Intradialytic hypotension (IDH) is sometimes defined as a decrease in systolic BP by ≥20 mm Hg or a decrease in mean arterial pressure of 10 mm Hg associated with symptoms. There are, however, other definitions of IDH in the literature. Whereas some of these studies define IDH based on a need to implement various corrective measures (eg administration of saline, reduction in ultrafiltration volume, or reduction in blood flow), others base the definition on a threshold decline in systolic BP, change from predialysis BP, or absolute nadir in the absence of symptoms.

Despite these inconsistencies in definition, IDH has been associated with several adverse clinical outcomes: cardiovascular (reduced myocardial perfusion, decreased LVEF), vascular (increased risk of AVF thrombosis), cerebral (decreased cerebral blood flow), and  decline in residual kidney function. IDH has also been independently associated with higher risk for cardiovascular mortality, myocardial infarction, and hospitalization for heart failure/volume overload.

Several management strategies have been recommended for the treatment and prevention of IDH. Immediate management includes stopping ultrafiltration [UF], Trendelenburg position, saline or albumin infusion, and decreasing blood flow [Qb] and/ or dialysate flow [Qd] rate. From there, preventive measures include:

• • First-line: adjustment of EDW or UF rate, dietary Na and fluid restriction, avoidance of food ingestion during hemodialysis, adjustment of antihypertensives, adjustment of dialysate composition
  • Second-line: dialysate cooling, evaluation for underlying cardiac disease, increased dialysis treatment time
  • Third-line: midodrine, change dialysis modality

Mannitol has been utilized for ameliorating symptoms such as muscle cramps associated with hemodialysis. Theoretically, use of hypertonic solutions in patients on hemodialysis can promote intravascular filling but there are concerns about eventual development of hypervolemia. In this double-blind, placebo-controlled, single-center, pilot randomized trial, Mc Causland et al attempted to assess the effect of mannitol on average intradialytic decline in systolic blood pressure (SBP) and the proportion of dialysis sessions complicated by IDH.

Patients were randomized 1:1 to receive mannitol or placebo, with the primary endpoint defined as intradialytic decline in SBP (predialysis SBP minus lowest intradialytic SBP).  Secondary endpoint was IDH occurrence, defined as any drop of 20 mm Hg or more from predialysis SBP.

Systolic blood pressure (SBP) values measured predialysis (Pre-SBP) and lowest intradialysis (Min-SBP) and postdialysis (Post-SBP) at each hemodialysis session according to randomized treatment assignment. Figure 2 from Mc Causland et al, AJKD © National Kidney Foundation.

The use of mannitol (vs placebo) showed no significant difference in decline in intradialytic SBP.

Table 2 from Mc Causland et al, AJKD © National Kidney Foundation.

There was, however, a lower frequency of IDH episodes with use of mannitol (25% in mannitol group vs 43% in placebo group), but recall the small cohort of 52 patients that were randomized.

Table 3 from Mc Causland et al, AJKD © National Kidney Foundation.

There was no significant difference in cardiac biomarker levels or adverse events between the 2 groups and there was no signal for elevations in levels of biomarkers of kidney injury.

There are several important limitations, namely: modest sample size, inclusion of participants with AKI, as well as lack of information regarding mannitol concentrations and intradialytic plasma osmolality, timing of intradialytic symptoms, timing of administration of antihypertensive agents, bioimpedance, etc. There was also no follow-up regarding long-term outcomes, e.g., hospitalization, residual kidney function decline, or mortality.

As a pilot study, mannitol appeared relatively safe, but long-term data and firm recommendations for routine use of mannitol remain inconclusive. Whether there is any long-term benefit of preventing IDH with mannitol is unclear, and Mc Causland et al conclude that further research with a larger multicenter study is needed to answer this question.

– Post prepared by Trisha Patel @TrishaKPatelDO (PGY-2, Internal Medicine, UIC/Advocate Christ Medical Center), AJKDBlog Guest Contributor, and Edgar Lerma @edgarvlermamd, AJKD Social Media Advisory Board member.

To view Mc Causland et al (subscription required), please visit AJKD.org.

Title: Hypertonic Mannitol for the Prevention of Intradialytic Hypotension: A Randomized Controlled Trial
Authors: F.R. Mc Causland, B. Claggett, V.S. Sabbisetti, P. Jarolim, and S.S. Waikar
DOI: 10.1053/j.ajkd.2019.03.415