Nancy A. Melville

January 21, 2013

SAN JUAN, Puerto Rico — Mortality rates are reduced when patients with severe sepsis and septic shock are provided fluid resuscitation within 3 hours of onset, according to research presented here at the Society of Critical Care Medicine 42nd Critical Care Congress.

Early goal-directed therapy is a widely practiced approach for severe sepsis and septic shock, and fluid resuscitation within 6 hours is recommended (N Engl J Med. 2001;345:1368-1377). Research on a faster approach has been lacking, according to lead author Sarah Lee, MD, a critical care internal medicine fellow at the Mayo Clinic in Rochester, Minnesota.

"It makes physiological sense that decreasing the time of hypoperfusion of vital organs would have less end-organ damage," which would lead to better outcomes," Dr. Lee told Medscape Medical News. "However, giving fluid faster than the 3 hours just wasn't thought of before, at least in the literature. We are hoping to challenge this ingrained doctrine that 6 hours for fluid resuscitation may not be a good enough goal."

In their study, Dr. Lee and colleagues evaluated 594 patients who had been admitted to the hospital with severe sepsis and septic shock and who had detailed fluid data available.

A univariate analysis showed that the median amount of fluid within the first 3 hours was higher in those who survived to discharge than in those who died (2085 vs 1600 mL; = .007).

The investigators adjusted for factors such as age, admission weight, total fluid administration in the first 6 hours after sepsis onset, Apache III score at admission, and Charlson score. The receipt of more total fluid in the first 3 hours after sepsis onset was associated with a decrease in hospital mortality (odds ratio, 0.34; 95% confidence interval, 0.15 - 0.75; = .008).

"Even though the 2 groups — survivors and patients who died in the hospital — received the same total amount of fluid in the first 6 hours, there was a big difference in mortality and other clinical outcomes in the group that received a greater proportion of fluid in the first 3 hours," Dr. Lee reported.

Timing Fluids Important

This study underscores the role of central venous oxygen saturation (ScVO2) in sepsis, she noted.

In general, the median and mean values of the patients who died met the early goal-directed therapy for central venous pressure and mean arterial pressure, but not for ScVO2," Dr. Lee explained. "This correlates with studies saying that ScVO2 may be one of the more important clinical markers for tissue hypoperfusion," she said.

The importance of early fluid resuscitation in sepsis patients even in the prehospital phase has gained attention in recent years. Dr. Lee noted that emergency responders now start fluids in the field if they suspect sepsis.

We hope that this will help guide physicians to emphasize early aggressive fluid resuscitation in sepsis and that every hour of hypoperfusion counts.

This study provides evidence to support such practices, Dr. Lee said. "We hope that this will help guide physicians to emphasize early aggressive fluid resuscitation in sepsis and that every hour of hypoperfusion counts."

Lance Becker, MD, professor of emergency medicine at the University of Pennsylvania in Philadelphia, agrees that logic dictates that earlier fluid resuscitation benefits sepsis patients.

"Part of what we know is that the physiology of shock is such that when you let a person stay in shock, their tissues respond in some ways by making that shock even worse, so it sort of becomes an amplification cycle," he told Medscape Medical News.

"Some of those signals, when the blood pressure is low, continue to keep the blood pressure low and make the patient get worse. That's why people can ultimately die if they're not treated at all," he explained.

With guidelines for early fluid resuscitation somewhat lacking, the study's findings are particularly important, Dr. Becker said.

"There is good physiology to support this, but there has not been a lot of study in this area. Scientific societies are very hesitant to put down hard and fast recommended timelines, in part because some communities are simply different than others, and there are actually very few guidelines on how quickly you need to do something," he said.

"I think this will help in the national discussion in the community of people who take care of people in shock and what they need to consider when they make guidelines," Dr. Becker explained.

This study did not receive outside funding. Dr. Lee and Dr. Becker have disclosed no relevant financial relationships.

Society of Critical Care Medicine (SCCM) 42nd Critical Care Congress: Abstract 26. Presented January 20, 2013.