What are the guidelines for adding vasopressin in a critically ill adult patient with hypotension (low blood pressure) who is not responding to noradrenaline (norepinephrine)?

Adding Vasopressin When Norepinephrine Fails to Control Blood Pressure

Add vasopressin at 0.03 units/minute when norepinephrine alone fails to maintain a mean arterial pressure (MAP) ≥65 mmHg despite adequate fluid resuscitation (minimum 30 mL/kg crystalloid). 1

When to Add Vasopressin: Specific Thresholds

Start vasopressin when norepinephrine requirements reach 0.1-0.25 mcg/kg/min without achieving target MAP, rather than continuing to escalate norepinephrine to higher doses. 1, 2 The Society of Critical Care Medicine explicitly recommends adding vasopressin at this threshold to either raise MAP to target or decrease norepinephrine dosage while maintaining hemodynamic stability. 1

Critical Pre-Vasopressin Requirements

• Confirm adequate volume resuscitation first: minimum 30 mL/kg crystalloid fluid bolus must be administered before or concurrent with any vasopressor therapy. 1, 2
• Ensure norepinephrine is already running as the first-line vasopressor—vasopressin must never be used as initial monotherapy or the sole vasopressor. 1, 3
• Place an arterial catheter as soon as practical for continuous blood pressure monitoring in all patients requiring vasopressors. 1

Vasopressin Dosing Protocol

Standard Dosing for Septic Shock

• Start vasopressin at 0.01 units/minute and titrate upward by 0.005 units/minute at 10-15 minute intervals until MAP ≥65 mmHg is achieved. 1
• Maximum dose: 0.03-0.04 units/minute for routine use. 1, 3, 4 The FDA label specifies a dosing range of 0.01-0.07 units/minute for septic shock, but guideline evidence strongly recommends not exceeding 0.03-0.04 units/minute. 1, 3
• Doses above 0.03-0.04 units/minute are associated with cardiac, digital, and splanchnic ischemia and should be reserved only for salvage therapy when all other vasopressors have failed. 1

Post-Cardiotomy Shock Dosing

• Start vasopressin at 0.03 units/minute (higher than septic shock starting dose). 1, 3
• FDA-approved dosing range: 0.03-0.1 units/minute for post-cardiotomy shock. 3

What to Do After Adding Vasopressin

Norepinephrine Tapering Strategy

Once vasopressin is added at 0.03 units/minute, you have two options:

• Either raise MAP to target (≥65 mmHg) while maintaining current norepinephrine dose, OR
• Decrease norepinephrine dosage while maintaining hemodynamic stability at MAP ≥65 mmHg. 1

Gradual dose reduction of norepinephrine is preferred over abrupt discontinuation, though specific tapering increments are not defined in guidelines. 1

When Vasopressin Alone Isn't Enough

If norepinephrine requirements remain high despite vasopressin addition, add epinephrine (0.05-2 mcg/kg/min) as a third agent rather than increasing vasopressin beyond 0.03-0.04 units/minute. 1, 2 Epinephrine is particularly useful when myocardial dysfunction is present due to its inotropic effects. 1

For persistent hypoperfusion despite adequate vasopressor support, add dobutamine (2.5-20 mcg/kg/min) rather than escalating vasopressors further. 1, 2 This addresses cardiac output rather than vascular tone.

Monitoring Beyond Blood Pressure Numbers

MAP ≥65 mmHg alone is insufficient—you must assess tissue perfusion using:

• Lactate clearance (repeat within 6 hours if initially elevated) 1
• Urine output (target ≥0.5 mL/kg/h) 1
• Mental status and skin perfusion (capillary refill) 1
• Heart rate and rhythm (continuous ECG monitoring) 1

Critical Pitfalls to Avoid

Never Use Dopamine for "Renal Protection"

The Society of Critical Care Medicine strongly discourages using low-dose dopamine for renal protection—it provides no benefit and increases arrhythmia risk. 1, 2

Don't Delay Vasopressin Addition

Avoid escalating norepinephrine to very high doses (>0.25 mcg/kg/min) before adding vasopressin. 1 Patients receiving ≥15 mcg/min of norepinephrine (approximately 0.2 mcg/kg/min in a 70 kg patient) already have severe septic shock and should receive additional vasopressin to spare norepinephrine. 1 High-dose norepinephrine is associated with increased mortality. 1

Avoid Phenylephrine as First-Line Therapy

Phenylephrine should not be used except in specific circumstances: when norepinephrine causes serious arrhythmias, when cardiac output is documented to be high with persistently low blood pressure, or as salvage therapy when all other agents have failed. 1 Phenylephrine may raise blood pressure numbers on the monitor while actually worsening tissue perfusion through excessive vasoconstriction. 1

Don't Use Vasopressors as a Substitute for Fluids

Never use vasopressors as a substitute for adequate fluid resuscitation—this leads to excessive vasoconstriction and organ ischemia without addressing underlying hypovolemia. 2 Blood volume depletion must be corrected as fully as possible before vasopressors are administered, though in emergency situations where cerebral or coronary ischemia is imminent, vasopressors can be started concurrently with volume replacement. 2

Special Considerations

Trauma Patients with Hemorrhagic Shock

In trauma patients with hemorrhagic shock, prioritize restricted volume replacement with permissive hypotension (target systolic BP 80-90 mmHg) until bleeding is controlled. 5 Add norepinephrine only if systolic BP falls below 80 mmHg to maintain life and tissue perfusion. 5, 2 Consider low-dose arginine vasopressin (bolus of 4 IU followed by 0.04 IU/min) to decrease blood product requirements in severe hemorrhagic shock. 5

Patients with Chronic Hypertension

Target MAP may need to be higher (70-75 mmHg) in patients with chronic hypertension due to impaired autoregulation from atherosclerosis. 1, 2

Elderly Patients

In elderly patients >75 years, consider lower MAP targets of 60-65 mmHg, which may reduce mortality. 2