A strategy of high positive-end expiratory pressure combined with low tidal volume ventilation failed to improve mortality rates, although it improved oxygenation and reduced the need for rescue actions in patients with acute lung conditions, based on results from a randomized, controlled trial.

Although mechanical ventilation is essential to keep lung injury patients alive, the ventilation process can worsen their injuries, and previous studies have explored the effectiveness of various mechanical ventilation protocols. In patients with acute lung injury and acute respiratory distress syndrome (ARDS) who have increased lung weight due to edema, studies have shown that a higher positive-end expiratory pressure (PEEP) can help keep the lung from collapsing, but at the risk of further damage. Conversely, a PEEP that is too low can increase the risk for hypoxemia and the need for rescue procedures.

In the multicenter study, Dr. Maureen O. Meade of McMaster University in Hamilton, Ont., and her colleagues enrolled 985 adult patients with acute lung injury and ARDS at 30 intensive care units in Canada, Australia, and Saudi Arabia to receive two PEEP protocols to evaluate the impact on all-cause hospital mortality (JAMA 2008;299:637–45).

The experimental group was treated with a “lung open ventilation” strategy, which included recruitment maneuvers, a target tidal volume of 6 mL/kg of predicted body weight, and plateau airway pressure not to exceed 40 cm H₂O. The control group was treated with a target tidal volume of 6 mL/kg of predicted body weight and plateau airway pressure not exceeding 30 cm H₂O. Recruitment maneuvers were not used in the control group.

A total of 475 patients who received the experimental ventilation and 508 who received the control ventilation were included in the primary analysis. One patient in each group withdrew consent. The average age of experimental group patients was 55 years, and of control group patients was 57 years. There were no significant demographic differences between the groups.

All-cause hospital mortality was lower in the experimental group than in the control group (36% vs. 40%), but the difference was not significant. The researchers found no association between baseline injury severity and response to either treatment.

A total of 53 experimental patients and 47 controls developed barotrauma, and this difference was not significant.

But the experimental group's rates of refractory hypoxemia and death with refractory hypoxemia were half those of the control group: 5% vs. 10%, and 4% vs. 9%, respectively. The differences were statistically significant.

A total of 366 patients in the experimental group received at least one recruitment maneuver, and 81 of these (22%) developed a complication as a result. The most common complications were a mean arterial pressure lower than 60 mm Hg (4.5%), oxygen saturation less than 85% (4.2%), and brachycardia or tachycardia (1.8%).

The use of cointerventions was similar in both groups, and the most common interventions were sedative or narcotic infusion, vasopressors, and neuromuscular blockades. Overall use of rescue therapies was significantly lower in the experimental group than in controls (8% vs. 12%).

The study might have been limited by insufficient power to show a small mortality reduction, the researchers noted, and by the fact that the greatest benefits of the higher PEEP strategy might have been to an undefined subgroup.

They added, however, that the absence of significant harm or increased barotrauma in this study supports findings from previous research that justify a higher PEEP for the benefits of better oxygenation in patients with acute lung injury and ARDS. “The 'open-lung' strategy appeared to improve oxygenation, with fewer hypoxemia-related deaths and a lower use of rescue therapies by clinicians,” the investigators said. But the best choice of PEEP protocol remains controversial.

A higher level of PEEP will be useless if edema is not present in an injured lung, Dr. Luciano Gattinoni and Dr. Pietro Caironi of the University of Milan wrote in an accompanying editorial (JAMA 2008;299:691–3).

“Ideally, the direct assessment of lung recruitability by a dynamic lung imaging technique would allow the best physiological titration of PEEP,” they said. The lack of benefit from higher PEEP in this study and other clinical trials contrasts with findings from several experimental studies, they added, and suggests that future studies should take care to identify patients with greater lung injury and lung edema.

Until such a technique becomes widely available, results from the current study suggest that PEEP “at the highest level compatible with a plateau pressure of 28 to 30 cm H₂O and a tidal volume of 6 mL/kg of predicted body weight seems to be a reasonable alternative,” they noted.

None of the investigators disclosed any financial conflicts.

Higher Lung Ventilation Doesn't Lower Mortality Rates