The Bucharest ESTES consensus statement on peritonitis

Abstract

IntroductionPeritonitis is still an important health problem associated with high morbidity and mortality. A multidisciplinary approach to the management of patients with peritonitis may be an important factor to reduce the risks for patients and improve efficiency, outcome, and the cost of care.Methods
Expert panel discussion on Peritonitis was held in Bucharest on May 2017, during the 17th ECTES Congress, involving surgeons, infectious disease specialists, radiologists and intensivists with the goal of defining recommendations for the optimal management of peritonitis.Conclusion
This document is an updated presentation of management of peritonitis and represents the summary of the final recommendations approved by a panel of experts.

Full text

Vol.:(0123456789)
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European Journal of Trauma and Emergency Surgery
https://doi.org/10.1007/s00068-020-01338-9
GUIDELINE
The Bucharest ESTES consensus statement onperitonitis
BogdanDiaconescu1· SelmanUranues2· AbeFingerhut3· MihaelaVartic4· MauroZago5· HayatoKurihara6·
RifatLati7· DorinPopa8· AriLeppäniemi9· JonathanTilsed10· MateiBratu1· MirceaBeuran11
Received: 3 October 2018 / Accepted: 27 February 2020
© Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract
Introduction Peritonitis is still an important health problem associated with high morbidity and mortality. A multidiscipli-
nary approach to the management of patients with peritonitis may be an important factor to reduce the risks for patients and
improve efficiency, outcome, and the cost of care.
Methods Expert panel discussion on Peritonitis was held in Bucharest on May 2017, during the 17th ECTES Congress,
involving surgeons, infectious disease specialists, radiologists and intensivists with the goal of defining recommendations
for the optimal management of peritonitis.
Conclusion This document is an updated presentation of management of peritonitis and represents the summary of the final
recommendations approved by a panel of experts.
Keywords Peritonitis· Sepsis· Antibiotics
* Bogdan Diaconescu
bogdan.diaconescu@yahoo.com
1 Anatomy Department, Carol Davila University ofMedicine
andPhamacy, Bucharest, Romania
2 Surgical Research Department ofSurgery Medical,
University ofGraz, Graz, Austria
3 MeduniGraz, Paris, France
4 Intensive Care Unit, Emergency Clinic Hospital Bucharest,
Bucharest, Romania
5 General andEmergency Surgery Division, Department
ofEmergency andRobotic Surgery, A. Manzoni Hospital,
ASST Lecco, Lecco, Italy
6 Emergency Surgery andTrauma Section, Department
ofGeneral Surgery, Humanitas Clinical andResearch
Hospital Head, Milan, Italy
7 Westchester Medical Center, Valhalla, NewYork, USA
8 Surgery Department, University Hospital Linkoping,
Linköping, Sweden
9 Division ofGastrointestinal Surgery, Helsinki University
Central Hospital, Helsinki, Finland
10 Honorary Senior Lecturer Hull York Medical School,
Chairman UEMS Division ofEmergency Surgery,
Heslington, UK
11 Surgery Department, Carol Davila University ofMedicine
andPhamacy, Bucharest, Romania

B.Diaconescu et al.
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Peritonitis denition, classications
andseverity scores
Peritonitis is a form of complicated intra-
abdominal infection but is not synonymous with it
Abdominal sepsis refers to sepsis caused by an
intra-abdominal infection
Peritonitis can be classified as primary, secondary
or tertiary peritonitis, and as localized or diffuse
Physiologic scores and the Mannheim peritonitis
index (MPI) should be used to predict short-term risk of
morbidity and mortality
According to the Merriam-Webster medical dictionary,
peritonitis is defined as inflammation of the peritoneum, the
serous membrane lining the abdominal cavity and organs
contained within. The cause of inflammation can be infec-
tious (bacteria or fungus) or non-infectious, related to chem-
ical irritants such as gastro-intestinal contents, pancreatic
enzymes, bile or foreign substances such as barium from
radiological investigations.
There are many related terms found in the literature, some-
times used synonymously, including intra-abdominal infection
(IAI), intra-abdominal sepsis, or more commonly peritoneal
contamination, infection or sepsis, terminology that is some-
times used for grading of intra-abdominal infection.
In fact, IAI is not synonymous with peritonitis [1]. Peritoni-
tis might be a form of IAI and/or might be caused by IAI. Both
terms should not be used interchangeably [1, 2]. Abdominal
sepsis refers to a systemic inflammatory response to infection,
caused by an IAI. Sepsis with acute dysfunction of at least
one organ was called severe sepsis and when accompanied
by hemodynamic instability refractive to fluid administra-
tion and/or requiring vasopressor support was called septic
shock [3]. However, Singer etal. and the recently convened
European Society of Intensive Care Medicine and the Society
of Critical Care Medicine task force redefined sepsis as life-
threatening organ dysfunction caused by a deregulated host
response to infection [4]. Organ dysfunction is present when
there is an increase in the Sequential (Sepsis-related) Organ
Failure Assessment (SOFA) score of two points or more.
Patients with septic shock can be clinically identified by a
vasopressor requirement to maintain a mean arterial pressure
of 65mmHg or greater and serum lactate level greater than
2mmol/L (> 18mg/dL) in the absence of hypovolemia. The
bedside clinical score termed quickSOFA (qSOFA) consists
of respiratory rate of 22/min or greater, altered mentation, or
systolic blood pressure of 100mmHg or less. The task force
concluded the term severe sepsis was redundant and should
be abandoned [4].
One of the first classifications of IAI was described in 1982
by Meakins etal. [5] based on ten possible anatomic locations
of IAI. It was later combined with the Acute Physiology Score
and then coined Surgical Stratification System [6]. Based on
the anatomy of the source and severity measured by physi-
ological compromise, this classification was far from satisfac-
tory as it only took into account secondary bacterial perito-
nitis, and in further studies outcome was similar irrespective
of the category [7]. For these reasons, the classification was
rapidly surpassed and the APACHE II severity score became
commonplace. The APACHE II severity score, however, is not
strictly speaking a classification, nor specific for peritonitis,
although it is correlated with morbidity and mortality.
The so-called Hamburg classification [1] divides peri-
tonitis into three types: primary, secondary and tertiary, to
which one can add a fourth type, called peritoneal dialysis-
related peritonitis.
Primary bacterial peritonitis refers to spontaneous bacte-
rial invasion of the peritoneal cavity, occurring mainly in
infancy and early childhood, in patients with cirrhosis or
who are immuno-compromised.
Secondary bacterial peritonitis refers to those infections
due to intra-abdominal perforation (traumatic, iatrogenic
or disease-related), anastomotic dehiscence, translocation
of bacteria, gastro-intestinal inflammation or necrosis (the
latter including pancreatic necrosis), or sometimes, non-
bacterial peritonitis or penetrating infectious processes.
Tertiary peritonitis refers to persistent or recurrent infec-
tions, sometimes described being related to organisms of
low intrinsic virulence or the immune-compromised patient,
usually following unsuccessful operative attempts to treat
secondary peritonitis.
Clinically, peritonitis is often classified either as local
or as diffuse. Local peritonitis refers to loculi of infection,
usually walled-off or contained by adjacent organs, whereas
diffuse is synonymous with generalized peritonitis, that is
spread to the entire cavity.
Several scoring systems have been developed to stratify
disease and predict outcome.
These include, among others, the Acute physiology and
chronic health evaluation (APACHE) II score, the Simplified
Acute Physiology Score (SAPS), the Sepsis Severity Score
(SSS) and the Mannheim Peritonitis Index (MPI) [8, 9]. The
Hinchey score is specific to complicated diverticular disease
[10].
Age, once used as a “score” has not lived up to expecta-
tions and has been abandoned.
There are also organ dysfunction scores, originally
developed for use in the critically ill, that have a place in
severe peritonitis [11–15]. The most commonly used organ

The Bucharest ESTES consensus statement onperitonitis
1 3
dysfunction scores include the Multiple Organ Dysfunction
Score (MODS) [12] and the Sequential Organ Failure Assess-
ment (SOFA) scores [11]. As mentioned above the SOFA
score has been integrated into the new definition of sepsis [4].
The Mannheim peritonitis index (MPI) was developed
by Wacha and colleagues in 1983 [16], based on the retro-
spective analysis of data from 1253 patients with peritoni-
tis; 20 possible risk factors were considered. Of these only
eight proved to be of prognostic relevance and were retained
for the MPI, classified according to their predictive power.
These included fecal exudate (12 points), diffuse generalized
peritonitis (6 points), purulent exudate (6 points), organ fail-
ure (kidney, lung, shock, or intestinal obstruction) (7 points),
age > 50years (5 points), female sex (5 points), preopera-
tive duration of peritonitis > 24h (4 points), malignancy (4
points), non-colonic sepsis (4 points). Patients with a score
exceeding 26 were associated with high mortality [17].
Prospective studies have confirmed that the MPI was not
only as efficient as APACHE II in predicting the short-term
risk of mortality of a patient with peritonitis [18, 19], but
it is one of the easiest scoring systems to apply. It can be
calculated at the time of surgery whereas the APACHE II
score requires assessment over a 24-h period and it is more
or less organ specific. The MPI has been found to be highly
predictive of morbidity and mortality [19, 20]. Moreover, the
latter group was the only team to perform a true sensitivity
analysis with a Receiver-Operator-Characteristic curve [20].
Yet, the MPI has not yet gained wide acceptance. How-
ever, no score can predict the outcome of peritonitis with
certainty in an individual patient.
Other factors affecting prognosis are age, fecal peritonitis,
metabolic acidosis, blood pressure, pre-operative organ fail-
ure, serum albumin, cardiac function, malnutrition, malig-
nancy, cause of infection, site of origin of peritonitis and
number of organs involved in multi-organ-failure (MOF).
Management (techniques andindications)
Initial uid resuscitation strategy
Resuscitation in sepsis is initially based on goal-
directed fluid therapy
Colloids remain a viable therapeutic option based
on their superior hemodynamic properties and plasma
volume expanding capacity
The initial target mean arterial pressure (MAP) in
patients with septic shock should be at least 65 mmHg
Intravenous fluids are an integral component of the multi-
modal resuscitation strategy. In widespread use for years,
uncertainty hovers over their relative safety and efficacy.
Fluidresuscitationis the mainstay in the initial treatment
of sepsis, but the choice of fluid is unclear. The ideal resus-
citative fluid should restore intravascular volume while
minimizing edema. However, edema and edema-related
complications are common consequences of currentresus-
citationstrategies [21]. Interest in the comparative effec-
tiveness of different intravenous solutions continues and
international debates still flourish [22].
The previous definitions of severe sepsis and septic shock,
stated in 1991 and updated in 2001 were: severe sepsis
(defined as acute organ dysfunction secondary to infection)
and septic shock (defined as severe sepsis plus hypotension
not reversed with fluid resuscitation) originate in the sys-
temic inflammatory response following infection and lead to
cardiovascular and organ dysfunction. Initial infection can
be located anywhere in the body including skin and soft tis-
sues, pulmonary, urinary, or digestive tract as in the case of
peritonitis. As new guidelines were being developed, new
definitions for sepsis and septic shock (Sepsis-3) were pub-
lished. Sepsis is now defined as life-threatening organ dys-
function caused by a dysregulated host response to infection.
Septic shock is a subset of sepsis with circulatory and cel-
lular/metabolic dysfunction associated with a higher risk of
mortality [23]. The Sepsis-3 definition also proposed clinical
criteria to operationalize the new definitions.
Resuscitation in sepsis is initially based on goal-directed
fluid therapy. The timing, rather than the type, of fluid ther-
apy has been proposed as being crucial [24]. The relative
proportion of the different fluids used for initial resuscitation
varies between countries [20]. Cost is invariably included as
a factor in guidelines on the choice of fluids, with the higher
cost of colloids, particularly albumin, being emphasized.
Colloids are more expensive than crystalloids, but remain
a viable therapeutic option based on their superior hemody-
namic properties and plasma volume expanding capacity,
despite a lack of survival benefit in systematic reviews of
heterogenous patient populations [25, 26].
A consensus committee of 55 international experts
recently proposed the new guidelines for management of
sepsis [27]. They recommend that, in the initial resuscita-
tion from sepsis-induced hypoperfusion, at least 30mL/kg
of intravenous crystalloid fluid be given within the first 3h
(strong recommendation, low quality of evidence). They
also recommend that, following initial fluid resuscitation,
additional fluids be guided by frequent reassessment of
hemodynamic status (clinical examination, as well as other
noninvasive or invasive monitoring, as available). Where
available, dynamic over static variables should be used to

B.Diaconescu et al.
1 3
predict fluid responsiveness. The initial target should be a
minimum mean arterial pressure (MAP) of 65mmHg in
patients with septic shock requiring vasopressors and all
efforts should be made to normalize serum lactate levels as
a marker of tissue hypoperfusion.
Avoiding fluid overload by choosing the appropriate
amount of fluids in patients who are fluid-responsive on
one hand, and treating intravenous fluids like other medica-
tions, on the other hand, are the major changes. Whenever
clinicians decide to prescribe intravenous fluids, they need
to weigh the risks and benefits of giving fluid and also the
advantages and side effects of each fluid type in order to
optimize patient outcomes [28].
Supportive andantibiotic management
inperitonitis
Antimicrobial therapy should start no later than
1 h after the recognition of peritonitis
Early administration of enteral nutrition (EN) is
recommended against early parenteral nutrition in
hemodynamically stable patients
High protein intake is recommended (1.2–
3 g/kg/day)
Peritonitis is the second cause of Intensive Care Unit (ICU)
admission after complicated pneumonia and recent studies
have reported increasing rates of healthcare-associated peri-
tonitis remaining a leading cause of death and morbidity in
ICU patients [29]. Management of peritonitis is becoming
increasingly complex mostly because of growing prevalence
of multidrug-resistant (MDR) bacteria.
Antibiotics
The cornerstone of appropriate antimicrobial therapy is the
timing, spectrum and dosing of antibiotics [30]. Microbio-
logic cultures must be obtained before starting any antibiotic
treatment but should not delay administration of antimicro-
bials (maximum 1h after the recognition of peritonitis)
because failure to initiate appropriate empiric therapy is
associated with a considerable increase in morbidity and
mortality. Empiric broad spectrum antimicrobial therapy is
recommended to cover all likely pathogens (bacteria and
fungi). Antibiotic doses must be optimized according to their
pharmacokinetic and pharmacodynamic properties in order
to improve outcome and avoid side effects. Furthermore,
once pathogen identification and sensitivities are available
empiric antibiotic therapy must be narrowed to avoid resist-
ance. As soon as patients improve clinically and inflamma-
tory signs decrease, antibiotics must be stopped promptly
to minimize toxic side effects and to reduce infections from
multi-resistant pathogens [31–33]. Antibiotic therapy can
be suspended after 4days in the absence of fever, elevated
white count or temperature for 48h, but it should be adapted
to the pathology that produced the peritonitis.
In primary peritonitis, which represents a minority of
cases (1%), infection is mainly sustained by Streptococci,
Pneumococci and Haemophilus influenzae and antibiotics
currently employed are ceftriaxone, cefotaxime, ceftazi-
dime as well as acylaminopenicillins. In continuous ambu-
latory peritoneal dialysis (CAPD) peritonitis agents more
frequently involved are coagulase-negative Staphylococci
and Staphylococcus aureus and empirical therapy is based
on vancomycin plus gentamicin or a group 2 cephalosporin
with or without ciprofloxacin [34].
Community acquired secondary peritonitis is sustained
most frequently by E. coli, Bacteroides fragilis and other
anaerobes and enterococci [35]. In peritoneal contamination
of less than 6h duration the usual antibiotics employed are
aminopenicillin/BLI (beta-lactamase inhibitor), acylami-
nopenicillin/BLI, ertapenem or group 2 cephalosporin in
combination with metronidazole or ceftriaxone. In pro-
longed, diffuse and fecal peritonitis empirical therapy
includes acylaminopenicillin/BLI, or group 1 (ertapenem) or
group 2 (imipenem/cilastatin, meropenem) carbapenems or
combinations of metronidazole with group 2, 3a or 4 cepha-
losporins, ciprofloxacin, levofloxacin or a monotherapy with
moxifloxacin [33, 36].
Tertiary peritonitis shows a bacterial spectrum similar
to that of postoperative secondary peritonitis. Group 1 or 2
carbapenems, tigecycline, acylaminopenicillin/BLI or group
3a cephalosporins in combination with metronidazole are
recommended [37].
Tigecycline fails to cover Proteus, Providentia and
Pseudomonas, so it should be combined with antip-
seudomonal therapy in tertiary peritonitis (ciprofloxa-
cin, ceftazidime, amikacin, imipenem/meropenem and
piperacillin-tazobactam).
In IAI with MRSA (multi resistant Staphylococcus
aureus) colonization has been seen in abdomens left open
and Tigecycline represents a good therapeutic option [33,
38].
Peritonitis sustained by vancomycin-resistant enterococci
(VRE) is treated with the same antibiotics used against
MRSA except for vancomycin. Carbapenems, fluoroqui-
nolones, tobramycin and tigecycline are the antibiotics of
choice for pathogens producing extended spectrum beta lac-
tamases (ESBL). In the case of pan drug resistance (PDR)
Pseudomonas, colistin remains the unique effective treat-
ment [39].

The Bucharest ESTES consensus statement onperitonitis
1 3
New antimicrobial agents have been developed against
resistant pathogens: Ceftolozane/Tazobactam, Ceftazidime/
Avibactam, Aztreonam/Avibactam, Imipenem/Relebactam
and S-649266 are all novel antibiotics targeted against
extended spectrum beta lactamase pathogens. Two other
new antibiotics, Eravacycline and Plazomicin, represent a
good therapeutic option against carbapenemase producing
Klebsiella pneumoniae, carbapenem-resistant Acinetobacter
baumanii and ESBL producers. New lipoglycopeptides and
oxazolidinones play a role against resistant Gram-positive
pathogens.
Of note, in recent years prevalence of Candida infections
in ICU patients with peritonitis has increased; in general,
high dose Fluconazole is sufficient but resistance of Can-
dida against Fluconazole is increasing and Echinocandin or
Amphotericin B are viable options. [40]. Risk factors for
invasive fungal infections include immunocompromised
states, including, neutropenia; intravascular or other cath-
eters (especially if parenteral nutrition is involved); prosthe-
ses and broad-spectrum antimicrobial usage.
Nutrition
Early administration of enteral nutrition (EN) is recom-
mended rather than parenteral nutrition (PN) in hemody-
namically stable patients because of its potential physiologic
advantages related to the maintenance of gut integrity,
modulation of the inflammatory response and reduction of
insulin resistance in the first 7days of ICU stay. PN can be
added to EN to provide the recommended caloric and protein
intake (1.2 and 3g/kg/day to improve nitrogen balance) [41].
Despite the risk of gastroparesis and feeding intolerance
in critically ill patients, post-pyloric placed feeding tubes
and routine monitoring of gastric residual volumes are justi-
fied only in patients at high risk of aspiration. Prokinetics
are weakly recommended in treating feeding intolerance
and their use must be assessed daily and stopped as soon
as possible.
Omega 3 fatty acids, carnitine, arginine and glutamine
are not recommended as supplements in critically ill patients
with peritonitis because of the absence of evidence of out-
come improvement [42].
Sedation andanalgesia
Minimizing sedation in critically ill patients with peritonitis
reduces the duration of mechanical ventilation, allows early
mobilization and decreases length of ICU and hospital stay.
Several strategies have been adopted including intermittent
sedation, daily sedation interruption and avoidance of seda-
tives. Pain management depends on the extent of tissue dam-
age. Multimodal analgesia is preferred in order to decrease
the adverse events of a single agent at high dose: non-opioid
analgesics, alone or combined with opioids, are the drugs
most commonly used [43].
Damage control andopen abdomen
Damage control laparotomy and open abdomen
treatment are viable solutions in the treatment of
secondary peritonitis with severe physiological
derangement
The principles of damage control surgery
(DCS) are based on abbreviated surgery with control of
bleeding and contamination, leaving the abdomen open
(OA), restoration of physiology in an intensive care unit,
planned re-operation and definitive repair with delayed
fascial closure
Negative pressure therapy (NPT) strategy has
improved bowel protection and prevented fascial
retraction allowing a reduction in terms of complication
and higher rates of fascial closure
Damage control laparotomy and open abdomen treatment
are viable solutions in the treatment of secondary peritonitis
with severe physiological derangement, but accurate patient
selection is essential.
Damage control surgery (DCS) also known as abbrevi-
ated laparotomy and planned re-operation or staged abdomi-
nal repair surgery is a concept of abbreviated laparotomy
designed to prioritize physiological recovery over ana-
tomical reconstruction in the severely injured patient. The
principles of DCS are based on abbreviated surgery with
bleeding and contamination control, leaving the abdomen
open (OA), restoration of physiology in an intensive care
unit, planned re-operation and definitive repair with delayed
fascial closure. This staged approach leads to prevention of
patient’s physiological exhaustion caused by shock and per-
mits a definitive treatment after restoration of physiological
parameters. DCS, especially if combined with damage con-
trol resuscitation (DCR) is associated with improved out-
comes in trauma patients [44]. Immediate definitive repair of
severe injuries in patients with deranged physiology is well
known to be detrimental to outcome [45].
Due to similarities in impaired physiology between
trauma surgery and non-trauma surgical emergencies (or
the need to plan a second look laparotomy in secondary or
post-operative peritonitis, bowel ischemia or severe acute

B.Diaconescu et al.
1 3
pancreatitis) some centers have extended the DCS principles
to treat non-trauma acute conditions [46].
In secondary or tertiary peritonitis DCS consists of post-
poning restoration of intestinal continuity to a subsequent
operation and leaving the abdomen open with a temporary
abdominal closure (TAC) [47]. This approach is indicated
essentially in cases where it has not been possible to obtain
source control at the first operation or in patients with sig-
nificantly impaired physiology. The basic concept of an OA
strategy in peritonitis instead of either abdominal closure
with planned re-laparotomy or re-laparotomy on demand
is that the contaminated peritoneal cavity is treated as an
open abscess. The temporary abdominal closure facilitates
repeated peritoneal lavage. OA is also indicated in cases
with, or at high risk of, abdominal compartment syndrome
(ACS) and where it is impossible to obtain a primary direct
fascial closure due to visceral edema.
At the present time, only level III and IV data support the
benefits of a DCS approach with OA and TAC in patients
with non-traumatic surgical emergencies such as peritonitis.
The retrospective nature of these studies with no standard
definition of damage control techniques and heterogeneous
assessment of physiology impairment and lack of prospec-
tive randomized trials suggest only a cautious advocacy for
DCS in non-trauma setting [2].
An OA strategy following DCS is associated with
high complication rates including enteroatmospheric fis-
tula (EAF) and fascial retraction with difficult/impossible
delayed fascial closure [48]. Patient selection is therefore
essential in order to avoid over-treatment. As in trauma sur-
gery several authors have estimated that a small proportion
of non-traumatic abdominal emergencies would benefit from
this strategy [49–51] since most of these abdominal emer-
gencies never reach a critical level of physiological derange-
ments at which DCS is indicated.
Further research will need to focus on correct selection
of patients that might clearly benefit from a DCS approach.
TAC with NPT and mesh-mediated fascial traction seems
to provide best results in terms of fewer complications and
better primary delayed fascial closure rates.
Choice of TAC is a key element in the OA management.
Static TAC methods used at the beginning of the era of DCS,
such as simple skin closure, towel-clips closure or Bogotá
bag, were used to contain abdominal viscera, but did not
prevent lateral fascial retraction hindering definitive fascial
closure. Furthermore, mortality was close to 40% [47] and
severe complications such as EAF, especially in the septic
abdomen, were frequently associated [52, 53].
At the present time, the most commonly used NPT tech-
niques are commercial devices and the so-called “Barker”
vacuum-pack, a limited cost system where viscera are pro-
tected by a plastic sheet and sterile surgical towels are sealed
and connected through a drain with continuous negative
pressure [54].
Introduction of NPT devices and a more comprehensive
understanding of pathophysiology of OA has improved the
outcome of this population of patients. NPT strategy has
improved bowel protection and prevented fascial retraction
allowing a reduction in terms of complications and higher
rates of delayed fascial closure, especially if abdomen clo-
sure is obtained within 8days [48]. Benefits in terms of
reduction of systemic effects through cytokine removal by
negative pressure have been demonstrated in porcine models
[55] and improved outcomes have also been documented in
a prospective observational study [56]. A recent randomized
controlled study could not find any statistically significant
difference in the reduction of systemic inflammatory mark-
ers between NPT and the Vacuum-pack technique [57].
At the present time, the most promising results in terms
of primary delayed fascial closure have been reported when
a combined technique using NPT with a polypropylene mesh
sutured to the fascial margins. The fascial margins are pro-
gressively approximated by increased tension via the mesh
until a direct suture can be performed [58]. The results of
this technique, although mostly reported in single centers
with limited number of cases seem to be promising.
Further prospective studies are needed in order to evalu-
ate the efficacy of NPT on the reduction of inflammatory
mediators and its potential relation to prevention of mul-
tiorgan failure. Larger prospective series to determine the
best treatment for primary delayed fascial closure are also
needed.
Particularities according todisease
andorgan
Upper GI anastomosis leakage andperforated
gastroduodenal ulcer
Post-surgical upper gastro-intestinal anastomotic leaks are
the most common and feared complications for any anasto-
moses. For this short review we will address post-operative
leaks following esophagectomy and sleeve gastrectomy, the
most frequent bariatric procedure today. The factors and
causes responsible for upper gastro-intestinal anastomotic
leaks (patient, surgeon or technique related) as well as the
diagnosis and current management will be examined.

The Bucharest ESTES consensus statement onperitonitis
1 3
Anastomotic leaks followingesophagectomy
The risk factors are cervical and hiatal location of
the anastomosis, positive margins for malignancy, local
ischemia and technical errors
The diagnosis is usually made clinically and/or
by contrast esophagogram/flexible endoscopy or CT scan
The management depends on clinical
presentation and location of the anastomosis and extent of
anastomotic disruption, and grading of the leak
Nonoperative, conservative management such as
delayed initiation of oral feeding and antibiotics may
suffice for occult (Grade I) leaks
General principles of management include
systemic antibiotics, closure or occlusion of the defect as
soon as possible which can either be done by stents or
surgically
In more serious situations, if sepsis is poorly
controlled with more conservative measures, esophageal
diversion or resection can be entertained
After bariatric surgery, the chances are higher
that the leak will close using a stent and providing enteral
nutrition support
The prevalence of anastomotic leakage following esophagec-
tomy ranges from 0 to 35%, with cervical anastomotic leaks
being more frequent. The main risk factors for anastomotic
leakage are cervical and hiatal location of the anastomosis,
positive margins for malignancy, local ischemia and techni-
cal errors. Other factors for anastomotic leak are higher ASA
score, malnutrition, diabetes, renal failure, steroids, obesity,
smoking, surgeon’s experience (and frequency with which
the operation is performed by individual surgeon as well
as institutional overall experience). Moreover, whether the
anastomosis is performed hand sewn or stapler influences
the frequency of leaks. Recent evidence favors use of sta-
pling in preventing an anastomotic leak. In the meta-analysis
by Liu etal. [59] of 15 RCTs (n = 2337) comparing stapling
vs. hand-sewn anastomosis use of stapler reduced the risk of
leak by 34%. In another recent study by Ryan etal. [60] of
21 RCTs combining prospective/retrospective cohort studies
(n = 7167) of transthoracic vs transhiatal approaches (TTE
vs THE) there was no difference between TTE and THE. Use
of an omentoplasty to reduce the leak rate was reported as
favorable by Schaheen etal. [61]. Interestingly, Zhou etal.
[62] reported no differences in leak according to whether
esophagectomy was done minimally invasively or via an
open approach.
Clinical presentation of the leak varies according to the
location of the anastomosis and other factors, such as degree
of spillage, whether the leak is early (mechanical failure)
or late (ischemia), patient defense mechanisms, and patient
status (fully awake, under respiratory assistance, vasopres-
sive support, associated sepsis). The diagnosis is usually
made clinically and/or via contrast esophagogram/flexible
endoscopy or CT scan. The management depends on clini-
cal presentation and location of the anastomosis and extent
of anastomotic disruption, i.e., grading of the leak that may
be without clinical signs (Grade 1) to major leak (Grade 3)
or Grade 4, with entire gastric conduit necrosis. Nonopera-
tive, conservative management such as delayed initiation of
oral feeding and antibiotics may suffice for occult (Grade I)
leaks. The general principles of management include sys-
temic antibiotics and closure or occlusion of the defect as
soon as possible, which could be done by stents or surgically.
Drain associated fluid collections, prevent distal obstruction
and minimize factors that are keeping the perforation open
(e.g., tumor, foreign body, persistent infection). If sepsis is
poorly controlled with conservative measures esophageal
diversion or resection should be entertained. In recent years
laser-assisted fluorescent-dye angiography (LAA) has been
used to assess perfusion in the gastric graft and to correlate
perfusion with subsequentanastomotic leak. In a study of
150 patients undergoing esophagectomy with planned gas-
tric pull up reconstruction aleakwas found in 24 patients
(16.7%) and was significantly less likely when the anasto-
mosis was placed in an area of good perfusion [63]. Use
of stents has been recently reported in 267 patients by van
Boeckel etal. [64] with success a rate of 81–94%. The com-
monest complication, stent migration, occurred more often
with self-expanding plastic stents [n = 47 (31%)].
Leaks followinglaparoscopic sleeve gastrectomy
formorbid obesity
The definitive management of these leaks
depends on the patient’s condition and the ability to
provide enteral nutritional support
Using a stent and providing enteral nutritional
support increase the chances that the leak will close

B.Diaconescu et al.
1 3
Morbid obesity has risen to true world-wide epidemic pro-
portion. Laparoscopic and robotically assisted sleeve gas-
trectomy has become one of the most common bariatric pro-
cedures world-wide. In large published case series of open
and laparoscopic cases, the leak rate varies between 1 and
8.3% after gastric bypass [65]. However, although post-oper-
ative complications are not common in all these procedures,
they must be recognized and addressed promptly in order to
minimize possible mortality and significant morbidity.
The etiology of GI leaks is multiple but generally falls
into mechanical/tissue causes or ischemic causes, both of
which involve intraluminal pressure that exceeds the strength
of the tissue and/or staple line [66].
Identifying the best technique with lowest complication
such as reinforcement of the stapled resection of the stomach
after gastric bypass has been studied extensively. A system-
atic review by Gagner and Buchwald [67] of 88 RCTs, ret-
rospective or prospective studies (n = 8920) of laparoscopic
sleeve gastrectomy (LSG) compared 4 staple-line reinforce-
ment methods. The study compared LSG staple-line leak
rates of 4 prevalent surgical options: no reinforcement, over
sewing, nonabsorbable bovine pericardial strips (BPS), and
absorbable polymer membrane (APM). There were 191
leaks in 8920 patients; an overall leak rate of 2.1%. Leak
rates ranged from 1.09% (APM) to 3.3% (BPS). APM leak
rate was significantly lower than other groups (p < 0.05). The
percentage of leak was the lowest with absorbable mem-
brane 1.09 (N/A); Over sewing 2.04 (p = 0.02); No reinforce-
ment 2.60 (p = 0.001); while the highest leak rate was using
bovine pericardium 3.30 (p = 0.0006). A meta-analysis by
Parikh etal. [3] of 112 studies (n = 9991) of LSG found that
use of a Bougie ≥ 40 Fr significantly (47%) reduced the odds
of a leak [OR 0.53 (0.37, 0.77)] while there were no sig-
nificant effects for distance to pylorus or use of buttressing.
Recognizing the leak early and addressing it promptly is
necessary if complications are to be minimized. Tradition-
ally, any leak from the gastric anastomosis or any form of
bariatric surgery would have meant re-operating, wide drain-
age or a combination of both. The definitive management of
these leaks depends on the patient’s condition, and the abil-
ity to provide nutritional support enterally. Using a stent, and
providing enteral nutritional support the chances are higher
that the leak will close. Recently, the American Society for
Metabolic and Bariatric Surgery issued a position state-
ment and recommendations on prevention, detection, and
treatment of gastrointestinal leak after gastric bypass and
sleeve gastrectomy, including the roles of imaging, surgi-
cal exploration, and nonoperative management [65]. While
meticulous tissue handling, use of proper tissue thickness,
and avoidance of inadvertent narrowing, undue tension, and
twisting or kinking of the mesentery and tissues are most
important, other elements in this statement should be exam-
ined by every surgeon doing a GI anastomosis.
Biliary peritonitis
The standard for acute cholecystitis is surgical
treatment and laparoscopic cholecystectomy is a safe and
effective treatment
The optimal time for this approach is as soon as
possible after diagnosis, better in the first 3 days after the
presentation of symptoms
For critically ill patients with biliary sepsis
percutaneous cholecystostomy is an alternative for
patients at high risk for surgery
For patients with severe inflammation partial
cholecystectomy, it is also a safe option but it should be
associated with the closure of the cystic duct or suture of
the infundibulum and drainage
For acute cholangitis, endoscopic drainage is the
preferable option for management because serious
complications are very rare
Biliary peritonitis is in important cause of morbidity and
mortality and now is the second commonest cause of perito-
nitis after appendicitis according to the CIAO study, a mul-
ticenter investigation performed in 68 medical centers in
Europe during a 6-month observational period in 2012 [68].
Cholecystectomy is gold standard treatment for patients
with acute cholecystitis but percutaneous cholecystostomy
could be an alternative for patients at high risk for surgery in
elderly or critically ill patients with biliary sepsis [69–71].
In a systematic review of severely ill patients with comor-
bidities treated by percutaneous cholecystostomy, 40% of
patients were later cholecystectomized, with a mortality rate
of 1.96%. Procedure mortality was 0.36%, but 30-day mor-
tality rates were 15.4% in patients treated with percutane-
ous cholecystectomy and 4.5% in those treated with acute
cholecystectomy (p < 0.001) [72].
Early diagnosis and emergency surgical treatment of gall-
bladder perforation are the key points for reducing morbid-
ity and mortality rates associated with this condition, but
unfortunately gallbladder perforation is rarely diagnosed
pre-operatively. Delayed surgical intervention is associ-
ated with elevated morbidity and mortality rates, increased
likelihood of ICU admission, and prolonged post-operative
hospitalization [2, 74].
Biliary leaks are an iatrogenic injury to the biliary canals
and can develop after laparoscopic cholecystectomy in

The Bucharest ESTES consensus statement onperitonitis
1 3
0.4–0.7% of cases. Bile leakage has been defined as the
bilirubin concentration in the drainage at least 3 times the
serum bilirubin concentration on or after postoperative day
3, or as the need for radiologic or operative intervention
resulting from biliary collections or biliary peritonitis in
patients who underwent hepato-biliary or pancreatic opera-
tions [74]. Endoscopic treatment of biliary leaks in the form
of sphincterotomy and stent placement is associated with a
high rate of success. Closure of the leak has been reported
in 91.0% of cases [75].
Acute cholangitis differs in severity, from a mild form,
which can be managed with parenteral antibiotics alone,
to severe or suppurative cholangitis requiring early biliary
drainage [76]. Treatment of acute cholangitis requires treat-
ment of the underlying cause in addition to administration
of antimicrobial agents and biliary drainage [77].
In 2001, Hui etal. reported on a prospective study of
142 consecutive patients with acute cholangitis. Emergency
ERCP was performed in patients who did not respond to
medical therapy. Thirty-one patients (21.8%) required
emergency ERCP. A maximum heart rate of more than 100/
min, albumin of less than 30g/L, bilirubin of more than 50
micromole/L and prothrombin time of more than 14s on
admission were associated with failure of medical treatment
and the need for emergency ERCP (p = 0.001, < 0.001, 0.006
and 0.004, respectively) [78].
Biliary drainage can be performed by an endoscopic or
percutaneous transhepatic approach. For critically ill patients
with acute cholangitis, endoscopic biliary drainage is equally
effective for malignant or benign biliary disease [79]. To
date no RCTs have been published comparing the safety and
effectiveness of endoscopic and percutaneous transhepatic
biliary drainage in the treatment of acute cholangitis. Endo-
scopic drainage is preferable to open drainagedue to the
shortened length of hospitalization and because significant
complications are rare [80].
Patients with biliary peritonitis should be operated on
without delay and the surgery should include drainage of
the abdomen and repair of the underlying cause. However,
in certain circumstances the operative findings may dictate
that drainage is the only option. After surgery for general-
ized postoperative peritonitis, a strategy of planned relapa-
rotomy is suggested when source control is uncertain. An on
demanded relaparotomy approach is adequate for purulent
and biliary peritonitis if the septic source has been con-
trolled [81].
Small bowel perforation
Surgery is the first choice of treatment for small
bowel perforation
Primary repair of perforated bowel is preferable
to resection in the absence of gross fecal peritonitis and
during the first 6 h after perforation
Primary anastomosis should be avoided in the
presence of gross or fecal peritonitis because it is
associated with a high risk of complications
Surgery is the first choice of treatment for small bowel per-
forations. The surgeon has several options including simple
suture and wedge or segmental resections. Primary repair is
preferred over resection whenever possible because of lower
complication rates. Better outcomes could also reflect the
limited tissue injury in these patients [82, 83].
The technique of anastomosis (whether stapled or hand-
sewn) in small bowel resection appears to have little influ-
ence on the anastomotic complication rate. If an enterectomy
is required, the entire unhealthy segment is resected, leaving
fit and well-perfused ends for anastomosis. For patients with
malignant lesions, perforations associated with mesenteric
vascular injuries, necrotic bowel, or multiple adjacent perfo-
rations primary repair should not be performed [31, 82, 84].
A laparoscopic approach may be performed if the
patient’s overall health status and the surgeon’s experience
are appropriate [84]. There is no RCT comparing laparo-
scopic with open surgery despite the management of small
bowel perforation being well represented in the literature
[85].
Primary anastomosis should be considered carefully in
the presence of gross or fecal peritonitis because it is associ-
ated with a high risk of complications [31]. In delayed pres-
entations, a protective ileostomy may be prudent to address
fecal peritonitis in order to reduce mortality rates [86, 87].
Thorough systematic abdominal lavage is essential in cases
of serious abdominal suppuration [86, 87].
Patients with duodenal perforation post-Endoscopic
Retrograde Cholangiopancreatography (ERCP) require
early detection and prompt treatment. The development of

B.Diaconescu et al.
1 3
abdominal pain, pyrexia or signs of critical illness should
prompt consideration of urgent surgical exploration for
repair or drainage. Successful non-operative management of
sphincterotomy-related retroperitoneal perforations is possi-
ble in stable patients even if there is extensive retroperitoneal
gas observed on CT. A high number of pancreaticobiliary
and duodenal perforations (70%) secondary to periampul-
lary endoscopic interventions can be treated non-operatively
by nasogastric drainage, antibiotic coverage and nutritional
support [86, 88].
Appendicitis
Complicated appendicitis is represented by
perforation, abscess or localized/generalized peritonitis
The laparoscopic approach in complicated
appendicitis is still a subject of discussion
Complicated appendicitis is represented by perforation,
abscess or localized/generalized peritonitis. Clearly, some
prefer open appendectomy in this setting [89, 90], but it is
of note that most uncomplicated cases of acute appendicitis
can be treated through a single 15–20mm incision in the
right iliac fossa [91]. The laparoscopic approach in compli-
cated appendicitis is still a subject of discussion, essentially
as concerns the postoperative complications. Special atten-
tion should be paid to the complexity of adhesiolysis and
peritoneal lavage: in the pouch of Douglas, peri-cecal space,
hepato-phrenic space and infrahepatic space. One potential
advantage of laparoscopy is that it allows a better view of
the entire peritoneal cavity and of all the spaces without
the necessity to make a large incision, or enlarge a smaller
one if a complication is found or an anatomic variation
(ectopic appendix) is discovered [91–93]. In cases with dif-
ficult access to an ectopic appendix (retrocecal, subhepatic
or mesoceliac) or limited mobility of the cecum or discovery
of peritonitis, conversion to laparoscopy (coined “reversed
conversion” by Schrenk etal. [94] and developed by Navez
etal. [95] with three to five 5–10mm incisions is an excel-
lent solution to explore the entire abdomen and treat the
disease instead of enlarging the right iliac fossa oblique inci-
sion or deciding to perform a large midline incision, both of
which can lead to postoperative parietal co-morbidity (surgi-
cal site infection or incisional hernia) [91]. However, there
are reports stating that laparoscopic appendicectomy (LA)
has been associated with higher rates of organ space infec-
tions, especially in complicated cases [96]. Thereaux etal.
recently published an article with 141 patients operated for
diffuse appendicular peritonitis. The most important point in
this paper is that all the patients were operated by the same
experienced team with a conversion rate of 3.5% and 7.1%
(10 cases) intraabdominal abscesses [97]. In a very recent
RCT on complicated appendicitis, Thomson etal. stated that
for 114 patients and 7% conversion rate, also operated by the
same team of senior laparoscopic surgeons, LA is at least
as safe as the open approach for complicated appendicitis
[98]. The conclusions are controversial, but recent studies
with experienced laparoscopic surgeons have not been able
to find any statistically significant differences in terms of
postoperative abscesses [99, 100]. Surgeons who have better
and extensive experience in laparoscopic surgery can obtain
better results with LA than with open surgery [91]. The best
surgical approach should be the approach that best suits the
surgeon’s experience.
For perforation during endoscopy, endoscopic treatment
with placement of a clip is possible when the perforation site
is recognized during or within 6h of the procedure and the
bowel preparation is adequate. The decision for endoscopic
treatment depends on the size and the cause of perforation
as well as the endoscopist’s experience and access to endo-
scopic devices. Clips are suitable for closure of small thera-
peutic perforations less than 1cm.
Colorectal perforations
Perforation from colorectal malignancy is a
surgical emergency and source control and aggressive
supportive care for sepsis physiology must be the
primary goal
Perforation is a pathological condition in which
saving life is prioritized, and some aspects such as the
extent of lymph node dissection may be compromised
Primary anastomosis should be avoided in the
presence of gross or fecal peritonitis because it is
associated with a high risk of complications
Perforation from colorectal malignancy is a surgical emer-
gency characterized by numerous challenges for the surgical
team as well as for the anesthetic one [101]. The surgeon
is faced with a multitude of unfavorable factors including
septic shock, poorly defined tissue planes and the technical
demands of an oncologic resection without the leisure of
time or adequate oncologic work-up. [102] How aggressive
the treating surgeon should be in these unstable patients is
still an ongoing controversy. In addition, advances in critical

The Bucharest ESTES consensus statement onperitonitis
1 3
care and adjuvant therapy have improved outcomes in septic
shock and metastatic colon cancer. The incidence of malig-
nant perforation from colorectal cancer ranges from 1.2 to
9%, total mortality can reach 12–48% [103] and large series
analyzing the perioperative and long-term outcome in these
patients are lacking [103]. There are two types of perfora-
tion associated with colon cancer: direct perforation from
tumor necrosis and perforation of the proximal colon due to
obstruction by the tumor [103]. Source control and aggres-
sive supportive care for sepsis physiology must be the pri-
mary goal. This approach is supported by the substantial risk
of peri-operative mortality faced by these patients [102]. Tan
etal. reported a series of 45 patients with colonic perforation
[101]. Sigmoid colon (37.8%) and cecum (28.9%) were the
most common sites of perforation. Hartmann’s procedure
and right hemicolectomy were performed most frequently
in 17 (37.8%) and 15 (33.4%) patients, respectively. 17.8%
patients died in the perioperative period. Independent vari-
ables predicting worse peri-operative complications (Cla-
vien/Dindo grades III to V) [106] were ASA score ≥ 3 and
worse peritoneal contamination (MPI > 26). Left-sided per-
foration was the only independent factor predicting stoma
creation. The only factor predicting long-term survival was
the stage of malignancy (p < 0.001). The overall mean sur-
vival time for stage II, III, and IV disease were 63.7, 38.1,
and 13.8months, respectively. 41.7% patients had disease
recurrence. The median time to recurrence was 13months
(6–48months).
Zielinski etal. reported eighty-six patients with colonic
perforations associated with primary colon cancer in whom
the overall survival (OS) was significantly worse in those
with diffuse peritonitis compared to those with contained
perforations, with 5-year estimated OS at 24% vs. 62%
(p = 0.003). Post-operative mortality was significantly higher
for the diffuse peritonitis patients (19% vs. 0% in contained
perforations group) and only 5% in a case matched control
group of patients undergoing resection for colon cancer who
did not have colonic perforations. Perioperative mortality is
the main reason for inferior OS in the unadjusted analysis
when compared to non-perforated controls. R0 resection
could be achieved in 62–68% of patients with perforated
colon cancer. Ping Song etal. [103] reported a series of
twenty-six consecutive patients with an overall mortality
rate during hospitalization of 15.4%. All deaths occurred in
patients with perforation proximal to the tumor. Perforation
proximal to the tumor occurred more commonly in patients
with advanced age (> 70), higher American Society of Anes-
thesiologists (ASA) score and higher preoperative lactate.
Hiroshi Asano etal. [105] reported a review of 44 colorectal
cancer perforation patients. In-hospital mortality was 25.0%
(8 of 32 patients) for proximal site perforation but 8.3% (1 of
12 patients) in the cancer site perforation patients. There was
no significant difference in recurrence rates between the two
groups. The recurrence rates in the patients who underwent
surgery with R0 resection were 18.2% in those at stage II and
54.5% in those at stage III.
In terms of conclusions, the patient has two possible ele-
vated risk sources: from the malignancy and from the septic
complications secondary to perforation. Perforated colorec-
tal malignancy is associated with high morbidity and mortal-
ity rates. However, perforation is a pathological condition
in which saving life is prioritized, and some aspects such as
the extent of lymph node dissection may be compromised.
Short-term outcome is determined by ASA score and sever-
ity of peritonitis while long-term outcome by the stage of
the cancer. Perforated colorectal cancer is a high-risk factor
for recurrence, and the application of postoperative adjuvant
chemotherapy is expected to contribute to improvement of
prognosis.
Primary anastomosis should be avoided in the presence
of gross or fecal peritonitis because it is associated with a
high risk of complications.
Anastomotic leakage
There is no consensus on the management of
anastomotic leaks
The diagnostic methods commonly used when a
leakage is suspected are CT scan, contrast enema,
endoscopic examination, and reoperation
Nonoperative management can be performed
successfully in both diverted (at the initial operation) and
nondiverted patients
Patients with overt sepsis requiring surgical
intervention almost always require a diverting stoma as
part of their treatment, which might well become
permanent
Anastomotic leak continues to be a feared surgical complica-
tion, leading to significant patient morbidity and mortality.
Leak rates described in the literature are significant, ranging
from 3 to 21% [106] with mortality rates of 3–22%. There
is no consensus on the management of anastomotic leaks.
Although operative intervention has traditionally been pre-
ferred, selected patients with anastomotic leaks have been
managed nonoperatively with or without percutaneous inter-
vention. Varying definitions of anastomotic leak may lead
to some confusion as to the best treatment. Risk factors for
leakage have been extensively studied, and the most frequent

B.Diaconescu et al.
1 3
factors mentioned are male sex, high age, a low anastomo-
sis, malignant disease, high (ASA) score, long operation
time, emergency operation, preoperative radiotherapy and
perioperative blood loss or transfusion. [107]. The anas-
tomotic leak definition proposed by Rahbari etal. is often
used: grade A requires no therapeutic intervention; grade
B includes active intervention without laparotomy, and if
laparotomy is required, the leakage is classified as grade C
[108]. The diagnostic methods commonly used when a leak-
age is suspected are CT scan, contrast enema, endoscopic
examination, and reoperation [109]. Bodil and al. proved
that almost one quarter of all CT scans were negative in
patients who later were diagnosed with anastomotic leakage.
It took a mean of 8.5days before leakage was confirmed,
compared to 4.3days in patients who were diagnosed dur-
ing a reoperation [107]. Blumetti etal. showed that median
time to diagnosis of nonoperative leaks was 27days (range
3–1400days), and the median time to diagnosis of operative
leaks was 6days (range 2–660days) [110]. Treatment of an
anastomotic leakage differs with the severity and the loca-
tion of the anastomosis. Often, there is a high frequency of
permanent stoma after a reoperation and anastomotic take
down. Salvage of the anastomosis is more common in grade
A and B leakages with the treatment consisting of drainage
and/or antibiotics [111]. Novel procedures to preserve the
leaking anastomosis have also been described, including lap-
aroscopic diverting ileostomy combined with an endoscopi-
cally placed polyurethane vacuum sponge at the site of the
leak or endoluminal stenting combined with diverting stoma
[112]. Chen and other several authors have highlighted the
possibility of treating low-lying anastomotic leaks via a
hybrid approach in which the anastomosis is managed endol-
umenally, while the peritoneal cavity is explored and treated
via laparoscopy (a hydrid approach) [113]. The use of a pro-
tecting stoma should theoretically attenuate the severity of
an anastomotic leak and allow wider use of nonoperative
therapies. Studies have shown no difference in the number of
symptomatic leaks in patients with a stoma, although the rate
of reoperation for leak was significantly lower [114]. This
demonstrates that the absence of fecal diversion should not
affect the choice of management of anastomotic leak (opera-
tive vs. nonoperative). Rather, treatment should be based on
the patient’s overall clinical status [110].
Conclusion: Anastomotic leak in colon and rectal sur-
gery continues to be an ongoing source of patient morbidity
and mortality. Diverse presentation of leaks mandates that
clinicians tailor the management of this condition to the
individual patient. For a grade C low anastomotic leakage
the recommendation is colostomy. For a right hemicolec-
tomy anastomotic leak a new anastomoses is recommended
for patients in good condition, without evidence of a severe
inflammatory response and in the absence of gross fecal
contamination. Nonoperative management can be performed
successfully in both diverted (at the initial operation) and
nondiverted patients. For an accessible and small abscess
of less than 4cm percutaneous drainage is the best option if
it is available. Patients with overt sepsis requiring surgical
intervention almost always require a diverting stoma as part
of their treatment, which might well become permanent.
Complicated diverticular disease
Patients with overt sepsis requiring
surgical intervention almost always
require a diverting stoma as part of
their treatment, which might well
become permanent
Laparoscopic peritoneal lavage (LPL)
has failed to demonstrate significant
benefits
More than 80% of the patients with acute colonic diver-
ticulitis heal without complications. Current studies have
shown that in many patients without immunosuppressive
medication or other factors associated with poor healing
even antibiotics are not needed [115–117].
Complicated diverticulitis is characterized with perfora-
tion that can be either contained or uncontained. Based on
the surgical findings of abscesses and peritonitis, Hinchey
etal. classified the severity of acute diverticulitis into four
grades [10]: Stage 1. Pericolic abscess; Stage 2. Pelvic, intra-
abdominal, or retroperitoneal abscess; Stage 3. Generalized
purulent peritonitis; Stage 4. Generalized fecal peritonitis.
Recently, Sallinen etal. published a new classification
that takes into account organ dysfunction as one of the deter-
minants [118]. Based on a retrospective analysis it sets the
stage for the treatment of acute diverticulitis based on clini-
cal, radiologic and physiologic parameters: Stage 1. Uncom-
plicated diverticulitis; Stage 2. Complicated diverticulitis
with small abscess (< 6cm); Stage 3. Complicated diverticu-
litis with large abscess (≥ 6cm) or distant intraperitoneal or
retroperitoneal air; Stage 4. Generalized peritonitis without
organ dysfunction; Stage 5. Generalized peritonitis with
organ dysfunction. In their series, patients with Stages 1 or
2, only 1% and 5% needed surgery, none needed intensive
care and the mortality rates were 0% and 1%, respectively.
About half of the patients with Stage 3 disease needed sur-
gery, 8% needed intensive care and the mortality rate was
3%. Surgery was required in nearly all (98%) of the patients
with generalized peritonitis but no organ dysfunction (Stage

The Bucharest ESTES consensus statement onperitonitis
1 3
4), only 11% needed intensive care and the mortality rate
was 4%. In contrast, of patients with peritonitis and organ
dysfunction (Stage 5), all needed surgery and 50% needed
intensive care resulting in a mortality rate of 32% emphasiz-
ing the importance of the physiological state of the patient
in determining outcome.
The major current controversy in the management of
acute colonic diverticulitis evolves around the management
of patients with purulent peritonitis (Hinchey stage 3). Based
on three randomized studies and a meta-analysis [118–122],
it seems that while laparoscopic peritoneal lavage (LPL) is
comparable to sigmoid resection in terms of mortality, it is
associated with higher rate of reoperations and higher rate
of intra-abdominal abscesses.
In colonic perforation or perforated diverticulitis ini-
tial lavage with or without simple suture and drainage was
introduced in the late nineteenth century, then replaced pro-
gressively by the three-stage Mayo Clinic or the two-stage
Mickulicz procedures. The technique of lavage and drainage
regained popularity during the 1990s. This procedure can
also be performed laparoscopically with the advantage of
faster recovery and shorter hospital stay. In a prospective
multi-center study of 100 patients, the authors concluded
that LPL for perforated diverticulitis with generalized peri-
tonitis is feasible, with short-term results showing a low
recurrence risk [123].
Three recent randomized controlled trials, the DILALA
trial, SCANDIV trial and LADIES trial with a total of 343
patients (178 in the lavage group versus 175 in the resec-
tion group) showed inconsistent outcomes when LPL alone
was compared with resection. These three randomized trials
all had serious deficiencies regarding the risk of bias and
imprecision; their quality of evidence was low. Statistically
the laparoscopic lavage group had a significantly higher rate
of postoperative intra-abdominal abscess (RR 2.54, 95% CI
1.34–4.83), lower rate of postoperative wound infection (RR
0.10, 95% CI 0.02–0.51) and shorter length of postsurgi-
cal hospital stay (weighted mean difference = − 2.03, 95%
CI − 2.59 to − 1.47). There was no statistically significant
difference in postoperative mortality after index admission
or within 30days of intervention in all Hinchey stages. In
Hinchey stage III there was no significant difference in post-
operative mortality at 12months, surgical reintervention
at index admission or within 30-90days from index inter-
vention, stoma rate at 12months, or adverse events within
90days of any Clavien-Dindo grade between groups.
The authors found a significantly higher rate of postopera-
tive intra-abdominal abscess in patients who underwent LPL
than in those who underwent surgical resection. Since the
aim of surgery was to treat the sepsis, and if this technique
was associated with more postoperative abscesses, then this
technique should be considered ineffective [124].
In conclusionlaparoscopic peritoneal lavage (LPL) has
failed to demonstrate significant benefits. Overall, the qual-
ity of evidence was low and there were serious concerns
regarding the risk of bias and lack of precision. There was a
significantly increased rate of intra-abdominal abscess for-
mation with this approach. All in all, however, LPL does
not appear inferior to traditional surgical resection and may
achieve reasonable outcomes while consuming fewer hos-
pital resources.
Tertiary peritonitis
At least 20% of patients treated for secondary peritonitis
have a complicated outcome including anastomotic leaks
and abscesses. While these are well known and defined, ter-
tiary peritonitis is a rarer complication that is characterized
by organ dysfunction and prolonged systemic inflammation
associated with recurrent peritoneal infection by organisms
of low intrinsic pathogenicity [38]. It can also be defined as
persistence or recurrence of IAI after apparently adequate
therapy for primary or secondary peritonitis.
In a study by Nathens and co-workers from 1998 includ-
ing 59 patients with secondary peritonitis, tertiary peritonitis
was defined as culture-proved IAI persisting or recurring at
least 48h after apparently adequate treatment of secondary
bacterial peritonitis, and was observed in 44 patients (74%)
[38]. Enterococcus, Candida, Staphylococcus epidermidis,
and Enterobacter were the most common pathogens identi-
fied. Infectious foci were usually not amenable to percu-
taneous drainage and were poorly localized at laparotomy.
Compared with patients with uncomplicated secondary peri-
tonitis, tertiary peritonitis was associated with higher ICU
mortality (64% vs. 33%), higher organ dysfunction scores
and ICU length of stay.
More recently, the term “complicated intra-abdominal
infections” has been introduced, and newer studies have
grouped tertiary peritonitis among this group defined as per-
sisting peritonitis despite adequate surgical and initial anti-
microbial therapy [125]. In addition, other characterizations
have been used, such as “persistent and tertiary chronic”
peritonitis with distinct changes in immuno-responsiveness
[126], and showing the microbiological shift from aerobic
gram-negative bacteria towards gram-positive bacteria over
time when the condition persists [127].
A study of 69 patients with secondary peritonitis identi-
fied 15 patients (22%) who developed tertiary peritonitis
[128]. The transition to tertiary peritonitis was associated
with higher Mannheim Peritonitis Index at initial operation,
higher SAPS II score and C-reactive protein level on the
second postoperative day, higher relaparotomy rate and mor-
tality (60% vs. 9%), and longer ICU length of stay.
It seems that specifically Candidal peritonitis is increas-
ing in incidence and continuing to be associated with high

B.Diaconescu et al.
1 3
mortality. Factors that have been identified with increasing
risk of development of Candidal peritonitis include hollow
viscus perforation, abdominal and thoracic surgery, surgical
drains insitu, intravenous and urinary catheters, total par-
enteral nutrition, sepsis, antibiotic therapy more than 48h
before peritonitis, immunosuppression, diabetes mellitus and
extensive Candidal colonization [129].
The true nature and exact characterization of tertiary
peritonitis is still somewhat obscure. Is it a true entity and
if so, what are the definitive clinical, microbiological and
biochemical markers that help to identify it? Once this is
elucidated, perhaps more relevant guidelines for the diag-
nosis and management can then be formulated.
What can estes add?
During the course of this conference peritonitis has been
classified into four types: primary, secondary, tertiary [1]
and peritoneal dialysis (PD) related. The literature is awash
with guidelines for the management of primary and PD
related peritonitis which are generally the preserves of the
hepatologist and nephrologist respectively. There is uncer-
tainty as to the true nature of tertiary peritonitis. Is it the
result of inadequate treatment of secondary peritonitis, or is
it a separate entity? Even if future research clearly proves the
latter, it is likely that many cases considered to be tertiary
peritonitis under current definitions may not fulfil the new
diagnostic criteria. It therefore follows that the focus of the
surgical community should be on the optimal management
of secondary peritonitis.
The management of secondary peritonitis requires a com-
bination of source control, supportive therapy to overcome
organ dysfunction and antimicrobial therapy.
Secondary peritonitis is polymicrobial and the rapid
initiation of antimicrobial therapy essential for the effec-
tive management of sepsis will require combination ther-
apy determined on an empirical basis until the results of
appropriate cultures with microbiological sensitivities are
available. This should include antimicrobials with efficacy
against bacteria and fungi. There are numerous national and
international guidelines to help inform this process, but the
most effective selection will be based on local surveillance
of antimicrobial resistance and adapted for clinical risk fac-
tors for resistance on an individual patient basis [130].
Secondary peritonitis is often classified as either com-
munity acquired or healthcare acquired. This may affect
the efficacy of antimicrobial agents in terms of both spec-
trum adequacy and microbial susceptibility [131] resulting
in fewer healthcare acquired cases of peritonitis being as
susceptible to a standard antimicrobial regimen as cases
acquired in the community. In these cases, the choice of
antimicrobial therapy may need to be modified, but unless
this is done empirically at the outset, the distinction is of no
practical value as far as antibiotic selection is concerned.
Moreover, the prognosis in terms of morbidity and mortal-
ity is determined by the severity of the peritonitis rather
than the geographical location within which it originated
[132]. Community acquired fecal peritonitis resulting from
a diverticular perforation might be expected to have more
in common with fecal peritonitis due to the dehiscence of a
colonic anastomosis than it would with a localized peritoni-
tis resulting from a grade 2 cholecystitis [133]. The recent
classification of acute diverticulitis that includes organ dys-
function suggests that this is also a better discriminator of
outcome than the nature of the peritoneal contaminant [118].
We have sought to define the principles of management:
optimizing the physiology with appropriate fluid resusci-
tation and organ support, effective use of antibiotics and
interventional procedures. We have described the current
state of knowledge regarding damage control surgery and
the role of the open abdomen. We have looked in detail at
specific organ systems and pathology.
Unlike the trauma patient, where control of exsanguinat-
ing hemorrhage mandates immediate intervention, the opti-
mum timing for surgery in the septic patient with secondary
peritonitis has yet to be determined and remains controver-
sial. A balance has to be struck between ensuring adequate
pre-operative resuscitation in terms of improving circulating
volume and tissue perfusion whilst at the same time limiting
the relentless progression of sepsis and organ dysfunction
that follows in the absence of adequate source control. The
use of goal-directed fluid therapy, ensuring a mean arterial
pressure of at least 65mmHg and normalizing serum lactate
levels are worthy targets, but are they the best, and should
they be modified in light of other factors?
The review of damage control surgery highlighted both
the importance of patient selection in non-trauma emergency
surgery and the paucity of strong evidence supporting the
use of this therapeutic modality in this group of patients.
The small-scale studies of the technique of combining nega-
tive pressure wound therapy with a polypropylene mesh are
encouraging, but again, larger studies are required to subject
this to appropriate scientific rigor.
These areas of immense uncertainty can be summarized
succinctly as being when to open and when and how to close
the abdomen in secondary peritonitis. That should remain
the preserve of the surgeon and is an area where ESTES,
with its extensive networks and wealth of individual experi-
ence can help.
As with most academic activity, this conference has raised
more questions for the surgical body. When is the best time
to obtain surgical source control in secondary peritonitis?
How can that moment be determined? Which patients should
be selected for damage control surgery and how should this
be done? Finally, is the combined use of negative pressure

The Bucharest ESTES consensus statement onperitonitis
1 3
therapy and polypropylene mesh really the best method for
achieving ultimate closure of the fascia in these patients?
Compliance with ethical standards
Conflict of interest Ideclare that Bogdan Diaconescu, Selman Uranues,
Abe Fingerhut, Mihaela Vartic, Mauro Zago, Hayato Kurihara, Rifat
Latifi, Dorin Popa, Ari Leppäniemi, Jonathan Tilsed, Matei Bratu,
Mircea Beuran have no conflict of interest.
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