What is the role of midodrine (Midodrine) in treating hypotension (low blood pressure) associated with shock?

From the Guidelines

Midodrine is not recommended as a first-line treatment for shock, and its use should be limited to specific cases where patients have vasodilatory or distributive shock and remain hypotensive despite adequate fluid resuscitation and vasopressor support, as evidenced by the 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope 1.

Key Considerations

• The primary treatment for shock should focus on fluid resuscitation and intravenous vasopressors like norepinephrine, as recommended by the Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016 1.
• Midodrine, an alpha-1 adrenergic agonist, can cause peripheral vasoconstriction and increase blood pressure, but its use is generally reserved for patients with neurogenic orthostatic hypotension, as suggested by the 2017 ACC/AHA/HRS guideline 1.

Clinical Use of Midodrine

• When used, the typical dosing of midodrine is 5-10 mg orally every 6-8 hours, with a maximum daily dose of 30 mg.
• Important precautions include avoiding use in patients with severe coronary artery disease, urinary retention, or acute kidney injury, as the vasoconstriction may worsen these conditions.
• Blood pressure should be monitored regularly during treatment, and the medication should be held if supine hypertension develops.

Prioritizing First-Line Treatments

• Norepinephrine is recommended as the first-choice vasopressor for treating septic shock, with a strong recommendation and moderate quality of evidence 1.
• The use of midodrine should not replace first-line treatments for shock, which include fluid resuscitation and intravenous vasopressors like norepinephrine.
• In cases where midodrine is considered, it should be used as an adjunctive medication to support blood pressure management, rather than as a primary treatment for shock.

From the FDA Drug Label

Midodrine forms an active metabolite, desglymidodrine, that is an alpha1-agonist, and exerts its actions via activation of the alpha-adrenergic receptors of the arteriolar and venous vasculature, producing an increase in vascular tone and elevation of blood pressure. Administration of midodrine results in a rise in standing, sitting, and supine systolic and diastolic blood pressure in patients with orthostatic hypotension of various etiologies Standing systolic blood pressure is elevated by approximately 15 to 30 mmHg at 1 hour after a 10 mg dose of midodrine, with some effect persisting for 2 to 3 hours.

Midodrine can be used to increase blood pressure in patients with shock, as it has been shown to elevate blood pressure in patients with orthostatic hypotension. The alpha1-agonist effect of midodrine's active metabolite, desglymidodrine, increases vascular tone, which can help to counteract hypotension. However, it is essential to note that midodrine is not specifically indicated for shock, and its use in this context should be approached with caution 2.

• Key points:
  • Midodrine increases blood pressure in patients with orthostatic hypotension
  • The alpha1-agonist effect of desglymidodrine increases vascular tone
  • Midodrine's use in shock should be approached with caution
  • Midodrine is not specifically indicated for shock 2

From the Research

Midodrine for Shock

• Midodrine is a peripheral alpha-adrenergic agonist that has been used to manage orthostatic hypotension and secondary hypotensive disorders 3.
• It has also been studied as a potential treatment for vasodilatory shock, with some studies suggesting that it can help liberate patients from intravenous vasopressor therapy 4, 5.
• The use of midodrine for shock has been explored in various studies, including those on its role in facilitating the liberation from vasopressor support in the ICU 4, 5.
• A systematic review and semi-quantitative analysis of midodrine initiation criteria, dose titration, and adverse effects when administered to treat shock found that the literature is heterogeneous and comprised primarily of low or very low quality data 6.

Mechanism of Action and Efficacy

• Midodrine works by increasing standing blood pressure and improving symptoms of orthostatism, such as weakness, syncope, blurred vision, and fatigue, without associated cardiac stimulation 3.
• It has been shown to be clinically at least as effective as other sympathomimetic agents and dihydroergotamine in managing orthostatic hypotension 3.
• In patients with vasodilatory shock, midodrine has been demonstrated to lead to faster time to liberation from IV vasopressor therapy and shorter ICU length of stay in some studies 4, 5.

Safety and Adverse Effects

• The most commonly experienced adverse effects of midodrine are piloerector reactions, gastrointestinal disorders, and cardiovascular complaints, which are generally mild and can be controlled by reducing the dosage 3.
• A systematic review found that bradycardia, hypertension, and ischemia are potential adverse effects of midodrine when used to treat shock, but the incidence of these events is relatively low 6.
• The use of midodrine in patients with shock has been found to be feasible and safe in some studies, with no significant increase in adverse events or complications 5.