In an adult with septic shock and chronic hypertension, should norepinephrine or vasopressin be titrated first?

Titrate Norepinephrine First, Then Add Vasopressin

In septic shock with chronic hypertension, you should titrate norepinephrine first as your sole vasopressor, then add vasopressin at a fixed dose of 0.03 units/minute when norepinephrine requirements remain elevated (typically at 0.1–0.25 µg/kg/min or approximately 10–20 µg/min absolute dose). 1, 2, 3

Initial Vasopressor Strategy

• Start norepinephrine immediately as the mandatory first-line vasopressor when hypotension persists after initial fluid resuscitation (minimum 30 mL/kg crystalloid within 3 hours). 1, 2, 3
• Target a MAP of 65 mmHg initially, though patients with chronic hypertension may benefit from a higher target of 70–85 mmHg to reduce renal replacement therapy requirements. 1, 2, 3
• Begin norepinephrine at 0.02–0.05 µg/kg/min and titrate upward based on MAP response and tissue perfusion markers (lactate clearance, urine output ≥0.5 mL/kg/h, mental status, capillary refill). 1
• Establish central venous access for safe administration and place an arterial catheter for continuous blood pressure monitoring as soon as practical. 1, 2, 3

When to Add Vasopressin (Second-Line)

• Add vasopressin at 0.03 units/minute when norepinephrine reaches 0.1–0.25 µg/kg/min (approximately 10–20 µg/min in a 70 kg patient) and MAP remains below target despite adequate fluid resuscitation. 1, 4
• Vasopressin should never be used as monotherapy or as the initial vasopressor—it must be added to norepinephrine. 1, 2, 3
• Do not titrate vasopressin—use a fixed dose of 0.03 units/minute. Doses exceeding 0.03–0.04 units/minute cause cardiac, digital, and splanchnic ischemia without additional hemodynamic benefit and should only be used as salvage therapy. 1, 4

Rationale for This Sequence

• Norepinephrine has superior mortality data compared to all other first-line agents, with an 11% absolute risk reduction versus dopamine and significantly fewer arrhythmias. 1
• Early norepinephrine administration (even before complete fluid resuscitation in profound hypotension with diastolic BP ≤40 mmHg) rapidly stabilizes arterial pressure, improves organ perfusion, and prevents fluid overload. 5, 6
• Vasopressin corrects relative deficiency that occurs in septic shock (60% of patients have inadequate vasopressin response) and provides norepinephrine-sparing effects through catecholamine-independent vasoconstriction via V1a receptors. 1, 4
• Adding vasopressin at moderate norepinephrine doses (rather than escalating norepinephrine to very high doses) follows the concept of "decatecholaminization"—reducing catecholamine load to minimize cardiac and immunologic adverse effects. 4

If Hypotension Remains Refractory

• Add epinephrine (0.05–2 µg/kg/min) as a third vasopressor if norepinephrine plus vasopressin fail to achieve target MAP. 1, 2, 3
• Add dobutamine (2.5–20 µg/kg/min) if MAP is adequate but signs of tissue hypoperfusion persist, particularly with evidence of myocardial dysfunction (low cardiac output, elevated filling pressures). 1, 2, 3
• Consider hydrocortisone 200 mg/day IV if hypotension remains refractory after ≥4 hours of high-dose vasopressor therapy. 1, 3

Critical Pitfalls to Avoid

• Never delay norepinephrine while pursuing aggressive fluid resuscitation in severe hypotension—early vasopressor use is appropriate when diastolic BP is critically low. 1, 5
• Never use dopamine as first-line therapy; it increases mortality and arrhythmias compared to norepinephrine and should only be considered in highly selected patients with bradycardia and low arrhythmia risk. 1, 2, 3
• Never use phenylephrine except in three specific scenarios: norepinephrine-induced serious arrhythmias, documented high cardiac output with persistent hypotension, or salvage therapy when all other agents have failed. 1, 2, 3
• Do not use low-dose dopamine for renal protection—this is strongly contraindicated (Grade 1A recommendation). 1, 2
• Do not exceed vasopressin 0.03–0.04 units/minute except as salvage therapy, as higher doses cause end-organ ischemia. 1, 4

Special Consideration for Chronic Hypertension

• In your patient with chronic hypertension, target a MAP of 70–85 mmHg rather than 65 mmHg, as this reduces the need for renal replacement therapy in this subgroup. 1, 2
• Monitor closely for increased arrhythmias with higher MAP targets. 2

Monitoring Requirements

• Continuous arterial blood pressure via arterial catheter. 1, 2, 3
• Tissue perfusion markers: lactate every 2–4 hours, urine output hourly (target ≥0.5 mL/kg/h), mental status, skin perfusion, capillary refill. 1, 3
• Consider cardiac output monitoring when using pure vasopressors like vasopressin to ensure adequate flow is maintained. 2, 3