What is the next best treatment for orthostatic hypotension in a patient with autonomic dysfunction secondary to diabetes, who also has supine hypertension?

From the Guidelines

The best treatment for orthostatic hypotension in a diabetic patient with autonomic dysfunction and complicating supine hypertension is midodrine, as recommended by the most recent guidelines 1. Start with 2.5-5mg three times daily (morning, midday, and mid-afternoon, but not after 6pm to avoid worsening supine hypertension at night). Midodrine is an alpha-1 agonist that increases peripheral vascular resistance and blood pressure. For this patient, timing is crucial - they should take the medication during daytime hours when upright and avoid taking it before lying down. Non-pharmacological measures should also be implemented, including:

• compression stockings
• adequate hydration
• slow positional changes
• increased salt intake if not contraindicated
• elevating the head of the bed 4-6 inches at night to reduce supine hypertension. Fludrocortisone is an alternative but may worsen supine hypertension more than midodrine, as noted in previous guidelines 1. The goal is to improve orthostatic symptoms while minimizing supine hypertension, which requires careful medication timing and regular blood pressure monitoring in both positions. It's also important to consider the patient's overall health and adjust the treatment plan accordingly, taking into account the potential benefits and risks of each treatment option, as discussed in the latest standards of care 1.

From the FDA Drug Label

Midodrine should be used with caution in orthostatic hypotensive patients who are also diabetic, as well as those with a history of visual problems who are also taking fludrocortisone acetate, which is known to cause an increase in intraocular pressure and glaucoma. The potential for supine hypertension should be carefully monitored in these patients and may be minimized by either reducing the dose of fludrocortisone acetate or decreasing the salt intake prior to initiation of treatment with midodrine The next best treatment for a patient with orthostatic hypotension secondary to diabetes, who also has supine hypertension, is to use midodrine with caution. The patient should be monitored closely for signs of supine hypertension, and the dose of midodrine should be adjusted as needed to minimize this risk. Additionally, the patient's salt intake should be decreased prior to initiation of treatment with midodrine, and the dose of any concomitant medications that may increase blood pressure, such as fludrocortisone acetate, should be reduced 2. Key considerations for treatment include:

• Monitoring blood pressure closely
• Adjusting the dose of midodrine as needed
• Decreasing salt intake
• Reducing the dose of concomitant medications that may increase blood pressure It is also important to note that midodrine has not been studied in patients with renal impairment, and therefore should be used with caution in these patients, with a starting dose of 2.5 mg 2.

From the Research

Orthostatic Hypotension Management

The management of orthostatic hypotension, especially in the context of autonomic dysfunction secondary to diabetes and complicated by supine hypertension, requires a careful approach.

• The condition is characterized by an excessive fall in blood pressure while standing, resulting from decreased cardiac output or defective vasoconstrictor mechanisms 3.
• Fludrocortisone, a mineralocorticoid, is considered for increasing blood volume and blood pressure, and is used as first- or second-line pharmacological therapy alongside mechanical and positional measures 3.

Treatment Considerations

When considering treatment, it's essential to distinguish between neurogenic and non-neurogenic orthostatic hypotension, as this distinction has therapeutic implications 4.

• For neurogenic orthostatic hypotension, management aims at improving quality of life and reducing symptoms rather than normalizing blood pressure 4.
• Nonpharmacologic measures are key to success, and pharmacologic options include volume expansion with fludrocortisone and sympathetic enhancement with midodrine, droxidopa, and norepinephrine reuptake inhibitors 4.
• The presence of supine hypertension complicates management and is primarily ameliorated by avoiding the supine position and sleeping with the head of the bed elevated 4.

Evidence for Fludrocortisone

The evidence for using fludrocortisone in orthostatic hypotension is limited, with very low-certainty evidence about its effects on blood pressure, orthostatic symptoms, or adverse events in people with orthostatic hypotension and diabetes or Parkinson disease 3, 5.

• There is a need for standardized reporting of outcomes and for standardization of measurements of blood pressure in orthostatic hypotension 3.
• Non-pharmacological therapies, such as avoidance of precipitating factors and physical and dietary interventions, have a pivotal role in the management of orthostatic hypotension and supine hypertension 6.