What initial norepinephrine (noradrenaline) infusion rate should be used for a 65‑year‑old, 70‑kg patient to achieve a mean arterial pressure of at least 65 mm Hg?

Initial Norepinephrine Infusion Rate for Septic Shock

For a 65-year-old, 70-kg patient requiring norepinephrine to achieve a MAP ≥65 mmHg, start at 0.02 µg/kg/min (approximately 1.4 µg/min or 0.5 mg/h), administered through central venous access after or concurrent with at least 30 mL/kg crystalloid resuscitation. 1, 2

Pre-Administration Requirements

Before initiating norepinephrine, you must address hypovolemia first:

• Administer a minimum 30 mL/kg crystalloid bolus (2,100 mL for a 70-kg patient) within the first 3 hours, either before or simultaneously with vasopressor initiation 1, 2
• Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) preferentially over normal saline 2
• Exception for profound hypotension: If systolic BP <70 mmHg or diastolic BP ≤40 mmHg, start norepinephrine emergently while fluid resuscitation continues rather than waiting for complete volume repletion 2

Specific Starting Dose

The most recent guidelines provide weight-based dosing:

• Initial rate: 0.02 µg/kg/min 1, 2
• For a 70-kg patient, this equals 1.4 µg/min or approximately 0.5 mg/h 2
• Alternative guideline recommendation: 0.02–0.05 µg/kg/min (0.5 mg/h) 2

The FDA label provides concentration-based dosing that translates similarly:

• Standard dilution: Add 4 mg norepinephrine to 1,000 mL D5W (yielding 4 µg/mL) 3
• Initial infusion rate: 2–3 mL/min (8–12 µg/min of base) 3
• Maintenance rate: 0.5–1 mL/min (2–4 µg/min of base) 3

Administration Route & Monitoring

Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis 1, 2. However, if central access is unavailable:

• Starting norepinephrine via a large peripheral vein is safe until central access is established 1
• This approach reduces treatment delays in critically ill patients 1

Monitoring requirements:

• Place an arterial catheter for continuous blood pressure monitoring as soon as practical 1, 2
• Check blood pressure and heart rate every 5–15 minutes during initial titration 1, 2
• Monitor urine output hourly (target ≥0.5 mL/kg/h) 2
• Measure lactate levels every 2–4 hours during early resuscitation 2
• Assess mental status, capillary refill, and peripheral perfusion regularly 2

Target Blood Pressure

Target MAP of 65 mmHg for most patients with septic shock 1, 2. This represents the minimum threshold for adequate organ perfusion.

Important nuances:

• Patients with chronic hypertension may require a higher target of 70–75 mmHg to reduce the need for renal replacement therapy 1, 2
• A recent UK study in patients >65 years showed that allowing MAP to drop to 60 mmHg resulted in no difference in 90-day mortality compared to targeting 65 mmHg 1
• Do not target MAP >85 mmHg routinely—a multicenter trial found no mortality benefit (36.6% vs 34.0% at 28 days) and increased risk of arrhythmias 1

Titration Strategy

Titrate to both MAP and tissue perfusion markers:

• Increase dose gradually based on hemodynamic response 2
• Monitor lactate clearance, urine output, mental status, and capillary refill in addition to MAP 2
• The typical maintenance range is 0.1–0.5 µg/kg/min 2

Escalation for Refractory Hypotension

If MAP ≥65 mmHg cannot be achieved with norepinephrine alone:

1. Add vasopressin at 0.03 units/min when norepinephrine reaches 0.1–0.25 µg/kg/min 1, 2

   • Do not exceed 0.03–0.04 units/min for routine use 2
   • Vasopressin should never be used as monotherapy 2

2. Add epinephrine 0.1–0.5 µg/kg/min as an alternative to vasopressin 2

3. Add dobutamine 2.5–20 µg/kg/min if persistent hypoperfusion exists despite adequate MAP, particularly with myocardial dysfunction 1, 2

4. Consider hydrocortisone 50 mg IV every 6 hours (or 200 mg/day continuous infusion) for refractory shock 1, 2

Critical Pitfalls to Avoid

• Never use dopamine as first-line therapy—it is associated with 11% absolute increase in mortality and higher arrhythmia rates compared to norepinephrine 4
• Do not use low-dose dopamine for renal protection—it provides no benefit 1, 5
• Avoid phenylephrine as first-line agent—it may raise blood pressure while worsening tissue perfusion 5, 4
• Do not delay norepinephrine while pursuing aggressive fluid resuscitation alone in severe hypotension 2
• Do not mix norepinephrine with sodium bicarbonate or other alkaline solutions, as this inactivates the drug 5

Extravasation Management

If extravasation occurs:

• Infiltrate phentolamine 5–10 mg diluted in 10–15 mL normal saline intradermally at the site immediately to prevent tissue necrosis 1, 5, 2

Special Considerations for This Patient

For a 65-year-old patient specifically:

• The recent UK study suggests that in patients >65 years, targeting MAP 60–65 mmHg may be acceptable and reduces vasopressor exposure without increasing mortality 1
• However, start with the standard target of 65 mmHg and individualize based on chronic hypertension status and tissue perfusion markers 1, 2
• If the patient has a history of hypertension, consider targeting MAP 70–75 mmHg to reduce risk of acute kidney injury requiring renal replacement therapy 1