Norepinephrine Dosing in Shock
Start norepinephrine at 0.1-0.5 mcg/kg/min (approximately 0.5 mg/h or 8-12 mcg/min in a 70 kg adult) via continuous IV infusion, targeting a mean arterial pressure of 65 mmHg, with central venous access strongly preferred and concurrent fluid resuscitation of at least 30 mL/kg crystalloid. 1, 2, 3
Critical Pre-Administration Requirements
Administer a minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation—do not delay vasopressors while pursuing aggressive fluid resuscitation in severe hypotension (systolic <70 mmHg or diastolic ≤40 mmHg). 1, 2, 3 Vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure numbers. 2, 3
In patients with profound, life-threatening hypotension (diastolic ≤40 mmHg or diastolic shock index ≥3), early norepinephrine administration simultaneously with fluid resuscitation should be prioritized, as duration and depth of hypotension strongly worsen outcomes. 4
Administration Route and Monitoring
Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis. 1, 2, 5, 3 If central access is unavailable or delayed, peripheral IV or intraosseous administration can be used temporarily with strict monitoring. 5
Place an arterial catheter as soon as practical for continuous blood pressure monitoring in all patients requiring vasopressors. 2, 3
Monitor blood pressure and heart rate every 5-15 minutes during initial titration. 5, 3
Titration Protocol
Start at 0.1-0.5 mcg/kg/min (0.5 mg/h using standard concentration of 4 mg in 250 mL D5W = 16 mcg/mL). 5, 3
Increase by 0.5 mg/h every 4 hours as needed, to a maximum of 3 mg/h. 5, 3
Target MAP ≥65 mmHg for most patients, though patients with chronic hypertension may require higher targets (70-75 mmHg). 1, 2, 3
Titrate to both MAP and tissue perfusion markers: lactate clearance ≥10%, urine output >50 mL/h for 4 hours, normalization of capillary refill, age-appropriate heart rate, and mental status. 1, 2, 3
Escalation Strategy for Refractory Hypotension
When norepinephrine reaches 0.25 mcg/kg/min (approximately 15-20 mcg/min) and hypotension persists, add vasopressin 0.03 units/min as second-line therapy rather than continuing to escalate norepinephrine alone. 2, 3 Patients requiring ≥15 mcg/min of norepinephrine have significantly elevated mortality, and doses above 0.6 mcg/kg/min are associated with higher organ dysfunction scores. 6, 7
Vasopressin 0.03 units/min can be added to raise MAP or decrease norepinephrine dosage. 1, 2 Never use vasopressin as monotherapy, and do not exceed 0.03-0.04 units/min except for salvage therapy. 1, 2
Epinephrine 0.05-2 mcg/kg/min may be added as a third agent when norepinephrine plus vasopressin fail to achieve target MAP. 1, 2, 3 However, epinephrine causes transient lactic acidosis through β2-adrenergic stimulation and increases arrhythmia risk. 2, 8
Dobutamine 2.5-20 mcg/kg/min should be added for persistent hypoperfusion despite adequate MAP and vasopressors, particularly when myocardial dysfunction is evident. 1, 2, 3
Special Populations
Patients with Cardiovascular Disease
Norepinephrine may increase myocardial oxygen requirements but does not contraindicate its use in ischemic heart disease. 2
Continue chronic beta-blockers unless acute hemodynamic decompensation or cardiogenic shock is present. 2
Consider adding dobutamine earlier if myocardial dysfunction is evident, starting at 2.5 mcg/kg/min and titrating based on response. 2, 8
Trauma Patients
High-dose norepinephrine (≥0.6 mcg/kg/min) in hemorrhagic shock is associated with higher organ dysfunction scores and likely reflects inadequate volume resuscitation. 6
Ensure adequate non-blood resuscitation volume (≥9 mL/kg/h) to avoid excessive vasoconstriction in hypovolemic states. 6
Pregnant Patients
Start at 0.02 mcg/kg/min with target MAP 65 mmHg. 3
Consider more restrictive initial fluid boluses (1-2 L) due to lower colloid oncotic pressure and higher pulmonary edema risk. 3
Pediatric Patients
Start at 0.1 mcg/kg/min, titrating to desired clinical effect. 1, 5, 3
Typical range: 0.1-1.0 mcg/kg/min; maximum doses up to 5 mcg/kg/min may be necessary. 1, 5, 3
Infants <6 months may have age-specific insensitivity to dopamine due to immature sympathetic innervation, making norepinephrine preferred. 1
Critical Pitfalls to Avoid
Do not use dopamine as first-line therapy—it is associated with 11% absolute increase in mortality and significantly more arrhythmias (53% risk reduction for supraventricular arrhythmias and 65% for ventricular arrhythmias with norepinephrine). 1, 2, 3 Dopamine should only be used in highly selected patients with absolute bradycardia and low risk of tachyarrhythmias. 1
Do not use low-dose dopamine for "renal protection"—this practice is strongly discouraged and provides no benefit. 1, 2, 3
Do not use phenylephrine as first-line therapy—it may raise blood pressure numbers while worsening tissue perfusion through pure alpha-agonism without cardiac stimulation. 1, 2, 3 Reserve phenylephrine only for norepinephrine-induced serious arrhythmias, documented high cardiac output with persistent hypotension, or salvage therapy. 1, 2
Do not delay norepinephrine in profound hypotension—early administration (within the first hour) in patients with diastolic BP ≤40 mmHg or diastolic shock index ≥3 may reduce mortality and fluid requirements. 4
Do not escalate vasopressin above 0.03-0.04 units/min—higher doses are associated with cardiac, digital, and splanchnic ischemia. 2, 3
Extravasation Management
If extravasation occurs, immediately infiltrate phentolamine 5-10 mg diluted in 10-15 mL saline intradermally at the site to prevent tissue necrosis. 5, 3 Pediatric dose: 0.1-0.2 mg/kg up to 10 mg. 5, 3
Indicators of Futility
Treatment with high-dose norepinephrine is futile when: 7
- APACHE II score >40
- Bicarbonate <9.0 mEq/L
- Epinephrine dose ≥0.25 mcg/kg/min required
These thresholds are associated with 100% mortality and should prompt consideration of goals-of-care discussions. 7