Prone positioning attenuates and redistributes ventilator-induced lung injury in dogs.

BACKGROUND: We previously demonstrated a markedly dependent distribution of ventilator-induced lung injury in oleic acid-injured supine animals ventilated with large tidal volumes and positive end-expiratory pressure > or =10 cm H2O. Because pleural pressure distributes more uniformly in the prone position, we hypothesized that the extent of injury induced by purely mechanical forces applied to the lungs of normal animals might improve and that the distribution of injury might be altered with prone positioning. OBJECTIVE: To compare the extent and distribution of histologic changes and edema resulting from identical patterns of high end-inspiratory/low end-expiratory airway pressures in both supine and prone normal dogs. DESIGN/SETTING: We ventilated 10 normal dogs (5 prone, 5 supine) for 6 hrs with identical ventilatory patterns (a tidal volume that generated a peak transpulmonary pressure of 35 cm H2O when implemented in the supine position before randomization, positive end-expiratory pressure = 3 cm H2O). Ventilator-induced lung injury was assessed by gravimetric analysis and histologic grading. MEASUREMENTS AND MAIN RESULTS: Wet weight/dry weight ratios (WW/DW) and histologic scores were greater in the supine than the prone group (8.8+/-2.8 vs. 6.1+/-0.7; p = .01 and 1.4+/-0.3 vs. 1+/-0.3; p = .037, respectively). In the supine group, WW/DW and histologic scores were significantly greater in dependent than nondependent regions (9.4+/-1.9 vs. 6.7+/-0.9; p = .01 and 2.0+/-0.4 vs. 0.9+/-0.4; p = .043, respectively). In the prone group, WW/DW also was greater in dependent regions (6.7+/-1.1 vs. 5.8+/-0.5; p = .054), but no significant differences were found in histologic scores between dependent and nondependent regions (p = .42). CONCLUSION: In this model of lung injury induced solely by mechanical forces, the prone position resulted in a less severe and more homogeneous distribution of ventilator-induced lung injury. These results parallel those previously obtained in oleic acid-preinjured animals ventilated with higher positive end-expiratory pressure.

Influence of prone position on the extent and distribution of lung injury in a high tidal volume oleic acid model of acute respiratory distress syndrome.

OBJECTIVE: To evaluate the influence of body position on the extent and distribution of experimental lung damage in an oleic acid canine model of acute respiratory distress syndrome, using mechanical ventilation with high tidal volumes and positive end-expiratory pressure (PEEP). DESIGN: Prospective, randomized study. SETTING: Experimental animal laboratory. SUBJECTS: Twelve anesthetized and paralyzed dogs. INTERVENTIONS: Ninety minutes after lung injury was induced by injection of oleic acid, 12 animals were randomized to be ventilated for 4 hrs, in either the supine (supine group, n = 6) or prone (prone group, n = 6) positions, using the same ventilatory pattern (F10(2) 0.6, PEEP > or = 10 cm H2O, and a tidal volume that generated a peak transpulmonary pressure of 35 cm H2O when implemented in the supine position). Regardless of randomization to position, the tidal volumes, F10(2), and PEEP were kept constant and the pulmonary artery occlusion pressure was maintained between 4 and 6 mm Hg for the duration of the study. MEASUREMENTS AND MAIN RESULTS: At the end of the protocol, the lungs were excised for gravimetric determination (wet/dry weight ratio) and histologic examination (histologic score). Changes over time in the static pressure-volume curve of the lungs (obtained in the supine position) were also used as end-point variables. At baseline, hemodynamic and respiratory variables did not differ between groups. Just before randomization to position (90 mins after oleic acid injection), both groups presented similar lung static pressure-volume curves. Pulmonary artery occlusion pressure (4.3 +/- 1.9 vs. 4.8 +/- 1.3 mm Hg [supine vs. prone group]), cardiac output (4.1 +/- 0.4 vs. 5.2 +/- 1.3 L/min [supine vs. prone group]), and venous admixture (36.7 +/- 20.7% vs. 28.3 +/- 19.4% [supine vs. prone group]) were also not significantly (p > .05) different when measured in the supine position. At the end of the experiment, lung gravimetric data in the two experimental groups were not statistically different, suggesting a similar extent of edema. Histologic abnormalities, however, were less in the prone group than in the supine group (p < .01), due primarily to marked differences in extent and severity in the dependent regions of the lungs. Static lung compliance improved over time in the prone group (34 +/- 9 to 46 +/- 19 mL/cm H2O)(p = .02), but not in the supine group (34 +/- 6 to 36 +/- 6 mL/cm H2O). CONCLUSIONS: After oleic acid-induced lung injury, animals ventilated with high tidal volume and PEEP undergo less extensive histologic change in the prone position than in the supine position. The prone position alters the distribution of histologic abnormalities.

Morphologic and quantitative changes in blood and marrow cells following growth factor therapy.

Sequential blood and bone marrow specimens from 53 patients receiving recombinant granulocyte (G-CSF) or granulocyte macrophage colony stimulating growth factor (GM-CSF) for neutropenia were evaluated. The blood findings were marked by a neutrophilia with a prominent left shift, increased azurophilic granulation, Döhle bodies, and an elevated leukocyte alkaline phosphatase; circulating myeloblasts were observed but did not exceed 2% of the leukocytes. Nuclear segmentation abnormalities consisting of hyposegmentation, hypersegmentation, and ring nuclei were noted but were not a prominent finding. A leukoerythroblastosis was present in 54% of patients. No consistent effect on cell lines other than neutrophils was found. A monocytosis was present in 12 patients, a transient lymphocytosis in 2 and an eosinophilia in 1. No effect was evident on basophils. The morphologic changes in the neutrophils in the bone marrow specimens were most pronounced in the early period of growth factor therapy with a relative neutrophil hyperplasia with a marked increase in promyelocytes and myelocytes. With increasing duration of therapy, the myeloid to erythroid ratio normalized and the percentage of promyelocytes decreased while myelocytes and band neutrophils increased. Thirteen patients had no response to growth factor. The nonresponding patients were clinically diverse; all bone marrow biopsy specimens in this group were virtually acellular. No differences were noted between G-CSF and GM-CSF.