What is the initial dose of norepinephrine (levarterenol) to start in a patient with septic shock?

From the Guidelines

For septic shock, start norepinephrine at 0.01-0.5 μg/kg/min as a continuous IV infusion, titrating every 5-15 minutes to maintain a mean arterial pressure (MAP) of at least 65 mmHg, as recommended by the most recent guidelines 1. The maximum dose is typically 2-3 mcg/kg/min, though requirements vary by patient. Administer through a central venous catheter whenever possible to avoid extravasation risks. Norepinephrine is the first-line vasopressor for septic shock because it increases vascular tone through alpha-1 receptor stimulation while maintaining cardiac output through its beta-1 effects. This balanced action helps improve tissue perfusion while supporting blood pressure. Monitor the patient closely for signs of peripheral ischemia, arrhythmias, and tachyphylaxis. Once the patient stabilizes and infection control is achieved, gradually wean the infusion by decreasing the dose by 0.02-0.05 mcg/kg/min while monitoring hemodynamic response.

Some key points to consider when using norepinephrine in septic shock include:

• The optimal timing of vasopressors relative to fluid infusion has been debated, but norepinephrine is now the first-line vasopressor agent used to correct hypotension in the event of septic shock 1.
• Dopamine may cause more tachycardia and may be more arrhythmogenic than norepinephrine, and as an alternative vasopressor agent to norepinephrine, it should be used only in patients with low risk of tachyarrhythmias and absolute or relative bradycardia 1.
• The use of dobutamine as an inotropic agent to treat septic shock patients has raised serious questions regarding its safety in the treatment of septic shock 1.
• Increased global availability of vasopressors together with a better understanding of their indications, pharmacodynamics, and important adverse effects are mandatory to fight sepsis worldwide 1.

It is essential to note that the management of septic shock requires a comprehensive approach, including fluid resuscitation, antimicrobial therapy, and supportive care, in addition to the use of vasopressors like norepinephrine 1.

From the Research

Norepinephrine Dosage in Septic Shock

• The optimal dosage of norepinephrine to start in septic shock is not explicitly stated in the provided studies, but the general consensus is to start with a low dose and titrate to effect 2, 3, 4.
• A study published in 2019 found that early administration of low-dose norepinephrine increased shock control by 6 hours compared to standard care 4.
• The dose of norepinephrine can be adjusted based on the patient's response, with the goal of achieving a mean arterial pressure (MAP) of at least 65 mmHg 2, 5, 6.
• Increasing the MAP from 65 to 85 mmHg with norepinephrine did not improve renal function or affect metabolic variables in one study 6.

Factors Influencing Norepinephrine Dosage

• Central venous pressure (CVP) and the difference between the usual MAP and the current MAP can be used to guide adjustments to norepinephrine dosage 5.
• The presence of a low diastolic arterial pressure can be used as a trigger to initiate norepinephrine urgently 3.
• The optimal blood pressure target should be individualized, taking into account the patient's underlying condition and response to treatment 2.

Clinical Considerations

• Early administration of norepinephrine is beneficial for septic shock patients to restore organ perfusion 2, 3, 4.
• Adding vasopressin is recommended in case of shock refractory to norepinephrine 2.
• The dose of norepinephrine should be titrated carefully to avoid excessive vasoconstriction and potential adverse effects 2, 4.