hg if necessary. The instillation volume was
adjusted according to the wound size and depth. Dwell
time was set to 20 minutes. Subsequently wound dress-
ings consisting of fat gauze, sterile dressings, and
compression bandages were applied and frequently chan-
ged until complete wound closure was attained. Low
molecular weight heparine was administered subcutane-
ously during the entire hospital stay preoperatively and
postoperatively once a day. Postoperative wound assess-
ments were performed on a regular basis at our outpa-
tient clinic especially during the first 3 months after
hospital discharge. The frequency of outpatient visits was
usually reduced after the first 3 months according to indi-
vidual wound conditions. Wounds were assessed by expe-
rienced surgeons. Images and notes were taken during
each outpatient visit. If necessary, dressing changes were
performed by wound managers or GPs on a regular basis
after hospital discharge. Cut-off values determining the
wound healing success were set at 3 and 24 months after
our triple treatment. Wound healing was defined as
epithelialisation of the wound bed after our triple treat-
ment was performed. Additional charts were reviewed
for bacterial colonisation of the included lower leg ulcers.
Data of the first and the last wound swab before wound
coverage with split-thickness skin graft were collected.
This allows an assessment of changes in the bacterial
load and flora after NPWT(i-d) and multiple surgical
debridements. Wound swabs were performed by the sur-
geon in charge in a standardised fashion before wound
disinfection and prior to surgical debridement. Wound
swabs were analysed for the number of different bacterial
species (NDB) and the amount of bacteria under culture
(AB) according to the local Institute for Clinical Microbi-
ology. Semi-quantitative examination of the AB gives a
rough estimate of the bacterial colonisation of a wound
on an ordinal scale
1-4
for each bacteria (1: sparse, 2: mod-
erate, 3: several, and 4: plenty). Because of the heteroge-
neity of the wounds and their bacterial colonisation, the
amount of all bacteria found in the wound was calculated
through summation of those semi-quantitative ordinal
scaled numbers of each bacteria.
28
All relevant data
according to the inclusion criteria were extracted, veri-
fied, and documented by two authors on a bespoke pre-
defined Excel sheet (Microsoft, Redmond, Washington).
The following data were collected for comparison:
1 Patient demographics (gender, age, relevant concomi-
tant diseases, wound location, wound duration, previ-
ous local treatments, immunosuppressive medication
(Table 1), and American Society of Anaesthesiologists
[ASA] score).
2 Leg ulcer characteristics (length of hospital stay, days
from initial ultra-radical debridement to STSG (Table
2), and number of blood product transfusions).
3 Leg ulcer outcomes (number of completely healed
ulcers after 3 and 24 months (Table 2), time to com-
plete wound healing).
GEIERLEHNER ET AL.3
TABLE 1 Patient characteristics
Patient
no.
Patient baseline
characteristics
Relevant concomitant
diseases
Immunosuppressive
medication Previous local treatments
Age (in
years) Gender
1 62 M PAD, sepsis, LV heart failure,
HTN, AS, lymphedema lower
legs, ARF
Wound antiseptics,
antimicrobial wound dressings
2 47 M PG, RA, high-grade left IAD,
HTN, nicotine abuse
Infliximab, methotrexate,
abatacept, prednisolone
Wound antiseptic, antimicrobial
wound dressings
3 50 F MCTD (sharp syndrome), PF,
HTN, AFL
Prednisolone Antimicrobial wound dressing,
wound disinfection, surgical
debridement, STSG
4 62 F CV Rituximab, mycophenolate
mofetil, prednisolone
Steroids
5 66 F PG, CVI, CHD, IC, HTN, ARF,
lymphedema
Mycophenolate mofetil,
prednisolone
Wound antiseptics,
antimicrobial wound dressing,
topical steroids
6 57 M VTE (DVT), CML, HTN Mycophenolate mofetil,
ciclosporine
Surgical debridement, negative
pressure therapy, STSG
7 62 M CVI, DM, HTN, obesity Surgical debridement, negative
pressure therapy, wound
antiseptic, antimicrobial
wound dressing, topical
steroids, compression therapy,
STSG
8 79 F CVI, PCV, HTN Hydroxycarbamide Surgical and biomechanical
debridement, negative
pressure therapy, wound
antiseptic, silicone wound
dressing, zinc
9 74 F PAD, varicosis, PNP,
lymphedema, HTN, CRF
Surgical and biomechanical
debridement, wound
antiseptics, polyurethane
wound dressings, compression
therapy
10 77 M PAD (Stage I), CHD, HTN Wound dressings
11 35 M VTE (SVT), lipedema (Stage III),
lymphedema (Stage III),
obesity
Antimicrobial wound dressings,
wound desinfection,
physiotherapy, lymphatic
drainage
12 39 M PTS, NF, lower leg phlegmon Compression therapy, surgical
debridement, negative
pressure therapy, STSG
13 64 F Bullous erysipelas, RA, HTN,
CRF, obesity
Methotrexate Antimicrobial wound dressings,
wound desinfection,
compression therapy, topical
steroids
14 64 M PAD (Stage II), CHD Surgical debridement, STSG,
antimicrobial wound dressing,
compression therapy
15 55 F PAD (Stage IV), DM, HTN,
CHD, obesity, cardiac valve
Wound antiseptics, topical
steroids
4GEIERLEHNER ET AL.
4 Bacterial load and flora (number of different bacteria,
amount of bacteria (Table 3), bacteria shift [gram +/−],
and multidrug resistant bacteria).
Our primary outcome measure was the number of
completely healed lower leg ulcers after 3 and 24 months.
Wound closure was classified into three different catego-
ries (A: complete wound closure, B: wound control [75%-
99% wound closure], and C: leg ulcerations with less than
75% wound closure which were recorded as failures). Sec-
ondary outcome measures included time to complete
wound healing within category A, change of bacterial
TABLE 1 (Continued)
Patient
no.
Patient baseline
characteristics
Relevant concomitant
diseases
Immunosuppressive
medication Previous local treatments
Age (in
years) Gender
replacement, left fore foot
amputation
16 78 F CVI, HTN, heart failure, CRF,
obesity
Wound antiseptics, antibiotics,
antimicrobial wound
dressings, compression
therapy, topical steroids
Abbreviations: AFL, atrial flutter; ARF, acute renal failure; AS, ankylosing spondylitis; B, both; CHD, chronic heart disease; CV,
cryoglobulinemic vasculitis; CVI, chronic venous insufficiency; DM, diabetes mellitus; F, female; HTN, hypertension; IAD, iliac artery dis-
ease; IC, ischemic cardiomyopathy; L, left; M, male; MCTD, mixed connective tissue disease; NF, necrotizing fasciitis; PAD, peripheral artery
disease; PCV, polycythemia vera; PF, pulmonary fibrosis; PG, pyoderma gangrenosum; PNP, polyneuropathy; R, right; RA, rheumatoid
arthritis; STSG, split-thickness skin graft; SVT, superficial vein thrombosis.
TABLE 2 Leg ulcer characteristics
Wound location Wound duration
Initial ultra-radical
debridement to STSG Hospital stay
Wound closure
after 3 months
Wound closure
after 24 months
Patient no. Lower legs
Categories A-C
in months in days in days Left leg Right leg Left leg Right leg
1 B 13 15 30 B B A A
2 L 25 12 19 B A
3 B 48 11 20 B B B A
4 B 192 13 27 B B A A
5 B 48 10 32 B A A A
6 R 16 43 50 A A
7 B 120 12 19 B B A A
8 B 36 12 23 C A C A
9R 3 13 21 B A
10 B 3 9 24 B A A A
11 B 10 11 23 B B A A
12 R 120 8 20 B A
13 L 5 12 19 B A
14 L 96 10 17 A A
15 R 60 21 29 C C
16 L 36 11 20 A A
Note: B = both, R = right, L = left. Categories (A-C)—A: complete wound closure; B: wound control (75%-99% wound closure); C: failed
wound closure (<75% wound closure).
GEIERLEHNER ET AL.5
load and flora of those chronic wounds during NPWT(i-d),
and surgical debridements. The time to complete wound
healing was measured from the day of STSG.
2.1 |Statistical analysis
Descriptive analyses were applied to characterise patient
demographics. Univariate analyses were performed using
Chi-squared and Fisher's exact tests for categorical vari-
ables and paired or unpaired Student's t-tests for continu-
ous normally distributed variables. Mann-Whitney-U and
the Kruskal-Wallis test were used for unpaired non-
normally distributed variables. The Wilcoxon signed rank
test was used for paired non-normally distributed vari-
ables. Statistical analyses were performed using Gra-
phPad Prism (GraphPad Software, Inc., California).
3|RESULTS
3.1 |Patient demographics
Between March 2003 and December 16, 2019,
multimorbid patients (8 female, 8 male) with a total of 24
severe cases of chronic, non-healing lower leg ulcers were
eligible for inclusion. All these wounds were unre-
sponsive to previous non-surgical and surgical treat-
ments. The age of this highly selected collection of
critically ill and immunocompromised patients at the
time of ultra-radical debridement ranged from 35 to
79 years (mean age 60.7 years). CLUs were either located
at both lower legs (n = 7), or solely at the right (n = 5) or
left (n = 4) lower leg. The median ulcer duration was
36 months (range 3-192 months) (Figure 1). The included
patients suffered from peripheral artery disease (n = 5),
chronic venous insufficiency (n = 4), venous thromboem-
bolism (n = 3), autoimmune diseases such as pyoderma
gangrenosum (n = 2), mixed connective tissue disease
(n = 1), ankylosing spondylitis (n = 1), and
cryoglobulinemic vasculitis (n = 1) with several concomi-
tant diseases such as myeloproliferative neoplasm
(n = 2), renal failure (n = 5), hypertension (n = 12), dia-
betes (n = 2), cardiac diseases (n = 7), lymphedema
(n = 4), and obesity (n = 5). A total of seven patients
received immunosuppressive medication before or during
hospital stay. All patients received several local treat-
ments such as wound antiseptics, antimicrobial wound
dressings, topical steroids, and antibiotics as well as the
application of compression garments prior to hospital
admission. A total of five patients received previous
unsuccessful wound closure attempts with STSG. All
TABLE 3 Change of bacterial colonisation of included leg ulcers during ultra-radical debridement and negative pressure wound therapy
Patient no.
Wound location Left leg Right leg
Lower legs First wound swab Last wound swab First wound swab Last wound swab
Left/right/both NDB AB NDB AB NDB AB NDB AB
1B 3103931039
2L 2700
3B 3121231213
4B 26371426
5 B 4 6 6 21 5 17 6 18
6R 2611
7B 3122651800
8R 3101431100
9R 27414
10 B 3 7 4 10 1 2
11 B 0 01 43 71 2
12 R 2 6 0 0
13 L 1 4 0 0
14 L 2 8 0 0
15 R 3 11 1 3
16 L 1 4 3 9
Abbreviations: AB, amount of bacteria; NDB, number of different bacteria.
6GEIERLEHNER ET AL.
patients received systemic antibiotics during and after
their hospital stay in accordance with the wound swab
results. A total of 12 patients and 19 leg ulcers were
treated with an additional instillation of the wound using
an antiseptic solution and only 4 patients received basic
NPWT. The median duration of NPWT with or without
instillation and dwell time (i-d) from the initial radical
debridement to STSG was 12 days with a range of 8 to
43 days. The median hospital stay was 22 days with a
range of 17 to 50 days. However, one specific case with a
hospital stay of 50 days and NPWT for 43 days addition-
ally suffered from chronic myeloid leukaemia. Therefore,
the patient was transferred to the Department of
Haematology and Oncology for bone marrow transplan-
tation between surgical treatments and during NPWT(i-
d). The median ASA score was 3. A total of six patients
(37.5%) received between two and six units of red blood
cells during their hospital stay.
3.2 |Wound healing outcomes
By 3 months, complete wound closure was achieved in
six leg ulcers (25%). The number of completely healed
wounds (Category A) increased to 21 leg ulcers (87.5%) in
15 patients (94%) 24 months after STSG (Figures 2 and
3). The average time to complete wound healing within
Category A was 6.9 months ranging from 2 to 20 months.
Wound control (Category B) was achieved in 11 patients
(69%) and 16 CLUs (67%) 3 months after STSG. By
24 months, the number of wounds under controlled
healing was reduced to one leg ulcer (4%) in one patient
(6%) (Category B). Wound closure with ultra-radical sur-
gical debridement, NPWT(i-d), and STSG failed in two
CLUs (8%) after 3 and 24 months (Category C). Two
patients required further surgical revision with surgical
debridements, NPWT(i-d) and STSG 7 and 14 months
after initial STSG. However, only one of these two
patients could achieve complete wound healing after
another triple treatment attempt. The other patient
received further local treatment modalities at other
departments. The total limb salvage rate of this critically
ill patient population was 100%.
3.3 |Bacterial load and flora
The average number of different bacterial species during
initial ultra-radical debridement was 2.6 NDB (1.2 SD)
ranging from 0 to 5 different bacteria. In 83.3% of the
lower leg ulcers, two or more different bacteria were
found whereas in 12.5% and in 4.2% of the cases, one and
FIGURE 2 Wound healing outcome of chronic leg ulcers in
percentage. Category A: completely healed ulcers; Category B:
wound control (75%-99% wound closure); Category C: failed wound
closure
FIGURE 1 Wound duration of included chronic lower leg
ulcers
FIGURE 3 Kaplan-Meier estimate of time to complete wound
healing
GEIERLEHNER ET AL.7
no bacteria was cultivated, respectively. At the time of
the last wound swab before STSG, the average number of
different bacterial species was reduced to an average of
1.7 NDB (1.8 SD) (P< .036) (Figure 4). The bacterial cul-
ture of the last wound swab showed two or more differ-
ent bacteria in 39.1% of the CLU cases. In 34.8% and
26.1% of the included cases, one and no bacteria was
found, respectively. The average amount of bacteria (AB)
at the time of the first wound swab was 8.6 (4.2 SD). The
last wound swab before STSG showed a significant reduc-
tion of 41% (P< .018) with an average bacteria amount
of 5.2 (5.9 SD) (Figure 4). The average NDB of the last
swab did not show any significant difference between leg
ulcers with complete wound closure (category A) and leg
ulcers in categories B and C after 3 months. The average
amount of bacteria of the last swab did also not signifi-
cantly differ between leg ulcers classified as category A
and leg ulcers classified as categories B and C after
3 months. There was no significant difference in the NDB
and AB in leg ulcers classified as category A after
24 months compared with leg ulcers classified as
Category B or C after 24 months. A shift of bacteria from
Gram-positive to Gram-negative or vice versa was not
observed. A total of four different patients had wounds
colonised with multidrug resistant bacteria during
NPWT (i-d).
4|DISCUSSION
CLUs were estimated at 1.51 per 1000 with a lifetime
prevalence of 10 per 1000 population.
30-32
Chronic
wounds in general are associated with exorbitant costs
for health care systems worldwide.
33-36
Total costs for
venous ulcer management including hospitalisation, out-
patient and emergency department visits, home health
care and prescribed drugs were estimated to be approxi-
mately 15 billion USD (United States dollar) in the
United States and 1.94 billion GBP (Great Britain
pounds) in the United Kingdom annually.
37,38
Treatment
costs for non-healing wounds were calculated to be
almost 2.5 times higher than those for healed wounds
within 1 year.
38,39
These numbers demonstrate the global
economic burden of CLUs and underlines the importance
of adequate wound care and complete wound closure at
an early stage.
40
Besides the economic standpoint, CLUs with its
adverse sequelae including the amputation of the limb
constitute a huge personal burden. The underlying prob-
lems causing CLUs are manifold and its treatment usu-
ally requires a multidisciplinary approach. The ultimate
goal of leg ulcer treatment is to preserve the affected
limb. This is known to reduce socioeconomic costs and
improve health-related quality of life.
8,41
Despite the
common consensus of limb preservation if any possible,
about 45 000 limb amputations are inevitably performed
as a result of non-healing chronic wounds in Germany
each year.
16
Various reconstructive wound closure
methods with different levels of complexity such as skin
grafting, local flaps, and free tissue transfer often remain
the only way to save the affected limb from an amputa-
tion.
42,43
Wound size, location, and severity as well as the
general health condition determines the choice of the
reconstructive surgery procedure for each individual
patient. Surgical debridement and NPWT are well-
established tools for wound bed preparation prior to defi-
nite wound closure.
22,44
NPWT has been successfully
applied to various complex non-healing wounds. NPWT
showed to reduce the complexity of the required surgical
procedure.
22,45
Surgical debridement is a fast and effec-
tive way of removing necrotic or infectious tissue in order
to restore the wound bed.
44,46
The extent of surgical
debridement is highly dependent on the severity of the
wound condition.
This study represents a clinical series of CLU patients
non-responsive to previous wound treatments, in a criti-
cal general health condition and at high risk of limb
amputation. Ultra-radical debridement, NPWT with or
without instillation, and STSG were considered as a last
resort for limb salvage. Any microvascular free tissue
transfer with or without arteriovenous extension was
considered unfeasible because of the poor general health
condition and vascular status of included patients.
47
CLUs especially those of a certain depth and circular con-
strictive tissue alterations are at risk of developing a
chronic compression syndrome of lower leg muscles.
Multifactorial processes, as in calciphylaxis can cause a
FIGURE 4 Wound swabs. Average number of different
bacteria (NDB) at the time of the first and last wound swabs.
Average amount of bacteria (AB) in chronic lower leg ulcers at the
time of the first and last wound swab (summation of bacteria load
1-4
of different bacteria) (* indicates significant difference.)
8GEIERLEHNER ET AL.
stiffened and tightened connective tissue of the crural fas-
cia.
48
Crural fasciotomy reduces the pressure within the
fascial compartments of the lower leg and has shown to
improve wound healing in CLU patients.
49
Therefore, the
severity of included wounds
4
made our ultra-radical
surgical debridement strategy inevitable. A total of five
patients in our study have a history of STSG. Previous
STSG failure in these patients was most likely caused
by insufficient surgical debridement. All patients with
previous STSG achieved complete wound healing in
this study. The ratio of the underlying diseases in this
highly selective study population roughly reflects
results of previously published epidemiologic stud-
ies.
2,3,6,32
Similar to other studies, vascular compromise
was the main contributor to CLUs in this case series.
All included patients received multiple local and sys-
temic treatment approaches over the course of several
months or even years. The fact that seven patients in
this study received immunosuppressive medication fur-
ther demonstrates their critical health condition. The
relatively long median wound duration of 36 months
corroborates the severity and personal burden of the
included cases.
This study illustrates the outcome of our triple treat-
ment approach (ultra-radical debridement, NPWT with
or without instillation, and STSG) in a patient population
refractory to multiple treatment approaches with limb
amputation as the only other treatment option remaining
(Figure 5). Complete wound closure of almost 90%, only
two surgical revisions (8%) and no limb amputation high-
lights its treatment success in such a highly selective
study population with no other limb salvage alternative.
Similar results were shown in previously published stud-
ies. Härmä et al reported on complete wound closure in
78% of the included patients and a wound failure rate of
12% after surgical debridement and split-thickness skin
graft. A total of four patients (10%) had small residual
ulcerations (similar to Category B in our study) after a
follow-up of 36 months. Authors claim that an insuffi-
cient radical debridement might be responsible for poor
wound healing outcomes. Reoperation was required to
achieve complete wound healing.
50
A histomorphological
examination of recurrent leg ulcers showed increasing
signs of dermatoliposclerosis such as extensive fibrosis at
the edges of the wound. Authors conclude that an aggres-
sive debridement of the affected tissue benefits CLU
healing.
51
Fasciotomy in addition to the removal of infec-
tious, devitalized tissue including the deep fascia, ten-
dons and muscles if necessary, is considered a crucial
step in our concept. In contrast, other remedies such as a
more superficial “ulcer shaving”approach led to an early
relapse of chronic venous leg ulcers and showed a poor
healing tendency of skin grafts.
51
A meta-analysis
reported on the outcome of diabetic, non-infected leg and
foot ulcers after a mean period of 2 years. A total of 86%
diabetic ulcers achieved complete wound closure. The
recurrence rate was 4.2% in this meta-analysis.
52
Diabetic
leg, foot, and ankle wounds had wound healing rates of
up to 70% after STSG in previously published case
series.
53,54
Rose et al, however, reported on a major limb
amputation rate of 6% in diabetic wounds.
54
This again
underlines the seriousness of the underlying pathology
with the ultimate goal of early wound healing and
limb salvage. The outcome following previous local non-
surgical and less radical surgical approaches remained
suboptimal among these critically ill and partly immuno-
compromised patients. Recurrent therapy-resistant com-
plex leg ulcerations of a certain wound size led to the
implementation of our triple treatment strategy. Results
of our study outline the success of this triple treatment
approach as a last resort for limb salvage in such a critical
patient population.
Computer-controlled topical NPWT showed to reduce
bacteria levels along with granulation tissue formation,
wound size reduction, improvement of local blood circu-
lation, and various improvements at cellular and
FIGURE 5 A, Chronic, therapy-
resistant circumferential lower leg ulcer
of a 47-year-old immunocompromised
patient. B, Wound at the lower leg after
ultra-radical debridement and negative
pressure wound therapy. C, Split-
thickness skin grafting (STSG) of the
lower leg defect. D, Wound healing
outcome 3 months after STSG
GEIERLEHNER ET AL.9
molecular levels.
22,55-58
This led to its application to vari-
ous different wound types over the course of the last few
decades.
22,59
Bacterial colonisation impairs leg ulcer
healing ultimately leading to its chronification.
60
Espe-
cially the presence of Pseudomonas aeruginosa negatively
affects wound healing and split-thickness skin graft
take.
61
The application of various antiseptic fluids to the
wound bed for a pre-defined time period (NPWT(i-d)) as
an adjunct to the basic NPWT device allows an additional
removal of debris, exudate and biofilm bacteria ulti-
mately favouring the wound healing process with or
without subsequent reconstruction measures.
25,62,63
Ludolph et al could significantly reduce bacterial coloni-
sation in complex CLUs after NPWT(i-d).
28
A compara-
tive evaluation of wound colonisation after NPWT versus
NPWT(i-d) was not performed because of the highly
selective small number of included cases. In our study,
the combination of NPWT irrespective of wound instilla-
tion and multiple radical debridements showed a reduced
bacterial load in CLUs. The additional administration of
systemic antibiotics might also have an impact on the
reduced bacterial load and the overall outcome in our
study population. The literature, however, still lacks evi-
dence to what extent each of those different interventions
individually influence bacterial wound colonisation. This
also lies beyond the scope of this study and probably
requires a larger sample size in the setting of a prospec-
tive study. Our study merely aims to analyse the success
of the triple treatment concept in this highly selective
immunocompromised patient population. However,
wound colonisation in terms of the amount of bacteria
and the number of different bacteria at the time of
wound closure did not differ between completely
healed (Category A) and incompletely healed leg ulcers
(Categories B and C). A total of three leg ulcers were
colonised with Pseudomonas aeruginosa at the time of
the last wound swab prior to STSG. Pseudomonas
colonised ulcers could not achieve complete wound
closure in 66% of the cases over the course of 2 years
after STSG. Additionally, both leg ulcers requiring sur-
gical revision in our study were colonised with Pseudo-
monas at the time of the last wound swab. This
reflects results of previous studies, claiming that the
reduction of bacterial load remains of utmost impor-
tance for the outcome of CLUs after STSG. In our cen-
tre, we routinely apply NPWT for the first 5 days after
STSG. This not only protects the wound from external
factors but also enables the removal of exudate and
stabilises the graft by reducing friction between the
graft and the wound bed. A meta-analysis showed
increased graft take and reduced reoperations rates
using NPWT after STSG compared with conventional
dressings.
64
The authors of this study are aware of its vulnerability
to a variety of biases because of its retrospective study
design. Robust methods, however, aimed to increase the
reliability of those results. Although our department is a
high-volume centre for reconstructive surgery, this study
only includes a relatively small number of cases. The low
number of included patients introduces the possibility of
participation bias. However, this was expected because
our criteria aim to include only very specific therapy-
resistant cases in a critically ill and immunocompromised
patient population. The authors were aware that wound
swabs as used in this study are limited by semi-quantita-
tive measurements. However, it most likely reflects the
entire bacterial flora across the wound bed and is proba-
bly the most common clinical way to assess bacterial
wound colonisation.
65
Tissue samples by contrast possess
the potential of exact volumetric quantitative assessment
of the bacterial load. This would require punch biopsies
of a pre-defined tissue size risking to expose or even dam-
age vital structures such as nerves or vessels. Tissue sam-
ples rather enable a selective assessment of a small
particular wound area. Because of an inhomogeneity of
bacteria colonisation across the wound bed, tissue sam-
ples usually fail to reflect the bacterial load of the entire
wound bed. Despite its limitations, this study shows
promising results of the triple treatment approach as a
final limb salvage procedure for a highly selective patient
population.
5|CONCLUSION
This study demonstrates the efficacy and safety of a surgi-
cal approach including ultra-radical debridement and
NPWT with or without instillation followed by split-
thickness skin graft in critically ill leg ulcer patients as an
effective limb salvage procedure. This work aims to
increase the awareness of its efficacy. Surgeons should
consider such a wound closure approach especially if no
other options remain and if there is a slight chance of
avoiding limb amputation.
CONFLICT OF INTEREST
R. E. H. has received third party funding for scientific
research on NPWT from KCI—an Acelity company in
the past and has served as a member of a Scientific Advi-
sory Board of KCI-Acelity in the past. R. E. H. and A. A.
served as speakers on scientific symposia of KCI-Acelity
in the past. The authors have no other relevant affilia-
tions or financial involvement with any organisation or
entity with a financial interest in or financial conflict
with the subject matter or materials discussed in the
manuscript apart from those disclosed.
10 GEIERLEHNER ET AL.
ORCID
Raymund E. Horch https://orcid.org/0000-0002-6561-
2353
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How to cite this article: Geierlehner A,
Horch RE, Müller-Seubert W, Arkudas A,
Ludolph I. Limb salvage procedure in
immunocompromised patients with therapy-
resistant leg ulcers—The value of ultra-radical
debridement and instillation negative-pressure
wound therapy. Int Wound J. 2020;1–12. https://
doi.org/10.1111/iwj.13428
12 GEIERLEHNER ET AL.
