EUROANESTHESIA 2007 Munich, Germany, 9-12 June RC4

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1 POSTOPERATIVE PNEUMONIA EUROANESTHESIA 2007 Munich, Germany, 9-12 June RC4 HERVÉ DUPONT Anaesthesiology and Intensive Care Medicine North University Hospital Amiens, France Saturday Jun 9, :00-16:45 Room 14c Postoperative pneumonia (POP) is a component of hospital associated pneumonia (HAP) [1]. Nosocomial pneumonia is the second highest cause of nosocomial infection after urinary tract infection in the US [2]. POP can occur either in surgical wards or in ICU, either in the non-ventilated or in the ventilated patient. In the most important published study evaluating the risk of POP, 1.5% of postoperative patients developed POP with a mortality of 21 % [3]. Risks factors for POP have been studied and will be presented in this review. However, little data is available concerning the specific outcome of POP [4]. The treatment of POP is essentially little different to that for HAP. EPIDEMIOLOGY AND RISK FACTORS The epidemiology of POP is not very well known. A prospective study of 160,805 patients undergoing noncardiac surgery, reported the overall POP rate as 1.5% [3]. The rate of pneumonia in postoperative patients may be higher than that observed in medical wards as assed in a one-year survey in general wards in Canada [5]. The rate of pneumonia was higher in surgical patients (81% vs. 19%). However, medical patients were significantly older, were hospitalized longer prior to onset of pneumonia, were more frequently on steroids, had a higher mean creatinine concentration and had a higher mortality (47% vs. 14%). A prospective French survey has described POP in a large multicentre study including 837 cases [6]. POP occurred most frequently in 53 to 63 year old males. More than 60% of the patients had no underlying disease and only 36% of patients had a ventilator associated POP. The rate of POP varied with the type of surgery: abdominal surgery was the most frequent followed by thoracic, vascular and neurosurgery [6]. The mean time of POP onset was 4 to 5 days after surgery in this study. A recent multicentre study of patients who underwent an intra abdominal operation, showed a POP rate of 10.7% [7]. The POP rate per 1000 procedures according to the type of surgery is shown in Figure 1. In multivariate analysis, ethnicity and sex were statistically reliable predictors for developing POP, whereas age was not a predictor. Women were twice as likely to develop POP after intra abdominal surgery compared with men [7]. POP is the most common nosocomial infection following cardiac surgery, however the rate reported is low: 3.8-5% [6,8]. In a study evaluating POP after major lung resection, the incidence of POP was 25% [9]. Multivariate analysis showed that COPD, extent of resection, bronchial colonization and male sex were independent risk factors for POP [9]. A study comparing adult ICU populations demonstrated that postoperative patients had consistently higher rates of nosocomial pneumonia than medical ICU patients, with a RR of 2.2 [10]. Post surgical patients are at high risk for ventilator-associated pneumonia (VAP), which accounts for nearly one-third of the pulmonary infiltrates seen on chest x-ray in these ICU patients [11]. The most important study looking at risk factors for POP was published in 2001 [3]. A risk index was developed using data from patients undergoing major noncardiac surgery and further validated using the data from different patients. The main independent risk factors for POP are shown in table 2. Point values were assigned to each risk factor by multiplying the ß-coefficients from the logistic regression by 10 and rounding off to the nearest integer [3]. The POP Risk Index score is shown in figure

2 FIGURE 1. POP RATE PER 1000 PROCEDURES AFTER ABDOMINAL SURGERY [7]. FIGURE 2. POP RATE ACCORDING TO THE PREOPERATIVE RISK CLASS INDEX DEVELOPED BY AROZULLAH ET AL. N THE DEVELOPMENT COHORT AND IN THE VALIDATION COHORT [3]. TABLE 1. PREOPERATIVE RISK FACTORS INDEPENDENTLY ASSOCIATED WITH THE POSTOPERATIVE OCCURRENCE OF PNEUMONIA IN A DEVELOPMENT COHORT OF PATIENTS AFTER MAJOR NON CARDIAC SURGERY [3]. COPD, Chronic Obstructive Pulmonary Disease Risk class: 1 (0-15 points) ; 2 (16-25 points) ; 3 (26-40 points) ; 4 (41-55 points) ; 5 (> 55 points)

3 DELAY OF POP AND MICROBIOLOGY None of the published studies has specifically addressed the delay to the onset of POP. That is why the definitions of the ATS may be applied to POP. Briefly, early onset POP occurred between admission and day 5 and late onset POP after 5 days of hospitalization [1]. Late onset POP is associated with an increased risk of multidrug resistant pathogens [1]. In the Eole study, the mean interval between surgery and POP was 4±4 days [6]. However, this was not the time since admission and the standard deviation was wide allowing early and late onset POP definitions. POP after lung resection occurred in 83.3% in the first postoperative week with 60% before day 5 [9]. POP after major general surgery occurred in 74% in the first post operative week with 63% before day 5 [12]. In general wards, the number of days reported in hospital before the onset of pneumonia has been reported as 27±66 [5]. In the Eole study, 450 organisms were cultured from pulmonary samples taken from 328 patients with POP [6]. In 94 cases, the pulmonary infection was polymicrobial (29%). In patients in whom the diagnosis of pneumonia was confirmed before the fifth post operative day, the following organisms were isolated; 61 % Enterobacteriacae, 51 % Pseudomonas aeruginosa, and 57% Staphylococcus aureus [6]. In documented POP after major lung resection, POP was polymicrobial in 33% of the cases [9]. The bacteria isolated were Haemophilus, Streptococcus pneumoniae and non-resistant Gram-negative bacteria [9]. These are the pathogens more frequently involved in early onset POP [1]. DIAGNOSIS The diagnosis of POP might be difficult, especially in surgical wards. The Clinical Pneumonia Index Score (CPIS) has been developed and is based on clinical data, leucocytosis, oxygenation and radiographic findings [13]. However, this score has not been specifically developed for POP but for nosocomial pneumonia. Furthermore, the sensitivity of the CPIS has been reported to be low in surgical patients (50%) although the specificity was good (90%) [14]. The Eole study looked at the diagnosis and treatment of POP in a large prospective multi-centre trial [6]. The quality of the diagnosis of pneumonia was assessed by an expert panel which looked at cases according to clinical, radiological, and microbiological criteria. Patients were classified into 3 groups: group I was cases of definite pneumonia who fulfilled the clinical, microbiological and radiological criteria for nosocomial pneumonia; group II was cases of possible pneumonia who had 2 out of the 3 criteria for POP; and group III corresponded to cases of a lower probability of pneumonia, in which the diagnosis was based on one of the three criteria [6]. The diagnostic criteria used and the severity of the 3 groups is shown in table 2. Patients presented as respiratory failure with hypoxemia, leucocytosis, mild fever, purulent sputum, abnormal breath sounds and radiological evidence of pneumonia. There seems to be a relationship in this study between the quality of diagnosis of POP (group class I to III) and the proportion of patients with the signs of pneumonia. TABLE 2. MAIN PHYSICAL, LABORATORY AND RADIOGRAPHIC FINDINGS OF POP ACCORDING TO THE GROUP OF DIAGNOSIS IN THE EOLE STUDY [6]. Group I, definite pneumonia; Group II, possible pneumonia; Group III, low probability of pneumonia. For definitions, refer to the text

4 The American Thoracic Society guidelines emphasise the importance of a specimen of sputum for microbiological culture and quantitative reporting of the positive specimens [1]. Thresholds, sensitivity and specificity of the different techniques of quantitative culture of lower respiratory secretions are shown in table 3. The data for plugged telescopic catheter was not shown in the American guidelines. The results of the different techniques of microbiological diagnosis of POP from the Eole study are shown in figure 3 [6]. There was a strong relationship between the quality of POP diagnosis with quantitative culture and the group class. TABLE 3. MAIN CHARACTERISTICS OF VALIDATED TECHNIQUES FOR MICROBIOLOGICAL DIAGNOSIS OF NOSOCO- MIAL PNEUMONIA [1,11,15]. cfu, colony forming unit FIGURE 3. PROPORTION OF MICROBIOLOGICAL DIAGNOSIS TECHNIQUE ACCORDING TO THE GROUP OF POP DIAG- NOSIS IN THE EOLE STUDY [6]. EA, endotracheal aspirates ; PTC, plugged telescopic catheter ; PSB, protected specimen brush ; BAL, bronchoalveolar lavage, Group I, definite pneumonia ; Group II, possible pneumonia ; Group III, low probability of pneumonia. For definitions, refer to the text. TREATMENT The treatment of POP depends upon the many factors that may influence the type of bacteria and its pattern of resistance [1,15]. The two main factors are the late onset of pneumonia ( 5 days from admission to hospital) and/or risk factors for multi drug resistance pathogens [1,15]. The risks factors for multiresistant pathogens have been extensively described in the ATS guidelines: antimicrobial therapy in preceding 90 days, current hospitalization of 5 days or more, high frequency of antibiotic resistance in the community or in the specific hospital unit, presence of risk factors for healthcare associated pneumonia, immunosuppressive disease and/or therapy [1]. One prospective study of 135 patients with VAP has reported that only 3 factors were independently associated with potentially resistant bacteria in ICU: duration of mechanical ventilation (MV) 7 days (odds ratio (OR)=6.0), prior antibiotic use (OR=13.5), and prior use of broad-spectrum drugs (third-generation cephalosporin, fluoroquinolone, and/or imipenem) (OR=4.1) [16]. Recommended empiric antimicrobial therapy for early onset POP is ceftriaxone / cefotaxime or levofloxacin / moxifloxacin / ciprofloxacin or ampicillin plus sulbactam or ertapenem [1,15]. A combination antibiotic therapy is recommended for late onset POP or where there are risk factors for multiresistant pathogens: an antipseudomonal cephalosporin (cefepime, ceftazidime) or an antipseudomonal carbapenem (imipenem, meropenem) or piperacillin-tazobactam plus an antipseudomonal fluoroquinolone (ciprofloxacin) or an aminoglycoside (amikacin) plus vancomycin or linezolid [1,15]. Inappropriate empiric antimicrobial therapy is associated with an increase in the mortality of nosocomial pneumonia [1,11,15]. Only one study has addressed this issue in POP [4]. Mortality in those who received inappropriate initial antibiotic therapy was 23% when compared to 17% in the appropriate group (p=0.18). However, this result was mainly due to a lack of power to detect a significant difference [4]. In the Eole study, empirical therapy of POP was started on the day of diagnosis in 637 patients (80%) and during the following 48h in another 115 patients (14%) [6]. Interestingly, a combination of antibiotics was used more frequently in patients with signs of greater severity. Unfortunately, the type of antibiotic therapy has not been stratified with the onset of POP in this study [6]

5 OUTCOME The occurrence of POP after surgery has a major impact on mortality and morbidity. In the study by Arozullah et al. looking at major noncardiac surgery, the mortality was 21 % in the POP group when compared to 2% in the control group [3]. The mortality of patients with POP after major lung resection was 19% when compared to 2.4% in the control group [9]. Patients with POP after abdominal surgery have a mortality ranging from 10.7% to 19.2% [7,12] when compared to mortality in the control groups of 1.2% and 1.7%, respectively. In the Eole study, only three parameters were independently associated with mortality in patients with POP: ASA score 3 (OR=4.3), hypotension with systolic blood pressure <80 mmhg (OR=2.6) and delay of the onset of POP> 3 days (OR=2.6) [4]. POP has a direct impact on morbidity too. Patients with POP required non-invasive ventilation and intubation more frequently, with an increased duration of mechanical ventilation [9,12]. POP was independently associated with a 4.1 fold increase in the risk of requiring discharge to a nursing facility after abdominal surgery [7]. Moreover, POP is associated with an increase length of stay in ICU [9,12] and in the hospital [7,9,12]. It is associated with a 75% mean increase in total hospital charge after abdominal surgery [7]. PREVENTION Numerous recommendations have been made for preventing VAP [1,11,15]. However, little data is available specifically looking at preventing POP. Two major studies have been recently published [17,18]. Preoperative intensive muscle training in high risk patients undergoing coronary artery bypass surgery has shown to be effective in reducing POP from 16.1% in the control group to 6.5% in the intervention group (OR=O.4, 95%CI= ) [17]. The continuous positive airway pressure for treatment of postoperative hypoxemia was compared with standard oxygen treatment after abdominal surgery [18]. Patients who received oxygen plus continuous positive airway pressure had a lower occurrence rate of POP (2% vs. 10% in the oxygen only group, p=0.02) [18]. Smoking and the timing of cessation has not shown a major benefit in the rate of POP, even in thoracic surgery [19]. The prevention of VAP has not been looked at in this review. CONCLUSION POP occurs in about 2% of patients after surgery. It is classified as a hospital acquired pneumonia, and may be ventilator associated. The number of days after admission to hospital that POP occurs and the risks factors for multiresistant pathogens are the main factors to take into account when prescribing empiric antimicrobial therapy. A quantitative culture of respiratory samples should be performed to confirm the diagnosis and to adapt antimicrobial therapy. POP has a major impact on morbidity and mortality after surgery. Few interventions have been shown to be effective in reducing POP

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