What is the recommended initial dose and administration of levophed (norepinephrine) for an adult with hypotension due to septic or cardiogenic shock after fluid resuscitation?

Norepinephrine Dosing and Administration in Septic and Cardiogenic Shock

Initial Dose and Route

Start norepinephrine at 0.02–0.05 µg/kg/min (approximately 0.5 mg/h or 1.4 µg/min for a 70-kg adult) via continuous IV infusion, preferably through central venous access, after administering at least 30 mL/kg crystalloid within the first 3 hours. 1

• The initial dose range of 0.02–0.05 µg/kg/min allows for individualized titration based on the severity of hypotension 1
• Central venous catheter placement is strongly preferred to minimize the risk of extravasation and tissue necrosis 1
• If central access is unavailable, initiate norepinephrine through a large-bore peripheral IV to avoid treatment delays, then transition to central access as soon as feasible 1, 2

Fluid Resuscitation Requirements

• Administer a minimum crystalloid bolus of 30 mL/kg within the first 3 hours (approximately 2 L for a 70-kg adult) before or concurrently with vasopressor initiation 1, 3
• In profound hypotension (SBP < 70 mmHg or DBP ≤ 40 mmHg), start norepinephrine emergently while fluid resuscitation continues rather than delaying for complete volume repletion 1, 4
• Early norepinephrine administration (within 93 minutes of emergency room arrival) significantly increases shock control rates by 6 hours compared to delayed initiation (76.1% vs 48.4%, P < 0.001) 5

Hemodynamic Targets

• Target a minimum MAP of 65 mmHg as the primary endpoint for most patients with septic or cardiogenic shock 1, 3
• In patients with chronic hypertension, consider targeting MAP 70–75 mmHg to reduce the incidence of renal replacement therapy 1
• Monitor blood pressure and heart rate every 5–15 minutes during the initial titration phase 1
• Place an arterial catheter for continuous blood pressure monitoring as soon as practical 6, 1

Monitoring Beyond MAP

MAP alone is insufficient—assess tissue perfusion using lactate clearance (repeat every 2–4 hours), urine output ≥ 0.5 mL/kg/h, mental status, capillary refill ≤ 2 seconds, and skin perfusion. 1, 3

• Lactate clearance provides a dynamic marker of global tissue perfusion and resuscitation adequacy 1
• Urine output ≥ 0.5 mL/kg/h for at least 2 consecutive hours indicates adequate renal perfusion 1

Escalation Strategy for Refractory Hypotension

• When norepinephrine reaches 0.1–0.25 µg/kg/min without achieving MAP ≥ 65 mmHg, add vasopressin at 0.03 units/min as a second-line agent 1, 3
• Do not exceed vasopressin doses of 0.03–0.04 units/min except as salvage therapy, as higher doses cause cardiac, digital, and splanchnic ischemia 6, 1
• If myocardial dysfunction persists despite adequate MAP, add dobutamine at 2.5–20 µg/kg/min to improve cardiac output rather than further escalating vasopressors 1, 2
• For refractory shock after ≥ 4 hours of high-dose vasopressor therapy, administer hydrocortisone 50 mg IV every 6 hours (or 200 mg/day continuous infusion) 1, 3

Agents to Avoid

• Dopamine should not be used as first-line therapy; it is associated with an 11% absolute increase in mortality and significantly higher arrhythmia rates compared to norepinephrine 1, 3
• Low-dose dopamine for renal protection provides no benefit and is strongly discouraged (Grade 1A recommendation) 6, 1
• Phenylephrine should be avoided as first-line therapy because it may raise blood pressure without improving tissue perfusion and can decrease stroke volume 6, 1

Extravasation Management

• If norepinephrine extravasates, immediately infiltrate phentolamine 5–10 mg diluted in 10–15 mL normal saline intradermally at the site to prevent tissue necrosis 1

Special Populations

• In pregnant patients with sepsis, limit the initial fluid bolus to 1–2 L due to higher risk of pulmonary edema, then start norepinephrine at 0.02 µg/kg/min 1
• For pediatric patients, start norepinephrine at 0.1 µg/kg/min, titrating within a range of 0.1–1.0 µg/kg/min, with maximum doses up to 5 µg/kg/min in refractory cases 1

Critical Pitfalls to Avoid

• Do not delay norepinephrine while pursuing aggressive fluid resuscitation alone in severe hypotension (SBP < 70 mmHg or DBP ≤ 40 mmHg), as prolonged hypotension independently worsens mortality 1, 4, 7
• Early norepinephrine administration reduces fluid overload, cardiogenic pulmonary edema (14.4% vs 27.7%, P = 0.004), and new-onset arrhythmias (11% vs 20%, P = 0.03) 5
• Do not mix norepinephrine with sodium bicarbonate or other alkaline solutions, as this inactivates the drug 1