The faster fluid is removed using continuous dialysis from patients with failing kidneys, the higher the likelihood they will die in the next several months, according to a study published today in JAMA Network Open by University of Pittsburgh School of Medicine researchers.
Nearly two-thirds of critically ill patients with acute kidney injury have extra fluid accumulating in their bodies, which can put pressure on their lungs and cause injury to other organs.
To relieve that pressure, clinicians routinely remove the excess fluid from the blood while performing dialysis in the intensive care unit.
But there is no guidance on how fast that fluid should be removed.
“We want to get this excess fluid out of our patients before it causes damage but, in removing it, we’re actually causing a controlled loss of fluid that can sometimes cause stress on the heart and lead to dangerously low blood pressure,” said lead author Raghavan Murugan, M.D., M.S., associate professor in Pitt’s Department of Critical Care Medicine and UPMC physician.
“So the question – how rapidly to remove fluid? – has been asked in the critical care community for many years, but there’s been no good answer.”
Previous studies in outpatients who are not critically ill found that routine dialysis – a procedure to remove waste, toxins, salt and extra water from the blood of people whose kidneys have failed – when performed too quickly, is associated with increased risk of death.
Murugan partnered with senior author Rinaldo Bellomo, M.D., Ph.D., a professor of intensive care medicine at the University of Melbourne in Australia to find out if that finding extends to critically ill patients.
Their team examined data from 1,434 patients that Bellomo had previously collected for the Randomized Evaluation of Normal vs. Augmented Level of Renal Replacement Therapy trial, which was conducted between December 30, 2005 and November 28, 2008 in 35 intensive care units in Australia and New Zealand.
The research team found that for every 0.5 milliliter increase in fluid removed per kilogram of the patient’s weight per hour (0.5 mL/kg/hr), their risk of death increases.
That translates to a 51% to 66% higher risk of death in the next three months for critically ill patients for whom excess fluid is removed at a rate greater than 1.75 mL/kg/hr, compared to patients for whom excess fluid is removed at a rate less than 1.01 mL/kg/hr.
For the average older American male, that’s a difference of removing a gallon of fluid in about one day versus a little under two days.
Murugan is quick to point out that his analysis shows association, not causation; until a clinical trial is performed to specifically test the effects of removing fluid faster versus slower, he cannot say for sure that removing fluid slowly is better for the patient.
And, in some cases, such as imminent heart failure, Murugan says a more rapid removal of fluid might be warranted to prevent sudden death.
“You have to balance the pros and the cons, and decide how fast to remove fluid based on your patient’s clinical condition,” said Murugan, who also is a member of Pitt’s Clinical Research, Investigation, and Systems Modeling of Acute Illness Center and the Center for Critical Care Nephrology.
“But in a patient where I can’t find an immediate need to get fluid out quickly, I’ll be removing fluid at a slower rate until we get definitive results and guidance from a clinical trial.”
The United States is home to more than 350,000 hemodialysis (HD) patients.1
Dialysis patients experience high rates of mortality, driven largely by an exceptionally high rate of cardiovascular (CV)-related mortality, which exceeds that of the general population by 10- to 20-fold.2,3
Dialysis patients have a high prevalence of traditional CV risk factors such as diabetes and hypertension, as well as a number of additional risk factors related to their kidney dysfunction and/or to the dialytic procedure such as autonomic dysfunction, vascular calcification and stiffness, and increased levels of circulating inflammatory mediators.1,4,5
Unfortunately, many of these factors have proven to be either non-modifiable or difficult to modify within the scope of current dialytic practice.
One compelling and potentially modifiable putative CV risk factor is ultrafiltration rate (UFR; the rate at which fluid is removed during the course of dialysis).
As native kidney function wanes, ultrafiltration is necessary to maintain volume control (i.e., salt and water balance), but it simultaneously and disadvantageously promotes non-physiological fluid shifts and hemodynamic instability.
In turn, these factors contribute to tissue ischemia, maladaptive cardiac structural changes, myocardial stunning, arrhythmia, and cardiac sudden death.6–14
Despite obvious biological plausibility, the association between UFR and CV morbidity and mortality has not been well studied.
The only previous study in this regard examined UFR > 10 (versus ≤10) ml/h/kg, showing a small increase in all-cause mortality (adjusted RR = 1.09; P = 0.02) but no increase in cardiopulmonary mortality (adjusted RR = 1.04; P = 0.41).15 Subsequent data suggest that the cut point of 10 ml/h/kg may have been too low to observe a true UFR–CV mortality association,16 and the issue remains unsettled.
Therefore, we undertook this study in order to clarify the associations between UFR and both all-cause and CV-related mortality among patients undergoing chronic, thrice-weekly HD. We hypothesized that higher UFR would be associated with greater CV-related mortality that, in turn, would drive all-cause mortality. We used the data from the Hemodialysis Study (HEMO), as this study is one of very few large-scale prospective studies in chronic dialysis patients in which the CV outcomes were rigorously adjudicated according to standardized criteria.17
Moreover, we sought to leverage these data to identify a threshold at which higher UFR may be detrimental to CV health and survival.
More information:JAMA Network Open (2019). DOI: 10.1001/jamanetworkopen.2019.5418
Journal information: JAMA Network Open
Provided by University of Pittsburgh
