What is the recommended norepinephrine (Norad) infusion dose, titration, line selection, and monitoring for an adult with hypotensive shock after fluid resuscitation to achieve a target mean arterial pressure of ≥65 mmHg?

Norepinephrine Administration in Shock

Norepinephrine is the mandatory first-line vasopressor for hypotensive shock after fluid resuscitation, initiated immediately when hypotension persists despite adequate volume replacement, targeting a mean arterial pressure (MAP) ≥65 mmHg. 1, 2

Initial Fluid Resuscitation Before Vasopressors

• Administer at least 30 mL/kg of crystalloid within the first 3 hours before or concurrent with vasopressor initiation 1, 2
• Continue fluid challenges while hemodynamic improvement is observed, using dynamic variables (pulse-pressure variation, stroke-volume variation) or static variables (arterial pressure, heart rate, urine output) to guide further boluses 1
• Do not delay norepinephrine in severe hypotension while pursuing aggressive fluid resuscitation—early vasopressor use is appropriate when diastolic blood pressure is critically low 1, 2

Norepinephrine Dosing and Titration

• Starting dose: 0.02–0.05 µg/kg/min (approximately 2–5 µg/min for a 70 kg adult) 2, 3
• Titration: Increase in increments of 0.02–0.05 µg/kg/min every 5–10 minutes based on hemodynamic response 2
• Target MAP: ≥65 mmHg for most patients 1, 2
• Higher MAP targets (70–85 mmHg): Consider in patients with chronic hypertension to reduce need for renal replacement therapy 1, 2, 3

Line Selection and Administration

• Central venous access is strongly preferred to minimize risk of tissue necrosis from extravasation 1, 2
• If central access is delayed, norepinephrine can be administered through a large peripheral vein with close monitoring for signs of extravasation and local tissue necrosis 1
• If extravasation occurs, stop infusion immediately and infiltrate 5–10 mg phentolamine diluted in 10–15 mL saline into the affected site 2
• Vasopressors can also be administered via intraosseous needles if necessary 1

Hemodynamic Monitoring Requirements

• Arterial catheter placement is recommended for all patients requiring vasopressors as soon as practical for continuous blood pressure monitoring 1, 2, 3
• Monitor beyond MAP alone—assess tissue perfusion using:
  • Lactate clearance: Obtain baseline and repeat within 6 hours if elevated; aim for normalization 1, 2
  • Urine output: Target ≥0.5 mL/kg/h 1, 2
  • Mental status, skin perfusion, and capillary refill 1, 2

Escalation Strategy for Refractory Hypotension

Second-Line: Add Vasopressin

• Add vasopressin at a fixed dose of 0.03 units/min when norepinephrine reaches 0.1–0.25 µg/kg/min and MAP remains <65 mmHg 1, 2
• Never use vasopressin as monotherapy—it must always be added to norepinephrine 1, 2
• Do not exceed 0.03–0.04 units/min except as salvage therapy; higher doses cause cardiac, digital, and splanchnic ischemia without additional benefit 1, 2

Third-Line: Add Epinephrine

• Add epinephrine starting at 0.05 µg/kg/min, titrating up to 0.3 µg/kg/min when MAP cannot be achieved with norepinephrine plus vasopressin 1, 2

For Persistent Hypoperfusion Despite Adequate MAP

• Add dobutamine 2.5–20 µg/kg/min when MAP is adequate (≥65 mmHg) but signs of tissue hypoperfusion persist (elevated lactate, low urine output, altered mental status), especially when myocardial dysfunction is evident 1, 2, 3

Refractory Shock

• Consider hydrocortisone 200 mg/day IV for shock refractory to vasopressors after at least 4 hours of high-dose therapy 1, 2

Critical Agents to Avoid

Dopamine

• Dopamine is strongly contraindicated as first-line therapy (Grade 1A recommendation) 1, 2, 3
• Associated with 11% absolute increase in mortality and significantly higher rates of supraventricular arrhythmias (RR 0.47) and ventricular arrhythmias (RR 0.35) compared to norepinephrine 1, 2
• Reserve only for highly selected patients with absolute or relative bradycardia and low risk of tachyarrhythmias 1, 2
• Low-dose dopamine for renal protection is strongly discouraged (Grade 1A)—it provides no benefit 1, 2, 3

Phenylephrine

• Not recommended except in three specific circumstances: (1) norepinephrine-induced serious arrhythmias, (2) documented high cardiac output with persistent hypotension, or (3) salvage therapy when all other agents have failed 1, 2, 3
• Pure α-agonist vasoconstriction can compromise microcirculatory flow and tissue perfusion despite raising blood pressure numbers 2

Practical Titration Algorithm

1. After 30 mL/kg crystalloid bolus, if MAP <65 mmHg, start norepinephrine at 0.02–0.05 µg/kg/min via central line 2
2. Place arterial catheter for continuous monitoring 2
3. Titrate norepinephrine in increments of 0.02–0.05 µg/kg/min every 5–10 minutes to maintain MAP ≥65 mmHg 2
4. When norepinephrine reaches 0.1–0.25 µg/kg/min and MAP remains <65 mmHg, add vasopressin 0.03 units/min (fixed dose) 2
5. If MAP is still inadequate, add epinephrine beginning at 0.05 µg/kg/min, titrating up to 0.3 µg/kg/min 2
6. If MAP is adequate but hypoperfusion persists, add dobutamine 2.5–20 µg/kg/min 2

Common Pitfalls to Avoid

• Do not delay norepinephrine while pursuing excessive fluid resuscitation in profound hypotension 1, 2
• Do not focus solely on MAP—tissue perfusion markers (lactate, urine output, mental status) are equally critical 1, 2
• Do not escalate vasopressin beyond 0.03–0.04 units/min—this causes end-organ ischemia without hemodynamic benefit 1, 2
• Do not use dopamine for renal protection—this is strongly contraindicated and delays appropriate therapy 1, 2
• Do not combine dopamine with norepinephrine—excessive sympathomimetic stimulation increases adverse events 2