Grand Rounds: “Acute Respiratory Distress Syndrome and Acute Lung Injury”

September 17, 2008

Bellevue Amphitheater

Commentary by Matthias Kugler MD, PGY-3

Please also see the Grand Rounds Clinical Vignette

Leonhard D Hudson, M.D., Professor of Medicine, Pulmonary and Critical Division, University of Washington, Seattle, spoke at Medical Grand Rounds about the Acute Respiratory Distress Syndrome (ARDS) and Acute Lung Injury (ALI). He started his lecture with a history of the disease, starting with the first published description of ARDS in The Lancet 1967, where it was defined by the presence of diffuse alveolar damage, increasing pulmonary capillary leak, non-cardiogenic pulmonary edema and widespread lung atelectasis. The authors suggested that treatment with high tidal volumes and PEEP to improve oxygenation might decrease the high mortality of the disease.

For the remainder of his talk Dr. Hudson gave an update on ARDS and ALI by presenting the latest epidemiological data, new evidence from basic science research, clinical management and the health sequelae of ARDS/ALI survivors.
Some of the controversies surrounding ARDS stem from the difficulty in making the diagnosis. With no biomarker and even some evidence that some patients with wedge pressures elevated wedge pressures may still have the disease, we are left with the following clinical criteria put forth by the American-European Consensus Conference (AECC) in 1992 to define a disease that arises from a very heterogenous group of clinical signs and symptoms. 1. Presence of ALI for PaO2/FiO2 < 300 and ARDS for PaO2/FiO2 < 200, 2. chest radiograph with bilateral lung infiltrates, 3. Pulmonary capillary wegde pressure (PCWP) < 18 or no clinical evidence of elevated LVEDP.

Unfortunately, it is almost impossible to predict who will develop the disease. To estimate the impact of ARDS/ALI on the US population and to try and detect any possible predictors, several epidemiologic studies were performed from 1972 to 2002; however, the results showed a wide disparity in prevalence, which Dr. Hudson attributed both to differences in study populations and the definitions of ARDS that the studies used. However, using data from the Kings County Lung Injury Project (KCLIP) in 1985 which used hospitalized patients in the ICU, a prevalence of 79 cases per 100,000 people was found. By extrapolating this data to the total US population, it would result in 190,000 cases of ARDS/ALI per year and 74,500 deaths per year – a considerable public health problem!

One of the exciting areas of research in the field of ARDS/ALI is examining the role of various cytokines (e.g. Il-1b, MIP-1a, ENA, IL-8, TNF-R, IL-6R) as possible mediators in the pathogenesis of the disease. Many have been shown to be elevated in various clinical studies of ARDS. Furthermore, many conditions (such as sepsis) can lead to release of many of these mediators which, while fighting the initial insult/disease, are in fact toxic to the lung tissue where they are also released. As a consequence, these mediators can result in acute lung injury with diffuse edema, capillary leak and alveolar damage. Unfortunately, despite the increasing evidence supporting this pathophysiologic concept, no clinical benefit of interrupting this cascade has been shown.

Dr. Hudson went on to discuss the management of ARDS, stressing early diagnosis, treating the underlying disease efficiently, using lung-protective ventilation (LPV) and managing the patient’s volume status with conservative fluid management. He reviewed many early trials that showed evidence supporting LPV, which refuted the initial treatment recommendation from 1967. With publication of the ARDSnet trials, low tidal volume ventilation and conservative fluid management were shown to clearly be of benefit. In a well described statement by Slutsky et al, ARDS was described to be a “biotrauma” that contains the extremes “Volutrauma” and “Atelectrauma”.

Dr. Hudson closed his talk by briefly commenting on the outcome of ARDS/ALI survivors. A significant number of patients suffered from depression, posttraumatic stress disorder (PTSD) and muscular weakness in comparison with the control group. In conclusion, ARDS/ALI are still severe disease entities that have a high mortality (30%) with grave outcomes despite extensive effort to optimize treatment.