Jorge Puig de la Bellacasa

Pulmonary aspiration of gastric contents in patients receiving mechanical ventilation: the effect of body position.

OBJECTIVE To determine if the semirecumbent position (45-degree angle) decreases aspiration of gastric contents to the airways in intubated and mechanically ventilated patients. DESIGN A randomized, two-period crossover trial. SETTING Respiratory intensive care unit. PATIENTS Nineteen patients requiring intubation and mechanical ventilation. INTERVENTIONS Patients were studied in the supine and semirecumbent positions on two separate days. MEASUREMENTS After technetium (Tc)-99m sulphur colloid labeling of gastric contents, sequential radioactive counts in endobronchial secretions were measured at 30-minute intervals over a 5-hour period. Samples of endobronchial secretions, gastric juice, and pharyngeal contents were obtained for qualitative bacterial cultures. RESULTS Mean radioactive counts in endobronchial secretions were higher in samples obtained while patients were in the supine position than in those obtained while patients were in the semirecumbent position (4154 cpm compared with 954 cpm; P = 0.036). Moreover, the aspiration pattern was time-dependent for each position: For the supine position, radioactivity was 298 cpm at 30 min and 2592 cpm at 300 min (P = 0.013); for the semirecumbent position, radioactivity was 103 cpm at 30 min and 216 cpm at 300 min (P = 0.04). The same microorganisms were isolated from stomach, pharynx, and endobronchial samples in 32% of studies done while patients were semirecumbent and in 68% of studies done while patients were in the supine position. CONCLUSIONS We conclude that the supine position and length of time the patient is kept in this position are potential risk factors for aspiration of gastric contents. Elevating the head of the bed for patients who can tolerate the semirecumbent position may be a simple, no-cost prophylactic measure.

Incidence and etiology of pneumonia acquired during mechanical ventilation

A total of 77 consecutive patients submitted to mechanical ventilation (MV) for greater than 48 h in a respiratory ICU (RICU) were studied to investigate the incidence, etiology, and consequences of ventilator-associated pneumonia. Eighteen (23%) patients developed a bacterial pneumonia after 5.6 +/- 1.0 days (mean +/- SEM; range 2 to 17) of MV. Three additional cases were demonstrated at autopsy, raising the incidence to 27%. Overall, the mean duration of MV increased from 9.7 +/- 0.9 to 32.2 +/- 5.1 days (p less than .0001) when pneumonia developed. A longer period of hospital stay before RICU admission and the presence of chronic obstructive pulmonary disease were significant characteristics of patients with pneumonia when compared to patients without nosocomial pulmonary infection. One or more etiological agents were identified in 14 patients from the pneumonia group by means of a highly specific technique (protected brush catheter, transthoracic needle aspiration, pleural fluid, and/or blood cultures). The predominant pathogens isolated were Gram-negative bacilli (Acinetobacter sp. and Pseudomonas sp.). Half of the cases were polymicrobial. Compared to other series, our results may reflect with more accuracy the actual incidence of nosocomial pneumonia in mechanically ventilated patients, since we used highly accurate techniques along with autopsy findings which allowed us to confirm or discard the diagnosis of bacterial pneumonia.

Cytokine expression in severe pneumonia: a bronchoalveolar lavage study.

OBJECTIVE To assess the cytokine expression (tumor necrosis factor-alpha [TNF-alpha], interleukin [IL]-1beta, and IL-6) in severe pneumonia, both locally (in the lungs) and systemically (in blood). DESIGN Prospective sequential study with bronchoalveolar lavage (BAL) and blood sampling. SETTING Six-bed respiratory intensive care unit of a 1,000-bed teaching hospital. PATIENTS Thirty mechanically ventilated patients (>48 hrs) were allocated to either the pneumonia group (n = 20) or a control group (n = 10). INTERVENTIONS Protected specimen brush and BAL samples for quantitative cultures, and serum and BAL fluid TNF-alpha, IL-1beta, and IL-6 levels were measured on days 1, 3, and 7. In the control group, the procedure was done on day 1 only. MEASUREMENTS AND MAIN RESULTS Serum TNF-alpha levels were significantly higher in patients with pneumonia compared with controls (35 +/- 4 vs. 17 +/- 3 pg/mL, respectively, p = .001). IL-6 levels in serum and BAL fluid were higher in pneumonia than in control patients (serum, 837 +/- 260 vs. 94 +/- 35 pg/mL, respectively, p = .017; BAL fluid, 1176 +/- 468 vs. 234 +/- 83 pg/mL, respectively, p = .05). On days 1, 3, and 7 in patients with pneumonia, IL-1beta levels turned out to be higher in BAL fluid than in serum (71 +/- 17 vs. 2 +/-1 pg/mL on day 1; 49 +/- 8 vs. 6 +/- 2 pg/mL on day 3; and 47 +/- 16 vs. 3 +/- 2 pg/mL on day 7 for BAL fluid and serum, respectively, p < .05). No significant correlation between BAL fluid cytokine levels and lung bacterial burden was shown in presence of antibiotic treatment. Although no clear relationship was found between BAL fluid and serum cytokines and mortality, there was a trend toward higher serum IL-6 levels in nonsurvivors (1209 +/- 433 pg/mL) with pneumonia compared with survivors (464 +/- 260 pg/mL). In addition, serum TNF-alpha and IL-6 correlated with multiple organ failure score (r2 = .36, p = .004 for both) and with lung injury score (r2 = .30, p = .01, and r2 = .22, p = .03, for TNF-alpha and IL-6, respectively). CONCLUSIONS The present study describes the lung and systemic inflammatory response in severe pneumonia. The lung cytokine expression seems to be independent from the lung bacterial burden in the presence of antibiotic treatment. Because of the limited sample size, we did not find a clear relationship between serum and BAL fluid cytokine levels and outcome.

Utility of Selective Digestive Decontamination in Mechanically Ventilated Patients

Nosocomial pneumonia is a frequent complication of prolonged mechanical ventilation [1-3]. Oropharyngeal and gastric colonization, because of potentially pathogenic microorganisms and their subsequent aspiration to the lower airways, play a substantial role in the pathogenesis of ventilator-associated nosocomial pneumonia [4, 5]. Selective digestive decontamination has been widely used as a prophylactic regimen for ventilator-associated nosocomial pneumonia. The first to describe this complication, Stoutenbeek and colleagues [6] suggested that the best combination for preventing nosocomial pneumonia was the use of topical nonabsorbable antibiotics in the oropharynx and stomach together with systemic antibiotics. Most studies have shown a substantial decrease in the carriage of gram-negative bacilli of the upper and lower airways and also in the incidence of nosocomial pneumonia [7, 8], and a few studies have shown a substantial decrease in the overall mortality rate [9-11]. Several important considerations in most of the studies still make selective digestive decontamination a controversial issue. First, several studies were not randomized or used historical controls [6, 12-19]. Second, most of the randomized studies used only nonspecific methods to diagnose nosocomial pneumonia [9, 11, 20-28]. Finally, despite the apparent decrease in the incidence of nosocomial pneumonia, mortality did not change in most of the studies [12-28], including two recent randomized and double-blind studies [29, 30] of a large population sample of patients in an intensive care unit. We did a randomized, double-blind study of selective digestive decontamination in a general population of patients requiring mechanical ventilation. The main end points of this study were to assess the effect of selective digestive decontamination in decreasing nosocomial pneumonia and mortality. Additional end points of this study were to determine the effect of selective digestive decontamination on the morbidity (length of stay and duration of mechanical ventilation) and the mortality rate. Methods Patients The study was done in the Respiratory Intensive Care Unit of the Hospital Clinic of Barcelona, Spain, a 1000-bed teaching hospital, during a period of 12 months. All mechanically ventilated patients admitted to the respiratory intensive care unit and expected to remain intubated for more than 3 days were included in the study. The only exclusion criterion was the presence of immunosuppression (human immunodeficiency virus [HIV] infection, HIV-related diseases, patients who received transplants, and patients treated with antineoplastic chemotherapy). Patients who were extubated or who died before receiving 72 hours of selective digestive decontamination or placebo were also excluded from the analysis. Study Design Patients were randomly allocated to either the selective digestive decontamination or the placebo group. The randomization was done using a computer-generated table, and the patients were enrolled consecutively. Severity of illness was evaluated by means of the Simplified Acute Physiologic Score after randomization. The authors of the study were blinded in the recovery of the results. The study ended after extubation or death of the patient in the intensive care unit. Administration of Antibiotics After samples for the bacteriologic assessment were obtained, antibiotics were administered for selective digestive decontamination. An aqueous suspension of 10 mL containing polymyxin E, 100 mg (Dumex; Dumex Limited, Denmark); tobramycin, 80 mg (Tobradistin; Dista SA, Madrid, Spain); and amphotericin B, 500 mg (Fungizona; Squibb Industria Farmaceutica SA, Madrid) was administered through a nasogastric tube to patients in the selective digestive decontamination group. Carboxymethyl-cellulose with pectin and with gelatin (0.5 mL, Orabase; Drogfesa, Mollet del Valles, Spain) containing polymyxin E, tobramycin, and amphotericin B, at 2% concentration, was applied four times a day. In the placebo group, an aqueous suspension of Maxipro (Scientific Hospital Supplies Limited, Liverpool, United Kingdom) and Orabase, both colored with tartrazine, were administered through the nasogastric tube and in the oropharynx at the same dosage as for patients who received selective digestive decontamination. Systemic Antibiotic and Stress Ulcer Prophylaxis Patients were treated with 2 g of intravenous cefotaxime four times a day (Primafen, Hoechst Iberica SA, Barcelona, Spain) for the first 4 days of mechanical ventilation if they did not have infection on admission. Infected patients who were admitted to the intensive care unit received other parenteral antibiotics according to clinical decisions. Prophylaxis for stress ulcers was done using 1 g of sucralfate every 4 hours (Urbal; Merck-Igoda SA, Mollet del Valles) through a nasogastric tube, except in patients with paralytic ileus or with upper gastrointestinal bleeding, who were treated with 50 mg of intravenous ranitidine, four times a day (Zantac; Glaxo SA-Allen Farmaceutica SA, Madrid). Bacteriologic Assessment Endotracheal aspirates, pharyngeal swabs, and gastric juice samples were obtained three times a week for quantitative cultures. Endotracheal aspirate samples were obtained by means of sterile tubes (Mocstrap; Productes Clinics, SA, La Llagosta, Barcelona). Samples obtained were diluted and homogenized in distilled water to 1/2 concentration using a vortex-style shaker (Reax 2000; Heidolph, Germany) and were rediluted in distilled water to 1/20 and 1/200 concentrations. Pharyngeal swabs were obtained using sterile swabs with Amies transport media (Eurotubo; Industrias Aulabor SA, Barcelona), were homogenized in 1 mL of distilled water, and were diluted to concentrations of 1/10, 1/102, and 1/103. Gastric juice samples were obtained by aspiration through a nasogastric tube using a sterile feeding syringe. The pH was determined in all the samples using paper indicators (Acilit, pH 0 to 6 and Spezialindikator, pH 6.5 to 10; Merck, Darmstadt, Germany). The samples were homogenized using a vortex-style shaker and were diluted in distilled water to concentrations of 1/10 and 1/100. All samples were plated on the following agar media: blood; chocolate; McConkey-2; buffered, charcoal, and yeast extract (BCYEa); Sabouraud-dextrose; Sabouraud with nalidixic acid; and blood with nalidixic acid. If negative, the plates were discarded after 5 days of testing for aerobic bacteria, after 10 days of testing for Legionella and anaerobic bacteria, and after 4 weeks of testing for fungi. If positive, counts of colony-forming units per milliliter and identification using standard methods [31] were done for the microorganisms. Definitions Potentially pathogenic microorganisms were defined [32] as those causing infection in a person with impaired defense mechanisms. They can be classified into community microorganisms, which cause infections in previously healthy persons with intact carriage defense, and nosocomial microorganisms, which cause infections in persons with impaired carriage defense. Colonization was defined as the isolation of the same strain of a potentially pathogenic microorganism from at least two consecutive surveillance samples in any concentration. The clinical diagnosis of pneumonia was based on the presence of all of the following criteria: new or progressive pulmonary radiologic infiltrate or both for 48 hours or more, purulent tracheal secretions, temperature of 38.5 C or more, and leukocytosis ( 12 109/L) or leukopenia ( 4 109/L). The diagnosis of pneumonia was confirmed by the isolation of a potentially pathogenic microorganism in a protected specimen brush sample in concentrations of 103 CFU/mL or more or in a bronchoalveolar lavage sampling in concentrations of 104 CFU/mL or more [33]. We defined definite pneumonia when all the clinical criteria and one bacteriologic criterion were present or by the presence of histologic signs of pneumonia at autopsy. Probable pneumonia was defined when only clinical criteria were present. Primary endogenous pneumonia was diagnosed when pneumonia developed within the first 4 days of mechanical ventilation and when etiologic microorganisms were isolated previously or concomitantly in pharyngeal swabs or in gastric juice. Secondary endogenous pneumonia was pneumonia that developed after the fourth day of mechanical ventilation. Exogenous pneumonia was diagnosed when the etiologic microorganism was not isolated in pharyngeal swabs or in gastric juice before the development of pneumonia. Community flora was defined as the isolation of normal buccal flora (Neisseria species, Streptococcus viridans, among others), Streptococcus pneumoniae, or Haemophilus influenzae. A catheter-related infection was diagnosed when inflammatory signs occurred in a catheterized blood vessel together with a temperature of 38.3 C or more, irrespective of the isolation of a potentially pathogenic microorganism in the culture of the removed catheter. Likewise, this diagnosis was considered if the fever improved within 12 hours after removing the catheter. A urinary tract infection was diagnosed after fresh-voided catheter urine containing five or more leukocytes per high-power light-microscopic field were identified and a potentially pathogenic microorganism was isolated in urine culture in concentrations of 105 CFU/mL or more. A wound infection was diagnosed if purulent secretions from wounds occurred with signs of inflammation and the isolation of a potentially pathogenic microorganism in concentrations of 105 CFU/mL or more from the purulent wound secretions. Septicemia was diagnosed if clinical signs of systemic infection occurred, such as fever, leukocytosis, increased percentage of band forms, and metabolic acidosis, combined with a positive blood culture. Multiple organ system failure was defined as three or more organ systems failing for more than 2 consecutive days. Infection-relat

Histopathologic and Microbiologic Aspects of Ventilator-associated Pneumonia

BackgroundThe relationship between microbiology and histology in patients with ventilator-associated pneumonia has been sparsely described.MethodsTwenty-five patients who died in the intensive care unit after their lungs had been mechanically ventilated for 72 h were studied. Twenty of the 25 died w

Bronchoscopic validation of the significance of sputum purulence in severe exacerbations of chronic obstructive pulmonary disease

Background: Antibiotics are commonly prescribed in exacerbations of chronic obstructive pulmonary disease (COPD). However, the role of bacteria in these exacerbations is controversial. Objective: To identify clinical predictors of bacterial infection as a cause of exacerbation, considering the protected specimen brush (PSB) as the gold standard. Methods: Clinical data, sputum and PSB samples were collected from 40 patients with COPD requiring hospitalisation due to severe exacerbations who had not received previous antibiotic treatment. Results: Quantitative cultures of PSB samples (n = 40) yielded 23 potential pathogenic microorganisms (PPMs) at concentrations of ⩾102 colony-forming units/ml in 18 (45%) patients. Sputum samples were obtained from all 40 patients. Culture of good-quality sputum samples (n = 18) yielded 16 PPMs corresponding to 14 (35%) patients. The concordance between the PSB and sputum rate was high (κ = 0.85, p<0.002). The self-reporting patient observation of sputum purulence (odds ratio (OR) 27.20 (95% confidence interval (CI) 4.60 to 60.69), p = 0.001), the percentage predicted forced expiratory volume in 1 s (FEV1%) <50 (OR 2.27 (95% CI 1.55 to 3.21), p = 0.014), >4 exacerbations in the past year (OR 6.9 (95% CI 0.08 to 1.08), p = 0.028) and previous hospitalisations due to COPD (OR 4.13 (95% CI 1.02 to 16.07), p = 0.041) were associated with the presence of PPMs in the distal airways. The operative characteristics for predicting distal airway infection when patients presented with purulent exacerbation were as follows: sensitivity 89.5%, specificity 76.2%, positive predicted value 77.3% and negative predicted value 88.9%. Conclusions: The self-reporting presence of purulence in the sputum, as well as common previous exacerbations and hospitalisations due to COPD in patients with severe airflow obstruction (FEV1% <50) predict the presence of bacterial infection in the distal airways. The use of these clinical variables may help in selecting candidates to receive antibiotic treatment.

Bacterial and fungal bloodstream isolates from 796 hematopoietic stem cell transplant recipients between 1991 and 2000

To examine shifts in the etiology, incidence, evolution, susceptibility, and patient mortality of bacterial and fungal bloodstream isolates (BSIs) from hematopoietic stem cell transplantation (HSCT) recipients, we reviewed the BSIs of 796 patients who underwent an HSCT in our institution during a 10-year period. Four hundred eighty-nine episodes of bacterial and fungal BSI were detected in 330 patients (41%). Three hundred ten isolates (63%) were gram-positive bacteria, 142 (29%) were gram-negative, and 18 and 19 isolates were different species of anaerobic organism and Candida spp. (both 4%). Coagulase-negative staphylococci (CoNS), with 210 isolates, were the organism most frequently isolated in each year of study and during the three phases of immune recovery after HSCT. The ratio of gram-positive to gram-negative has declined from 3.3 (1991–1992) to 1.8 (1999–2000). Crude mortality occurred in 47 cases of 489 BSI episodes (10%). Mortality according to groups was gram-negative, 7%; gram-positive, 9%; and anaerobic bacteria, 11%. Candida spp. was the group that accounted for the highest crude mortality, with 42%. Gram-positive microorganisms were isolated more often than gram-negative organisms, but the trend is reversing. CoNS were the leading pathogen during the 10 years of study and during the three phases of immune recovery after HSCT. Crude mortality of HSCT patients with BSI was low except for infections caused by Candida spp.

Community-acquired polymicrobial pneumonia in the intensive care unit: aetiology and prognosis

IntroductionThe frequency and clinical significance of polymicrobial aetiology in community-acquired pneumonia (CAP) patients admitted to the ICU have been poorly studied. The aim of the present study was to describe the prevalence, clinical characteristics and outcomes of severe CAP of polymicrobial aetiology in patients admitted to the ICU.MethodsThe prospective observational study included 362 consecutive adult patients with CAP admitted to the ICU within 24 hours of presentation; 196 (54%) patients had an established aetiology.ResultsPolymicrobial infection was present in 39 (11%) cases (20% of those with defined aetiology): 33 cases with two pathogens, and six cases with three pathogens. The most frequently identified pathogens in polymicrobial infections were Streptococcus pneumoniae (n = 28, 72%), respiratory viruses (n = 15, 39%) and Pseudomonas aeruginosa (n = 8, 21%). Chronic respiratory disease and acute respiratory distress syndrome criteria were independent predictors of polymicrobial aetiology. Inappropriate initial antimicrobial treatment was more frequent in the polymicrobial aetiology group compared with the monomicrobial aetiology group (39% vs. 10%, P < 0.001), and was an independent predictor of hospital mortality (adjusted odds ratio = 10.79, 95% confidence interval = 3.97 to 29.30; P < 0.001). The trend for higher hospital mortality of the polymicrobial aetiology group compared with the monomicrobial aetiology group (n = 8, 21% versus n = 17, 11%), however, was not significantly different (P = 0.10).ConclusionsPolymicrobial pneumonia occurs frequently in patients admitted to the ICU. This is a risk factor for inappropriate initial antimicrobial treatment, which in turn independently predicts hospital mortality.

Pulmonary Infiltrates in Immunosuppressed Patients: Analysis of a Diagnostic Protocol

ABSTRACT A diagnostic protocol was started to study the etiology of pulmonary infiltrates in immunosuppressed patients. The diagnostic yields of the different techniques were analyzed, with special emphasis on the importance of the sample quality and the role of rapid techniques in the diagnostic strategy. In total, 241 patients with newly developed pulmonary infiltrates within a period of 19 months were included. Noninvasive or invasive evaluation was performed according to the characteristics of the infiltrates. Diagnosis was achieved in 202 patients (84%); 173 patients (72%) had pneumonia, and specific etiologic agents were found in 114 (66%). Bronchoaspirate and bronchoalveolar lavage showed the highest yields, either on global analysis (23 of 35 specimens [66%] and 70 of 134 specimens [52%], respectively) or on analysis of each type of pneumonia. A tendency toward better results with optimal-quality samples was observed, and a statistically significant difference was found in sputum bacterial culture. Rapid diagnostic tests yielded results in 71 of 114 (62.2%) diagnoses of etiological pneumonia.

Prospective evaluation of procalcitonin in adults with febrile neutropenia after haematopoietic stem cell transplantation

Serum procalcitonin (PCT) levels have been proposed as a new discriminative marker for bacterial and fungal infections. We analysed the diagnostic relevance of PCT in febrile episodes of neutropenic adult patients after haematopoietic stem cell transplantation (HSCT). PCT was determined prospectively in 92 febrile episodes, classified according to the final diagnosis as: neutropenic fever of unknown origin (n = 51), microbiological (n = 26) or clinical (n = 5) documented infection and non‐infectious febrile episodes (n = 10). On first day of fever, mean (±SD) PCT level was 0·3 ng/ml (0·2) in neutropenic fever of unknown origin, 0·5 ng/ml (0·7) in microbiologically confirmed infections, 0·2 ng/ml (0·2) in clinically documented infections and 1·7 (4·2) in non‐infectious fever (P = not significant). Five days after the antibiotic therapy was started, fever persisted in 29 neutropenic episodes (32%). Cases that were eventually diagnosed with invasive aspergillosis had PCT values significantly higher [10·1 ng/ml (6·7)] than all remaining groups (P = 0·027; Kruskal–Wallis). Our analysis indicates that the PCT level on first day of fever did not facilitate the differential diagnosis of neutropenic febrile episode. However, when fever persisted for more than 5 d, PCT values ≥3 ng/ml had a high sensitivity and specificity for the diagnosis of invasive aspergillosis.