Short-term and long-term outcomes of intrathoracic vacuum therapy of empyema in debilitated patients
Sziklavari et al. Journal of Cardiothoracic Surgery
Short-term and long-term outcomes of intrathoracic vacuum therapy of empyema in debilitated patients
Zsolt Sziklavari 0
Christian Grosser 0
Tamas Szöke 0
Rudolf Schemm 0
Hans-Stefan Hofmann 0
0 Department of Thoracic Surgery, Krankenhaus Barmherzige Brüder Regensburg , Prüfeningerstraße 86, 93049 Regensburg , Germany
Background: This retrospective study analyzed the effectiveness of intrathoracic negative pressure therapy for debilitated patients with empyema and compared the short-term and long-term outcomes of three different intrapleural vacuum-assisted closure (VAC) techniques. Methods: We investigated 43 consecutive (pre)septic patients with poor general condition (Karnofsky index ≤ 50 %) and multimorbidity (≥ 3 organ diseases) or immunosuppression, who had been treated for primary, postoperative, or recurrent pleural empyema with VAC in combination with open window thoracostomy (OWT-VAC) with minimally invasive technique (Mini-VAC), and instillation (Mini-VAC-Instill). Results: The overall duration of intrathoracic vacuum therapy was 14 days (5-48 days). Vacuum duration in the Mini-VAC and Mini-VAC-Instill groups (12.4 ± 5.7 and 10.4 ± 5.4 days) was significantly shorter (p = 0.001) than in the group treated with open window thoracostomy (OWT)-VAC (20.3 ± 9.4 days). No major complication was related to intrathoracic VAC therapy. Chest wall closure rates were significantly higher in the Mini-VAC and Mini-VACInstill groups than in the OWT-VAC group (p = 0.034 and p = 0.026). Overall, the mean postoperative length of stay in hospital (LOS) was 21 days (median 18, 6-51 days). LOS was significantly shorter (p = 0.027) in the Mini-VACInstill group (15.1 ± 4.8) than in the other two groups (23.8 ± 12.3 and 22.7 ± 1.5). Overall, the 30-day and 60-day mortality rates were 4.7 % (2/43) and 9.3 % (4/43), and none of the deaths was related to infection. Conclusions: For debilitated patients, immediate minimally invasive intrathoracic vacuum therapy is a safe and viable alternative to OWT. Mini-VAC-Instill may have the fastest clearance and healing rates of empyema.
Negative pressure wound therapy; VAC; Vacuum-assisted closure; Intrapleural; Intrathoracic; Empyema
Reports on pleural diseases and therapeutic modalities
in the pleural cavity go back for centuries, and
particularly thoracic empyema has been a source of fascination
for physicians from different cultures. Nowadays,
treatment of pleural empyema generally depends on the
estimated stage of disease progression . In critically ill
patients or in the case of recurrent empyema, surgical
treatment still represents a big challenge. In such cases, open
window thoracostomy (OWT) allows rapid evacuation of
pus, extensive debridement, and decortication.
Fenestration of the chest wall is an ideal method for
accelerating drainage in patients with bronchial stump
insufficiency, bronchopleural fistula, or pleural
empyema. Nevertheless, OWT has several disadvantages;
for instance, this method requires division of the chest
wall muscles and resection of several ribs, resulting in
a partial thorax defect (Fig. 1a). OWT also necessitates
obliteration of the pleural space, which, in turn,
requires the often painful and time-consuming
procedure of packing on a daily basis. In addition, the chest
wall should be closed; however, chest wall closure after
OWT is not always possible .
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Fig. 1 OWT, OWT-VAC, Mini-VAC, Mini-VAC-Instill
In contrast, previous studies  have shown that
accelerated OWT empyema drainage and resolution may be
achieved with intrathoracic vacuum-assisted closure
(OWT-VAC and also NPWT: negative pressure wound
therapy). Intrathoracic negative pressure therapy can be
minimally invasive without altering the integrity of the
chest wall (Mini-VAC) . Various modifications have been
reported for treatment optimization, such as
vacuumassisted closure with instillation (Mini-VAC-Instill) .
Recent studies have shown that Mini-VAC and
Mini-VACInstill may produce equivalent resolution rates and better
OWT closure rates than open approaches .
Here, we report our biggest cohort to date of 43
debilitated or septic patients with pleural empyema due
to various etiologies. This retrospective study
investigated the effectiveness of intrathoracic negative
pressure therapy for debilitated patients with empyema and
compared the short-term and long-term outcomes of
three different intrapleural vacuum-assisted closure
Between September 2009 and December 2014, 379
patients had been treated for primary and postoperative
pleural empyema at the Center of Thoracic Surgery in
Regensburg, Germany (Krankenhaus Barmherzige Brüder
Regensburg, University Medical Center Regensburg). In
this retrospective study, we investigated 43 of 379
(11.34 %) consecutive (pre)septic patients with poor
general condition (Karnofsky index ≤ 50 %) and
multimorbidity (≥ 3 organ diseases) or immunosuppression, who had
been treated for primary, postoperative, or recurrent
pleural empyema with intrapleural VAC therapy. We
reviewed the medical records of all patients with
intrapleural VAC; no patient was excluded. The study was
reviewed and approved by the Ethics Committee of the
University of Regensburg.
Parameters as well as demographic and clinical
characteristics are summarized in Table 1. Seventeen (40 %) of
43 patients had presented with parapneumonic or
postpneumonic empyema. Twenty-six (60 %) of 43 patients
had postoperative pleural empyema, of whom six
patients presented with postpneumonectomy (three of
these six patients had undergone completion
pneumectomy due to postlobectomy empyema), five with
postlobectomy empyema, and five with bronchopleural fistula
(BPF). Two patients had esophageal-pulmonary fistula.
The remaining 8 patients had developed empyema after
other thoracic procedures. Indication for surgery was
thoracic empyema at American Thoracic Society (ATS)
stage II (n = 37) and stage III (n = 6) and pre-septic or
septic condition. Four patients had developed septic shock.
The patients were grouped according to the VAC
treatment modality received (OWT-VAC vs. Mini-VAC
vs. Mini-VAC-Instill). Grouping was done by
chronologic selection: OWT-VAC (n = 20) procedures were
carried out between 2009 and 2011, Mini-VAC (n = 8)
between 2011 and 2013, and Mini-VAC-Instill (n = 15)
from 2014 onwards. The three groups did not
substantially differ with regard to clinical features (Table 1).
Some evaluations were also conducted according to the
genesis of pleural empyema (primary vs. postoperative).
Table 1 Patient demographics with non-parametric methods for testing whether clinical features and samples of OWT-VAC,
Mini-VAC, and Mini-VAC-Instill originate from the same distribution
Age [years], mean (range)
Empyema side, n (%)
Immunosuppression, n (%)
Previous antibiotics, n (%)
Empyema genesis, n (%)
ATS empyema stage, n (%)
Recurrent empyema with previous treatment, n (%)
aANOVA, cChi: Exact Pearson’s chi-squared Test
OWT-VAC group (2009 to 2011, n = 20). Surgery
consisting of OWT and VAC (Fig. 1b) under general
anesthesia included CT-guided partial resection of 2 to 4
ribs (marsupialization), pus evacuation, debridement,
local decortication, and flushing of the cavity with ringer
solution and 10 % Betaisodona (Povidon-Iod,
Mundipharma, Limburg, Germany) solution. Suturing the skin
flaps on the margins of the OWT constituted
thoracostoma. VAC sponges (black GranuFoam, Standard
Dressings Kits, KCI Medical, Wiesbaden, Germany) were
inserted into the residual pleural cavity through the
thoracostoma to fill the entire pleural space. Suction was
normally set to −100 mmHg from the start (maximum
suction −125 mmHg) and to −75 mmHg after
pneumonectomy. Sponges were changed twice a week under
intravenous propofol anesthesia with short laryngeal
mask airway ventilation. After the inpatient stay, OWT
was either treated with continuing VAC therapy on an
outpatient basis or with conventional wound care in an
outpatient clinic. The chest wall was closed after an
average of 3 months. Persistent BPF was treated with
additional muscle flap transposition (n = 2) or pericardial
flap (n = 3).
Mini-VAC group (2011 to 2013, n = 8). Patients of this
group underwent mini-thoracotomy (thoracotomy with
a 5–6 cm incision without insertion of a rib spreader)
followed by the positioning of an ALEXIS® (Applied
Medical, Rancho Santa Margarita, CA, USA) retractor
(Fig. 1c). After debridement, local decortication, and
flushing of the pleural cavity, VAC sponges were inserted
through the tissue retractor to fill the entire pleural
space. The level of suction was set to −125 mmHg from
the start. Sponges were changed twice a week under
short general anesthesia. The residual space was filled
with an aminoglycoside antibiotic gentamicin sponge
(Genta-Coll® resorb, Resorba, Nürnberg, Germany).
Mini-VAC-Instill group (2013 to 2014, n = 15). This
updated procedure is a combination of Mini-VAC and
intrapleural instillation of antiseptic fluid . After
debridement, the cavity was flushed with polyhexanide
solution (LAVANID® 0.02 %, Serag-Wiessner KG, Naila,
Germany). Special sponges (Instill Dressings, KCI
Medical, Wiesbaden, Germany) were introduced via the soft
tissue retractor. Here, the VAC pad had two tubes: one
for suction and one for fluid instillation (Fig. 1d). The
amount of instilled antiseptic volume was determined by
the volume of the pleural wound. The level of suction
was set to −75 mmHg from the start with a maximum
of −125 mmHg. The system had a program of
automated fluid instillation and vacuum cycles of 20 min six
times a day. The Mini-VAC-(Instill) system was changed
every Tuesday and Friday under intravenous propofol
anesthesia with short laryngeal mask airway ventilation.
Only minor debridement was required at each sponge
change. In all patients, the remaining pleural space after
Mini-VAC-Instill therapy was very small and only filled
with an aminoglycoside antibiotic gentamicin sponge.
The chest wall was closed by simply suturing the soft
All patients were intravenously treated with
antibiotics; if necessary, treatment was adapted and
occasionally modified according to antibiogram results. When
the pleural cavity was macroscopically peaceful and the
patients had two microbiological negative cultures or
when the microbiological culture did not show any
further pathogenic bacteria colonisation, antibiotics were
discontinued after 7 days.
In the case of BPF, the stump was closed by
circumferential suturing of an intra- or extrathoracic muscle flap
or pericardial flap. In patients with post(bi)lobectomy
empyema in association with necrotizing pneumonia,
surgical management consisted of completion
pneumectomy (n = 3) and muscle flap or pericardial flap
transposition followed by intrathoracic VAC therapy. In
the absence of BPF, debridement and local decortication
were conducted before negative pressure wound therapy.
To avoid direct contact of the VAC device with the
mediastinum after lobectomy and pneumectomy, the
area was covered with a gentle wound contact layer with
open mesh design which enables good transfer of
exudate to a secondary dressing and easy delivery of topical
treatments (Mepitel®, Mölnlycke Health Care,
ErkrathUnterfeldhaus, Germany), during the first session.
Chest wall closure required two sterile cultures and
complete macroscopic cover of granulation tissue of
mediastinal and visceral pleura. Furthermore, the presence
of viable tissue due to manipulation was eligible (Fig. 2.).
Continuous variables are presented as mean ± standard
deviation (SD) or range, categorical variables as absolute
numbers and relative frequencies. Categorical variables
Fig. 2 Good macroscopic cover of granulation tissue of visceral pleura
were compared with chi-square tests. Differences in the
duration of intrathoracic vacuum therapy and length of
hospital stay among the different surgical techniques
were analyzed using analysis of variance (ANOVA).
Estimated marginal means (EMM) of the duration of
vacuum therapy and the length of hospital stay − adjusted
by the type of surgical indication (primary vs.
postoperative empyema) − were computed and compared among
the different surgical techniques. Paired differences and
the corresponding 95 % confidence intervals are
presented as effect estimates.
Overall survival time was defined as the date of
commencing OWT-VAC or Mini-VAC (Instill) treatment to
the date of death or the last follow-up. Univariate Cox
proportional hazard models were used to analyze the
relationship between overall survival and the variables of
age, malignancy, surgery indication, empyema treatment,
and successful chest wall closure. Hazard ratios and
corresponding 95 % CIs are presented as effect estimates. A
p-value of < 0.05 was considered statistically significant.
Due to the exploratory nature of this study, no
adjustments for multiple testing were made. All statistical
analyses were done with the IBM SPSS software program
Version 23.0 (IBM Corporation, Armonk, New York,
Overall, the mean duration of intrathoracic vacuum
therapy was 14 days, ranging from 5 to 48 days. Paired
comparison of the VAC procedures (Table 2) showed
that the mean vacuum duration in the Mini-VAC and
Mini-VAC-Instill groups (12.4 ± 5.7 and 10.4 ± 5.4 days)
was significantly shorter than that in the OWT-VAC
group (20.3 ± 9.4 days). The mean durations of VAC in
the primary empyema group and postoperative
empyema group were almost equal (14.4 days vs. 14.3 days;
p = 0.968).
No major complication was related to intrathoracic
VAC therapy. The median number of VAC changes was
2 (range: 1 to 6 changes). In the OWT-VAC group, the
chest wall was closed secondarily after recovery in 12
(60 %) of 20 patients (Table 3). In the minimally invasive
vacuum therapy groups, all patients but one underwent
primary chest wall closure during the same hospital stay
(22 of 23, 96 %).
The success rate was higher (p = 0.034, Table 3.) in
the minimally invasive vacuum group (8 of 8, 100 %)
than in the OWT-VAC group (12 of 20, 60.0 %). The
success rate was also higher (p = 0.026) in the
minimally invasive vacuum group with instillation (14 of 15,
93.3 %) than in the OWT-VAC group (12 of 20,
60.0 %). The success rates in the two minimally invasive
groups were similar (p = 0.455).
Table 2 ANOVA post-hoc pairwise comparisons of OWT-VAC, Mini-VAC, and Mini-VAC-Instill regarding vacuum duration and length
of hospital stay
Vacuum duration in daysa
Estimated marginal means
Postoperative length of stay in hospital in daysb
Estimated marginal means
Difference (95 %-CI)
2.0 (−4.9; 8.8)
Difference (95 %-CI)
0.7 (−8.7; 10.1)
8.2 (−0.8; 17.1)
95 %-CI 95 % confidence interval
aMain effects: Vacuum duration (p = 0.003), surgery indication (p = 0.968); bMain effects: Vacuum duration (p = 0.052), surgery indication (p = 0.744)
Pairwise therapy comparisons
OWT-VAC vs Mini-VAC
OWT-VAC vs Mini-VAC-Instill
Mini-VAC vs Mini-VAC-Instill
Pairwise therapy comparisons
OWT-VAC vs Mini-VAC
OWT-VAC vs Mini-VAC-Instill
Mini-VAC vs Mini-VAC-Instill
The mean postoperative length of stay (LOS) in
hospital of all patients was 21 days (median 18, range 6 to
51 days, Table 2). LOS was significantly shorter (p =
0.027) in the Mini-VAC-Instill group (15.1 ± 4.8) than in
the other two groups (23.8 ± 12.3, 22.7 ± 1.5). The mean
LOS did not differ between the primary empyema group
and the postoperative empyema group (21.8 days vs.
20.6 days; p = 0.744).
Overall, the 30-day and 60-day mortality rates were
4.6 % (2 of 43) and 9.3 % (4 of 43), and none of the
deaths was related to infection.
In 9 patients, fenestrations were left open; 2 patients
died before closure, 3 rejected reoperation, 4 had
permanent bacterial colonization of the window, and 1 was
treated with definitive OWT because of acute recurrence
after primary closure. Therefore, the overall success rate
for the final closure of the chest wall without empyema
recurrence was 76.7 % (33 of 43).
The 1-year, 2-year, 3-year, and 4-year survival rates
were 74.6, 60, 56, and 50 % respectively (Fig. 3). There
were no significant differences in the 4-year survival
rates of the three subgroups (40 % in the OWT-VAC,
62.5 % in the Mini-VAC, and 60 % in the
No case of death was related to intrapleural vacuum
therapy. The Cox regression analysis of overall survival
Table 3 Pairwise comparison of different OP procedures for
primary chest wall closure
Chest wall closure Paired comparison of success
12/20 (60 %) OWT-VAC vs. Mini-VAC,
p = 0.034
Mini-VAC n = 8
Mini-VAC-Instill n = 15 14/15 (87 %)
showed no prognostic factors (Table 4). Only malignancy
showed a slight tendency (HR = 2.37 (0.87-6.41), p =
Treatment of debilitated and pre-septic or septic
patients with pleural empyema is still a challenge. Even in
the case of successful empyema management, patients
with multimorbidity, malignancy, and/or
immunosuppression have a worse short-term prognosis (mortality
up to 15 %, Table 5) and long-term prognosis with a
median survival of 22.8 to 67 months [7, 8] than patients
without such additional complications.
Our study showed that intrathoracic VAC technique
offers a safe treatment option for pleural empyema with
good short-term and long-term outcomes, particularly in
Minimally invasive treatment with Mini-VAC and
MiniVAC-Instill significantly reduces the duration of vacuum
Fig. 3 Cumulative survival
Table 4 Relationship between investigated factors and survival
Successful final chest wall closure (yes/no)
treatment in comparison to OWT-VAC. The length of
stay in hospital could also be reduced by the
MiniVAC(−Instill) procedure, although − in almost all
minimally invasive treated patients (22/23) − final chest wall
closure was conducted during the same hospital stay,
which additionally extended LOS. In addition, a previous
study of our group showed the efficacy of wound
flushing in combination with vacuum in invasive aggressive
empyema thoracis – i.e. highly aggressive bacteria or
reduced immunity of patients .
So, the last treatment period (2013 to 2014) showed
that both treatment duration and LOS could be
significantly reduced by Mini-VAC-Instill therapy in
comparison to the OWT-VAC and Mini-VAC technique.
To date, only few authors have achieved similar LOS
for thoracic empyema [10, 11]. Schneiter at al. reported
a mean hospitalization of 18 days for early and late
postpneumectomy empyema with repeated open surgical
debridements and antimicrobial therapy . The thorax
was definitively closed in 71 of 75 (94.6 %) patients.
Thourani et al. treated 78 empyema patients with
definitive OWT (modified Eloesser flap) and reported a mean
LOS of 16 days . But the modified Eloesser flap
procedure was intended as a permanent one-stage
procedure. So, in the study by Thourani et al., treatment
duration was equivalent to LOS.
In our opinion, the dressings should be routinely
changed every three to four days, in the operating room, to
allow precise and continued monitoring of infection. In
the presence of residual lung tissue we often use the
thoracoscope for better visualisation of poorly visible
This means that repeat debridement treatment can be
performed as required to keep the wound bed clean for
We treated two patients with definitve BPF and in all
the installation of vacuum was possible. In one patient
with a one mm fistula, the BPF was sufficiently closed
after VAC therapy. The other BPF, with a diameter of
eight millimetres, could not be closed by VAC, which
was not a problem in the VAC treatment. Future studies
should investigate the diameter of BPF that can be
closed by negative pressure in VAC therapy.
The largest literature series of OWT patients with
heterogeneous causes of empyema (excluding
postpneumectomy empyema) showed 30-day mortality rates
between 5 and 15 % (Table 5). The OWT procedure
may result in a good prognosis in medical unstable and
debilitated patients. The most common causes of death
after OWT are sepsis and multiorgan failure [7, 8, 11–13].
In our study, we lost only 2 patients due to cardiac and
multiorgan failure, which resulted in a 30-day mortality
rate of 4.6 % (2 of 43). Therefore, VAC treatment,
particularly of the minimally invasive type, offers the same
survival prognosis than classical OWT treatment but a
higher rate of chest wall closures.
The most important advantage of Mini-VAC and
Mini-VAC-Instill therapy is probably immediate chest
wall closure after VAC treatment. We preferred
conducting chest wall closure during the same hospital stay
to avoid later complications including hospitalization
and to improve quality of life. In the Mini-VAC group,
all thoracic windows were closed, and only one definitive
fenestration was left in the Mini-VAC-Instill group.
Indispensable requirements for chest wall closure were
good macroscopic aspects and negative microbiological
cultures. In the study by Palmen et al. , 50 % of
patients died of OWT-related complications (bleeding and
recurrent infections) during follow-up.
Although empyema thoracis recurred once in the
Mini-VAC-Instill group, there were no pitfalls on this
A recent Cox proportional hazard model showed a
significant association of the closure of OWTs (HR
0.31, 95 % CI 0.10–0.88; p = 0.03) with overall survival
. In our study, successful chest wall closure was not
Table 5 Overview; outcomes of OWT therapy in debilitated patients
Number of patients Empyema cause
Closure of OWT Recurrence
Maruyama et al. 2001 53
Thourani et al. 2003
Massera et al. 2009
Reyes et al. 2010
Mean 128.0+/−32.1 days
definitive OWT definitive OWT
Median 5 (3-9 months)
Median 454 (90–1068 days)
significantly associated with survival (HR 0.81, 95 % CI
0.29–2.31; p = 0.695).
The 4-year survival rate of all patients was 50 %, and no
case of death was related to intrapleural vacuum therapy.
We found no prognostic factor for death or survival, and
even malignancy had a p-value of 0.091 (Table 4).
Reyes et al. achieved survival rates of 74 and 60 % at
12 months and 60 months , when treating 78
debilitated patients with empyema with OWT. In the study by
Hato et al., the 60-month survival rate of OWT patients
was 34.7 % (12 of 35), whereas the median survival
period was 22.8 months. According to the univariate
analyses, variables significantly associated with increased
overall survival included closure of the OWT (p = 0.03)
and absence of diabetes mellitus (p = 0.04) . The
longterm survival of this vulnerable patient population is
mainly determined by secondary diseases rather than by
the type of treatment. Taking this fact into consideration,
the primary goal should be prompt empyema therapy to
enable treatment of the underlying disease.
No patient developed systemic symptoms due to the
instillation of the 0.02 % polyhexanide solution. We have
not seen a negative effect of VAC-(Instill) on the pleura
carcinosis. Nevertheless, the use of VAC-Instill therapy
can trigger clinically significant complications and there
are also some contraindications , including:
coagulopathy, larger bronchial stump insufficiency, ongoing pain
and contact allergy or anaphylactic reactions. Because of
this, cautious monitoring of the VAC system must be
exercised in the hospital. Therefore, outpatient
management for Mini-VAC-Instill is not recommended.
Although the cost of materials in the Mini VAC (−Instill)
groups was considerably higher than in the OWT-VAC
group, in the final effect, on grounds of the shorter LOS,
the treatment costs were lower in the minimally invasive
The main limitations of our study are its design as a
retrospective single-center study and the limited number
of patients included. To overcome these biases, a
prospective multicenter study should be conducted.
Minimally invasive VAC treatment (Mini-VAC and
Mini-VAC-Instill) fulfills the aim of a safe and fast
therapy in debilitated and near-septic or septic patients with
empyema. The great advantage of minimally invasive
VAC treatment is the high rate of chest wall closure
during the same hospital stay. This offers better quality of
life for the patients, a very low reinfection rate, and fast
treatment of secondary diseases (e.g. tumour therapy).
Additional instillation therapy is particularly beneficial
for septic patients with highly infected or bacterially
colonized pleural empyema. Based on our data, we
recommend generally the use of Mini-VAC-Instill in the
abscence of BPF. Mini-VAC is also one of the choices
if there is a permanent supply of causative organisms
due to a smaller than 1 cm BPF. If there is a large BPF
(≥ 1 cm), we recommend muscle or pericardium flap
transposition after OWT-VAC pretreatment. The
techniques presented support a non-delayed application of
intrathoracic vacuum-closure therapy.
ANOVA: Analyzed using analysis of variance; ATS: American Thoracic Society;
BPF: Bronchopleural fistula; CT-guided: Computertomography guided;
EMM: Estimated marginal means; LOS: Length of stay in hospital;
MiniVAC: Minimally invasive vacuum-assisted closure; Mini-VAC-Instill: Minimally
invasive vacuum-assisted closure with instillation; OWT-VAC: Open window
thoracostomy with vacuum-assisted closure; VAC: Vacuum-assisted closure
CG, RS, RN and MR participated in the design of the study. FZ carried out the
statistical analysis. TS participated in the sequence alignment and drafted the
manuscript. ZS and HH conceived of the study and participated in its design
and coordination. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Ethics approval and consent to participate
The study was reviewed and approved by the ethics Ethics Committee of
the University of Regensburg (approval number: 15-101-0265).
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