Potential risks in using midodrine for persistent hypotension after cardiac surgery: a comparative cohort study

Abstract

Background Persistent hypotension is a frequent complication after cardiac surgery with cardiopulmonary bypass (CPB). Midodrine, an orally administered alpha agonist, could potentially reduce intravenous vasopressor use and accelerate ICU discharge of otherwise stable patients. The main objective of this study was to explore the clinical impacts of administering midodrine in patients with persistent hypotension after CPB. Our hypothesis was that midodrine would safely accelerate ICU discharge and be associated with more days free from ICU at 30 days. Results We performed a retrospective cohort study that included all consecutive patients having received midodrine while being on vasopressor support in the ICU within the first week after cardiac surgery with CPB, between January 2014 and January 2018 at the Montreal Heart Institute. A contemporary propensity score matched control group that included patients who presented similarly prolonged hypotension after cardiac surgery was formed. After matching, 74 pairs of patients (1:1) fulfilled inclusion criteria for the study and control groups. Midodrine use was associated with fewer days free from ICU (25.8 [23.7–27.1] vs 27.2 [25.9–28] days, p = 0.002), higher mortality (10 (13.5%) vs 1 (1.4%), p = 0.036) and longer ICU length of stay (99 [68–146] vs 68 [48–99] hours, p = 0.001). There was no difference in length of intravenous vasopressors (63 [40–87] vs 44 [26–66] hours, p = 0.052), rate of ICU readmission (6 (8.1%) vs 2 (2.7%), p = 0.092) and occurrence of severe kidney injury (11 (14.9%) vs 10 (13.5%) patients, p = 0.462) between groups. Conclusion The administration of midodrine for sustained hypotension after cardiac surgery with CPB was associated with fewer days free from ICU and higher mortality. Routine prescription of midodrine to hasten ICU discharge after cardiac surgery should be used with caution until further prospective studies are conducted.

Impact of Adjuvant Use of Midodrine to Intravenous Vasopressors: A Systematic Review and Meta-Analysis

“… ICU readmissions: the heterogeneity was already low in this outcome. However, excluding Tremblay et al [ 16 ] or Fiorenza et al [ 19 ] dropped I 2 from 11% to 0%. Leave-one-out analyses of the studies evaluating this outcome did not show any significant changes in the results (Supplementary Figures 1E and 2E ).…”

“…Based on our meta-analysis, the addition of midodrine had no effect on the ICU LOS, hospital LOS, mortality, ICU readmission, or IVV reinstitution. To the best of our knowledge, this is the first meta-analysis that includes the data from the MIDAS trial [ 6 ] and Tremblay et al [ 16 ] study.…”

“…Previous retrospective studies and one RCT have been conducted with conflicting results; some showed that midodrine is helpful in this process [ 13 , 14 , 17 , 19 ], and others including the RCT showed no benefit of adding midodrine to facilitate weaning off IVV [ 6 , 15 , 18 ]. Surprisingly, two studies showed that midodrine increases hospital and ICU LOS [ 16 , 20 ]. Based on these conflicting results, our meta-analysis was performed to solve this dilemma as new studies have been published after the last meta-analysis by Hammond et al [ 27 ].…”

“…Fiorenza et al [19] (abstract) was the only study to include just extubated patients who still require IVV (less than 15 mcg/hr of norepinephrine equivalent) with different etiologies; this study showed that midodrine decreased hospital LOS, ICU readmission, and IVV reinstitutions. Tremblay et al [16] was the only study to include patients after cardiac surgery with cardiopulmonary bypass, and it showed increased ICU LOS and higher mortality among the midodrine group.…”

“…Various observational studies have been done evaluating the effect of midodrine to facilitate IVV weaning [13][14][15][16][17][18][19][20]. Recently, the results from the "Effect of midodrine versus placebo on time to vasopressor discontinuation in patients with persistent hypotension in the intensive care unit (MI-DAS) -an international randomized controlled trial (RCT)" [6] have also been published.…”