Dilution Factor of Quantitative Bacterial Cultures Obtained by Bronchoalveolar Lavage in Patients with Ventilator-Associated Bacterial Pneumonia.

Ventilator-associated bacterial pneumonia (VABP) is a difficult therapeutic problem. Considerable controversy exists regarding the optimal chemotherapy for this entity. The recent guidelines of the Infectious Diseases Society of America and the American Thoracic Society recommend a 7-day therapeutic course for VABP based on the balance of no negative impact on all-cause mortality, less resistance emergence, and fewer antibiotic treatment days, counterbalanced with a higher relapse rate for patients whose pathogen is a nonfermenter. The bacterial burden causing an infection has a substantial impact on treatment outcome and resistance selection. We describe the baseline bronchoalveolar lavage (BAL) fluid burden of organisms in suspected VABP patients screened for inclusion in a clinical trial. We measured the urea concentrations in plasma and BAL fluid to provide an index of the dilution of the bacterial and drug concentrations in the lung epithelial lining fluid introduced by the BAL procedure. We were then able to calculate the true bacterial burden as the diluted colony count times the dilution factor. The median dilution factor was 28.7, with the interquartile range (IQR) being 11.9 to 53.2. Median dilution factor-corrected colony counts were 6.18 log10(CFU/ml) [IQR, 5.43 to 6.46 log10(CFU/ml)]. In a subset of patients, repeat BAL on day 5 showed a good stability of the dilution factor. We previously showed that large bacterial burdens reduce or stop bacterial killing by granulocytes. (This study has been registered at ClinicalTrials.gov under registration no. NCT01570192.).

Comparison of 1.5 and 3.0 T for contrast-enhanced pulmonary magnetic resonance angiography.

OBJECTIVE: In a recent multi-center trial of gadolinium contrast-enhanced magnetic resonance angiography (Gd-MRA) for diagnosis of acute pulmonary embolism (PE), two centers utilized a common MRI platform though at different field strengths (1.5T and 3T) and realized a signal-to-noise gain with the 3T platform. This retrospective analysis investigates this gain in signal-to-noise of pulmonary vascular targets. METHODS: Thirty consecutive pulmonary MRA examinations acquired on a 1.5T system at one institution were compared to 30 consecutive pulmonary MRA examinations acquired on a 3T system at a different institution. Both systems were from the same MRI manufacturer and both used the same Gd-MRA pulse sequence, although there were some protocol adjustments made due to field strength differences. Region-of-interests were manually defined on the main pulmonary artery, 4 pulmonary veins, thoracic aorta, and background lung for objective measurement of signal-to-noise, contrast-to-noise, and bolus timing bias between centers. RESULTS: The 3T pulmonary MRA protocol achieved higher spatial resolution yet maintained significantly higher signal-to-noise ratio (≥13%, p = 0.03) in the main pulmonary vessels relative to 1.5T. There was no evidence of operator bias in bolus timing or patient hemodynamic differences between groups. CONCLUSION: Relative to 1.5T, higher spatial resolution Gd-MRA can be achieved at 3T with a sustained or greater signal-to-noise ratio of enhanced vasculature.

Hospitalists and intensivists in the medical ICU: a prospective observational study comparing mortality and length of stay between two staffing models.

BACKGROUND: A shortage of critical care specialists or intensivists, coupled with expanding United States critical care needs, mandates identification of alternate qualified physicians for intensive care unit (ICU) staffing. OBJECTIVE: To compare mortality and length of stay (LOS) of medical ICU patients cared for by a hospitalist or an intensivist-led team. DESIGN: Prospective observational study. SETTING: Urban academic community hospital affiliated with a major regional academic university. PATIENTS: Consecutive medical patients admitted to a hospitalist ICU team (n = 828) with selective intensivist consultation or an intensivist-led ICU teaching team (n = 528). MEASUREMENTS: Endpoints were ICU and in-hospital mortality and LOS, adjusted for patient differences with logistic and linear regression models and propensity scores. RESULTS: The odds ratio adjusted for disease severity for in-hospital mortality was 0.8 (95% confidence interval [CI]: 0.49, 1.18; P = 0.23) and ICU mortality was 0.8 (95% CI: 0.51, 1.32; P = 0.41), referent to the hospitalist team. The adjusted LOS was similar between teams (hospital LOS difference 0.9 days, P = 0.98; ICU LOS difference 0.3 days, P = 0.32). Mechanically ventilated patients with intermediate illness severity had lower hospital LOS (10.6 vs 17.8 days, P < 0.001) and ICU LOS (7.2 vs 10.6 days, P = 0.02), and a trend towards decreased in-hospital mortality (15.6% vs 27.5%, P = 0.10) in the intensivist-led group. CONCLUSIONS: The adjusted mortality and LOS demonstrated no statistically significant difference between hospitalist and intensivist-led ICU models. Mechanically ventilated patients with intermediate illness severity showed improved LOS and a trend towards improved mortality when cared for by an intensivist-led ICU teaching team.

Gadolinium-enhanced magnetic resonance angiography for pulmonary embolism: a multicenter prospective study (PIOPED III).

BACKGROUND: The accuracy of gadolinium-enhanced magnetic resonance pulmonary angiography and magnetic resonance venography for diagnosing pulmonary embolism has not been determined conclusively. OBJECTIVE: To investigate performance characteristics of magnetic resonance angiography, with or without magnetic resonance venography, for diagnosing pulmonary embolism. DESIGN: Prospective, multicenter study from 10 April 2006 to 30 September 2008. SETTING: 7 hospitals and their emergency services. PATIENTS: 371 adults with diagnosed or excluded pulmonary embolism. MEASUREMENTS: Sensitivity, specificity, and likelihood ratios were measured by comparing independently read magnetic resonance imaging with the reference standard for diagnosing pulmonary embolism. Reference standard diagnosis or exclusion was made by using various tests, including computed tomographic angiography and venography, ventilation-perfusion lung scan, venous ultrasonography, d-dimer assay, and clinical assessment. RESULTS: Magnetic resonance angiography, averaged across centers, was technically inadequate in 25% of patients (92 of 371). The proportion of technically inadequate images ranged from 11% to 52% at various centers. Including patients with technically inadequate images, magnetic resonance angiography identified 57% (59 of 104) with pulmonary embolism. Technically adequate magnetic resonance angiography had a sensitivity of 78% and a specificity of 99%. Technically adequate magnetic resonance angiography and venography had a sensitivity of 92% and a specificity of 96%, but 52% of patients (194 of 370) had technically inadequate results. LIMITATION: A high proportion of patients with suspected embolism was not eligible or declined to participate. CONCLUSION: Magnetic resonance pulmonary angiography should be considered only at centers that routinely perform it well and only for patients for whom standard tests are contraindicated. Magnetic resonance pulmonary angiography and magnetic resonance venography combined have a higher sensitivity than magnetic resonance pulmonary angiography alone in patients with technically adequate images, but it is more difficult to obtain technically adequate images with the 2 procedures.

SPECT in acute pulmonary embolism.

The purpose of this review was to evaluate the accuracy of SPECT in acute pulmonary embolism. Sparse data are available on the accuracy of SPECT based on an objective reference test. Several investigations were reported in which the reference standard for the diagnosis of pulmonary embolism was based in part on the results of SPECT or planar ventilation-perfusion (V/Q) imaging. The sensitivity of SPECT in all but one investigation was at least 90%, and specificity also was generally at least 90%. The sensitivity of SPECT in 4 of 5 investigations was higher than that of planar V/Q imaging. The specificity of SPECT was generally higher, equal, or only somewhat lower than that of planar V/Q imaging. Most investigators reported nondiagnostic SPECT V/Q scans in no more than 3% of cases. Methods of obtaining SPECT images, methods of obtaining planar V/Q images, and the criteria for interpretation varied. The general impression is that SPECT is more advantageous than planar V/Q imaging.

Diagnosis of pulmonary embolism in the coronary care unit.

The clinical diagnosis of pulmonary embolism (PE) is difficult in coronary care units (CCUs) because many findings of PE are similar to those of acute coronary syndromes and heart failure. Immobilization of only 1 or 2 days may predispose to PE. Heart failure and acute myocardial infarction add to the risk. Dyspnea may be absent or occur only with exertion. The onset of dyspnea may occur over seconds to days. Orthopnea occurs with PE as well as heart failure. When the clinical probability and results of objective testing are discordant, the posttest probability of PE may be neither sufficiently high nor sufficiently low to permit therapeutic decisions. Objective scoring systems for clinical assessment have not been developed for patients in a CCU. d-dimer is likely to be of little value for the exclusion of PE in CCUs, because elevations occur with heart failure, unstable angina, and myocardial infarction. Computed tomographic pulmonary angiography with venous phase imaging of the low pelvic and proximal leg veins (computed tomographic venography) is recommended for imaging. Scintigraphy in women aged <50 years with normal or nearly normal results on chest x-ray may be the preferred imaging test to reduce the risk for radiation. Echocardiography with leg ultrasonography is a rapidly obtainable combination of bedside tests that may be useful for young patients and patients in extremis. In conclusion, the choice of diagnostic test depends on the clinical probability of PE, the condition of the patient, the availability of diagnostic tests, the risks of iodinated contrast material, radiation exposure, and cost.

Reconstructed 4-chamber views compared with axial imaging for assessment of right ventricular enlargement on CT pulmonary angiograms.

PURPOSE: To test the hypothesis that right enlargement assessed from right ventricular/left ventricular (RV/LV) dimension ratios of computed tomographic (CT) angiograms are equivalent irrespective of whether measured on axial views or reconstructed 4-chamber views. METHODS: RV/LV dimension ratios were calculated from measurements on axial views, manually reconstructed 4-chamber views and computer generated reconstructed 4-chamber views of CT angiograms in 152 patients with PE. RESULTS: Paired readings of the axial view and manually reconstructed 4-chamber view showed agreement with RV/LV > or =1 or RV/LV <1 in 114 of 127 (89.8%). Paired readings also showed agreement in 119 of 127 (93.7%) with axial views and computer generated reconstructed 4-chamber views. The McNemar test showed no statistically significant difference between assessments of RV enlargement (RV/LV > or = 1) with any method. CONCLUSION: Right ventricular enlargement can be determined from axial views on CT angiograms, which are readily and immediately available, without obtaining 4-chamber reconstructed views.

Early microbiological response to linezolid vs vancomycin in ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of ventilator-associated pneumonia (VAP). This prospective, open-label, multicenter clinical trial compared the early microbiological efficacy of linezolid (LZD) therapy with that of vancomycin (VAN) therapy in patients with MRSA VAP. METHODS: A total of 149 patients with suspected MRSA VAP were randomized to receive either LZD, 600 mg, or VAN, 1 g every 12 h. Patients with baseline bronchoscopic BAL (BBAL) fluid quantitative culture findings that were positive for MRSA (>or= 10(4) cfu/mL) comprised the study population. The primary outcome was microbiological response (

Health care-associated pneumonia: identification and initial management in the ED.

Traditionally, pneumonia is categorized by epidemiologic factors into community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). Microbiologic studies have shown that the organisms which cause infections in HAP and VAP differ from CAP in epidemiology and resistance patterns. Patients with HAP or VAP are at higher risk for harboring resistant organisms. Other historical features that potentially place patients at a higher risk for being infected with resistant pathogens and organisms not commonly associated with CAP include history of recent admission to a health care facility, residence in a long-term care or nursing home facility, attendance at a dialysis clinic, history of recent intravenous antibiotic therapy, chemotherapy, and wound care. Because these "risk factors" have health care exposure as a common feature, patients presenting with pneumonia having these historical features have been more recently categorized as having health care-associated pneumonia (HCAP). This publication was prepared by the HCAP Working Group, which is comprised of nationally recognized experts in emergency medicine, infectious diseases, and pulmonary and critical care medicine. The aim of this article is to create awareness of the entity known as HCAP and to provide knowledge of its identification and initial management in the emergency department.

Challenges in the diagnosis of acute pulmonary embolism.

The state of the art of diagnostic evaluation of hemodynamically stable patients with suspected acute pulmonary embolism was reviewed. Diagnostic evaluation should begin with clinical assessment using a validated prediction rule in combination with measurement of D-dimer when appropriate. Imaging should follow only when necessary. Although with 4-slice computed tomography (CT) and 16-slice CT, the sensitivity for detection of pulmonary embolism was increased by combining CT angiography with CT venography, it is not known whether CT venography increases the sensitivity of 64-slice CT angiography. Methods to reduce the radiation exposure of CT venography include imaging only the proximal leg veins (excluding the pelvis) and obtaining discontinuous images. Compression ultrasound can be used instead. In young women, radiation of the breasts produces the greatest risk of radiation-induced cancer. It may be that scintigraphy is the imaging test of choice in such patients, but this pathway should be tested prospectively. A patient-specific approach to the diagnosis of pulmonary embolism can be taken safely in hemodynamically stable patients to increase efficiency and decrease cost and exposure to radiation.

Prognostic value of the shock index along with transthoracic echocardiography in risk stratification of patients with acute pulmonary embolism.

The initial clinical presentation and echocardiography have key roles in risk stratification of patients with acute pulmonary embolism (PE). To assess the value of shock index and echocardiographic abnormalities as predictors of in-hospital complications and mortality, echocardiographic features of 159 patients diagnosed with acute PE were reviewed. A shock index > or =1, independent of echocardiographic findings, was associated with increased in-hospital mortality. Regardless of shock index, moderate to severe right ventricular (RV) hypokinesis and a ratio of RV to left ventricular (LV) end-diastolic diameter >1 was significantly associated with in-hospital mortality and demonstrated the best predictive values for short-term outcomes. The sensitivity and negative predictive value of diastolic LV impairment (E/A wave <1), RV hypokinesis, RV/LV >1, and end-diastolic RV diameter >3 cm for in-hospital mortality were 100%. Systolic pulmonary artery pressure (PAP) was higher in patients who died before discharge. A cut-off point >50 mm Hg for systolic PAP was significantly associated with increased in-hospital death. In conclusion, among conventional echocardiographic abnormalities attributed to RV dysfunction (E/A wave <1, RV hypokinesis, RV/LV >1, RV end-diastolic diameter >3 cm, and interventricular septal flattening), moderate to severe RV hypokinesis and RV/LV >1 have better predictive values for short-term outcomes of patients with acute PE. In addition, a shock index > or =1 and systolic PAP >50 mm Hg could also be helpful in the triage of these patients.

Enlarged right ventricle without shock in acute pulmonary embolism: prognosis.

OBJECTIVE: An unsettled issue is the use of thrombolytic agents in patients with acute pulmonary embolism (PE) who are hemodynamically stable but have right ventricular (RV) enlargement. We assessed the in-hospital mortality of hemodynamically stable patients with PE and RV enlargement. METHODS: Patients were enrolled in the Prospective Investigation of Pulmonary Embolism Diagnosis II. Exclusions included shock, critical illness, ventilatory support, or myocardial infarction within 1 month, and ventricular tachycardia or ventricular fibrillation within 24 hours. We evaluated the ratio of the RV minor axis to the left ventricular minor axis measured on transverse images during computed tomographic angiography. RESULTS: Among 76 patients with RV enlargement treated with anticoagulants and/or inferior vena cava filters, in-hospital deaths from PE were 0 of 76 (0%) and all-cause mortality was 2 of 76 (2.6%). No septal motion abnormality was observed in 49 patients (64%), septal flattening was observed in 25 patients (33%), and septal deviation was observed in 2 patients (3%). No patients required ventilatory support, vasopressor therapy, rescue thrombolytic therapy, or catheter embolectomy. There were no in-hospital deaths caused by PE. There was no difference in all-cause mortality between patients with and without RV enlargement (relative risk=1.04). CONCLUSION: In-hospital prognosis is good in patients with PE and RV enlargement if they are not in shock, acutely ill, or on ventilatory support, or had a recent myocardial infarction or life-threatening arrhythmia. RV enlargement alone in patients with PE, therefore, does not seem to indicate a poor prognosis or the need for thrombolytic therapy.

Methods of Prospective Investigation of Pulmonary Embolism Diagnosis III (PIOPED III).

In this work, the methods of the Prospective Investigation of Pulmonary Embolism Diagnosis III (PIOPED III) are described in detail. PIOPED III is a multicenter collaborative investigation sponsored by the National Heart, Lung and Blood Institute. The purpose is to determine the accuracy of gadolinium-enhanced magnetic resonance angiography in combination with venous phase magnetic resonance venography for the diagnosis of acute pulmonary embolism (PE). A composite reference standard based on usual diagnostic methods for PE is used. All images will be read by 2 blinded and study-certified central readers. Patients with no PE according to the composite reference test will be randomized to undergo gadolinium-enhanced magnetic resonance angiography in combination with venous phase magnetic resonance venography. This procedure will reduce the proportion of patients with negative tests at no loss in evaluation of sensitivity and specificity.

Newer modalities for detection of pulmonary emboli.

Pulmonary embolism (PE) is the third most common cardiovascular disease after myocardial infarction and stroke in the United States. Early and accurate diagnosis of this condition is imperative because many patients die within hours of presentation. Clinical and laboratory tests can be used to accurately determine the pretest probability of PE. When necessary, imaging techniques are then used to exclude or diagnose PE. Pulmonary angiography is the reference standard for the diagnosis of PE, but it is invasive and has a high morbidity and mortality rate. Ventilation and perfusion (V/Q) scanning in the past has been recommended as the initial diagnostic test for PE; however, this technique also has limitations. Recently, new modalities for the diagnosis and exclusion of PE have been evaluated. These techniques include V/Q single photon emission computed tomography (SPECT), single- and multi-detected computed tomography, and magnetic resonance angiography (MRA) including gadolinium-enhanced MRA, real-time magnetic resonance imaging (RT-MR), and magnetic resonance perfusion imaging.

Clinical characteristics of patients with acute pulmonary embolism: data from PIOPED II.

BACKGROUND: Selection of patients for diagnostic tests for acute pulmonary embolism requires recognition of the possibility of pulmonary embolism on the basis of the clinical characteristics. Patients in the Prospective Investigation of Pulmonary Embolism Diagnosis II had a broad spectrum of severity, which permits an evaluation of the subtle characteristics of mild pulmonary embolism and the characteristics of severe pulmonary embolism. METHODS: Data are from the national collaborative study, Prospective Investigation of Pulmonary Embolism Diagnosis II. RESULTS: There may be dyspnea only on exertion. The onset of dyspnea is usually, but not always, rapid. Orthopnea may occur. In patients with pulmonary embolism in the main or lobar pulmonary arteries, dyspnea or tachypnea occurred in 92%, but the largest pulmonary embolism was in the segmental pulmonary arteries in only 65%. In general, signs and symptoms were similar in elderly and younger patients, but dyspnea or tachypnea was less frequent in elderly patients with no previous cardiopulmonary disease. Dyspnea may be absent even in patients with circulatory collapse. Patients with a low-probability objective clinical assessment sometimes had pulmonary embolism, even in proximal vessels. CONCLUSION: Symptoms may be mild, and generally recognized symptoms may be absent, particularly in patients with pulmonary embolism only in the segmental pulmonary branches, but they may be absent even with severe pulmonary embolism. A high or intermediate-probability objective clinical assessment suggests the need for diagnostic studies, but a low-probability objective clinical assessment does not exclude the diagnosis. Maintenance of a high level of suspicion is critical.

Electrocardiographic score and short-term outcomes of acute pulmonary embolism.

Risk stratification of patients with a diagnosis of acute pulmonary embolism (PE) is crucial in deciding appropriate management. An electrocardiographic (ECG) scoring system may potentially be useful in identifying patients at high risk of increased hospital morbidity and mortality from acute PE. Electrocardiography and echocardiography of 159 patients with a diagnosis of acute PE using ventilation/perfusion scan or spiral computed tomographic scan at 2 Emory-affiliated hospitals were reviewed. The 21-ECG score was compared with the presence or absence of right ventricular (RV) dysfunction and the 2 major end points of complicated in-hospital course or death. ECG score was significantly higher in patients with RV dysfunction (p <0.001) and a complicated in-hospital course (p <0.05). Although the ECG score was higher in nonsurvivors, it was not significantly different. Based on receiver-operator characteristic curves, an ECG score > or =3 could predict RV dysfunction with sensitivity, specificity, and positive and negative predictive values of 76%, 82%, 76%, and 86%, respectively. An ECG score > or =3 could predict a complicated in-hospital course and mortality with sensitivities of 58% and 59%, specificities of 60% and 58%, positive predictive values of 16% and 10%, and negative predictive values of 89% and 95%, respectively. In conclusion, the current 21-ECG scoring system can predict RV dysfunction in patients with acute PE well. However; its ability to predict an adverse in-hospital course is limited. Nevertheless, an ECG score <3 predicts better short-term outcome in these patients.

Usefulness of multidetector spiral computed tomography according to age and gender for diagnosis of acute pulmonary embolism.

Data from the Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) were evaluated to test the hypothesis that the performance of multidetector computed tomographic (CT) pulmonary angiography and CT venography is independent of a patient's age and gender. In 773 patients with adequate CT pulmonary angiography and 737 patients with adequate CT pulmonary angiography and CT venography, the sensitivity and specificity for pulmonary embolism for groups of patients aged 18 to 59, 60 to 79, and 80 to 99 years did not differ to a statistically significant extent, nor were there significant differences according to gender. Overall, however, the specificity of CT pulmonary angiography was somewhat greater in women, but in men and women, it was > or =93%. In conclusion, the results indicate that multidetector CT pulmonary angiography and CT pulmonary angiography and CT venography may be used with various diagnostic strategies in adults of all ages and both genders.

Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II investigators.

PURPOSE: To formulate comprehensive recommendations for the diagnostic approach to patients with suspected pulmonary embolism, based on randomized trials. METHODS: Diagnostic management recommendations were formulated based on results of the Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) and outcome studies. RESULTS: The PIOPED II investigators recommend stratification of all patients with suspected pulmonary embolism according to an objective clinical probability assessment. D-dimer should be measured by the quantitative rapid enzyme-linked immunosorbent assay (ELISA), and the combination of a negative D-dimer with a low or moderate clinical probability can safely exclude pulmonary embolism in many patients. If pulmonary embolism is not excluded, contrast-enhanced computed tomographic pulmonary angiography (CT angiography) in combination with venous phase imaging (CT venography), is recommended by most PIOPED II investigators, although CT angiography plus clinical assessment is an option. In pregnant women, ventilation/perfusion scans are recommended by many as the first imaging test following D-dimer and perhaps venous ultrasound. In patients with discordant findings of clinical assessment and CT angiograms or CT angiogram/CT venogram, further evaluation may be necessary. CONCLUSION: The sequence for diagnostic test in patients with suspected pulmonary embolism depends on the clinical circumstances.