Survey of U.S. Critical Care Practitioners on Net Ultrafiltration Prescription and Practice Among Critically Ill Patients Receiving Kidney Replacement Therapy

Fluid overload is prevalent in two-thirds of critically ill patients with acute kidney injury when kidney replacement therapy is initiated in an intensive care unit and is independently associated with morbidity and mortality and impaired recovery of kidney function among survivors [1, 2, 3]. Net ultrafiltration (UF_NET), also known as net fluid removal during kidney replacement therapy, is frequently used by clinicians to treat fluid overload for more than seven decades and is currently recommended by several international clinical practice guidelines [4, 5, 6]. This recommendation is based on several observational studies suggesting that fluid removal is associated with a lower risk of death [1, 7, 8]. However, several aspects of UF_NET among acutely ill patients_, including optimal timing of initiation, specific indications, rate, barriers, and management of complications, remain uncertain. In addition, several quality metrics have also been developed for fluid removal based on observational studies without solid evidence for practice from randomised clinical trials [9, 10].

Current observational studies suggest a “J” shaped relationship between the rate of UF_NET (i.e., the net fluid removal rate) and mortality. Specifically, both slower and faster rates of UF_NET are associated with an increased risk of death compared to moderate UF_NET rates [11, 12, 13, 14, 15]. However, data on net ultrafiltration practice patterns in the intensive care unit (ICU) and clinician perspectives on fluid removal are scarce.

In the U.S., intensivists, nephrologists, and advanced practice providers typically prescribe fluid removal; intensive care unit and dialysis nurses perform UF_NET and manage hemodynamics following a provided prescription.

Thus, it would be essential to understand perspectives towards UF_NET and the barriers and challenges related to fluid removal among physicians and nurses. For example, a previous study by Murugan et al. (2020) using a multinational survey of critical care practitioners revealed wide regional variations in dosing of diuretics, criteria used for initiation and prescription of UF_NET, modality of kidney replacement therapy used for UF_NET, the assessment of prescription dose of UF_NET, the monitoring of fluid balance, management of complications and perceived barriers to UF_NET [16]. Among critical care practitioners in Europe, there was also variation noted in attitudes toward UF_NET prescription and processes of care between physicians and nurses [17].

In the present study, a secondary analysis was conducted using data from a multinational survey [16] to understand attitudes of U.S. critical care practitioners regarding the prescription and practice of UF_NET.

Specifically, the criteria for initiation and prescription of UF_NET, monitoring fluid balance, managing complications, and perceived barriers to successful fluid removal were examined. Additionally, the attitudes of U.S. practitioners toward protocol-based management and willingness to enrol patients in clinical trials comparing protocol-based ultrafiltration versus usual care was explored.

In this survey of U.S. physicians, nurses, and advanced practice providers, significant variation in attitudes toward the practice of UF_NET was found. Most practitioners were ICU nurses, had an average of 8.7 years of experience, and were from university-based hospitals. Although this survey predominantly reflects nurses attitudes towards the practice of UF_NET, variations were noted in the assessment of prescribed-to-delivered dose of UF_NET, the use of continuous kidney replacement therapy for UF_NET, the methods used to achieve UF_NET, and assessment of net fluid balance during CKRT. There was also variation in interventions performed for hemodynamic instability such as decreasing or stopping UF_NET and increasing or starting a new vasopressor, administration of albumin and mannitol bolus, as well as barriers to UF_NET such as unavailability of machines, belief that early and protocol-based fluid removal is beneficial, and willingness to enrol patients in a clinical trial.

The survey findings of U.S. practitioners were similar to findings in a global survey and Europe in that there is important practice variation in several care processes for UF_NET [16, 17]. This is partly due to the lack of evidence-based guidelines for UF_NET prescription and practice in critically ill patients. Unlike solute clearance management, where there is strong evidence for dosing, timing, and modality of kidney replacement therapy, no such evidence exists for UF_NET prescription and practice in critically ill patients [19, 20, 21]. In addition, we found variation in the assessment of prescribed-to-delivered dose of UF_NET between physicians and nurses. This finding may either represent actual challenges to implementing UF_NET due to various reasons (e.g., hemodynamic instability) despite current quality guidelines to target >80% of prescribed dose [10].

As is the case in Europe, CKRT was the most frequent modality volume management in the U.S. However, while 90% of practitioners in Europe reported using CKRT for volume management, only 60% of the U.S. practitioners used CKRT, with physicians reporting higher use than nurses [17]. This difference in practice might be due to a lack of evidence from randomised clinical trials confirming the benefit of CKRT among patients treated with UF_NET. In addition, while CKRT is superior for volume control in critically ill patients, no randomised control trials have been conducted comparing CKRT with other modalities of kidney replacement therapy for fluid removal [22].

Although no reported variation was found between clinicians among the rate of UF_NET prescription for hemodynamically stable and unstable patients on CKRT, we found substantially lower reported UF_NET rates in the U.S. compared with practitioners in Europe and the global survey [16, 17]. Previous research showed that among patients with >5% fluid overload before initiation of kidney replacement therapy, a UF_NET intensity >25 mL/kg/day was associated with lower 1-year mortality [23]. In contrast, a secondary analysis of the Randomised Evaluation of Normal versus Augmented Level (RENAL) trial reported that a UF_NET rate >1.75mL/kg/h was associated with a higher risk of 90-day mortality [11].

Significantly, more negative daily fluid balance attenuated the harmful mortality effect of high UF_NET (>1.75 mL/kg/h) rate group compared with moderate (1.01-1.75 mL/kg/h) and low (<1.01 mL/kg/h) UF_NET rate groups. However, despite this attenuation, the high UF_NET rate group remained significantly and directly associated with higher mortality than the moderate UF_NET rate group and lower renal recovery [15, 24].

Similarly, a recent study supported that a UF_NET rate >1.75mL/kg/h in the first 48 h was associated with increased mortality, lower potassium, higher hypophosphatemia, longer duration of CKRT, and more extended ICU stay [12]. Observational studies in chronic hemodialysis patients showed similar results: high fluid removal rates were associated with increased cardiovascular mortality, possibly due to impaired plasma refilling rate and myocardial stunning independent of interdialytic fluid gain [25, 26].

There was also a variation between clinicians in the approach to performing UF_NET during CKRT. While most clinicians (62%) reported achieving UF_NET by varying ultrafiltration rate, nearly a third of clinicians reported achieving UF_NET by combining varying ultra-filtration and replacement fluid rates, which may reflect institutional practice patterns for achieving UF_NET. In addition, nurses and nurse practitioners evaluated fluid balance hourly, more frequently than physicians, which may be due to the continued presence of the nursing staff at the bedside while delivering UF_NET in an ICU.

There was also variation in approach to managing hemodynamic instability and perceived barriers. For example, nurses and advanced practice providers more likely reported to start or increase the vasopressor dose or administer albumin than physicians. This variation might be due to the lack of guidelines for hemodynamic management during kidney replacement therapy in critically ill patients, unlike clear guidelines for managing hemodynamic instability in the outpatient setting [27]. Additionally, U.S. physicians are more likely to report the unavailability of dialysis machines as a significant barrier for fluid removal than the nurses and advanced practice providers.

Despite lack of evidence, most practitioners believed in early initiation of UF_NET despite several trials showing no difference in patient outcomes among patients with early initiation of kidney replacement therapy, even though these trials did not evaluate the timing of volume management [20]. Thus, despite variation in attitudes toward the use of protocol and timing of initiation of UF_NET, U.S. critical care practitioners were willing to enrol patients in a protocol-based clinical trial of UF_NET.

Thematic analysis of practitioner comments revealed the need for precision medicine tools to assess intravascular volume to individualise and titrate UF_NET. Clinicians also focused on various challenges related to UF_NET in the U.S. population, including lack of training, uncertainty in the timing of volume removal, communication issues between clinicians, availability of kidney replacement therapy modality for volume removal, and educational issues. These findings outline the multifactorial challenges that underlie volume management in critically ill patients and highlight the need to generate evidence-based treatment guidelines to reduce practice variation and improve patient outcomes.

The present study has several significant limitations. First, most practitioners were intensivists and ICU nurses; thus, a comparison could not be made between the responses of nephrologists and dialysis nurses. Across many hospitals in the U.S., nephrologists typically prescribe volume removal during intermittent hemodialysis in the ICU, whereas intensivists and ICU nurses typically manage volume removal during CKRT. Nevertheless, the current survey is the first to explore the clinician practice variation in UF_NET in the U.S. Second, we could not determine the actual response rate for U.S. practitioners since the survey was emailed via the society membership and one member may belong to multiple societies. Thus, there may be a selection bias by clinicians who were volunteering to complete the survey, and perspectives may not be representative of the entire range of U.S. practitioners.

Third, if multiple participants from the same institutions completed surveys, it could lead to similar practice patterns. Fourth, we did not assess clinician practice patterns across patient populations (e.g., medical versus surgical population), and thus the reported practise patterns may vary by patient subpopulation. Fifth, since most practitioners were from university-based hospitals, their perspectives may not reflect clinicians from community hospital settings. Despite these limitations, this survey provides insight into U.S. clinician practice variation in UF_NET, which may help plan future research and quality implementation initiatives.

In this secondary analysis of a multinational survey involving critical care practitioners in the U.S., a significant practice variation was found between physicians and nurses in methods used to achieve UF_NET during CKRT, the frequency in monitoring net fluid balance, the perceived barriers of UF_NET, and interventions performed for patients with hemodynamic instabilities during UF_NET. Nevertheless, there is a considerable willingness on the part of U.S. practitioners to enrol patients in clinical trials of UF_NET. These findings emphasise the need to generate