Early Trends in Plateau Pressure Can Predict ALI Mortality

SAN DIEGO—Change in inspiratory plateau pressure (P_plat) may be associated with 60-day mortality in patients with acute lung injury (ALI) independently of APACHE III scores, according to research presented at the 2009 International Conference of the American Thoracic Society.

“Why use P_plat?” asked William Checkley, MD, PhD, from the Division of Pulmonary and Critical Care, Johns Hopkins School of Medicine. “Mainly because it’s an easy, quick, and noninvasive bedside maneuver that represents stretching forces of the respiratory system and it correlates with mortality.” P_plat is the average pressure in the aerated lung at end inspiration during positive pressure ventilation; it is determined by three variables: tidal volume, respiratory system compliance, and PEEP, he explained.

ARDS NETWORK

The researchers used 1999-2006 data from the ARDS Clinical Trials Network—which involved 1,142 patients who received lung protective ventilation. Among the studies examined was the Lower Tidal Volume Trial, originally published in 2000, which assessed lower tidal volume ventilation versus traditionally recommended larger tidal volume approach in 861 patients with ALI. Results of that study showed that lower tidal volume resulted in improved survival. The 2004 Assessment of Low Tidal Volume and Elevated End-Expiratory Volume to Obviate Lung Injury (ALVEOLI) study compared the clinical outcomes of patients with ALI and ARDS treated with higher PEEP/lower fraction of inspired oxygen (Fio₂) versus a lower PEEP/higher Fio₂ ventilation strategy in 549 patients; it found no improvement in survival with higher PEEP. In the 2006 Fluid and Catheter Treatment Trial (FACTT), investigators compared two different strategies for managing IV and fluid balance in 1,000 patients with ALI and observed that pulmonary artery catheter guided fluid therapy showed no benefit over central venous catheter guided therapy. In addition, they found that the conservative approach of fluid balance management was superior to the traditional liberal approach.

In the current study, Dr. Checkley and colleagues observed that 60-mortality did not substantially change over time (average, 27%). When evaluating the averages of APACHE III scores and day 1 P_plat in each trial, they found that APACHE III scores were higher in the ALVEOLI and FACTT studies, compared with the Lower Tidal Volume Trial.

“On the other hand, there was less of a consistent trend in the mean value of Pplat over time,” Dr. Checkley noted. Data also indicated a direct relationship between 60-day mortality and APACHE III scores. Similarly, they observed that day 1 P_plat was directly related to mortality.

DIAMOND PLOT

Hospital admission represented in a diamond plot (ie, a graphical method to depict mortality in relation to both the change in P_plat between days 1 and 3 and APACHE III scores), the investigators observed a steady increase in mortality associated with APACHE III scores. Furthermore, within each quintile of APACHE III scores, they found an increase in mortality with Pplat.

In terms of relative risk, the highest quintile showed the largest increase in mortality. “However, when we explored an interaction between day 1 P_plat and APACHE III, it was not significant,” Dr. Checkley noted.

Additional analysis showed considerable variability between mortality and change in P_plat between day 1 and 3 (range, generally between -15 to 15 cm of water). “Also, mortality was directly related to the change in P_plat.” The diamond plot indicated approximately 10% mortality in the lowest quintile, compared with 66% in the highest quintile.

“Quite similarly, one can see that within quintiles of APACHE III scores there appears to be a consistent increase in mortality, as change P_plat increases,” Dr. Checkley observed. Similar observations were made in the diamond plot representing relative risk.

Logistic regression analysis yielded that change in P_plat, APACHE III scores, and age were all predictors of mortality. Change in P_plat was associated with 60-day mortality independently of APACHE III, so that mortality significantly increased in correlation with change in P_plat. “However, we did not find an interaction between change in P_plat and APACHE III,” Dr. Checkley acknowledged.

“P_plat may serve as a lung-specific indicator of mortality in patients with ALI, more so because it is an easy measurement to make at the bedside,” he concluded. “This is not only useful for disease prognosis, but it may also be useful to stratify patients in clinical trials.”

—Frederique H. Theuvenin

Suggested Reading
Checkley W, Brower R, Korpak A, et al. Effects of clinical trial on mechanical ventilation practices in patients with acute lung injury. Am J Respir Crit Care Med. 2008;177(11):1215-1222.
Hager DN, Krishnan JA, Hayden DL, et al. Tidal volume reduction in patients with acute lung injury when plateau pressures are not high. Am J Respir Crit Care Med. 2005; 172(10):1241-1245.

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