Mediastinitis

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Background

Mediastinitis is a life-threatening condition with an extremely high mortality rate if recognized late or treated improperly.[1, 2, 3] 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).[3] 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.

Epidemiology

Frequency

In the United States, mediastinitis most commonly occurs in the postoperative setting following coronary bypass grafting.[3] The incidence rate 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.

Etiology

Pathophysiology

Infection from either bacterial pathogens or more atypical organisms can inflame any of the mediastinal structures, causing physiological 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.

Presentation

History

Mediastinitis manifests within a spectrum that ranges from the subacute patient to the fulminate 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

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.

Indications

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 recently is aided by vacuum-assisted closure.[1, 14, 15]

Sterile sternal dehiscence, which is described as a sternal nonunion, is usually not treated. Occasionally, patients abruptly separate their 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.

Relevant 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 defining the location of specific mediastinal masses. 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 3 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.

Contraindications

For simple sternal dehiscence (postoperative mediastinitis), take great care 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.

Laboratory Studies

Imaging Studies

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.[12] 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.[18]

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

Medical Therapy

Prevention

Medical care in the 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 up to 20% of organisms cultured from infected sternotomy sites are methicillin-resistant S aureus and because another 20% are gram-negative organisms, institute very broad and deep antibiotic coverage that includes Pseudomonas species. Culture results should then guide antibiotic use, as 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.[19]

Institute enteral nutritional support immediately, with a duodenal feeding tube, if necessary. Recent 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

Treat chronic fibrosing mediastinitis, which is often caused by H capsulatum infection, with close observation for signs of superior vena cava compression or other mediastinal organ compromise.[20] The role of antifungal therapy is controversial, although 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.[9] 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 immediate closure after sternal debridement, delayed closure after sternal debridement, and sternal irrigation after sternal debridement. Each has its advantages and disadvantages. The best strategy for accomplishing this 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.[1, 14, 15, 21] 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 muscle flaps are used. Occasionally, the rectus abdominus muscle, 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.[22, 23] 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.[24] 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.[25]

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 is sometimes observed with chronic fibrosing mediastinitis.

Outcome and Prognosis

The development of mediastinitis dramatically raises the chance of 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 rate from 2% to 8% following coronary bypass grafting. Patients with postoperative mediastinitis stay in the hospital 6-7 times longer than those without the condition, and total costs may triple.[26]

Future and Controversies

Fortunately, mediastinitis is fairly uncommon in relation to the hundreds of thousands of cardiac surgeries performed each year in the United States. However, when it occurs, the results are often devastating and the costs of care increase substantially.

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 CT scan findings are not reliable. However, the key to successful management remains 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.

Author

Dale K Mueller, MD, Clinical Associate Professor of Surgery, Section Chief, Department of Surgery, University of Illinois College of Medicine; Co-Medical Director, Thoracic Center of Excellence, Vice-Chair, Department of Cardiovascular Medicine and Surgery, OSF St Francis Medical Center; Director, Adult ECMO, Cardiovascular and Thoracic Surgeon, HeartCare Midwest, SC

Disclosure: Provation Medical Consulting fee 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

Benson B Roe, MD, Emeritus Chief, Division of Cardiothoracic Surgery, Emeritus Professor, Department of Surgery, University of California at San Francisco Medical Center

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

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.

Paolo Zamboni, MD, Professor of Surgery, Chief of Day Surgery Unit, Chair of Vascular Diseases Center, University of Ferrara, Italy

Disclosure: Nothing to disclose.

Chief Editor

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

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.