What is the recommended initial dose of noradrenaline (norepinephrine) for an adult patient with shock, particularly those with a history of cardiovascular disease, trauma, or severe infection?

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, up 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 tissue perfusion markers beyond just MAP: lactate clearance ≥10%, urine output >50 mL/h for at least 4 hours, normalization of capillary refill, appropriate mental status, and age-appropriate heart rate. 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. 1, 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 and likely represent hypovolemia. 6, 7

• Vasopressin 0.03 units/min can be added to raise MAP to target or decrease norepinephrine dosage, but should never be used as monotherapy. 1, 2, 3 Do not increase vasopressin above 0.03-0.04 units/min—reserve higher doses for salvage therapy only, as they are associated with cardiac, digital, and splanchnic ischemia. 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 myocardial oxygen consumption more than norepinephrine. 2

• Dobutamine 2.5-20 mcg/kg/min should be added if persistent hypoperfusion exists despite adequate MAP and vasopressor therapy, particularly when myocardial dysfunction is evident. 1, 2, 3 Start at 2.5 mcg/kg/min and double every 15 minutes according to response, with dose titration usually limited by excessive tachycardia or arrhythmias. 2

Special Populations

Patients with Cardiovascular Disease

• Norepinephrine may increase myocardial oxygen requirements, mandating cautious use in patients with ischemic heart disease, but this does not contraindicate its use. 2

• Continue chronic beta-blockers in the absence of acute hemodynamic decompensation or cardiogenic shock; temporarily reduce or omit them if the patient is clinically unstable with signs of low cardiac output. 2

• In sepsis specifically, norepinephrine improves renal blood flow and urine output despite typically causing renal vasoconstriction in other contexts. 2

Trauma Patients

• High-dose norepinephrine (≥0.6 mcg/kg/min) in traumatic hemorrhagic shock is associated with higher organ dysfunction scores and likely represents inadequate volume resuscitation. 6

• Ensure adequate non-blood resuscitation volume (≥9 mL/kg/h) to avoid the deleterious effects of excessive vasoconstriction in hypovolemic trauma patients. 6

Pregnant Patients

• Start norepinephrine at 0.02 mcg/kg/min with a target MAP of 65 mmHg. 3

• Consider more restrictive initial fluid boluses of 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, with a typical range of 0.1-1.0 mcg/kg/min. 1, 5, 3

• Maximum doses up to 5 mcg/kg/min may be necessary in some children, mandating central line placement. 1, 5

Critical Pitfalls to Avoid

Do not use dopamine as first-line therapy—it is associated with 11% higher absolute 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, 2

Do not use low-dose dopamine for "renal protection"—this is strongly discouraged and has no benefit. 1, 2, 3

Do not use phenylephrine as first-line therapy—it may raise blood pressure numbers while actually worsening tissue perfusion through excessive vasoconstriction. 1, 2, 3 Reserve phenylephrine only for specific circumstances: norepinephrine-induced serious arrhythmias, documented high cardiac output with persistent hypotension, or salvage therapy when all other agents have failed. 1, 2

Do not escalate norepinephrine beyond 0.6 mcg/kg/min without adding second-line agents—this likely represents inadequate volume resuscitation or irreversible circulatory failure. 6, 7 Scores >40 on APACHE II, bicarbonate <9.0 mEq/L, or epinephrine dose ≥0.25 mcg/kg/min are associated with 100% mortality. 7

Extravasation Management

If extravasation occurs, immediately infiltrate phentolamine 5-10 mg diluted in 10-15 mL of saline intradermally at the site to prevent tissue necrosis. 2, 5, 3 Pediatric dose: 0.1-0.2 mg/kg up to 10 mg. 5, 3