Weaning Norepinephrine: A Practical Protocol
Wean norepinephrine gradually once hemodynamic stability is achieved, reducing the infusion rate in small decrements while continuously monitoring blood pressure and tissue perfusion markers—avoid abrupt discontinuation. 1
When to Begin Weaning
Start weaning as soon as hemodynamic stabilization is achieved, defined as sustained adequate organ perfusion with MAP ≥65 mmHg and improving lactate clearance, urine output, mental status, and capillary refill. 2
Do not maintain higher blood pressure targets or continue supra-therapeutic doses unnecessarily—physicians and nurses commonly overestimate the risk of re-aggravation and delay appropriate de-escalation. 2
Ensure adequate fluid resuscitation has been completed before aggressive weaning, as occult hypovolemia may cause hemodynamic instability during vasopressor reduction. 1
Gradual Dose Reduction Protocol
The FDA label explicitly states: "When discontinuing the infusion, reduce the flow rate gradually. Avoid abrupt withdrawal." 1
Reduce norepinephrine in small decrements while monitoring blood pressure every 2-5 minutes during active titration. 1
A practical approach based on dobutamine weaning principles (which share similar pharmacokinetic considerations) suggests decreasing by approximately 2 mcg/min steps with simultaneous optimization of oral therapy. 2
Computerized assisted weaning may reduce unnecessary exposure to vasoactive drugs and should be considered when available. 2
One high-quality randomized trial demonstrated that fuzzy logic-based automated weaning reduced median duration of norepinephrine therapy from 57.5 hours to 28.5 hours (p<0.0001) compared to clinician discretion, suggesting that systematic protocols outperform empirical decision-making. 3
Monitoring During Weaning
Monitor blood pressure every 2 minutes initially, then every 5 minutes once stable during dose reduction. 1
Assess tissue perfusion markers continuously: lactate clearance, urine output (target >50 mL/h), mental status, capillary refill, and skin perfusion. 2, 4
Use arterial catheter monitoring for continuous blood pressure assessment throughout the weaning process. 2, 4
Managing Multiple Vasopressors
If vasopressin was added to norepinephrine, wean norepinephrine first—withdrawing vasopressin before norepinephrine causes more hemodynamic instability. 2
This sequence was established in the VASST and VANISH trials and represents standard practice. 2
Once norepinephrine is discontinued and remains off for at least 24 hours, then begin tapering vasopressin if still required. 5
Common Pitfalls to Avoid
Never discontinue norepinephrine abruptly—this can precipitate cardiovascular collapse even in apparently stable patients. 1
Do not delay weaning due to arbitrary dose thresholds—low doses of norepinephrine (0.12 mcg/kg/min) during recovery do not preclude successful liberation from mechanical ventilation or ICU discharge. 6
Avoid maintaining vasopressors at low doses "just in case"—the importance of de-escalation is comparable to the indication for initiation. 2
Do not wean if occult hypovolemia is suspected—address volume status first before reducing vasopressor support. 1
Adjunct Oral Agents for Prolonged Weaning
Consider droxidopa (starting at 100-200 mg three times daily) for patients with persistent low-dose vasopressor requirements preventing ICU liberation, particularly when norepinephrine equivalents are ≤0.05 mcg/kg/min. 5
Median time to vasopressor discontinuation after droxidopa initiation was 70 hours in critically ill patients with prolonged hypotension. 5
Patients on lower norepinephrine equivalents prior to droxidopa initiation (<0.05 vs 0.12 mcg/kg/min) were more likely to wean within 72 hours. 5
Target Hemodynamics During Weaning
Maintain MAP ≥65 mmHg as the minimum target during weaning, though patients with chronic hypertension may require higher targets. 4, 7
Accept MAP values at the lower end of the target range (65-70 mmHg) if tissue perfusion markers remain adequate—do not maintain unnecessarily elevated blood pressure. 7