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Ann Thorac Surg 2001;72:719-723
© 2001 The Society of Thoracic Surgeons


Original article: cardiovascular

Sternal wound infection after heart transplantation: incidence and results with aggressive surgical treatment

Michel Carrier, MDa, Louis P. Perrault, MDa, Michel Pellerin, MDa, Richard Marchand, MDa, Pierre Auger, MDa, Guy B. Pelletier, MDa, Michel White, MDa, Normand Racine, MDa, Denis Bouchard, MDa

a Department of Surgery and Medicine and the Microbiology Laboratory, Montreal Heart Institute and University of Montreal, Montreal, Quebec, Canada

Accepted for publication May 3, 2001.

Address reprint requests to Dr Carrier, Department of Surgery, Montreal Heart Institute, 5000 Belanger St East, Montreal, QB, H1T 1C8, Canada
e-mail: carrier{at}icm.umontreal.ca


    Abstract
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 
Background. Sternal wound infection remains a significant complication. We reviewed the incidence and the treatment of sternal wound infection after heart transplantation.

Methods. Of 226 patients who had a heart transplantation, 20 (8.8%) underwent postoperative wound debridement for superficial or deep sternal wound infection. The incidence and the survival of patients with sternal wound infection were analyzed.

Results. The incidence of sternal wound infection was similar among patients treated with four protocols of immunosuppressive drugs: cyclosporine and prednisone (0 of 22; 0%); cyclosporine, prednisone, and azathioprine (2 of 24; 8.3%); cyclosporine, prednisone, azathioprine, and antithymocyte globulin (15 of 139; 10.8%); and cyclosporine, prednisone, mycophenolate mofetil, and antithymocyte globulin (3 of 41; 7.3%) (p = 0.4). Six-month and 5-year survival of patients with sternal wound infection averaged 85% ± 8% and 74% ± 10% compared with 92% ± 2% and 82% ± 3% in patients without wound infection (p = 0.15). Patients with deep sternal wound infection, debridement, and reconstruction had a 5-year survival averaging 80% ± 10%.

Conclusions. The incidence of sternal wound infection remains similar between patients treated with the triple drug therapy. Surgical debridement and reconstruction can result in long-term survival after heart transplantation.


    Introduction
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 
Sternal wound infection remains a serious complication after cardiac operations, with rates ranging from 1% to 10% [14]. Although most wound infection episodes are superficial and self limited, deep sternal infection and acute mediastinitis can be life-threatening, especially in heart transplantation recipients to whom immunosuppressive agents are administered during the postoperative period. Not only was sternal wound infection not reported in the most recent clinical trials comparing newer immunosuppression agents after heart transplantation [5, 6], but the incidence of wound infection was almost never analyzed in single-center studies on clinical results after heart transplantation. Yet, sternal wound infection is a major cause of morbidity and occasionally of mortality among these patients.

The objective of the present study was to review the variation in the incidence of sternal wound infection according to different protocols of immunosuppressive drugs immediately after heart transplantation. The clinical outcome of sternal wound infection treatment after heart transplantation was also reviewed.


    Material and methods
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 
Heart transplantation program
From 1983 to September 2000, 237 patients underwent heart transplantation at the Montreal Heart Institute. Eleven patients died during or immediately after their surgical procedures, precluding any significant analysis of the risk of wound infection. All patients were followed prospectively and data were collected in a computerized database. Four protocols of immunosuppressive agents were used during the study period. Cyclosporine and prednisone were administered to patients who underwent heart transplantation between 1983 and 1987. Cyclosporine, prednisone, and azathioprine were used in 1988; the combination of cyclosporine, prednisone, azathioprine, and rabbit antithymocyte globulin from 1989 to 1997; and cyclosporine, prednisone, mycophenolate mofetil, and antithymocyte globulin was used from 1997 to 2000 [7, 8].

Patients who underwent open heart operations between 1983 and 2000 were administered preoperative and postoperative antibiotic prophylaxis with either cefazolin or vancomycin for penicillin-allergic patients. The antibiotics were administered during the first 48 hours after operation in heart transplantation patients.

Definition of the type of infection
Sternal wound infection was classified as superficial infection characterized by purulent drainage from the wound limited to cutaneous and subcutaneous involvement. Deep wound infection involved deep fascial and muscular tissue. Acute mediastinitis was defined as purulent drainage involving the sternal bone and surrounding mediastinal tissue. Cultures of drainage of all suspected surgical wound infections were obtained and analyzed routinely.

Statistical analysis
Data are expressed in mean and standard deviation. Differences between means were analyzed with the Student’s t test, and the Fisher exact test was used for categorical variables. The actuarial method was used to analyze survival and event-free survival in our groups of patients. A logistic regression analysis was used to study the risk factors correlated with wound infection after heart transplantation. Factors included in the analysis were recipient age, sex, pretransplant diabetes, mechanical support before transplantation, and the protocols of immunosuppressive drugs.


    Results
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 
Patient population
Among 226 patients who had a heart transplantation, preoperative diagnoses included 118 (52%) with end-stage ischemic cardiomyopathy, 50 (22%) with congestive cardiomyopathy, and 38 (17%) with various forms of end-stage heart disease. Of the 226 patients, 20 (8.8%) showed evidence of sternal wound infection: 9 (of 226; 3.9%) had superficial wound infections, 4 (of 226; 1.8%) had deep wound infections, and 7 (of 226; 3%) had acute mediastinitis. Of these 20 patients, 3 (15%) were women and 17 (85%) were men; of the 206 free from sternal infection, 37 (18%) were women and 169 (82%) were men (p = 0.7). Patients with sternal wound infection averaged 52 ± 9 years of age compared with 46 ± 10 years in patients free from sternal infection (p = 0.01). Diabetes was noted in 1 of the 20 patients (5%) who developed a sternal wound infection and in 12 of 206 patients (6%) without wound infection after transplantation (p = 0.9).

Superficial wound infections were treated with local debridement and dressing changes in an outpatient clinic. Deep wound infections were treated with surgical debridement and sternal rewiring including Robiscek weave in 3 patients and local debridement in another patient. Acute mediastinitis was treated with surgical debridement, drainage, and sternal rewiring in 5 patients. Omentoplasty and pectoralis muscle flaps were used in 2 other patients.

Sixteen patients (of 20; 80%) who developed sternal wound infections after transplantation were followed at our outpatient clinic while waiting for heart transplantation (recipient UNOS status 2) compared with 116 (of 206; 56%) UNOS status 2 recipients without wound infection after transplantation. Four patients (of 20; 20%) with sternal wound infection after transplantation were hospitalized before transplantation (recipient UNOS status 1) compared with 89 (of 206; 43%) UNOS status 2 recipients who remained free from wound infection after transplantation.

Twenty-five patients were mechanically supported before heart transplantation, 5 with the CardioWest total artificial heart, 3 with a Thoratec (Pleasanton, CA) left ventricular assistance, and 17 with an intraaortic balloon pump. All other mechanically supported patients did not show any evidence of sternal infection throughout the periods of support and transplantation. One patient (of 20; 5%) was on mechanical assistance with the CardioWest (Tucson, AZ) total artificial heart and developed an episode of acute mediastinitis after heart transplantation.

Patients who developed sternal wound infection after transplantation waited 15 ± 23 weeks for a donor heart compared with 24 ± 38 weeks for patients who did not show any evidence of wound infection after transplantation (p = 0.13). Donor ischemic time in these two groups averaged 139 ± 49 minutes and 134 ± 63 minutes, respectively (p = 0.5).

Sternal wound infection and regimens of immunosuppressive drugs
There was no sternal wound infection among the 22 patients treated with cyclosporine and prednisone. Evidence of sternal wound infection after heart transplantation was found in 2 of 24 (8.3%) patients who were administered cyclosporine, prednisone, and azathioprine; 15 of 139 patients (10.8%) who were administered cyclosporine, prednisone, azathioprine, and antithymocyte globulin; and 3 of 41 patients (7.3%) who were administered cyclosporine, prednisone, mycophenolate mofetil, and antithymocyte globulin (p = 0.4).

Of the 20 sternal wound infections after heart transplantation, most were superficial (9; 45%), 4 (20%) were deep, and 7 (35%) were episodes of acute mediastinitis. The acute mediastinitis was caused by various bacterial agents in various combinations: bacteroides (n = 1), Escherichia coli (n = 2), Staphylococcus epidermidis (n = 5), Staphylococcus aureus (n = 6), methicillin-resistant S aureus (n = 2), Aspergillus fumigans (n = 1). For superficial and deep wound infections, S aureus (8 of 20; 40%) and S epidermidis (5 of 20; 25%) were the most common bacteria responsible.

Survival and rejection
Six-month and 5-year survival of patients with sternal wound infection averaged 85% ± 8% and 74% ± 10%, compared with 92% ± 2% and 82% ± 3% in patients without wound infection (p = 0.15) (Fig 1). Eleven patients with deep sternal wound infection or acute mediastinitis underwent aggressive surgical debridement, drainage, and reconstruction with 6-month and 5-year survival rates averaging 91% ± 9% and 80% ± 10%, respectively (Fig 2). One patient with acute mediastinitis died from uncontrolled sternal wound infection after implantation of a total artificial heart and transplantation and another patient died from massive hemorrhage secondary to erosion of the ascending aorta. Two patients underwent successful reconstruction of the ascending aorta, with a Dacron (C. R. Bard, Haverhill, PA) graft in 1 and a cryopreserved homograft in the other after the appearance of infected false aneurysms of the ascending aorta (Fig 3). Omentoplasty and pectoralis muscle flaps were also used in these 2 patients to control the infected mediastinal space (Fig 4). Three patients recovered successfully after surgical debridement, mediastinal drainage, and sternal reclosure associated with the proper antibiotic treatment.



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Fig 1. Actuarial survival of patients with superficial, deep, and acute mediastinitis (infection) compared with patients without sternal wound infection. Survival was lower among patients with sternal wound infection, but the difference is not statistically significant (p = 0.15).

 


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Fig 2. Actuarial survival of patients with deep sternal wound infection and acute mediastinitis compared with patients without deep wound and mediastinal infection. Survival was similar in the two groups.

 


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Fig 3. Computed tomography scan showing (A) a false aneurysm of the ascending aorta (arrow) and (B) a mediastinal abscess behind the ascending aorta (arrow). The patient was treated for a deep sternal wound infection immediately after heart transplantation but showed evidence of mediastinal infection 6 months later. Cultures of the abscess isolated a methicillin-resistant Staphylococcus aureus bacteria.

 


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Fig 4. A patient underwent resection of the false aneurysm, drainage of the retroaortic abscess, reconstruction of the ascending aorta with a cryopreserved homograft, omentoplasty to control mediastinal dead space, and pectoralis muscle flap to secure the sternal closure. The patient had a successful outcome and remains free from recurrence 6 months after the operation.

 
The freedom rate from acute rejection averaged 47% ± 4% 6 months after transplantation in patients who did not show evidence of sternal wound infection, compared with 43% ± 11% in patients with sternal wound infections (p = 0.5). The number of treated acute rejection episodes averaged 1.1 ± 1.2 per patient in those who did not show evidence of sternal wound infection compared with 1.0 ± 0.9 episode per patient in those with sternal wound infections (p = 0.8).

Multivariate analysis
Recipient age (odds ratio 1.08, 95% confidence interval, 1.05 to 1.1) was the only risk factor significantly correlated with the appearance of wound infection after heart transplantation. The use of mycophenolate mofetil, azathioprine, and antithymocyte globulin was not associated with wound infection, nor was the presence of diabetes before transplantation.


    Comment
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 
Heart transplantation is an established treatment for patients in end-stage heart failure. Although rejection and systemic infections episodes have been well characterized among transplant patients, sternal wound infection is seldom reported and rarely discussed. Yet, sternal wound infection after standard cardiac operations and after heart transplantation is the major source of morbidity and mortality. The present study showed that sternal wound infection after heart transplantation correlates directly with patient age. There was no significant relationship between the incidence of sternal wound infection and protocols of immunosuppressive drugs used in the present experience, although the incidence was slightly higher among patients with the quadruple drug therapy. There was no sternal infection in patients with the double drug therapy of cyclosporine and prednisone, but the later protocol was used in the earliest part of our experience with heart transplantation enrolling only young patients. Moreover, survival of patients with sternal wound infection remains similar to those without wound infection after transplantation suggesting that, in most cases, aggressive surgical debridement and appropriate reconstructive approaches were successful.

From 1992 to 2000, including 13,199 patients undergoing cardiac operation in our institution, the annual incidence of acute mediastinitis varied from 0.13% to 1.33%. Our experience with acute mediastinitis occurring in transplant patients showed a high rate of 3%. Although recipient age was the only risk factor associated with sternal wound infection in the present study, a larger cohort of patients could show the effect of pretransplant general nutritional status, mechanical support, and immunosuppressive drugs.

Nine patients in the present study had superficial wound infections and were treated at the outpatient clinic without significant morbidity. Eleven patients had deep sternal wound infections or acute mediastinitis requiring prolonged hospital stay and multiple surgical procedures of mediastinal drainage, debridement, reoperation, and in 2 cases reconstruction of the ascending aorta (Dacron graft in 1 case and cryopreserved homograft in another) associated with pectoralis muscle flaps and omentoplasty to control the mediastinal infected space. Other authors have also reported the use of muscle flaps and of omentoplasty in patients with mediastinal infection after conventional operation [9] or heart transplantation [10, 11].

Coselli and colleagues [12] described the use of cryopreserved homografts in patients with thoracic aortic graft infections, an approach that we used in combination with omentoplasty and pectoralis muscle flaps in patients who showed evidence of infected pseudoaneurysms of the ascending aorta at the site of the aortic anastomosis [13]. Although Argenziano and colleagues [14] showed that wound infection in patients with left ventricular assist support does not adversely affect survival, local infection surrounding a total artificial heart carries a dismal prognosis [15], as was the case with 1 of our patients.

There is no clear guideline as to the level of immunosuppression that should be maintained in patients with significant sternal wound infection after transplantation. Our practice has been to rely on cyclosporine and prednisone while azathioprine or mycophenolate mofetil were stopped until we were confident that the sternal or mediastinal infection was controlled. The use of cyclosporine and prednisone was effective in preventing the rejection process during these episodes of sternal wound infection.

Sternal wound infection and acute mediastinitis remain a serious complication after heart transplantation. Although there was no significant difference in the incidence of sternal wound infection among the four protocols of immunosuppressive agents used, older patients and those with quadruple drug treatment had the highest rate of wound complications. Although old age was shown to increase the incidence of wound infection, the selection criteria remain based on risks and benefits of the transplantation procedure. Immediate and aggressive surgical debridement of all infected sternal tissue is mandatory with cultures and proper antibiotic treatment. Mediastinal drainage, debridement of all infected and necrotic tissue, and closure is most often successful, but omentoplasty and pectoralis muscle flaps may be necessary whenever sternal or mediastinal dead space needs to be controlled. Cryopreserved homograft appears to be a suitable conduit for aortic reconstruction in the presence of acute mediastinitis and infected pseudoaneurysm of the aorta; prosthetic material should probably be avoided. Aggressive surgical treatment of sternal wound complications results in good short- and long-term survival after heart transplantation.


    References
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 

  1. Loop F.D., Lytle B.W., Cosgrove D.M., et al. Sternal wound complications after isolated coronary artery bypass grafting: early and late mortality, morbidity, and cost of care. Ann Thorac Surg 1990;49:179-186.[Abstract]
  2. Mossad S.B., Serkey J.M., Longworth D.L., Cosgrove D.M., Gordon S.M. Coagulase-negative staphylococcal sternal wound infections after open heart operations. Ann Thorac Surg 1997;63:395-401.[Abstract/Free Full Text]
  3. Harbath S., Samore M.H., Lichtenberg D., Carmeli Y. Prolonged antibiotic prophylaxis after cardiovascular surgery and its effect on surgical site infections and antimicrobial resistance. Circulation 2000;101:2916-2926.[Abstract/Free Full Text]
  4. Jakob H.G., Borneff-Lipp M., Bach A., et al. The endogenous pathway is a major route for deep wound infection. Eur J Cardiothorac Surg 2000;17:154-160.[Abstract/Free Full Text]
  5. Eisen J.E., Hobbs R.E., Davis S.F., et al. Safety, tolerability, and efficacy of cyclosporine microemulsion in heart transplant recipients. A randomized, multicenter, double-blind comparison with the oil based formulation of cyclosporine—results at six months after transplantation. Transplantation 1999;68:663-671.[Medline]
  6. Kobashigawa J., Miller L., Renlund D., et al. A randomized active-controlled trial of mycophenolate mofetil in heart transplant recipients. Transplantation 1998;66:507-515.[Medline]
  7. Carrier M., White M., Perrault L.P., et al. A 10-year experience with intravenous thymoglobuline in induction of immunosuppression following heart transplantation. J Heart Lung Transplant 1999;18:1218-1223.[Medline]
  8. Mathieu P., Carrier M., White M., et al. Effect of mycophenolate mofetil in heart transplantation. Can J Surg 2000;43:202-206.[Medline]
  9. Jurkiewicz J.G., Bostwick J., Wood R., et al. Management of the infected median sternotomy wound with muscle flaps. The Emory 20-year experience. Ann Surg 1997;225:766-776.[Medline]
  10. Ascherman J.A., Hugo N.E., Sultan M.R., Patsi M.C., Smith C.R., Rose E.A. Single-stage treatment of sternal wound complications in heart transplant recipients in whom pectoralis major myocutaneous advancement flaps were used. J Thorac Cardiovasc Surg 1995;110:1030-1036.[Abstract/Free Full Text]
  11. Sood R., Cavarocchi N.C., Mitra A., McClurken J.B., Kolff J. Muscle flap closure for infected wounds after heart transplantation. Transplant Proc 1990;22:2394-2399.[Medline]
  12. Coselli J.S., Koksoy C., LeMaire S.A. Management of thoracic aortic graft infections. Ann Thorac Surg 1999;677:1990-1993.
  13. Katsumata T., Moorjani N., Vaccari G., Westaby S. Mediastinal false aneurysm after thoracic aortic surgery. Ann Thorac Surg 2000;70:547-552.[Abstract/Free Full Text]
  14. Argenziano M., Catanese K.A., Moazami N., et al. The influence of infection on survival and successful transplantation in patients with left ventricular assist devices. J Heart Lung Transplant 1997;16:822-831.[Medline]
  15. Griffith B.P., Kormos R.L., Hardesty R.L., Armitage J.M., Dummer J.S. The artificial heart: infection-related morbidity and its effect on transplantation. Ann Thorac Surg 1988;45:409-414.[Abstract]

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