Interventions to prevent hemodynamic instability during renal replacement therapy for acute kidney injury: a systematic review protocol

Episodes of hemodynamic instability during renal replacement therapy (HIRRT) in the form of intradialytic hypotension (IDH) frequently complicates maintenance hemodialysis treatments in end-stage kidney disease (ESKD) patients [1]. Minor consequences of this form of HIRRT include symptoms such as post-dialysis fatigue [1, 2]. More serious complications include bowel ischemia, myocardial infarction, and access thrombosis [2]. Recent studies have highlighted that myocardial stunning [3] and brain white-matter changes [4] are also associated with HIRRT in the form of IDH. Furthermore, the occurrence of HIRRT can limit delivery of adequate dialysis treatment as interventions frequently undertaken in response to HIRRT include terminating dialysis sessions early or reducing ultrafiltration goals [1, 2]. Lastly, in maintenance hemodialysis patients, more frequent episodes of HIRRT (as IDH) may result in more rapid loss of residual renal function over time [5, 6].

Most studies of interventions to prevent or limit HIRRT have focused specifically on IDH in maintenance hemodialysis patients with ESKD; however, IDH is only one form of HIRRT which is also an important concern amongst critically ill patients who require hemodialysis or other forms of RRT (such as slow low-efficiency dialysis (SLED) or continuous renal replacement therapy (CRRT)) in the context of acute kidney injury (AKI). AKI that necessitates RRT is a frequent and serious complication of critical illness with an incidence of 2 to 3% amongst all patients admitted to the intensive care unit (ICU) [7]. One study suggests that HIRRT complicates an estimated 30% of hemodialysis treatments for AKI patients in the ICU [8]. This is particularly important since there is some evidence to suggest that HIRRT negatively impacts renal recovery in AKI [9], possibly similar to how HIRRT (in the form of IDH) accelerates the loss of residual kidney function in those on maintenance hemodialysis [5, 6].

The goal of this study is to summarize all observational and trial evidence related to interventions to prevent or limit HIRRT in AKI patients. This encompasses AKI that is treated with the most commonly utilized RRT modalities in the setting of critical illness (intermittent hemodialysis, SLED, and CRRT).

The primary objective of this systematic review is to synthesize the evidence surrounding interventions to limit HIRRT in critically ill patients with AKI. In particular, we wish to assess the impact of various dialysis-related interventions that have been studied to minimize its occurrence.

This protocol is reported in accordance with the PRISMA-P 2015 checklist [10] (see Additional file 1).

HIRRT is a common complication of renal replacement therapy not only in ESKD but also in the critically ill AKI population. The consequences of HIRRT can range from minor to serious events including bowel ischemia, myocardial infarction, and access thrombosis [2]. HIRRT can lead to further loss of residual renal function over time [5, 6]. Research suggests that HIRRT can also adversely impact renal recovery in critically ill patients with AKI [9]. To date, most studies on HIRRT and interventions to prevent it are conducted on maintenance hemodialysis patients with ESKD and thus do not necessarily apply to critically ill patients with AKI who require RRT.

This review proposes to use a systematic approach to identify, gather, and summarize the currently existing evidence on interventions to prevent HIRRT in critically ill patients with AKI on RRT from interventional and observational studies as well any ongoing trials. We aim to assess the effectiveness of strategies used to limit or prevent HIRRT in AKI by assessing specific, clinically important outcomes. In addition to exploring strategies to limit HIRRT in AKI, we will also review the available evidence for major outcomes associated with HIRRT, which includes mortality, ICU/hospital length of stay, and renal recovery. This summary of evidence can help guide clinical decisions regarding RRT parameters in AKI.

We expect that most of the evidence will come from observational studies rather than RCTs. As there is a higher risk of bias in observational studies, we have chosen to implement in our protocol three accepted assessment tools, the Cochrane ACROBAT-NRSI [10], the STROBE checklist [11], and the Newcastle-Ottawa Scale [12]. We will also use an accepted risk of bias assessment tool for any RCTs [13]. The information we obtain will be dependent on the quality of available evidence, and as such, there will likely be the need for cautious interpretation of the findings. The information from this systematic review will inform clinicians of the current evidence for interventions to limit or prevent HIRRT in AKI and will highlight areas in need of further study. We expect that our summary of evidence will be useful in formulating further research protocols to expand our knowledge in this area, which will ultimately serve to better care for critically ill AKI patients requiring RRT.