Reducing mortality in sepsis: new directions

Abstract

Considerable progress has been made in the past few years in the development of therapeutic interventions that can reduce mortality in sepsis. However, encouraging physicians to put the results of new studies into practice is not always simple. A roundtable was thus convened to provide guidance for clinicians on the integration and implementation of new interventions into the intensive care unit (ICU). Five topics were selected that have been shown in randomized, controlled trials to reduce mortality: limiting the tidal volume in acute lung injury or acute respiratory distress syndrome, early goal-directed therapy, use of drotrecogin alfa (activated), use of moderate doses of steroids, and tight control of blood sugar. One of the principal investigators for each study was invited to participate in the roundtable. The discussions and questions that followed the presentation of data by each panel member enabled a consensus recommendation to be derived regarding when each intervention should be used. Each new intervention has a place in the management of patients with sepsis. Furthermore, and importantly, the therapies are not mutually exclusive; many patients will need a combination of several approaches--an "ICU package". The present article provides guidelines from experts in the field on optimal patient selection and timing for each intervention, and provides advice on how to integrate new therapies into ICU practice, including protocol development, so that mortality rates from this disease process can be reduced.

Figure 1

Mortality prior to hospital discharge in patients receiving a tidal volume of 6 and 12 ml/kg ideal body weight.

Figure 2

Proportion of patients alive and off the ventilator having been ventilated with a tidal volume of 6 and 12 ml/kg ideal body weight.

Figure 3

Median number of ventilator-free days in patients receiving a tidal volume of 6 and 12 ml/kg ideal body weight.

Figure 4

Twenty-eight-day survival in patients treated with drotrecogin alfa (activated) or placebo: all-cause mortality.

Figure 5

Most important effects on morbidity [46]. CVVH, continuous venovenous hemofiltration; ICU, intensive care unit; NNT, number needed to treat; RRR, relative risk reduction.