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Ann Thorac Surg 1998;65:36-40
© 1998 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Mediastinitis After Cardiovascular Operations: A Case-Control Study of Risk Factors

Department of Cardiothoracic Surgery, Karolinska Hospital, Stockholm, Sweden
Department of Infectious Diseases, Karolinska Hospital, Stockholm, Sweden

Accepted for publication July 5, 1997.

Dr Bitkover, Department of Cardiothoracic Surgery, Karolinska Hospital, S-171 76 Stockholm, Sweden.

	Abstract

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Background. An analysis of risk factors for postoperative mediastinitis can lead to a better understanding of the pathogenesis of this complication and to more effective preventive measures.

Methods. This case-control study of 37 patients and 74 matched controls evaluated 54 potential risk factors.

Results. Nine variables were significantly associated with increased risk of postoperative mediastinitis: total operation time (p = 0.0013), high body-mass index (p = 0.0033), use of ß-adrenergic drugs before the onset of infection (p = 0.0037), long cardiopulmonary bypass time (p = 0.0072), long aortic cross-clamp time (p = 0.0075), presence of diabetes (p = 0.0122), high body weight (p = 0.0130), and use and duration of temporary pacing wires (p = 0.0293 and p = 0.0241 respectively). In a conditional logistic regression analysis, use of ß-adrenergic drugs before the onset of infection (p = 0.0058; odds ratio 19.7; 95% confidence limits, 2.37 and 163.7) and body mass index (p = 0.0082; odds ratio 1.27; 95% confidence limits, 1.06 and 1.52) were independently associated with a significantly increased risk of postoperative mediastinitis.

Conclusions. Obesity and use of ß-adrenergic drugs, which is indicative of obstructive respiratory problems, were the most important risk factors suggesting that mechanical strain on the sternotomy and sternal instability may precede infection. Targeted preventive measures for these groups could be justified.

	Introduction

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Postoperative mediastinitis is a serious complication in thoracic surgery that adds cost and suffering and substantially increases mortality. It still occurs despite the use of strict sterility in the operating room, preoperative scrubbing with a skin disinfectant, nonabrasive preoperative hair removal, antibiotic prophylaxis, and nontraumatic surgical intervention with sparing use of electrocautery. The reported incidence ranges from a fraction of a percent to more than 2% of all cardiothoracic operations. The average incidence of mediastinitis was 1.3% of all operations in ten large studies comprising more than 59,000 patients [1][2][3][4][5][6][7][8][9][10]. Previous studies [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] have recognized a number of risk factors, sometimes with conflicting results. Analysis of risk factors can lead to a better understanding of the pathogenesis of this complication, more effective preventive measures, better identification of high-risk patients, and better risk assessment of individual patients. The present case-control study was aimed at identifying risk factors for postoperative mediastinitis as it appears in our hospital.

	Patients and Methods

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Study Population
The study population comprised 1,935 consecutive adult patients who underwent sternotomy or thoracotomy for a cardiovascular operation with cardiopulmonary bypass during the 2-year period 1992 and 1993 at the Department of Cardiothoracic Surgery, Karolinska Hospital, Stockholm. The patients were usually admitted to the hospital the day before the operation. Preoperative preparation by the patient included three showers with hexachlorophene soap. Excessive hair in the operative area was removed by electric razor. Antibiotic prophylaxis was given intravenously 30 to 60 minutes before skin incision, after 4 hours, and then every 6 hours for a total of five doses. Cloxacillin, 2 g per dose, was the standard choice, and in the case of penicillin allergy, cefuroxime, 1.5 g per dose, was given. The skin was disinfected with ethyl alcohol in the operating theater.

Cases and Controls
Postoperative deep sternal wound infections (mediastinitis) occurred in 40 patients (coronary artery bypass = 22 patients, valve replacement = 6, combined procedures = 8, and aneurysm of the aorta = 4). The diagnosis was made on the basis of a positive bacterial culture from the mediastinum at the time of reexploration, a positive culture from pericardial effusion, or obvious clinical signs of mediastinitis on reexploration. Two controls for each patient were selected blindly from the operating room log with a match for age ±5 years and type of operation. For 3 patients with mediastinitis, no adequate matches could be found, and they were not included in the case-control calculations.

Variables
The data were obtained by a retrospective review of the patients’ charts. The following patient-related factors were recorded: age, sex, weight, height, body mass index (BMI) (weight in kilograms divided by height in meters squared), smoker (no, yes, formerly), chronic obstructive pulmonary disease (COPD), diabetes (insulin dependent or not), preoperative antibiotic treatment, cortisone medication, permanent pacemaker, other severe underlying noncardiac disease, previous myocardial infarction, estimated left ventricular ejection fraction, transferred for operation from another clinic as opposed to admission from home, days in hospital before operation, preoperative stay in intensive care unit, New York Heart Association class, and skin condition (eg, ulcers or eczema).

The following operation-related factors were recorded: day of the week, time of day, urgency of operation (elective, urgent, emergency), duration of operation, duration of cardiopulmonary bypass, duration of aortic cross-clamping, use of internal mammary artery, number of bypass grafts, use of jump graft, type of valve prosthesis, operating room used (number 1, 2, 3, or 4), consecutive operation in a particular operating room that day, experience of surgeon (senior attending surgeon, junior attending surgeon, resident), number of staff present in operating room, technical problems, problems weaning off cardiopulmonary bypass, number of chest drains, use of temporary pacing wires, operative blood loss, units of blood products transfused, use of Cell Saver, antibiotic prophylaxis given, and number of doses.

The following postoperative risk factors were assessed: time on mechanical ventilator, use of autotransfusion, postoperative blood loss, duration of temporary pacing wires, duration of central venous lines, use of ß-adrenergic drugs for respiratory problems (before onset of infection), APACHE II score in the first postoperative 24 hours [23], days with chest drains, use of intraaortic balloon pump, need of hemodialysis, days in the intensive care unit, and reoperations or other invasive procedures in the chest. Sternal instability was recorded but was not included in the risk-factor analysis.

Statistical Analysis
For evaluation of factors associated with the development of mediastinitis, a univariate conditional logistic regression analysis was done. In a subsequent multivariate conditional logistic regression analysis, the factors with a p value of less than 0.2 in the univariate analysis were entered in a stepwise manner. For analysis of correlation between continuous variables, the Pearson correlation analysis was used; for analysis of correlation between dichotomous variables, the ² test; and for analysis of correlation between continuous and dichotomous variables, a t test (after logarithmic transformation when appropriate). Two-sided analyses were done throughout. The statistical analyses were performed using SAS and Statistica software.

	Results

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Of the 1,935 patients studied, postoperative mediastinitis developed in 40 (2.1%). Because the patients were matched with controls on the basis of age, type of operation, and date of operation, the significance of these risk factors for mediastinitis could not be evaluated in the case-control study, but they were evaluated by comparing the patients with the entire study population. There were no clusters of cases in time. Patients operated on for aortic aneurysm carried a greater risk of postoperative mediastinitis (p = 0.047) than those operated on with valve replacement, coronary artery bypass grafting, or combined procedures. The age distribution did not differ between patients with mediastinitis and the rest of the patient population (mean and standard deviation, 64.3 and 11.7 and 64.2 and 11.6 years, respectively; p = 0.89).

In the univariate analysis of factors associated with the development of mediastinitis in the case-control study, 15 factors with a p value of less than 0.2 were identified (Table 1). Among the patient-related risk factors, BMI, need of ß-adrenergic drugs before the onset of infection, diabetes, and body weight were significantly associated with the development of postoperative mediastinitis (p < 0.05). Of the operation-related risk factors, total operation time, cardiopulmonary bypass time, aortic cross-clamp time, and use of temporary pacing wires were significantly associated with subsequent mediastinitis. Of the postoperative risk factors, only duration of temporary pacing wires was significantly associated with mediastinitis. Fifteen risk factors were entered into a logistic regression analysis. Only BMI and use of ß-adrenergic drugs before the onset of infection were independently associated with a significantly increased risk of postoperative mediastinitis (Table 2).

Sternal instability with dehiscence was evident in the postoperative period in 22 (59%) of the 37 patients with mediastinitis. In most instances, the diagnosis was made on clinical examination, was seen on computed tomographic scan, or both before signs of infection occurred. In some cases, the extent of the dehiscence with costal and sternal fractures was not evident until reexploration.

Signs of mediastinitis appeared an average of 7.4 days after the initial operation. In all but one instance, bacterial cultures from the mediastinal space or pericardial effusions were positive. The organisms grown are shown in Table 3. Most patients with mediastinitis had reoperation without delay and were treated with both a closed irrigation system containing antibiotics and intravenously administered antibiotics. The in-hospital mortality was 7 (18.9%) of the 37 patients with mediastinitis and 5 (6.8%) of the 74 matched controls (p = 0.052). The hospital mortality rate attributable to mediastinitis was 12.1%. The high mortality in the control group is partly due to the inclusion of 3 patients operated on for acute dissecting aortic aneurysm who died shortly after operation. The average hospital stay was 9.9 days in the control group and 39.4 days in the group with mediastinitis.

	Comment

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

In our extensive evaluation of 54 different risk factors, only obesity (expressed as BMI) and use of ß-adrenergic drugs in the perioperative period were identified as significant independent predictors of mediastinitis. We regard the need for perioperative treatment with ß-adrenergic drugs as a reliable sign of COPD or postoperative obstructive pulmonary problems. The use of ß-adrenergic drugs before the onset of infection increased the risk of postoperative mediastinitis almost 20-fold. A 10-kg increase in body weight in a patient of normal height more than doubled the risk of mediastinitis. We recognize that additional factors may also be important contributing risk predictors in our patients but were not identified because of the limited size of the study.

Apart from the possible problems with statistical power and the possibility of false-positive significance, there are other unavoidable limitations of studies such as this. Important risk factors may not have been evaluated at all as a result of insufficient prestudy experience and a low level of suspicion as well as a lack of detection techniques. For example, the degree of tissue traumatization or ischemia in the operative area or the extent of perioperative bacterial contamination of the wound may be important, but these potentially crucial factors do not allow reliable quantification.

Other previously published studies on risk factors for postoperative mediastinitis have sometimes showed conflicting results. Contrary to the risk of wound infection in other types of surgical procedures, most studies including the present one do not identify age as a risk factor in cardiac operations, although older age was a significant risk factor in one study [12] and younger age in another study [9]. Obesity has been shown to be a risk factor for postoperative mediastinitis by some authors [12][14][16][17][19], whereas others have failed to show such a relation [1][9][11][18][20]. Diabetes is a significant risk factor in some studies [4][6][9][14][16][17][20] but not in others [1][5][7][10][11][13][18], and COPD has been identified as a risk factor in some [5][18][22] but not all studies [6][7][9][17][20]. The severity of underlying heart disease has been found to be a risk factor for postoperative infection in some studies [5][6] but again not in others [1][7][9][17][18].

Length of stay in the hospital before operation, which may reflect the severity of the underlying conditions and perhaps allow time for colonization with hospital flora, has been described as a risk factor by some authors [3][15] but not others [7][9][14][17][18]. Operation-related factors such as prolonged operation time, long aortic cross-clamp time, and increased perioperative blood loss are often found to be significantly related to the development of mediastinitis [3][4][5][7][13][16][20]. However, this is not true of other studies [1][4][9][10][17][18]. Reoperation for bleeding or other reasons is associated with increased risk of mediastinitis in several studies [1][2][3][5][7][10][20]. The use of both internal mammary arteries for grafting has been implicated in some studies [8][16][17]. In the present study, bilateral internal mammary artery grafting was done only on rare occasions, and the risk was therefore not possible to evaluate. Even the presence of a particular member of the staff in the operating room has been found to be associated with increased risk of postoperative infections in some reports [15][20], a finding not confirmed in other studies [5][12][17].

Postoperative risk factors such as time on ventilator, days with a central venous line, use of dialysis, and days in the intensive care unit have often been associated with the occurrence of mediastinitis and other complications. However, these factors are influenced by the severity of the patient’s postoperative condition and could be the consequence of and not the cause of mediastinitis. The time spent on mechanical ventilation in our study was longer in the mediastinitis group, but these data were not included in the multivariate analysis for reasons already mentioned.

The lack of agreement between various studies can be explained to a certain extent by methodologic problems. In some studies [1][2][3][5][7][9][17], the risk of developing deep sternal wound infections (mediastinitis) was evaluated, and in others [10][14][15][19][20], both deep and superficial infections were evaluated together. Further, in other studies [12][16][18], all sternal complications including instability were analyzed together, whereas in others, sternal infection was not defined at all. This makes interpretation of results difficult and comparison between studies futile. Some studies with only a few cases of mediastinitis have severe statistical power problems. In addition, if only a few patients have the risk factor in question, its potential importance may not be recognized. On the other hand, multiple statistical testing may lead to false-positive significance, a problem that can occur when a large number of factors are analyzed. However, even in studies that do not have most of these problems [2][3][5][7][9][17], the risk factors recognized differ substantially. In three of these reports [2][3][7], operation-related risk factors seem to be most important (length of operation, duration of cardiopulmonary bypass, type of operation, reoperation for bleeding, and blood loss). In another three [5][9][17], patient-related risk factors dominate (diabetes, smoking, COPD, BMI, preoperative cardiac performance, and nasal carriage of Staphylococcus aureus).

We have observed sternal instability to be strongly associated with the development of mediastinitis, but this factor was not included in the multivariate analysis because we were not certain that the instability occurred before and not as a consequence of the infection in all instances. Sternal instability was significantly associated with both use of ß-adrenergic drugs and BMI but not with operation-related risk factors. A possible interpretation of the data is that in the overweight patient with a high BMI, strong lateral forces tend to pull the sternal halves apart; if the patient also has obstructive pulmonary problems, intense postoperative coughing can lead to excessive strain on the sternal wiring, thereby creating a high risk of sternal dehiscence. This may lead to the inward spread of bacteria from the subcutaneous region and the development of mediastinitis. Other studies have also shown that sternal instability is associated with mediastinitis [2][3][7][12] and that obesity and respiratory problems can lead to sternal dehiscence [24][25].

Microorganisms inoculated into the subcutaneous tissue did not cause mediastinitis in dogs [26]. However, if the subcutaneous tissue is traumatized with excessive use of electrocautery, mediastinitis could develop even with intact sternal fixation. This illustrates that technical surgical factors may be of importance. Prolonged operation time, shown to be a significant risk factor in this and other studies, may reflect technical surgical problems, a longer period of skin and subcutaneous tissue ischemia because of instrumentation, and a prolonged exposure to possible bacterial contamination in the wound.

It would appear that the development of postoperative mediastinitis is a multifactorial event and that the most important risk factors may, in fact, differ between institutions and perhaps even from one time to another in the same institution. A risk factor identified in one hospital may not be relevant in another. Continued reevaluation of infectious complications and risk factors seems warranted to provide a basis for preventive measures. We conclude that in our hospital, patient-related risk factors dominate. Cost-effective measures in our institution could be to optimize preoperative and postoperative medication for patients with COPD and patients with excessive coughing and to recognize the risk associated with obesity. Weight loss programs before elective operations or more selective acceptance of high-risk patients for nonvital surgical procedures could be considered. In other hospitals where other risk factors predominate, other interventions may be more appropriate.

	Acknowledgments

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
This study was supported by grants from the Karolinska Institute. We thank statistician Elisabeth Berg for her assistance.

	Footnotes

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
This article has been selected for the open discussion forum on the STS Web site: http://www.sts.org/annals

	References

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 

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				A. Combes, J.-L. Trouillet, J. Baudot, M. Mokhtari, J. Chastre, and C. Gibert Is it possible to cure mediastinitis in patients with major postcardiac surgery complications? Ann. Thorac. Surg., November 1, 2001; 72(5): 1592 - 1597. [Abstract] [Full Text] [PDF]

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				A. Borer, J. Gilad, N. Meydan, K. Riesenberg, F. Schlaeffer, M. Alkan, and P. Schlaeffer Impact of active monitoring of infection control practices on deep sternal infection after open-heart surgery Ann. Thorac. Surg., August 1, 2001; 72(2): 515 - 520. [Abstract] [Full Text] [PDF]

				R. Astudillo, J. Vaage, U. Myhre, A. Karevold, and B. Gardlund Fewer reoperations and shorter stay in the cardiac surgical ward when stabilising the sternum with the Ley prosthesis in post-operative mediastinitis Eur. J. Cardiothorac. Surg., July 1, 2001; 20(1): 133 - 139. [Abstract] [Full Text] [PDF]

				M. De Feo, R. Gregorio, A. Della Corte, C. Marra, C. Amarelli, A. Renzulli, R. Utili, and M. Cotrufo Deep sternal wound infection: the role of early debridement surgery Eur. J. Cardiothorac. Surg., June 1, 2001; 19(6): 811 - 816. [Abstract] [Full Text] [PDF]

				M. De Feo, A. Renzulli, G. Ismeno, R. Gregorio, A. Della Corte, R. Utili, and M. Cotrufo Variables predicting adverse outcome in patients with deep sternal wound infection Ann. Thorac. Surg., January 1, 2001; 71(1): 324 - 331. [Abstract] [Full Text] [PDF]

				C. Y. Bitkover, E. Marcusson, and U. Ransjo Spread of coagulase-negative staphylococci during cardiac operations in a modern operating room Ann. Thorac. Surg., April 1, 2000; 69(4): 1110 - 1115. [Abstract] [Full Text] [PDF]

				T. Szerafin, O. Jaber, and A. Peterffy Reduction of wound healing problems after median sternotomy Ann. Thorac. Surg., December 1, 1999; 68(6): 2388 - 2388. [Full Text] [PDF]

				C. Y. Bitkover, K. Cederlund, B. Aberg, and J. Vaage Computed tomography of the sternum and mediastinum after median sternotomy Ann. Thorac. Surg., September 1, 1999; 68(3): 858 - 863. [Abstract] [Full Text] [PDF]