Positive End-expiratory Pressure Strategy Research Articles

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.

Refining Ventilatory Treatment for Acute Lung Injury and Acute Respiratory Distress Syndrome

ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) IS the clinical manifestation of inflammatory lung edema originating from a variety of insults. Since its first description 40 years ago, the mainstays of management have been institution of mechanical ventilation to ventilate the incompliant lungs, inspired oxygen for hypoxemia, and when hypoxemia is severe, the addition of positive end-expiratory pressure (PEEP) to increase end-expiration lung volume, which facilitates O2 gas exchange. Early on, physicians recognized that the high intrathoracic pressures of mechanical ventilation caused parenchymal stress or rupture, known as barotrauma. However, it took several years to identify the local injury resulting from intratidal opening and closing of parts of the lung (atelectrauma) and the inflammatory reaction of the lung to nonphysiological stress (biotrauma). Subsequently computed tomographic scanning showed that the lung fraction open to gas exchange in ARDS is small, equivalent in size to that of a young child (baby lung model). This observation provided the anatomical basis for the concept of volutrauma, focused on the excessive strain within the baby lung induced by tidal ventilation. Taken together, these multiple potentially damaging factors are now called ventilatorinduced lung injury (VILI). In the last decade, prevention of VILI through gentle lung treatment, by adjusting either tidal volume or PEEP, has become the major goal of mechanical ventilatory support not just for ARDS but for the broader population of patients with acute lung injury (ALI). With regard to tidal volume, this line of reasoning and research was most conclusively supported by the National Heart, Lung, and Blood Institute ARDS Network trial demonstrating an improvement in survival for patients with ALI or ARDS who were ventilated with low tidal volumes (6 mL/kg of predicted body weight) compared with those ventilated with higher tidal volumes (12 mL/kg of predicted body weight). Although many argued that the tidal volume in the control group might have been higher than existing practice, the tidal volume in the interventional group marked a stark departure from usual care and has resulted in a dramatic change in the approach to tidal volume setting for ALI and ARDS. The optimal PEEP strategy, however, has remained unresolved. Evidence from animal studies suggested that higher PEEP (in the range of 10-15 cm H2O) could prevent VILI. Thus, many clinicians were surprised when the first large randomized clinical trial comparing higher levels of PEEP with lower levels of PEEP in patients with ALI and ARDS, the National Heart, Lung, and Blood Institute’s ARDS Network Assessment of Low Tidal Volume and Elevated EndExpiratory Lung Volume to Obviate Lung Injury (ALVEOLI) study, was stopped for futility. In this issue of the JAMA, 2 new large international randomized trials examining the effects of PEEP on outcome in patients with ALI and ARDS are presented. In the Lung Open Ventilation (LOV) trial, the level of PEEP administered, either lower or higher, was selected according to an oxygenation scale conceptually similar to the one used in the previous ALVEOLI study. In the Expiratory Pressure (Express) trial, PEEP selection was based on a more subtle and refined approach, using bedside assessment of lung mechanics instead of gas exchange. This method identified a minimal distention strategy (lower level of PEEP) and an increased recruitment strategy (higher level of PEEP). Despite the different criteria used for PEEP selection, the PEEP levels tested were similar in the 2 studies. In the LOV study, mean PEEP levels on day 1 were 15.6 cm H2O and 10.1 cm H2O, and the subsequent hospital mortality rates were 36.4% and 40.4%. In the Express study, mean PEEP levels on day 1 were 15.8 cm H2O and 8.4 cm H2O, and the

Positive End-Expiratory Pressure Setting in Adults With Acute Lung Injury and Acute Respiratory Distress Syndrome

The need for lung protection is universally accepted, but the optimal level of positive end-expiratory pressure (PEEP) in patients with acute lung injury (ALI) or acute respiratory distress syndrome remains debated. To compare the effect on outcome of a strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation to one aimed at minimizing alveolar distension in patients with ALI. A multicenter randomized controlled trial of 767 adults (mean [SD] age, 59.9 [15.4] years) with ALI conducted in 37 intensive care units in France from September 2002 to December 2005. Tidal volume was set at 6 mL/kg of predicted body weight in both strategies. Patients were randomly assigned to a moderate PEEP strategy (5-9 cm H(2)O) (minimal distension strategy; n = 382) or to a level of PEEP set to reach a plateau pressure of 28 to 30 cm H(2)O (increased recruitment strategy; n = 385). The primary end point was mortality at 28 days. Secondary end points were hospital mortality at 60 days, ventilator-free days, and organ failure-free days at 28 days. The 28-day mortality rate in the minimal distension group was 31.2% (n = 119) vs 27.8% (n = 107) in the increased recruitment group (relative risk, 1.12 [95% confidence interval, 0.90-1.40]; P = .31). The hospital mortality rate in the minimal distension group was 39.0% (n = 149) vs 35.4% (n = 136) in the increased recruitment group (relative risk, 1.10 [95% confidence interval, 0.92-1.32]; P = .30). The increased recruitment group compared with the minimal distension group had a higher median number of ventilator-free days (7 [interquartile range {IQR}, 0-19] vs 3 [IQR, 0-17]; P = .04) and organ failure-free days (6 [IQR, 0-18] vs 2 [IQR, 0-16]; P = .04). This strategy also was associated with higher compliance values, better oxygenation, less use of adjunctive therapies, and larger fluid requirements. A strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation did not significantly reduce mortality. However, it did improve lung function and reduced the duration of mechanical ventilation and the duration of organ failure. clinicaltrials.gov Identifier: NCT00188058.

Effects of High versus Low Positive End-Expiratory Pressures in Acute Respiratory Distress Syndrome

A recent study by the Acute Respiratory Distress Syndrome Network compared the traditional lower end-expiratory pressure strategy with a higher end-expiratory pressure strategy in patients with the acute respiratory distress syndrome ventilated with low tidal volumes. Clinical outcomes were similar whether lower or higher positive end-expiratory pressure (PEEP) levels were used. We applied both the lower (9 +/- 2 cm H2O) and higher (16 +/- 1 cm H2O) PEEP strategy in 19 patients. In nine recruiters, the higher end-expiratory pressure strategy resulted in significant alveolar recruitment (587 +/- 158 ml), improvement in arterial oxygen partial pressure/inspired oxygen fraction ratio (from 150 +/- 36 to 396 +/- 138), and reduction in static lung elastance (from 23 +/- 3 to 20 +/- 2 cm H2O/L). In 10 nonrecruiters, alveolar recruitment was minimal, oxygenation did not improve, and static lung elastance significantly increased (from 26 +/- 5 to 28 +/- 6 cm H2O/L). The increase in oxygenation, the reduction in static lung elastance, and the shape of the volume-pressure curve during the lower PEEP strategy were independently associated with alveolar recruitment. In conclusion, the protocol proposed by the Acute Respiratory Distress Syndrome Network, lacking solid physiologic basis, frequently fails to induce alveolar recruitment and may increase the risk of alveolar overinflation.

Positive end-expiratory pressure above lower inflection point minimizes influx of activated neutrophils into lung*

To compare the effects of low vs. high tidal volume (Vt) with three positive end-expiratory pressure (PEEP) strategies on activated neutrophil influx into the lung. Prospective, randomized controlled animal study. Animal laboratory in a university hospital. Newborn piglets. Surfactant-depleted piglets were randomized in littermate pairs; to PEEP of either 0 (zero end-expiratory pressure [ZEEP]; n = 6), 8 cm H2O (PEEP 8; n = 5), or 1 cm H2O above the lower inflection point (LIP) (PEEP>LIP; n = 6). Within each pair piglets were randomized to a low VT (5-7 mL/kg) or high VT strategy (17-19 mL/kg). After 4 hrs of mechanical ventilation, 18-fluorodeoxyglucose (18FDG) was injected and positron emission tomography scanning was performed. VT and PEEP changes on influx constants of 18FDG were assessed by analysis of variance. A within-litter comparison of Vt was nonsignificant (p = .50). A between-litter comparison, ordered in linear trend rank, from ZEEP, to PEEP 8, to PEEP>LIP, showed a strong effect of PEEP on influx constant (p = .019). PEEP set above the LIP on the inspiratory limb of the pressure-volume curve affords a stronger lung protection than VT strategy.

Acute respiratory failure in children.

Recent studies in the treatment of acute respiratory failure in children have been targeted at reducing ventilator-induced lung injury, providing treatment adjuncts to mechanical ventilation, and assessing innovative therapies directed at immunomodulation. Ventilator-associated lung injury has been demonstrated in animal models during the delivery of moderate-to-large tidal volumes and has also been described in adult populations. Subsequently, a significant survival benefit of a low tidal volume, high positive end expiratory pressure strategy on the ventilatory was found in adults. Investigation of the effects of inhaled nitric oxide in acute respiratory failure patients continues to show transient improvements in oxygenation, but no evidence of improved outcomes. The use of intratracheal surfactant within 24 hours of intubation in pediatric respiratory failure may be beneficial in reducing the days of mechanical ventilation. Neutrophil oxidative damage has been demonstrated, but therapies directed at decreasing neutrophil adherence have failed to demonstrate improvements. Enteral anti-inflammatory and antioxidant therapy may be promising, because these modalities have been shown to improve a number of surrogate outcomes in patients with respiratory failure. The use of corticosteroids in the late stages of lung injury has also recently been shown to have promise.