Volume management is an essential component in maintaining hemodynamic stability, tissue perfusion and organ function. Several studies have demonstrated that early volume administration is critical to reverse tissue hypoperfusion and influence prognosis15
. However, when volume resuscitation is excessive, it may be detrimental. Indeed, fluid overload increases morbidity and mortality in patients with acute respiratory distress syndrome18, 19
, and surgical ICU patients21, 22
and lesser fluid gains are associated with better outcomes in abdominal compartment syndrome23, 24
and after colon resection21
. Because patients with AKI have impaired ability to regulate volume, they may be particularly susceptible to volume-related increases in morbidity and mortality. Some data suggests that this may be true in pediatric patients; fluid overload at the initiation of CRRT is associated with increased mortality2, 7, 8
, but even less information is available in adult patients with AKI. Recently, Payen et al
. used the “Sepsis Occurrence in Acutely ill Patients” (SOAP) database17
to evaluate whether a positive fluid balance is associated with worse outcomes in patients admitted to the ICU. They reported that patients with AKI, non-survivors had a more positive fluid balance than the survivors. The PICARD cohort group recently extended these findings25
. They analyzed the data from their cohort of critically ill adult patients with AKI and found that patients with fluid overload had a significantly higher mortality, irrespective of renal replacement therapy.
Our present study focused on the sickest of AKI patients: those requiring CRRT. These patients are usually hypotensive, and have impaired tissue perfusion and oliguria. Consequently, they usually receive aggressive volume resuscitation putting them at risk of volume overload. In fact, oliguria and fluid gains of ≥10% of body weight were common in our cohort (65% and 47%, respectively). The severity of illness of our patient cohort is underscored by the fact that the overall mortality in these patients was higher (50.6%) than that in the general ICU population with AKI that was analyzed by the SOAP investigators (35.7%). Our central finding was that despite being similar in all other aspects (severity of illness, sepsis, oliguria, etc.) the patients with VRWG ≥10% had a higher mortality than those with <10% (63% vs. 39%). Moreover, the mortality appears to further increase with VRWG ≥20%, suggesting a dose response effect of progressive fluid accumulation.
Our present study could not discern whether VRWG contributed to the increased mortality or selected out those with a higher risk of death. Fluid overload can directly worsen outcomes by increasing interstitial pressure and impairing tissue perfusion/oxygenation. In fact, it is directly associated with adverse clinical endpoints such as increased ventilator dependency, skin breakdown with sacral decubiti and poor wound healing21
. It also dilutes the serum creatinine, which may delay the detection of AKI and the initiation of therapy; indeed, we observed lower creatinine and a delay in initiating CRRT in the patients with higher VRWG. It is, therefore, tempting to speculate that the excessive mortality observed in the high VRWG was due to volume overload. However, because severely ill patients develop vasodilatation, capillary leak, third spacing26
, and hemodynamic instability, which prompts aggressive fluid resuscitation, we cannot exclude the possibility that excessive VRWG is simply a surrogate of hypotension, capillary leak and severity of illness. One argument against this possibility is that the impact of VRWG on mortality did not diminish in our multivariate analysis in which we adjusted for severity of illness. Regardless, the severity of illness scoring systems are known to perform poorly in cohorts with AKI4, 27
, thus our study may not be robust enough to detect associations between severity of illness and mortality. Therefore, our results must be interpreted cautiously. Further studies are clearly warranted to determine whether excessive VRWG is a culprit or marker of mortality and whether different fluid resuscitation strategies alter mortality in these patients.
Another strong prognostic factor of worse outcomes in our study was oliguria; mortality was 60.4% compared to 32.1% in non-oliguric subjects. This is consistent with previous reports; oliguria is consistently associated with worse outcomes in patients with AKI3, 4, 17
. However, the mechanism by which oliguria leads to worse outcomes is not known. It is tempting to speculate that oliguric patients have worse outcomes because they may are susceptible to developing fluid overload. By the same token, increased mortality in the fluid overload groups may be the result of a higher incidence of oliguria. However, this was not the case in our study as the incidence of oliguria was not different between the groups, yet there was a large difference in mortality. Our results found that oliguria and weight gain were independent predictors of mortality by mechanisms that remain to be elucidated.
The limitations of our study include the relatively small size, single center design and lack of randomization. Oliguria was not defined based on weight (mL/kg/hour) and not identical to the current definition of the Acute Kidney Injury Network. Sepsis was not based on standardized definitions, recovered as “chart diagnosis” only and subject to physicians’ bias. Weights were subject to the imprecision frequently encountered in clinical practice. The dichotomous separation of weight gain at 10%, while a meaningful value and quoted in the literature 2, 8, 22
was, in fact, a post hoc
separation of the cohort. The cohort studied is a specific subset of ICU patients, those with AKI receiving CRRT. Thus our conclusions are strictly limited this specific cohort and may not be directly extrapolated to other populations or to weight gains taking place after CRRT initiation. The practice of ICU care, CRRT and fluid management is steadily evolving, posing an important external bias on our observations. In particular, delays in obtaining renal consults may have influenced timing of CRRT initiation and led to some of the extreme weight gains observed. Further studies are needed to determine a) whether fluid overload actively contributes to the increased mortality, and b) whether targeted strategies that prevent, ameliorate or reverse fluid overload, will improve survival.