What criteria warrant holding midodrine in an adult treated for symptomatic orthostatic hypotension?

Parameters to Hold Midodrine

Hold midodrine when supine systolic blood pressure exceeds 180-200 mmHg, when symptomatic supine hypertension occurs (headache, nausea), or when severe bradycardia develops, particularly in patients on concurrent negative chronotropic agents. 1, 2, 3

Critical Blood Pressure Thresholds

Supine Hypertension - Primary Concern

• The FDA label explicitly warns that midodrine can cause marked elevation of supine blood pressure (>200 mmHg systolic), which is the primary dose-limiting adverse effect 1
• Supine hypertension occurs in 22% of patients at 10 mg doses and 45% at 20 mg doses 3
• Hold midodrine if supine systolic BP exceeds 180-200 mmHg or if the patient develops symptomatic supine hypertension 1, 4

Symptomatic Indicators

• Discontinue if patient experiences nighttime headaches, nausea, transient rash, or itchy/prickly scalp, which are signs of supine hypertension 5
• Note that supine hypertension may persist for up to 19 days after discontinuation, requiring prolonged monitoring 5

Cardiac Parameters

Heart Rate Considerations

• Hold midodrine if significant bradycardia develops, especially in patients taking beta-blockers, digoxin, or non-dihydropyridine calcium channel blockers 2, 6
• Midodrine causes reflex bradycardia through vagal stimulation in response to increased peripheral vascular resistance 6
• The combination of midodrine with beta-blockers can lead to more pronounced bradycardia and potentially reduced ejection fraction 6

Cardiac Function Monitoring

• Hold in patients with decompensated congestive heart failure, as increased afterload may unmask or worsen subclinical left ventricular dysfunction 2, 6
• Discontinue if echocardiography shows increased end-diastolic volumes and pressures due to impedance of left ventricular ejection 6

Urinary Retention

• Hold midodrine if urinary retention or significant urinary urgency develops (occurs in 4% of patients) 2, 7
• This is particularly important in patients taking alpha-adrenergic blockers (terazosin, prazosin, doxazosin), as midodrine can antagonize their effects 2

Lack of Symptomatic Improvement

• The FDA label mandates discontinuation if patients do not report significant symptomatic improvement after initiation of treatment 1
• The therapeutic goal is minimizing postural symptoms, not restoring normotension - continue only if symptoms improve 2, 3

Timing Considerations for Routine Dosing

• Always hold the final daily dose if it would be taken within 4 hours of bedtime to reduce supine hypertension risk 3, 4
• For hemodialysis patients, midodrine is effectively cleared during dialysis (half-life reduced to 1.4 hours), so timing relative to dialysis is critical 2, 6

Practical Monitoring Algorithm

Before each dose, assess:

• Supine blood pressure - hold if systolic >180-200 mmHg 1
• Presence of headache, nausea, or scalp symptoms 5
• Heart rate - hold if symptomatic bradycardia present 2, 6
• Urinary symptoms - hold if retention develops 2, 7
• Time until bedtime - hold if <4 hours 3, 4

After 1-2 weeks of therapy:

• Discontinue permanently if no symptomatic improvement in orthostatic symptoms 1, 2