Mediastinitis

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Background

Mediastinitis is a life-threatening condition that carries an extremely high mortality if recognized late or treated improperly.[1, 2, 3, 4] Although long recognized as a complication of certain infectious diseases, most cases of mediastinitis are associated with cardiac surgery (>300,000 cases per year in the United States).[4] This complication affects approximately 1-2% of these patients. Although small in proportional terms, the actual number of patients affected by mediastinitis is substantial. This significantly increases mortality and cost. After 10 years of evolution, the optimal therapy for mediastinitis is more clearly understood.

Future directions for research should focus on prevention, including timely antibiotic administration, sterile technique, prophylactic measures such as topical bacitracin, and meticulous hemostasis. Focus should also include more accurate methods of diagnosis during the first 14 days after surgery, when computed tomography (CT) findings are not reliable. However, the keys to successful management remain early recognition and aggressive treatment, including sternal reopening and debridement. Further research should also focus on the optimal timing and method of wound closure and the duration of antibiotic therapy required for optimal treatment.

Anatomy

The portion of the thorax defined as the mediastinum extends from the posterior aspect of the sternum to the anterior surface of the vertebral bodies and includes the paravertebral sulci when the locations of specific mediastinal masses are defined. It is limited bilaterally by the mediastinal parietal pleura and extends from the diaphragm inferiorly to the level of the thoracic inlet superiorly.

Traditionally, the mediastinum is artificially subdivided into three compartments for better descriptive localization of specific lesions. When the location or origin of specific masses or neoplasms is discussed, the compartments or spaces are most commonly defined as the anterior, middle, and posterior.

The anterior compartment extends from the posterior surface of the sternum to the anterior surface of the pericardium and great vessels. It normally contains the thymus gland, adipose tissue, and lymph nodes. The physiology of the anterior mediastinum includes the lymphatics and thymus gland. The physiology of the middle mediastinum includes the bronchi, the heart and pericardium, the hila of both lungs, the lymph nodes, the phrenic nerves, the great vessels, and the trachea. The physiology of the posterior mediastinum includes the azygos vein, the descending aorta, the esophagus, the lymph nodes, the thoracic duct, and the vagus and sympathetic nerves.

Pathophysiology

Infection from either bacterial pathogens or more atypical organisms can inflame any of the mediastinal structures, causing physiologic compromise by compression, bleeding, systemic sepsis, or a combination of these.

The origin of infection following open heart operations is not known in most patients. Some believe that the process begins as an isolated area of sternal osteomyelitis that eventually leads to sternal separation. Others hold that sternal instability is the inciting event, and bacteria then migrate into deeper tissues. Inadequate mediastinal drainage in the operating room may also contribute to the development of a deeper chest infection. The patient's own skin flora and the bacteria in the local surgical environment are possible sources of infection. Because some bacterial contamination of surgical wounds is inevitable, host risk factors are likely critical in promoting an active infection.

Etiology

Causes

Most cases of mediastinitis in the United States occur following cardiovascular surgery. Risk factors for the development of mediastinitis in this setting include the following:

Additional causes include the following:

Microbiology

Most mediastinitis cases occur after cardiac surgery and indicate gram-positive cocci,[7] with Staphylococcus aureus[15] and Staphylococcus epidermidis accounting for 70-80% of cases (see the image below).[10] Mixed gram-positive and gram-negative infections account for approximately 40% of cases. Isolated gram-negative infections are rare causes.



View Image

The frequency of various microbiological pathogens isolated in cases of postoperative mediastinitis.

Fibrosing mediastinitis is most commonly associated with Histoplasma capsulatum and Mycobacterium tuberculosis, though mediastinitis is an extremely rare complication of these infections.[13]

Acute mediastinitis has also been reported as a complication of Epstein-Barr virus infection.[16]

Epidemiology

In the United States, mediastinitis most commonly occurs in the postoperative setting following CABG.[4] The incidence is 1-2% at most large surgical centers; however, certain subsets of patients, such as patients who have undergone a heart transplant, are at much higher risk.

Prognosis

The development of mediastinitis dramatically increases mortality and lengthens the hospital stay. One study showed that postoperatively, a patient's chance of dying doubled to 12% when mediastinitis developed compared with 6% for those without the condition. Some studies report death rates as high as 47%. Mediastinitis also raises the 2-year mortality from 2% to 8% following CABG. Patients with postoperative mediastinitis stay in the hospital six to seven times longer than those without the condition, and total costs may triple.[17]

History

Mediastinitis manifests within a spectrum that ranges from the subacute patient to the fulminant critically ill patient who requires immediate intervention in order to prevent death.

The typical postoperative patient presents with fever, high pulse, and reports suggestive of a sternal wound infection such as sternal instability. Approximately two thirds of patients present within 14 days following surgery. Although a delay of months is occasionally observed, signs or symptoms typically develop within 1 month of the operation. Patients may report sternal pain that has increased since surgery, drainage from the wound site, an audible click due to sternal nonunion, and progressive redness over a variable period.

Physical Examination

Vital signs generally may show tachycardia and fever. In more advanced cases of sepsis, hypotension may be present and the patient may require large volumes of crystalloid or vasopressor medication for support.

The Hamman sign is a crunching sound heard with a stethoscope over the precordium during systole. Its presence should alert the clinician to possible mediastinitis, although its absence does not change the probability of disease.

Direct signs of sternal infection may be among the initial presenting signs or may be delayed until after the diagnosis is already considered. Sternal pain, instability, or click; local cellulitis; and drainage can all be observed.

Distinguishing between a superficial wound infection and a deeper chest infection associated with mediastinitis can be challenging. Systemic signs of sepsis strongly suggest mediastinal involvement. Local wound exploration should be utilized as a mechanism to distinguish a superficial wound infection from a deep sternal wound infection.

Laboratory Studies

A complete blood count (CBC) shows leukocytosis, often with a left shift on the white blood cell (WBC) count differential. The hematocrit value decreases if bleeding has occurred. The platelet count increases in the early stages of sepsis or decreases as sepsis worsens or disseminated intravascular coagulation (DIC) occurs.

Bacteremia can be observed, and blood cultures should be obtained as clinically indicated. Results from properly collected blood cultures should be reflexive in the workup when mediastinitis is considered, especially in the postoperative patient several days after cardiothoracic surgery in the presence of sepsis.

Samples of any sternal drainage should be sent for Gram stain and culture. This helps to establish a diagnosis and to tailor antimicrobial therapy. At operative exploration, additional cultures should be taken to direct antibiotic therapy.

Mediastinal pacing wires should be sent for culture if they are still present and no longer needed. One study found that results from pacing wire culture have a sensitivity of 75%, a specificity of 83%, a positive predictive value of 12%, and a negative predictive value of 99%.[18]

Imaging Studies

Delays in the diagnosis of mediastinitis greatly increase morbidity and mortality. The condition is typically recognized because of high clinical awareness in susceptible populations. Occasionally, radiology studies, including computed tomography (CT) of the chest, can be helpful in diagnosis if it is in question.[10] Local wound exploration is the predominant method of distinguishing between superficial wound infection and deep sternal wound infection.

Chest radiography

Findings include pneumomediastinum and air-fluid levels within the mediastinum. Air-fluid levels are often best seen on lateral films. Mediastinal widening is not a reliable sign of mediastinitis, especially postoperatively.

Computed tomography

CT is more accurate for helping to identify air-fluid levels and pneumomediastinum. A CT scan may demonstrate sternal separation and substernal fluid collections. These examinations can be helpful when the diagnosis is in question or in the late postoperative period. They should not take the place of prudent wound exploration to identify a deep sternal wound infection.

The later the scans are performed following surgery, the more accurate the results.[19] If performed after postoperative week 2, CT scans have a sensitivity and specificity of almost 100%, though most wound infections occur before this time.[19] The specificity of CT findings is clearly time-dependent.

CT findings consistent with mediastinitis can also be found in patients without sternal wound infections after cardiac surgery for as many as 21 days following the procedure. This makes integrating CT findings with clinical data and awareness critical.

Magnetic resonance imaging

Magnetic resonance imaging (MRI) is poorly suited as a diagnostic modality in persons with mediastinitis. Postoperatively, patients may have sternal wires, vascular clips, metallic valves, and pacing wires that contraindicate MRI. In addition, it is difficult to perform an MRI study on an intubated, critically ill patient.

Nuclear medicine

Findings from nuclear medicine scans/radioactive WBC scans involving labeled WBCs are reported to have very high specificity; however, few studies have been performed on postoperative patients.

Histologic Findings

As mediastinitis develops, an increasingly thick layer of fibrin is formed, causing the mediastinal structures to become progressively less mobile. As the infection spreads throughout the mediastinum through sinus tracts, a growing area of dead space develops beneath the sternum. The belief that this retrosternal dead space must be obliterated to achieve a cure after mediastinitis develops is becoming more popular.

A more indolent form of mediastinitis, termed chronic fibrosing mediastinitis, occurs as a complication of granulomatous infections, most commonly H capsulatum.[13] Rupture of mediastinal lymph nodes and the release of caseous material generate an intense inflammatory reaction. The patient becomes symptomatic from obstruction of major mediastinal structures, especially the superior vena cava.[20]

A significant minority of patients may be asymptomatic and present with an isolated mediastinal mass on chest radiograph.

Approach Considerations

Operative exploration includes reopening the previous sternotomy and debridement of necrotic and infected tissue. The sternum is separated from the ventricle bypass grafts and the aorta carefully to not cause bleeding. Cultures are sent to direct antibiotic therapy. Wound closure is usually delayed until reasonable control of infection is achieved; however, some surgeons perform closure with muscle flaps at the initial debridement with good results. Delayed closure is usually accomplished with muscle flaps (pectoralis, rectus) and may be aided by vacuum-assisted closure.[2, 21, 22]

Sterile sternal dehiscence, which is described as a sternal nonunion, is usually not treated. Occasionally, patients have abrupt separation of the sternum in close proximity to cardiac surgery, necessitating sternal reclosure. Also, some have extreme pain or cannot tolerate the clicking and discomfort of the nonunion and require sternal reclosure.

For simple sternal dehiscence (postoperative mediastinitis), great care must be taken to exclude active infection before rewiring the sternum. Surgery is seldom recommended for cases of chronic fibrosing mediastinitis unless compression of the major mediastinal structures has occurred. In cases of sternal nonunion, surgery should be deferred except when patients have extreme pain.

Medical Therapy

Prevention

Measures for preventing mediastinitis include the following:

Medical care in postoperative period

Appropriate, well-directed antibiotic therapy is crucial to successful treatment of mediastinitis.

Most patients have already received prophylactic antibiotics, usually a first-generation cephalosporin. Because as many as 20% of organisms cultured from infected sternotomy sites are methicillin-resistant S aureus and because another 20% are gram-negative organisms, it is vital to institute very broad and deep antibiotic coverage that includes Pseudomonas species. Culture results should then guide antibiotic use; multiple regimens are available for use with patients who have mediastinitis.

Therapy is usually prolonged, ranging from weeks to months. One study suggests that 4-6 weeks of therapy is adequate for most patients.[23]

Enteral nutritional support should be instituted immediately, with a duodenal feeding tube, if necessary. Data suggest that the use of diets formulated with various anti-inflammatory compounds to include omega-3 long-chain fatty acids and arginine provide clinically important benefits for critically ill patients with sepsis. If enteral feedings are contraindicated, consider hyperalimentation.

Chronic fibrosing mediastinitis

Chronic fibrosing mediastinitis, which is often caused by H capsulatum infection, should be treated with close observation for signs of superior vena cava compression or other mediastinal organ compromise.[24] The role of antifungal therapy is controversial, though amphotericin B has been used.

Surgical Therapy

Surgical options for mediastinitis after cardiac surgery

Effective treatment for simple sternal dehiscence without infection is rewiring the sternum.[10] This usually yields reasonable long-term results. Cultures should be taken to exclude active infection in the cases of sternal dehiscence.

Failure to adequately debride and sterilize the mediastinum during the first reoperation is the most common cause of repeat postoperative mediastinitis. Options for mediastinitis after cardiac surgery are as follows:

Each has its advantages and disadvantages. The optimal strategy for a given case depends on the duration of the infection, the condition of the mediastinal structures, and the experience of the surgeon.

Most surgeons prefer to leave the wound open or treat with vacuum-assisted closure for subsequent debridement efforts after initial sternal reexploration.[2, 21, 22, 25] In this case, the wound is packed daily until it appears clean with adequate granulation tissue. At this point, muscle flap closure is achieved. Usually, bilateral pectoralis flaps are used. Occasionally, the rectus abdominis, which is opposite the internal mammary artery used for bypass, is used for coverage.

Both the surgeon's experience and patient factors influence the type of flap procedure used. If a large anterior retrosternal dead space exists, it must be obliterated in order to achieve cure. Although often achieved with a muscle flap, the omentum provides lymphocytes and angiogenesis factors that may prove beneficial.[26, 27] Disadvantages of this delayed approach are the altered thoracic mechanics, which may lead to ventilator dependence, and a risk of bleeding from the exposed heart and vessels, with muscle flap closure for mediastinitis in an attempt to decrease the incidence of this bleeding.

Some surgeons uniformly perform muscle flap closure at the initial debridement with good results.[28] Other surgeons elect to close the wound site primarily in less advanced cases of mediastinitis and use large-bore drainage and irrigation tubes to infuse various antibiotic or antiseptic solutions for many days. Although the most commonly used solution in the past has been povidone-iodine, this should be used with caution; case reports have indicated the development of serious iodine toxicity manifesting as seizures and renal failure.[29]

The lack of a bony anterior sternal wall may be unacceptable to some patients and has prompted some surgeons to attempt sternum-sparing procedures, even in more advanced cases. This is often a difficult decision, requiring excellent surgical judgment. Clearly advanced cases of sternal osteomyelitis are extremely difficult to cure, and most patients with muscle or omental flaps do very well from a functional standpoint.

Chronic fibrosing mediastinitis

Surgery is seldom recommended for cases of chronic fibrosing mediastinitis unless compression of major mediastinal structures has occurred. Whether surgical debulking early in the process minimizes the development of superior vena cava syndrome or cardiac compression has not been adequately studied.

Oropharyngeal descending infections

In cases of descending mediastinitis due to infections that began in the oropharynx, some surgeons attempt to limit drainage and debridement to the cervical region. In a more advanced infection, often the best plan to offer a maximal chance of cure is to proceed with formal thoracic drainage and debridement.

Complications

Systemic sepsis is a major complication of mediastinitis and manifests with tachycardia, hypotension, poor urine output, and other signs of poor systemic perfusion. The aim of early aggressive therapy, both surgical and medical, is to prevent this often lethal complication.

Pneumoperitoneum and pneumothorax can produce serious local problems and eventual hemodynamic compromise.

If pleural effusions become infected and develop into empyema, systemic sepsis may occur.

Severe and life-threatening bleeding from ruptured vessels or the heart itself can occur when the chest is packed and left open to await definitive closure.

Superior vena cava syndrome and compression of critical mediastinal structures are sometimes observed with chronic fibrosing mediastinitis. Compression of the pulmonary vessels may give rise to pulmonary hypertension.[30]

Author

Dale K Mueller, MD, Co-Medical Director of Thoracic Center of Excellence, Chairman, Department of Cardiovascular Medicine and Surgery, OSF Saint Francis Medical Center; Cardiovascular and Thoracic Surgeon, HeartCare Midwest, Ltd, A Subsidiary of OSF Saint Francis Medical Center; Section Chief, Department of Surgery, University of Illinois at Peoria College of Medicine

Disclosure: Received consulting fee from Provation Medical for writing.

Coauthor(s)

Michael J Dacey, MD, Consulting Staff, Department of Internal Medicine, Division of Critical Care, Kent County Hospital

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Shreekanth V Karwande, MBBS, Chair, Professor, Department of Surgery, Division of Cardiothoracic Surgery, University of Utah School of Medicine and Medical Center

Disclosure: Nothing to disclose.

Chief Editor

Mary C Mancini, MD, PhD, MMM, Professor and Chief of Cardiothoracic Surgery, Department of Surgery, Louisiana State University School of Medicine in Shreveport

Disclosure: Nothing to disclose.

Additional Contributors

Benson B Roe, MD,

Disclosure: Nothing to disclose.

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The frequency of various microbiological pathogens isolated in cases of postoperative mediastinitis.

The frequency of various microbiological pathogens isolated in cases of postoperative mediastinitis.