What is the recommended initial dose of noradrenaline (norepinephrine) for an adult patient in septic shock?

Noradrenaline Dose in Septic Shock

Start norepinephrine as the first-line vasopressor as soon as hypotension persists after initial fluid resuscitation, targeting a mean arterial pressure (MAP) of 65 mmHg, with no specific initial dose mandated by guidelines—titrate to achieve the MAP target. 1

Initial Administration Protocol

Norepinephrine is the mandatory first-choice vasopressor in septic shock with a strong recommendation (Grade 1B). 1

Pre-Vasopressor Requirements

• Administer a minimum of 30 mL/kg of crystalloids in the first 3 hours before or concurrent with vasopressor initiation 2, 3
• Establish central venous access for safe norepinephrine administration 2, 4, 3
• Place an arterial catheter as soon as practical for continuous blood pressure monitoring 1, 2

Dosing Strategy

Guidelines do not specify a fixed starting dose—instead, they mandate titration to achieve MAP ≥65 mmHg. 1 The typical starting range in clinical practice is 0.05-0.1 mcg/kg/min, though this is not explicitly stated in the Surviving Sepsis Campaign guidelines.

• Target MAP of 65 mmHg in most patients 1, 2, 3
• Consider higher MAP targets (70-85 mmHg) in patients with chronic hypertension 3
• Titrate continuously based on hemodynamic response and tissue perfusion markers (lactate clearance, urine output ≥0.5 mL/kg/h, mental status) 2, 5

Timing Considerations

Do not delay norepinephrine while pursuing aggressive fluid resuscitation if severe, life-threatening hypotension is present. 2 Early norepinephrine administration (within 93 minutes of emergency room arrival) significantly increases shock control rates by 6 hours (76.1% vs 48.4%, P<0.001) and reduces complications including cardiogenic pulmonary edema and new-onset arrhythmias. 5

• Consider immediate norepinephrine when diastolic blood pressure ≤40 mmHg or diastolic shock index (heart rate/diastolic BP) ≥3 6, 7
• Early administration prevents prolonged severe hypotension, which strongly worsens outcomes 6, 7

Escalation for Refractory Hypotension

Second-Line Agent: Vasopressin

Add vasopressin at 0.03 units/minute (range 0.01-0.03 units/min) when norepinephrine alone fails to achieve target MAP, particularly when norepinephrine doses reach 0.25-0.50 mcg/kg/min. 1, 2, 8

• Vasopressin should never be used as monotherapy—always add to norepinephrine 2, 4, 3
• Do not exceed 0.03-0.04 units/minute except as salvage therapy when all other agents have failed 1, 2
• Doses above 0.03-0.04 units/minute are associated with cardiac, digital, and splanchnic ischemia 2

Factors predicting better vasopressin response: higher norepinephrine infusion rate (≥0.30 mcg/kg/min), normal BMI, and lower lactate levels. 8 Obesity and hyperlactatemia are negatively associated with vasopressin responsiveness. 8

Third-Line Options

Add epinephrine (0.05-2 mcg/kg/min) when norepinephrine plus vasopressin fail to achieve target MAP. 1, 2

Add dobutamine (2.5-20 mcg/kg/min) for persistent hypoperfusion despite adequate MAP and vasopressor therapy, particularly when myocardial dysfunction is evident. 1, 2

• Dobutamine addresses cardiac output rather than vascular tone 2
• Titrate to endpoints reflecting tissue perfusion 1
• Reduce or discontinue if worsening hypotension or arrhythmias develop 1

Adjunctive Therapy for Refractory Shock

Consider hydrocortisone 200 mg/day IV when hemodynamic stability cannot be restored with adequate fluid resuscitation and vasopressor therapy. 1, 2

Agents to Avoid

Do not use dopamine as first-line therapy—it is associated with 11% absolute increase in mortality and significantly more arrhythmias (53% increase in supraventricular arrhythmias, 65% increase in ventricular arrhythmias) compared to norepinephrine. 2, 4

• Use dopamine only in highly selected patients with low risk of tachyarrhythmias or absolute/relative bradycardia 1, 4

Strongly avoid low-dose dopamine for renal protection (Grade 1A recommendation against). 1, 4

Do not use phenylephrine except in specific circumstances: norepinephrine causes serious arrhythmias, cardiac output is documented high with persistently low blood pressure, or as salvage therapy when all other agents have failed. 1, 2, 4

Critical Pitfalls to Avoid

• Do not rely solely on blood pressure numbers—monitor tissue perfusion markers including lactate clearance, urine output, mental status, and capillary refill 2
• Do not delay norepinephrine waiting to complete entire fluid resuscitation if life-threatening hypotension is present 2, 6
• Do not use vasopressin as initial monotherapy—always add to norepinephrine 2, 4, 3
• Do not escalate vasopressin beyond 0.03-0.04 units/minute routinely—add epinephrine instead 2
• Recognize that norepinephrine doses >0.15 mg/min (approximately 0.25 mcg/kg/min in a 70kg patient) indicate severe shock requiring additional vasopressor agents 2, 8

Very High Dose Norepinephrine

In catecholamine-resistant septic shock, very high doses of norepinephrine (>4 mcg/kg/min) can be safe and effective, significantly increasing MAP and systemic vascular resistance while decreasing lactate concentrations, with a survival rate of 33.4% in otherwise extremely high mortality patients. 9 However, this represents salvage therapy for refractory shock after all other interventions have been optimized.