When to hold or maintain norepinephrine (vasopressor) in patients with septic shock or severe hypotension?

Norepinephrine Management in Septic Shock

Norepinephrine should be initiated when patients have persistent hypotension despite initial fluid resuscitation, and should be weaned when the patient maintains target MAP ≥65 mmHg without vasopressor support for 8 hours. 1, 2

When to Start Norepinephrine

• Begin norepinephrine when persistent hypotension (MAP <65 mmHg) occurs despite initial fluid challenge of 30 mL/kg crystalloids within the first 3 hours 2
• Start norepinephrine immediately when diastolic blood pressure is critically low (e.g., ≤40 mmHg), threatening organ perfusion, even before completing fluid resuscitation 2, 3
• Early administration of norepinephrine is beneficial as it increases cardiac output, improves microcirculation, and avoids fluid overload 3, 4
• Initial dosing should be 0.02-0.05 μg/kg/min, titrating to maintain target MAP ≥65 mmHg 2

Monitoring During Norepinephrine Administration

• Place an arterial catheter as soon as practical for continuous blood pressure monitoring 1, 2
• Monitor for signs of adequate perfusion including:
  • Mental status
  • Capillary refill
  • Lactate clearance
  • Urine output 2
• Target MAP should be individualized:
  • Initial target of 65 mmHg for most patients 1, 5
  • Higher targets (e.g., 75-85 mmHg) may be appropriate for patients with chronic hypertension 5

Management of Refractory Hypotension

• If target MAP cannot be achieved with norepinephrine at 0.1-0.2 μg/kg/min, consider adding:
  • Vasopressin (up to 0.03 U/min) to either raise MAP or decrease norepinephrine requirements 1, 2, 6
  • Epinephrine as an alternative second agent 1, 2
• Phenylephrine is not recommended except in specific circumstances:
  • When norepinephrine causes serious arrhythmias
  • When cardiac output is known to be high but blood pressure remains low
  • As salvage therapy when other vasopressors have failed 7, 5

When to Wean Norepinephrine

• After target blood pressure has been maintained for 8 hours without the use of additional catecholamines, begin tapering vasopressin by 0.005 units/minute every hour as tolerated to maintain target blood pressure 6
• For norepinephrine, gradually decrease the dose while monitoring hemodynamic response 1
• Continue fluid resuscitation during weaning of vasopressors to maintain adequate intravascular volume 5
• Monitor for recurrent hypotension during the weaning process, which may indicate:
  • Inadequate volume status
  • Ongoing sepsis requiring further source control
  • Adrenal insufficiency 2

Pitfalls and Caveats

• Avoid relying solely on fluid resuscitation in profound shock as this may prolong hypotension and worsen outcomes 2, 3
• Do not use low-dose dopamine for renal protection as this practice is not supported by evidence 1, 2
• Be cautious with high doses of vasopressors (>0.1 units/minute for vasopressin) as adverse reactions are expected to increase 6
• Early administration of norepinephrine may be particularly beneficial in patients with profound hypotension (diastolic BP ≤40 mmHg) or high diastolic shock index (heart rate/diastolic blood pressure ≥3) 3
• In patients with cardiac dysfunction (LVEF ≤45%), be cautious when targeting MAP ≥75 mmHg as this may not improve cardiac output 8