What is the recommended rate of vasopressin infusion for a patient in septic shock or vasodilatory shock with a history of heart disease or renal disease?

Vasopressin Infusion Rate in Septic Shock with Cardiac or Renal Comorbidities

For patients with septic shock and heart disease or renal disease, initiate vasopressin at 0.01 units/minute and titrate by 0.005 units/minute every 10-15 minutes to a maximum of 0.03 units/minute, never as monotherapy but only added to norepinephrine. 1

Initial Vasopressor Strategy Before Vasopressin

• Start norepinephrine as the mandatory first-line vasopressor after administering at least 30 mL/kg crystalloids in the first 3 hours, targeting a mean arterial pressure (MAP) of 65 mmHg 2, 3
• Establish central venous access for safe vasopressor administration and place an arterial catheter for continuous blood pressure monitoring as soon as practical 2, 3
• Norepinephrine improves renal blood flow and urine output in sepsis despite typically causing renal vasoconstriction in other contexts, making it safe in patients with renal disease 3

When to Add Vasopressin

• Add vasopressin when norepinephrine alone fails to maintain MAP ≥65 mmHg despite adequate fluid resuscitation 3
• Never use vasopressin as the sole initial vasopressor—it must always be added to norepinephrine, not used as monotherapy 2, 3, 1
• The FDA-approved starting dose for septic shock is 0.01 units/minute, which is lower than the 0.03 units/minute starting dose used for post-cardiotomy shock 1

Titration Protocol

• Titrate vasopressin up by 0.005 units/minute at 10-15 minute intervals until target MAP ≥65 mmHg is achieved 1
• The maximum dose should not exceed 0.03-0.04 units/minute for routine use 2, 3
• Doses higher than 0.03-0.04 units/minute should be reserved exclusively for salvage therapy when other vasopressor agents have failed to achieve adequate MAP 2, 3
• Limited data exist for doses above 0.07 units/minute in septic shock, and adverse reactions increase substantially with higher doses 1

Special Considerations for Cardiac Disease

• Vasopressin may cause cardiac ischemia, digital ischemia, and splanchnic ischemia at doses above 0.03-0.04 units/minute 3
• In patients with heart failure or ischemic heart disease, norepinephrine increases myocardial oxygen requirements, but this does not contraindicate its use 3
• Add dobutamine (starting at 2.5-20 mcg/kg/min) if persistent hypoperfusion exists despite adequate MAP and vasopressor therapy, particularly when myocardial dysfunction is evident 2, 3
• Several studies demonstrated clinically significant reduced cardiac output after vasopressin initiation, necessitating cautious use in patients with cardiac dysfunction 4

Special Considerations for Renal Disease

• Low-dose dopamine should never be used for renal protection—this is a strong recommendation with no benefit 2, 3
• Vasopressin substantially enhances urine production, likely due to increased glomerular filtration rate, which may be beneficial in patients with renal dysfunction 4
• The need for renal replacement therapy may be affected by vasopressor choice, making careful monitoring essential 2

Escalation Strategy for Refractory Hypotension

• If target MAP is not achieved with norepinephrine plus vasopressin at 0.03 units/minute, add epinephrine (0.05-2 mcg/kg/min) as a third agent rather than increasing vasopressin beyond 0.03-0.04 units/minute 3, 1
• Consider adding low-dose corticosteroids (hydrocortisone 200 mg/day IV) for shock reversal if hypotension remains refractory to vasopressors 3, 5
• Dobutamine up to 20 mcg/kg/min should be considered if there is evidence of myocardial dysfunction with persistent hypoperfusion 2, 3

Critical Monitoring Requirements

• Monitor for signs of excessive vasoconstriction: digital ischemia, decreased urine output, rising lactate, or worsening organ dysfunction despite adequate MAP 3
• Assess tissue perfusion using lactate clearance, urine output, mental status, and skin perfusion in addition to MAP ≥65 mmHg 3
• Watch for vasopressin-associated adverse effects including ischemia of mesenteric mucosa, skin, and myocardium; elevated hepatic transaminases; hyponatremia; and thrombocytopenia 4

Tapering Protocol

• After target blood pressure has been maintained for 8 hours without the use of catecholamines, taper vasopressin by 0.005 units/minute every hour as tolerated to maintain target blood pressure 1
• Taper hydrocortisone when vasopressors are no longer required if corticosteroids were initiated 2, 5

Common Pitfalls to Avoid

• Do not delay norepinephrine initiation while pursuing aggressive fluid resuscitation in severe hypotension—early vasopressor use is appropriate when diastolic blood pressure is critically low 3
• Do not use dopamine as first-line therapy; it is associated with 11% higher absolute mortality and significantly more arrhythmias compared to norepinephrine 3
• Avoid phenylephrine except in specific circumstances: norepinephrine-induced serious arrhythmias, documented high cardiac output with persistent hypotension, or salvage therapy 2, 3
• Do not escalate vasopressin above 0.03-0.04 units/minute routinely—add epinephrine instead 3
• Recent observational data suggest that earlier vasopressin initiation (at lower norepinephrine-equivalent doses around 9 µg/min) may be associated with lower mortality compared to initiation at higher doses (28 or 72 µg/min), though this requires confirmation in randomized trials 6