Research Viewpoints A Re-Evaluation of the Efficacy of Midodrine in Management of Intra-Dialytic Hypotension

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Brunelli SM, Cohen DE, Marlowe G, Van Wyck D: The Impact of Midodrine on Outcomes in Patients with Intradialytic Hypotension. Am J Nephrol 2018;48:381–388

Hypotension occurring during hemodialysis treatment sessions is a common and vexing problem. It can often be traced to excessive or to rapid ultrafiltration with inadequate or delayed refilling of the intra-vascular volume, sometimes compounded by anti-hypertensive drug use. But, some patients develop symptomatic intradialytic hypotension (IDH) despite relatively normal volume status and in the absence of anti-hypertensive drug use. Such patients frequently are given midodrine (*off-label), an alpha-1 adrenergic receptor agonist, having both veno- and arteriolo- constrictive properties, in an attempt to alleviate IDH and its symptoms. Small, short term trials have generally supported a beneficial effect of midodrine for these indications, but each has had deficiencies in study design, so the evidence for safety and efficacy of midodrine for IDH is weak.

Brunelli and co-workers sought to evaluate the role of midodrine in IDH in a large, retrospective observational matched cohort study involving 1043 midodrine treated patients and 2033 controls. Midodrine use was associated with higher mortality, cardiovascular and all-cause hospitalization rates, even after adjustment for co-variates. This association might have been due to a bias introduced by indications for the use of midodrine.

Importantly, blood pressure (BP) changes during dialysis were initially similar in the two groups, but over time BP fell to a bigger extent in midodrine treated patients despite comparable ultra-filtration rates.

Taken together, and considering the limitations of the study design, these findings raise doubts about the overall efficacy (and safety) of midodrine treatment of IDH. Nonetheless, patient-specific reporting of symptoms were not routinely collected. So, this study is primarily hypothesis-generating. A well designed, adequately powered, long-term randomized, placebo-controlled, double blinded clinical trial embedded with patient self-reported data on symptoms is still required to establish a clear and convincing role for midodrine treatment of IDH.