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Lung Cancer Pain

Bronchial colonization and postoperative respiratory infections in patients undergoing lung cancer surgery

Jose Belda

Study objectives: To evaluate the risk factors associated with postoperative respiratory infection in patients undergoing lung cancer surgery, with special emphasis on the perioperative pattern of airway colonization.

Design: Prospective cohort study.

Setting: Department of Pneumology and Thoracic Surgery of a tertiary hospital.

Patients: Seventy-eight consecutive patients undergoing lung cancer surgery were evaluated. Patients were followed up until hospital discharge or death.

Interventions: Fiberoptic bronchoscopies with bilateral protected specimen brush or bronchial aspirates were performed during anesthesia prior to the initiation of the surgical procedure.

Results: Sixty-five patients (83%) had perioperative bronchial colonization by either potentially pathogenic microorganisms (PPMs) [28 patients, 36%] or nonpotentially pathogenic microorganisms (56 patients, 72%). The 24 patients (31%) with a postoperative respiratory infection (pneumonia, purulent tracheobronchitis, or pleural empyema) had significantly higher perioperative bronchial colonization by PPMs (15 patients [63%] vs 13 patients [24%], p = 0.003) and a higher bacterial index (mean [+ or -] SD, 3.6 [+ or -] 3.3 vs 0.9 [+ or -] 1.4; p = 0.003), compared to patients without infection. The agreement between pathogens found in perioperative evaluation and during postoperative infection was total in 5 patients (21%), partial in 5 patients (21%), and no concordance in 14 patients (58%). In the multivariate analysis, the presence of perioperative airway colonization by a PPM (odds ratio [OR], 6.9; p = 0.001) and a higher postoperative pain score (OR, 4.1; p = 0.014) were independent predictors of postoperative respiratory infection.

Conclusion: Adequate control of postoperative pain, as well as the conditions that potentially cause airway colonization by PPMs, could be beneficial in preventing postoperative respiratory infections after lung cancer surgery.

Key words: bronchial colonization; lung cancer; nosocomial pneumonia; postoperative respiratory infection

Abbreviations: BAS = bronchial aspirate; BMI = body mass index; DLCO = diffusing capacity of the lung for carbon monoxide; OR = odds ratio; PPM = potentially pathogenic microorganism; PSB = protected specimen brush; RIICU = respiratory intensive and intermediate care unit; VAS = visual analog scale

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Patients submitted to lung cancer resection are at special risk for postoperative respiratory infections, with an incidence among these patients ranging from 2 to 20%. (1-4) Moreover, the mortality of these patients remains high, ranging from 22 to 67%, especially with the presence of postoperative pneumonia. (4,5) The different definitions of postoperative respiratory infection and the different percentage of pneumonectomies in the published studies may explain this wide variation in the incidence of pneumonia and its attributed mortality.

To our knowledge, no study has specifically evaluated the risk factors associated with the development of postoperative respiratory infections among patients with lung cancer submitted to surgery. Prior airway colonization could be a potential risk factor for postoperative infections. Previous studies (6,7) have found rates of airway bacterial colonization in patients with lung cancer at approximately 40%. However, an association between previous bacterial colonization and the incidence of postoperative respiratory infections could not be demonstrated by Ioanas and co-workers, (7) probably due to small sample size.

We hypothesized that patients with colonization of the airways by potentially pathogenic microorganisms (PPMs) are at increased risk for postoperative respiratory infections due to the potential spread of colonizing PPMs during surgery. The aim of the present study was to identify risk factors for postoperative respiratory infections in patients submitted to pulmonary resection for lung cancer, with special emphasis on perioperative bronchial colonization.

MATERIALS AND METHODS

Patients

This study prospectively enrolled all consecutive patients with histologic diagnosis of lung cancer and suitability for resection using the TMN classifications (8,9) and treated in our institution during a 1-year period. Patients who used of antibiotics within the previous month, those hospitalized for > 48 h within 14 days prior to surgery, and those allergic to cefazolin were excluded. The Ethics Committee of the Hospital Clinic approved the study protocol. Informed consent was obtained from all patients.

Procedures and Data Collection

Perioperative bronchoscopy was performed in all patients during anesthesia and endotracheal intubation immediately before the surgical procedure. Bronchoscopic respiratory sampling consisted of bilateral protected specimen brush (PSB) or bronchial aspirate (BAS) in the distal part of the two main bronchi, or proximal to the tumor in those occluding the airway. Samples were quantitatively cultured according to standard procedures. (10-12) After bronchoscopy, each patient received cefazolin (1 g q8h) for 24 h, according to our current hospital policy for prophylaxis of surgical wound infection. Control chest radiographs were systematically obtained during the postoperative period and if respiratory infections were clinically suspected. In this case, blood, respiratory secretions (sputum, endotracheal aspirates, or bronchoscopic samples), and pleural fluid, if puncture was indicated, were cultured. Susceptibility tests were carried out in case of positive growth.

Pain was controlled by inserting an epidural thoracic catheter for administration of analgesia from 3 to 4 days; this was achieved in 95% patients. In the remaining 5% of patients, this catheter could not be inserted, so we used subcutaneous opioids. In all patients, we administered nonsteroidal anti-inflammatory drugs as well as IV paracetamol. In all cases, patients tried to sit up 1 day after surgery if clinically feasible, and ambulation was attempted as soon as possible. In addition, there is a specific physiotherapy protocol applied in all patients.

All relevant data from patients were recorded before and after surgery, and patients were followed up until hospital discharge. COPD was defined, and the degree of severity was stratified according to the Global Initiative for Chronic Obstructive Lung Disease strategy. (13) Body mass index (BMI [weight in kilograms/ height in meters] (2)) was calculated. Lung function tests (FVC, FE[V.sub.1], diffusing capacity of the lung for carbon monoxide [DLCO]) had been performed preoperatively, and predicted postoperative lung function was calculated according to the number of resected segments and perfusion lung scan. (14) The subjective postoperative pain score was evaluated by a linear visual analog scale (VAS) [0 = no pain, 10 = maximal imaginable pain], performed by the attending nursing staff every 8 h during the initial 48 h after surgery. The reported values are the average of these determinations.

Definitions

For the purpose of this study, a cut-off [greater than or equal to] [10.sup.2] cfu/mL was used to define perioperative colonization using PSB, and [greater than or equal to] [10.sup.4] cfu/mL for BAS. (6,15) Patients were considered to have colonization whenever a microorganism was isolated above these thresholds.

Isolated bacteria were classified as PPMs or non-PPMs. The PPM group included the microorganisms usually implicated in respiratory infections in nonimmunosuppressed hosts (eg, Haemophilus influenzae, Staphylococcus aureus, Streptococcus pneumoniae, Moraxella catarrhalis, Pseudomonas aeruginosa, Klebsiella pneumoniae, among others). (6) Non-PPMs included microorganisms not responsible for respiratory infections in nonimmunosuppressed hosts (eg, Streptococcus viridans, Neisseria spp, Corynebacterium spp, Candida spp, coagulase-negative Staphylococcus, among others). (6) The bacterial index, obtained as the stun of the logarithmic concentrations of individual species of PPM, (16) was calculated only in patients with PSB sampling.

Pneumonia was defined by the presence of a new pulmonary infiltrate, together with two of the following: fever or hypothermia, leukocytosis or leukopenia, and purulent respiratory secretions. (17) Purulent tracheobronchitis was defined when these same clinical signs were present, in the absence of pulmonary infiltrate. (18) Pleural empyema was defined as the presence of purulent aspirate from the pleural cavity (with or without pathogens). Microbiological confirmation was made by the presence of at least one PPM in respiratory samples above predefined thresholds ([greater than or equal to] [10.sup.3] cfu/mL using PSB, [greater than or equal to] [10.sup.4] cfu/mL using BAL, and [greater than or equal to] 10s cfu/mL using sputum or BAS) (19,20) or positive culture results of blood and/or pleural fluid. Agreement (total, partial, or no agreement) between perioperative lung microbiology and postoperative respiratory infections was evaluated only with isolated PPMs.

Statistical Analysis

Results are expressed as percentage and mean [+ or -] SD. Categorical variables were contrasted by [chi square] test or Fisher Exact Test. The quantitative continuous variables were compared using the Student t test or Mann-Whitney U test. Univariate analyses of risk factors for postoperative respiratory infection were performed, and the quantitative continuous variables significantly associated with postoperative infection were categorized by the optimal cut-off values using receiver operator characteristic curve analyses. Lastly, a multivariate analysis using logistic regression with a conditional stepwise forward model (Pin < 0.05) was performed. Results are expressed as odds ratio (OR) and 95% confidence interval. The level of significance was set at 0.05, all two tailed.

RESULTS

One hundred four patients underwent lung cancer surgery during the study period; 26 patients had exclusion criteria, and 78 patients were included in this study. The main characteristics of patients with and without postoperative respiratory infections are summarized in Tables 1 and 2.

Perioperative Airway Colonization

Bilateral PSB was performed in 65 patients, and BAS was performed in 13 patients. The pattern of airway colonization in the two groups is summarized in Table 3. Thirty-seven PPMs were isolated from 28 patients, most frequently H influenzae, S pneumoniae, P aeruginosa, and S aureus; and 103 nonPPMs were isolated from 56 patients, predominantly S viridans. There were 13 patients (17%) who showed no airway colonization. However, there were 65 patients (83%) with bronchial colonization, either by PPMs or non-PPMs; 19 patients had colonization by one microorganism, 23 patients by two microorganisms, 16 patients by three microorganisms, and 7 patients by four microorganisms. Fifteen patients (19%) had bronchial colonization only on the side of the tumor, 5 patients (6%) had bronchial colonization only on the contralateral lung, and 45 patients (58%) had bilateral bronchial colonization. In patients with bilateral bronchial colonization, the concordance between microorganisms isolated on both sides was partial in 22 patients (49%) and total in 23 patients (51%).

The proportion of patients with bronchial colonization either by PPMs or non-PPMs was not different among patients with and without postoperative respiratory infection. However, the proportion of patients with PPM colonization was higher among those with subsequent postoperative respiratory infections (13 patients [24%] vs 15 patients [63%], p = 0.003). Patients with postoperative respiratory infections also had a significantly higher bacterial index (3.6 [+ or -] 3.3 vs 0.9 [+ or -] 1.4, p = 0.003) than those without postoperative respiratory infections (Fig 1).

[FIGURE 1 OMITTED]

Patients with COPD more frequently had PPM colonization (24 patients [57%] vs 5 patients [14%], p < 0.001), compared to those without COPD. Patients with COPD were not hospitalized in the last 6 months prior to surgery.

Antimicrobial Susceptibility of the Most Frequently Isolated PPMs

Among the six isolated strains of S pneumoniae, four presented intermediate and one presented high penicillin resistance, four presented macrolide resistance, and one presented intermediate third-generation eephalosporin resistance. There were one [beta]-1actamase-positive H influenzae and one methicillin-resistant S aureus. The remaining PPMs were susceptible to their ordinarily tested antibiotics.

Postoperative Respiratory Infection

Twenty-four patients (31%) had at least one postoperative respiratory infection. There were 9 cases (12%) of pneumonia, 19 cases (24%) of purulent tracheobronchitis, and 5 cases (6%) of pleural empyema. In 17 patients, one single infection was diagnosed, while 5 patients had two different infections and 2 patients had three different infections. Purulent tracheobronchitis preceded pneumonia in the four patients with both infections. The microbiological findings of these patients are summarized in Table 4.

Among the 24 patients with postoperative respiratory infection, 21 patients (88%) had perioperative colonization by PPMs. Specifically in the case of pneumonia, 6 patients (67%) had perioperative colonization by PPM. Among the three cases of postoperative respiratory infection without perioperative colonization by any microorganism, all of them had purulent traeheobronchitis.

An etiologic diagnosis based on the isolation of at least one PPM was obtained in 17 patients (71%) with a postoperative respiratory infection. Comparing the PPMs isolated during the perioperative examination and those isolated at the onset of infection, total concordance of PPMs was obtained in 5 patients (21%) [in two cases with and in three cases without etiologic diagnosis], partial concordance was obtained in 5 patients (21%), and no concordance occurred in 14 patients (58%). With regard to the location of the pulmonary infection (pnemnonia or empyema plus pneumonia) in relation to the lung side operated, it was eontralateral in four eases, ipsilateral in four cases, and bilateral in the remaining three.

Risk Factors for Postoperative Respiratory Infection

The variables associated with an increased risk for postoperative respiratory infection in the univariate analysis were the presence of moderate-to-severe COPD, perioperative airway colonization by a PPM, and a higher postoperative pain score, as shown in Table 5. In the multivariate analysis, the presence of perioperative airway colonization by a PPM (p = 0.001) and a higher postoperative pain score (p = 0.014) were the only independent predictors of postoperative respiratory infection.

The following variables were not associated with postoperative infectious complications: age, gender, tobacco consumption, renal or cardiac morbidity, BMI, nutritional parameters, lung function tests (except FE[V.sub.1], which was lower in patients with COPD), airway colonization by non-PPMs, tumor characteristics (location, histopathology, TNM stage), surgical data (type of resection, duration, side of intervention), and postoperative data (transfusion of blood derivates, air leak, reintervention, prolonged mechanical ventilation).

Length of Stay and Hospital Mortality

Length of stay and outcome variables are shown in Table 6. Patients with postoperative respiratory infections had a significantly higher length of respiratory intensive and intermediate care unit (RIICU) and hospital stay when compared with those without a postoperative infectious complication. When considering pneumonia, purulent bronchitis, and pleural empyema together, we found a nonsignificant trend of higher hospital mortality rate among patients with a postoperative respiratory infection (p = 0.116). However, only postoperative pneumonia was associated with a significantly higher mortality when compared to those patients without this specific postoperative infection (two patients [3%] vs three patients [33%], p = 0.010).

DISCUSSION

Summary of Results

This study shows that the presence of perioperative airway colonization by a PPM and greater postoperative pain are independent predictors of postoperative respiratory infection.

Microbial Airway Colonization

The bronchial tree is normally sterile in healthy people. However, among patients with impaired local defenses to infection, such as stable COPD, bronchiectasis, and patients with tracheotomy, the bronchial tree is frequently colonized either by PPMs and non-PPMs. (6,12,21-23) In our study, we found that in patients undergoing lung cancer surgery, the rates of perioperative colonization were 37% for PPMs, 71% for non-PPMs, and 83% for the presence of any microorganism. Only two previous studies (6,7) have addressed this issue in a similar population, and both found lower rates of colonization compared with the present study, approximately 40%. The explanation for these discrepancies is probably that we used bilateral sampling of respiratory secretions, as compared with Cabello and coworkers, (6) who performed unilateral sampling. Most of the patients studied in the previous investigations and in the present study had COPD, and our findings on colonization might merely reflect what is happening in this population.

The pathogenesis of lower airway colonization in patients with stable COPD and lung cancer is still not well understood. The knowledge of risk factors for colonization in these populations may help the clinicians to detect those patients with the potential for colonization. In stable COPD patients, current smoking and lower puhnonary function were risk factors associated with bacterial eolonization. (22,23) In patients with lung resection for bronchial careinoma, a high BMI and the central location of the tumor were the variables related to colonization. (7) A potential pitfall of all these studies is that the risk for colonization was investigated pooling together PPMs and non-PPMs. The role of non-PPMs in relation to local bronchial damage or in the potential development of infections is probably less important, (24) Several studies have demonstrated an increased local inflammatory response in patients with stable COPD (24,25) or bronchiectasis, (12) especially in the presence of colonization by PPMs and a high bacterial load. (24)

Postoperative Respiratory Infections

Several studies (2,4,26-28) have reported an incidence of postoperative pneumonia ranging from 5 to 22%, similar to the present study. This variability may be explained by differences in the type of populations undergoing lung surgery and in the definitions of pneumonia.

Previous studies have evaluated the risk factors for puhnonary complications among patients submitted to lung cancer resection, but unfortunately these studies have considered infectious and noninfectious complications together. Preoperative length of hospital stay, poor nutritional status, COPD, arterial hypertension, smoking habits, advanced age, poor lung function, operating time, extended resection, the side of surgical intervention, postoperative mechanical ventilation, and increased anesthetic risk were associated with a higher risk of postoperative complications in different studies. (26,27,29-34) However, the specific risk factors for the development of respiratory infections after lung resection have not been studied.

In our study, the multivariate analysis showed that a higher postoperative pain score (OR, 4.1) and the presence of perioperative colonization by PPMs in the lower airways (OR, 6.9) were the main factors related with postoperative respiratory infections. In regard to the higher pain score, this was no surprise since we can expect that greater postoperative pain decreased the effectiveness of cough and removal of respiratory secretions. Conversely, the development of postoperative respiratory infection may also cause worsening of pain. This factor can be potentially modified by medical intervention. Regarding the prior colonization by PPMs, there are two potential explanations for this finding. First, the microorganisms colonizing the airways could be spread out throughout the lungs during the surgical proeedure. However, we have to admit that the relationship between perioperative colonization and postoperative microbiology of respiratory infections is relatively weak, showing partial or total eoineidence in 42% cases of infection. Moreover, patients without perioperative colonization by PPM are still at risk for postoperative respiratory infection, since in nine cases no PPM was isolated. Another study, (28) looking at preoperative microbiology, found only a coincidence of 18% with microorganisms eausing postoperative infection after lung cancer resection. Secondly, the development of complications could be related to the likely higher baseline inflammation of the lower airway in patients with PPM colonization. The relationship of colonization by PPMs and bronchial inflammation is described in patients with both stable (24,35) and exacerbated (36) COPD; indeed, the presence of moderate-to-severe COPD was associated with an increased risk of both colonization and postoperative respiratory infections in our study. A new injury, such as surgery, in a previously damaged lung may potentially lead to the development of new infections. However, our study was designed to assess colonization but not inflammation of the lower airways, and therefore this hypothesis remains to be demonstrated.

In our series, we found that not only the presence of airway colonization by a PPM was significantly higher among patients with a postoperative respiratory infection, but the bacterial index was also higher. When evaluating only patients in whom PSB was performed, the bacterial index of the patients with postoperative respiratory infection was significantly higher than in those without a postoperative respiratory infection. However, this variable was not entered into the prediction model because PSB was performed only in 65 patients (83%), and baeterial indexes cannot be compared among PSB and BAS samples.

The development of postoperative respiratory infection was associated with a significantly higher length of RIICU and hospital stays. Furthermore, higher mortality could be demonstrated only among the patients with postoperative pneumonia, confirming the results found by other authors. (4,5)

These results open some light for future prophylactic strategies for postoperative infections after lung surgery. The administration of prophylactic antibiotics in patients with colonization before surgery, with the aim to eradicate microorganisms or decrease lung bacterial burden and decrease bronchial inflammation, deserves future investigation. However, the potential efficacy of such a measure in preventing postoperative infection is uneertain since little relation was found among PPMs isolated perioperatively and those causing postoperative infection. Decreasing inflammation with anti-inflammatory drugs could also be another potential prophylactic strategy. Indeed, a recent investigation (37) from our group found the use of corticosteroids to be related with better response to treatment in patients with ICU-aequired pnemnonia.

Our study has several limitations. First, we did not measure inflammatory markers in respiratory samples; consequently, we have speculated on this, taking the information from previous investigations. (24,25) Second, our study was not designed to systematically investigate the microbiological diagnosis of postoperative respiratory infections with invasive techniques. This could be a bias when comparing bronchoscopic perioperative colonization with postoperative infection. However, this limitation is inherent of these clinical studies in patients with postoperative infection and acute respiratory failure in whom the risks derived from performing bronchoscopy have to be taken into account. Finally, the study was not designed to establish a relationship between prior colonization and mortality. For this particular purpose, the sample size should be much higher.

CONCLUSION

Adequate control of postoperative pain without interfering with secretion clearance and cough reflex, as well as the conditions that potentially cause airway colonization by PPM, could be beneficial in preventing postoperative respiratory" infections after lung cancer surgery. The relationship between prior colonization, postoperative infection, and potential prophylactic measures needs to be studied in more detail.

REFERENCES

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(18) Nseir S, Di Pompeo C, Pronnier P, et al. Nosocomial tracheobronchitis in mechanically ventilated patients: incidence, aetiology and outcome. Eur Respir J 2002; 20:1483-1489

(19) Meduri GU, Chastre J. The standardization of bronchoscopic techniques for ventilator-associated pneumonia. Chest 1992; 102 (suppl 1):5578-5648

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(33) Dyszkiewicz W, Pawlak K, Gasiorowski L. Early post-pneumonectomy complications in the elderly. Eur J Cardiothorac Surg 2000; 17:246-250

(34) Uramoto H, Nakanishi R, Fujino Y, et al. Prediction of pulmonary complications after a lobectomy in patients with non-small cell lung cancer. Thorax 2001; 56:59-61

(35) Wilkinson TMA, Patel IS, Wilks M, et al. Airway bacterial load and FE[V.sub.1] decline in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2003; 167: 1090-1095

(36) White AJ, Gompertz S, Bayley DL, et al. Resolution of bronchial inflammation is related to bacterial eradication following treatment of exacerbations of chronic bronchitis. Thorax 2003; 58:680-685

(37) Ioanas M, Ferrer M, Cavalcanti M, et al. Causes and predictors of non-response to treatment of the ICU-acquired pneumonia. Crit Care Med 2004; 32:938-945

* From the Institut Clinic de Pneumologia i Cirurgia Toracica (Drs. Belda, Cavalcanti, Ferrer, Serra, Canalis, and Torres), and Servei de Microbiologia (Dr. Puig de la Bellacasa), Hospital Clinic, and Institut d'Investigacions Biomediques August Pi i Sunyer, Universitat de Barcelona, Barcelona Spain. Dr. Cavalcanti is a Research Fellow from Pavilhao Pereira Filho, PPG Pneumologia-UFRGS, Brazil, supported by an European Respiratory Society Research Fellowship.

Supported by Red GIRA FIS-ISCIII-03/063, Red Respira FIS-ISCIII-RTIC-03/11, Grant 1999SGR00228, and IDIBAPS.

Manuscript received March 30, 2004; revision accepted March 10, 2005.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtm]).

Correspondence to: Antoni Torres, MD, PhD, FCCP, Servei de Pneumologia, Hospital Clinic, Villarroel 170. 08036 Barcelona, Spain; e-mail: atorres@ub.edu

Table 1--Baseline Characteristics of Patients
Undergoing Lung Cancer Surgery *

                                    Without                With
                                   Infection             Infection
          Characteristics           (n = 54)              (n = 24)

Male/female gender, No.              48/6                  24/0
Age, yr                           64 [+ or -] 10       64 [+ or -] 9
COPD                                27 (50)               15 (63)
Modclute-to-severe COPD             18 (33)               14 (58)
Current smoker/ex-smoker, No.        21/37                11/12
BMI, kg/[m.sup.2]               25.4 [+ or -] 4.9    25.3 [+ or -] 4.1
Peripheral vasculopathy             17 (32)                9 (38)
Cardiopathy                         12 (22)                6 (25)
Diabetes mellitus                    8 (15)                5 (21)
Preoperative lung function
    testing
  FE[V.sub.1], % predicted      79.2 [+ or -] 18.6   68.9 [+ or -] 13.3
  FVC, % predicted              86.5 [+ or -] 17.8     79 [+ or -] 11.2
  FF[V.sub.1]/FVC               68.8 [+ or -] 10.6   65.1 [+ or -] 10.7
  DLCO, % predicted             73.8 [+ or -] 17.3   72.3 [+ or -] 18.1
  Pa[O.sub.2], mm Hg            78.1 [+ or -] 13.6   72.4 [+ or -] 18.2
  PaC[O.sub.2], mm Hg           34.7 [+ or -] 7.7    35.5 [+ or -] 8.7
Predicted postoperative lung
    function testing
  FE[V.sub.1], % predicted      60.6 [+ or -] 15.7   55.8 [+ or -] 12
  DLCO, % predicted             56.6 [+ or -] 15.1   59.5 [+ or -] 17.4
Nutritional parameters
  Albumin, g/L                  38.9 [+ or -] 4.8    36.6 [+ or -] 4..8
  Pre-albumin, g/L              0.21 [+ or -] 0.05   0.19 [+ or -] 0.06
  Total protein, g/L            67.1 [+ or -] 6.9    65.7 [+ or -] 5.6
  Cholesterol, mg/dL             186 [+ or -] 37      171 [+ or -] 43
  Transferring, g/L              2.1 [+ or -] 0.5     2.0 [+ or -] 0.4
  Total lymphocyte count,
    [10.sup.9]/L                 1.8 [+ or -] 0.8     1.9 [+ or -] 0.8
  Hematocrit, %                 40.5 [+ or -] 4      41.7 [+ or -] 4.6
  Zinc, %                       64.3 [+ or -] 13.3   62.4 [+ or -] 9.5

                                          p
          Characteristics               Value

Male/female gender, No.                 0.169
Age, yr                                 0.785
COPD                                    0.336
Modclute-to-severe COPD                 0.048
Current smoker/ex-smoker, No.           0.580
BMI, kg/[m.sup.2]                       0.901
Peripheral vasculopathy                 0.795
Cardiopathy                           > 0.999
Diabetes mellitus                       0.524
Preoperative lung function
    testing
  FE[V.sub.1], % predicted              0.017
  FVC, % predicted                      0.062
  FF[V.sub.1]/FVC                       0.164
  DLCO, % predicted                     0.748
  Pa[O.sub.2], mm Hg                    0.140
  PaC[O.sub.2], mm Hg                   0.705
Predicted postoperative lung
    function testing
  FE[V.sub.1], % predicted              0.185
  DLCO, % predicted                     0.488
Nutritional parameters
  Albumin, g/L                          0.055
  Pre-albumin, g/L                      0.199
  Total protein, g/L                    0.396
  Cholesterol, mg/dL                    0.163
  Transferring, g/L                     0.517
  Total lymphocyte count,
    [10.sup.9]/L                        0.584
  Hematocrit, %                         0.260
  Zinc, %                               0.542

* Data are presented as mean [+ or -] SD or No. (%) unless otherwise
indicated.

Table 2--Tumor Histology, Perioperative Surgical
Data, and Postoperative Complications *

                                        Without               With
                                       Infection            Infection
Characteristics                        (n = 54)             (n = 24)

Histopathology of the tumor
  Squamous cell carcinoma               25 (46)             13 (54)
  Adenocarcinoma                        24 (44)              5 (21)
  Large cell carcinoma                   1 (2)               5 (21)
  Carcinoid tumor                        3 (6)               1 (4)
  Pleomorphic carcinoma                  1 (2)
Type of resection
  Pnemonectomy                          12 (22)              4 (17)
  Single lobectomy                      32 (59)             14 (61)
  Bilobectomy                            1 (2)               1 (4)
  Segmental resection                    4 (7)               2 (9)
  Exploratory thoracotomy                5 (9)               2 (9)
Tumor stage based on TNM
  IA                                    10 (19)              4 (17)
  IB                                    19 (35)              9 (38)
  IIA                                    3 (6)
  IIB                                    5 (9)               6 (25)
  IIIA                                   8 (15)              1 (4)
  IIIB                                   3 (6)               3 (13)
  IV                                     6 (11)              1 (4)
Central location of the tumor           22 (41)             10 (42)
Intervention on right/left
  side, No.                              25/29               17/7
Surgery duration, min              164 [+ or -] 43     172 [+ or -] 44
Postoperative pain score           3.9 [+ or -] 1.2    4.8 [+ or -] 1.4
Postsurgical complications
  Necessity of transfusion              4 (7)                4 (17)
  Air leak > 7 d                        4 (7)                6 (25)
  Reintervention                        3 (6)                1 (4)
  Prolonged mechanical                  1 (2)                3 (13)
    ventilation (> 24 h)

                                          p
Characteristics                         Value

Histopathology of the tumor             0.027
  Squamous cell carcinoma
  Adenocarcinoma
  Large cell carcinoma
  Carcinoid tumor
  Pleomorphic carcinoma
Type of resection                       0.961
  Pnemonectomy
  Single lobectomy
  Bilobectomy
  Segmental resection
  Exploratory thoracotomy
Tumor stage based on TNM                0.247
  IA
  IB
  IIA
  IIB
  IIIA
  IIIB
  IV
Central location of the tumor           0.939
Intervention on right/left side, No.    0.118
Surgery duration, min                   0.477
Postoperative pain score                0.111
Postsurgical complications
  Necessity of transfusion              0.242
  Air leak > 7 d                        0.000
  Reintervention                        0.999
  Prolonged mechanical                  0.000
    ventilation (> 24 h)

* Data are presented as No. (%) or mean [+ or -] SD unless otherwise
indicated.

Table 3--Pattern of Perioperative Airway Colonization Among Patients
Undergoing Lung Cancer Surgery With or Without Postoperative
Respiratory Infection *

                                                Without Infection
                                                     (n = 54)

              Microorganisms                  PS B     BAS    Total

Patients with colonization, No./total         38/47    6/7    44/54
Patients with PPM                              12       1      13
  H influenzae                                  1       1       3
  S pneumoniae                                  3               3
  P aeruginosa                                  1               1
  S aureus                                      2               2
  Haemophilus parainfluenzae                    2               2
  Escherichia coli                              1               1
  Proteus spp (including Proteus mirabilis)
  K pneumoniae
  Aspergillus flavus
  Citrobacter freundii
  Moraxella catarrhalis                         1               1
  Enterococcus spp                              1               1
  Klebsiella oxytoca
Patients with non-PPM                          35       6      41
  S viridans                                   34       5      39
  Neisseria spp                                15       1      16
  Coagulase-negative Staphylococcus            11       1      12
  Corynebacterium spp                           9       1      10
  Streptococcus group D (non-Enterococcus)      2               2
  Streptococcus agalactiae

                                              With Infection (n = 24)

              Microorganisms                   PSB     BAS    Total

Patients with colonization, No./total         18/18    3/6    21/34
Patients with PPM                              13              15
  H influenzae                                  6       2       8
  S pneumoniae                                  3               3
  P aeruginosa                                  3       1       4
  S aureus                                      1               1
  Haemophilus parainfluenzae
  Escherichia coli                              1               1
  Proteus spp (including Proteus mirabilis)     3               3
  K pneumoniae                                  1               1
  Aspergillus flavus                            1               1
  Citrobacter freundii                          1               1
  Moraxella catarrhalis
  Enterococcus spp
  Klebsiella oxytoca                            1               1
Patients with non-PPM                          12       3      15
  S viridans                                   11       3      14
  Neisseria spp                                 3       1       4
  Coagulase-negative Staphylococcus             2       1       3
  Corynebacterium spp                           2               2
  Streptococcus group D (non-Enterococcus)
  Streptococcus agalactiae                      1

* Data are presented as No.

Table 4--Perioperative and Postoperative Microbiological
Characteristics of Patients With Respiratory Infections

Patient              Perioperative Bronchial
  No.                      Colonization

3         P mirabilis
10        S viridans
13        P mirabilis, S pneumoniae
15        S viridans, coagulase-negative Staphylococcus,
            Corynbacterium
20        S viridans, H influenzae
24        No
25        No
27        H infuenzae, S viridans
34        S viridans, coagulase-negative Staphylococcus
35        H influenzae
46        H influenzae, S viridans, S aureau
47        No
50        S viridans
53        H influenzae, S viridans, Neisseria,
            Corynebacterium
53        S aureus, S agalactiae, S pneumoniae
          P aeruginosa
55        H influenzae, S viridans
57        S viridans, Neisseria, coagulase-negative
            Staphylococcus
59        P aeruginosa, S viridans
63        C freundii, E coli
64        H influenzae, K oxytoca, S viridans
66        H influenzae, S pneumoniae
68        S viridans, Neisseria
75        K pneumoniae, P aeruginosa, Proteus
78        S viridans, Neisseria, A flavus

Patient
  No.                   Type of Infection

3         Tracheobronchitis
10        Tracheobronchitis, pneumonia
13        Tracheobronchitis, pneumomia,
            empyema
15        Pneumonia
20        Pneumonia, empyema
24        Tracheobronchitis
25        Tracheobronchitis
27        Pneumonia
34        Tracheobronchitis, empyema
35        Tracheobronchitis, empyema
46        Tracheobronchitis, pneumonia
            empyema
47        Tracheobronchitis
50        Tracheobronchitis, pneumonia
53        Tracheobronchitis
53        Tracheobronchitis
55        Pneumonia
57        Tracheobronchitis
59        Tracheobronchitis
63        Pneumonia
64        Tracheobronchitis
66        Tracheobronchitis
68        Tracheobronchitis
75        Tracheobronchitis
78        Tracheobronchitis

Patient     Isolated Microorganisms at Onset of Infection
  No.

3         P mirabilis (Sputum)
10        S pneumoniae, A fumigatus (sputum)
13        P mirabilis (sputum), E faecalis (pleural fluid)
15        E coli (sputum), Ciuidida spp, coagulase-negative
            Staphylococcus (BAS)
20        Methicillin-resistant S aureus (pleural fluid,
            blood), Aerococcus viridans (pleural fluid)
24        H influenzae (sputum)
25        No
27        S pneumoniae (sputum)
34        S aureus (sputum, blood, pleural fluid), H
            influenzae (sputum)
35        H influenzae (sputum), S aureus (sputum, pleural
            fluid)
46        H influenzae (sputum), S milleri (pleural fluid)
47        S. pneumoniae (sputum), P aeruginosa (blood)
50        A fumigatus (BAS)
53        H influenzae (sputum)
53        S aureus, S agalactiae (sputum)
55        E faecalis, K pneumoniae (sputum)
57        S. viridans, Neisseria (BAL), coagulase-negative
            Staphylococcus (PSB)
59        No
63        Candida spp (BAL, PSB), coagulase-negative
          Staphylococcus (BAS)
64        S aureus (pleural fluid)
66        H influenzae (sputum)
68        No
75        No
78        No

Table 5--Predictive Factors for the Development of Postoperative
Respiratory Infection

                                            95% Confidence
             Variables                OR       Interval      p Value

Univariate
  Moderate-to-severe COPD *           3.8      1.04-7.5        0.048
  Perioperative airway colonization   6.3       2.2-18.1       0.001
  by a PPM
  Postoperative pain score            3.6       1.3-9.9        0.020
  (VAS > 4 points)
Multivariate
  Perioperative airway colonization   6.9       2.2-21.5       0.001
  by a PPM
  Postoperative pain score            4.1       1.3-12.9       0.014
  (VAS > 4 points)

* According to the Global Initiative for Chronic Obstructive
Lung Disease strategy. (13)

Table 6--Lengths of Stay and Mortality in Patients
With and Without Postoperative Respiratory Infection *

                                     Without                With
                                    Infection            Infection
          Variables                  (n = 54)             (n = 24)

Length of preoperative stay, d    2.3 [+ or -] 0.9    2.9 [+ or -] 1.4
Length of RIICU stay, d           2.1 [+ or -] 1.1    6.1 [+ or -] 6.9
Length of hospital stay, d       10.1 [+ or -] 2.9   20.8 [+ or -] 12.5
Hospital mortality                      2 (4)              3 (13)

                                        P
          Variables                   Value

Length of preoperative stay, d        0.090
Length of RIICU stay, d               0.009
Length of hospital stay, d          < 0.001
Hospital mortality                    0.166

* Data are presented as mean [+ or -] SD or No. (%).

COPYRIGHT 2005 American College of Chest Physicians
COPYRIGHT 2005 Gale Group




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