Hypertonic Mannitol for the Prevention of Intradialytic Hypotension: A Randomized Controlled Trial

Abstract

Rationale & objective: Intradialytic hypotension (IDH) is a common complication at the initiation of hemodialysis (HD) therapy, is associated with greater mortality, and may be related to relatively rapid shifts in plasma osmolality. This study sought to evaluate the effect of an intervention to minimize intradialytic changes in plasma osmolality on the occurrence of IDH.

Study design: Double-blind, single-center, randomized, controlled trial.

Setting & participants: Individuals requiring initiation of HD for acute or chronic kidney disease.

Intervention: Mannitol, 0.25g/kg/h, versus a similar volume of 0.9% saline solution during the first 3 HD sessions.

Outcomes: The primary end point was average decline in systolic blood pressure (SBP). The secondary end point was the proportion of total sessions complicated by IDH (defined as a decrease ≥ 20mm Hg from the pre-HD SBP). Exploratory end points included biomarkers of cardiac and kidney injury.

Results: 52 patients were randomly assigned and contributed to 156 study visits. There were no significant differences in average SBP decline between the mannitol and placebo groups (15±11 vs 19±16mm Hg; P = 0.3). The proportion of total sessions complicated by IDH was lower in the mannitol group compared to placebo (25% vs 43%), with a nominally lower risk for developing an episode of IDH (OR, 0.38; 95% CI, 0.14-1.00), though this finding was of borderline statistical significance (P = 0.05). There were no consistent differences in cardiac and kidney injury biomarker levels between treatment groups.

Limitations: Modest sample size and number of events.

Conclusions: In this pilot randomized controlled trial studying patients requiring initiation of HD, we found no difference in absolute SBP decline between those who received mannitol and those who received saline solution. However, there were fewer overall IDH events and a nominally lower risk for dialysis sessions being complicated by IDH in the mannitol group. A larger multicenter randomized controlled trial is warranted.

Funding: Government funding to an author (Dr Mc Causland is supported by National Institute of Diabetes and Digestive and Kidney Diseases grant K23DK102511).

Trial registration: Registered at ClinicalTrials.gov with study number NCT01520207.

Keywords: Mannitol; acute kidney injury (AKI); dialysis disequilibrium; dialysis initiation; end-stage renal disease (ESRD); hemodialysis; hemodynamic instability; intradialytic hypotension (IDH); kidney injury biomarker; osmolality; randomized controlled trial (RCT); systolic blood pressure (SBP).

Conflict of interest statement

Peer Review: Received _______. Evaluated by 2 external peer reviewers, with direct editorial input from a Statistics/Methods Editor and an Associate Editor, who served as Acting Editor-in-Chief. Accepted in revised form March 4, 2019. The involvement of an Acting Editor-in-Chief was to comply with AJKD’s procedures for potential conflicts of interest for editors, described in the Information for Authors & Journal Policies.

Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.

Enrollment flow chart

Figure 2.

Systolic blood pressure measurements measured pre-dialysis (Pre-HD), lowest intra-dialysis (Nadir) and post-dialysis (Post-HD) at each HD session according to randomized treatment assignment.