Because it reports data from one of the very few "positive" trials in the field of sepsis.

  Does it describe a new discovery or a new methodology that's useful to others?

This paper reports a new therapeutic strategy using a combination of a glucocorticoid and a mineralocorticoid for patients with septic shock.

Sepsis is present when a site of infection is apparent and there is evidence of body-wide, systemic inflammation. Systemic inflammation is usually defined by two or more of the following criteria: fever or low body temperature, an increase or decrease in white blood cells, an increase in the heart rate, and rapid breathing. Septic shock is when sepsis is combined with a fall in systemic blood pressure that does not improve even when health staffs give intravenous fluids. Many people die from sepsis in the USA. In 1993 the age-adjusted death rate was 7.9 per 100,000 people. Some authorities estimate the hospital incidence of severe sepsis to be two cases per 100 admissions, and septic shock is present at onset of sepsis syndrome in 25% of patients. The most recent data were obtained from 1995 state hospital discharge records from seven states. This large observational cohort study provided national estimates of 751,000 cases of severe sepsis, i.e. 3.0 cases per 1,000 people and 2.26 cases per 100 hospital discharges. The overall hospital mortality was 28.6% and the authors estimated that, in 1995, severe sepsis accounted for 9.3% of all deaths in the United States. The 28-day mortality from septic shock remains between 50% and 60%, and people usually die from hypotension or progressive multiple organ failure. So far, there is no specific treatment for sepsis, except antibiotics. Researchers have explored the biological mechanisms of shock for potential interventions. Corticosteroids have been a particular focus because of their influence on the immune response. In sepsis, the hypothalamic-pituitary gland hormonal pathway to the adrenal glands stimulate corticosteroid production. These hormones affect inflammation through the white blood cells, cytokines (proteins that influence the immune response), and nitric oxide production. In septic shock, cytokines may suppress cortisol response to the adrenocorticotropin hormone. This causes poor adrenal activity in almost half of patients, and possibly body tissues become resistant to corticosteroids, through fewer corticosteroids receptors or receptors with lower affinity. Corticosteroid treatment improves survival in various experimental models of septic shock. For these reasons, we would anticipate that corticosteroid treatment is of benefit in human septic shock. Then, we conducted a large multicenter, randomized, placebo-controlled, double blind trial evaluating the combination of 200 mg of hydrocortisone to 50 mcg of fludrocortisone given daily for seven days. This study was ended in March 1999 and showed that the corticosteroid treatment was associated with an almost 30% relative risk reduction of mortality. In other words, one additional life could be saved for every seven patients given corticosteroid treatment.

We’ve been involved in this research since 1991 after discovering the high prevalence of adrenal gland dysfunction in patients with severe infections.

Professor Djillali Annane, M.D., Ph.D.
University of Paris
Faculty of Medicine Paris Quest
Medical Intensive Care Unit
Raymond Poincaré University Hospital
Garches, France