Lung-protective Mechanical Ventilation Research Articles

Plasma levels of surfactant protein D and KL-6 for evaluation of lung injury in critically ill mechanically ventilated patients

BackgroundPreventing ventilator-associated lung injury (VALI) has become pivotal in mechanical ventilation of patients with acute lung injury (ALI) or its more severe form, acute respiratory distress syndrome (ARDS). In the present study we investigated whether plasma levels of lung-specific biological markers can be used to evaluate lung injury in patients with ALI/ARDS and patients without lung injury at onset of mechanical ventilation.MethodsPlasma levels of surfactant protein D (SP-D), Clara Cell protein (CC16), KL-6 and soluble receptor for advanced glycation end-products (sRAGE) were measured in plasma samples obtained from 36 patients - 16 patients who were intubated and mechanically ventilated because of ALI/ARDS and 20 patients without lung injury at the onset of mechanical ventilation and during conduct of the study. Patients were ventilated with either a lung-protective strategy using lower tidal volumes or a potentially injurious strategy using conventional tidal volumes. Levels of biological markers were measured retrospectively at baseline and after 2 days of mechanical ventilation.ResultsPlasma levels of CC16 and KL-6 were higher in ALI/ARDS patients at baseline as compared to patients without lung injury. SP-D and sRAGE levels were not significantly different between these patients. In ALI/ARDS patients, SP-D and KL-6 levels increased over time, which was attenuated by lung-protective mechanical ventilation using lower tidal volumes (P = 0.02 for both biological markers). In these patients, with either ventilation strategy no changes over time were observed for plasma levels of CC16 and sRAGE. In patients without lung injury, no changes of plasma levels of any of the measured biological markers were observed.ConclusionPlasma levels of SP-D and KL-6 rise with potentially injurious ventilator settings, and thus may serve as biological markers of VALI in patients with ALI/ARDS.

Acute respiratory distress syndrome: insights gained from clinical and translational research.

Acute lung injury and its more severe form acute respiratory distress syndrome (ARDS) are characterized by diffuse impairment of alveolocapillary membrane in the settings of different predisposing conditions such as sepsis, trauma and shock. Many intrahospital exposures, including aspiration, delayed resuscitation, high tidal volume mechanical ventilation and non critical use of transfusions may contribute or worsen ARDS. Therapy is targeted to treatment of predisposing condition, life supportive measures and prevention of nosocomial complications. Rigorous adherence to lung-protective mechanical ventilation is critical to prevent ventilator induced lung injury and decrease mortality. Although survival of ARDS patients has improved in the last decades ARDS mortality rates are still high and survivors encounter significant physical and psychological impairments.

Comparison of Optimal Positive End-Expiratory Pressure and Recruitment Maneuvers During Lung-Protective Mechanical Ventilation in Patients With Acute Lung Injury/Acute Respiratory Distress Syndrome

In patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), the use of alveolar-recruitment maneuvers to improve oxygenation is controversial. There is lack of standardization and lack of clinical studies to compare various recruitment maneuvers. Recruitment maneuvers are closely linked to the selection of positive end-expiratory pressure (PEEP), which is also a subject of debate. With 12 intubated and mechanically ventilated patients with early ALI/ARDS we conducted a recruitment maneuver (sustained inflation at 40 cm H(2)O for 30 s), then set PEEP at 24 cm H(2)O, and then we reduced PEEP stepwise, by 4 cm H(2)O every 10 min. We kept the fraction of inspired oxygen (F(IO(2))) at 0.8. After each PEEP decrement step we measured P(aO(2)). We defined the "optimal" PEEP as the PEEP step above which P(aO(2)) decreased by > or = 20%. All the patients then underwent a period of ventilation on the same settings: tidal volume 6 mL/kg, PEEP at the level set by the physician before the experiment, plateau pressure < 30 cm H(2)O. Then each patient underwent 3 ventilation strategies, each applied for one hour: optimal PEEP alone; optimal PEEP plus one sustained inflation (40 cm H(2)O for 30 s); and optimal PEEP plus sigh breaths (ie, twice the baseline tidal volume, plateau pressure < 40 cm H(2)O) every 25 breaths. After the application of each PEEP strategy we measured arterial blood gas values and the static compliance of the respiratory system. The mean +/- SD optimal PEEP was 12 +/- 4 cm H(2)O. The measurements from the standardization periods were comparable between the 3 PEEP groups. In the optimal-PEEP-plus-sighs group the changes in P(aO(2)) (85 +/- 96%) and static compliance (14 +/- 20%) were significantly greater than in the 2 other groups. Sighs superimposed on lung-protective mechanical ventilation with optimal PEEP improved oxygenation and static compliance in patients with early ALI/ARDS.

Supportive und adjunktive Therapie der Sepsis

Severe sepsis and septic shock have an increasing incidence but an unchanged mortality. It has been demonstrated that the time until the start of supportive therapy affects the progress of multiorgan failure and patient outcome. Early goal-directed therapy guided by central venous oxygen saturation is associated with a significant reduction in mortality, as is the use of lung-protective mechanical ventilation and recombinant activated protein C (rhAPC) in eligible patients. The use of starches for volume resuscitation, low-dose dopamine and hydrocortison as well as an intensive insulin protocol for restoration of euglycemia is not recommended. The German Competence Network Sepsis (SepNet) is currently studying further relevant questions.

Effect of endotracheal air leakages on the monitoring of ventilation and respiratory mechanics in ventilated newborns

The prevention of lung over-distension and ventilator induced lung injury (VILI) requires a lung protective mechanical ventilation with careful monitoring of ventilation and lung mechanics. However, this will be impaired by endotracheal tube (ET) leakages. The aim of this study was to investigate the effect of ET leakages on the monitoring of tidal volume (VT) and respiratory mechanics using an in-vitro model. Methods: A neonatal lung model was ventilated via a 3mm ET using 3 ventilators: Babylog 8000 (BL), Leoni (LE), Stephanie (SE). VT and lung mechanics were measured by the pneumotach of the ventilator at the Y-piece. Additionally, VT delivered to the lung model was measured by a second pneumotach (CO2SMO+). ET leakages were simulated by open silicone tubes of different lengths. PIP (20cmH2O) and PEEP (5cmH2O) were kept constant, respiratory rate (RR) was changed from 20 to 70/min (I: E=1: 1). Results: The displayed leakage varied between 0 and 78% and was dependent on RR. VT measured by the ventilator decreased with increasing leakage up to 21%(BL), 30%(LE) and 33%(ST) independent of RR,. whereas VT delivered to the lung was nearly constant. With increasing ET leakage for BL and ST the displayed compliance was overestimated, while for LE the compliance was underestimated. The displayed resistance increased with increasing ET leakage for all ventilators, however, in different way: distinctly for BL and ST, minimally for LE. Conclusion: The effect of ET leakage on the displayed ventilatory and lung mechanic parameters are ventilator dependent which impairs the between ventilators comparability. General recommendations what level of ET leakage can be tolerated are not possible.

The pulmonary protein C system: preventive or therapeutic target in acute lung injury?

Acute lung injury or its more severe form—acute respiratory distress syndrome (ARDS)—are common and important intensive care syndromes affecting many patients. Acute lung injury is characterised by damage to the...

The complex role of fibrin in acute lung injury

in the last decade there have been many advances in our understanding of the pathogenesis of acute lung injury (ALI), but there have been frustratingly few successful therapeutic interventions. In fact, the only treatment proven to reduce mortality is low tidal volume lung-protective mechanical

Experimental Therapeutic Strategies for Severe Sepsis

Severe sepsis is the leading cause of mortality in intensive care units. The limited ability of current therapies to reduce sepsis mortality rates has fueled research efforts for the development of novel treatment strategies. Through the close collaboration between clinicians and scientists, progress can be seen in the struggle to develop effective therapeutic approaches for the treatment of sepsis and other immune and inflammatory disorders. Indeed, significant advances in intensive care, such as lung protective mechanical ventilation, improved antibiotics, and superior monitoring of systemic perfusion, are improving patient survival. Nonetheless, specific strategies that target the pathophysiological disorders in sepsis patients are essential to further improve clinical outcomes. This article reviews current clinical management approaches and experimental interventions that target pleiotropic or late-acting inflammatory mediators like caspases, C5a, MIF, and HMGB1, or the body's endogenous inflammatory control mechanisms such as the cholinergic anti-inflammatory pathway. These inflammatory mediators and anti-inflammatory mechanisms, respectively, show significant potential for the development of new experimental therapies for the treatment of severe sepsis and other infectious and inflammatory disorders.

Beatmung von Patienten mit Adipositas per magna in Anästhesie und Intensivmedizin

Sculptures from the Stone Age hint at the possibility that morbidly obese humans have always existed. Today, obesity represents a global epidemic with far-reaching consequences affecting health systems worldwide. Increasingly often, anaesthetists and intensivists are challenged with the treatment of extremely obese patients perioperatively. In addition to insufficient logistics and inappropriate technical equipment, the large number of obesity-related diseases, combined with the distinct pathophysiological changes of the respiratory system, put the morbidly obese patient at a significantly increased risk of perioperative complications. If, however, elaborate logistics and adequate airway management--followed by lung protective mechanical ventilation--are combined with appropriately conducted anaesthesia and intensive care, the morbidly obese patients' intensive care survival rates and hospital survival rates can be similar to those of patients of normal weight.

Ventilator-induced coagulopathy in experimental Streptococcus pneumoniae pneumonia

Pneumonia, the main cause of acute lung injury, is characterised by a local pro-inflammatory response and coagulopathy. Mechanical ventilation (MV) is often required. However, MV can lead to additional injury: so-called ventilator-induced lung injury (VILI). Therefore, the current authors investigated the effect of VILI on alveolar fibrin turnover in Streptococcus pneumoniae pneumonia. Pneumonia was induced in rats, followed 48 h later by either lung-protective MV (lower tidal volumes (LV(T)) and positive end-expiratory pressure (PEEP)) or MV causing VILI (high tidal volumes (HV(T)) and zero end-expiratory pressure (ZEEP)) for 3 h. Nonventilated pneumonia rats and healthy rats served as controls. Thrombin-antithrombin complexes (TATc), as a measure for coagulation, and plasminogen activator activity, as a measure of fibrinolysis, were determined in bronchoalveolar lavage fluid (BALF) and serum. Pneumonia was characterised by local (BALF) activation of coagulation, resulting in elevated TATc levels and attenuation of fibrinolysis compared with healthy controls. LV(T)-PEEP did not influence alveolar coagulation or fibrinolysis. HV(T)-ZEEP did intensify the local procoagulant response: TATc levels rose significantly and levels of the main inhibitor of fibrinolysis, plasminogen activator inhibitor-1, increased significantly. HV(T)-ZEEP also resulted in systemic elevation of TATc compared with LV(T)-PEEP. Mechanical ventilation causing ventilator-induced lung injury increases pulmonary coagulopathy in an animal model of Streptococcus pneumoniae pneumonia and results in systemic coagulopathy.

From low-tidal-volume ventilation to lowest-tidal-volume ventilation

The therapeutic measures of lung-protective mechanical ventilation used in treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) have revived the interest in high-frequency ventilation (HFV). The reduction of the tidal volume during the conventional ventilation (CV) in terms of low-tidal-volume ventilation is not unboundedly feasible. However, HFV allows a further reduction of tidal volume. Established HFV techniques are high-frequency oscillation (HFO), high-frequency percussive ventilation (HFPV) and superimposed high-frequency jet ventilation (SHFJV). The aim of this study was to evaluate the amelioration of the oxygenation index (OI).

Optimal ventilator settings in acute lung injury and acute respiratory distress syndrome

Despite recent advances in intensive care medicine, acute lung injury and its more severe form, acute respiratory distress syndrome pose major therapeutic problems. While mechanical ventilation is integral to the care of these patients, its adverse consequences including ventilator-induced lung injury are determinants of disease progression and prognosis. Among several important ventilator parameters, the use of low tidal volumes is probably the most important feature of lung-protective mechanical ventilation. Intensivists should be trained to recognize acute lung injury and acute respiratory distress syndrome and encouraged to use low-tidal-volume ventilation in clinical practice. Alternative modes of ventilation such as high-frequency ventilation and prone position should be reserved for selected patients in whom conventional lung-protective ventilation strategies have failed.

Akutes Lungenversagen - Therapeutische Optionen im Überblick

The treatment of acute lung injury is one of the most challenging tasks in intensive care medicine. Conventional therapeutic options cover lung protective mechanical ventilation with low tidal volumes and adequate PEEP, restrictive fluid management, prone positioning, and early recruitment maneuvers. These options should be used in parallel and should be accompanied by a suitable anti-infective therapy. In cases of refractory hypoxemia, inhaled nitric oxide offers in most patients a successful rescue option. In specialized centers the application of ECMO remains as a final ultima ratio.

Pediatric acute lung injury

Among ventilated children, the incidence of acute lung injury (ALI) was 9%; of that latter group 80% developed the acute respiratory distress syndrome (ARDS). The population-based prevalence of pediatric ARDS was 5.5 cases/100.000 inhabitants. Underlying diseases in children were septic shock (34%), respiratory syncytial virus infections (16%), bacterial pneumonia (15%), near-drowning 9%, and others. Mortality ranged from 18% to 27% for ALI (including ALI-non ARDS and ARDS) and from 29% to 50% for ARDS. Mortality was only 3%-11% in children with ALI-non ARDS. As risk factors, oxygenation indices and multi-organ failure have been identified. New insights into the pathophysiology (for example the interplay between intraalveolar coagulation/fibrinolysis and inflammation and the genetic polymorphism for the angiotensin-converting enzyme) offer new therapeutic options. Lung protective mechanical ventilation with optimal lung recruitment is the mainstay of supportive therapy. New therapeutic modalities refer to corticosteroid and surfactant treatment. Well-designed follow up studies are needed.

Mechanical ventilation with lower tidal volumes does not influence the prescription of opioids or sedatives

IntroductionWe compared the effects of mechanical ventilation with a lower tidal volume (VT) strategy versus those of greater VT in patients with or without acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) on the use of opioids and sedatives.MethodsThis is a secondary analysis of a previously conducted before/after intervention study, which consisting of feedback and education on lung protective mechanical ventilation using lower VT. We evaluated the effects of this intervention on medication prescriptions from days 0 to 28 after admission to our multidisciplinary intensive care unit.ResultsMedication prescriptions in 23 patients before and 38 patients after intervention were studied. Of these patients, 10 (44%) and 15 (40%) suffered from ALI/ARDS. The VT of ALI/ARDS patients declined from 9.7 ml/kg predicted body weight (PBW) before to 7.8 ml/kg PBW after the intervention (P = 0.007). For patients who did not have ALI/ARDS there was a trend toward a decline from 10.2 ml/kg PBW to 8.6 ml/kg PBW (P = 0.073). Arterial carbon dioxide tension was significantly greater after the intervention in ALI/ARDS patients. Neither the proportion of patients receiving opioids or sedatives, or prescriptions at individual time points differed between pre-intervention and post-intervention. Also, there were no statistically significant differences in doses of sedatives and opioids. Findings were no different between non-ALI/ARDS patients and ALI/ARDS patients.ConclusionConcerns regarding sedation requirements with use of lower VT are unfounded and should not preclude its use in patients with ALI/ARDS.

The Effects of Repetitive Alveolar Recruitment on Oxygenation and Compliance in ARDS Patients

Background: If the effects of alveolar recruitment are beneficial, but of short duration, repetitive recruitment maneuvers (RMs) will be necessary to maintain oxygenation. This study was performed to assess the effect of repetitive alveolar recruitment, with high-sustained inflation pressure on oxygenation and compliance of the respiratory system, in patients with acute respiratory distress syndrome. Methods: Ten adult patients on ventilator support, with controlled mechanical ventilation, received three repetitive RMs with a high-sustained inflation pressure. The time intervals from the first to second RM and from the second to third RM were 8.42 ± 0.56 hours and 12.43 ± 1.45 hours, respectively. Recruitment was conducted by setting the ventilator mode to a continuous positive airway pressure of 40 cmH2O for 40 seconds. After each alveolar recruitment, the previous ventilator settings in the pressure control mode were re-established with a high positive end expiratory pressure. The FIO2, PaO2/FIO2 and lung compliance (tidal volume/[plateau pressure - PEEP]) were recorded with reference to the arterial blood gas analysis at both 30 minutes pre and post recruitment. Results: The FIO2 was able to be decreased from 0.9 to 0.5 while maintaining the PaO2 at higher than 80 mmHg after three recruitments. The PaO2/FIO2 improved from 98 to 288 and the compliance of the respiratory system improved from 26 to 41 ml/cmH2O after three recruitments. Conclusions: Our results suggest that repetitive recruitment can be used to maintain the beneficial effects of alveolar recruitment in patients with acute respiratory distress syndrome when supported using a lung protective mechanical ventilation strategy.

High-frequency oscillatory ventilation following prone positioning prevents a further impairment in oxygenation*

The improvement in oxygenation with prone positioning is not persistent when patients with acute respiratory distress syndrome (ARDS) are turned supine. High-frequency oscillatory ventilation (HFOV) aims to maintain an open lung volume by the application of a constant mean airway pressure. The aim of this study was to show that HFOV is able to prevent the impairment in oxygenation when ARDS patients are turned back from the prone to the supine position. Prospective, comparative randomized study. A medical intensive care unit. Forty-three ARDS patients with a Pao2/Fio2 ratio <150 at positive end-expiratory pressure > or =5 cm H2O. After an optimization period, the patients were assigned to one of three groups: a) conventional lung-protective mechanical ventilation in the prone position (12 hrs) followed by a 12-hr period of conventional lung-protective mechanical ventilation in the supine position (CV(prone)-CV(supine)); b) conventional lung-protective mechanical ventilation in the supine position (12 hrs) followed by HFOV in the supine position (12 hrs) (CV(supine)-HFOV(supine)); or c) conventional lung-protective mechanical ventilation in the prone position (12 hrs) followed by HFOV in the supine position (CV(prone)-HFOV(supine) group). Pao2/Fio2 ratio was higher at the end of the study period in the CV(prone)-HFOV(supine) group than in the CV(prone)-CV(supine) group (p < .02). Venous admixture at the end of the study period was lower in the CV(prone)-HFOV(supine) group than in the two other groups. HFOV maintained the improvement in oxygenation related to prone positioning when ARDS patients were returned to the supine position.

Lung-protective mechanical ventilation strategy for acute lung injury and acute respiratory distress syndrome

Mechanical ventilation (MV) is critical for survival of many patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS). However, MV can also cause ventilator-induced lung injury (VILI) which may delay or prevent recovery of some patients. Experimental models demonstrated that VILI could be reduced by modifying traditional MV approaches. Some clinical trials demonstrated improved clinical outcomes in patients who received lower tidal volumes and inspiratory airway pressures to prevent VILI from overdistention. Experimental models suggest that VILI may occur from cyclic opening and closing of small bronchioles and alveoli, and that this can be reduced by applying positive end-expiratory pressure (PEEP). Some clinical studies suggested that clinical outcomes may be improved with the use higher levels of PEEP than are used with traditional MV strategies. However, in these studies higher PEEP was combined with lower tidal volumes and inspiratory airway pressures. It is not yet clear th...

Feedback and Education Improve Physician Compliance in Use of Lung-Protective Mechanical Ventilation

Feedback and Education Improve Physician Compliance in Use of Lung-Protective Mechanical Ventilation

Acute Lung Injury and the Acute Respiratory Distress Syndrome

In 2005, the American Thoracic Society marks its 100th year of existence. For over a third of this span, since 1967, clinicians and investigators have struggled with a common, often lethal condition originally termed the adult respiratory distress syndrome (ARDS) (1).* While the syndrome almost certainly occurred in earlier times well before the advent of intensive care units, this date establishes its modern era. Subsequently, ARDS has more correctly come to indicate the acute respiratory distress syndrome because it occurs in children as well as in adults (2). ARDS causes severe acute respiratory failure with dynamic impairment in oxygen and carbon dioxide transfer, with the need for high levels of supplementary oxygen and a high minute ventilation (3, 4). Efforts to understand the pathophysiologic events underlying ARDS, a constellation that is now generally termed acute lung injury (ALI), have been substantial and remain a priority of the National Institutes of Health (5). The expectation has been that basic, translational, and clinical studies will result in new strategies for management of ALI/ARDS based on clear definition of the cellular and molecular events requisite in lung injury and repair. While important discoveries have been made, the goal of fundamental characterization of ALI/ARDS in a way that results in highly effective prevention and treatment remains incomplete and elusive. One major advance in supportive care, a strategy of lung protective mechanical ventilation, has substantially reduced mortality in ALI/ARDS (6, 7). This therapeutic intervention resulted from both experimental and clinical studies that evaluated the effect of different ventilation strategies on the course of ALI, and continues a theme initiated in the original description of ALI/ARDS in which positive end-expiratory pressure was introduced as a management modality (1). In spite of the advances in supportive care of patients with ALI/ARDS, unacceptable morbidity and mortality persist and formidable challenges remain. Our objective here is to review briefly what we knew in 1967 regarding pathogenesis and what we know in 2005, and to provide a perspective on how insights have evolved over the last four decades.