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BACKGROUND: Although placing patients with acute respiratory failure in a prone (face down) position improves their oxygenation 60 to 70 percent of the time, the effect on survival is not known. METHODS: In a multicenter, randomized trial, we compared conventional treatment (in the supine position) of patients with acute lung injury or the acute respiratory distress syndrome with a predefined strategy of placing patients in a prone position for six or more hours daily for 10 days. We enrolled 304 patients, 152 in each group. RESULTS: The mortality rate was 23.0 percent during the 10-day study period, 49.3 percent at the time of discharge from the intensive care unit, and 60.5 percent at 6 months. The relative risk of death in the prone group as compared with the supine group was 0.84 at the end of the study period (95 percent confidence interval, 0.56 to 1.27), 1.05 at the time of discharge from the intensive care unit (95 percent confidence interval, 0.84 to 1.32), and 1.06 at six months (95 percent confidence interval, 0.88 to 1.28). During the study period the mean (+/-SD) increase in the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen, measured each morning while patients were supine, was greater in the prone than the supine group (63.0+/-66.8 vs. 44.6+/-68.2, P=0.02). The incidence of complications related to positioning (such as pressure sores and accidental extubation) was similar in the two groups. CONCLUSIONS: Although placing patients with acute respiratory failure in a prone position improves their oxygenation, it does not improve survival.

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In a model of acute lung injury, we showed that positive end-expiratory pressure (PEEP) and tidal volume (VT) are interactive variables that determine the extent of lung recruitment, that recruitment occurs across the entire range of total lung capacity, and that superimposed pressure is a key determinant of lung collapse. Aiming to verify if the same rules apply in a clinical setting, we randomly ventilated five ALI/ARDS patients with 10, 15, 20, 30, 35, and 45 cm H2O plateau pressure and 5, 10, 15, and 20 cm H2O of PEEP. For each PEEP-VT condition, we obtained computed tomography at end inspiration and end expiration. We found that recruitment occurred along the entire volume-pressure curve, independent of lower and upper inflection points, and that estimated threshold opening pressures were normally distributed (mode = 20 cm H2O). Recruitment occurred progressively from nondependent to dependent lung regions. Overstretching was not associated with hyperinflation. Derecruitment did not parallel deflation, and estimated threshold closing pressures were normally distributed (mode = 5 cm H2O). End-inspiratory and end-expiratory collapse were correlated, suggesting a plateau-PEEP interaction. When superimposed gravitational pressure exceeded PEEP, end-expiratory collapse increased. We concluded that the rules governing recruitment and derecruitment equally apply in an oleic acid model and in human ALI/ARDS.

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We studied 16 patients with acute lung injury receiving volume-controlled ventilation to assess the relationships between gas exchange and respiratory mechanics before, during, and after 2 h in the prone position. We measured the end-expiratory lung volume (EELV, helium dilution), the total respiratory system (Cst,rs), the lung (Cst,L) and the thoracoabdominal cage (Cst,w) compliances (end-inspiratory occlusion technique and esophageal balloon), the hemodynamics, and gas exchange. In the prone position, PaO2 increased from 103.2 +/- 23.8 to 129.3 +/- 32.9 mm Hg (p < 0.05) without significant changes of Cst,rs and EELV. However, Cst,w decreased from 204.8 +/- 97.4 to 135.9 +/- 52.5 ml/cm H2O (p < 0.01) and the decrease was correlated with the oxygenation increase (r = 0.62, p < 0.05). Furthermore, the greater the baseline supine Cst,w, the greater its decrease in the prone position (r = 0.82, p < 0.01). Consequently, the oxygenation changes in the prone position were predictable from baseline supine Cst,w (r = 0.80, p < 0.01). Returning to the supine position, Cst,rs increased compared with baseline (42.3 +/- 14.4 versus 38.4 +/- 13.7 ml/cm H2O; p < 0.01), mainly because of the lung component (57.5 +/- 25.1 versus 52.4 +/- 23.3 ml/cm H2O; p < 0.01). Thus, (1) baseline Cst,w and its changes may play a role in determining the oxygenation response in the prone position; (2) the prone position improves Cst,rs and Cst,L when the supine position is resumed.

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We compared the performance of a heparinized hollow fiber artificial lung (Medtronic, Minimax) featuring standard hollow fibers (Group A) and experimental hollow fibers with a smaller pore size (Group B). Four sheep in each group underwent a veno-venous bypass for 72 hours. Every 6 hours, at 3 different blood flow rates (BFr) (400, 800, 1200 ml/min), at a constant gas flow rate (Gfr = 4 L/min), and at a constant blood inlet PCO2 (45-55 mmHg), we measured the oxygenation performance (O2 transfer = VO2 and blood outlet PO2 = PO2out), CO2 removal (CO2 transfer = VCO2 and PCO2 outlet = PCO2out) and pressure drop across the device (delta P). A total of about 50 measurement sets were obtained for each group at different time points and blood flow rates. Both groups showed a good oxygenation performance (PO2out always higher than 200 mmHg) and no differences were observed between the two groups (at 1200 ml/min BFr, the average VO2 of all time points was 47 +/- 15 ml/min in group A and 44 +/- 11 ml/min in group B, mean +/- SD, NS). During the first 24 hours, the VCO2 was higher in Group B than in Group A at each BFr (at 1200 ml/min BFr, 81 +/- 18 vs 67 +/- 20 ml/min, p < 0.01), while no differences were observed during the subsequent 48 hours. Throughout the entire experiment, VCO2 increased with increasing BFr in both groups, (in group B, from 43 +/- 14 ml/min at 400 ml/min BFr, to 73 +/- 17 ml/min at 1200 ml/min BFr, average of all time points, p < 0.01). In both groups the delta P increased with the increasing BFr, but it was lower in Group B than in Group A at BFr 800 and 1200 ml/min (at 1200 ml/min BFr, 51 +/- 15 mmHg vs 65 +/- 17 mmHg, p < 0.01), and remained stable for the entire experimental period.

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Single lung transplantation (SLT) is now successfully used in patients with severe emphysema. Mechanical imbalance between the native emphysematous and the healthy transplanted lung can be easily managed, unless severe graft failure occurs, leading to acute respiratory failure. Emergency retransplantation has been used in this setting, since the conventional approach to adult respiratory distress syndrome (ARDS) (mechanical ventilation and positive end-expiratory pressure [PEEP]) fails, due to the mechanical discrepancy between the two lungs. We describe two cases of severe graft failure following SLT in emphysema patients that were successfully treated with prolonged independent respiratory treatment. Mechanical ventilation and PEEP were applied to the failing transplanted lung while the native emphysematous lung was maintained on spontaneous breathing to avoid hyperexpansion and barotrauma. The independent lung respiratory treatment lasted 35 and 25 days, respectively: to our knowledge, these are among the longest-lasting independent respiratory treatments reported. The management was simplified by the early use of a double-lumen tracheostomy cannula as an alternative to orotracheal double lumen tube.

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Persistent pulmonary hypertension of the neonate (PPHN), described initially by Gersony in 1969 as persistent foetal circulation (PFC syndrome), results from a flawed transition from foetal to extrauterine pulmonary circulation. It is primarily characterised by persistence of, or return to, the suprasystemic pulmonary vascular resistance and pressure normally found in the foetus. The increased pulmonary pressure causes right to left shunting through the ductus arteriosus or the foramen ovale, or both. The resulting hypoxaemia and acidosis may produce further pulmonary vasoconstriction and lead to a vicious cycle of shunting, hypoxia and acidosis. Infants with a wide variety of underlying clinical conditions develop PPHN. This condition is reversible, but can cause very severe and unrelenting respiratory failure and ultimate death when uncontrolled. Although vasodilating agents, such as tolazoline, have been used with variable success in the treatment of PPHN, a generally acceptable therapy is still lacking. We report here the use of prostacyclin (epoprostenol, PGI2) in two infants with severe and refractory hypoxaemia secondary to pulmonary vasoconstriction.

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We describe the combined use of mask CPAP (continuous positive airway pressure) and minitracheotomy as an alternative to conventional endotracheal intubation in 3 patients requiring CPAP, secretion removal and diagnostic procedures such as bronchoalveolar lavage and bronchial cultures. These requirements were fulfilled with the combined technique approach, thus preserving glottic function and avoiding the disadvantages of endotracheal intubation of tracheotomy. This approach seems particularly suitable in the treatment of immunocompromised patients because of its reduced invasiveness.

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Ten patients with parenchymal acute respiratory failure (ARF) underwent computed tomography (CT) scans while in the supine and prone positions. At equal levels of positive end-expiratory pressure, the authors measured the changes of CT density in dorsal and ventral basilar lung regions induced by the change of position as well as alterations of gas exchange. The level of venous admixture did not change with body position. The CT scan image of each lung was fractionated into ten levels from dorsal to ventral, each constituting 10% of the lung height. After measuring each lung fraction, the volume, the average CT number, its frequency distribution, and the expected normal value, we computed the lung tissue mass, the excess tissue mass, and the fraction of normally inflated tissue (excess tissue mass = amount of "tissue," which includes edema, cells, and blood in excess of the expected normal value). We also estimated the superimposed hydrostatic pressure on each lung region. We found that the excess lung tissue mass is independent of position. However, in patients in the supine position, lung CT density increased and regional inflation decreased from ventral to dorsal, suggesting progressive deflation of gas-containing alveoli along the gravity gradient. A similar ventral-dorsal deflation pattern occurred within 10 min in patients in the prone position. We conclude that the lung in patients with ARF behaves like an elastic body with a diffusely increased mass; dependent lung regions are compressed by the pressure of overlying structures.(ABSTRACT TRUNCATED AT 250 WORDS)

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Twenty-two patients with acute respiratory failure underwent lung computed tomography (CT) and physiological measurements at 5, 10, and 15 cm H2O positive end-expiratory pressure (PEEP) to investigate the relationship between morphology and function. Lung densities were primarily concentrated in the dependent regions. From the frequency distribution of CT numbers (difference in x-ray attenuation between water and lung) and lung gas volume measurements the authors obtained a quantitative estimate of normally inflated, poorly inflated, and non-inflated lung tissue weight. This estimated average lung weight was increased twofold above normal and excess lung weight correlated with the mean pulmonary artery pressure (P less than 0.01). Venous admixture correlated with the non-inflated tissue mass (P less than 0.01). Increasing PEEP caused progressive clearing of radiographic densities and increased the mass of normally inflated tissue (anatomic recruitment), while reducing venous admixture. The cardiac index decreased after increasing PEEP while oxygen delivery was unchanged. The authors conclude that CT scan lung density and oxygen exchange efficiency are correlated; the main effect of augmenting PEEP is to recruit perfused alveolar units that were previously collapsed.

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The gas exchange and hemodynamics were evaluated before, during, and after a two-hour period of prone position in 13 moderate-severe ARDS patients. Lung computerized tomography was obtained in both the supine and prone positions in two of these patients. Average arterial oxygenation improved after prone positioning (p less than 0.01). A PaO2 improvement of at least 10 mm Hg after 30 minutes of prone position was used as a criterion to discriminate between responders and nonresponders to the postural change. Eight patients met the "responders" group criterion, and in the five nonresponder patients, the PaO2 did not change significantly throughout the study. Computerized tomograms in the prone position showed disappearance of posterobasal densities and appearance of new densities in the anterior regions, in both patients studied. One of these was a responder, the other a nonresponder. A brief test period in prone position is indicated in ARDS patients to identify those who may benefit from this postural treatment. The definite mechanism of the arterial oxygenation improvement observed remains to be clarified.

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Functional residual capacity (FRC) was measured before and after induction of anaesthesia for jejunoileal bypass surgery in 30 morbidly obese patients. The onset of anaesthesia was associated with a 51% reduction in FRC from 2.2 litre to 1.0 litre. Eighteen of the patients were investigated more extensively; in these subjects FRC was reduced below the control values of residual volume (RV) with the onset of anaesthesia, but recovered towards baseline after laparotomy incision. Reduction in FRC is related to baseline vital capacity (VC) and FRC and is much greater than that reported for patients of normal weight.

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The pulmonary effects of hyperventilation following infusion of sodium salicylate into the cisterna magna was studied in 16 spontaneously breathing adult sheep. We found a fall in PaO2, a decrease in the static compliance of the respiratory system, abnormal chest roentgenographic films, and grossly abnormal lungs following 3.5 to 13 h of hyperventilation. A control group of 15 sheep (10 sheep similarly injected with sodium salicylate, but then sedated and paralyzed and ventilated at normal tidal volume and respiratory rate on a mechanical ventilator, and 5 sheep infused with saline alone and breathing spontaneously) showed no pulmonary or arterial blood gas abnormalities. We conclude that prolonged hyperventilation under the conditions of this experiment precipitated events that resulted in acute lung injury.

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We explored the pulmonary effects of continuous mechanical ventilation (MV) at a peak inspiratory pressure of 50 cm H2O in healthy, paralyzed, and anesthetized adult sheep during a period of 48 h. The 9 control sheep (Group A) were ventilated with 40% oxygen at a tidal volume of about 10 ml/kg and a peak inspiratory pressure of 15 to 20 cm H2O. All these animals remained stable throughout the 48 h of MV with no change in lung function. The 7 sheep in Group B were ventilated with 40% oxygen using a pressure-controlled ventilator at 50 cm H2O peak inspiratory pressure, at a VT of 50 to 70 ml/kg. All sheep in Group B developed severe respiratory failure and died or were killed within 2 to 35 h, and showed parenchymal consolidation at autopsy. The 9 sheep in Group C were ventilated as in Group B, except that 3.8% CO2 was added to the inspired gases: the Group C animals deteriorated more slowly, with little change in PaO2 but with a severely reduced FRC, VT, total static lung compliance, and grossly abnormal lungs at autopsy. We conclude that in this model, mechanical ventilation at peak airway pressure of 50 cm H2O will lead to progressive impairment in pulmonary mechanics, lung function, acute respiratory failure, and alveolar cellular dysfunction, as demonstrated by highly abnormal minimal surface tension values of saline lung lavage fluid in both study groups.

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The volume/pressure (V/P) curve of the total respiratory system in paralysed patients is drawn assuming that volume changes of the respiratory system (delta V resp) equals volume displacement of the measuring apparatus (delta V syr), usually a supersyringe. However, in 93 VP curves we found that O2 removed from the lung-syringe system during the procedure (proportional to the time) largely exceeds the CO2 added to the lung-syringe system (delta V gas). This results in a net loss of volume from the system (delta V resp less than delta V-syr). Deflation compliance, hysteresis area and ratio are significantly affected by this phenomenon. Inflation compliance is less influenced by delta V gas, partially compensated by the intrapulmonary gas expansion due to the temperature changes. We conclude that the parameters computed on the deflation limb of V/P curve are misleading if proper correction of the volume scale is not introduced.

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Forty-three patients were entered in an uncontrolled study designed to evaluate extracorporeal membrane lung support in severe acute respiratory failure of parenchymal origin. Most of the metabolic carbon dioxide production was cleared through a low-flow venovenous bypass. To avoid lung injury from conventional mechanical ventilation, the lungs were kept "at rest" (three to five breaths per minute) at a low peak airway pressure of 35 to 45 cm H2O (3.4 to 4.4 kPa). The entry criteria were based on gas exchange under standard ventilatory conditions (expected mortality rate, greater than 90%). Lung function improved in thirty-one patients (72.8%), and 21 patients (48.8%) eventually survived. The mean time on bypass for the survivors was 5.4 +/- 3.5 days. Improvement in lung function, when present, always occurred within 48 hours. Blood loss averaged 1800 +/- 850 mL/d. No major technical accidents occurred in more than 8000 hours of perfusion. Extracorporeal carbon dioxide removal with low-frequency ventilation proved a safe technique, and we suggest it as a valuable tool and an alternative to treating severe acute respiratory failure by conventional means.

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