Acute respiratory distress syndrome (ARDS) is the most lethal form of acute respiratory failure.
It is characterized by rapid onset of severe inflammation of the respiratory lobules with exudative pulmonary edema and hypoxemia. Major precipitative conditions include shock, sepsis, and trauma.

In the U.S., 150,000 patients are affected by ARDS each year and mortality is 50%. More patients die each year from ARDS than from breast cancer or AIDS. Inflammation is not limited to the lungs but is systemic leading to multiple organ failure.

Until recently treatment has been only supportive. The MLRP recently completed the first randomized study evaluating prolonged methylprednisolone administration in patients failing to improve after 7 days of mechanical ventilation. Treatment was highly effective in decreasing pulmonary and systemic inflammation. Mortality in intensive care units was decreased to 0% and hospital mortality to 12% (62% in placebo).

At present we are investigating prolonged methylprednisolone infusion started within 3 days of ARDS development.

Our mission is to decrease ARDS mortality to less than 20%.

 

 

Sepsis is the most common cause of death in medical and surgical ICU's....[and] is reported to occure in 400,000 to 500,000 patients each year.... Mortality rates between 20% and 60% are reported for severe cases. The acute and chronic sequelae of severe sepsis represents the 13th leading cause of death in the U.S. (1)

Sepsis and septic shock result from activation of host defenses in response to invading pathogenic microorganisms and their products. The excessive release of inflammatory mediators causes diffuse capillary injury, intravascular coagulation with microvascular thrombosis, hypotension, myocardial depression, and multiple organ failure.(1)

Hypercortisolemia associated with stress inhibits the host defense response cascade at virtually all levels; its gradual and generalized suppressive influences in the most important mechanism protecting the host from overshooting.(2) In patients dying with severe sepsis…however, cortisol’s ability to immunomodulate the host defense response is impaired.

1. Meduri GU. The role of the host defense response in the progression and outcome of ARDS. Eur Respir Journal 1996.
2. Headley AS, Tolley E, Meduri GU. Infections and the inflammatory response in acute respiratory distress syndrome. Chest 1997.

We are investigating the use of glucocorticoid supplementation therapy in patients with severe sepsis. Supporting evidence of its effectiveness is provided by the results of recent controlled and uncontrolled studies…showing that prolonged glucocorticoid treated was associated with a rapid, significant, and sustained reduction in circulating levels of markers of inflammatory activity, and progressive physiological improvement.

Meduri GU. An historical review of glucocorticoid treatment in sepsis. Disease pathophysiology and the design of treatment investigation. Sepsis

 

 

 

Patients with acute respiratory failure require mechanical ventilation for life support. Conventionally, the patient is connected to the ventilator via an endotracheal tube. Placement of the endotracheal tube is associated with increased morbidity and mortality.

We have shown that mechanical ventilation can be delivered effectively in many patients with acute respiratory failure by using a mask, i.e. noninvasive positive pressure ventilation (NPPV) instead of an endotracheal tube.

Randomized studies have proven the benefits of noninvasive ventilation showing a significant reduction in rate of intubation septic complications, duration of intensive care unit stay, mortality, and cost.

The MLRP is conducting collaborative studies with European investigators to advance knowledge of noninvasive ventilation. We have developed educational material to familiarize health professionals with the correct use of this safe and effect methodology.

 

 

 

History