Midodrine for Norepinephrine Weaning
Initiate midodrine at 10 mg orally every 8 hours (or preferably every 6 hours) when norepinephrine requirements are low and stable (typically ≤0.1 mcg/kg/min or ≤0.5 mg/h), then taper norepinephrine by 50% every 4-6 hours while monitoring mean arterial pressure (MAP) ≥65 mmHg.
Patient Selection Criteria
Start midodrine only when the patient meets ALL of the following:
- Norepinephrine dose ≤0.1 mcg/kg/min (approximately 0.5 mg/h in a 70 kg adult) for at least 24 hours 1
- Hemodynamically stable with adequate volume resuscitation completed 1
- Able to tolerate oral medications 2
- No contraindications: severe coronary artery disease, acute myocardial infarction, urinary retention, or supine hypertension 2
Midodrine Dosing Protocol
Initial dose: 10 mg orally every 8 hours, though every 6 hours may be more effective based on pharmacokinetics 3
Dose range: 5-20 mg per dose, with most patients requiring 10 mg 3, 4
Timing: Administer 30-60 minutes before attempting norepinephrine reduction to allow peak effect 2
Recent evidence suggests that every 6-hour dosing may optimize midodrine's pharmacokinetic profile better than traditional every 8-hour dosing, as one study demonstrated vasopressor requirements decreased from 0.10 to 0.05 norepinephrine equivalents within 24 hours of switching to every 6-hour dosing 3.
Norepinephrine Tapering Algorithm
Step 1: After first midodrine dose, wait 30-60 minutes, then reduce norepinephrine by 50% if MAP remains ≥65 mmHg 1
Step 2: Monitor MAP every 15-30 minutes for the first 2 hours after each reduction 1
Step 3: If MAP remains ≥65 mmHg for 4 hours, reduce norepinephrine by another 50% 1
Step 4: Continue this pattern until norepinephrine is discontinued 4
Step 5: Continue midodrine for 24-48 hours after norepinephrine discontinuation before attempting to wean midodrine itself 4
Monitoring Parameters
Blood pressure: Check MAP every 15-30 minutes during active tapering, then every 4 hours once stable 1
Heart rate: Monitor for reflex bradycardia, which can occur with midodrine 2
Tissue perfusion markers: Assess urine output (target >50 mL/h for 4 hours), lactate clearance, mental status, and capillary refill 1
Supine hypertension: Check blood pressure in supine position, as this occurs in <10% of patients on chronic midodrine but is rare with short-term use 2
Expected Timeline
Median time to vasopressor discontinuation: 1.2 days (range 0.5-2.8 days) after midodrine initiation 4
ICU discharge: Typically occurs 0.8 days after vasopressor discontinuation in midodrine-treated patients 4
Success rate: 96% of patients remain off IV vasopressors after midodrine treatment 4
Critical Pitfalls to Avoid
Do not start midodrine on high-dose vasopressors: Midodrine is ineffective when norepinephrine exceeds 0.1 mcg/kg/min, as it provides only marginal peripheral vascular resistance increase 2, 5
Do not use as monotherapy for acute shock: Midodrine is a weaning adjunct, not a replacement for IV vasopressors in unstable patients 5, 6
Avoid in volume-depleted patients: Ensure adequate fluid resuscitation before initiating midodrine, as vasoconstriction without adequate preload worsens organ perfusion 1
Use caution with negative chronotropes: Midodrine can cause bradycardia when combined with beta-blockers, digoxin, or non-dihydropyridine calcium channel blockers 2
Do not combine with other alpha-agonists: Concurrent use with ephedrine, pseudoephedrine, or phenylpropanolamine may cause severe hypertension 2
Special Populations
Hepatorenal syndrome context: In liver transplant candidates with type 1 hepatorenal syndrome, midodrine (5-15 mg three times daily) is used with octreotide and albumin as an alternative when terlipressin is unavailable, though this represents a different indication than vasopressor weaning 2
Dialysis patients: Midodrine 5 mg given 30 minutes before dialysis effectively prevents intradialytic hypotension, with a half-life reduced to 1.4 hours during hemodialysis 2
End-stage heart failure: Midodrine has been used successfully in palliative cases to facilitate discharge on oral therapy when advanced therapies are not options 7
Evidence Quality Considerations
The evidence for midodrine as a vasopressor weaning agent is mixed. Early retrospective studies showed promise 4, but recent randomized controlled trials have largely failed to demonstrate clear benefit when dosed every 8 hours 5, 6. The pharmacokinetic rationale for more frequent (every 6 hours) dosing is compelling 3, though this requires prospective validation. Despite conflicting trial data, midodrine remains a reasonable adjunct in carefully selected patients with low-dose vasopressor requirements who are otherwise ready for ICU discharge 5, 4.