Immunomodulation in Sepsis
Immunomodulation in Sepsis
Despite advances in supportive care of critically ill patients, sepsis remains an important cause of death worldwide. More than 750,000 individuals develop severe sepsis in North America annually, with a mortality rate varying between 35 and 50%. Over recent years, numerous efforts have been committed to understanding the pathophysiology of septic syndrome, as well as attempts to intervene in the inflammatory cascade with the aim of altering the outcome of the syndrome and to improve survival. Not all of these attempts have been successful. Issued guidelines by the International Sepsis Forum have incorporated only the use of corticosteroids, tight glycemic control and the use of recombinant activated protein C as recommendations for the management of the septic patient along with the initial resuscitation and infection-site control measures. These strategies along, with novel attempts of immunomodulation, are thoroughly reviewed in this article.
Sepsis is one of the leading causes of death, accounting for more than 1.5 million deaths annually in Europe and North America. Data from the Hellenic Sepsis Study Group report an almost 68% mortality rate from septic shock for patients hospitalized outside an intensive care unit (ICU) and 55% for patients hospitalized inside an ICU. Initial resuscitation of the septic patient requires prompt administration of oxygen and fluids and early administration of appropriate antibiotics. It has been proved that one of the most important factors determining outcome of a patient with septic shock is the initiation and administration of proper antimicrobial therapy. This should start within the first hour from the advent of hypotension; every hour of delay results in a relative decrease of survival by 7.6%.
Even when antimicrobials are administered early, the mortality rate remains high. This problem may be further aggravated for sepsis developing after ICU admission when multidrug-resistant pathogens are implicated and available antimicrobials are limited. It is thus obvious that proper management of the septic patient cannot solely rely on the single administration of antimicrobials and on the eradication of the septic focus and that further insight in the complex pathogenesis of sepsis is mandatory. This may allow the modulation of the inflammatory cascade, an approach known as immunomodulation.
The applied agents that have been developed to modulate the septic cascade differ according to the pathogenesis pathway they interfere with. This article provides an overview of the results of major clinical trials that have been conducted in recent decades in the attempt to modulate the inflammatory response of the septic host.
Abstract and Introduction
Abstract
Despite advances in supportive care of critically ill patients, sepsis remains an important cause of death worldwide. More than 750,000 individuals develop severe sepsis in North America annually, with a mortality rate varying between 35 and 50%. Over recent years, numerous efforts have been committed to understanding the pathophysiology of septic syndrome, as well as attempts to intervene in the inflammatory cascade with the aim of altering the outcome of the syndrome and to improve survival. Not all of these attempts have been successful. Issued guidelines by the International Sepsis Forum have incorporated only the use of corticosteroids, tight glycemic control and the use of recombinant activated protein C as recommendations for the management of the septic patient along with the initial resuscitation and infection-site control measures. These strategies along, with novel attempts of immunomodulation, are thoroughly reviewed in this article.
Introduction
Sepsis is one of the leading causes of death, accounting for more than 1.5 million deaths annually in Europe and North America. Data from the Hellenic Sepsis Study Group report an almost 68% mortality rate from septic shock for patients hospitalized outside an intensive care unit (ICU) and 55% for patients hospitalized inside an ICU. Initial resuscitation of the septic patient requires prompt administration of oxygen and fluids and early administration of appropriate antibiotics. It has been proved that one of the most important factors determining outcome of a patient with septic shock is the initiation and administration of proper antimicrobial therapy. This should start within the first hour from the advent of hypotension; every hour of delay results in a relative decrease of survival by 7.6%.
Even when antimicrobials are administered early, the mortality rate remains high. This problem may be further aggravated for sepsis developing after ICU admission when multidrug-resistant pathogens are implicated and available antimicrobials are limited. It is thus obvious that proper management of the septic patient cannot solely rely on the single administration of antimicrobials and on the eradication of the septic focus and that further insight in the complex pathogenesis of sepsis is mandatory. This may allow the modulation of the inflammatory cascade, an approach known as immunomodulation.
The applied agents that have been developed to modulate the septic cascade differ according to the pathogenesis pathway they interfere with. This article provides an overview of the results of major clinical trials that have been conducted in recent decades in the attempt to modulate the inflammatory response of the septic host.
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