Effect of airway pressure display on interobserver agreement in the assessment of vascular pressures in patients with acute lung injury and acute respiratory distress syndrome.

BACKGROUND: Previous investigations have identified significant interobserver variability in the measurements of central venous pressure and pulmonary artery occlusion pressure in critically ill patients. Large interobserver variability in the measurement of vascular pressures could potentially lead to inappropriate treatment decisions. OBJECTIVE: We postulated that adding an airway pressure signal (Paw) to pressure tracings of central venous pressure and pulmonary artery occlusion pressure would improve interobserver agreement by facilitating identification of end-expiration. DESIGN: To test this hypothesis, six independent experts used a standard protocol to interpret strip-chart recordings of central venous pressure and pulmonary artery occlusion pressure with or without Paw. Two observers were said to agree if their measurements were within 2 mm Hg of each other. SETTING/SUBJECTS/INTERVENTIONS: A total of 459 strip-chart recordings (303 without Paw and 156 with Paw) were obtained from 121 patients enrolled in the ARDSnet Fluids and Catheters Treatment Trial (FACTT) in 16 different hospitals. RESULTS: Agreement within 2 mm Hg between two measurements was 79% for central venous pressure strips without Paw vs. 86% with Paw. For pulmonary artery occlusion pressure, agreement increased from 71% without Paw to 83% with Paw. The increase in agreement with the addition of Paw was greater for strips demonstrating >8 mm Hg phasic respiratory variation compared with strips demonstrating less phasic respiratory variation. CONCLUSION: Paw display is a simple, inexpensive method to facilitate the identification of end-expiration that can significantly improve interobserver agreement.

Keratinocyte growth factor attenuates hydrostatic pulmonary edema in an isolated, perfused rat lung model.

Hydrostatic pulmonary edema is a common complication of congestive heart failure, resulting in substantial morbidity and mortality. Keratinocyte growth factor (KGF) is a mitogen for type II alveolar epithelial and microvascular cells. We utilized the isolated perfused rat lung model to produce hydrostatic pulmonary edema by varying the left atrial and pulmonary capillary pressure. Pretreatment with KGF attenuated hydrostatic edema formation. This was demonstrated by lower wet-to-dry lung weight ratios, histological evidence of less alveolar edema formation, and reduced alveolar accumulation of intravascularly administered FITC-labeled large-molecular-weight dextran in rats pretreated with KGF. Thus KGF attenuates injury in this ex vivo model of hydrostatic pulmonary edema via mechanisms that prevent increases in alveolar-capillary permeability.

Filgrastim in patients with pneumonia and severe sepsis or septic shock.

STUDY OBJECTIVES: Evaluate the safety of filgrastim (recombinant methionyl human granulocyte colony-stimulating factor) administration, combined with standard therapy, in patients with pneumonia and either septic shock or severe sepsis who were receiving mechanical ventilation. DESIGN: Multicenter, double-blind, randomized, placebo-controlled study. SETTING: ICU, multicenter. PATIENTS: Eighteen patients with pneumonia and hypotension, or in the absence of shock, two or more end-organ dysfunctions, were enrolled and treated. Baseline acute physiology and chronic health evaluation II scores and median age for the filgrastim (n = 12) and placebo (n = 6) groups were 25.0 and 49.5 years and 31.5 and 56.5 years, respectively. INTERVENTION: Filgrastim (300 microg) or placebo was administered IV daily for up to 5 days. MEASUREMENTS AND RESULTS: Study end points included safety; biological response, including endogenous cytokine levels, endotoxin levels, and neutrophil counts; and mortality. Cytokine and endotoxin levels were highly variable in both groups. By day 29, 3 of 12 filgrastim-treated patients and 4 of 6 placebo-treated patients had died. There were no differences in types and occurrences of adverse events, including ARDS, or in outcome between the two groups. Three of four placebo-treated patients had persistent bacterial growth on bronchoscopy repeated after 48 h compared with 2 of 10 filgrastim-treated patients. CONCLUSION: Filgrastim appeared to be well tolerated in this population of patients with pneumonia and severe sepsis or septic shock. Larger studies to determine the benefit of filgrastim in patients with pneumonia and sepsis or organ dysfunction are warranted.

Randomized trial of the use of heliox as a driving gas for updraft nebulization of bronchodilators in the emergent treatment of acute exacerbations of chronic obstructive pulmonary disease.

OBJECTIVE: To determine whether the bronchodilator effects of albuterol and ipratropium bromide are greater if updraft nebulization is driven by 80% helium and 20% oxygen (HELIOX) than if driven by compressed room air (AIR) during the treatment of an acute exacerbations of chronic obstructive pulmonary disease (COPD). SETTING: The emergency department of a 750-bed inner-city community hospital. METHODS: Over a 12-month period, a convenience sample of 50 normoxic patients presenting with signs and symptoms of an acute exacerbation of COPD were prospectively randomized to receive either HELIOX or AIR as the driving gas for updraft nebulization of a mixture of albuterol 2.5 mg and ipratropium bromide 0.5 mg. Additional aerosol treatments with albuterol 2.5 mg were given at 20, 40, and 120 mins after randomization using the assigned gas. Spirometry was obtained while breathing room air before the first treatment (baseline) and at 1 hr and 2 hrs after the initiation of treatment. The primary measure of efficacy was the change in percent of predicted forced expiratory volume in 1 sec (FEV1) over the treatment period. A secondary measure of efficacy was the change in percentage of predicted forced expiratory flow after 25% to 75% of vital capacity had been expelled (FEF25-75). RESULTS: Twenty-five patients were randomized to each treatment group. Three patients (1 HELIOX, 2 AIR) were unable to complete the study. The baseline FEV1was 44% (95% confidence interval, 35% to 52%) of predicted in the HELIOX group and 39 (31% to 46%) of predicted in the AIR group. There were no adverse outcomes observed in either the HELIOX group or the AIR group. There were no significant differences in the change of FEV1 between the two groups by either the 1 hr or 2 hr time point (1 hr, HELIOX + 10% [7% to 13%], AIR + 9% [5% to 13%]; 2 hr HELIOX + 10% [6% to 15%], AIR + 10% [6% to 14%]). The improvement in FEF25-75 was significantly greater in the HELIOX group than in the AIR group at both the 1 hr time point (HELIOX + 14% [7% to 22%] vs. AIR + 7% [3% to 10%], p = .05) and at the 2 hr time point (HELIOX + 15% [8% to 21%] vs. AIR + 7% [4% to 11%], p = .05). CONCLUSION: Use of HELIOX as a driving gas for the updraft nebulization of bronchodilators during the first 2 hrs of treatment of an acute COPD exacerbation failed to improve FEV1 faster than the use of AIR. The faster improvement in FEF25-75 during the first 2 hrs of treatment was small and of uncertain clinical significance.

A comparison of pulmonary arterial occlusion algorithms for estimation of pulmonary capillary pressure.

Using the arterial occlusion method, we compared five literature-based estimates of pulmonary capillary pressure (Ppc) with the corresponding double occlusion pressures (Pdo) in anesthetized dogs whose chests had been closed after sternotomy for instrumentation. Arterial occlusions were performed with a balloon-tipped pulmonary artery catheter that housed pressure transducers immediately proximal and distal to the balloon. Separation of the proximal and distal pressure waveforms during balloon inflation allowed us to precisely define the moment of occlusion. We fit a monoexponential curve to pressure data beginning 200 ms after the onset of occlusion and a biexponential curve to data beginning at the instant of occlusion, with data obtained over a range of vascular states (control, serotonin infusion, histamine infusion). In addition, we investigated the use of sampling of the raw data to estimate capillary pressure. Three of the five literature-based estimates of Ppc yielded values similar to Pdo. The optimal (least average difference from Pdo) interpolation/extrapolation time points of the curve fits varied, depending on the type of curve fitting and the state of the pulmonary vasculature. We also determined that a close approximation of Pdo may be derived from the raw data, as an alternative to exponential curve fitting.

A low-calorie unrestricted protein diet attenuates kidney damage in uninephrectomized spontaneously hypertensive rats.

BACKGROUND/AIMS: Uninephrectomized, spontaneously hypertensive rats (UNX-SHR) develop glomerular hyperfiltration, hyperfusion, and interstitial infiltrate of the remnant kidney. Consequently, UNX-SHR is a useful animal model to investigate mechanisms involved in the progression of hypertensive renal disease. METHODS: Body weight; tail systolic blood pressure (SBP); urine excretion of protein, urea, and electrolytes; and serum biochemistry were determined in UNX-SHR at 2 months of age prior to uninephrectomy (week 0), prior to treatment (week 8) with a low-calorie (LC) or control diet, and one month after diet treatment (week 12). The LC diet was modified to allow equal intake of protein, sodium phosphorus, and other nutrients in both groups. RESULTS: UNX-SHR treated with the LC diet had significantly lower body weights and SBP at the end of the experiment than did the controls (p < 0.0001). Changes in serum biochemistry and 24-hour urinary excretion of protein, sodium, potassium, and urea nitrogen in both groups were not statistically significant. The final glomerular filtration rate and renal plasma flow were similar in both groups, but the LC diet significantly reduced the glomerular damage index (0.0007), mesangial expansion index (p < 0.002), volume of interstitium per cortex (p < 0.0003), tubular interstitium volume fraction (p < 0.0008), glomerular volume (p < 0.02), and remnant kidney weight (p < 0.01). CONCLUSION: We demonstrated that in UNX-SHR, the prevention of renal damage by LC diet may involve diminished glomerular growth and interstitial infiltrate without changes in renal hemodynamics. Consequently, LC diet, regardless of protein ingestion, may be an important tool in the prevention of renal damage in hypertension. Additional studies of obese-hypertensive rats may confirm the beneficial effect of a LC diet and weight reduction on the renal damage of obesity-hypertension.

Fluticasone propionate powder: oral corticosteroid-sparing effect and improved lung function and quality of life in patients with severe chronic asthma.

BACKGROUND: Many patients with severe asthma are dependent on oral corticosteroids for maintenance control of their disease. Treatments that allow patients to be weaned off oral corticosteroids may help to minimize the risk of side effects associated with their chronic use. OBJECTIVE: This study evaluated whether inhaled fluticasone propionate powder could maintain pulmonary function while reducing the dose of oral prednisone in patients with chronic, severe asthma. METHODS: Oral prednisone-dependent (5 to 40 mg/day) adolescents and adults with asthma (n = 111; mean FEV1 = 61% of predicted value) were randomized to placebo or twice daily fluticasone propionate 500 or 1000 microg administered by means of a multidose powder inhaler for 16 weeks in a double-blind, parallel-group study. Patients underwent controlled prednisone reduction on the basis of predetermined asthma stability criteria. RESULTS: Oral prednisone was eliminated by 75% and 89% of patients in the twice daily 500 and 1000 microg fluticasone propionate groups, respectively, versus 9% of the placebo group (P <.001). FEV1, morning and evening peak expiratory flow, asthma symptoms, albuterol use, and nighttime awakenings improved with fluticasone propionate treatment, achieving statistical significance (P

A randomized controlled trial of filgrastim as an adjunct to antibiotics for treatment of hospitalized patients with community-acquired pneumonia. CAP Study Group.

Because of the critical role of neutrophils in host defenses, it was hypothesized that stimulation of neutrophil production and function with Filgrastim would improve the outcome of hospitalized patients with community-acquired pneumonia. To test this hypothesis, a randomized, placebo-controlled, multicenter trial of Filgrastim (300 micrograms/day up to 10 days) as an adjunct to antibiotics was conducted for these patients. Outcome measures included time to resolution of morbidity (TRM, a composite measure of temperature, respiratory rate, blood oxygenation, and chest radiograph), 28-day mortality, length of stay, and adverse events. Filgrastim increased blood neutrophils 3-fold, but TRM, mortality, and length of hospitalization were not affected. Treatment, however, accelerated radiologic improvement and appeared to reduce serious complications (e.g., empyema, adult respiratory distress syndrome, and disseminated intravascular coagulation). Filgrastim administration was safe and well tolerated in these patients. Additional trials are needed to establish the value of this approach to treatment of infectious diseases.

Steroid therapy for chronic obstructive pulmonary disease.

Both inhaled and oral corticosteroids have proven benefit in the management of asthma, but their efficacy in nonasthmatic, smoking-related chronic obstructive pulmonary disease (COPD) remains controversial. Recent data suggest that responsiveness to beta 2-agonists predicts oral and inhaled steroid responsiveness in most patients with COPD, however, a poor bronchodilator response does not preclude a good response to steroids. COPD patients with histologic, cytologic, or biochemical indices of inflammation characteristic of asthma, such as sputum eosinophilia, are more likely to be steroid responsive than are COPD patients without these characteristics. Contrary to previous experience, steroid responsiveness does not appear to be an all-or-nothing phenomenon; rather there appears to be a continuous spectrum of steroid responses from none to marked. The effects of long-term inhaled steroid use on the natural progression of chronic airflow obstruction are currently under investigation.

Pulmonary stress injury within physiological ranges of airway and vascular pressures.

PURPOSE: The aim of this study was to assess the respective role of a small elevation in pulmonary capillary pressure, airway pressure, or both on alveolar capillary barrier permeability in an isolated perfused rat lung model. MATERIALS AND METHODS: Four groups were studied with low or high airway pressure (LA: 10 mL/kg (tidal volume); HA: 20 mL/kg), low or high pulmonary artery pressure (LP: 9 mm Hg; HP: 12 mm Hg): LALP, HALP, LAHP, and HAHP. The lungs were ventilated and perfused ex vivo for 30 minutes. Quantification of fluorescein isothiocyanate-labeled (FITC) dextran in bronchoalveolar lavage (BAL) fluid and radiolabeled tracers assessed alveolar capillary barrier permeability. RESULTS: BALF FITC-dextran was similar in the three groups with either one or two low-pressure parameters (LALP, LAHP, HALP), but high amounts were found in the HAHP group (375.2 x 10(-6) mg/mL v, respectively, 21.4, 26.2, and 30 x 10(-6) mg/mL, P = .0001). These results were consistent with the albumin space and extravascular lung water: higher values only in the HAHP group statistically different from the other groups (P < .002). Interalveolar pore examined with scanning electron microscopy showed an increase in diameters between LALP and HAHP (P < .0001). CONCLUSIONS: We can conclude that elevation of either the pulmonary artery pressure from 8 to 11 mm Hg or the alveolar pressure from 10 to 15 mm Hg alone does not change the permeability of the alveolar capillary membrane; however, there is an additive effect of these pressures.

Reactive airways dysfunction syndrome after exposure to dinitrogen tetroxide.

BACKGROUND: Reactive airways dysfunction syndrome (RADS) is characterized by persistent bronchial hyperreactivity and asthmatic symptoms in a previously healthy individual after a single intense exposure to an irritant fume, vapor, or gas. On October 23, 1995, a cloud of dinitrogen tetroxide (N2O4) escaped from a railroad tanker car in Bogalusa, Louisiana, exposing an estimated 4,000 citizens to the gas. METHODS: A sample of 234 patients with respiratory complaints after the spill received a complete history and physical examination, a symptom questionnaire, and pulmonary function tests. Patients whose previously undocumented asthma-like symptoms persisted for 3 months after exposure to N2O4 had methacholine challenge testing. RESULTS: Of the 234 patients evaluated, six met the criteria for a diagnosis of RADS. The distance of these six patients from the source of the leak, their durations of exposure, and initial symptoms were not different from those of the sample patients who did not have RADS. CONCLUSIONS: After evaluation of 234 symptomatic patients who were exposed to N2O4, we diagnosed six cases of RADS. There were no demographic characteristics or initial symptoms that identified patients who were at risk of having this syndrome. We believe we are the first to report cases of RADS due to N2O4 exposure.

Pharmacotherapy of chronic obstructive pulmonary disease.

Despite a significant reduction in cigarette consumption, chronic obstructive pulmonary disease continues to be an important cause of mortality in the United States. COPD is characterized by progressive airflow obstruction which is punctuated by acute exacerbations. Nicotine substitution and use of bupropion have been shown to double long-term smoking cessation success. The combination of albuterol and ipratropium bromide produces a synergistic beneficial effect on pulmonary function and symptoms. Long-acting inhaled beta 2-agonists improve symptoms better than as needed albuterol. Oral corticosteroids appear to be helpful during acute exacerbations; however, the chronic use of steroids benefits only a minority of patients. Broad- spectrum antibiotics are indicated during acute exacerbations if there is increased sputum volume and purulence. System-oriented administration of pneumococcal and influenza vaccinations is more successful than provider or client-oriented approaches.

Diagnosis and management of asthma: a summary of the National Asthma Education and Prevention Program guidelines. National Institutes of Health.

Asthma is a common disease that affects persons of all ages. It is responsible for more than 5,000 deaths annually in the United States and countless days absent from school and work. For these reasons, the National Institutes of Health established the National Asthma Education Program whose expert panels have published two reports: Guidelines for the Diagnosis and Management of Asthma in 1991 and a revised report in 1997. A summary of the Expert Panel Report 2 published in 1997 is presented with emphasis on the outpatient diagnosis, prevention, and treatment of asthma. Education of the clinician and the patient is essential for effective management of asthma, and effective communication between clinician and patient is essential for implementing asthma education. The goal of this summary is to communicate and disperse the asthma education provided by the Guidelines for the Diagnosis and Management of Asthma: Expert Panel Report 2 in hopes of improving asthma care and decreasing morbidity and mortality-attributed asthma.