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Ann Thorac Surg 2001;72:143-148
© 2001 The Society of Thoracic Surgeons

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Original article: cardiovascular

Pneumonia after cardiac surgery is predictable by tracheal aspirates but cannot be prevented by prolonged antibiotic prophylaxis

Accepted for publication March 27, 2001.

Address reprint requests to Dr Carrel, Clinic for Cardiovascular Surgery, University Hospital, CH-3010 Berne, Switzerland
e-mail: thierry.carrel{at}insel.ch

	Abstract

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Background. The purpose of this study was to assess the value of tracheal aspirate as a predictor of pneumonia after coronary artery bypass grafting and to evaluate the efficacy of prolonged perioperative antibiotic prophylaxis.

Methods. Tracheal aspirates of 500 patients undergoing coronary artery bypass grafting were taken immediately after intubation and analyzed for microorganisms by Gram stain and semiquantitative microbiologic cultures. All patients received 2 g ceftriaxone as a single-dose perioperative antibiotic prophylaxis before operation. Results of Gram stains were available before the patients were transferred to the intensive care unit. After the results were known, both groups of patients (positive Gram stain, group 1; negative Gram stain, group 2) were randomly assigned to either conventional antibiotic prophylaxis (A), consisting of ceftriaxone 2 g on postoperative day 1, or prolonged antibiotic prophylaxis (B), with ticarcillin + clavulanic acid 3 x 5.2 g during 72 hours.

Results. From 500 patients, 91 had a positive Gram stain whereas 409 had a negative one. The incidence of pneumonia was significantly higher in patients with preoperative positive tracheal aspirates (15.3%) than in patients with a negative one (3.6%; p < 0.01). However, prolonged prophylaxis did not reduce the rate of postoperative pneumonia, which was as high as 13% in untreated positive patients versus 17% in treated positive patients, and 2% in untreated negative patients versus 4% in treated patients. In patients who had pneumonia, there was a high correlation between the microorganisms found in preoperative aspirates and those observed when aspirates were repeated (100% correlation in patients with conventional antibiotic prophylaxis and 87% in those with prolonged prophylaxis).

Conclusions. Early postoperative pneumonia (<7 days) is most likely caused by microorganisms that colonize the respiratory tract before operation. The risk of pulmonary infection after coronary artery bypass grafting can be predicted from the preoperative tracheal aspirates. Prolonged perioperative antibiotic prophylaxis has no efficacy in reducing the incidence of pulmonary infections.

	Introduction

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Nosocomial infections still represent a serious problem among surgical patients; they usually adversely influence the early outcome and lead to prolonged recovery with substantially longer hospitalization. Lower respiratory tract infections are among the most frequently reported complications in intensive care unit (ICU) patients [1–3]. This type of infection is not only found in patients requiring prolonged mechanical ventilation but can also appear early in the postoperative period after coronary artery bypass grafting (CABG); not rarely it accounts for a prolonged recovery time, a delayed hospital discharge, and increased costs [4, 5].

Bacterial infection of the lower respiratory tract is most probably initiated by colonization of the upper respiratory tract, followed by microaspiration of contaminated oropharyngeal secretions into the lungs [6–8]. Failure of lung antibacterial defense mechanisms, which might be promoted by the use of cardiopulmonary bypass (CPB), results in pneumonia. The beneficial role of preoperative cessation of smoking in reducing the incidence of pulmonary complications was already demonstrated for patients undergoing CABG [9].

The aims of this study were to (1) assess the incidence of preoperative tracheal aspirates positive for pathogens, (2) assess the predictive value of preoperative tracheal aspirates for postoperative pneumonia in patients undergoing CABG, (3) clarify whether preoperative bacteriology of the tracheal aspirates correlates with bacteriology performed after the onset of pneumonia, and (4) evaluate the efficacy of a prolonged perioperative antibiotic prophylaxis in reducing the rate of pulmonary infection.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
In a prospective, double-blind, randomized trial, tracheal aspirates of 500 patients undergoing CABG (414 men, 86 women, mean age, 63 ± 7.5 years) were collected by carefully suctioning material from the lower respiratory tract immediately after intubation. Gram stain and semiquantitative bacteriologic cultures were performed immediately thereafter to allow comparison with isolates in those patients who developed early postoperative pneumonia. Positive Gram stain was defined as the presence of bacteria or fungi under high-power field (x1,000). All patients received perioperative antibiotic prophylaxis with 2 g of intravenous ceftriaxone starting 30 to 45 minutes before incision. All patients with suspicion of contemporary infection (clinical signs, laboratory measures) and those with antibiotics immediately before operation were excluded.

Results of the Gram stains were available before the patients were transferred to the ICU. Upon results of the Gram stains (positive or negative), the patients were randomly assigned to receive either a conventional antibiotic prophylaxis (subgroup A), with ceftriaxone 2 g on postoperative day 1, or a prolonged antibiotic prophylaxis (subgroup B), using ticarcillin and clavulanate (Timenten, SmithKline Beecham, Thörishans, Switzerland) 3 x 5.2 g per day during 3 days. In those patients receiving only 24 hours of perioperative antibiotic prophylaxis, placebo was administered to blind for the prolonged prophylaxis.

Cardiac operation was performed through a midline sternotomy according to standard protocol, which includes moderate hypothermic CPB and cold antegrade or retrograde blood cardioplegia for myocardial protection. No steroids were used in the priming volume of the CPB. Usual perioperative monitoring was performed, including recording arterial and central venous pressures, electrocardiogram, urine production, and rectal temperature. Endotracheal suctioning was performed with sterile, disposable catheters after each turn of the patients in the ICU, or more frequently if needed. Tracheal aspirate was collected from each patient every morning up to postoperative day 3, and bacteriologic examinations were repeated. When the result was pathologic presence of microorganisms, aspirate was repeated up to postoperative day 7. Tracheal instillation of 5 to 10 mL of sterile saline was sometimes necessary to recover an adequate volume of secretion. Chest physiotherapy was started in the intubated patient and maintained after extubation. Early mobilization (usually on postoperative day 1) was implemented. Antacids were administered routinely.

Early postoperative pneumonia was suspected if purulent sputum was collected or bronchial secretion showed more than 25 leukocytes and yielded growth of relevant pathogens on culture and if at least two of the following additional criteria were met: (1) white blood cell count greater than 10,000/mm³, (2) temperature more than 38°C, and (3) new or increasing lung infiltrate on conventional chest roentgenogram (radiologist was blinded to the patient’s clinical status). Definitive diagnosis of pneumonia was made according to the definitions of the Centers for Disease Control and Prevention [10].

All patients were evaluated daily for infections until hospital discharge. Blood cultures were performed (3x) when temperature was greater than 38.5°C. Daily laboratory studies included hemoglobin and hematocrit, white blood cell and platelet count, C-reactive protein, creatinine, electrolytes, and phosphate.

For each patient, we recorded 12 variables that were considered as potential factors influencing the postoperative outcome and probably also the development of early postoperative pneumonia: sex, smoking history, preoperative left ventricular ejection fraction, New York Heart Association functional class, diabetes, arterial and pulmonary hypertension, chronic obstructive pulmonary disease requiring medical therapy, use of bilateral internal thoracic artery, CPB time, number of transfused concentrates, and postoperative low cardiac output requiring inotropic support.

This study was approved by the Ethic Committee of the University Hospital. A full-time study nurse (E.E.) followed each patient on a daily basis and collected necessary data specified on the trial protocol.

Continuous variables were analyzed by the Mann-Whitney test. The relative risk of pneumonia was calculated by the statistical program EPED [11]. The remaining statistical analyses were performed with the BMDP statistical package (BMDP, Los Angeles, CA). Differences (group 1 versus group 2 and group 1A versus 1B) were calculated with Fisher’s exact test for dichotomous or categorical variables. Continuous variables were subjected to independent samples Student’s t test. To assess the ability of independent variables to predict postoperative pneumonia, the odds ratio was calculated. The risk factors found to be predictive of pneumonia on univariate analysis were subjected to multivariate regression analysis, which identified those independent variables that contributed to fit with the Hosmer-Lemeshow model of goodness-to-fit statistic. A p value lower than 0.05 was considered as statistically significant.

	Results

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Of 500 patients, 91 had a positive Gram stain whereas 409 had a negative one. The incidence of pneumonia was significantly higher in patients with preoperative positive tracheal aspirates (15.3%) than in patients with negative tracheal aspirates (3.6%; p < 0.01). However, prolonged perioperative prophylaxis did not reduce the rate of postoperative pneumonia: from all patients with a positive tracheal aspirate, 13% had pneumonia without prolonged antibiotics and 17% with prolonged antibiotics (not significant), whereas from those with a negative aspirate, 2% had pneumonia without prolonged antibiotics versus 4% with prolonged antibiotic prophylaxis (Table 1). Early postoperative pneumonia was predominantly caused by gram-positive bacteria (Coag neg Staphylococcus aureus, Streptococcus pneumoniae, mixed flora with Haemophilus influenzae). Of 500 patients, 29 had an infection, of which 24 were caused by gram-positive and 5 by gram-negative microorganisms (Table 2). All patients but one in the group with positive preoperative tracheal aspirate showed identical bacteriology in the preoperative and postoperative studies. Sensitivity of the bacteria found to be responsible for pneumonia during the same period in our institution is summarized for the most frequent antibiotics on Table 3, whereas Table 4 reflects the sensitivity of the bacteria found in tracheal aspirates of our patients.

Overall mortality was 1.8% in this series (9 of 500 patients). It was not significantly different within the different subgroups, and pulmonary infection could not be associated with higher mortality. However, pneumonia accounted for delayed recovery time in the ICU and prolonged hospitalization time (Table 6).

	Comment

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

The main findings of this trial are that (1) early postoperative pneumonia after CABG is most probably caused by microorganisms that colonize the respiratory tract before operation, (2) such microorganisms are more frequently found in smokers and in patients with obstructive lung disease, (3) the risk of early pneumonia after CABG is higher in patients with positive preoperative tracheal aspirates than in those with negative preoperative tracheal aspirates, and (4) prolonged perioperative prophylaxis does not help in reducing this type of infection.

The benefits of a short (24 hours) perioperative antibiotic prophylaxis is nowadays established [12]. However, the role of prolonged prophylaxis in high-risk patients (smokers, chronic obstructive pulmonary disease, and those with preoperative positive microbiology of the tracheal smear) has yet not been extensively addressed [13, 14].

More recently, Niederhäuser and colleagues [15] were not able to demonstrate any benefit of a prolonged postoperative prophylactic antibiotic regimen in the particular group of high-risk patients who exhibited postoperative low cardiac output (requiring treatment by inotropic support and intraaortic balloon counterpulsation). Our data support this finding.

Pneumonia remains the most frequently reported infection in ICU patients. Adequate monitoring is therefore important, and suspicion of pneumonia should rapidly be confirmed by repeated microbiologic examinations. Because of the poor outcome in cases of secondary complications (eg, adult respiratory distress syndrome, sepsis), efforts should be directed toward the prevention of these infections.

Infections are associated with a prolonged intubation time, a delayed recovery on the ICU, and a delayed discharge, and therefore also with increased costs [5]. In patients whose respiratory tract is colonized before operation, several mechanisms inherent to the operation itself and the use of CPB may promote the pulmonary infection: depression of cough reflex and mucociliary clearance, systemic inflammatory response syndrome after exposure to the CPB circuit, interstitial sequestration of leukocytes, depression of humoral factors, hemodilution, and hypothermia.

Several investigators have suggested antibiotic prophylaxis as a strategy to prevent pneumonia or eliminate bacterial colonization of the oropharynx and trachea [6, 14]. Prevention of colonization of the upper respiratory tract in patients scheduled for open heart operations would provide the most effective means to reduce the rate of postoperative pneumonia, because colonization initiates the pathogenetic sequences [8]. However, inappropriate institution of antibiotics may predispose to superinfection with resistant pathogens, and in practice, selective oropharyngeal decontamination has been shown to decrease significantly the incidence of ventilator-associated pneumonia only in patients receiving long-term ventilation.

In the literature, a large majority of bacterial nosocomial pneumonias are caused by aerobic gram-negative bacilli [1–3, 5, 6]. In the present trial, coagulase-negative staphylococcus and S pneumoniae were the most often isolated microorganisms. Because infection developed early in the postoperative course, we believe that pneumonia was not a consequence of intubation, but that colonization—and perhaps subclinical infection—were present at the time of operation. All patients were antibiotic naive before operation.

Using a relative risk factor analysis, we were able to show that reduced forced expiratory volume in 1 second, continued smoking up to the day of admission before operation, and a positive tracheal microbiology, as well as reduced left ventricular ejection fraction, CPB duration, low cardiac output, and number of required transfusions, were independent risk factors for early pneumonia after CABG. The relatively high overall incidence of pneumonia (29 of 500, 5.8%) was most probably related to the prospective aspect of the trial.

We believe that better control of risk factors before operation—especially abstention from smoking and treatment of chronic obstructive pulmonary disease as well as expedient operation and clear-cut criteria for blood transfusion—may help contribute to reducing the incidence of early postoperative pneumonia. The impact of antibiotic treatment of a positive tracheal microbiology before open heart operations remains hypothetical but should be investigated prospectively. It may help to reduce morbidity and perhaps mortality of elective cardiac procedures [16, 17]. Perioperative antibiotics are of little extra benefit to these specific patients

	Acknowledgments

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
We thank the staff of Cardiovascular Anesthesia for helping us to collect the tracheal aspirates, the staff of the Division of Infectiology for their help and recommendations, and the nursing staff from the Cardiovascular Intensive Care Unit for active participation in this trial. We appreciate the help of Dr. H. Zimmermann for statistical consultation.

	References

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Thierry P. Carrel Marko I. Turina Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Carrel, T. P. Articles by Turina, M. I. Search for Related Content PubMed PubMed Citation Articles by Carrel, T. P. Articles by Turina, M. I. Related Collections Cardiac - other