First 24 Hours of Severe Sepsis May Be Most Important

DES PLAINES, Ill. Organ function improvement, or lack thereof, in the first 24 hours of severe sepsis is highly predictive of the overall disease course, according to an article in the October issue of Critical Care Medicine.

The researchers found that improvement in respiratory, cardiovascular or renal function during the first day of severe sepsis was associated with improved 28-day survival. Subsequent clinical improvement had little impact on survival likelihood. Improvement in other organ systems beyond the first study day was not associated with prediction of survival. 

These data suggest that the outcome for patients with severe sepsis may largely be determined within the first post-baseline day of therapy and that frequent reassessment of the direction of change in organ dysfunction is imperative to maximize survival in severe sepsis, says lead author Mitchell M. Levy, MD, professor of medicine at Brown University in Providence, R.I.

Sepsis incidence has been on the rise during the last 20 years, and mortality rates are between 20 percent and 50 percent depending on sepsis severity. Major organs and systems become dysfunctional or fail as the disease progresses to severe sepsis and possibly septic shock.

If patients are not getting worse at the end of 24 hours, many times they are considered to be stable, Levy says. Our data suggest that this interpretation of patient stable may be a false sense of comfort.

The researchers analyzed organ dysfunction data from two placebo-controlled severe sepsis trials (PROWESS and sPLA2 Inhibitor trials) to determine if a risk-prediction model based on organ function assessment at baseline and day one would be predictive of 28-day survival.

The hypothesis generating aspect of our data is whether future interventions should really be targeted at identifying and treating patients with severe sepsis in the first 24 hours, comments Levy. At Rhode Island Hospital, we already aggressively resuscitate septic patients within the first six hours of identification. We are already pursuing the natural implications of the data from our study.

The researchers believe that study is an important contribution to the challenge to improve critical care research. They suggest that potential implications include stratifying patients by change in Sequential Organ Failure Assessment scores over the first several hours to assess the efficacy of a new therapy.

In an accompanying editorial, Jürgen Graf, MD, notes that much of critical care medicine involves risk assessment and outcome prediction. Graf says that initial risk assessment may influence timing and institution of potentially life saving therapeutic interventions and thereby improve outcomes.

Graf, from Philipps-University Marburg in Marburg, Germany, concludes, Immediate and targeted orientated correction of cardiovascular and pulmonary dysfunction currently seems the most encouraging approach to substantially reduce the incidence of the multiple organ dysfunction syndrome and thus subsequent mortality in patients with severe sepsis. Treatment algorithms proposing a rational decision making process have already been published but need to be applied in both routine clinical practice and future clinical trials. Levy et al. have reassured us that attention must be paid to the initial care of the patient with severe sepsis and septic shock, since lost time may never be found again (Benjamin Franklin).

A growing body of literature points to the importance of early identification and intervention in patients with severe sepsis who might have better chances of surviving with early, aggressive therapy says Joseph E. Parrillo, MD, editor-in-chief of Critical Care Medicine. Data that may help intervention timing is of crucial importance.

Source: Society of Critical Care Medicine