14.1 Introduction

Rapid initial source control and an adequate antimicrobial and supportive intensive care therapy are the key elements to treat secondary peritonitis successfully [1, 2]. Nevertheless some patients develop a complex clinical state, which is characterized by:

  • A persistent abdominal infection

  • An altered microbial flora

  • A progressive or resistant organ dysfunction

These patients are a challenge for nowadays’ emergency surgeons and require two essential approaches:

  1. 1.

    An everyday reassessment of the intensive care patient

  2. 2.

    An interdisciplinary everyday round and discussion of the critical state

In literature the term “tertiary peritonitis” is often used to describe the abovementioned situation.

According to the ICU Consensus Conference from 2005, tertiary peritonitis is defined as a severe recurrent or persistent intra-abdominal infection >48 h after apparently successful and adequate surgical source control in secondary peritonitis [3, 4]. Mortality rate is inacceptably high and ranges between 30 and 65% [3]!

In everyday routine, the term “ongoing peritonitis” as a “smoldering fire” within the peritoneal cavity is used more often and will be used in the following.

Review of the literature reveals that certain premorbid factors result in an increased risk for impaired control of an intra-abdominal focus: patients with increased age [5], with chronic renal insufficiency, diabetes mellitus, and HIV infection, or under corticosteroid [6] and other immunosuppressives should be monitored carefully concerning development of ongoing peritonitis. Despite these risk factors, the identification of the “typical patient” with ongoing peritonitis failed in the literature [7].

Despite preexisting morbidity, an unsuccessful source control and an inadequate antimicrobial therapy of a secondary peritonitis should be seen as main reasons for persistent peritonitis. As published recently, severe intra-abdominal infection, inadequate source control, and fungal isolates were independent risk factors for an ongoing peritonitis [8].

14.2 Diagnosis of Ongoing Peritonitis

After initial surgical source control, in particular, signs and symptoms of sepsis or an ongoing peritonitis are unspecific and often missed by clinicians and nurses. Early signs of an abdominal reinfection or persistence of an intra-abdominal inflammation require an expert view on the patient. Literature reveals that especially non-intensivists have a dramatic lack of knowledge on the signs of (intra-abdominal) sepsis and peritonitis [9,10,11]. Even experienced surgeons misdiagnose a recurrence or persistence of an intra-abdominal infection after initial source control, because peritonitis can be masked by and attributed to “normal” postoperative problems like intestinal paralysis, under-resuscitation, postoperative mental deterioration, etc. [12]. In ongoing peritonitis after initial surgery abdominal pain, rebound tenderness and fever occurred less often than in secondary peritonitis after intestinal perforation [13].

Signs and symptoms of an ongoing or recurrent peritonitis are often masked and misinterpreted.

Besides clinical examination of the abdomen, an elevated respiratory frequency is a clinical parameter to detect patients with an ongoing intra-abdominal sepsis. It thus became part of many established ICU scores like quickSOFA, CURB-65 score, or APACHE II.

Due to the masked clinical signs and symptoms, a slight suspicion of a recurrence/persistence of peritonitis should lead to a radiographic imaging like CT, ultrasound, or X-ray. During everyday rounds, the patient should be reevaluated concerning persistence/occurrence of organ dysfunctions (urinary output, ventilation parameters, cardiovascular support), inflammatory parameters, quality of drainage secretion, etc.. In an interdisciplinary approach, the decision to perform radiographic imaging has to be reevaluated everyday. Although CT shows highest sensitivity (97.2%) in cases of secondary peritonitis, it is significantly lower in ongoing peritonitis. Thus, a negative CT scan in a critically ill patient with an ongoing peritonitis should lead to the critical discussion, if a relaparotomy/relaparoscopy is indicated [14]. As a bedside technique, ultrasound allows an immediate examination of the peritoneal cavity, which includes the possibility to drain intra-abdominal fluid collections. CT- or ultrasound-guided drainages are of diagnostic value on the one hand (pus? clear fluid? hematoma? etc.). On the other hand, drainage of intra-abdominal abscesses or bilioma can be one kind of source control with minor morbidity compared to surgery in ongoing peritonitis.

CT-/ultrasound-guided drainage of intra-abdominal fluid collections is one important element for diagnosis and therapy of ongoing peritonitis.

Routine parameters of intra-abdominal infections are white blood cell count (WBC) and C-reactive protein (CRP). While specificity of CRP is low [15], it is a routine parameter to monitor septic patients on intensive care units. During sepsis therapy, a secondary increase of CRP can indicate an infectious complication. The same is true for a CRP persistence. A landmark study from Heidelberg showed that an elevated CRP (>140 mg/dl) on the fourth day after elective surgery is a predictor for inflammatory complications [16]. During ongoing peritonitis, procalcitonin (PCT) has been shown to be a sensitive and rapid parameter for a bacterial (re-)infection. While systemic infections go in line with an up to 5000-time increase within 4 h, located sources of infection can be PCT negative. So far it remains nebulous, if PCT can distinguish between (“sterile”) SIRS and sepsis [17,18,19]. In contrast PCT is a helpful tool to monitor a patient with an intra-abdominal infection [20]. It furthermore can indicate when to finish antimicrobial therapy [20, 21]. As published recently, PCT guidance stimulates reduction of duration of treatment and by this reduces mortality [22].

Immunological research on biomarkers indicating sepsis mainly focusses on rapid detection of the septic patients. Modern research could identify markers like interleukin (IL)-6, IL-1α, TNFα, HMGB-1, MMP-9 VEGF, ICAM-1 MPO, methylglyoxal, and caspase 3 as sensitive indicators of sepsis development [23]. Whether these markers could also help to detect the patient with a complicated, recurrent, and refractive peritonitis remains unclear up to date.

On intensive care units, the regular collection of specimen, e.g., from urinary catheters, drainages, and bronchial secretion, is necessary to detect hospital-acquired (re-)infections. The examination of blood cultures plays a central role in the diagnosis of persistent peritonitis: two to three pairs (aerobic and anaerobic) of blood culture bottles should be collected regularly from both peripheral blood and also from central venous catheters [24]. Especially in cases of ongoing peritonitis, the preexisting antibiotic therapy reduces the detection rate of blood culture technique, which furthermore cannot differentiate between infection and colonization [25].

The latter is an important risk factor for the development of ongoing peritonitis. These patients are threatened by hospital-acquired infections. The colonization with multidrug-resistant pathogens like methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and multidrug-resistant gram-negative bacteria (MRGN) is often diagnosed in surgical patients and leads to isolation of the patient. The simple colonization of our patients with multidrug-resistant germs nevertheless is not treated routinely nowadays. Results of the REDUCE (Randomized Evaluation of Decolonization versus Universal Clearance to Eliminate) MRSA trial could change our view on antimicrobial therapy of the colonized patient: results reveal that intensive care patients clearly profit from a universal decolonization compared to screening and isolation methods [26]. If patients with ongoing peritonitis, who are colonized with MDR germs, should be decolonized, has to be shown in future studies.

In contrast to blood culture, PCR-based techniques like IRIDICA System (Abbott) or the next-generation sequencing (NGS) could provide a more rapid detection of bacteria and certain resistant phenotypes [27]. So far prospective studies are still missing. As published recently, these new techniques could play a crucial role to monitor therapy of a septic patient with an ongoing peritonitis in the future [28, 29].

14.3 Therapy

14.3.1 Surgery

Surgical source control is the only causal and life-saving treatment option for patients with secondary peritonitis. It is based on the four crucial elements: debridement, removal of infected devices, drainage of purulent cavities, and decompression of the abdominal cavity. To avoid a prolonged primary emergency operation, the reconstruction of anatomy and function could be performed in a second intervention 24–48 h after emergency. This goes in line with modern concepts of damage control surgery, which were established for trauma patients first [12, 14]. Indication for damage control surgery is the lethal triad of coagulopathy, inflammation, and cardiovascular instability. This easy rule is not only true for the emergency room situation but can also be established for the critically ill patient with a persistent or recurrent peritonitis, who dynamically develops this critical health state after initial source control (Fig. 14.1).

Fig. 14.1
figure 1

The lethal triad of abdominal sepsis consists of coagulopathy, inflammation, and cardiovascular instability. These clinical conditions are indicators for immediate surgery. In ongoing peritonitis, patients have to be monitored both technically and clinically and carefully be reevaluated during everyday rounds [14] (Reproduced with permission from Springer)

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As mentioned above, the mortality of ongoing peritonitis is incredibly high and reaches up to 65% in literature! The most important independent risk factor is an insufficient source control during initial surgery. A bundle of trials could prove that non-successful source control leads to a dramatically increase in mortality (Table 14.1).

Table 14.1 Impact of surgical source control on the mortality of patients with secondary peritonitis [14]
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Besides adequacy of initial source control, the importance of the timing of surgery gets into the focus of research. Several trials analyzed the importance of the “time to intervention” for the outcome of patients with secondary peritonitis [30,31,32,33,34].

In cases of ongoing peritonitis, there are three different surgical strategies for patients in general:

  1. 1.

    Relaparotomy on demand

  2. 2.

    Planned relaparotomy within 36–48 h

  3. 3.

    Open abdomen technique

The concept of planned relaparotomy is based on the a priori decision to reexplore the peritoneal cavity independent from its necessity. This is in contrast to the relaparotomy on demand, which is performed, if there are hints of clinical deterioration of the critically ill patient. Of course, the critical everyday reevaluation of the patient during interdisciplinary rounds is necessary to perform this concept (Fig. 14.2). In a landmark study from Ruler et al., there was no difference between “on-demand” (n = 116) and “planned” (n = 116) laparotomy concerning patients’ mortality (29% on demand, 36% planned), but intervention rates and hospital costs were significantly lower in the “on-demand” study group [35].

Fig. 14.2
figure 2

Second look 48 h after initial emergency operation. In cases of persisting or new organ failure, a relaparotomy should be evaluated. If so, surgery should be performed within 48 h after the first operation

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The decision to perform a “relook” on demand is difficult and requires much surgical experience. Besides the abovementioned lethal triad of sepsis, there are no clinical selection criteria for patients with an ongoing peritonitis [3, 36]. Van Ruler et al. analyzed 219 patients with secondary peritonitis and emergency laparotomy concerning the indication for surgical reintervention. Neither the initial origin of the intra-abdominal focus nor the findings of the surgeon during primary emergency surgery could indicate the need for a “second look.” In contrast the persistence and occurrence of organ failure after emergency surgery were indicators for ongoing peritonitis and independent risk factors for an early surgical reexploration [37].

If the decision for surgical relaparotomy (on demand) is made, it should be performed rapidly. Koperna et al. analyzed 523 patients, who had undergone initial emergency surgery in cases of secondary peritonitis. In 105 patients, therapy failed, and a relaparotomy was indicated. In these cases mortality was significantly lower, if surgical relook was performed within 48 h after initial emergency surgery [38]. In contrast to open abdomen surgery, both concepts of relaparotomy “on demand” and of planned relaparotomy bear the risk to develop an acute abdominal compartment syndrome (ACS) in ongoing peritonitis. Thereby, the patient with ongoing peritonitis can develop a combination of a primary ACS, caused by the peritonitis itself, and a secondary ACS, which is caused by a capillary leakage, volume resuscitation, etc. [39]. Surveys revealed that, despite its hazardousness, ACS is often misdiagnosed or diagnosed too late. Only 47% of the physicians interviewed could define ACS [39]. As the diagnostic of choice, intra-abdominal pressure is typically measured indirectly through the bladder. ACS is defined as a sustained intra-abdominal pressure >20 mmHg associated with a new organ dysfunction. Due to its importance for the survival of patients with ongoing peritonitis, the guidelines recommend the monitoring of the intra-abdominal pressure by measurement through the bladder every 6 h in these patients [40].

Despite the preferred concept of an on-demand laparotomy, there are still clearly defined indications for a staged laparotomy like reevaluation of the intestinal viability in cases of mesenteric ischemia with secondary peritonitis [14].

Current clinical guidelines do not recommend the routine use of open abdomen surgery for abdominal sepsis [3]. Although, of course, a regular second look is easy to perform, open abdomen treatment bears the risk of enteroatmospheric fistulas and fascial deviation [41]. This increased surgical morbidity in the critically ill patient with ongoing peritonitis can result in higher mortality rates, which was published recently [42]. Although not standard, open abdomen surgery nevertheless is one important tool for trauma surgeons: open abdomen surgery is the gold standard surgical approach for patients with ongoing peritonitis, who bear the risk of abdominal compartment syndrome (ACS) development. As published recently, it is also a safe and effective technique for patients, in whom a second look is expected to be performed [3]. This is the case for severe cases of secondary (and ongoing) peritonitis [3]. The World Society of Emergency Surgeons (WSES) published a landmark position paper on the open abdomen procedure in this emergency setting [3].

14.3.2 Intensive Care

As for the secondary peritonitis, supportive intensive care medicine is essential for patients with ongoing peritonitis. In contrast to patients with secondary peritonitis, the intensivists could be confronted with open abdomen surgery. Patients with ongoing peritonitis are typically threatened by increased fluid loss, muscle proteolysis, heat loss (especially in open abdomen surgery), and an impaired immune function. For patients with an open abdomen, intensive care furthermore has to focus on:

  • Restrictive fluid management

  • Monitoring of the body weight

  • Tailored ventilatory support (low tidal volume)

  • Rewarming

  • Sedation and pain control

  • Monitoring of pH (>7.2) and serum lactate

In ongoing peritonitis especially the surgical “on-demand” concept requires a vigilant observation of the patient in the ICU. According to the guidelines of the Surviving Sepsis Campaign [43], patients with a persisting peritonitis should be treated in concordance with certain target criteria:

  1. 1.

    Prophylaxis of ulcers (e.g., proton pump inhibitor)

  2. 2.

    Lung-protective ventilation (ARDS network protocol)

  3. 3.

    Hemodynamic stabilization

    • Mean arterial pressure >65 mmHg

    • Volume according to clinical examination

    • Inotropics in cases of myocardial dysfunction

    • Invasive hemodynamic monitoring, echocardiography

    • Glomerular filtration rate >0.5 ml/kg body weight

    • Repetitive measurement of serum lactate

  4. 4.

    Blood glucose 110–180 mg/dl

  5. 5.

    Prophylaxis of thrombosis

  6. 6.

    Enteral nutrition, if possible

While these core values could be a valuable guideline for everyday rounds, the exact doses, the amount of monitoring, etc. are—at least in part—a controversial topic of debate in modern literature.

As one example for one ongoing debate, recent literature reveals that a conservative/restrictive way of ventilation (paO2 70–100 mmHg, SpO2 94–98%) is advantageous for critically ill (long-term) ventilated patients in contrast to a conventional ventilation regimen (paO2 up to 150 mmHg, SpO2 97–100%) [44].

While hydrocortisone is one adjunctive tool to treat patients with septic shock, its use in patients with severe sepsis does not reduce the risk to develop cardiovascular instability/septic shock (HYPRESS trial) [45]. An update of recent literature furthermore reveals that calcium-sensitizing drugs like levosimendan are not associated with a decreased mortality or an improved organ function [46].

During everyday rounds, intensivists should monitor key aspects of modern intensive care medicine, according to the “FAST-HUG” (feeding, analgesia, sedation, thromboembolic prophylaxis, head-of-bed elevation, stress ulcer prevention, and glucose control) principle published by Vincent et al. [47] before. As shown in Fig. 14.3, any lack of clinical improvement or deterioration after initial source control should lead to an interdisciplinary discussion, if a relaparotomy (on demand), a second look (into the opened abdominal cavity), or any radiographic imaging should be performed.

Fig. 14.3
figure 3

Schematic drawing of the three columns of modern therapy of ongoing peritonitis. Essential is the interdisciplinary everyday reevaluation of the patients [14]. (Reproduced with permission from Springer)

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14.3.3 Antimicrobial Therapy

Broad-spectrum antibiotics (Tarragona strategy) are the third therapeutic column in sepsis therapy. While in secondary peritonitis the broad-spectrum antimicrobial therapy often can be de-escalated and focused according to resistograms from blood culture or other specimen, ongoing peritonitis often requires an escalation and modification of antibiotics. In ongoing peritonitis, the antimicrobial state of a patient has to be reevaluated during daily rounds on intensive care units. In contrast to secondary peritonitis, patients with a persistent or recurrent peritonitis are more often confronted with multiresistant germs or fungi [7, 14]. Furthermore the hospital-specific individual microbial flora has to be considered, when choosing the appropriate antimicrobial therapy. There are hints from recent literature that a permanent intravenous infusion of β-lactam antibiotics could be more effective than the standard intermittent infusion in severe sepsis [48]. Whether this is also true for patients with ongoing peritonitis remains nebulous.

If the intra-abdominal infection is not under control, the antibiotic therapy has to be critically reevaluated after 48 h.

Depending on the suspected location of the infectious source (ongoing/recurrent infection of the peritoneal cavity, pulmonary infection, catheter-associated infection, etc.), intensivists have an impression on the bacterial flora and can treat the patient accordingly. Figure 14.4 gives an overview on the microbial flora of intra-abdominal infections and the corresponding “standard schemes” of antimicrobial therapy.

Fig. 14.4
figure 4

Typical microbial flora in intra-abdominal sepsis. In cases of ongoing peritonitis, the spectrum shifts to nosocomial flora with typical pathogens (in red) [14] (Reproduced with permission from Springer)

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As stated above, the antimicrobial therapy can be adapted to certain results of bacterial cultures or PCR-based methods from specimen collected at different sources of infection.

Antibiotic stewardship is gaining importance on nowadays’ ICUs. The surveillance on the use of antimicrobials is essential both for the patient and to avoid antibiotic resistance.

Ongoing peritonitis could be seen as a nosocomial infection of the peritoneal cavity. The spectrum of MDR microorganisms includes enterococci, Enterobacteriaceae, Pseudomonas, and candida. Additionally ongoing peritonitis is often accompanied by pulmonary (30%) or urinary (8%) infections. Inadequate use of antibiotics threatens especially patients with ongoing peritonitis. As published by Hackel et al., none of the ten most frequently isolated bacteria from intra-abdominal infections was sensitive to ampicillin/sulbactam [1, 49] in the USA. New antibiotics and combinations were designed also for intra-abdominal infections and could be life-saving for patients with ongoing peritonitis. Table 14.2 provides an overview on “new-generation” antibiotics, which could be used as second-/third-line therapy in cases of ongoing peritonitis.

Table 14.2 New-generation antibiotics and their potential indications
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In patients with ongoing peritonitis, germs like Staphylococcus epidermidis, Enterococcus, and Enterobacter are selected out by initial broad-spectrum antibiotics. The same is true for candida species. If a patient has a neutropenia, immunosuppression, or a prolonged peritonitis, an antimycotic drug should be integrated into the antimicrobial therapy. Fungal isolates have been identified as independent risk factors for the development of a persistent peritonitis/ongoing peritonitis [1]. Bassetti et al. underlined the relevance of intra-abdominal candidiasis for intensive care patients. While mortality of ICU patients with intra-abdominal candidiasis was 50% (!), it was only half for non-ICU patients [60]. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recommends echinocandins as first-choice medication for intensive care patients with candida infection [61]. In cases of Candida parapsilosis, fluconazole could be a rational alternative. The antimycotic should be applied until 14 days after the patient is candida negative in culture. Inadequate therapy of intra-abdominal candidiasis has been proven to be one important negative prognostic parameter for the survival of ICU patients [1, 60]. In contrast, the use of micafungin as a routine empirical treatment in critically ill patients with suspected fungal infection did not improve fungal infection-free survival at 28 days, as published recently [62].