Sepsis: lessons learned in the last century and future directions.

In 1997, of a global total of 52.2 million deaths, 17.3 million were caused by infectious and parasitic diseases. This exceeds the number of deaths caused by circulatory diseases, cancer, and respiratory diseases, and thus infections remain a major problem in the world. It has also been reported that every day in 1997, about 365 000 babies were born, and about 140 000 people died, giving a natural increase of about 220 000 people a day. The proportion of older people requiring support from adults of working age has increased from 10.5% in 1955 to 12.3% in 1995 and will further increase to 17.2% in 2025. Furthermore, the number of people over age 65 years is expected to rise from 390 million currently to 800 million by 2025, reaching 10% of the total population, and this important factor should also be taken into account in all future studies of all diseases and particularly sepsis. Although the introduction of antibiotics more than 50 years ago resulted in a decline of sepsis-induced mortality from 55% to approximately 35%, there has been no significant reduction in the mortality of patients with sepsis since the introduction of antibiotics. Trauma is the leading cause of death in the United States for those between the ages of 1 and 38 years, and despite numerous advances in resuscitation of trauma victims that have resulted in increased short-term survival, sepsis and multiple organ failure are responsible for upwards of 60% of deaths in the intensive care unit. Moreover, the mortality rate of trauma patients each year far exceeds the total number of patients with acquired immunodeficiency syndrome dying over a 10-year period. A MEDLINE search under the heading sepsis currently lists nearly 54 000 articles, including animal studies as well as human clinical trials. Although numerous studies of sepsis are being carried out, a report in 1996 indicated that, despite newer advances in antimicrobial therapy, the death rate from sepsis has actually increased from 4.2 to 7.7 per 100 000 from 1980 to 1992, which represents an increase of 83% in mortality rates over this 12-year period. Patients with severe injuries, transplantations, cancer, diabetes, and similar illnesses are surviving longer now. These patients, however, have an increased risk of infection. Moreover, the increasing use of devices such as bladder and intravenous catheters for hyperalimentation raises the risk of sepsis. It is encouraging, however, that the complex pathophysiology of bacterial sepsis is gradually becoming better understood as more studies are reported. Through more concentrated research, information should be forthcoming that will lead to better care of patients with sepsis. Although extensive research is being carried out to determine the mechanism of sepsis-induced organ dysfunction and failure, we still do not have the clear-cut answers. It is difficult to perform controlled studies in patients with sepsis because of the diversity of organisms, preexisting diseases, and other variables. In view of this, intensive study of animal models that simulate clinical conditions would be useful, even though the final testing of any results will eventually have to be carried out in patients with sepsis. From the Center for Surgical Research, Brown University and Rhode Island Hospital, Providence. PRESIDENTIAL ADDRESS