First experiences with negative pressure wound therapy and instillation in the treatment of infected orthopaedic implants: a clinical observational study.
ABSTRACT Infections associated with orthopaedic implants remain a serious complication. The main objective in acute infection control is component retention, whereas this option is usually not considered for chronic infections.
This multi-centre prospective, non-randomised observational study investigated one possible treatment option for implant retention in combination with negative pressure wound therapy with instillation (NPWTi). Thirty-two patients with an infected orthopaedic implant were analysed. Twenty-two patients had an acute infection (< 8 weeks after implantation) and ten patients had a chronic infection (> 8 weeks and < 36 weeks after implant placement). Polyhexanide was used as the instillation solution in 31 of the 32 cases.
Nineteen patients (86.4%) with an acute infection and eight patients (80%) with a chronic infection retained their implant at 4-6 months follow-up after treatment.
Our study showed that NPWTi can be used as adjunctive therapy for salvage of acutely infected orthopaedic implants and may even be considered for early chronically infected implants.
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ABSTRACT: Negative pressure wound therapy with instillation (NPWTi) is increasingly utilized as an adjunct therapy for a wide variety of wounds. Despite its growing popularity, there is a paucity of evidence and lack of guidance to provide effective use of this therapy. A panel of experts was convened to provide guidance regarding the appropriate use of NPWTi. This included a face-to face meeting where the available evidence was discussed as well as individual clinical experience with this therapy was shared. Follow-up communication amongst the panelists continued until consensus was achieved. The final consensus recommendations were derived through >80% agreement amongst the panelists. Nine consensus statements were generated that address the appropriate use of NPWTi. The question of clinical effectiveness of NPWTi was not directly addressed by this consensus panel. This document serves as preliminary guidelines until more robust evidence emerges that will support or modify these consensus recommendations. Therapeutic, V.Plastic and reconstructive surgery 09/2013; · 2.74 Impact Factor
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ABSTRACT: Infections of contaminated or colonised acute or chronic wounds remain a grave risk for patients even today. Despite modern surgical debridement concepts and antibiotics, a great need exists for new therapies in wound management. Since the late 1990s, advantageous effects of negative pressure wound therapy (NPWT) have been combined with local antiseptic wound cleansing in the development of NPWT with instillation (NPWTi). This article summarises the current scientific knowledge on this topic. MEDLINE literature searches were performed on the subject of negative pressure wound and instillation therapy covering publications from the years 1990 to 2013 (36 peer-reviewed citations) and regarding randomised controlled trials (RCTs) covering wound care with bone involvement (27 publications) or soft-tissue wounds without bone participation (11 publications) from 2005 to 2012. The use of NPWTi in the therapy of infected wounds appears to be not yet widespread, and literature is poor and inhomogeneous. However, some reports indicate an outstanding benefit of NPWTi for patients, using antiseptics such as polyhexanide (concentration 0·005-0·04%) and acetic acid (concentration 0·25-1%) in acute and chronic infected wounds and povidone-iodine (10% solution) as prophylaxis in contaminated wounds with potential viral infection. Soaking times are recommended to be 20 minutes each, using cycle frequencies of four to eight cycles per day. Additionally, the prophylactic use of NPWTi with these substances can be recommended in contaminated wounds that cannot be closed primarily with surgical means. Although first recommendations may be given currently, there is a great need for RCTs and multicentre studies to define evidence-based guidelines for an easier approach to reach the decision on how to use NPWTi.International Wound Journal 12/2013; 10(s1):32-42. · 1.60 Impact Factor
- Journal of wound care. 10/2012; 21(Sup10):S11-S15.
First experiences with negative pressure wound therapy
and instillation in the treatment of infected orthopaedic
implants: a clinical observational study
Burkhard Lehner & Wim Fleischmann & Rolf Becker &
Gerrolt N. Jukema
Received: 19 January 2011 /Accepted: 27 April 2011 /Published online: 17 May 2011
# Springer-Verlag 2011
Purpose Infections associated with orthopaedic implants
remain a serious complication. The main objective in acute
infection control is component retention, whereas this
option is usually not considered for chronic infections.
Methods This multi-centre prospective, non-randomised
observational study investigated one possible treatment
option for implant retention in combination with negative
pressure wound therapy with instillation (NPWTi). Thirty-
two patients with an infected orthopaedic implant were
analysed. Twenty-two patients had an acute infection (<
8 weeks after implantation) and ten patients had a chronic
infection (> 8 weeks and < 36 weeks after implant
placement). Polyhexanide was used as the instillation
solution in 31 of the 32 cases.
Results Nineteen patients (86.4%) with an acute infection
and eight patients (80%) with a chronic infection retained
their implant at 4–6 months follow-up after treatment.
Conclusions Our study showed that NPWTi can be used as
adjunctive therapy for salvage of acutely infected orthopaedic
implants and may even be considered for early chronically
Infections associated with orthopaedic implants (OI) such as
hip and knee prostheses often results in serious disability of
the patients. The number of total hip and knee replacements
has increased over the years, leading to an overall increased
number of associated infections. The incidence of infected
primarytotal hiparthroplasty(THA)ortotal kneearthroplasty
(TKA) is 1.5–2.5%. Revision THA or TKA carries a
respective infection risk of 3.2–5.6% and up to 15% in
mega-implants . The estimated cost of treating an
infected arthroplasty is over US $50,000 per episode [1,
17]. The major clinical objective in treating an infected OI
without signs of loosening is eradication of the infection with
retention of the implant since exchange revision surgery may
be associated with serious complications, such as bone loss,
impaired function of the joint and restricted patient mobility.
In most cases, infections associated with OIs are difficult to
manage and require a longer period of systemic antibiotic
therapy and often-repeated surgical procedures [15, 23, 26].
The four commonly used surgical interventions for
treatment of an infected joint prosthesis are (1) debridement
plusretentionofthe prosthesis(with orwithout temporary use
of antibiotic-loaded bead chains) [2, 14], (2) one-stage
replacement , (3) two-stage replacement [21, 28] and
(4) removal of the infected implant without replacement .
Surgical debridement in combination with systemic
antibiotic therapy is the preferred approach because this
option allows for retention of the prosthesis and can be
B. Lehner (*)
Department of Orthopedic Oncology and Septic Orthopedic
Surgery, Orthopedic University Hospital,
Schlierbacher Landstrasse 200a,
69118 Heidelberg, Germany
Department of Trauma and Reconstructive Surgery,
Ludwigsburg-Bietigheim Kliniken gGmbH,
G. N. Jukema
Department of Trauma Surgery, University Hospital of Zurich,
International Orthopaedics (SICOT) (2011) 35:1415–1420
successful in patients with early postoperative or early
diagnosed late haematogenous infection of well-fixed THA/
TKA . Surgeons have reported success rates between
30 and 80% with surgical debridement and retention of the
implant . A variation on the method of debridement plus
retention of the prosthesis is suction irrigation drainage,
which has a reported success rate of up to 60% .
The one-stage replacement approach is more likely to be
successful when the microorganism in the wound is known
and the implant usually has to be inserted with cement.
The two-stage replacement approachis themostcommonly
used therapy for chronic prosthetic joint infection. It involves
removal of the infected implant, placement of an antimicrobial
carrier and placement of a new joint prosthesis after at least
6 weeks. This approach is believed to result in infection
eradication in up to 90% of cases, thus preserving the function
of the joint [3, 11, 20]. However, the two-stage procedure is
expensive and may result in large skeletal defects, increased
hospitalisations and costs, severe functional impairment with
delayed mobility, and sometimes death .
Removal of the infected implant without replacement
 is directly associated with significantly impaired
function of the extremity. This option is only used when
no other treatment options are available.
The treatment of wound infections by combining
negative pressure wound therapy with instillation (NPWTi)
was first described by Fleischmann et al. in 1998 . In
2009, Timmers et al. reported successful results from the
first use of NPWTi to treat post-traumatic osteomyelitis
. Our study was designed as a next step to collect
clinical outcome information on patients with infected OIs
that were treated with NPWTi using V.A.C. Instill® Wound
Therapy (KCI USA, Inc., San Antonio, TX, USA).
This study was designed as a prospective, multi-centre,
single-arm, post-market, observational study. The study
protocol was reviewed and approved by the applicable
Ethics Committees, and informed consent was obtained for
all patients. The main inclusion criteria were infection of an
OI (knee, hip, other osteosynthesis material) occurring
within 8 weeks after implant or infection older than 8 weeks
of “stable” OI if NPWTi could be used as first-line adjunct
treatment after adequate debridement. The main exclusion
criteria were multiple organ failure or high risk for
developing multiple organ failure, fistulas in the area of
the wound, malignancy in the wound and/or medication
The primary efficacy endpoint was percentage of implant
retention without infection at follow-up (4–6 months after
start of treatment with NPWTi) for patients with an acutely
infected OI. Acute infection was defined as infection
occurring within 8 weeks of implant placement, whereas
chronic infection was defined as infection occurring any
time after 8 weeks of implant placement. The secondary
endpoints were percentage of implant retention for patients
with a chronic infection, incidence of treatment-related
adverse events (AEs) and incidence of infection recurrence.
Additional criteria that were evaluated included duration of
NPWTi, duration of clinical signs of infection and length of
hospital stay. Safety assessments were conducted throughout
the observational study.
NPWTi allows for a combination of NPWT with timed,
intermittent delivery of topical solutions. The NPWTi therapy
unit has an additional instillation tube that connects the
dressing with an infusion bag containing the solution.
Separate vacuum and instillation clamps open and close at
set intervals, allowing for automated delivery of the solution
incubation (hold phase), and resumption of negative pressure
toextractthe solutionfromthe woundbedanddressingandto
apply NPWT to the wound (vacuum phase). The three phases
together are called a cycle.
In this study, treatment with NPWTi varied on a patient-
by-patient basis. The decision regarding which agent or
solution to use was at the discretion of the treating surgeon
as long as the solution used was compatible with the
dressings and NPWTi system.
The sample size was based on clinical and practical
considerationsandnotonformal statisticalpower calculations.
Patients who had no follow-up information, were withdrawn
by an investigator or received “off-label” treatment (which did
notfollowthe manufacturer’s guidelinesforappropriate useof
NPWTi) were omitted from the analysis.
Continuous patient characteristics were summarised using
descriptivestatistics(n, mean, median and standard deviation).
Categorical patient characteristics were summarised as
proportions. Statistical comparisons for continuous data
were conducted using the Wilcoxon rank sum test, which
is based on ranks of the data and was used to compare
location parameters (such as the median between OI
retained groups vs OI not-retained groups) without the
assumption of normally distributed data. Statistical
comparisons for categorical data or proportions were
conducted using either Fisher’s exact test or a binomial
test, based on the 5% significance level. All statistical
analyses were performed using SAS® version 9.1.3.
Forty-two patients from eight centres in Germany, The
Netherlands and the UK were enrolled in the study (Fig. 1).
Four patients did not meet the inclusion criteria (OI
1416International Orthopaedics (SICOT) (2011) 35:1415–1420
explanted prior to NPWTi) and were excluded from the
analysis because retention of the OI at follow-up could not
be analysed. One patient was lost to follow-up, one patient
was discontinued by the investigator and four patients
received off-label treatment and were omitted from the
analysis. This left 32 patients from which data were
analysed. Of 32 patients, 20 (62.5%) had an infected hip
implant, 10 (31.3%) an infected knee implant and 2 (6.2%)
infected osteosynthesis material (acetabulum fixation device,
metal plate upper arm). Of 32 patients, 22 (68.7%) had an
acute infection and 10 (31.3%) a chronic infection. Table 1
shows an overview of the patient characteristics.
Treatment consisted of surgical debridement of the
wound in combination with lavage, systemic antibiotic
therapy and NPWTi. In 25 of 32 (78.1%) cases, debridement
of the wound was documented, and in all cases (100%)
lavage was performed (jet lavage (4/32, 12.5%) with
polyhexamethylene biguanide 0.04% solution (polyhexanide
or PHMB, B. Braun Melsungen AG, Melsungen,
Germany) (16/32, 50.0%), Ringer’s solution (1/32, 3.1%),
povidone-iodine (9/32, 28.1%) or octenidine dihydrochloride
(Octenisept, Schülke & Mayr, Norderstedt, Germany)
Prior to NPWTi, all wounds (39/39, 100%) were
clinically infected. Infection was defined as: presence of
at least one of the following: positive culture, abnormally
elevated C-reactive protein/white blood cell count and in
addition clinical signs, such as exudating wound, redness,
swelling or pain. Positive cultures were obtained from 28 of
32 patients (87.5%) (Table 2). Typical microorganisms
were present prior to NPWTi, and 8 of 32 cases had more
than one type of microorganism present (Table 2). No
multi-resistant microorganisms were discovered. Systemic
antibiotic treatment depended on the microorganism(s)
present in the wound and was administered per institutional
standards. Generally, antibiotic treatment was given for
6 weeks after termination of NPWTi.
Thirty-two patients had a mean of 11.8 days (median
6.0 days, range 1.0–109.0 days) between diagnosis of
infection and start of NPWTi. The results showed that the
The analysis of the primary endpoint, implant retention at
follow-up,issummarisedinTable3. The mean time of follow-
up was 176 days (median 164 days, range 57–490 days).
Overall findings showed that 27 of 32 patients (84.4%)
retained their implant (Table 3): 19 of 22 patients (86.4%)
with an acute infection (< 8 weeks) and 8 of 10 patients (80%)
with a chronic infection (>8 weeks and <36 weeks). Statistical
comparisons between the groups (retained vs not-retained
OIs) showed no statistical significance in sex, risk factors,
race, OIs and acute or chronic infection (p>0.05).
For acutely infected OIs, assuming an average retention
rate of 65% based on published data [4, 5, 15, 19], there
Assessed for Eligibility (n=42)
Lost to follow-up (n=1)
Discontinued intervention (n=1)
Patient withdrawn due to age and
Excluded from analysis (n=4)
Received “off-label” treatment (n=4)
Patients Excluded (n=4)
-Did not meet inclusion criteria
Allocated to intervention (n=38)
Received allocated intervention (n=38)
Did not receive allocated intervention (n=0)
Fig. 1 CONSORT Statement 2010 flow diagram
Table 1 Patient characteristics
BMI body mass index
International Orthopaedics (SICOT) (2011) 35:1415–14201417
was a significant difference between patients who retained
their implant versus those patients who did not retain their
implant (i.e. 86.4 and 13.6%, respectively, p=0.036).
Likewise, for chronically infected OIs, assuming an average
retention rate of 30% [4, 7, 18], there was a significant
difference between patients who retained their implant
versus those patients who did not retain their implant (i.e.
80 vs 20%, respectively, p=0.001). When considering
overall implant retention (acutely and chronically infected
OIs), and assuming an average retention rate of 50% [4, 5,
7, 15, 18, 19], a significant difference was detected between
patients who retained their implant versus patients who
did not retain their implant (84.4 vs 15.6%, respectively,
The mean duration of NPWTi was 16.3 days (median
15.0 days, range 9–46, p=0.486). Reasons to discontinue
treatment were local negative bacterial culture (25/32,
78.1%) as per institutional procedure and clinical judgment
of the surgeon (6/32, 18.7%). One case was not documented.
PHMB was used in 31 of 32 (96.9%) cases (concentrations
0.04–0.2%); in 1 case (3.1%), saline was used. The mean
NPWTi negative pressure setting was 138.3 mmHg (median
125 mmHg, range 125–200 mmHg). Instillation time was in
all cases <1 min. The mean hold time was 19 min (median
20.0, range 5–30 min), and the mean vacuum time was
70.3 min (median 60.0, range: 30–270 min). A mean of 16.5
cycles (instillation+hold+vacuum) per day were applied
(median 18.0 cycles, range 5–40 cycles per day).
Recurrence of infection was monitored by the investigator
or general practitioner through regular wound checks as per
institutional standard. In cases of wound problems such as
pain, swelling, redness, discharge or systemic signs of
infection patients were required to return to the hospital for
clinical control to confirm recurrence of infection. Infection
eradication was reported in24 of 32 patients (75%).In 6 of 32
patients (18.8%) recurrence of infection was reported and 2 of
32 patients (6.2%) had an ongoing infection. In 3 of 32
patients (9.4%), where recurrence of infection was diagnosed,
No. of patients with polymicrobial woundsNo. of patientsNo. of wounds with microorganism
No microorganisms present in the wound
One microorganism in the wound
Two microorganisms in the wound
Three microorganisms in the wound
Four microorganisms in the wound
Microorganisms present prior to NPWTi (n=39)
Not retained Retained Overall (not
Staphylococci (aureus, epidermidis)
Anaerobic Gram-negative rod
Negative bacterial strain
Table 2 Microorganisms
present in wound prior
n=32Acutely infected OI (n=22)Chronically infected OI (n=10)
RetainedNot retainedRetainedNot retained
Published retention dataa
65% [4, 5, 15, 19]
35% [4, 5, 15, 19]
30% [4, 7, 18]
70% [4, 7, 18]
Table 3 Retention of acutely
and chronically infected OIs
aAverage of published results
for patients with infected OIs
who were treated without
1418International Orthopaedics (SICOT) (2011) 35:1415–1420
the surgeons decided to perform a second treatment with
NPWTi and were thereafter able to eradicate the infection and
retain the implant.
Thirty patients (93.8%) had a mean duration of clinical
signs of infection of 27.3 days (median 20.5 days, range
10–125 days). Duration of clinical signs of infection was
defined as the date that the infection was diagnosed until
For all 32 patients evaluated, the mean number of
dressing changes was 3.5 (median 4.0 dressing changes,
range 1–8 dressing changes). The mean hospital stay was
39.5 days (median 35 days, range 12–97 days).
The influence of known major risk factors was not
significant. Four of six patients with diabetes were able to
retain their implant (p=0.228), as did all eight patients who
were smokers or had a history of smoking (p=1.0).
Safety analyses were described by the secondary
endpoints: incidence of treatment-related complications
and device complaints. Of 32 patients, 12 (37.5%)
experienced a total of 17 AEs; however, none of the AEs
were treatment or device related. One patient (3.1%) died
prior to follow-up due to age and condition. In two
instances, device problems were reported (not able to reset
alarm), and the systems had to be replaced.
This post-market, non-randomised, observational study
sought to provide insight into disease course and treatment
outcomes of patients with infected OIs who were treated
with NPWTi. NPWTi provides an automated, repetitive
lavage of the infected area. Historical data from the clinical
literature indicate an average retention rate of 65% [4, 5,
15, 19] in patients with an acutely infected OI not treated
with NPWTi. The results from this observational study
seem to confirm or exceed retention rates reported in the
literature [8, 16] and suggest that NPWTi, in combination
with debridement and systemic antibiotic therapy, is an
effective adjunctive therapy in managing acutely infected
OIs. In this study, negative pressure settings of 125–
200 mmHg were applied. Timmers et al. showed in their
experimental randomised study that negative pressure
settings higher than 125 mmHg (international standard)
can be favourable to promote perfusion and reduce the risk
of recurrence of infection .
This treatment modality also seems to be effective for
treatment of chronically infected OIs. Retention rates of
approximately 30% have been published [4, 7, 18], whereas
in this study in 80% of the cases the OIs were retained. One
reason could be that in this study all patients were treated
within 36 weeks of implant placement, which is a relatively
early chronic infection.
Retention of chronically infected knee implants is
generally associated with a poor outcome , due to
problems with the critical soft tissue coverage. It was
interesting to note that five of seven (71.4%) chronically
infected knee implants were retained with the use of
NPWTi as adjunctive therapy. While this sample is much
too small to draw any conclusions, the results may warrant
This observational study has two limitations. The first
limitation is that this was a single-arm, prospective, non-
randomised, observational study with no control group.
Comparison to historical data is often difficult since
different criteria are being used and no simple one-to-one
comparison is possible. On the other hand, this study was
observational, and the cases reflect the “real-life” situations
found in the participating centres. Thus, these findings may
be valuable for other centres to compare their results to the
results of this observational study .
The second limitation is the short follow-up period (4–
6 months after treatment). Clinical experience shows that
recurrence of infection in acute wounds usually occurs
within this time frame. A longer follow-up period is
required to confirm retention of the OI over the long term.
Results of treatment of infected OIs with NPWTi are
similar and independent of the type of implant. However,
NPWTi is an adjunctive therapy and must be used in
combination with mechanical debridement and systemic
antibiotic therapy when used for treatment of infected OI.
Microorganisms that are usually difficult to eradicate with
retained implants, such as Enterococci and Staphylococcus
aureus/epidermidis, could be effectively treated with this
treatment modality .
All centres used the same antiseptic instillation solution
(PHMB) , except for one patient treated with saline.
More research is required with different concentrations and
other solutions, such as saline, antibiotics, etc., to find the
optimal solution for managing infection and allowing for
OI retention .
The advantages of NPWTi are that it is relatively easy to
use, has minimal side effects and is associated with
relatively short therapy duration and length of hospital stay.
The results from this observational study are promising and
suggest that NPWTi with PHMB may be effective as an
adjunctive therapy to manage infected OIs by removing
infectious materials and helping to retain the implant,
independent of the type of infection (i.e. acute or chronic)
or microorganism. The results exceed, or are similar to,
what has been reported in the literature without the use of
International Orthopaedics (SICOT) (2011) 35:1415–14201419