Background Excessive tidal volume, respiratory rate, and positive end-expiratory pressure (PEEP) are all potential causes of ventilator-induced lung injury, and all contribute to a single variable: the mechanical power. The authors aimed to determine whether high tidal volume or high respiratory rate or high PEEP at iso-mechanical power produce similar or different ventilator-induced lung injury. Methods Three ventilatory strategies—high tidal volume (twice baseline functional residual capacity), high respiratory rate (40 bpm), and high PEEP (25 cm H 2 O)—were each applied at two levels of mechanical power (15 and 30 J/min) for 48 h in six groups of seven healthy female piglets (weight: 24.2 ± 2.0 kg, mean ± SD). Results At iso-mechanical power, the high tidal volume groups immediately and sharply increased plateau, driving pressure, stress, and strain, which all further deteriorated with time. In high respiratory rate groups, they changed minimally at the beginning, but steadily increased during the 48 h. In contrast, after a sudden huge increase, they decreased with time in the high PEEP groups. End-experiment specific lung elastance was 6.5 ± 1.7 cm H 2 O in high tidal volume groups, 10.1 ± 3.9 cm H 2 O in high respiratory rate groups, and 4.5 ± 0.9 cm H 2 O in high PEEP groups. Functional residual capacity decreased and extravascular lung water increased similarly in these three categories. Lung weight, wet-to-dry ratio, and histologic scores were similar, regardless of ventilatory strategies and power levels. However, the alveolar edema score was higher in the low power groups. High PEEP had the greatest impact on hemodynamics, leading to increased need for fluids. Adverse events (early mortality and pneumothorax) also occurred more frequently in the high PEEP groups. Conclusions Different ventilatory strategies, delivered at iso-power, led to similar anatomical lung injury. The different systemic consequences of high PEEP underline that ventilator-induced lung injury must be evaluated in the context of the whole body. Editor’s Perspective What We Already Know about This Topic Ventilator-induced lung injury results from a complex interaction of physical variables involved in mechanical ventilation (tidal volume, respiratory rate [RR], positive end-expiratory pressure [PEEP], driving pressure, resistances, and flow). Although each variable has been previously studied in isolation, their overall effects within the recent construct of mechanical power (the product of change of lung volume and absolute pressure) delivered to the lung per unit of time (J/min) remains controversial. Previous animal studies have demonstrated mechanical power thresholds related to ventilator-induced lung injury, the adverse effects of high respiratory rate on low tidal volume ventilation in ventilator-induced lung injury, and the adverse effects of PEEP above a certain mechanical power threshold on ventilator-induced lung injury. What This Article Tells Us That Is New The authors studied 42 healthy sedated pigs ventilated in the prone position for 48 h, controlling anesthetic level, hemodynamics, and temperature. Three ventilatory strategies (high tidal volume, high RR, or high PEEP) were studied at two levels of mechanical power (15 or 30 J/min, regulated by manipulating the other component variables). Measurements included hemodynamics, lung mechanics, gas exchange, lung histology, and lung weight. High PEEP, as expected, had the greatest adverse hemodynamic impact. For all strategies, similar degrees of histologic lung injury and extravascular lung water accumulation occurred by 48 h, despite different time courses. Paradoxically, a greater degree of alveolar edema occurred at lower mechanical power, perhaps explained by different hemodynamic patterns that favored or reduced extravascular fluid accumulation. These data suggest that over time, the integrated effects resulting from high tidal volume, high RR, or high PEEP are more important than the direct and immediate consequence of any one of them alone. Ventilator-induced lung injury should be considered holistically in the context of whole-body physiology rather than as an isolated effect on the lung alone.

This review focuses on the use of veno-venous extracorporeal membrane oxygenation for respiratory failure across all blood flow ranges. Starting with a short overview of historical development, aspects of the physiology of gas exchange ( i.e. , oxygenation and decarboxylation) during extracorporeal circulation are discussed. The mechanisms of phenomena such as recirculation and shunt playing an important role in daily clinical practice are explained. Treatment of refractory and symptomatic hypoxemic respiratory failure ( e.g. , acute respiratory distress syndrome [ARDS]) currently represents the main indication for high-flow veno-venous-extracorporeal membrane oxygenation. On the other hand, lower-flow extracorporeal carbon dioxide removal might potentially help to avoid or attenuate ventilator-induced lung injury by allowing reduction of the energy load ( i.e. , driving pressure, mechanical power) transmitted to the lungs during mechanical ventilation or spontaneous ventilation. In the latter context, extracorporeal carbon dioxide removal plays an emerging role in the treatment of chronic obstructive pulmonary disease patients during acute exacerbations. Both applications of extracorporeal lung support raise important ethical considerations, such as likelihood of ultimate futility and end-of-life decision-making. The review concludes with a brief overview of potential technical developments and persistent challenges.

Background There is a lack of consensus on how to manage anticoagulation during veno-venous extracorporeal membrane oxygenation, including antithrombin monitoring and supplementation. The authors’ aim was to determine current practice in a large number of extracorporeal membrane oxygenation centers around the world. Methods This was an electronic survey disseminated in 2018 to directors and coordinators of extracorporeal membrane oxygenation centers as well as to extracorporeal membrane oxygenation experts. Participating centers were classified according to some covariates that may affect practice, including 2017 gross national income per capita, primary patient population, and annual extracorporeal membrane oxygenation patient volume. Results The authors analyzed 273 unique responses from 50 countries. Systemic anticoagulation was routinely prescribed in 264 (96.7%) centers, with unfractionated heparin being the drug of choice in 255 (96.6%) of them. The preferred method to monitor anticoagulation was activated partial thromboplastin time in 114 (41.8%) centers, activated clotting time in 82 (30.0%) centers, and anti-factor Xa activity in 62 (22.7%) centers. Circulating antithrombin activity was routinely monitored in 133 (48.7%) centers. Antithrombin supplementation was routinely prescribed in 104 (38.1%) centers. At multivariable analyzes, routine antithrombin supplementation was associated with national income, being less likely in lower- than in higher-income countries (odds ratio, 0.099 [95% CI, 0.022 to 0.45]; P = 0.003); with primary patient population being more frequent in mixed (odds ratio, 2.73 [1.23 to 6.0]; P = 0.013) and pediatric-only centers (odds ratio, 6.3 [2.98 to 13.2]; P < 0.001) than in adult-only centers; but not with annual volume of extracorporeal membrane oxygenation cases, being similarly common in smaller and larger centers (odds ratio, 1.00 [0.48 to 2.08]; P = 0.997). Conclusions There is large practice variation among institutions regarding anticoagulation management and antithrombin supplementation during veno-venous extracorporeal membrane oxygenation. The paucity of prospective studies and differences across institutions based on national income and primary patient population may contribute to these findings. Editor’s Perspective What We Already Know about This Topic Managing anticoagulation during veno-venous extracorporeal membrane oxygenation varies around the world among clinical sites. Understanding clinical practice is important when developing multicenter clinical studies. What This Article Tells Us That Is New Based on 273 responses from 50 countries, unfractionated heparin is used in 96.6% of centers, with partial thromboplastin time monitoring in 41.8%, activated clotting time in 30.0%, and anti-factor Xa activity in 22.7% of centers. Antithrombin is monitored in 48.7% of centers and actively repleted in 38.1% of centers, mainly in high-income regions and in pediatric patients.

Editor’s Perspective What We Already Know about This Topic Extracorporeal membrane oxygenation is used in severe acute respiratory distress syndrome; whereas the long-term complications among survivors of acute respiratory distress syndrome treated without extracorporeal membrane oxygenation are well described, the status of extracorporeal membrane oxygenation survivors is poorly understood What This Article Tells Us That Is New In a single-center cohort of acute respiratory distress syndrome survivors, management with ( vs . without) extracorporeal membrane oxygenation resulted in similar survival at 1 yr, pulmonary function, and computed tomography lung imaging, but less impairment in quality of life Background Survivors of acute respiratory distress syndrome (ARDS) have long-term impairment of pulmonary function and health-related quality of life, but little is known of outcomes of ARDS survivors treated with extracorporeal membrane oxygenation. The aim of this study was to compare long-term outcomes of ARDS patients treated with or without extracorporeal membrane oxygenation. Methods A prospective, observational study of adults with ARDS (January 2013 to December 2015) was conducted at a single center. One year after discharge, survivors underwent pulmonary function tests, computed tomography of the chest, and health-related quality-of-life questionnaires. Results Eighty-four patients (34 extracorporeal membrane oxygenation, 50 non–extracorporeal membrane oxygenation) were studied; both groups had similar characteristics at baseline, but comorbidity was more common in non–extracorporeal membrane oxygenation (23 of 50 vs . 4 of 34, 46% vs . 12%, P < 0.001), and severity of hypoxemia was greater in extracorporeal membrane oxygenation (median Pa o 2 / Fio 2 72 [interquartile range, 50 to 103] vs . 114 [87 to 133] mm Hg, P < 0.001) and respiratory compliance worse. At 1 yr, survival was similar (22/33 vs . 28/47, 66% vs. 59%; P = 0.52), and pulmonary function and computed tomography were almost normal in both groups. Non–extracorporeal membrane oxygenation patients had lower health-related quality-of-life scores and higher rates of posttraumatic stress disorder. Conclusions Despite more severe respiratory failure at admission, 1-yr survival of extracorporeal membrane oxygenation patients was not different from that of non–extracorporeal membrane oxygenation patients; each group had almost full recovery of lung function, but non–extracorporeal membrane oxygenation patients had greater impairment of health-related quality of life.

EDITOR’S PERSPECTIVE What We Already Know about This Topic Positive end-expiratory pressure protects against ventilation-induced lung injury by improving homogeneity of ventilation, but positive end-expiratory pressure contributes to the mechanical power required to ventilate the lung What This Article Tells Us That Is New This in vivo study (36 pigs mechanically ventilated in the prone position) suggests that low levels of positive end-expiratory pressure reduce injury associated with atelectasis, and above a threshold level of power, positive end-expiratory pressure causes lung injury and adverse hemodynamics Background Positive end-expiratory pressure is usually considered protective against ventilation-induced lung injury by reducing atelectrauma and improving lung homogeneity. However, positive end-expiratory pressure, together with tidal volume, gas flow, and respiratory rate, contributes to the mechanical power required to ventilate the lung. This study aimed at investigating the effects of increasing mechanical power by selectively modifying its positive end-expiratory pressure component. Methods Thirty-six healthy piglets (23.3 ± 2.3 kg) were ventilated prone for 50 h at 30 breaths/min and with a tidal volume equal to functional residual capacity. Positive end-expiratory pressure levels (0, 4, 7, 11, 14, and 18 cm H 2 O) were applied to six groups of six animals. Respiratory, gas exchange, and hemodynamic variables were recorded every 6 h. Lung weight and wet-to-dry ratio were measured, and histologic samples were collected. Results Lung mechanical power was similar at 0 (8.8 ± 3.8 J/min), 4 (8.9 ± 4.4 J/min), and 7 (9.6 ± 4.3 J/min) cm H 2 O positive end-expiratory pressure, and it linearly increased thereafter from 15.5 ± 3.6 J/min (positive end-expiratory pressure, 11 cm H 2 O) to 18.7 ± 6 J/min (positive end-expiratory pressure, 14 cm H 2 O) and 22 ± 6.1 J/min (positive end-expiratory pressure, 18 cm H 2 O). Lung elastances, vascular congestion, atelectasis, inflammation, and septal rupture decreased from zero end-expiratory pressure to 4 to 7 cm H 2 O ( P < 0.0001) and increased progressively at higher positive end-expiratory pressure. At these higher positive end-expiratory pressure levels, striking hemodynamic impairment and death manifested (mortality 0% at positive end-expiratory pressure 0 to 11 cm H 2 O, 33% at 14 cm H 2 O, and 50% at 18 cm H 2 O positive end-expiratory pressure). From zero end-expiratory pressure to 18 cm H 2 O, mean pulmonary arterial pressure (from 19.7 ± 5.3 to 32.2 ± 9.2 mmHg), fluid administration (from 537 ± 403 to 2043 ± 930 ml), and noradrenaline infusion (0.04 ± 0.09 to 0.34 ± 0.31 μg · kg −1 · min −1 ) progressively increased ( P < 0.0001). Lung weight and lung wet-to-dry ratios were not significantly different across the groups. The lung mechanical power level that best discriminated between more versus less severe damage was 13 ± 1 J/min. Conclusions Less than 7 cm H 2 O positive end-expiratory pressure reduced atelectrauma encountered at zero end-expiratory pressure. Above a defined power threshold, sustained positive end-expiratory pressure contributed to potentially lethal lung damage and hemodynamic impairment.

Background We evaluate the clinical feasibility of spontaneous breathing on extracorporeal membrane oxygenation and the interactions between artificial and native lungs in patients bridged to lung transplant or with acute exacerbation of chronic obstructive pulmonary disease (COPD) or acute respiratory distress syndrome. Methods The clinical course of a total of 48 patients was analyzed. Twenty-three of 48 patients were enrolled in the prospective study (nine bridged to lung transplant, six COPD, and eight acute respiratory distress syndrome). The response to the carbon dioxide removal was evaluated in terms of respiratory rate and esophageal pressure swings by increasing (“relief” threshold) and decreasing (“distress” threshold) the extracorporeal membrane oxygenation gas flow, starting from baseline condition. Results Considering all 48 patients, spontaneous breathing extracorporeal membrane oxygenation was performed in 100% bridge to lung transplant (9 of 9 extubated), 86% COPD (5 of 6 extubated), but 27% acute respiratory distress syndrome patients (6 of 8 extubated; P < 0.001) and was maintained for 92, 69, and 38% of the extracorporeal membrane oxygenation days ( P = 0.021), respectively. In all the 23 patients enrolled in the study, gas flow increase (from 2.3 ± 2.2 to 9.2 ± 3.2 l/min) determined a decrease of both respiratory rate (from 29 ± 6 to 8 ± 9 breaths/min) and esophageal pressure swings (from 20 ± 9 to 4 ± 4 cm H 2 O; P < 0.001 for all). All COPD and bridge to lung transplant patients were responders (reached the relief threshold), while 50% of acute respiratory distress syndrome patients were nonresponders. Conclusions Carbon dioxide removal through extracorporeal membrane oxygenation relieves work of breathing and permits extubation in many patients, mainly bridge to lung transplant and COPD. Only few patients with acute respiratory distress syndrome were able to perform the spontaneous breathing trial, and in about 50% of these, removal of large amount of patient’s carbon dioxide production was not sufficient to prevent potentially harmful spontaneous respiratory effort.

Background The ventilator works mechanically on the lung parenchyma. The authors set out to obtain the proof of concept that ventilator-induced lung injury (VILI) depends on the mechanical power applied to the lung. Methods Mechanical power was defined as the function of transpulmonary pressure, tidal volume (TV), and respiratory rate. Three piglets were ventilated with a mechanical power known to be lethal (TV, 38 ml/kg; plateau pressure, 27 cm H 2 O; and respiratory rate, 15 breaths/min). Other groups (three piglets each) were ventilated with the same TV per kilogram and transpulmonary pressure but at the respiratory rates of 12, 9, 6, and 3 breaths/min. The authors identified a mechanical power threshold for VILI and did nine additional experiments at the respiratory rate of 35 breaths/min and mechanical power below (TV 11 ml/kg) and above (TV 22 ml/kg) the threshold. Results In the 15 experiments to detect the threshold for VILI, up to a mechanical power of approximately 12 J/min (respiratory rate, 9 breaths/min), the computed tomography scans showed mostly isolated densities, whereas at the mechanical power above approximately 12 J/min, all piglets developed whole-lung edema. In the nine confirmatory experiments, the five piglets ventilated above the power threshold developed VILI, but the four piglets ventilated below did not. By grouping all 24 piglets, the authors found a significant relationship between the mechanical power applied to the lung and the increase in lung weight ( r 2 = 0.41, P = 0.001) and lung elastance ( r 2 = 0.33, P < 0.01) and decrease in Pa o 2 /F io 2 ( r 2 = 0.40, P < 0.001) at the end of the study. Conclusion In piglets, VILI develops if a mechanical power threshold is exceeded. Abstract Twenty-four anesthetized piglets ventilated with a range of tidal volume and respiratory rate developed widespread lung injury above a threshold of 12 J/min. This finding suggests that mechanical power applied may be taken into account for ventilator-induced lung injury prevention. Supplemental Digital Content is available in the text.

Background: During mechanical ventilation, stress and strain may be locally multiplied in an inhomogeneous lung. The authors investigated whether, in healthy lungs, during high pressure/volume ventilation, injury begins at the interface of naturally inhomogeneous structures as visceral pleura, bronchi, vessels, and alveoli. The authors wished also to characterize the nature of the lesions (collapse vs . consolidation). Methods: Twelve piglets were ventilated with strain greater than 2.5 (tidal volume/end-expiratory lung volume) until whole lung edema developed. At least every 3 h, the authors acquired end-expiratory/end-inspiratory computed tomography scans to identify the site and the number of new lesions. Lung inhomogeneities and recruitability were quantified. Results: The first new densities developed after 8.4 ± 6.3 h (mean ± SD), and their number increased exponentially up to 15 ± 12 h. Afterward, they merged into full lung edema. A median of 61% (interquartile range, 57 to 76) of the lesions appeared in subpleural regions, 19% (interquartile range, 11 to 23) were peribronchial, and 19% (interquartile range, 6 to 25) were parenchymal ( P < 0.0001). All the new densities were fully recruitable. Lung elastance and gas exchange deteriorated significantly after 18 ± 11 h, whereas lung edema developed after 20 ± 11 h. Conclusions: Most of the computed tomography scan new densities developed in nonhomogeneous lung regions. The damage in this model was primarily located in the interstitial space, causing alveolar collapse and consequent high recruitability. Abstract Ventilator-induced lung injury detected as an increased density on computed tomography scan, first occurred at inhomogeneous interfaces, including at the visceral pleura and the subpleural alveolar walls in anesthetized piglets ventilated with a tidal volume/end-expiratory lung volume more than 2.5. New lung densities were found within 8 h of the ventilation, and their number increased exponentially up to 15 h. Lung elastance and gas exchange deteriorated significantly after 18 h, and full lung edema developed after 20 h. Supplemental Digital Content is available in the text.

Background: It has been suggested that higher positive end-expiratory pressure (PEEP) should be used only in patients with higher lung recruitability. In this study, the authors investigated the relationship between the recruitability and the PEEP necessary to counteract the compressive forces leading to lung collapse. Methods: Fifty-one patients with acute respiratory distress syndrome (7 mild, 33 moderate, and 11 severe) were enrolled. Patients underwent whole-lung computed tomography (CT) scan at 5 and 45 cm H 2 O. Recruitability was measured as the amount of nonaerated tissue regaining inflation from 5 to 45 cm H 2 O. The compressive forces (superimposed pressure) were computed as the density times the sternum-vertebral height of the lung. CT-derived PEEP was computed as the sum of the transpulmonary pressure needed to overcome the maximal superimposed pressure and the pleural pressure needed to lift up the chest wall. Results: Maximal superimposed pressure ranged from 6 to 18 cm H 2 O, whereas CT-derived PEEP ranged from 7 to 28 cm H 2 O. Median recruitability was 15% of lung parenchyma (interquartile range, 7 to 21%). Maximal superimposed pressure was weakly related with lung recruitability ( r 2 = 0.11, P = 0.02), whereas CT-derived PEEP was unrelated with lung recruitability ( r 2 = 0.0003, P = 0.91). The maximal superimposed pressure was 12 ± 3, 12 ± 2, and 13 ± 1 cm H 2 O in mild, moderate, and severe acute respiratory distress syndrome, respectively, ( P = 0.0533) with a corresponding CT-derived PEEP of 16 ± 5, 16 ± 5, and 18 ± 5 cm H 2 O ( P = 0.48). Conclusions: Lung recruitability and CT scan–derived PEEP are unrelated. To overcome the compressive forces and to lift up the thoracic cage, a similar PEEP level is required in higher and lower recruiters (16.8 ± 4 vs. 16.6 ± 5.6, P = 1).

Background Tidal hyperinflation may occur in patients with acute respiratory distress syndrome who are ventilated with a tidal volume (VT) of 6 ml/kg of predicted body weight develop a plateau pressure (PPLAT) of 28 < or = PPLAT < or = 30 cm H2O. The authors verified whether VT lower than 6 ml/kg may enhance lung protection and that consequent respiratory acidosis may be managed by extracorporeal carbon dioxide removal. Methods PPLAT, lung morphology computed tomography, and pulmonary inflammatory cytokines (bronchoalveolar lavage) were assessed in 32 patients ventilated with a VT of 6 ml/kg. Data are provided as mean +/- SD or median and interquartile (25th and 75th percentile) range. In patients with 28 < or = PPLAT < or = 30 cm H2O (n = 10), VT was reduced from 6.3 +/- 0.2 to 4.2 +/- 0.3 ml/kg, and PPLAT decreased from 29.1 +/- 1.2 to 25.0 +/- 1.2 cm H2O (P < 0.001); consequent respiratory acidosis (Paco2 from 48.4 +/- 8.7 to 73.6 +/- 11.1 mmHg and pH from 7.36 +/- 0.03 to 7.20 +/- 0.02; P < 0.001) was managed by extracorporeal carbon dioxide removal. Lung function, morphology, and pulmonary inflammatory cytokines were also assessed after 72 h. Results Extracorporeal assist normalized Paco2 (50.4 +/- 8.2 mmHg) and pH (7.32 +/- 0.03) and allowed use of VT lower than 6 ml/kg for 144 (84-168) h. The improvement of morphological markers of lung protection and the reduction of pulmonary cytokines concentration (P < 0.01) were observed after 72 h of ventilation with VT lower than 6 ml/kg. No patient-related complications were observed. Conclusions VT lower than 6 ml/Kg enhanced lung protection. Respiratory acidosis consequent to low VT ventilation was safely and efficiently managed by extracorporeal carbon dioxide removal.

Background The authors studied the effects of the beach chair (BC) position, 10 cm H2O positive end-expiratory pressure (PEEP), and pneumoperitoneum on respiratory function in morbidly obese patients undergoing laparoscopic gastric banding. Methods The authors studied 20 patients (body mass index 42 +/- 5 kg/m2) during the supine and BC positions, before and after pneumoperitoneum was instituted (13.6 +/- 1.2 mmHg). PEEP was applied during each combination of position and pneumoperitoneum. The authors measured elastance (E,rs) of the respiratory system, end-expiratory lung volume (helium technique), and arterial oxygen tension. Pressure-volume curves were also taken (occlusion technique). Patients were paralyzed during total intravenous anesthesia. Tidal volume (10.5 +/- 1 ml/kg ideal body weight) and respiratory rate (11 +/- 1 breaths/min) were kept constant throughout. Results In the supine position, respiratory function was abnormal: E,rs was 21.71 +/- 5.26 cm H2O/l, and end-expiratory lung volume was 0.46 +/- 0.1 l. Both the BC position and PEEP improved E,rs (P < 0.01). End-expiratory lung volume almost doubled (0.83 +/- 0.3 and 0.85 +/- 0.3 l, BC and PEEP, respectively; P < 0.01 vs. supine zero end-expiratory pressure), with no evidence of lung recruitment (0.04 +/- 0.1 l in the supine and 0.07 +/- 0.2 in the BC position). PEEP was associated with higher airway pressures than the BC position (22.1 +/- 2.01 vs. 13.8 +/- 1.8 cm H2O; P < 0.01). Pneumoperitoneum further worsened E,rs (31.59 +/- 6.73; P < 0.01) and end-expiratory lung volume (0.35 +/- 0.1 l; P < 0.01). Changes of lung volume correlated with changes of oxygenation (linear regression, R2 = 0.524, P < 0.001) so that during pneumoperitoneum, only the combination of the BC position and PEEP improved oxygenation. Conclusions The BC position and PEEP counteracted the major derangements of respiratory function produced by anesthesia and paralysis. During pneumoperitoneum, only the combination of the two maneuvers improved oxygenation.

Background The authors propose that for a moderate reduction of perfusion during progressive irreversible ischemia, oxygen extraction increases to maintain aerobic metabolism, and arteriojugular oxygen difference (AJDo2) increases. Because of reduced carbon dioxide washout, venoarterial difference in carbon dioxide tension (DPco2) increases, with no change in the DPco2/AJDo2 ratio. With further reduction of cerebral perfusion, the aerobic metabolism will begin to decrease, AJDo2 will decrease while DPco2 will continue to increase, and the ratio will increase. When brain infarction develops, the metabolism will be abated, no oxygen will be consumed, and no carbon dioxide will be produced. Methods The authors studied 12 patients with acute cerebral damage that evolved to brain death and collected intermittent arterial and jugular blood samples. Results Four patterns were observed: (1) AJDo2 of 4.1 +/- 0.7 vol%, DPco2 of 6.5 +/- 1.9 mmHg, and a ratio of 1.55 +/- 0.3 with cerebral perfusion pressure of 62.5 +/- 13.4 mmHg; (2) a coupled increase of AJDo2 (5.8 +/- 0.7 vol%) and DPco2 (10.1 +/- 1.0 mmHg) with no change in ratio (1.92 +/- 0.14) and cerebral perfusion pressure (57.9 +/- 5.8 mmHg); (3) AJDo2 of 4.7 +/- 0.4 vol% with an increase in DPco2 (11.8 +/- 1 mmHg) and correspondingly higher ratio (2.7 +/- 0.2); in this phase, cerebral perfusion pressure was 39.7 +/- 10.5 mmHg; (4) immediately before diagnosis of brain death (cerebral perfusion pressure, 17 +/- 10.4 mmHg), there was a decrease of AJDo2 (1.1 +/- 0.1 vol%) and of DPco2 (5.3 +/- 0.6 mmHg) with a further ratio increase (5.1 +/- 0.8). Conclusions Until compensatory mechanisms are effective, AJDo2 and DPco2 remain coupled. However, when the brain's ability to compensate for reduced oxygen delivery is exceeded, the ratio of DPco2 to AJDo2 starts to increase.

Background Morbidly obese patients, during anesthesia and paralysis, experience more severe impairment of respiratory mechanics and gas exchange than normal subjects. The authors hypothesized that positive end-expiratory pressure (PEEP) induces different responses in normal subjects (n = 9; body mass index < 25 kg/m2) versus obese patients (n = 9; body mass index > 40 kg/m2). Methods The authors measured lung volumes (helium technique), the elastances of the respiratory system, lung, and chest wall, the pressure-volume curves (occlusion technique and esophageal balloon), and the intraabdominal pressure (intrabladder catheter) at PEEP 0 and 10 cm H2O in paralyzed, anesthetized postoperative patients in the intensive care unit or operating room after abdominal surgery. Results At PEEP 0 cm H2O, obese patients had lower lung volume (0.59 +/- 0.17 vs. 2.15 +/- 0.58 l [mean +/- SD], P < 0.01); higher elastances of the respiratory system (26.8 +/- 4.2 vs. 16.4 +/- 3.6 cm H2O/l, P < 0.01), lung (17.4 +/- 4.5 vs. 10.3 +/- 3.2 cm H2O/l, P < 0.01), and chest wall (9.4 +/- 3.0 vs. 6.1 +/- 1.4 cm H2O/l, P < 0.01); and higher intraabdominal pressure (18.8 +/-7.8 vs. 9.0 +/- 2.4 cm H2O, P < 0.01) than normal subjects. The arterial oxygen tension was significantly lower (110 +/- 30 vs. 218 +/- 47 mmHg, P < 0.01; inspired oxygen fraction = 50%), and the arterial carbon dioxide tension significantly higher (37.8 +/- 6.8 vs. 28.4 +/- 3.1, P < 0.01) in obese patients compared with normal subjects. Increasing PEEP to 10 cm H2O significantly reduced elastances of the respiratory system, lung, and chest wall in obese patients but not in normal subjects. The pressure-volume curves were shifted upward and to the left in obese patients but were unchanged in normal subjects. The oxygenation increased with PEEP in obese patients (from 110 +/-30 to 130 +/- 28 mmHg, P < 0.01) but was unchanged in normal subjects. The oxygenation changes were significantly correlated with alveolar recruitment (r = 0.81, P < 0.01). Conclusions During anesthesia and paralysis, PEEP improves respiratory function in morbidly obese patients but not in normal subjects.