Noradrenaline Dosing in Septic Shock
Start noradrenaline immediately when hypotension persists after initial fluid resuscitation (minimum 30 mL/kg crystalloid), titrating to achieve a mean arterial pressure (MAP) of 65 mmHg, with no specific "initial dose" recommended—rather, titrate continuously based on blood pressure response. 1, 2
Initial Administration Protocol
Noradrenaline is the mandatory first-choice vasopressor for septic shock with a Grade 1B recommendation from the Surviving Sepsis Campaign. 3, 1
Begin noradrenaline as soon as hypotension persists despite fluid resuscitation—do not delay vasopressor initiation waiting to complete all fluid administration if life-threatening hypotension exists. 1, 2
The target MAP is ≥65 mmHg in most patients, though higher targets may be considered in patients with chronic hypertension. 3, 1, 2
Require central venous access for safe administration and place an arterial catheter for continuous blood pressure monitoring as soon as practical. 3, 1, 2
Practical Dosing Considerations
While guidelines do not specify an exact "starting dose," clinical practice typically begins with low doses (e.g., 0.05-0.1 mcg/kg/min) and titrates upward. 4, 5
In one prospective study using a noradrenaline-based algorithm, the maximum dose required was 0.31±0.3 mcg/kg/min with 33% ICU mortality. 5
Consider early initiation in patients with profound hypotension, particularly when diastolic blood pressure is ≤40 mmHg or diastolic shock index (heart rate/diastolic BP) is ≥3, as these indicate severely depressed vascular tone. 6, 7
Early noradrenaline administration (simultaneously with fluid resuscitation) prevents prolonged hypotension, increases cardiac output, improves microcirculation, and avoids fluid overload. 4, 6, 7
Management of Refractory Hypotension
If MAP target cannot be achieved with noradrenaline alone, add vasopressin at 0.03 units/minute rather than escalating noradrenaline indefinitely. 3, 1, 2
Vasopressin should never be used as monotherapy—it must be added to noradrenaline. 1, 2
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. 1, 2
Noradrenaline doses ≥15 mcg/min indicate severe septic shock and warrant addition of vasopressin to spare noradrenaline requirements. 1
If additional support is needed, add epinephrine as a third agent (0.05-2 mcg/kg/min) rather than further escalating vasopressin. 3, 1, 2
Consider dobutamine (up to 20 mcg/kg/min) if persistent hypoperfusion exists despite adequate vasopressors and fluid loading, particularly with evidence of myocardial dysfunction. 3, 1, 2
Critical Pitfalls to Avoid
Do not use dopamine as first-line therapy—it is associated with higher mortality and more arrhythmias compared to noradrenaline, and should only be used in highly selected patients with low risk of tachyarrhythmias or absolute/relative bradycardia. 3, 1, 2
Strongly avoid low-dose dopamine for renal protection—this practice has no benefit and is explicitly discouraged. 1, 2
Do not use phenylephrine except in specific circumstances: when noradrenaline 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
Do not rely solely on blood pressure numbers—monitor markers of tissue perfusion including lactate, urine output, and mental status. 1, 2
Recognize that very high noradrenaline doses (>4 mcg/kg/min) indicate near-irreversible circulatory failure, though they can be administered safely when necessary with appropriate monitoring. 8