EC Emergency Medicine and Critical Care

Background: Midodrine, an oral alpha-1 adrenergic agonist, has been used as an adjunct therapy in critically ill patients for blood pressure stabilization, particularly in those requiring weaning from intravenous vasopressors. This study aimed to evaluate the effectiveness of Midodrine in stabilizing blood pressure and improving clinical outcomes among critically ill patients in the Intensive Care Unit (ICU).

Methods: A cross-sectional study was conducted in the ICUs of selected tertiary care hospitals. A total of 200 critically ill patients who received Midodrine were included. Data were collected on patient demographics, clinical characteristics, indications for Midodrine use, dosage, duration of therapy, and clinical outcomes, including blood pressure stabilization, reduction in intravenous vasopressors, length of ICU stay, and mortality. Descriptive and inferential statistics were used to analyze the data.

Results: The study population had a mean age of 65.3 ± 12.7 years, with 56% being male. Hypertension (72%) and sepsis (48%) were the most common underlying conditions. The primary indication for Midodrine use was persistent hypotension despite intravenous vasopressors (60%). The mean daily dose of Midodrine was 15.8 ± 6.4 mg, with a mean duration of therapy of 5.2 ± 2.7 days. Blood pressure stabilization was achieved in 170 patients (85%), with a significant reduction in the need for intravenous vasopressors (p < 0.001). The mean time to blood pressure stabilization was 2.3 ± 1.1 days. The length of ICU stay was slightly shorter in patients who responded to Midodrine therapy compared to non-responders, although the difference was not statistically significant (p = 0.065). Mortality was reported in 28 patients (14%), with no significant difference between those who achieved blood pressure stabilization and those who did not (p = 0.239). Adverse events occurred in 22 patients (11%), with bradycardia and supine hypertension being the most common.

Conclusion: Midodrine demonstrated effectiveness in stabilizing blood pressure and reducing the need for intravenous vasopressors among critically ill patients in the ICU. Although Midodrine did not significantly impact mortality, it facilitated the weaning process and shortened ICU stay for many patients. Vigilant monitoring for adverse events, such as bradycardia and supine hypertension, is recommended to optimize patient outcomes.

 Keywords: Midodrine; Intensive Care Unit; Blood Pressure Stabilization; Critically Ill Patients; Vasopressors

1. Thongprayoon C., et al. “Temporal trends in the utilization of vasopressors in intensive care units: an epidemiologic study”. BMC Pharmacology and Toxicology 1 (2016): 19.
2. Midodrine Information (2024).
3. Wright RA., et al. “A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension”. Neurology1 (1998): 120-124.
4. Low PA., et al. “Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine study group”. Journal of the American Medical Association13 (1997): 1046-1051.
5. Jankovic J., et al. “Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine”. American Journal of Medicine 1 (1993): 38-48.
6. Prakash S., et al. “Midodrine appears to be safe and effective for dialysis-induced hypotension: a systematic review”. Nephrology Dialysis Transplantation 10 (2004): 2553-2558.
7. Levine AR., et al. “Oral midodrine treatment accelerates the liberation of intensive care unit patients from intravenous vasopressor infusions”. Journal of Critical Care 5 (2013): 756-762.
8. Cardenas-Garcia JL., et al. “Safety of oral midodrine as a method of weaning from intravenous vasoactive medication in the medical intensive care unit”. Chest4 (2014): 224A.
9. Whitson MR., et al. “Feasibility, utility, and safety of midodrine during recovery phase from septic shock”. Chest6 (2016): 1380-1383.
10. O'Donnell B and Synnott A. “Midodrine, an alternative to intravenous vasopressor therapy after spinal surgery”. European Journal of Anaesthesiology 11 (2002): 841-842.
11. Sharma S and Bhambi B. “Successful treatment of hypotension associated with stunned myocardium with oral midodrine therapy”. Journal of Cardiovascular Pharmacology and Therapeutics 1 (2005): 77-79.
12. Sharma S., et al. “Oral midodrine is effective for the treatment of hypotension associated with carotid artery stenting”. Journal of Cardiovascular Pharmacology and Therapeutics 2 (2008): 94-97.
13. Best LM., et al. “Treatment for hepatorenal syndrome in people with decompensated liver cirrhosis: a network meta-analysis”. Cochrane Database of Systematic Reviews 9 (2019): CD013103.
14. Rizvi MS., et al. “Trends in use of midodrine in the ICU: a single-center retrospective case series”. Critical Care Medicine 7 (2018): e628-e633.
15. Gutman LB and Wilson BJ. “The role of midodrine for hypotension outside of the intensive care unit”. Journal of Population Therapeutics and Clinical Pharmacology 3 (2017): e45-e50.
16. Gonzalez-Cordero A., et al. “Midodrine in end-stage heart failure”. BMJ Supportive & Palliative Care (2020).
17. Anstey MH., et al. “Midodrine as adjunctive support for treatment of refractory hypotension in the intensive care unit: a multicenter, randomized, placebo controlled trial (the MIDAS trial)”. BMC Anesthesiology1 (2017): 47.
18. Whitson MR., et al. “Feasibility, utility, and safety of midodrine during recovery phase from septic shock”. Chest6 (2016): 1380-1383.
19. Poveromo LB., et al. “Midodrine for the weaning of vasopressor infusions”. Journal of Clinical Pharmacy and Therapeutics 3 (2016): 260-265.
20. Liu M., et al. “Use of oral midodrine in weaning off intravenous vasopressors in patients with septic shock”. Journal of Pharmacy Practice 23 (2010): 284.
21. Roach E., et al. “200: impact of oral midodrine on duration of intravenous vasopressor therapy”. Critical Care Medicine 1 (2018): 82.
22. Hammond DA., et al. “Midodrine as an adjuvant to intravenous vasopressor agents in adults with resolving shock: systematic review and meta-analysis”. Journal of Intensive Care Medicine 11 (2020): 1209-1215.
23. Tremblay JA., et al. “Potential risks in using midodrine for persistent hypotension after cardiac surgery: a comparative cohort study”. Annals of Intensive Care 1 (2020): 121.
24. Levine AR., et al. “Oral midodrine treatment accelerates the liberation of intensive care unit patients from intravenous vasopressor infusions”. Journal of Critical Care 5 (2013): 756-762.
25. Santer P., et al. “Effect of midodrine versus placebo on time to vasopressor discontinuation in patients with persistent hypotension in the intensive care unit (MIDAS): an international randomised clinical trial”. Intensive Care Medicine 10 (2020): 1884-1893.
26. Costa-Pinto R., et al. “A pilot, feasibility, randomised controlled trial of midodrine as adjunctive vasopressor for low-dose vasopressor-dependent hypotension in intensive care patients: the MAVERIC study”. Journal of Critical Care 67 (2022): 166-171.
27. Adly DHE., et al. “Midodrine improves clinical and economic outcomes in patients with septic shock: a randomized controlled clinical trial”. Irish Journal of Medical Sciences 6 (2022): 2785-2795.
28. Duschek S., et al. “Modulations of autonomic cardiovascular control following acute alpha-adrenergic treatment in chronic hypotension”. Hypertension Research 11 (2009): 938-943.
29. Duschek S., et al. “Hemodynamic determinants of chronic hypotension and their modification through vasopressor application”. Journal of Physiological Sciences 2 (2009): 105-112.
30. Pichot C., et al. “Alpha-2 agonists to reduce vasopressor requirements in septic shock?” Medical Hypotheses 6 (2010): 652-656.
31. Rizvi MS., et al. “Continuation of newly initiated midodrine therapy after intensive care and hospital discharge: a single-center retrospective study”. Critical Care Medicine 8 (2019): e648-e653.
32. Wecht JM., et al. “Effects of midodrine hydrochloride on blood pressure and cerebral blood flow during orthostasis in persons with chronic tetraplegia”. Archives of Physical Medicine and Rehabilitation 9 (2010): 1429-1435.
33. Phillips AA., et al. “Increased central arterial stiffness explains baroreflex dysfunction in spinal cord injury”. Journal of Neurotrauma 12 (2014): 1122-1128.
34. Riker RR and Gagnon DJ. “Letter to the Editor: "Midodrine to liberate ICU patients from intravenous vasopressors: another negative fixed-dose trial"”. Journal of Critical Care 69 (2022): 153995.
35. Costa-Pinto R and Bellomo R. “Randomised-control trials do not support midodrine as an intravenous vasopressor weaning strategy”. Journal of Critical Care 72 (2022): 153996.
36. Macielak SA., et al. “Hemodynamic effects of an increased midodrine dosing frequency”. Critical Care Explorations 4 (2021): e0405.
37. Costa-Pinto R., et al. “Midodrine use in critically ill patients: a narrative review”. Critical Care and Resuscitation4 (2022): 298-308.
38. Lal A., et al. “Oral midodrine administration during the first 24 hours of sepsis to reduce the need of vasoactive agents: placebo-controlled feasibility clinical trial”. Critical Care Explorations 5 (2021): e0382.
39. Ahmed Ali AT., et al. “Effect of oral vasopressors used for liberation from intravenous vasopressors in intensive care unit patients recovering from spinal shock: a randomized controlled trial”. Critical Care Research and Practice (2022): 6448504.