We studied a single-center, medical-surgical population of 173 septic patients, 78 % of whom had septic shock, with an overall ICU mortality of 34 %. A positive fluid balance was independently associated with an increase in the risk of death. We also observed a relationship between the change in fluid balance over time and mortality.
A positive association between fluid balance and mortality is quite well established. Results from the SOAP study, an observational study of 3,147 adult patients from 198 European ICUs, indicated that, in patients with sepsis, fluid balance was an independent risk factor for mortality [6]. Alsous et al. [7] also showed, in a single-center retrospective study of 36 patients with septic shock, that patients with a negative fluid balance (less than 500 ml) on at least 1 of the first 3 days after the onset of septic shock had better hospital survival. In ICU patients with sepsis or septic shock, Sirvent et al. [10] reported that the accumulated positive fluid balance at 48, 72, and 96 hours was associated with higher mortality, and in a retrospective study, de Oliveira et al. [12] noted that a late (between 24 and 48 hours after diagnosis) positive fluid balance was an independent risk factor for mortality in severe sepsis. In a pediatric septic population, Abulebda et al. [8] showed that a positive fluid balance was associated with worse outcomes (increased mortality and complicated course) in patients with a low initial mortality risk but not in patients at moderate or high risk of death.
However, it is important to consider a time-related relationship, because fluid administration is dynamic, changing according to the patient’s evolution. Recently, it has been suggested that fluid administration for patients in shock should be considered according to the ROSD mnemonic: rescue, optimization, stabilization, and de-escalation phases [15]. We did not focus on the initial, rescue phase of fluid resuscitation, but rather evaluated the time course over several days. Indeed, the role of early goal-directed therapy, including fluid administration, is controversial [16, 17]. In a prospective, multicenter, observational study, Smith and Perner [18] reported that patients with septic shock who initially received a large volume of fluid had improved survival compared to patients who received lower volumes, despite comparable admission severity of illness. However, as noted by Prowle in the accompanying commentary [19], the median of 7.5 liters that was administered in the first 72 hours was a relatively low volume for fluid resuscitation of septic patients. Lee et al. [20] also reported, in a retrospective study, that the initial amount of administered fluid was greater in survivors (at discharge) than in non-survivors. In patients with septic shock complicated by acute respiratory failure, Murphy et al. [21] noted that patients managed with the combination of adequate initial fluid resuscitation and conservative fluid management in the subsequent days had lower in-hospital mortality than other patients.
In our study population, the fluid balance was initially quite similar in the survivors and non-survivors but the non-survivors received more fluids so that already from the second day, the fluid balance was more positive in the non-survivors. After initial resuscitation, less fluid was administered in both groups, and the fluid balance decreased steadily in the survivors but not in the non-survivors. The differences in fluid balance were due to a greater fluid input in the non-survivors rather than to a lower fluid output. Survivors were more likely than non-survivors to have a negative fluid balance early in their ICU stay, and a positive fluid balance was an independent prognostic factor for ICU mortality. The relationship between positive fluid balance and mortality was present regardless of whether or not diuretics or RRT were used.
The single-center nature of our study may be seen as a limitation, but it can also be a strength by limiting variability in patient management as different centers may have different protocols for fluid administration and use of diuretics and RRT. Single-center studies may, therefore, have increased intrinsic validity.