On the basis of the source and nature of the microbial contamination, peritonitis can be classified into primary, secondary and tertiary. Primary peritonitis is a diffuse bacterial infection without loss of integrity of the gastrointestinal tract. It is a rare condition occurring mainly in infancy, early childhood and in cirrhotic patients. Secondary peritonitis is the most common form of peritonitis and results from loss of integrity of the gastrointestinal tract due to perforation (e.g. perforated duodenal ulcer) or by direct invasion from infected intra-abdominal viscera (e.g. gangrenous appendicitis). Tertiary or ongoing peritonitis is defined as a severe recurrent or persistent intra-abdominal infection >48 h after apparently successful and adequate surgical source control of secondary peritonitis. Although it is less common, it may comprise of a severe systemic inflammation response. Tertiary peritonitis is associated with microbial shift towards nosocomial flora including Staphylococci coagulase-negative, Candida, Enterococci, Pseudomonas, Enterobacter and other opportunistic bacteria and fungi. Mortality rate in tertiary peritonitis is very high.
Abdominal sepsis represents the host’s systemic inflammatory response to bacterial or yeast peritonitis. In the event of peritonitis gram-negative, gram-positive, as well as anaerobic bacteria, including common gut flora, such as Escherichia coli, Klebsiella pneumoniae, Streptococcus spp. and Bacteroides fragilis, enter the peritoneal cavity. Sepsis from an abdominal origin is initiated by the outer membrane component of gram-negative organisms (e.g., lipopolysaccharide [LPS], lipid A, endotoxin) or gram-positive organisms (e.g., lipoteichoic acid, peptidoglycan), as well anaerobe toxins. This lead to the release of proinflammatory cytokines such as tumor necrosis factor α (TNF-α), and interleukins 1 and 6 (IL-1, IL-6). TNF-α and interleukins lead to the production of toxic mediators, including prostaglandins, leukotrienes, platelet-activating factor, and phospholipase A2, that damage the endothelial lining, leading to increased capillary leakage. Cytokines lead to the production of adhesion molecules on endothelial cells and neutrophils. Neutrophil-endothelial cell interaction leads to further endothelial injury through the release of neutrophil components. Activated neutrophils release nitric oxide, a potent vasodilator that leads to septic shock. Cytokines also disrupt natural modulators of coagulation and inflammation, activated protein C (APC) and antithrombin. As a result, multiple organ failure may occur.
Early detection and timely therapeutic intervention can improve the prognosis and overall clinical outcome of septic patients. However, early diagnosis of abdominal sepsis can be difficult; determining which patients presenting with signs of infection during an initial evaluation, do currently have, or will later develop a more serious illness is not an easy or straightforward task.
Sepsis is a complex, multifactorial syndrome which can evolve into conditions of varying severity. If left untreated, it may lead to the functional impairment of one or more vital organs or systems.
Delineating the source of infection as accurately as possible prior to surgery is the primary aim and the first step in managing peritonitis. In severe abdominal sepsis however, delays in operative management may lead to worse outcomes and early exploration is always recommended when peritonitis is suspected even if the source of infection is not recognized pre-operatively with certainty.
The diagnosis of acute secondary peritonitis is based primarily on clinical assessment. Typically, the patient is admitted to the emergency department with abdominal pain or tenderness and a systemic inflammatory response, including fever, tachycardia, and tachypnoea. Abdominal rigidity suggests the presence of peritonitis. However, clinical assessment alone is not always reliable in critically ill patients due to a variety of clinical constraints (e.g., impaired consciousness, severe underlying disease, etc.). Hypotension, oliguria, and acute altered mental status are warning signs of the patient’s transition to organ failure. In many countries worldwide, a large proportion of patients with diffuse peritonitis still present to the hospital with unacceptable delay. This event reduces the percentage of surviving at the lowest rates in the world. In emergency departments of limited-resource hospitals, the diagnosis of peritonitis is mainly clinical; supported by basic laboratory tests like full blood count (complete blood count). Ultrasonography (US) is sometimes done to aid diagnosis, if available. Therefore, the clinician has to improve clinical diagnosis by looking carefully for those signs and symptoms. In rural and remote areas of LMICs, diagnostic imaging is often insufficient, and in some instances, completely lacking. In recent years, ultrasound use has increased worldwide, facilitated by ultrasound machines becoming smaller, more reliable, and less expensive. Ultrasound is reproducible and can be easily repeated, but remains highly user-dependent, and thus, experience should be taken into account for diagnostic accuracy and reliability. In stable patients, abdominal computerized tomography (CT) is the imaging modality of choice, especially when the diagnosis is uncertain. However, in critically ill patients, if the diagnosis of peritonitis is made clinically or by previous radiological examinations (plain films of the abdomen or US), additional CT scanning may be unnecessary and would only delay much-needed surgical intervention.
The timing and adequacy of source control are of outmost importance in the management ofabdominal sepsis, as late and/or incomplete procedures may have severely adverse consequences on outcome. Source control encompasses all measures undertaken to eliminate the source of infection, reduce the bacterial inoculum and correct or control anatomic derangements to restore normal physiologic function. This generally involves drainage of abscesses or infected fluid collections, debridement of necrotic or infected tissues and definitive control of the source of contamination. It is well known that inadequate source control at the time of the initial operation has been associated with increased mortality in patients with severe intra-abdominal infections. Early control of the septic source can be achieved using both operative and non-operative techniques. An operative intervention remains the most viable therapeutic strategy for managing intra-abdominal sepsis.
The initial aim of the surgical treatment of peritonitis is the elimination of bacterial contamination and inflammatory substances and prevention or reduction, if possible, of fibrin formation. Generally, the surgical source control employed depends on the anatomical source of infection, the degree of peritoneal inflammation and generalized septic response, and the patient’s pre-morbid condition.
Surgical source control entails resection or suture of a diseased or perforated viscus (e.g. diverticular perforation, gastroduodenal perforation), removal of the infected organ (e.g. appendix, gallbladder), debridement of necrotic tissue, resection of ischemic bowel and repair/resection of traumatic perforations with primary anastomosis or exteriorization of the bowel.
Laparotomies are usually performed using a midline incision. The primary objectives of surgical intervention include (a) determining the cause of peritonitis, (b) draining fluid collections, (c) controlling the origin of the abdominal sepsis. In certain circumstances, infection not completely controlled may trigger an excessive immune response and sepsis may progressively evolve into severe sepsis, septic shock, and organ failure.
Such patients would benefit from immediate and aggressive surgical treatment with subsequent re-laparotomy strategies, to curb the spread of organ dysfunctions caused by ongoing sepsis.
Three relaparotomy strategies are currently employed for management of abdominal sepsis following an initial laparotomy: (a) open abdomen, (b) planned re-laparotomy, and (c) on-demand re-laparotomy.
The on-demand re-laparotomy is recommended for patients with severe peritonitis because its ability to streamline healthcare resources, reduce overall medical costs, and prevent the need for further re-laparotomies. However the open abdomen may be a viable option for treating physiologically deranged patients with ongoing sepsis, facilitating subsequent exploration and control of abdominal contents, and preventing abdominal compartment syndrome.
A key component of the first-line management of the septic patient is the administration of IV antimicrobial therapy. Antimicrobial therapy plays a pivotal role in the management of intra-abdominal infections, especially in patients with severe sepsis who require immediate empiric antibiotic therapy. An insufficient or otherwise inadequate antimicrobial regimen is one of the variables more strongly associated with unfavorable outcomes in critical ill patients. Empiric antimicrobial therapy should be started as soon as possible in patients with sepsis with or without septic shock. Increasing rates of resistance and a more comprehensive understanding of the sepsis process have prompted many experts to advocate the use of broad-spectrum antimicrobial regimens in the initial stages of treatment for sepsis. Subsequent modification of the initial regimen becomes possible later, when culture results are available and clinical status can be better assessed, 48–72 hours after initiation of empiric therapy. However, apart from early timing of administration, selection of a pharmacological agent with penetration to the site of presumed infection, is necessary. Furthermore, the pathophysiological and immunological status of the patient and the pharmacokinetic properties of the chosen drugs warrant consideration. In the event of abdominal sepsis, clinicians must be aware that drug pharmacokinetics may be altered significantly in critically ill patients due to the pathophysiology of sepsis.
One of the most likely explanations for the high morbidity and mortality rates associated with sepsis is the development of cardiovascular insufficiency, which can lead to global tissue hypoxia. In sepsis, the early haemodynamic profile is characterized by hypovolaemia, vaso-regulatory dysfunction, and myocardial depression. Increased capillary leakage and venous capacitance ultimately result in decreased venous return to the heart. Additionally, cytokines released during the patient’s immune response may trigger further myocardial depression. These haemodynamic alterations associated with the early stages of sepsis are often accompanied by an increase in systemic oxygen demand and impaired oxygen delivery, thereby inducing global tissue hypoxia. Global tissue hypoxia may overstimulate endothelial cell activity, which can subsequently lead to the systemic inflammatory cascade characteristic of sepsis.
Fluid therapy to improve microvascular blood flow and increase cardiac output is an essential part of the treatment of patients with sepsis. Crystalloid solutions should be the first choice because they are well tolerated and cheap. They should be infused rapidly to induce a quick response but not so fast that an artificial stress response develops. They should be interrupted when no improvement of tissue perfusion occurs in response to volume loading. Basal lung crepitations may indicate fluid overload or impaired cardiac function. Recently, measuring inferior vena cava (IVC) diameter by ultrasound was suggested as a novel outcome measure to guide this resuscitative approach.
These data indicate that an early identification and prompt administration of intravenous fluids are mandatory. However, initial resuscitation should no longer be based on a predetermined protocol but on clinical endpoints. Hypotension is the most common indicator of inadequate perfusion.
Particularly in patients with abdominal sepsis, requiring urgent surgical intervention, overly aggressive fluid resuscitation may increase intra-abdominal pressure and worsen the inflammatory response, which is associated with a high risk of complications. In patients with septic shock fluid infusion during resuscitation, bowel oedema and forced closure of the abdominal wall can cause intra-abdominal hypertension and abdominal compartment syndrome that can consequently modify pulmonary, cardiovascular, renal, splanchnic, and central nervous system physiology causing significant morbidity and mortality.
Vasopressor agents should be administered to restore organ perfusion if fluid resuscitation fails optimizing blood flow and if hypotension persists following fluid loading. These agents should be globally available. Vasopressor and inotropic agents have increasingly become a therapeutic cornerstone for the management of sepsis. They have excitatory and inhibitory actions on the heart and vascular smooth muscle, as well as important metabolic, central nervous system, and presynaptic autonomic nervous system effects.
Increased global availability of vasopressors together with a better understanding of their indications, pharmacodynamics, and important adverse effects are mandatory to fight sepsis worldwide.
References
Sartelli M, Chichom-Mefire A, Labricciosa FM, Hardcastle T, Abu-Zidan FM, Adesunkanmi AK, et al. The management of intra-abdominal infections from a global perspective: 2017 WSES guidelines for management of intra-abdominal infections. World J Emerg Surg. 2017;12:29.
Sartelli M, Catena F, Di Saverio S, Ansaloni L, Malangoni M, Moore EE et al. Current concept of abdominal sepsis: WSES position paper. World Journal of Emergency Surgery : WJES. 2014;9:22. doi:10.1186/1749-7922-9-22.
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