THE ROLE OF MIDODRINE FOR HYPOTENSION OUTSIDE OF THE INTENSIVE CARE UNIT
Main Article Content
Keywords
Midodrine, Vasoplegia, Hypotension, Sepsis
Abstract
Midodrine is an oral, peripherally acting alpha-adrenergic agonist. After gaining Food and Drug Administration (FDA) approval in 1996 for orthostatic hypotension, its use has evolved to target vasoplegic conditions such as intradialytic hypotension in the end-stage renal disease population, refractory ascites in cirrhotic patients to support diuresis, and in hepatorenal syndrome.
Upon oral ingestion, the drug undergoes enzymatic hydrolysis to an active metabolite, desglymidodrine. Its use has been well tolerated at 2.5 mg, 5 mg, and 10 mg oral doses. The most frequently occurring side effects relate directly to its sympathomimetic profile and include piloerection, scalp pruritis, generalized paresthesias, and urinary retention.
The vasoplegic profile of sepsis would be a potential target for midodrine therapy. While its use to mediate recovery from septic shock has been suggested, there is a paucity of clinical data supporting its use. Such therapy may be uniquely appropriate in septic patients who are not candidates for intensive care unit (ICU) level of care.
Upon oral ingestion, the drug undergoes enzymatic hydrolysis to an active metabolite, desglymidodrine. Its use has been well tolerated at 2.5 mg, 5 mg, and 10 mg oral doses. The most frequently occurring side effects relate directly to its sympathomimetic profile and include piloerection, scalp pruritis, generalized paresthesias, and urinary retention.
The vasoplegic profile of sepsis would be a potential target for midodrine therapy. While its use to mediate recovery from septic shock has been suggested, there is a paucity of clinical data supporting its use. Such therapy may be uniquely appropriate in septic patients who are not candidates for intensive care unit (ICU) level of care.
References
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2. Cruz DN, Mahnensmith RL, Brickel HM, Perazella MA. Midodrine is effective and safe therapy for intradialytic hypotension over 8 months of follow-up. Clin Nephrol 1998 Aug;50:101–107.
3. Sourianarayanane A, Barnes D, McCullough A. Beneficial effect of midodrine in hypotensive cirrhotic patients with refractory ascites. Gastroenterol Hepatol 2011;7:2;132–34.
4. Cruz DN. Midodrine: a selective alpha-adrenergic agonist for orthostatic hypotension and dialysis hypotension, Exp Opin Pharmacother 2000;1:4;835–49.
5. Beck V, Chateau D, Bruson G, et al. Timing of vasopressor initiation and mortality in septic shock: a cohort study. Critical Care 2014;18:R97.
6. McClellan K, Wiseman L, Wilde M. Midodrine: A review of its therapeutic use in the management of orthostatic hypotension. Drugs Aging 1998 Jan;12(1):75–86.
7. Steinbach K, Weidinger P. The effect of midodrine on orthostatic hypotension. Wienier Klinische Wochenschrift 1973;85:621–24
8. Grobecker VH, Kees F, Linden M, et al. Studies on the bioavailability of midodrine and ?-2,5-dimethoxyphenyl-?-aminoethanol hydrochloride. Arzneimittelforschung 1987 Apr;37(4):447–50.
9. McTavish D, Goa K. Midodrine: a review of its pharmacological properties and therapeutic use in orthostatic hypotension and secondary hypotensive disorders. Drugs 1989;38:757–77.
10. Horger S, Kandrac S, Longyhore D. Taste and smell disturbance resulting from midodrine. JPP 2016 Dec;29(6):571–73.
11. Grant M. Treatment of orthostatic hypotension: preserving function and quality of life. Geriatr Aging 2003;6(7):32–36.
12. Levine A, Meyer M, Bittner E, et al. Oral midodrine treatment accelerates the liberation of intensive care unit patients from intravenous vasopressor infusions. J Crit Care 2013;28:756–62.
13. Hurst GC, Somerville KT, Alloway RR, et al. Preliminary experience with midodrine in kidney/pancreas transplant patients with orthostatic hypotension. Clin Transplantation 2000;14;42–47.
14. Low PA, Gilden JL, Freeman R, et al. Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, doubleblind multicenter study. Midodrine Study Group. JAMA 1997;277(13):1046–51.
15. Gilden JL, Berktold P, Larson K, et al. Efficacy of midodrine therapy for neurogenic orthostatic hypotension in diabetic patients. Drugs Aging 1998;12(1)12:75–86.
16. Freeman R, Wieling W, Axelrod FB, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Auton Neurosci 2011;161:46–8.
17. Low PA, Gilden JL, Freeman R et al. Efficacy of Midodrine vs placebo in neurogenic orthostatic hypotension. a randomized, double-blind multicenter study. JAMA 1997;277(13):388.
18. Parsaik AK, Singh B, Altayar O, et al. Midodrine for orthostatic hypotension: a systematic review and meta-analysis of clinical trials. J Gen Intern Med 2013 Nov;28(11):1496–503.
19. Singh V, Dhungana SP, Singh B, et al. Midodrine in patients with cirrhosis and refractory ascites: a randomized pilot study. J Hepatol 2012;56:348–54
20. Angeli P, Volpin R, Piovan D, et al. Acute effects of the oral administration of midodrine, an alpha-adrenergic agonist on renal hemodynamics and renal function in cirrhotic patients with ascites. Hepatology 1998;28:937–43.
21. Guo TT, Yang Y, Song Y, et al. Effects of midodrine in patients with ascites due to cirrhosis: Systematic review and meta-analysis. J Dig Dis 2016 Jan;17(1):11–9.
22. Esrailian E, Pantangeo Em Kyulo N, Hu K, Runyon B. Octreotide/midodrine therapy significantly improves renal function and 30-day survival in patients with type 1 hepatorenal syndrome. Dig Dis Sci 2007 Mar;52(3):742–48.
23. Ginès, P, Guevara M, Arroyo V, Rodes J. Hepatorenal syndrome. Lancet, 2003;362,(9398)1819–27.
24. Karwa R, Woodis C. Midodrine and octreotide in treatment of cirrhosis-related hemodynamic complications. Ann Pharmacother 2009;43:692–9.
25. Cavallin M, Fasolato S, Marenco S, et al. The treatment of hepatorenal syndrome. Dig Dis 2015;33:548–54.
26. Wong F. Treatment to improve acute kidney injury in cirrhosis. Curr Treat Options Gastroenterol 2015 Jun;13(2):235–48.
27. Velez JC, Kadian M, Taburyanskaya M, et al. Hepatorenal acute kidney injury and the importance of raising mean arterial pressure. Nephron 2015;131(3):191–201.
28. Prakash S, Garg A, Heidenheim P, House A. Midodrine appears to be safe and effective for dialysis-induced hypotension: a systematic review. Nephrol Dial Transplant 2003;19:2553–58.
29. Poveromo LB, Michalets EL, Sutherland SE. Midodrine for the weaning of vasopressor infusions. J Clin Pharm Therapeuti 2016;41:260–65.
30. Whitson MR, Mo E, Nabi T et al. Feasibility, utility, and safety of midodrine during recovery phase from septic shock. Chest 2016;149(6):1380–3.
31. Anstey MH, Wibrow B, Thevathasan T, 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 Anesthesiol 2017 Mar 21;17(1):47.
32. Sharma S, Lardizabal JA, Bhambi B. Oral midodrine is effective for the treatment of hypotension associated with carotid artery stenting. J Cardiovasc Pharmacol Ther 2008;13(2):94–7.
33. O’Donnell B, Synnott A. Midodrine, an alternative to intravenous vasopressor therapy after spinal surgery. Eur J Anaesthesiol 2002;19(11):841–2.
34. Besen BAMP, Gobatto ALN, Melro LMG, et al. Fluid and electrolyte overload in critically ill patients: An overview. World J Crit Care Med 2015;4(2):116–29. doi:10.5492/wjccm.v4.i2.116.
35. ClinicalTrials.gov. Midodrine hydrochloride in early sepsis. Available at: https://clinicaltrials.gov/ct2/show/NCT03129542.
36. Cheng A, West TE, Limmathurotsakul D, Peacock S. Strategies to reduce mortality from bacterial sepsis in adults in developing countries. PLoS Med 2008;5:1173–75.
2. Cruz DN, Mahnensmith RL, Brickel HM, Perazella MA. Midodrine is effective and safe therapy for intradialytic hypotension over 8 months of follow-up. Clin Nephrol 1998 Aug;50:101–107.
3. Sourianarayanane A, Barnes D, McCullough A. Beneficial effect of midodrine in hypotensive cirrhotic patients with refractory ascites. Gastroenterol Hepatol 2011;7:2;132–34.
4. Cruz DN. Midodrine: a selective alpha-adrenergic agonist for orthostatic hypotension and dialysis hypotension, Exp Opin Pharmacother 2000;1:4;835–49.
5. Beck V, Chateau D, Bruson G, et al. Timing of vasopressor initiation and mortality in septic shock: a cohort study. Critical Care 2014;18:R97.
6. McClellan K, Wiseman L, Wilde M. Midodrine: A review of its therapeutic use in the management of orthostatic hypotension. Drugs Aging 1998 Jan;12(1):75–86.
7. Steinbach K, Weidinger P. The effect of midodrine on orthostatic hypotension. Wienier Klinische Wochenschrift 1973;85:621–24
8. Grobecker VH, Kees F, Linden M, et al. Studies on the bioavailability of midodrine and ?-2,5-dimethoxyphenyl-?-aminoethanol hydrochloride. Arzneimittelforschung 1987 Apr;37(4):447–50.
9. McTavish D, Goa K. Midodrine: a review of its pharmacological properties and therapeutic use in orthostatic hypotension and secondary hypotensive disorders. Drugs 1989;38:757–77.
10. Horger S, Kandrac S, Longyhore D. Taste and smell disturbance resulting from midodrine. JPP 2016 Dec;29(6):571–73.
11. Grant M. Treatment of orthostatic hypotension: preserving function and quality of life. Geriatr Aging 2003;6(7):32–36.
12. Levine A, Meyer M, Bittner E, et al. Oral midodrine treatment accelerates the liberation of intensive care unit patients from intravenous vasopressor infusions. J Crit Care 2013;28:756–62.
13. Hurst GC, Somerville KT, Alloway RR, et al. Preliminary experience with midodrine in kidney/pancreas transplant patients with orthostatic hypotension. Clin Transplantation 2000;14;42–47.
14. Low PA, Gilden JL, Freeman R, et al. Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, doubleblind multicenter study. Midodrine Study Group. JAMA 1997;277(13):1046–51.
15. Gilden JL, Berktold P, Larson K, et al. Efficacy of midodrine therapy for neurogenic orthostatic hypotension in diabetic patients. Drugs Aging 1998;12(1)12:75–86.
16. Freeman R, Wieling W, Axelrod FB, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Auton Neurosci 2011;161:46–8.
17. Low PA, Gilden JL, Freeman R et al. Efficacy of Midodrine vs placebo in neurogenic orthostatic hypotension. a randomized, double-blind multicenter study. JAMA 1997;277(13):388.
18. Parsaik AK, Singh B, Altayar O, et al. Midodrine for orthostatic hypotension: a systematic review and meta-analysis of clinical trials. J Gen Intern Med 2013 Nov;28(11):1496–503.
19. Singh V, Dhungana SP, Singh B, et al. Midodrine in patients with cirrhosis and refractory ascites: a randomized pilot study. J Hepatol 2012;56:348–54
20. Angeli P, Volpin R, Piovan D, et al. Acute effects of the oral administration of midodrine, an alpha-adrenergic agonist on renal hemodynamics and renal function in cirrhotic patients with ascites. Hepatology 1998;28:937–43.
21. Guo TT, Yang Y, Song Y, et al. Effects of midodrine in patients with ascites due to cirrhosis: Systematic review and meta-analysis. J Dig Dis 2016 Jan;17(1):11–9.
22. Esrailian E, Pantangeo Em Kyulo N, Hu K, Runyon B. Octreotide/midodrine therapy significantly improves renal function and 30-day survival in patients with type 1 hepatorenal syndrome. Dig Dis Sci 2007 Mar;52(3):742–48.
23. Ginès, P, Guevara M, Arroyo V, Rodes J. Hepatorenal syndrome. Lancet, 2003;362,(9398)1819–27.
24. Karwa R, Woodis C. Midodrine and octreotide in treatment of cirrhosis-related hemodynamic complications. Ann Pharmacother 2009;43:692–9.
25. Cavallin M, Fasolato S, Marenco S, et al. The treatment of hepatorenal syndrome. Dig Dis 2015;33:548–54.
26. Wong F. Treatment to improve acute kidney injury in cirrhosis. Curr Treat Options Gastroenterol 2015 Jun;13(2):235–48.
27. Velez JC, Kadian M, Taburyanskaya M, et al. Hepatorenal acute kidney injury and the importance of raising mean arterial pressure. Nephron 2015;131(3):191–201.
28. Prakash S, Garg A, Heidenheim P, House A. Midodrine appears to be safe and effective for dialysis-induced hypotension: a systematic review. Nephrol Dial Transplant 2003;19:2553–58.
29. Poveromo LB, Michalets EL, Sutherland SE. Midodrine for the weaning of vasopressor infusions. J Clin Pharm Therapeuti 2016;41:260–65.
30. Whitson MR, Mo E, Nabi T et al. Feasibility, utility, and safety of midodrine during recovery phase from septic shock. Chest 2016;149(6):1380–3.
31. Anstey MH, Wibrow B, Thevathasan T, 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 Anesthesiol 2017 Mar 21;17(1):47.
32. Sharma S, Lardizabal JA, Bhambi B. Oral midodrine is effective for the treatment of hypotension associated with carotid artery stenting. J Cardiovasc Pharmacol Ther 2008;13(2):94–7.
33. O’Donnell B, Synnott A. Midodrine, an alternative to intravenous vasopressor therapy after spinal surgery. Eur J Anaesthesiol 2002;19(11):841–2.
34. Besen BAMP, Gobatto ALN, Melro LMG, et al. Fluid and electrolyte overload in critically ill patients: An overview. World J Crit Care Med 2015;4(2):116–29. doi:10.5492/wjccm.v4.i2.116.
35. ClinicalTrials.gov. Midodrine hydrochloride in early sepsis. Available at: https://clinicaltrials.gov/ct2/show/NCT03129542.
36. Cheng A, West TE, Limmathurotsakul D, Peacock S. Strategies to reduce mortality from bacterial sepsis in adults in developing countries. PLoS Med 2008;5:1173–75.
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Published
Aug 31, 2017
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How to Cite
Gutman, L. B., & Wilson, B. J. (2017). THE ROLE OF MIDODRINE FOR HYPOTENSION OUTSIDE OF THE INTENSIVE CARE UNIT. Journal of Population Therapeutics and Clinical Pharmacology, 24(3), e45-e50. https://doi.org/10.22374/1710-6222.24.3.4
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