Hubmayr, Rolf D.

We tested the hypothesis that diaphragm muscle shortening modulates volume displacement and kinematics of the lower rib cage in dogs and that posture and mode of ventilation affect such modulation. Radiopaque markers were surgically attached to the lower three ribs of the rib cage and to the midcostal region of the diaphragm in six dogs of ∼8 kg body masses, and the locations of these markers were determined by a biplane fluoroscopy system. Three-dimensional software modeling techniques were used to compute volume displacement and surface area of the midcostal diaphragm and the lower three ribs during quiet spontaneous breathing, mechanical ventilation, and bilateral phrenic nerve stimulation at different lung volumes spanning the vital capacity. Volume displaced by the diaphragm relative to that displaced by the lower ribs is disproportionately greater under mechanical ventilation than during spontaneous breathing in the supine position ( P < 0.05). At maximal stimulation, diaphragm volume displacement grows disproportionately larger than rib volume displacement as lung volume increases ( P < 0.05). Surface area of both the diaphragm and the lower ribs during maximal stimulation of the diaphragm is reduced compared with that at spontaneous breathing ( P < 0.05). In the prone posture, mechanical ventilation results in a smaller change in diaphragm surface area than spontaneous breathing ( P < 0.05). Our data demonstrate that during inspiration the lower rib cage moves not only through the pump- and bucket-handle motion, but also rotates around the spine. Taken together, these data support the observation that the kinematics of the lower rib cage and its mechanical interaction with the diaphragm are more complex than previously known.

Abstract Rationale Significant progress has been made in understanding the pathogenesis of acute respiratory distress syndrome (ARDS). Recent advances in hospital practice may have reduced the incidence of this lethal syndrome. Objectives To observe incidence trends and associated outcomes of ARDS. Methods This population-based cohort study was conducted in Olmsted County, Minnesota. Using a validated screening protocol, investigators identified intensive care patients with acute hypoxemia and bilateral pulmonary infiltrates. The presence of ARDS was independently confirmed according to American-European Consensus Conference criteria. The incidence of ARDS and associated outcomes were compared over the 8-year study period (2001–2008). Measurements and Main Results Over the 8-year period, critically ill Olmsted County residents presented with increasing severity of acute illness, a greater number of comorbidities, and a higher prevalence of major predisposing conditions for ARDS. The ARDS incidence decreased significantly from 82.4 to 38.9 per 100,000 person-years during the study period (P &lt; 0.001). A decline in hospital-acquired ARDS (P &lt; 0.001) was responsible for the fall in the incidence density with no change on admission (P = 0.877). Overall, mortality and hospital and intensive care unit lengths of stay decreased over time (P &lt; 0.001), whereas the ARDS case-fatality did not change significantly. Conclusions Despite an increase in patients' severity of illness, number of comorbidities, and prevalence of major ARDS risk factors, the incidence of ARDS in this suburban community decreased by more than half. Correlation of the observed findings with changes in health care delivery may have important implications for the planning of acute care services in other regions.

Abstract Type I alveolar epithelial cells (ATIs) are very large, thin cells, which extend across several air sacs and cover more than 95% of the alveolar surface area. ATIs are the target of many insults, including ventilator-induced lung injury, and are generally considered terminally differentiated cells arising from type II cell (ATII) lineage. ATIs have proven difficult to harvest and maintain in primary culture, which is why much of ATI biology has been inferred from studies on ex vivo, ATII-derived, so-called ATI-like cells. We report on a modified approach to rat ATI harvest and primary culture, which yielded the following observations: (1) rat ATI can be harvested and maintained with a high degree of purity in primary culture; (2) in vitro growth characteristics of primary ATIs differ from those of ATII-derived ATI-like cells; ATIs, but not ex vivo, ATII-derived ATI-like cells, are capable of cell division; (3) ATIs readily repair plasma membrane wounds without the subsequent loss of their ability to divide; (4) ATI monolayers heal scratch wounds primarily by cell spreading and migration. Although the ability of ATIs to divide may be limited to the in vitro environment, we do believe that their role in alveolar wound repair deserves to be revisited, and the molecular control of ATI–ATII plasticity further explored.

Abstract Rationale Acute lung injury (ALI) that develops 6 hours after transfusion (TRALI) is the leading cause of transfusion-related mortality. Several transfusion characteristics have been postulated as risk factors for TRALI, but the evidence is limited to retrospective studies. Objectives To compare patient and transfusion risk factors between patients who do and do not develop ALI. Methods In this prospective cohort study, consecutive transfused critically ill patients were closely observed for development of ALI. Donor samples were collected from the transfusion bags. Risk factors were compared between patients who developed ALI after transfusion and transfused control patients, matched by age, sex, and admission diagnosis. Measurements and Main Results Seventy-four of 901 transfused patients developed ALI within 6 hours of transfusion (8%). Compared with transfused control subjects, patients with ALI were more likely to have sepsis (37 vs. 22%, P = 0.016) and a history of chronic alcohol abuse (37 vs. 18%, P = 0.006). When adjusted for patient characteristics, transfusion of plasma from female donors (odds ratio [OR], 5.09; 95% confidence interval [95% CI], 1.37–18.85) rather than male donors (OR, 1.60; 95% CI, 0.76 to 3.37), number of pregnancies among the donors (OR, 1.19; 95% CI, 1.05 to 1.34), number of donor units positive for anti-granulocyte antibodies (OR, 4.85; 95% CI, 1.32–17.86) and anti–HLA class II antibodies (OR, 3.08; 95% CI, 1.15–8.25), and concentration of lysophosphatidylcholine in the donor product (OR, 1.69; 95% CI, 1.10 to 2.59) were associated with the development of ALI. Conclusions Both patient and transfusion risk factors determine the probability of ALI after transfusion. Transfusion factors represent attractive targets for the prevention of ALI.

Background Respiratory failure is a leading cause of postoperative morbidity and mortality in patients undergoing pneumonectomy. The authors hypothesized that intraoperative mechanical ventilation with large tidal volumes (VTs) would be associated with increased risk of postpneumonectomy respiratory failure. Methods Patients undergoing elective pneumonectomy at the authors' institution from January 1999 to January 2003 were studied. The authors collected data on demographics, relevant comorbidities, neoadjuvant therapy, pulmonary function tests, site and type of operation, duration of surgery, intraoperative ventilator settings, and intraoperative fluid administration. The primary outcome measure was postoperative respiratory failure, defined as the need for continuation of mechanical ventilation for greater than 48 h postoperatively or the need for reinstitution of mechanical ventilation after extubation. Results Of 170 pneumonectomy patients who met inclusion criteria, 30 (18%) developed postoperative respiratory failure. Causes of postoperative respiratory failure were acute lung injury in 50% (n = 15), cardiogenic pulmonary edema in 17% (n = 5), pneumonia in 23% (n = 7), bronchopleural fistula in 7% (n = 2), and pulmonary thromboembolism in 3% (n = 1). Patients who developed respiratory failure were ventilated with larger intraoperative VT than those who did not (median, 8.3 vs. 6.7 ml/kg predicted body weight; P < 0.001). In a multivariate regression analysis, larger intraoperative VT (odds ratio, 1.56 for each ml/kg increase; 95% confidence interval, 1.12-2.23) was associated with development of postoperative respiratory failure. The interaction between larger VT and fluid administration was also statistically significant (odds ratio, 1.36; 95% confidence interval, 1.05-1.97). Conclusion Mechanical ventilation with large intraoperative VT is associated with increased risk of postpneumonectomy respiratory failure.

Abstract Rationale Although the serial dilution technique for quantitative culture of bronchoalveolar fluid is considered to be the gold standard for the diagnosis of ventilator-associated pneumonia, it is more labor intensive than the calibrated loop technique. Objective We sought to determine the agreement between the calibrated loop and serial dilution techniques in the diagnosis of ventilator-associated pneumonia. Methods We prospectively measured bacterial colony counts by the serial dilution and calibrated loop techniques in 121 bronchoalveolar lavage samples of 104 patients with suspected ventilator-associated pneumonia. Measurements and Main Results At the time of bronchoscopy, patients had received mechanical ventilation for a median of 8 d. Patients were receiving antibiotics when 90 of the 121 (74.4%) bronchoalveolar samples were obtained. The colony counts of 13 bacterial isolates were too numerous to count by the calibrated loop technique; by serial dilution technique, their counts ranged from 4.70 to 6.74 log10 cfu/ml. Fifty other bacteria had paired colony counts measured by each of the two techniques: the bias (95% confidence interval) between the two techniques was −0.380 (−0.665 to −0.095) log10 cfu/ml, with precision of 1.002 log10 cfu/ml and 95% limits of agreement of −2.344 to 1.584 log10 cfu/ml. Using the threshold of 4 log10 cfu/ml as a criterion for the diagnosis of ventilator-associated pneumonia, there was discordance only for one bacterial organism between the two techniques. Conclusions The calibrated loop technique can be used for the diagnosis of ventilator-associated pneumonia using bronchoalveolar lavage fluid.