Oxygenation In Acute Lung Injury Research Articles

Robust closed-loop control of systemic oxygenation in acute lung injury

Tight control of systemic oxygenation is a key component of mechanical ventilation of critically ill patients. Yet, closed-loop control remains challenging due to the non-linear, uncertain, and time-varying relationship between the inspired oxygen and the resulting patient’s oxygen saturation, especially in cases of acute lung injury. This paper uses a Hammerstein model to combine a clinically validated static model incorporating ventilation-to-perfusion mismatch with uncertain linear dynamics to synthesize a robust closed-loop controller for regulating systemic oxygenation in subjects with acute lung injury. Data from an experimental lung injury model in five pigs, in combination with data augmentation, allowed modeling of the uncertainty in the system. Subsequently, gain-scheduled proportional–integral controllers were designed using the mixed-sensitivity H∞ approach. The resulting closed-loop systems were analyzed for robust stability, and the performance was evaluated in a thousand synthetically generated subjects spanning the overall parameter space in various combinations. A mean rise time of less than three minutes was achieved for recovering from the severely hypoxemic state for simulated subjects with a range of ventilation-to-perfusion mismatch and arterial acid–base status. Furthermore, the results from a pilot animal experiment matched the simulated results well, and the system could respond to significant disturbances. The system was safe and reliable in both simulations and the pilot animal experiment. The methodological approach for uncertainty modeling and controller synthesis is an essential step toward the practical deployment of closed-loop control of systemic oxygenation in the acutely injured lung.

Pulsed dosed delivery of oxygen in mechanically ventilated pigs with acute lung injury

Acute lung injury (ALI) is a condition that leads to impaired oxygen delivery. We demonstrated previously that using a portable oxygen concentrator (POC) with pulsed dose delivery of oxygen is an alternative option to conserve oxygen while still maintaining adequate oxygen delivery in a mechanical model. We hypothesized that using a modified POC, pulsed dose oxygen delivery can provide adequate oxygenation in an animal model. In a crossover study, we induced ALI in 15 pigs using an oleic acid model. We ventilated the pigs using equipment that is used by Critical Care Air Transport Teams of the US Air Force. We compared oxygen delivery using a POC in both continuous flow and pulsed dose modes, while in both volume-control and pressure-control mechanical ventilation. The PaO(2)/FIO(2) ratios were increased in both the continuous flow and pulsed dose delivery for volume control and pressure control. In volume control, the pulsed dose demonstrated a significant increase in the PaO(2)/FIO(2) ratio (168.8 [96.1] vs. 91.7 [65.4], p = 0.002) compared with continuous flow. However, this was not seen in pressure-control ventilation (89.0 [74.5] vs. 79.1 [65.4], p = 0.67). We were able to demonstrate that oxygen delivery using a POC in mechanically ventilated pigs with ALI is feasible. We were also able to demonstrate that pulsed dose delivery from a POC is superior to continuous flow oxygen delivery for oxygenation in ALI, when using volume control. We propose that this is a safe alternative to conserve oxygen in the transport of critically ill patients.

Positive end-expiratory pressure improves oxygenation inducing ventral-to-dorsal tidal ventilation redistribution: an electrical impedance tomography study

Positive end-expiratory pressure (PEEP) improves oxygenation in acute lung injury (ALI) patients by increasing end-expiratory lung volume (EELV). Electrical impedance tomography (EIT) is a relatively new non-invasive bedside method to monitor regional distribution of tidal ventilation and EELV changes, validated in preclinical studies. We tested EIT as a monitor of PEEP-induced tidal redistribution and EELV changes in ALI patients, and the relationship between EIT parameters and oxygenation.

Effects of Immune-Enhancing Enteral Nutrition on Mortality and Oxygenation in Acute Lung Injury and Acute Respiratory Distress Syndrome: A Meta-Analysis

Purpose The contribution of the immune system to the pathogenesis of acute respiratory distress syndrome (ARDS) has led to a recent interest in the use of immune-enhancing enteral nutrition as a treatment modality. The purpose of this meta-analysis was to determine the effectiveness of immune-enhancing enteral nutrition as compared with standard enteral nutrition, with respect to mortality and change in oxygenation status, in patients with acute lung injury (ALI)/ARDS. Methods A systematic review was conducted of randomized controlled trials comparing immune-enhancing enteral nutrition with standard enteral nutrition in adult intensive care unit (ICU) patients with ALI/ARDS. Data were combined in a meta-analysis with STATA SE version 9.2 (StataCorp) using a random effects model. Results Three studies fulfilled inclusion criteria, totaling 411 patients. These studies demonstrated a statistically significant relative risk (RR) for in-hospital mortality, favoring patients who received immune-enhancing enteral nutrition (RR, 0.58; 95% confidence interval [CI], 0.42-0.79). With respect to change in oxygenation status, a statistically significant standardized mean difference (SMD) was observed at day 4 (SMD, 1.97; 95% CI, 0.27-3.67), favoring the immune-enhancing enteral nutrition group. At study day 7, the SMD did not reach statistical significance (SMD, 1.71; 95% CI, −0.13 to 3.56). Conclusions Oxygenation and mortality benefits of immune-enhancing enteral nutrition in adult ICU patients with ALI/ARDS have been shown in individual trials and meta-analyses. Subsequent clinical trials and meta-analyses are required to fully elucidate the role of immune-enhancing enteral nutrition in this patient population.

Mechanism by Which a Sustained Inflation Can Worsen Oxygenation in Acute Lung Injury

Mechanism by Which a Sustained Inflation Can Worsen Oxygenation in Acute Lung Injury

Pulmonary net release of tissue-type plasminogen activator during porcine primary and secondary acute lung injury.

Tissue-type plasminogen activator (tPA) is a key mediator of fibrinolysis. Matching of pulmonary perfusion and ventilation is a critical denominator of oxygenation in acute lung injury (ALI). This study investigates pulmonary venoarterial plasma tPA gradients in association with acute ALI induced by bronchoalveolar lavage (BAL) and endotoxinemia (ETX). Twenty-one anaesthetized, ventilated pigs were allocated to control (CTRL, n=5), bronchoalveolar saline lavage (BAL, n=8) or infusion of Escherichia coli endotoxin (ETX, n=8). Total tPA was analyzed in plasma (ELISA calibrated for porcine tPA). The inflammatory response was assessed by TNFa levels (ELISA). All variables were assessed at baseline and 2 h following ALI. Bronchoalveolar lavage and ETX induced similar increases in pulmonary shunt whereas pulmonary vascular resistance was significantly more increased in ETX animals. Cardiac output remained stable in BAL animals but decreased in ETX animals. The pulmonary venoarterial tPA plasma gradient increased in ETX animals, yielding a positive pulmonary net flux of tPA, which was absent in BAL animals. TNFalpha levels increased in ETX, but not in BAL, animals. A significant correlation was observed between TNFalpha and tPA plasma levels in ETX animals. All variables remained unchanged in CTRL animals. Plasma changes of tPA levels support a pulmonary release of tPA in early experimental ALI induced by acute ETX but not lavage, and are related to the inflammatory response. Despite increased vascular fibrinolytic capacity in ETX animals, pulmonary dysfunction was not different from BAL animals. The results demonstrate the close relation between inflammation and coagulation in early ALI.

Mechanism by which a sustained inflation can worsen oxygenation in acute lung injury.

Sustained lung inflations (recruitment maneuvers [RMs]) are occasionally used during mechanical ventilation of patients with acute lung injury to restore aeration to atelectatic alveoli. However, RMs do not improve, and may even worsen, gas exchange in a fraction of these patients. In this study, the authors sought to determine the mechanism by which an RM can impair gas exchange in acute lung injury. The authors selected a model of acute lung injury that was unlikely to exhibit sustained recruitment in response to a lung inflation. In five sheep, lung injury was induced by lavage with 0.2% polysorbate 80 in saline. Positron emission tomography and [13N]nitrogen were used to assess regional lung function in dependent, middle, and nondependent lung regions. Physiologic data and positron emission scans were collected before and 5 min after a sustained inflation (continuous positive airway pressure of 50 cm H2O for 30 s). All animals showed greater loss of aeration and higher perfusion and shunting blood flow in the dependent region. After the RM, Pao2 decreased in all animals by 35 +/- 22 mmHg (P < 0.05). This decrease in Pao2 was associated with redistribution of pulmonary blood flow from the middle, more aerated region to the dependent, less aerated region (P < 0.05) and with an increase in the fraction of pulmonary blood flow that was shunted in the dependent region (P < 0.05). Neither respiratory compliance nor aeration of the dependent region improved after the RM. When a sustained inflation does not restore aeration to atelectatic regions, it can worsen oxygenation by increasing the fraction of pulmonary blood flow that is shunted in nonaerated regions.

Regional VA, Q, and VA/Q during PLV: effects of nitroprusside and inhaled nitric oxide.

Partial liquid ventilation (PLV) with high-specific-weight perfluorocarbon liquids has been shown to improve oxygenation in acute lung injury, possibly by redistributing perfusion from dependent, injured regions to nondependent, less injured regions of the lung. Our hypothesis was that during PLV in normal lungs, a shift in perfusion away from dependent lung zones might, in part, be due to vasoconstriction that could be reversed by infusing sodium nitroprusside (NTP). In addition, delivering inhaled NO during PLV should improve gas exchange by further redistributing blood flow to well-ventilated lung regions. To examine this, we used a single transverse-slice positron emission tomography camera to image regional ventilation and perfusion at the level of the heart apex in six supine mechanically ventilated sheep during five conditions: control, PLV, PLV + NTP, and PLV + NO at 10 and 80 ppm. We found that PLV shifted perfusion from dependent to middle regions, and the dependent region demonstrated marked hypoventilation. The vertical distribution of perfusion changed little when high-dose intravenous NTP was added during PLV, and inhaled NO tended to shift perfusion toward better ventilated middle regions. We conclude that PLV shifts perfusion to the middle regions of the lung because of the high specific weight of perflubron rather than vasoconstriction.

Soluble Nitric Oxide Donor and Surfactant Improve Oxygenation and Pulmonary Hypertension in Porcine Lung Injury

Acute lung injury (ALI) is associated with diminished surfactant activity and pulmonary hypertension. NONOates are soluble NO donors which release NO in solution. Intratracheal NONOates reduce pulmonary hypertension and improve oxygenation in ALI. We hypothesized that the pharmacologic properties of NO donors would be unaltered after surfactant admixture in vitro and that aerosolized NONOate activity would be enhanced by surfactant pretreatment in vivo. NO donors were added to saline or surfactant and analyzed for nitrite/nitrate production and aortic ring vasodilation. Surfactant did not alter nitrate/nitrite production or aortic ring vasodilation. A porcine model of ALI with pulmonary hypertension was produced using intravenous oleic acid. Animals were assigned to Surfactant–Saline, Surfactant–NONOate, Saline–Saline, or Saline–NONOate groups. Saline or surfactant was instilled into the trachea, followed by gas exchange, pulmonary function, and hemodynamic measurements. NONOate or saline was then aerosolized, and additional data were collected. Oxygenation was improved in the Surfactant–NONOate group, while pulmonary hypertension was selectively reduced in both NONOate groups. Aerosolized NONOate following surfactant pretreatment improves oxygenation and reduces pulmonary hypertension in ALI.

Influence du drainage bronchique dans l'amélioration des échanges gazeux observée en décubitus ventral au cours du SDRA

Mechanism by which the prone position improves oxygenation in acute lung injury, with NO inhalation or not: role of the bronchial drainage effect. Objectives: A bronchial secretion draining effect is frequently suggested as a mechanism for oxygenation improvement during prone positioning (PP) in patients with acute respiratory distresss syndrome (ARDS). Nevertheless, it has never really been evaluated. The aim of this study was to search for an interrelationship between the volume of the bronchial secretion and the improvement of the PaO 2/FIO 2 ratio during prone positioning, with NO inhalation or not. Study desing: Open prospective clinical study. Patients: The study included 15 consecutive patients with severe ARDS (PaO 2/FIO 2 < 200 after alveolar recruitment, Murray score > 2,5). Methods: They were returned to the prone position for 4 hours (h0-h4) combined with an inhalation of 5 ppm NO during 1 hour (h2-h3). Tracheal suctions were performed hourly between h-2 and h6 and weighed on a precision scale from h-1 to h6. Haemodynamic, blood gas and respiratory compliance were recorded at h0, h2, h3, h4 and h6. Results : No significant haemodynamic changes were observed in the various phases. Compared with the baseline condition at h0, PP and PP+NO respectively improved PaO 2/FIO 2 by 102 ± 62% at h2 ( P < 0.005) and 156 ± 79% at h3 ( P < 0.005/h0 and < 0.01/h2). 14/15 patients responded to PP and 15/15 to PP+NO (gain in PaO 2/FIO 2 >10%). Concerning secretions, we collected 3.0 ± 7.5 g, 4.4 ± 6.1 g, 1.7 ± 1.4 g and 1,7 ± 1,6 between h-2 and h0, h0 and h2, h2 and h4, h4 and h6. Individual assessments showed no relationship between the PaO 2/FIO 2 evolution at any time and the quantity of secretions obtained during the first 2 hours in the prone position. Six patients presented secretions of less than 1g between h0 and h2, and for whom the improvement in oxygenation was higher than average (115 ± 53% at h2). Conclusion: In patients with little or moderate secretions, the improvement observed in oxygenation, with or without NO, does not depend on their volume.

Effects of prone position on alveolar recruitment and oxygenation in acute lung injury.

To investigate the effects of prone position (PP) on alveolar recruitment and oxygenation in acute respiratory failure. Prospective physiologic study. Medical ICU two in a university hospital. Twelve adult patients intubated and mechanically ventilated with medical primary acute lung injury/adult respiratory distress syndrome (ALI/ARDS) in whom PP was indicated. We constructed the static inflation volume-pressure curves (V-P) of the respiratory system in the 12 patients and differentiated between lung and chest wall in ten of them. We determined the difference between end-expiratory lung volume on positive end-expiratory pressure (PEEP) and relaxation volume of the respiratory system on zero PEEP (delta FRC). The recruited alveolar volume was computed as the delta FRC times the ratio of static elastance of the respiratory system to the lung. These measurements together with arterial blood gases determination were made in supine position (SP1), after 1 h of PP and after 1 h of supine repositioning (SP2) at the same level of PEEP. The PaO2/FIO2 ratio improved from SP1 to PP (136 +/- 17 vs 204 +/- 24 mm Hg; p < 0.01). An PP-induced alveolar recruitment was found in five patients. The change in oxygenation correlated to the recruited volume. The static elastance of the chest wall decreased from 4.62 +/- 0.99 cmH2O/l in SP1 to 6.26 +/- 0.54 cmH2O/l in PP (p < 0.05) without any correlation to the change in oxygenation. Alveolar recruitment may be a mechanism of oxygenation improvement in some patients with acute hypoxemic respiratory failure. No correlation was found between change in oxygenation and chest wall elastic properties.

Prone ventilation--it's time.

Prone positioning to improve oxygenation in acute lung injury was first reported over 20 years ago. Although this and several subsequent studies have shown that prone positioning improved oxygenation in the majority of patients, it has failed to become common practice in intensive care units. This paper reviews the mechanism by which prone positioning improves oxygenation and the clinical studies of its use to date.

Mechanism by which the prone position improves oxygenation in acute lung injury.

The mechanism by which oxygenation improves when patients with ARDS are turned from supine to prone position is not known. From results of our previous studies we reasoned that (1) when supine, in the setting of lung injury, transpulmonary pressure will be less than airway opening pressure and (2) atelectasis will develop preferentially in dorsal lung areas, and (3) both ventilation and ventilation/perfusion ratios would improve in these regions on turning prone. To study this directly, we measured regional ventilation and perfusion using 81mKr and 99mTc-MAA, respectively, and single photon emission computed tomography, both prone and supine, in four control animals and four given oleic acid. After oleic acid, the prone position improved (1) oxygenation (mean +/- SD PaO2 = 140 +/- 112 versus 453 +/- 54 mm Hg), (2) median ventilation/perfusion ratios (0.77 versus 0.95), (3) ventilation/perfusion heterogeneity (coefficient of variation 86 +/- 15 versus 61 +/- 6), and (4) the gravitational ventilation/perfusion gradient (dependent to non-dependent slopes of 0.22 versus -0.02, all p < 0.05). The prone position generates a transpulmonary pressure sufficient to exceed airway opening pressure in dorsal lung regions, i.e., in regions where atelectasis, shunt, and ventilation/perfusion heterogeneity are most severe, without adversely affecting ventral lung regions.

Long-term effects of two different ventilatory modes on oxygenation in acute lung injury. Comparison of airway pressure release ventilation and volume-controlled inverse ratio ventilation.

A total of 18 patients with acute lung injury (ALI) were sequentially ventilated with two different modes of mechanical ventilation, each applied for a period of 24 h: (1) volume-controlled inverse ratio ventilation (VC-IRV), (2) airway pressure release ventilation (APRV). The individual sequence of both ventilatory modes was randomized. Ventilatory minute volume was adjusted for a PaCO2 of 35 to 45 mm Hg at the beginning of the study during the first ventilatory mode and then kept constant within preset limits. Hemodynamic variables were stable and similar during the 24-h periods of VC-IRV and APRV as well. Despite the lower sedation and spontaneous breathing during APRV, oxygen uptake was similar during both ventilatory modes. During the 24-h period of VC-IRV there was no relevant change of either airway pressures, alveolo-arterial O2 tension difference (AaDO2)/fraction of inspired oxygen (FIO2) or venous admixture. In contrast, peak airway pressures (Pawmax) during APRV were significantly lower (about 30%; p < 0.01), and decreased further within 24 h (p < 0.05). During APRV AaDO2/FIO2 and venous admixture improved significantly with time after more than 8 h (AaDO2/FIO2: 487 versus 414 mm Hg; p < 0.01; venous admixture: 20.6 versus 13.9%; p < 0.01; medians of onset versus end). The improvement was significantly different between both ventilatory modes (p < 0.01). We conclude that this indicates a progressive alveolar recruitment over time during ventilation with APRV.(ABSTRACT TRUNCATED AT 250 WORDS)