What is the appropriate norepinephrine infusion starting dose and drip rate for a 70‑kg adult with hypotension (e.g., septic shock)?

Norepinephrine Starting Dose and Drip Rate for Septic Shock

For a 70-kg adult with septic shock, start norepinephrine at 0.05–0.1 µg/kg/min (approximately 3.5–7 µg/min or 0.21–0.42 mg/h) via central venous access after administering at least 30 mL/kg crystalloid, and titrate to maintain a mean arterial pressure (MAP) ≥65 mmHg. 1

Initial Fluid Resuscitation (Mandatory First Step)

• Administer at least 30 mL/kg of crystalloid (approximately 2 liters for a 70-kg patient) within the first 3 hours, either before or concurrently with vasopressor initiation. 1, 2
• Balanced crystalloids (lactated Ringer's or Plasma-Lyte) are preferred over normal saline. 2
• In profound, life-threatening hypotension (e.g., diastolic BP ≤40 mmHg or diastolic shock index ≥3), do not delay norepinephrine while pursuing aggressive fluid resuscitation—start norepinephrine as an emergency measure while fluid resuscitation continues. 1, 3

Starting Dose and Preparation

• Initial dose: 0.05–0.1 µg/kg/min (3.5–7 µg/min for 70 kg) 1, 2
• Standard concentration: Add 4 mg norepinephrine to 250 mL D5W to yield 16 µg/mL. 2
• Alternative starting rate: 0.5 mg/h (approximately 8 µg/min), which falls within the recommended range. 2

Administration Route and Monitoring

• Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis. 1, 2, 4
• If central access is unavailable or delayed, peripheral IV administration can be used temporarily with strict monitoring, though this carries higher risk. 2, 5
• Place an arterial catheter as soon as practical for continuous blood pressure monitoring. 1, 2

Target Blood Pressure

• Standard target: MAP ≥65 mmHg for most patients. 1, 2, 4
• Chronic hypertension exception: Target MAP 70–85 mmHg in patients with pre-existing hypertension to reduce the need for renal replacement therapy. 1
• Titrate to both MAP target and tissue perfusion markers (lactate clearance, urine output ≥0.5 mL/kg/h, mental status, capillary refill). 1

Titration Protocol

• Monitor blood pressure every 5–15 minutes during initial titration. 2
• Titrate in incremental steps based on hemodynamic response to maintain MAP ≥65 mmHg. 1
• Typical dosing range: 0.1–2 µg/kg/min (7–140 µg/min for 70 kg), though most patients respond at lower doses. 2
• For hepatorenal syndrome specifically, increase by 0.5 mg/h every 4 hours to a maximum of 3 mg/h. 2

Escalation Strategy for Refractory Hypotension

Add Vasopressin (Second-Line)

• When norepinephrine reaches 0.1–0.25 µg/kg/min (7–17.5 µg/min for 70 kg) and MAP remains <65 mmHg, add vasopressin at a fixed dose of 0.03 units/min. 1, 6
• Never exceed 0.03–0.04 units/min except as salvage therapy; higher doses cause cardiac, digital, and splanchnic ischemia. 1
• Vasopressin must always be added to norepinephrine, never used as monotherapy. 1
• Factors associated with better vasopressin response include: NE dose ≥0.30 µg/kg/min, absence of obesity, and lower lactate levels. 6

Add Epinephrine (Third-Line)

• If MAP cannot be achieved with norepinephrine + vasopressin, add epinephrine starting at 0.05 µg/kg/min (3.5 µg/min for 70 kg), titrating up to 0.3 µg/kg/min. 1

Add Dobutamine (For Persistent Hypoperfusion)

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

Hemodynamic Effects of Early Norepinephrine

• Early norepinephrine administration (during life-threatening hypotension) increases cardiac output through increased cardiac preload and contractility, not just vasoconstriction. 7
• Norepinephrine transforms unstressed blood volume into stressed blood volume, increasing mean systemic filling pressure. 3
• This effect occurs in patients with both preserved (LVEF >45%) and reduced (LVEF ≤45%) left ventricular function. 7

Agents to Avoid

• Dopamine is contraindicated as first-line therapy—it increases mortality by 11% absolute risk and causes significantly more arrhythmias compared to norepinephrine. 1
• Low-dose dopamine for renal protection is strongly contraindicated (Grade 1A recommendation). 1
• Phenylephrine is not recommended except in three specific situations: (1) norepinephrine-induced serious arrhythmias, (2) documented high cardiac output with persistent hypotension, or (3) salvage therapy after all other agents have failed. 1

Critical Monitoring Beyond MAP

• Serum lactate: Obtain baseline and repeat within 6 hours if elevated; aim for lactate normalization. 1
• Urine output: Maintain ≥0.5 mL/kg/h (≥35 mL/h for 70 kg). 1, 2
• Mental status, capillary refill, and skin perfusion as indicators of adequate tissue perfusion. 1

Common Pitfalls to Avoid

• Delaying norepinephrine in profound hypotension: Duration and depth of hypotension strongly worsen outcomes; early norepinephrine reduces mortality and fluid overload. 3, 8
• Inadequate fluid resuscitation: Always give at least 30 mL/kg crystalloid before or with norepinephrine to optimize cardiac output. 1, 2
• Focusing solely on MAP: Tissue perfusion markers are equally critical for safe titration. 1
• Extravasation without treatment: If extravasation occurs, infiltrate 5–10 mg phentolamine diluted in 10–15 mL saline into the site immediately. 2, 4