​Sepsis - challenges and controversies

Sepsis is the tenth leading cause of death in industrialized countries, and the leading cause of death in the intensive care unit (ICU).

It represents a major burden on the medical care system. Direct costs in ICU patients with these conditions in Germany amount to around five billion Euros each year.

A recent analysis of administrative data from German hospitals indicated a continuous increase of 5.7% per year in the prevalence of sepsis between 2007 and 2013. Although mortality rates from septic shock slightly decreased in the last three years of the observation period, in-hospital mortality rates were as high as 58.8% in 33,815 patients treated from septic shock in 2013.

Specific sepsis therapies are lacking; however, several supportive interventions have been suggested to be effective in improving outcome in these patients. In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for severe sepsis and septic shock under the auspices of the Surviving Sepsis Campaign (SSC), an international effort to increase awareness and improve outcome in severe sepsis.

These guidelines have been subjected to repeated updates to adapt it to the evolving knowledge in this field. Early resuscitation of patients with sepsis-induced tissue hypo-perfusion is crucial and should not be delayed pending ICU admission. In a key randomized study by Rivers et al., early goal-directed therapy was shown to improve survival for emergency department patients presenting with septic shock. The results of this study have been challenged by three recent randomized trials.

Notably, optimal resuscitation of patients with sepsis implies early volume substitution, and vasopressor therapy should be initiated when volume resuscitation is not able to rapidly restore an acceptable hemodynamic profile. Nonetheless, there is a controversy concerning the choice of the most appropriate type of fluids and vasoactive agents and the optimal targets for resuscitation. 

Special emphasis should be directed towards treatment of the underlying infection. Intravenous antibiotic therapy should be started within the first hour of recognition of severe sepsis and should include one or more drugs that have activity against the likely pathogens and that penetrate into the presumed source of sepsis.

Reassessment of antibiotic therapy with microbiologic and clinical data is also helpful to narrow coverage and reduce the duration of therapy, which reduces the likelihood that the patient will develop superinfection with pathogenic or resistant organisms. Antibiotic stewardship programs are gaining popularity to optimize antibiotic administration in this context.

Diagnostic methods aiming at an early and precise detection of infection are currently being investigated for clinical utility, and these include methods for the rapid detection of microbial DNA.

Emerging new diagnostic tools will not only allow faster and more precise pathogen detection but will also improve our insight into the biochemical and biomolecular alterations which occur in sepsis. These insights will enable us to stratify sepsis patients into more homogenous subgroups which are more likely to respond to specific adjunctive therapeutic approaches.

Novel methods for early detection of microcirculatory disturbances, including microvascular imaging techniques, may also have major therapeutic implications in targeting resuscitation and identifying patients at risk of developing multi-organ dysfunction despite normal haemodynamic parameters.

New sepsis therapies are emerging and are currently being evaluated in terms of their safety and efficacy.