Objective: To determine whether central venous pressure and fluid balance after resuscitation for septic shock are associated with mortality.
Design: We conducted a retrospective review of the use of intravenous fluids during the first 4 days of care.
Setting: Multicenter randomized controlled trial.
Patients: The Vasopressin in Septic Shock Trial (VASST) study enrolled 778 patients who had septic shock and who were receiving a minimum of 5 μg of norepinephrine per minute.
Measurements and Main Results: Based on net fluid balance, we determined whether one's fluid balance quartile was correlated with 28-day mortality. We also analyzed whether fluid balance was predictive of central venous pressure and furthermore whether a guideline-recommended central venous pressure of 8–12 mm Hg yielded a mortality advantage. At enrollment, which occurred on average 12 hrs after presentation, the average fluid balance was +4.2 L. By day 4, the cumulative average fluid balance was +11 L. After correcting for age and Acute Physiology and Chronic Health Evaluation II score, a more positive fluid balance at both at 12 hrs and day 4 correlated significantly with increased mortality. Central venous pressure was correlated with fluid balance at 12 hrs, whereas on days 1–4, there was no significant correlation. At 12 hrs, patients with central venous pressure <8 mm Hg had the lowest mortality rate followed by those with central venous pressure 8–12 mm Hg. The highest mortality rate was observed in those with central venous pressure >12 mm Hg. Contrary to the overall effect, patients whose central venous pressure was <8 mm Hg had improved survival with a more positive fluid balance.
Conclusions: A more positive fluid balance both early in resuscitation and cumulatively over 4 days is associated with an increased risk of mortality in septic shock. Central venous pressure may be used to gauge fluid balance ≤12 hrs into septic shock but becomes an unreliable marker of fluid balance thereafter. Optimal survival in the VASST study occurred with a positive fluid balance of approximately 3 L at 12 hrs.
From the University of British Columbia Critical Care Research Laboratories, Heart + Lung Institute, St Paul's Hospital, Vancouver, British Columbia, Canada.
Supported by the Canadian Institutes of Health Research.
Dr. Boyd is a Providence Health Care Research Institute Physician Scholar. Dr. Walley is a Michael Smith Foundation for Health Research Distinguished Scholar.
The authors have not disclosed any potential conflicts of interest.
For information regarding this article, E-mail: John.Boyd@hli.ubc.ca