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Ann Thorac Surg 2001;72:1592-1597
© 2001 The Society of Thoracic Surgeons

Original article: cardiovascular

Is it possible to cure mediastinitis in patients with major postcardiac surgery complications?

Alain Combes, MD*a, Jean-Louis Trouillet, MDa, Jérôme Baudot, MDa, Mourad Mokhtari, MDa, Jean Chastre, MDa, Claude Gibert, MDa

a Service de Réanimation Médicale, Hôpital Bichat, Paris, France

Accepted for publication June 28, 2001.

* Address reprint requests to Dr Combes, Service de Réanimation Médicale, Pr Gibert, Hopital Bichat, 46, rue Henri-Huchard, 75877 Paris Cedex 18, France
e-mail: alain.combes{at}bch.ap-hop-paris.fr


   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Comment
 References
 
Background. The prognosis for mediastinitis after cardiac operation has improved during the last two decades, but most series do not include patients who already have a major postoperative complication when the infection developed.

Methods. Our 9-year prospective study of 371 consecutive patients with mediastinitis compared the characteristics of patients admitted to the intensive care unit primarily for mediastinitis with those who developed mediastinitis after intensive care unit admission for severe postoperative organ failure.

Results. We identified 323 (87%) primary and 48 (13%) secondary mediastinitis patients. The incubation time for mediastinitis was longer for secondary mediastinitis patients, despite similar initial operations. Staphylococcus aureus was responsible for approximately 60% of the episodes in both groups; however, the incidence of methicillin resistance was 2.5 times higher in secondary mediastinitis patients (p < 0.0001). The mediastinitis cure rate was similar for both groups. However, intensive care unit mortality (63% versus 21%), duration of mechanical ventilation (40 versus 9 days), and length of intensive care unit stay (53 versus 28 days) were significantly higher for secondary mediastinitis patients (p < 0.0001).

Conclusions. The presence of a prior major postoperative complication does not alter the cure rate of mediastinal infections, but does greatly reduce the survival rate.


   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Comment
 References
 
Mediastinitis is a feared complication of cardiac surgical procedures, with a reported incidence ranging from 0.25% to 2.3% in the most recent series [1–5]. Aggressive treatment with early surgical debridement, closed Redon catheter drainage [6–8], or plastic reconstruction procedures [9–13] have improved outcome. However mortality remains high, ranging from 7% to 40% [2–5, 7, 14–16]. It should be noted that, in those series, patients with organ failure before the development of surgical wound infection were generally excluded.

Hence, to date, no precise data are available concerning demographics and clinical outcome of patients experiencing mediastinitis after a first major complication of heart operation. Therefore, we undertook a prospective study more than 9 years on consecutive patients treated in our intensive care unit (ICU) for mediastinitis. The characteristics of patients whose primary reason for admission was treatment of mediastinitis (1°M group) were compared with those of patients admitted for treatment of a prior postoperative complication and who exhibited clinical signs of mediastinitis more than 48 hours after admission (2°M group).


   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Comment
 References
 
This prospective study was conducted from January 1991 to December 2000, in a 17-bed ICU in Hôpital Bichat, Paris, France. The protocol was in accordance with the ethical standards of our institution’s Committee for the Protection of Human Subjects. No informed consent was obtained, given that this epidemiologic study did not modify existing diagnostic or therapeutic strategies.

Patients
All consecutive patients treated for mediastinitis in our ICU during the past 9 years were included. These patients were referred from different local secondary or tertiary surgical centers. The study population was divided into two groups: primary mediastinitis (1°M), for patients referred to our ICU with the primary diagnosis of mediastinitis (surgical debridement was generally performed just before the patient was transferred), and secondary mediastinitis (2°M), for patients referred to our unit for treatment of another major cardiac surgical complication who developed their first signs of mediastinitis more than 48 hours after admission to our ICU.

Data collection
Each patient’s hospital chart was constituted prospectively and the following data were recorded: age, sex, type of initial cardiac operation, severity of underlying medical condition, stratified according to the criteria of McCabe and Jackson [17], simplified acute physiology score (SAPS II) [18], acute physiology and chronic health evaluation score (APACHE II) [19], Glasgow coma scale score, and organ dysfunction(s) or infection score (ODIN) [20]. All these measurements were recorded within the 24 hours after the patient’s admission to the ICU, with the worst value for each variable being retained for disease-severity score calculation.

In addition, the following measurements were recorded: primary admission diagnosis for 2°M patients, mediastinitis incubation time, defined as the interval between the initial cardiac operation and surgical debridement, time from ICU admission to mediastinal debridement for 2°M patients, organism(s) responsible for mediastinal infection (ie, those isolated from surgically removed tissues, needle wound aspiration, blood cultures, or effluent-drainage cultures), concomitant bacteremia, and type of mediastinal treatment after debridement (closed drainage with Redon catheters [7] applied whenever possible or open-wound treatment when immediate closing was impossible).

Outcome measures
Outcome measures included the following: ICU mortality, duration of mechanical ventilation, duration of ICU stay, time to mediastinal fluid sterilization (calculated as the interval between the time of debridement and the first day that the collected mediastinal fluid was sterile), duration of Redon drainage, and treatment failure to resolve local infection, defined as need for repeat debridement. Finally, life-threatening complications occurring after initial mediastinal debridement were recorded: organ dysfunction(s), secondary endocarditis, or massive mediastinal hemorrhage caused by vascular or cardiac rupture.

Statistical analyses
Clinical and laboratory data were statistically analyzed with Student’s t test for the comparison of continuous variables and the {chi}2 test or Fisher’s exact test for the comparison of percentages. Time-to-event variables were estimated according to the Kaplan-Meier method, and were compared with the log-rank test. Statistical significance was defined as p less than 0.05.


   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Comment
 References
 
Study population
Between January 1991 and December 2000, 371 patients were treated in our ICU for acute poststernotomy mediastinitis. Mediastinal infection was the primary reason for ICU admission for 323 patients. Forty-eight patients exhibited secondary mediastinitis more than 48 hours after admission to our institution for treatment of another major cardiac surgical complication: 21 (44%) had postoperative multiple organ dysfunction, 18 (38%) had respiratory failure, 6 (13%) had hemodynamic failure, and 3 (6%) had impaired neurologic status. On ICU admission, 18 (38%) 2°M patients had an ongoing infection: 15 (31%) had pneumonia and 3 (7%) had septicemia. Gram-negative bacteria (73%) were predominantly responsible for these infections but were never isolated subsequently from 2°M patients’ mediastinal fluid cultures.

Comparison of the characteristics of the two study groups at ICU admission (Table 1) showed no statistical differences for patients’ age, sex ratio, and type of initial cardiac operation. However, 2°M patients had signs of more severe illness at admission: 44% of them had a preexisting, rapidly or ultimately fatal disease; three of their organs on average were failing; and their disease-severity scores were higher. Incubation time was significantly longer for 2°M than 1°M patients (Table 2), and the former developed mediastinitis with an incubation time of 27 days (median, 19 days), that is to say a mean of 18 days (median, 13 days) after ICU admission. Finally, mediastinitis was treated with closed drainage using Redon catheters for the majority of patients regardless of group assignment (Table 2), and the interval between onset of symptoms and surgical wound debridement was no longer than 2 days for both groups of patients: in cases of unexplained fever, sternal instability, erythema, or wound discharge, our routine is to perform a needle aspiration of the mediastinum, and debridement is performed soon after evidence of infection.


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  		Table 1. Intensive Care Unit Admission Clinical Characteristics of 371 Postoperative Patients Treated for Primary and Secondary Mediastinitis

 

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  		Table 2. Mediastinal Infection Features of 371 Postoperative Patients Treated for Primary and Secondary Mediastinitis

 
Microbiologic findings in mediastinal samples
Staphylococci were the most frequent microorganisms cultured from mediastinal samples and were responsible for approximately 70% of the episodes in each group. Methicillin-resistant Staphylococcus aureus (MRSA) was responsible 2.5 times more frequently (p < 0.0001) in secondary infections (Fig 1). Conversely, gram-negative bacilli rates did not differ for the two groups. In addition, the percentages of bacteremic and multimicrobial infections did not differ significantly between groups as were the percentages of mediastinitis occurring less than 15 days after the initial operation (Table 2).



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  		Fig 1. Distribution of microorganisms causative of primary ({blacksquare}) or secondary () mediastinitis; *p < 0.0001. (CNS = coagulase-negative Staphylococcus; GNB = gram-negative bacilli; MRSA = methicillin-resistant S aureus; MSSA = methicillin-sensitive S aureus; Others = other pathogens grown from bacteriologic samples.)

 
Clinical outcomes
Kaplan-Meier estimates of the cumulative probabilities of mediastinal effluent sterilization and duration of Redon catheter drainage as a function of the numbers of days after mediastinal debridement were similar for both groups (Fig 2). The rate of first-line mediastinitis treatment failure was low and did not differ significantly for patients with primary or secondary infections. However, the outcome for 2°M patients was notably poorer (Table 3), with ICU length of stay, ICU mortality, and duration of mechanical ventilation being significantly higher. These patients also experienced multiple organ failure significantly more frequently. Finally, mortality tended to be higher in patients with incubation time less than 2 weeks in the 1°M group (24% versus 15%; p = 0.06), and was similar in the 2°M group (58% versus 64%; p = 0.6).



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  		Fig 2. Kaplan-Meier estimates of the cumulative probabilities of mediastinal effluent sterilization (A) and duration of Redon catheter drainage (B) as a function of the numbers of days after surgical debridement for patients with primary (•) and secondary ({circ}) mediastinitis.

 

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  		Table 3. Outcome Variables for Patients Treated for Primary or Secondary Mediastinitis

 

   Comment
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
References
 
To ascertain the epidemiologic and etiologic microbial aspects of mediastinitis occurring in patients with a major postcardiac surgical complication, we undertook a prospective study and compared the characteristics of patients whose reason for primary admission was treatment of mediastinitis with those hospitalized in our tertiary ICU for severe postoperative organ failure who developed 2°M more than 48 hours after admission. Of the 371 consecutive patients treated for mediastinitis in our department more than 9 years, we identified 48 (13%) 2°M patients. The primary reasons for ICU admission of these patients were respiratory, hemodynamic, neurologic, or multiple organ failure during the postoperative period. Our results indicate that 2°M patients had signs of more severe disease at ICU admission and that their mediastinitis incubation time was longer, despite the similar distribution of initial operation types in both groups. Staphylococci were responsible for 70% of the episodes in each group; however, MRSA predominated in 2°M patients. In addition, these patients had significantly higher ICU mortality rate, duration of mechanical ventilation, length of stay in the ICU, and percentage of patients who developed multiple organ failure, despite the similar efficacy of mediastinal treatment for the two groups.

This study prospectively evaluated the characteristics and outcome of mediastinitis occurring after a first major heart operation complication. Mediastinitis risk factors have been extensively studied during the past 20 years and have been classified as preoperative (diabetes mellitus, obesity, chronic obstructive pulmonary disease, male sex, renal insufficiency, New York Heart Association class, prior heart operation), intraoperative (duration of operation, use of bone wax, use of electrocautery, coronary artery bypass grafting with bilateral mammary arteries), and postoperative factors (use of inotropic agents, intraaortic balloon pump, postoperative bleeding, reoperation, use of blood products, prolonged mechanical ventilation) [1–3, 21–26]. Obviously, 2°M patients cumulated many of the known postoperative factors, such as use of inotropic agents, prolonged mechanical ventilation or altered renal function, all consequences of postoperative hemodynamic or multiple organ failure, and disease-severity scores for these patients attested to the gravity of their conditions at ICU admission as compared with those of 1°M patients.

The bacterial pathogens cultured in 1°M patients were similar to those previously reported by our group and others [2, 7, 16, 27–29], with methicillin-sensitive S aureus and all strains of staphylococci accounting for, respectively, approximately 50% and 70% of the isolates. Wound contamination by skin flora at the time or soon after operation was the main route of sternal infection in this setting [1–3, 30]. One could have postulated that secondary infection might have originated from hematogenous contamination by antibiotic-resistant gram-negative bacteria, such as Pseudomonas, Acinetobacter, or Stenotrophomonas. Actually, at ICU admission, 38% of the future 2°M patients had pneumonia or septicemia, mainly caused by gram-negative bacteria. However, none of these bacteria were later grown in mediastinal effluent cultures, and the only difference in the distribution of bacterial species collected from the mediastinum of patients in both groups was the inverted percentages of methicillin-sensitive S aureus and MRSA, with the latter predominating in 2°M. Thus, as observed in 1°M, the predominance of staphylococci in 2°M increases the likelihood of contamination through a local route. Obviously, this group had many of the known factors associated with MRSA infections, particularly previous use of broad-spectrum antibiotics and prolonged ICU stay [31]. Moreover, it could be argued that the high rate of MRSA in 2°M patients could partly account for their higher mortality. Indeed, a cohort study associated methicillin resistance with higher mortality in S aureus bacteremia [32]. However, this association was not confirmed in a recent case-control study that carefully controlled for underlying diseases [33], and, to date, MRSA virulence has never been identified as a predictor of adverse outcome of postcardiac operation deep wound infection. Our personal observations also suggest that methicillin resistance does not influence the outcome of S aureus mediastinitis.

To the best of our knowledge, few data are available in the literature regarding outcome measurements for patients with mediastinitis secondary to a major heart operation complication. Hospital mortality of patients with deep sternal wound infection ranges between 5% and 40% [1, 2, 4, 5, 7, 16]. Mortality for our entire population of 371 patients with mediastinitis accumulated during more than 9 years was 27%, and was significantly higher for 2°M than 1°M patients (63% versus 21%). However, patients treated in our department who did not have mediastinitis but who had three or more organ failures after heart operation had a comparably high mortality (data not shown), decreasing the likelihood of mediastinitis contributing to mortality in 2°M patients.

Thus, we clearly identified a subgroup of patients at very high risk of mortality after exhibiting mediastinitis. Our results are in accordance with those of a recent report on 112 patients with mediastinitis among 13,240 cardiac surgical patients accumulated for more than 20 years by De Feo and coworkers [5], who conducted a multivariate analysis and found that length of ICU stay more than 96 hours and bleeding more than 1,000 mL/24 hours, both postoperative factors, were two of the most significant variables predicting a poor outcome after mediastinitis. Other significant factors of poor prognosis were positive bacteriology (48% of the patients) and an interval between onset of symptoms and wound debridement of more than 20 days (19% of the patients). Indeed, this time interval was much shorter (< 48 hours) in our study population, and clinical signs of wound infection were similar in both groups. Mediastinitis is a permanent concern of our department, and in cases of unexplained fever, sternal instability, erythema, or wound discharge, our routine is to perform a needle aspiration of the mediastinum. Thus, debridement was performed soon after clinical or bacterial evidence of infection for both groups of patients.

Closed drainage with Redon catheters for mediastinitis treatment was first described in the late 1980s by Durandy and associates [6]. We [7] and others [8] have shown that this simple technique reduces primary treatment failure, superinfections, and mortality rates as compared with continuous mediastinal irrigation. We now use exclusively this mediastinal drainage technique except for massive sternum or skin necrosis, which requires initial open-wound treatment. In the present study, drainage with Redon catheters was applied to more than 94% of the patients, and we had similar high rates of mediastinal success in both groups: respectively, first-line failure rates of 11% and 17%, mean time to mediastinal sterilization of 8.6 and 6.4 days, and mean duration of Redon drainage of 19.2 and 18.5 days. Incubation time was longer for 2°M patients (27 days on average), and it has been hypothesized that closed-drainage techniques may be less appropriate in mediastinitis occurring later than 2 weeks after the initial heart operation [34]. However, in a recent study of 72 poststernotomy mediastinitis patients treated with Redon catheters, Kirsch and colleagues [15] demonstrated that an incubation time of 14 days or less was a significant factor of mediastinitis-related death. Indeed, we also observed a higher mortality for patients with an incubation time of 14 days or less. These results confirm the efficacy of the closed-drainage technique with Redon catheters, even for critically ill patients with multiple organ dysfunction and moderately late-onset (< 2 months) poststernotomy wound infection.

The results obtained in this study must be viewed in light of the recruitment bias of our ICU. This study was conducted in a single tertiary ICU whose patients originated from different secondary or tertiary surgical centers in the Paris area. Patients were referred to our department for severe complication(s) of cardiac operations. Thus, the percentage of 2°M patients in our population is probably higher than it would have been if every patient had come from a single surgical center. Together with the high mortality rate of 2°M patients, this setting may also explain the higher ICU mortality rate (29%) owing to mediastinitis in our department, as compared with rates reported by others [4, 5, 8]. Concerning other potential limitations, it can be argued that our population or the types of patient care may have changed during the 9 years of the study. However, we do not think that this is the case: our mediastinal and antibiotic treatment policies [7] have remained constant over time, as did the percentages of 1°M and 2°M patients, and annual mortality (data not shown).

In conclusion, the findings of this study indicate that mediastinitis occurring secondary to a major cardiac surgical complication is more frequently caused by MRSA and engenders a considerably higher mortality than 1°M, despite similar efficacy of mediastinal treatment. Thus, curing the secondary infection of the mediastinal wound in these critically ill patients is possible, but prognosis depends mostly on associated organ failure(s).


   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 

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