Intuition and the reigning treatment paradigm tell us that in critically ill patients with acute kidney injury (AKI), a.k.a. acute renal failure (ARF), fluid resuscitation should be beneficial. You’ve got to maintain renal perfusion to avoid a worsening of the insult, and extra intravenous fluids should help do that — or so the clinical reasoning goes — but it was always based on theory and medical lore, not outcomes data from good clinical trials. Multiple observational studies [Bouchard, Payen, Foland] have in fact suggested the opposite: that positive fluid balance in people with renal failure is linked with increased mortality.
Now Rinaldo Bellomo, Alan Cass, Louise Cole et al add their post-hoc crunching of the numbers from the randomized RENAL study, concluding that extra IV fluids may do much more harm than good. They found a negative fluid balance in ICU patients was strongly associated not only with survival and shorter ICU and hospital stays, but with a reduced need for dialysis and other renal replacement therapies. Their results are in the June 2012 Critical Care Medicine.
What They Did
Authors retrospectively analyzed the data from 1453 of the 1508 patients enrolled in the Randomized Evaluation of Normal vs. Augmented Level replacement therapy (RENAL study), published in NEJM in 2009. Subjects all had acute renal failure (ARF) requiring continuous renal replacement therapy. The RENAL trial tested high vs. low intensity renal replacement therapy in ICU patients, and found no difference in 90 day mortality.
Here, authors looked back at the RENAL study patients’ daily “ins and outs,” or daily fluid balance. Patients’ fluid balances were regressed against many variables in multiple regression models. They tried to control for likelihood for needing fluid resuscitation by correcting for severity of illness and creating a propensity scoring model for positive fluid balance. While clever, these statistical tricks should in no way be construed to be definitive “confounder-cleansers.”
What They Found
Survivors in the RENAL trial had a negative daily fluid balance (average -234 mL/day) compared to a positive fluid balance in nonsurvivors (+560 mL/day). During their entire ICU stays, survivors averaged -1941 mL compared to an average positive fluid balance of +1755 mL in those who died. A negative mean daily fluid balance was associated with a nearly 70% reduction in 90-day risk of death (odds ratio 0.32 with a 95% CI of 0.24 to 0.43).
Negative fluid balance was also independently associated with a reduced need for dialysis/renal replacement therapy (p=0.002) and fewer ICU and hospital days (p < 0.01). All these findings persisted through the application of various statistical models, intended to reduce confounding (e.g., a patient with hypotension requires more fluids and is also at higher risk of renal failure and mortality, but that’s likely due to the hypotension and its cause(s), not from the extra fluids she receives).
What It Means
In this retrospective, post-hoc analysis of data from a large randomized trial not designed to test this question, a negative fluid balance was independently associated with a significant reduction in 90-day mortality, hospital stays, and need for renal replacement among critically ill patients with acute renal failure requiring continuous renal replacement therapy.
While it’s only circumstantial evidence, add it to the multiple observational trials that suggest the same signal, and you’ve got sufficient grist to justify a large randomized trial to test this question specifically. It’s already known that conservative fluids are beneficial in trauma patients and those with acute lung injury/ARDS (although a recent trial raises a few concerns about cognitive function in ARDS survivors treated with conservative fluids). Perhaps “keeping the kidneys wet” with extra IV fluids when they’re failing is precisely the wrong approach (by provoking congestion, reducing hydrostatic gradients at the glomeruli, and impairing renal perfusion).
Until that trial is done, though, it may be hard for intensivists to keep our trigger fingers off the IV stopcock. It’s painful for a doctor to watch a patient’s kidneys fail and not “do something” about it. IV fluids have always seemed benign and plausibly beneficial for patients in acute renal failure–even if they later prove to be neither.
The RENAL Replacement Therapy Study Investigators. An Observational Study Fluid Balance and Patient Outcomes in the Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy Trial. Crit Care Med; 2012;40:1753-1760.