How should norepinephrine be administered to a critically ill adult with severe hypotension or septic shock, considering their medical history?

How to Administer Norepinephrine in Critically Ill Adults

Norepinephrine is the mandatory first-line vasopressor for septic shock and should be started at 0.1–0.5 mcg/kg/min (approximately 7–35 mcg/min in a 70-kg patient) through central venous access, targeting a mean arterial pressure (MAP) of 65 mmHg. 1, 2

Initial Administration Protocol

Route and Access

• Administer norepinephrine through central venous access whenever possible to minimize the risk of tissue necrosis from extravasation 2
• Peripheral administration can be used temporarily in emergency situations when central access is not immediately available, though this carries higher risk of local complications 3
• Place an arterial catheter for continuous blood pressure monitoring as soon as practical—this is essential for all patients requiring vasopressors 1, 2

Starting Dose and Titration

• Begin with 0.1–0.5 mcg/kg/min (7–35 mcg/min in a 70-kg patient) and titrate upward every 5-15 minutes to achieve target MAP 2
• Target MAP ≥65 mmHg in most patients 1, 2
• Consider higher MAP targets of 70-75 mmHg in patients with chronic hypertension 2

Timing of Initiation

• Start norepinephrine early—do not delay waiting to complete entire fluid resuscitation if life-threatening hypotension is present (systolic BP <80 mmHg or diastolic BP ≤40 mmHg) 4, 5
• Early norepinephrine administration (within 1-2 hours of shock recognition) significantly increases shock control rates and reduces fluid overload complications 5
• Administer a minimum of 30 mL/kg crystalloid fluid resuscitation in the first 3 hours, but this can occur simultaneously with vasopressor initiation 1

Escalation Strategy for Inadequate Response

When Norepinephrine Alone is Insufficient

• Add vasopressin at 0.03 units/minute when norepinephrine requirements remain elevated or reach 0.25-0.50 mcg/kg/min 2, 6
• Vasopressin should never be used as monotherapy—it must be added to norepinephrine, not substituted for it 2, 6
• Do not exceed vasopressin doses of 0.03-0.04 units/minute except as salvage therapy, as higher doses cause cardiac, digital, and splanchnic ischemia without additional benefit 1, 2

Third-Line Options

• Add epinephrine (0.05-2 mcg/kg/min) when norepinephrine plus vasopressin fail to achieve target MAP 1, 6
• Consider dobutamine (2.5-20 mcg/kg/min) for persistent hypoperfusion despite adequate MAP, particularly when myocardial dysfunction is evident (elevated cardiac filling pressures with low cardiac output) 1

Critical Agents to Avoid

• Do not use dopamine except in highly selected patients with low risk of tachyarrhythmias or absolute/relative bradycardia—it is associated with 11% higher absolute mortality and significantly more arrhythmias compared to norepinephrine 1, 2, 6
• Never use low-dose dopamine for renal protection—this practice is strongly discouraged and has no benefit 1, 2
• Avoid phenylephrine except in specific circumstances: when norepinephrine causes serious arrhythmias, when cardiac output is documented to be high with persistently low blood pressure, or as salvage therapy when all other agents have failed 1, 2

Monitoring Beyond Blood Pressure

Essential Perfusion Markers

• Assess tissue perfusion using multiple parameters beyond MAP alone 2, 6:
  • Lactate clearance (≥10% reduction from baseline)
  • Urine output (≥0.5 mL/kg/hr for 2 consecutive hours)
  • Mental status improvement
  • Capillary refill and skin temperature (warm extremities)
  • Decreasing heart rate

Signs of Excessive Vasoconstriction

• Monitor for cold extremities, digital ischemia, decreased urine output, rising lactate, or worsening organ dysfunction despite adequate MAP 2, 6
• These signs indicate excessive vasoconstriction that may compromise microcirculatory flow despite achieving blood pressure targets 6

Common Pitfalls and How to Avoid Them

Medication Compatibility

• Do not mix norepinephrine with sodium bicarbonate or other alkaline solutions in the IV line—adrenergic agents are inactivated in alkaline solutions 2

Extravasation Management

• If extravasation occurs, immediately infiltrate 5-10 mg of phentolamine diluted in 10-15 mL of saline into the affected site to prevent tissue necrosis and sloughing 2
• Even with central venous administration, skin necrosis can rarely occur, particularly with vasopressin, necessitating vigilant monitoring 7

Timing Errors

• Do not delay norepinephrine initiation in profound hypotension (diastolic BP ≤40 mmHg or diastolic shock index ≥3) while pursuing aggressive fluid resuscitation alone 8, 4
• Duration and depth of hypotension strongly worsen outcomes—norepinephrine rapidly increases and better stabilizes arterial pressure compared to fluids alone 8, 4

Weaning Strategy

• Once hemodynamic stability is achieved (sustained MAP ≥65 mmHg with adequate tissue perfusion for at least 2 hours), begin gradual dose reduction 6, 9
• When vasopressin has been added, wean norepinephrine first while maintaining vasopressin at 0.03 units/min, then discontinue vasopressin after norepinephrine is successfully weaned 9