Postpericardiotomy Syndrome 

Updated: Dec 27, 2017
Author: M Silvana Horenstein, MD; Chief Editor: Howard S Weber, MD, FSCAI 

Overview

Background

Postpericardiotomy syndrome (PPS) is a febrile illness secondary to an inflammatory reaction involving the pleura and pericardium.[1, 2, 3, 4] It is more common in patients who have undergone surgery that involves opening the pericardium (in the United States, the estimated frequency varies from 2% to 30% of these patients). However, postpericardiotomy syndrome has also been described following myocardial infarction (Dressler syndrome) and as an unusual complication after percutaneous procedures such as coronary stent implantation,[5] after implantation of epicardial pacemaker leads[6] and transvenous pacemaker leads,[7, 8, 9, 10, 11] and following blunt trauma,[12] stab wounds,[13] and heart puncture.[14]

Pericardial effusions often accompany the syndrome and may develop into early or late postoperative cardiac tamponade[15] and even recurrent cardiac tamponade.[16] The syndrome is also characterized by pericardial or pleuritic pain, friction rubs, pleural effusions, pneumonitis, and abnormal ECG and radiography findings (see Workup).

PPS usually occurs as a single episode; however, it can recur years later.[17] It is uncommon in patients younger than 2 years,[18]  but the frequency increases in children and adults to as much as 30%. It is more common after repair of tetralogy of Fallot, repair of atrial and ventricular septal defects,[19] and after cardiac transplantation.[20]

It is essential that clinicians diagnose and adequately treat PPS as well as recognize and treat impending or manifest cardiac tamponade.

 

Pathophysiology

Postpericardiotomy syndrome is often associated with the development of antiheart antibodies, leading to an inflammatory reaction within the pericardial space.[21]  Various viral agents, including coxsackie B, adenovirus, and cytomegalovirus, have been present in approximately two thirds of patients with postpericardiotomy syndrome, suggesting an autoimmune response associated with a viral infection. However, a prospective study found no evidence to support a viral etiology for postpericardiotomy syndrome.[22] This study suggested that the use of viral titers in the setting of cardiopulmonary bypass and recent blood transfusions is unreliable.

The etiology may be multifactorial; a systematic review found that the inflammatory response and perioperative bleeding and coagulation may play a role in the development of postpericardiotomy syndrome.[23]  Factors that were associated with a higher risk of this condition included the following[23] :

  • Lower levels of preoperative interleukin 8, platelets, and hemoglobin
  • Higher postoperative complement conversion products
  • Younger age
  • Red blood cell transfusions

Etiology

The precise etiology of postpericardiotomy syndrome is not known. Postpericardiotomy syndrome is postulated to be an autoimmune response involving autoantibodies which target antigens exposed after the percardium has been damaged.[21]

In a study of patients who had developed postpericardiotomy syndrome after transplantation, an increased proportion of activated helper T cells (CD4+/25+) and cytotoxic T cells (Leu-7+/CD8+) was found. This led the investigators to conclude that, in this population, postpericardiotomy syndrome was possibly secondary to cell-mediated immunity.[20]

Prognosis

Most cases of postpericardiotomy syndrome resolve within a few weeks. Rarely, symptoms may occur for more than 6 months.

Relapse may occur after tapering anti-inflammatory medications; it is estimated to occur in 10-15% of patients. Most recurrences occur within 6 months of the initial insult.

Morbidity/mortality

Postpericardiotomy syndrome usually manifests as a mild, self-limited inflammatory illness. Life-threatening pericardial tamponade can develop due to a rapidly increasing pericardial effusion.[3, 4] Tamponade occurs in less than 1% of patients with postpericardiotomy syndrome. Elevation of cardiac filling pressures, progressive limitation of ventricular diastolic filling, and reduction of stroke volume and cardiac output characterize cardiac tamponade.  This also correlates with the rapidity of pericardial effusion accumulation, because slow accumulation of even large pericardial effusions may not result in clinical signs and symptoms of tamponade. This is directly related to the ability of the pericardial space to enlarge significantly over an extended time period, thereby accomodating the fluid volume, and not resulting in cardiac tamponade.

A study that evaluated 822 patients undergoing nonemergent valve surgery found postpericardiotomy syndrome in 119 (14.5%), with a 20.9% incidence of reoperation for tamponade at 1 year in patients who developed the syndrome compared to 2.5% in those who did not, but also having similar 1-year mortality (4.2% vs 5.5%, respectively).[23]  Patients with postpericardiotomy syndrome also had longer median hospital stays (13 days vs 11 days, respectively) and were more likely to have had preoperative therapy for pulmonary disease without corticosteroids.[23]

Carriage of the Mediterranean Fever (MEFV) gene may affect the severity of postpericardiotomy syndrome. In a study of 86 patients who underwent cardiac surgery, of whom 45 developed this condition and 41 did not, investigators found a significantly lower rate of mutation carriage in patients with severe postpericardiotomy syndrome (4.8%) relative to those with mild-moderate postpericardiotomy syndrome (25%) (P <0.05).<ref>24</ref>​ However, the rate of MEFV mutation carriage between the groups with and without postpericardiotomy syndrome was similar.

Complications

Cardiac tamponade is a life-threatening complication of postpericardiotomy syndrome. Emergent pericardiocentesis and drainage of the pericardial effusion is necessary. As noted earlier, tamponade occurs in approximately 1% of patients with postpericardiotomy syndrome.

Constrictive pericarditis occurs late postoperatively in fewer than 0.5% of patients but may not be related to postpericardiotomy syndrome. The high prevalence of postpericardiotomy syndrome and quite low prevalence of constriction suggests that a direct association is unlikely. With constriction, the pericardium becomes thickened and adherent to the heart and restricts filling of the ventricles. A pericardiectomy may be required for treatment.

Patients with pain from the inflammatory response may demonstrate splinting during breathing. This can result in hypoxemia. Monitor oxygen saturation by pulse oximetry in patients presenting with these findings.

Coronary artery bypass grafting is an unusual procedure in children. Occlusion of the graft is reported as a rare, but fatal, complication of postpericardiotomy syndrome.

 

Presentation

History

Symptoms of postpericardiotomy syndrome (PPS) usually develop within 1-6 weeks after surgery involving pericardiotomy. Temperature after the first postoperative week usually reaches 38-39°C orally but may spike as high as 40°C. Despite the high temperature, the patient may not appear ill. The fever usually subsides within 2-3 weeks.

Malaise, chest pain, irritability, and decreased appetite are typical presenting symptoms. Patients may also report dyspnea and arthralgias. Children may report chest pain that worsens with inspiration and during the supine position, but improved while sitting upright and leaning forward. Emesis has also been reported as the main symptom in children with impending cardiac tamponade secondary to postpericardiotomy syndrome.[25]

Physical Examination

Patients often demonstrate tachycardia and a pericardial friction rub. The pericardial rub disappears either with improvement or with further accumulation of pericardial fluid. Systemic fluid retention and hepatomegaly can also occur in the setting of low cardiac output due to impaired ventricular filling. Pulses paradoxicus may also be evident and is represented by a decrease in systemic blood pressure over 10 mmHg during inspiration and diminished pulse-wave amplitude by palpation of the radial artery. Pleural friction rubs are common. Signs of pneumonitis, including cough, fever, and decreased oxygen saturation, may also be present.

 

DDx

Diagnostic Considerations

The diagnosis of postpericardiotomy syndrome is made when 2 of the following 5 criteria are met[3] :

  • Fever
  • Pericardial or pleuritic chest pain
  • Pericardial or pleuritic friction rub
  • Pericardial effusion
  • Pericardial effusion with elevated  levels of C-reaction protein (CRP)

The European Society of Cardiology established guidelines for the diagnosis and management of pericardial diseases in 2004.[26]  In 2015, these guidelines were updated.[27]

Other resources that may be helpful include the following:

  • Fardman A, Charron P, Imazio M, Adler Y. European guidelines on pericardial diseases: a focused review of novel aspects. Curr Cardiol Rep. 2016 May. 18 (5):46. [Medline].[28]

  • Johnston DR. Surgical management of pericardial diseases. Prog Cardiovasc Dis. 2017 Jan - Feb. 59 (4):407-16. [Medline]. [Full Text].[29]

  • Klein AL, Abbara S, Agler DA, et al. American Society of Echocardiography clinical recommendations for multimodality cardiovascular imaging of patients with pericardial disease: endorsed by the Society for Cardiovascular Magnetic Resonance and Society of Cardiovascular Computed Tomography. J Am Soc Echocardiogr. Sep 2013;26(9):965-1012.e15. [Medline].[30]

  • Imazio M, Adler Y, Ristic AD, Charron P. A new scoring system for the triage of cardiac tamponade. Expert Rev Cardiovasc Ther. Mar 2015;13(3):237-8. [Medline].[31]

  • Imazio M, Spodick DH, Brucato A, Trinchero R, Adler Y. Controversial issues in the management of pericardial diseases. Circulation. Feb 23 2010;121(7):916-28. [Medline].[32]

  • Khandaker MH, Espinosa RE, Nishimura RA, et al. Pericardial disease: diagnosis and management. Mayo Clin Proc. Jun 2010;85(6):572-93. [Medline]. [Full Text].[33]

  • Seferovic PM, Ristic AD, Maksimovic R, et al. Pericardial syndromes: an update after the ESC guidelines 2004. Heart Fail Rev. May 2013;18(3):255-66. [Medline].[34]

  • Snyder MJ, Bepko J, White M. Acute pericarditis: diagnosis and management. Am Fam Physician. Apr 1 2014;89(7):553-60. [Medline].[35]

  • Tamarappoo BK, Klein AL. Post-pericardiotomy syndrome. Curr Cardiol Rep. 2016 Nov. 18 (11):116. [Medline].[3]

  • Vogel-Claussen J, Elshafee ASM, Kirsch J, et al, for the Expert Panel on Cardiac Imaging. ACR Appropriateness Criteria dyspnea-suspected cardiac origin. J Am Coll Radiol. 2017 May. 14 (5S):S127-37. [Medline]. [Full Text].[29]

Differential Diagnoses

 

Workup

Laboratory Studies

The expected complete blood cell (CBC) count findings in patients with postpericardiotomy syndrome (PPS) include leukocytosis with a leftward shift.

As with other patients with suspected inflammatory versus infectious conditions, obtain blood cultures early in the workup. The results of the blood cultures should be negative.

Acute phase reactants, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, are elevated.

Antiheart antibodies are usually present in high titers (not usually obtained).

Cardiac enzyme testing is not usually helpful because the results vary. In addition, studies have reported no difference in enzyme levels compared with patients who underwent cardiopulmonary bypass that do not have clinical signs of postpericardiotomy syndrome.

If a pericardial drain is placed, fluid should be obtained for cell count, differential, cytology, culture, gram stain, triglyceride level, and total protein level.

Electrocardiography

Electrocardiographic (ECG) findings are abnormal in postpericardiotomy syndrome and may include the following:

  • Initial findings may simulate pericarditis, with global ST segment elevation and T-wave inversion.

  • Subepicardial injury, resulting from myocardial inflammation, causes ST segment elevation.

  • The ECG may also reveal low QRS amplitude, especially with a large pericardial effusion.

Chest Radiography

Chest radiography may be helpful, although it is not diagnostic in diagnosing postpericardiotomy syndrome. Chest radiographs usually reveal blunting of the costophrenic angles due to a pleural effusion. A pericardial effusion enlarges the cardiac silhouette, as in the image below.

Upright chest radiograph in a 3-year-old child wit Upright chest radiograph in a 3-year-old child with dyspnea and fever reveals a large opacity on the left, with obliteration of the left costophrenic angle and a fluid stripe. These findings indicate a pleural effusion.

The cardiac silhouette enlarges in proportion to the amount of fluid contained in the pericardial sac.

Echocardiography

Echocardiography is the diagnostic procedure of choice to confirm the diagnosis and assess the severity of postpericardiotomy syndrome.

Echocardiographic subcostal view demonstrating a l Echocardiographic subcostal view demonstrating a large global pericardial effusion, with evidence of right atrial collapse (<i>red arrow</i>) consistent with cardiac tamponade prior to pericardiocentesis.
Four-chamber echocardiographic view following emer Four-chamber echocardiographic view following emergent pericardiocentesis (800 mL removed) for clinical and echocardiographic evidence of cardiac tamponade. Virtually no residual pericardial effusion is evident.

In the early stages of postpericardiotomy syndrome, a small amount of fluid may be detected posterior to the left ventricle during systole. With increasing fluid accumulation, the pericardial effusion becomes more global and detection using echocardiography becomes easier.

Echocardiography assists in differentiating suspected postpericardiotomy syndrome from congestive heart failure; cardiac output is reduced in both conditions. In postpericardiotomy syndrome with a large effusion, the atria are usually compressed by the pericardial fluid and indicative of cardiac tamponade.

Echocardiography is particularly helpful in evaluating ventricular contractility.

Cardiac Magnetic Resonance Imaging

Cardiac magnetic resonance imaging (cMRI) has been used more frequently to evaluate cardiac dynamics and pericardial abnormalities, such as pericardial thickening and inflammation associated with postpericardiotomy syndrome.[3] This imaging modality may be more helpful in identifying posterior pericardial fluid collections that may have become loculated and are not easily viewed with transthoracic echocardiography.

Procedures

Pericardiocentesis

Tamponade is a life-threatening condition that can result from postpericardiotomy syndrome and the rapid accumulation of pericardial fluid. The inflammatory changes seen in postpericardiotomy syndrome may cause pericardial adhesions that result in a localized collection of pericardial fluid. Pericardiocentesis may be emergently required if cardiac tamponade is present.

The standard subxiphoid approach is recommended when the effusion is global and evident anterior and apical to the right ventricle. Because of the possible localized nature of the tamponade, echocardiographic guidance is recommended. Echocardiography-guided pericardiocentesis with extended catheter drainage is considered the primary management for patients with clinically significant pericardial effusions. The drainage tube is usually left in place for 24-48 hours and aspirated periodically, during which anti-inflammatory treatment is initiated.

 

Treatment

Medical Care

Evaluation of patients with suspected postpericardiotomy syndrome (PPS) is usually performed in an outpatient setting. The workup and treatment may continue on an outpatient basis if the patient is not hemodynamically affected, although close follow-up is warranted.

Medical management includes the use of nonsteroidal anti-inflammatory drugs (NSAIDs)[3, 4]  such as aspirin, which is given for 4-6 weeks and is tapered as the fluid decreases. For patients not responsive to aspirin, ibuprofen, or naproxen, corticosteroids such as prednisone may be administered for 1 week, followed by a 4-week tapering. There are very limited data, if any, regarding the efficacy of colchicine for managing PPS in the pediatric population.[36]

Anecdotally, successful treatment of recurrent pericardial effusion has been described using a single high-dose of intravenous immunoglobulin in one patient[37] and a low weekly dose of methotrexate in one other.[38]  More recently, two children with refractory recurrent pericarditis following cardiac surgery were successfully treated with 3 and 5 monthly high-dose (2 g/kg) intravenous immunoglobulin until resolution of their pericardial effusions.[39]

Inpatient care of patients with PPS is indicated in more severe cases, such as patients with symptoms and signs indicative of tamponade. Patients with tamponade must be admitted to the hospital for pericardial drainage.

After drainage of the pericardial effusion and improvement in the clinical symptoms, most patients can be treated on an outpatient basis.

Consultations

Consult a pediatric cardiologist to diagnose and treat as well as to follow care of patients with postpericardiotomy syndrome. Consult a pediatric cardiothoracic surgeon in cases of patients who cannot be effectively drained via pericardiocentesis or who have recurrent relapses after intervention. These patients may require a pericardial window.

Transfer

Patients whose conditions are refractory to medical management require transfer to a facility that has a pediatric cardiologist and/or pediatric cardiothoracic surgeon available. These patients may require a surgical pericardial window.

Diet and activity

Patients usually have decreased appetite; however, special dietary restrictions are usually not required in patients with postpericardiotomy syndrome.

Patients with suspected or confirmed postpericardiotomy syndrome should avoid strenuous activity. Bed rest alone may be adequate to treat mild cases. Enforce strict bed rest until the fever has resolved and chest radiography and ECG reveal near baseline findings.

Surgical Care

Immediate pericardiocentesis is necessary to relieve life-threatening cardiac tamponade.

A surgically created pericardial window may be necessary in patients with recurrent relapses after medical-  and catheter-based therapy. This may be achieved through an open thoracotomy[40, 41, 42] or through a video-assisted thoracoscopic technique.[43]

Percutaneous balloon pericardiotomy (PBP) may be another alternative for these patients. This is a less invasive procedure in which a pericardial window is created in the catheterization laboratory using a balloon catheter under fluoroscopic guidance.[44, 45, 46]  The procedure effectively results in the pericardial fluid draining into the abdominal cavity via a perforation of the diaphragm. 

Prevention

Currently, there is no known preventative therapy available for postpericardiotomy syndrome.[47]

A randomized controlled trial evaluating the use of colchicine to prevent postpericardiotomy syndrome (PPS) in patients undergoing cardiopulmonary bypass did not find a statistically significant difference from placebo.[48]  However, the authors noted a trend toward significance that may be more evident with larger study.[49, 50]

Preliminary findings from the Colchicine for Prevention of the Postpericardiotomy Syndrome and Postoperative Atrial Fibrillation (COPPS) trial in adults indicated that compared with placebo, perioperative use of colchicine reduced the incidence of PPS but not of postoperative atrial fibrillation or postoperative pericardial/pleural effusion.[51] However, there was also an increased risk of gastrointestinal adverse effects with colchicine administration, which offset the potential benefits.[51]

In a systematic review of the literature for prophylaxis and treatment of PPS, Cantinotti et al found three major medication classes were used: nonsteroidal anti-inflammatory agents (NSAIDs), and colchicine.[36] There were more data to support the use of colchicine prophylaxis in adults, but there was no significant prophylactic advantage with NSAIDs/corticosteroids in children.[36]

 

Medication

Medication Summary

The mainstay of medical therapy is use of anti-inflammatory agents. Various drugs are available; all have similar efficacy. Corticosteroids are often used in more severe or refractory cases. Corticosteroids have resulted in rapid improvement in clinical symptoms and decrease in antiheart antibodies.

No evidence suggests that steroids administered prior to cardiopulmonary bypass reduce the risk of developing postpericardiotomy syndrome.[21] One case has been reported of low-dose methotrexate used in postpericardiotomy syndrome refractory to standard therapy[38] ; however, this has not been further supported.

Anti-inflammatory agents

Class Summary

These agents decrease inflammatory responses and interfere with systemic events leading to inflammation.

Aspirin (Anacin, Ascriptin, Bayer Aspirin, Bayer Buffered Aspirin)

First-line medication for patients with PPS. Inhibits prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2.

Indomethacin (Indocin)

Nonsteroidal anti-inflammatory medication often used as a first-line drug in PPS. Rapidly absorbed; metabolism occurs in liver by demethylation, deacetylation, and glucuronide conjugation; inhibits prostaglandin synthesis.

Prednisone (Deltasone, Orasone, Sterapred)

May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Usually reserved for treating more severe cases or relapses. May also be used as a first-line drug. Corticosteroid use has been shown to result in faster resolution of symptoms than other therapies.