Robert Rodriguez-Roisin

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.

Endothelial dysfunction in pulmonary arteries of patients with mild COPD

To investigate whether endothelial dysfunction of pulmonary arteries (PA) is present in patients with mild chronic obstructive pulmonary disease (COPD) and to what extent it is related to the morphological abnormalities of PA, we studied 41 patients who underwent lung resection. Patients were divided into the following groups: nonsmokers ( n = 7), smokers with normal lung function ( n = 13), and COPD ( n = 21). Endothelium-dependent relaxation mediated by nitric oxide was evaluated in vitro in PA rings exposed to cumulative concentrations of acetylcholine (ACh) and ADP. Structural abnormalities of PA were assessed morphometrically. PA of COPD patients developed lower maximal relaxation in response to ADP than both nonsmokers and smokers ( P < 0.05 each) and a trend to reduced relaxation in response to ACh ( P = 0.08). Maximal relaxation to ADP correlated with the degree of airflow obstruction ( r = 0.48, P < 0.01). Morphometrical analysis of PA revealed thicker intimas, especially in small arteries, in both smokers and COPD compared with nonsmokers ( P < 0.05 each). We conclude that endothelial dysfunction of PA is already present in patients with mild COPD. In these patients, as well as in smokers with normal lung function, small arteries show thickened intimas, suggesting that tobacco consumption may play a critical role in the pathogenesis of pulmonary vascular abnormalities in COPD.To investigate whether endothelial dysfunction of pulmonary arteries (PA) is present in patients with mild chronic obstructive pulmonary disease (COPD) and to what extent it is related to the morphological abnormalities of PA, we studied 41 patients who underwent lung resection. Patients were divided into the following groups: nonsmokers (n = 7), smokers with normal lung function (n = 13), and COPD (n = 21). Endothelium-dependent relaxation mediated by nitric oxide was evaluated in vitro in PA rings exposed to cumulative concentrations of acetylcholine (ACh) and ADP. Structural abnormalities of PA were assessed morphometrically. PA of COPD patients developed lower maximal relaxation in response to ADP than both nonsmokers and smokers (P < 0.05 each) and a trend to reduced relaxation in response to ACh (P = 0.08). Maximal relaxation to ADP correlated with the degree of airflow obstruction (r = 0.48, P < 0. 01). Morphometrical analysis of PA revealed thicker intimas, especially in small arteries, in both smokers and COPD compared with nonsmokers (P < 0.05 each). We conclude that endothelial dysfunction of PA is already present in patients with mild COPD. In these patients, as well as in smokers with normal lung function, small arteries show thickened intimas, suggesting that tobacco consumption may play a critical role in the pathogenesis of pulmonary vascular abnormalities in COPD.

Community Outbreaks of Asthma Associated with Inhalation of Soybean Dust

Since 1981, 26 outbreaks of asthma have been detected in the city of Barcelona. The geographic clustering of cases close to the harbor led us to consider the harbor as the probable source of the outbreaks. We therefore studied the association between the unloading of 26 products from ships in the harbor and outbreaks of asthma in 1985 and 1986. All 13 asthma-epidemic days in these two years coincided with the unloading of soybeans (lower 95 percent confidence limit of the risk ratio, 7.2). Of the remaining 25 products, only the unloading of wheat was related to the epidemics of asthma, although when adjusted for the unloading of soybeans the relation was not statistically significant. High-pressure areas and mild southeasterly to southwesterly winds, which favored the movement of air from the harbor to the city, were registered on all epidemic days. Particles of starch and episperm cells that were recovered from air samplers placed in the city had morphologic characteristics identical to those of soybean particles. Furthermore, the lack of bag filters at the top of one of the harbor silos into which soybeans were unloaded allowed the release of soybean dust into the air. We conclude that these outbreaks of asthma in Barcelona were caused by the inhalation of soybean dust released during the unloading of soybeans at the city harbor.

Home hospitalisation of exacerbated chronic obstructive pulmonary disease patients

It was postulated that home hospitalisation (HH) of selected chronic obstructive pulmonary disease (COPD) exacerbations admitted at the emergency room (ER) could facilitate a better outcome than conventional hospitalisation. To this end, 222 COPD patients (3.2% female; 71±10 yrs (mean±sd)) were randomly assigned to HH (n=121) or conventional care (n=101). During HH, integrated care was delivered by a specialised nurse with the patients free-phone access to the nurse ensured for an 8‐week follow-up period. Mortality (HH: 4.1%; controls: 6.9%) and hospital readmissions (HH: 0.24±0.57; controls: 0.38±0.70) were similar in both groups. However, at the end of the follow-up period, HH patients showed: 1) a lower rate of ER visits (0.13±0.43 versus 0.31±0.62); and 2) a noticeable improvement of quality of life (Δ St Georges Respiratory Questionnaire (SGRQ), −6.9 versus −2.4). Furthermore, a higher percentage of patients had a better knowledge of the disease (58% versus 27%), a better self-management of their condition (81% versus 48%), and the patients satisfaction was greater. The average overall direct cost per HH patient was 62% of the costs of conventional care, essentially due to fewer days of inpatient hospitalisation (1.7±2.3 versus 4.2±4.1 days). A comprehensive home care intervention in selected chronic obstructive pulmonary disease exacerbations appears as cost effective. The home hospitalisation intervention generates better outcomes at lower costs than conventional care.

Hemodynamic and gas exchange effects of sildenafil in patients with chronic obstructive pulmonary disease and pulmonary hypertension.

RATIONALE Sildenafil, a phosphodiesterase-5 inhibitor, could be useful for treating pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD). However, vasodilators may inhibit hypoxic pulmonary vasoconstriction and impair gas exchange in this condition. OBJECTIVES To assess the acute hemodynamic and gas exchange effects of sildenafil in patients with COPD-associated PH. METHODS We conducted a randomized, dose comparison trial in 20 patients with COPD-associated PH. Eleven patients were assigned to 20 mg, and 9 patients to 40 mg, of sildenafil. Pulmonary hemodynamics and gas exchange, including ventilation-perfusion (V(A)/Q) relationships, were assessed at rest and during constant-work rate exercise, before and 1 hour after sildenafil administration. MEASUREMENTS AND MAIN RESULTS Both sildenafil doses reduced the mean pulmonary arterial pressure (PAP) at rest and during exercise, without differences between them. Overall, PAP decreased -6 mm Hg (95% confidence interval [95% CI], -7 to -4) at rest and -11 mm Hg (95% CI, -14 to -8) during exercise. After sildenafil, Pa(O(2)) decreased -6 mm Hg (95% CI, -8 to -4) at rest because of increased perfusion in units with low V(A)/Q ratio, without differences between doses. No change in Pa(O(2)) (95% CI, -3 to 0.2 mm Hg) or V(A)/Q relationships occurred during exercise after sildenafil. Changes induced by sildenafil in Pa(O(2)) and V(A)/Q distributions at rest correlated with their respective values at baseline. CONCLUSIONS In patients with COPD-associated PH, sildenafil improves pulmonary hemodynamics at rest and during exercise. This effect is accompanied by the inhibition of hypoxic vasoconstriction, which impairs arterial oxygenation at rest. The use of sildenafil in COPD should be done cautiously and under close monitoring of blood gases. Clinical trial registered with www.clinicaltrials.gov (NCT00491803).

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.

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

Gas exchange mechanism of orthodeoxia in hepatopulmonary syndrome

The mechanism of orthodeoxia (OD), or decreased partial pressure of arterial oxygen (PaO2) from supine to upright, a characteristic feature of hepatopulmonary syndrome (HPS), has never been comprehensively elucidated. We therefore investigated the intrapulmonary (shunt and ventilation‐perfusion [V̇A/Q̇] mismatching) and extrapulmonary factors governing PaO2 in 20 patients with mild to severe HPS (14 males, 6 females; 50 ± 3 years old SE) at upright and supine, in random order. We set out a cutoff value for OD, namely a PaO2 decrease ≥5% or ≥4 mm Hg (area under the receiver operating characteristic curve, 0.96 each). Compared to supine, 5 patients showed OD (PaO2 change, −11% ± 2%, −7 ± 1 mm Hg, P < .05) with further V̇A/Q̇ worsening (shunt + low V̇A/Q̇ mode increased from 19% ± 7% to 21% ± 7% of cardiac output [Q̇T], P < .05), as opposed to 15 patients who did not (+2% ± 2%, +1± 1 mm Hg) with V̇A/Q̇ improvement (from 20% ± 4% to 16% ± 4% of Q̇T, P < .01). Cardiac output was significantly lower in OD patients in both positions. Changes in extrapulmonary factors at upright, such as increased minute ventilation and decreased Q̇T, were of similar magnitude in both subsets of patients. In conclusion, our data suggest that gas exchange response to OD in HPS points to a more altered pulmonary vascular tone inducing heterogeneous blood flow redistribution to lung zones with prominent intrapulmonary vascular dilatations. (HEPATOLOGY 2004;40:660–666.)

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

Physical Activity and Clinical and Functional Status in COPD

BACKGROUND The mechanisms underlying the benefits of regular physical activity in the evolution of COPD have not been established. Our objective was to assess the relationship between regular physical activity and the clinical and functional characteristics of COPD. METHODS Three hundred forty-one patients were hospitalized for the first time because of a COPD exacerbation in nine teaching hospitals in Spain. COPD diagnosis was confirmed by spirometry under stable conditions. Physical activity before the first COPD hospitalization was measured using the Yale questionnaire. The following outcome variables were studied under stable conditions: dyspnea, nutritional status, complete lung function tests, respiratory and peripheral muscle strength, bronchial colonization, and systemic inflammation. RESULTS The mean age was 68 years (SD, 9 years), 93% were men, 43% were current smokers, and the mean postbronchodilator FEV(1) was 52% predicted (SD, 16% predicted). Multivariate linear regression models were built separately for each outcome variable and adjusted for potential confounders (including remaining outcomes if appropriate). When patients with the lowest quartile of physical activity were compared to patients in the other quartiles, physical activity was associated with significantly higher diffusing capacity of the lung for carbon monoxide (Dlco) [change in the second, third, and fourth quartiles of physical activity, compared with first quartile (+ 6%, + 6%, and + 9% predicted, respectively; p = 0.012 [for trend])], expiratory muscle strength (maximal expiratory pressure [Pemax]) [+ 7%, + 5%, and + 9% predicted, respectively; p = 0.081], 6-min walking distance (6MWD) [+ 40, + 41, and + 45 m, respectively; p = 0.006 (for trend)], and maximal oxygen uptake (Vo(2)peak) [+ 55, + 185, and + 81 mL/min, respectively; p = 0.110 (for trend)]. Similarly, physical activity reduced the risk of having high levels of circulating tumor necrosis factor alpha (odds ratio, 0.78, 0.61, and 0.36, respectively; p = 0.011) and C-reactive protein (0.70, 0.51, and 0.52, respectively; p = 0.036) in multivariate logistic regression. CONCLUSIONS More physically active COPD patients show better functional status in terms of Dlco, Pemax, 6MWD, Vo(2)peak, and systemic inflammation.