Original Article

Asian Cardiovascular & Thoracic Annals

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Does an enhanced recovery after surgery ! The Author(s) 2020
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DOI: 10.1177/0218492320966435
outcomes in stage III tubercular journals.sagepub.com/home/aan

empyema? A comparative analysis

of 243 patients

Mohan Venkatesh Pulle , Neha Tiwari, Belal Bin Asaf,

Harsh Vardhan Puri, Sukhram Bishnoi,
Srinivas Kodaganur Gopinath and Arvind Kumar

Abstract
Background: Enhanced recovery after surgery protocols in tuberculous empyema surgery have the potential for
improved outcomes, but have not been studied widely. This study aimed to analyze the outcomes after implementation
of an enhanced recovery after surgery protocol in patients undergoing surgery for tubercular empyema.
Methods: A retrospective analysis of patients who underwent surgery for tuberculous empyema in a dedicated thoracic
surgery center from March 2012 to March 2019 was performed. The control group included patients operated on
between March 2012 and March 2016. The enhanced recovery after surgery protocol was strictly introduced into our
practice from April 2016. The study group included patients operated on between April 2016 and March 2019. All
perioperative outcomes were measured, documented, analyzed, and compared between the two groups. There were
166 patients in the control group and 77 in the study group.
Results: Intraoperative blood loss (p ¼ 0.0001), prolonged air leak (p ¼ 0.04), chest tube duration (p ¼ 0.005), and
length of stay (p ¼ 0.003) were significantly reduced in the study group. Overall rates of postoperative complications
(p ¼ 0.04) including wound infection (p ¼ 0.01) were also significantly lower in the study group.
Conclusions: Implementation of an enhanced recovery after surgery protocol in patients undergoing surgery for
tuberculous empyema is feasible and effective. Application of such a protocol leads to less intraoperative blood loss,
shorter hospital stay and duration of chest drainage, and fewer complications. Application of enhanced recovery after
surgery protocols are strongly recommended in tubercular empyema surgery.

Keywords
Clinical protocols, empyema, tuberculous, postoperative complications, practice guidelines as topic, thoracic surgery,
video-assisted

Introduction performed by an open approach. However, video-

Tuberculosis is the major cause of empyema thoracis in
developing countries.1 While antitubercular therapy
continues to be the cornerstone of treatment, the role
of surgery (decortication) is also evident in the chronic
stage (stage III tubercular empyema). Decortication is
essential to remove the thickened visceral as well as
parietal pleura, which impede expansion of the under-
lying lung, as well as to remove the septic load of tuber-
culosis bacteria.2,3 Traditionally, this surgery was
assisted thoracoscopic surgery (VATS) has emerged
as an alternative in the treatment of stage III tubercular
Centre for Chest Surgery, Sir Ganga Ram Hospital, New Delhi, India
Corresponding author:
Arvind Kumar, Room No. 2328, SSRB, Sir Ganga Ram Hospital, Old
Rajinder Nagar, New Delhi 110060, India.
Email: arvindreena@gmail.com
2 Asian Cardiovascular & Thoracic Annals 0(0)
empyema.4 To achieve the best postoperative outcomes
and enhance recovery and quality of life, enhanced
recovery after surgery (ERAS) protocols have been
adopted by the majority of thoracic surgeons. These
protocols are directed at optimization of the patients
preoperative nutritional and physical status, minimiz-
ing the intraoperative stress response, and achieving
faster restoration of normal physiological status post-
operatively.5 The feasibility of an ERAS protocol
has been studied extensively in lung resection sur-
gery.6–8 However, literature on the benefits of ERAS
protocols in surgery for tubercular empyema is sparse.
This study aimed to evaluate the effect of an institu-
tional ERAS protocol on patients undergoing surgery
for tubercular empyema thoracis.
Patients and methods
This was a retrospective comparative analysis of empy-
ema surgery over a 7-year period (March 2012 to
March 2019) in a tertiary care thoracic surgery center
in India. Informed consent was obtained from all indi-
vidual participants included in the study. The study
was approved by Sir Ganga Ram Hospital
Institutional Ethical Board. A total of 243 patients
were enrolled in the study and categorized into two
groups: 77 patients in the ERAS group (operated on
between April 2016 and March 2019) and 166 patients
in the control group (operated on between March 2012
and March 2016). All patients in both groups had stage
III empyema. Both the groups were matched according
to demographic characteristics. Duration of symptoms
was 4.9  5.1 months in ERAS group and 5.2  4.8
months in the control group. Laterality of disease
and the frequency of preoperative interventions were
similar in both groups (Table 1).
The demographic data and details of the current
illness were recorded. Computed tomography of the
chest was performed to assess the stage of empyema
and status of the underlying lung. Indications for sur-
gery included a multiloculated pus collection, partial
drainage of empyema even after chest tube drainage,
and trapped lung. We ensured that all patients received
at least 4 weeks of antituberculosis therapy before the
surgical intervention. Surgery in all patients was initi-
ated by a VATS approach. However, the procedure
was converted to a posterolateral thoracotomy if
there was excessive oozing or bleeding from the lung
surface or pleura and/or a need for lung resection with
frozen hilum, or the presence of a large bronchopleural
fistula necessitating additional procedures.
The institutional enhanced recovery protocol is sum-
marized in Table 2 and categorized into preoperative,
intraoperative, and postoperative phases. The preoper-
ative phase consisted of counselling, detailed ERAS
education by a dedicated nurse coordinator, advice
by a dedicated dietician, adequate physical training
by a dedicated physiotherapist, and minimal fasting
in the preoperative period. Intraoperative measures
included strict adherence to pulmonary protective ven-
tilation strategies with avoidance of high positive end-
expiratory pressures and keeping a target of blood
oxygen saturation >90% on oximetry with the lowest
possible fraction of inspired O2, goal-directed fluid
replacement with avoidance of excess crystalloids,
and regular use of upper and lower body warmers for
the prevention of hypothermia. Several extra measures
were also considered to reduce intraoperative bleeding,
such as pressure packing of oozing surfaces with
sponges, routine use of an argon plasma coagulator
to coagulate the oozing areas, and intravenous injec-
tion of 1 g of tranexamic acid before starting parietal
pleurectomy. Protocols in the postoperative phase
included avoiding excess fluid replacement, early
resumption of oral fluids and diet, early ambulation
with chest physiotherapy, preferably 6–8 hours after
surgery, routine application of a digital negative-
suction device to the chest tubes, and routine use of
medications to deal with postoperative nausea and
vomiting. Adequate postoperative analgesia was
achieved with injectable paracetamol and nonsteroidal
antiinflammatory drugs on the 1st postoperative day,
which were converted to oral from the 2nd postopera-
tive day. Opioids were avoided as far as possible.
Complete pain relief with the patient able to perform
physiotherapy and ambulation without any distress or
opposition was our endpoint. The dosages of pain relief
measures were titrated according to the requirement of
each patient to achieve the above-mentioned endpoint.
Chest drains were removed when there was no air
leak, the drainage was not purulent or hemorrhagic,
and drainage was less than 100 mL in 24 hours.
Patients were discharged from hospital on oral medi-
cations, with/without an intercostal drain, depending
on the drainage or air leak. For those discharged
with a chest tube, its care at home was explained in
detail to the patient and relatives by the nurse coordi-
nator. All patients were reviewed by the attending sur-
geon in the outpatient department. Chest tube removal
and wound care were carried out as required. All
patients were followed up at 3-month intervals for
one year and yearly thereafter for 5 years.
Data regarding the intraoperative variables such as
operative time, blood loss, and number of conversions
were collected. The postoperative data included the
need for ventilation, intensive care unit stay, prolonged
air leak (>7 days), duration of intercostal drainage,
incidence of complications, hospital stay, and time to
return to normal activity.
Pulle et al. 3

Table 1. Preoperative and intraoperative variables in patients who underwent surgery for tuberculous empyema.

Variables ERAS group (n ¼ 77) Control group (n ¼ 166) p value

Preoperative variables
Male/female 60/17 (78%/22%) 123/43 (74%/26%) 0.63
Age (years) 34.5  12.9 31.2  13.6 0.07
Body mass index (kgm2) 21.1  2.9 21.4  2.8 0.44
No comorbidity 58 (75.3%) 133 (80.1%) 0.41
Comorbidity 19 (24.7%) 33 (19.9%)
Duration of symptoms (months) 4.9  5.1 5.2  4.8 0.65
Side of disease
Right 37 (48.2%) 89 (53.6%)
Left 38 (49.3%) 75 (45.2%)
Bilateral 2 (2.5%) 2 (1.2%)
Aspiration 62 (80.5%) 149 (89.7%) 0.06
ICD placement 34 (44.1%) 85 (51.2%) 0.33
Intraoperative variables
Operative time (min) 211  49.4 218  38.4 0.22
Intraoperative blood loss (mL) 212  42.9 288.7  37.3 0.0001
Conversion to open surgery 7 (9.09%) 11 (6.62%) 0.79
ERAS: enhanced recovery after surgery; ICD: implantable cardioverter-defibrillator.

Table 2. Institutional ERAS protocol for surgery for tubercular empyema.

Variable ERAS group Control group

Preoperative management
Detailed patient counselling þ ERAS education Routine Not routine
Respiratory exercise Routine Not routine
Nutritional build-up Routine Not routine
Intraoperative management
Ventilation Pulmonary protective Not standardized
ventilation, with lowest
possible FiO2 target SpO2
maintained > 90%
Upper and lower body warmers to prevent hypothermia Routine Not routine
Measures to reduce intraoperative bleeding Routine Not routine
Packing of areas of oozing
Routine use of argon plasma coagulator
Intravenous bolus of tranexamic acid 1 g intraoperatively
before starting parietal pleurectomy
Fluid replacement Goal-directed euvolemia Euvolemia
Predominantly crystalloid usage No Yes
Postoperative management
Antiemetic drug Routine Not routine
Measures for postoperative pain relief Routine Not routine
Morphine bolus or infusion via epidural catheter (if inserted)
Intravenous fentanyl (in required dose) in all other cases
Intravenous paracetamol and diclofenac injection
postoperatively, converted to oral
paracetamol þ ibuprofen from day 2
Digital negative suction on chest tubes Routine Not routine
Early oral feeding Routine Not routine
Respiratory exercise Routine Not routine
Early ambulation Routine Not routine
ERAS: enhanced recovery after surgery; FiO2: fraction of inspired oxygen; SpO2: blood oxygen saturation by pulse oximetry.
4 Asian Cardiovascular & Thoracic Annals 0(0)

Table 3. Postoperative outcomes in patients who underwent surgery for tuberculous empyema.

Variable ERAS group (n ¼ 77) Control group (n ¼ 166) p value

Need for ventilation 0 2 (1.2%) 1.0

Need for intensive care unit stay 1 (1.2%) 5 (3%) 0.66
Prolonged air leak (>7 days) 8 (10.3%) 35 (21%) 0.04
Postoperation ICD duration (days) 5.1  3.3 7.4  5.3 0.005
Hospital stay (days) 5.9  2.3 7.1  3.2 0.003
Time to return to normal activity (days) 18  4.1 24.5  3.8 0.0001
Total complications 8 (10.3%) 35 (21%) 0.04
Wound infection 3 (3.8%) 24 (14.4%) 0.01
Atelectasis þ pneumonia 1 (1.2%) 11 (6.6%) 0.11
Cardiac arrhythmias 1 (1.2%) 1 (0.6) 0.53
Renal complications 2 (2.5%) 2 (1.2%) 0.59
Recurrence 1 (1.2%) 5 (3%) 0.66
Perioperative mortality (<30 days) 0 0
ICD: implantable cardioverter-defibrillator; ERAS: enhanced recovery after surgery.

Statistical testing was conducted with Statistical
Package for the Social Sciences version 23.0 software
(SPSS, Inc., Chicago, IL, USA). Continuous variables
are presented as mean  standard deviation.
Categorical variables are expressed as frequencies and
percentages. The comparison of normally distributed
continuous variables between the two groups was per-
formed using Student’s t test. Non-normal distribution
continuous variables were compared using the Mann-
Whitney U test. Nominal categorical data were com-
pared between the groups using the chi-squared test or
Fisher’s exact test, as appropriate. A p value < 0.05 was
taken as significant.
Results
Although all the procedures in this series were started
by a VATS approach, 7 patients in the ERAS group
and 11 in control group had to be converted to open
surgery due to diffuse uncontrollable oozing or the
need for resection of lung parenchyma. We considered
conversion to open surgery as one of the outcomes to
compare between groups, rather than excluding these
cases from the study. The rate of conversion to open
surgery was no different between the two groups
(Table 1). Operative time was not different between
the two groups, but because of various intraoperative
measures to decrease blood loss after March 2016,
intraoperative blood loss was significantly lower in
the ERAS group (Table 1). The need for postoperative
ventilation and postoperative intensive care unit stay
were not different between the two groups. However,
the incidence of prolonged air leak, duration of post-
operative drainage, and time to return to normal activ-
ity were significantly reduced in the ERAS group. In
addition, the frequency of overall complications,
including wound infections, was significantly less in
ERAS group (Table 3). Complete resolution of symp-
toms and full lung expansion with no residual collec-
tion or air leak was considered a successful operation.
We did have the problem of residual lung space asso-
ciated with prolonged air leak in 6 patients. Our policy
in such cases was to wait with the chest tube in place
for up to 4 weeks, after which the chest tube was left
open to the atmosphere for 48 hours (in a sterile way)
to see if there was any further lung collapse or increase
in the residual space. We did not notice either of these,
possibly because by 4 weeks, the decorticated expanded
lung had become stuck to chest wall all around. After
48 hours, the chest tube was removed and the wound
was covered with sterile gauze to allow air to escape.
Within a few days, the chest tube wound healed and the
air leak stopped gradually, with residual space persist-
ing as such. At 1 month after surgery, all 6 patients had
an asymptomatic residual space (97.5% success rate).
Surprisingly, 3 months later, in 5 of these 6 patients, the
lung expanded completely (99.6% success rate) with no
residual space, but one patient continued to have an
asymptomatic residual space.
Discussion
Tuberculosis is a major cause of empyema in develop-
ing nations, and is experiencing a reemergence even in
the West.9 Empyema progresses through 3 stages: an
exudative stage (stage I), a fibrinopurulent stage (stage
II), and an organizing stage (stage III).10 All of our
patients were in the chronic organizing stage due to
delayed referral. In such patients, VATS decortication
is challenging due to narrowed intercostal spaces and
extensive pleural fibrosis.11 In addition, most of these
patients are malnourished and physically inactive due
Pulle et al.
to the underlying disease process, which adds to the
morbidity associated with a surgical intervention.
Therefore, the addition of interventions such as dietary
advice, chest physiotherapy, early oral feeding, and
ambulation is as essential as implementation of mini-
mally invasive surgery in ERAS protocols.
A retrospective analysis by Xia and colleagues12 of
92 patients undergoing surgery for tubercular empy-
ema, included 45 patients in the ERAS group and 47
in the conventional treatment group. They concluded
that the ERAS group had a shorter chest tube dura-
tion, less chest tube drainage, and a shorter length of
stay compared to the conventional group. However,
they did not evaluate the important outcome of
return to normal activity. So, in addition to demon-
strating the benefits of an ERAS protocol in terms of
intraoperative blood loss, chest tube duration, postop-
erative air leak, and hospital stay, our study also eval-
uated its role in influencing return to normal activity
which is a very important parameter to assess the effi-
cacy of the surgery. Another study reported a
decreased incidence of complications with increased
readmissions after ERAS protocol implementation in
patients undergoing thoracic surgery.13 Although our
study confirms the decreased incidence of postoperative
complications, readmission rates did not increase with
the ERAS protocol. This is because no patient was
discharged prematurely, and also due to strict adher-
ence to the discharge criteria and continuity of care on
the telephone by the nurse coordinators even after the
discharge.
In surgery for empyema thoracis, early mobilization
and aggressive physiotherapy are essential components
to help expansion of the chronically collapsed lung.
Nevertheless, after any major thoracic surgical inter-
vention, postoperative pain, nausea, and drowsiness
are the major obstacles to early ambulation.14 Several
components of our ERAS protocol contributed to
early ambulation. The most important was a rigorous,
standardized, pain control regimen, titrated to each
patient’s requirement, achieving zero pain without the
use of opioids as far as possible. Equally important
were preventing fluid overload during and after surgery
and effective control of postoperative nausea and vom-
iting. The use of digital negative suction devices for
chest tube drainage aided early chest tube removal.
Previous studies have also reported shorter chest tube
duration, shorter hospital stay, and higher satisfaction
rates in patients managed with digital drainage systems
compared to the traditional underwater seal drainage
devices.15
In thoracic surgery, adoption of the ERAS concept
is relatively recent and has been studied mostly in lung
resection surgery and esophageal resections.16,17 The
Enhanced Recovery After Surgery Society laid down
5
recommendations for perioperative care following
lung resection and esophagectomy.18,19 Because many
different interventions are involved in the ERAS pro-
tocol, it is difficult to conclude whether any particular
intervention is more important than the others, or if it
is the sum total of all interventions that contributes to
improved outcomes.20
Its retrospective nature is the major limitation of this
study. The second limitation is the nonrandomized
design with a particular timeline used for categoriza-
tion of patients into two groups, which predisposes this
study to selection bias. The third limitation is that the
study evaluated only the objective criteria of outcomes,
whereas the subjective outcomes (patient reported out-
comes) including quality of life were not evaluated. We
concluded that ERAS protocols are effective and fea-
sible in patients undergoing surgery for tubercular
empyema. Implementation of such protocols in addi-
tion to minimally invasive surgical techniques such as
VATS may help patients to have less intraoperative
blood loss, shorter durations of chest drainage and hos-
pital stay, and fewer complications. Application of
ERAS protocols are strongly advised in tubercular
empyema surgery. However, randomized controlled
trials with a larger number of patients are needed for
a higher level of evidence.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
ORCID iD
Mohan Venkatesh Pulle https://orcid.org/0000-0002-6868-
1477
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