What is the proper weaning protocol for a critically ill adult patient with septic shock who is receiving Levophed (norepinephrine), vasopressin, and Epi (epinephrine)?

Vasopressor Weaning Protocol for Triple-Agent Septic Shock

When weaning a patient on norepinephrine, vasopressin, and epinephrine, you should wean epinephrine first, then norepinephrine, and finally vasopressin last, as withdrawing vasopressin before norepinephrine causes hemodynamic instability. 1

Initiation of Weaning

• Begin weaning as soon as hemodynamic stabilization is achieved 1
• Do not maintain supra-therapeutic doses or higher blood pressure than necessary, as clinicians tend to overestimate the risk of re-aggravation 1
• Target weaning to effect using arterial line monitoring, not fixed doses 1

Monitoring Parameters During Weaning

Monitor these markers continuously to guide weaning decisions 1:

• Mean arterial pressure (MAP) - maintain ≥65 mmHg 1
• Lactate clearance - serial measurements to assess adequacy of perfusion 1
• Mixed or central venous oxygen saturation 1
• Urine output 1
• Skin perfusion, mental status, renal and liver function 1
• Cardiac output monitoring via echocardiography when possible 1

Specific Weaning Sequence

Step 1: Wean Epinephrine First

• Epinephrine carries the highest risk of adverse effects including arrhythmias (~15% incidence), metabolic derangements, and cardiac complications 1
• Decrease epinephrine incrementally every 30 minutes over 12-24 hours once hemodynamic stability is achieved 2
• Suggested decrements: 0.05-0.2 mcg/kg/min 2
• Epinephrine is considered second-line therapy and should be discontinued before adjusting first-line agents 1, 3

Step 2: Wean Norepinephrine Second

• After epinephrine is discontinued, begin weaning norepinephrine 1
• Computerized-assisted weaning may reduce unnecessary exposure and shorten weaning duration 1, 4
• Titrate down gradually while monitoring MAP and perfusion markers 1
• Studies show that controlled weaning protocols significantly reduce time to vasopressor cessation (28.5 vs 57.5 hours) 4

Step 3: Wean Vasopressin Last

• Vasopressin must be weaned after norepinephrine, not before 1
• This sequence was established in the VASST and VANISH trials, which demonstrated that withdrawing vasopressin first causes hemodynamic instability 1
• Vasopressin has the lowest arrhythmia risk (~1-2%) of all three agents 1
• Maximum dose is fixed at 0.03 units/min, so weaning involves gradual dose reduction then discontinuation 1

Common Pitfalls to Avoid

• Never wean vasopressin before norepinephrine - this causes hemodynamic instability and was specifically identified as problematic in major trials 1
• Do not maintain vasopressors at higher doses than needed - physicians commonly overestimate re-aggravation risk 1
• Avoid fixed-dose protocols - always titrate to hemodynamic effect and perfusion markers 1
• Do not rely solely on MAP - complement with lactate, urine output, and other perfusion markers 1

Timeframe Considerations

• Adjust doses every 10-15 minutes during active titration 2
• For epinephrine weaning: decrease every 30 minutes over 12-24 hours 2
• For norepinephrine: controlled weaning can reduce shock duration from 57.5 to 28.5 hours 4
• Early vasopressin addition (<3 hours) is associated with faster shock resolution (37.6 vs 60.7 hours), suggesting aggressive early management facilitates faster weaning 5