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Sternal Wound Infection After Heart

Transplantation: Incidence and Results With


Aggressive Surgical Treatment
Michel Carrier, MD, Louis P. Perrault, MD, Michel Pellerin, MD,
Richard Marchand, MD, Pierre Auger, MD, Guy B. Pelletier, MD, Michel White, MD,
Normand Racine, MD, and Denis Bouchard, MD
Department of Surgery and Medicine and the Microbiology Laboratory, Montreal Heart Institute and University of Montreal,
Montreal, Quebec, Canada

Background. Sternal wound infection remains a signif- sporine, prednisone, mycophenolate mofetil, and anti-
icant complication. We reviewed the incidence and the thymocyte globulin (3 of 41; 7.3%) (p ⴝ 0.4). Six-month
treatment of sternal wound infection after heart and 5-year survival of patients with sternal wound infec-
transplantation. tion averaged 85% ⴞ 8% and 74% ⴞ 10% compared with
Methods. Of 226 patients who had a heart transplanta- 92% ⴞ 2% and 82% ⴞ 3% in patients without wound
tion, 20 (8.8%) underwent postoperative wound debride- infection (p ⴝ 0.15). Patients with deep sternal wound
ment for superficial or deep sternal wound infection. The infection, debridement, and reconstruction had a 5-year
incidence and the survival of patients with sternal survival averaging 80% ⴞ 10%.
wound infection were analyzed. Conclusions. The incidence of sternal wound infection
Results. The incidence of sternal wound infection was remains similar between patients treated with the triple
similar among patients treated with four protocols of drug therapy. Surgical debridement and reconstruction
immunosuppressive drugs: cyclosporine and prednisone can result in long-term survival after heart transplanta-
(0 of 22; 0%); cyclosporine, prednisone, and azathioprine tion.
(2 of 24; 8.3%); cyclosporine, prednisone, azathioprine, (Ann Thorac Surg 2001;72:719 –24)
and antithymocyte globulin (15 of 139; 10.8%); and cyclo- © 2001 by The Society of Thoracic Surgeons

S ternal wound infection remains a serious complica-


tion after cardiac operations, with rates ranging from
1% to 10% [1– 4]. Although most wound infection epi-
Material and Methods
Heart Transplantation Program
sodes are superficial and self limited, deep sternal infec- From 1983 to September 2000, 237 patients underwent
tion and acute mediastinitis can be life-threatening, es- heart transplantation at the Montreal Heart Institute.
pecially in heart transplantation recipients to whom Eleven patients died during or immediately after their
immunosuppressive agents are administered during the surgical procedures, precluding any significant analysis
postoperative period. Not only was sternal wound infec- of the risk of wound infection. All patients were followed
tion not reported in the most recent clinical trials com- prospectively and data were collected in a computerized
paring newer immunosuppression agents after heart database. Four protocols of immunosuppressive agents
transplantation [5, 6], but the incidence of wound infec- were used during the study period. Cyclosporine and
tion was almost never analyzed in single-center studies prednisone were administered to patients who under-
on clinical results after heart transplantation. Yet, sternal went heart transplantation between 1983 and 1987. Cy-
wound infection is a major cause of morbidity and closporine, prednisone, and azathioprine were used in
occasionally of mortality among these patients. 1988; the combination of cyclosporine, prednisone, aza-
The objective of the present study was to review the thioprine, and rabbit antithymocyte globulin from 1989 to
variation in the incidence of sternal wound infection 1997; and cyclosporine, prednisone, mycophenolate
according to different protocols of immunosuppressive mofetil, and antithymocyte globulin was used from 1997
drugs immediately after heart transplantation. The clin- to 2000 [7, 8].
ical outcome of sternal wound infection treatment after Patients who underwent open heart operations be-
heart transplantation was also reviewed. tween 1983 and 2000 were administered preoperative and
Accepted for publication May 3, 2001. postoperative antibiotic prophylaxis with either cefazolin
or vancomycin for penicillin-allergic patients. The anti-
Address reprint requests to Dr Carrier, Department of Surgery, Montreal
Heart Institute, 5000 Belanger St East, Montreal, QB, H1T 1C8, Canada; biotics were administered during the first 48 hours after
e-mail: carrier@icm.umontreal.ca. operation in heart transplantation patients.

© 2001 by The Society of Thoracic Surgeons 0003-4975/01/$20.00


Published by Elsevier Science Inc PII S0003-4975(01)02824-7
720 CARRIER ET AL Ann Thorac Surg
STERNAL WOUND INFECTION 2001;72:719 –24

Definition of the Type of Infection sternal wound infection after transplantation were hos-
Sternal wound infection was classified as superficial pitalized before transplantation (recipient UNOS status
infection characterized by purulent drainage from the 1) compared with 89 (of 206; 43%) UNOS status 2 recip-
wound limited to cutaneous and subcutaneous involve- ients who remained free from wound infection after
ment. Deep wound infection involved deep fascial and transplantation.
muscular tissue. Acute mediastinitis was defined as pu- Twenty-five patients were mechanically supported be-
rulent drainage involving the sternal bone and surround- fore heart transplantation, 5 with the CardioWest total
ing mediastinal tissue. Cultures of drainage of all sus- artificial heart, 3 with a Thoratec (Pleasanton, CA) left
pected surgical wound infections were obtained and ventricular assistance, and 17 with an intraaortic balloon
analyzed routinely. pump. All other mechanically supported patients did not
show any evidence of sternal infection throughout the
Statistical Analysis periods of support and transplantation. One patient (of
Data are expressed in mean and standard deviation. 20; 5%) was on mechanical assistance with the Cardio-
Differences between means were analyzed with the Stu- West (Tucson, AZ) total artificial heart and developed an
dent’s t test, and the Fisher exact test was used for episode of acute mediastinitis after heart transplantation.
categorical variables. The actuarial method was used to Patients who developed sternal wound infection after
analyze survival and event-free survival in our groups of transplantation waited 15 ⫾ 23 weeks for a donor heart
patients. A logistic regression analysis was used to study compared with 24 ⫾ 38 weeks for patients who did not
the risk factors correlated with wound infection after show any evidence of wound infection after transplanta-
heart transplantation. Factors included in the analysis tion (p ⫽ 0.13). Donor ischemic time in these two groups
averaged 139 ⫾ 49 minutes and 134 ⫾ 63 minutes,
were recipient age, sex, pretransplant diabetes, mechan-
respectively (p ⫽ 0.5).
ical support before transplantation, and the protocols of
immunosuppressive drugs. Sternal Wound Infection and Regimens of
Immunosuppressive Drugs
Results There was no sternal wound infection among the 22
patients treated with cyclosporine and prednisone. Evi-
Patient Population
dence of sternal wound infection after heart transplanta-
Among 226 patients who had a heart transplantation, tion was found in 2 of 24 (8.3%) patients who were
preoperative diagnoses included 118 (52%) with end- administered cyclosporine, prednisone, and azathio-
stage ischemic cardiomyopathy, 50 (22%) with congestive prine; 15 of 139 patients (10.8%) who were administered
cardiomyopathy, and 38 (17%) with various forms of cyclosporine, prednisone, azathioprine, and antithymo-
end-stage heart disease. Of the 226 patients, 20 (8.8%) cyte globulin; and 3 of 41 patients (7.3%) who were
showed evidence of sternal wound infection: 9 (of 226; administered cyclosporine, prednisone, mycophenolate
3.9%) had superficial wound infections, 4 (of 226; 1.8%) mofetil, and antithymocyte globulin (p ⫽ 0.4).
had deep wound infections, and 7 (of 226; 3%) had acute Of the 20 sternal wound infections after heart trans-
mediastinitis. Of these 20 patients, 3 (15%) were women plantation, most were superficial (9; 45%), 4 (20%) were
and 17 (85%) were men; of the 206 free from sternal deep, and 7 (35%) were episodes of acute mediastinitis.
infection, 37 (18%) were women and 169 (82%) were men The acute mediastinitis was caused by various bacterial
(p ⫽ 0.7). Patients with sternal wound infection averaged agents in various combinations: bacteroides (n ⫽ 1),
52 ⫾ 9 years of age compared with 46 ⫾ 10 years in Escherichia coli (n ⫽ 2), Staphylococcus epidermidis (n ⫽ 5),
patients free from sternal infection (p ⫽ 0.01). Diabetes Staphylococcus aureus (n ⫽ 6), methicillin-resistant S au-
was noted in 1 of the 20 patients (5%) who developed a reus (n ⫽ 2), Aspergillus fumigans (n ⫽ 1). For superficial
sternal wound infection and in 12 of 206 patients (6%) and deep wound infections, S aureus (8 of 20; 40%) and S
without wound infection after transplantation (p ⫽ 0.9). epidermidis (5 of 20; 25%) were the most common bacteria
Superficial wound infections were treated with local responsible.
debridement and dressing changes in an outpatient
clinic. Deep wound infections were treated with surgical Survival and Rejection
debridement and sternal rewiring including Robiscek Six-month and 5-year survival of patients with sternal
weave in 3 patients and local debridement in another wound infection averaged 85% ⫾ 8% and 74% ⫾ 10%,
patient. Acute mediastinitis was treated with surgical compared with 92% ⫾ 2% and 82% ⫾ 3% in patients
debridement, drainage, and sternal rewiring in 5 pa- without wound infection (p ⫽ 0.15) (Fig 1). Eleven pa-
tients. Omentoplasty and pectoralis muscle flaps were tients with deep sternal wound infection or acute medi-
used in 2 other patients. astinitis underwent aggressive surgical debridement,
Sixteen patients (of 20; 80%) who developed sternal drainage, and reconstruction with 6-month and 5-year
wound infections after transplantation were followed at survival rates averaging 91% ⫾ 9% and 80% ⫾ 10%,
our outpatient clinic while waiting for heart transplanta- respectively (Fig 2). One patient with acute mediastinitis
tion (recipient UNOS status 2) compared with 116 (of 206; died from uncontrolled sternal wound infection after
56%) UNOS status 2 recipients without wound infection implantation of a total artificial heart and transplantation
after transplantation. Four patients (of 20; 20%) with and another patient died from massive hemorrhage sec-
Ann Thorac Surg CARRIER ET AL 721
2001;72:719 –24 STERNAL WOUND INFECTION

Fig 1. Actuarial survival of patients with superficial, deep, and


acute mediastinitis (infection) compared with patients without ster-
nal wound infection. Survival was lower among patients with ster-
nal wound infection, but the difference is not statistically significant
(p ⫽ 0.15).

ondary 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 suc-
cessfully after surgical debridement, mediastinal drain-
age, and sternal reclosure associated with the proper
antibiotic treatment.
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
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 ster-
nal 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.

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 trans-
Fig 2. Actuarial survival of patients with deep sternal wound infec- plantation. The use of mycophenolate mofetil, azathio-
tion and acute mediastinitis compared with patients without deep prine, and antithymocyte globulin was not associated
wound and mediastinal infection. Survival was similar in the two with wound infection, nor was the presence of diabetes
groups. before transplantation.
722 CARRIER ET AL Ann Thorac Surg
STERNAL WOUND INFECTION 2001;72:719 –24

From 1992 to 2000, including 13,199 patients undergo-


ing cardiac operation in our institution, the annual inci-
dence 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 im-
munosuppressive 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, reop-
eration, and in 2 cases reconstruction of the ascending
aorta (Dacron graft in 1 case and cryopreserved ho-
mograft in another) associated with pectoralis muscle
flaps and omentoplasty to control the mediastinal in-
fected space. Other authors have also reported the use of
muscle flaps and of omentoplasty in patients with medi-
astinal infection after conventional operation [9] or heart
transplantation [10, 11].
Coselli and colleagues [12] described the use of cryo-
preserved 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
Fig 4. A patient underwent resection of the false aneurysm, drainage the ascending aorta at the site of the aortic anastomosis
of the retroaortic abscess, reconstruction of the ascending aorta with
[13]. Although Argenziano and colleagues [14] showed
a cryopreserved homograft, omentoplasty to control mediastinal dead
that wound infection in patients with left ventricular
space, and pectoralis muscle flap to secure the sternal closure. The
patient had a successful outcome and remains free from recurrence 6 assist support does not adversely affect survival, local
months after the operation. infection surrounding a total artificial heart carries a
dismal prognosis [15], as was the case with 1 of our
patients.
Comment There is no clear guideline as to the level of immuno-
Heart transplantation is an established treatment for suppression that should be maintained in patients with
patients in end-stage heart failure. Although rejection significant sternal wound infection after transplantation.
and systemic infections episodes have been well charac- Our practice has been to rely on cyclosporine and pred-
terized among transplant patients, sternal wound infec- nisone while azathioprine or mycophenolate mofetil
tion is seldom reported and rarely discussed. Yet, sternal were stopped until we were confident that the sternal or
wound infection after standard cardiac operations and mediastinal infection was controlled. The use of cyclo-
after heart transplantation is the major source of morbid- sporine and prednisone was effective in preventing the
ity and mortality. The present study showed that sternal rejection process during these episodes of sternal wound
wound infection after heart transplantation correlates infection.
directly with patient age. There was no significant rela- Sternal wound infection and acute mediastinitis re-
tionship between the incidence of sternal wound infec- main a serious complication after heart transplantation.
tion and protocols of immunosuppressive drugs used in Although there was no significant difference in the inci-
the present experience, although the incidence was dence of sternal wound infection among the four proto-
slightly higher among patients with the quadruple drug cols of immunosuppressive agents used, older patients
therapy. There was no sternal infection in patients with and those with quadruple drug treatment had the high-
the double drug therapy of cyclosporine and prednisone, est rate of wound complications. Although old age was
but the later protocol was used in the earliest part of our shown to increase the incidence of wound infection, the
experience with heart transplantation enrolling only selection criteria remain based on risks and benefits of
young patients. Moreover, survival of patients with ster- the transplantation procedure. Immediate and aggres-
nal wound infection remains similar to those without sive surgical debridement of all infected sternal tissue is
wound infection after transplantation suggesting that, in mandatory with cultures and proper antibiotic treatment.
most cases, aggressive surgical debridement and appro- Mediastinal drainage, debridement of all infected and
priate reconstructive approaches were successful. necrotic tissue, and closure is most often successful, but
Ann Thorac Surg CARRIER ET AL 723
2001;72:719 –24 STERNAL WOUND INFECTION

omentoplasty and pectoralis muscle flaps may be neces- results at six months after transplantation. Transplantation
sary whenever sternal or mediastinal dead space needs 1999;68:663–71.
6. Kobashigawa J, Miller L, Renlund D, et al. A randomized
to be controlled. Cryopreserved homograft appears to be active-controlled trial of mycophenolate mofetil in heart
a suitable conduit for aortic reconstruction in the pres- transplant recipients. Transplantation 1998;66:507–15.
ence of acute mediastinitis and infected pseudoaneurysm 7. Carrier M, White M, Perrault LP, et al. A 10-year experience
of the aorta; prosthetic material should probably be with intravenous thymoglobuline in induction of immuno-
suppression following heart transplantation. J Heart Lung
avoided. Aggressive surgical treatment of sternal wound Transplant 1999;18:1218–23.
complications results in good short- and long-term sur- 8. Mathieu P, Carrier M, White M, et al. Effect of mycopheno-
vival after heart transplantation. late mofetil in heart transplantation. Can J Surg 2000;43:
202– 6.
9. Jurkiewicz JG, Bostwick J, Wood R, et al. Management of the
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INVITED COMMENTARY
Sternal wound infections following cardiac surgery have dence of superficial SWI and a 3.3% deep SWI rate. Not
been well defined. Subscribing to the CDC definition of that much different than Carrier’s incidence.
surgical wound infection (SWI) a “deep” infection is Could it be that different risk factors play a role in SWI
characterized by a subfascial location or involving the after heart transplantation? Malnutrition, cardiac ca-
bone or retrosternal space (mediastinitis). The incidence chexia, chronic low cardiac output state, anemia, pro-
is generally well below 1% for valve procedures and longed hospitalization on inotropic support through cen-
increases to 1% to 2% for coronary artery bypass grafting. tral lines, and infections or colonization with nosocomial
Risk factors are consistent across series and include older flora followed immediately by intense immunosuppres-
age, diabetes, obesity, chronic obstructive pulmonary sion may put these patients at increased infection risk.
disease, current smoking, use of bilateral internal tho- Unfortunately, very few variables were investigated in
racic arteries and surgical techniques that traumatize the this series. Inexplicably, 80% of the SWI occurred in what
tissue or interfere with wound healing. Mortality is would appear to be a low risk population of United
significant at 10% to 20%. Network for Organ Sharing status II patients waiting on
Heart transplantation SWI rate should be similar to average only 4 months for transplantation, and, unlike
that of a valve procedure. In fact, one could expect an SWI in nontransplant patients, mortality was not signif-
even lower incidence because many of the risk factors for icantly increased (although a trend was suggested). This
SWI are contraindications to transplantation and the undoubtedly reflects the small numbers affected.
sternum is not acutely devascularized. So on initial read- Their management paradigm supports an aggressive
ing, the 3.9% superficial SWI and 4.9% deep infection diagnostic and therapeutic approach, which I support.
rates reported by Carrier and colleagues appear quite Prevention is the best. All nonpermanent central venous
high. However as they point out there is very little lines are replaced at the time of transplant and in LVAD
information published to compare these rates with. A patients the pump pocket and mediastinum are debrided
quick (unconfirmed) review of our transplant database of all necrotic material and copiously irrigated before
(excluding left ventricular assist device [LVAD] patients) implanting the heart. If a deep SWI occurs, especially in
found a 5% SWI rate and a separate database managed the patient who has had multiple previous operations
by the Infectious Disease Department found a 2% inci- and a fixed mediastinum, obliteration of the infected

© 2001 by The Society of Thoracic Surgeons 0003-4975/01/$20.00


Published by Elsevier Science Inc PII S0003-4975(01)03043-0

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