Norepinephrine as first-line vasopressor in septic shock with AKI

AKImedium

A 76-year-old man presents to the emergency department with fever, chills, and shortness of breath. Past medical history includes CKD stage G3a/A2 attributed to poorly controlled type 2 diabetes and hypertension. BP is 82/54 mm Hg, heart rate is 112/min, respiratory rate is 22/min, and oxygen saturation is 84% breathing room air. On examination, he is somnolent with labored breathing. Heart examination reveals tachycardia and lung examination reveals coarse breath sounds, decreased in the right base. There is no edema. Laboratory data on admission is significant for creatinine 1.3 mg/dL (baseline, 0.9; reference range, 0.7–1.3). Chest x-ray shows a dense, right lower lobe consolidation. EKG is unremarkable. The patient is intubated, and broad-spectrum antibiotics and IV fluids are administered. After 3 hours, BP remains 80/52 mm Hg. Which of the following agents is the next BEST STEP in therapy?

  1. A.NorepinephrineCorrect
  2. B.Epinephrine
  3. C.Dobutamine
  4. D.Dopamine

Explanation

Adding norepinephrine to this patient's regimen is the next best step in therapy. This patent has developed AKI in the setting of septic shock. Management of septic shock focuses on treating the underlying infection, but hemodynamic support with volume resuscitation and vasoactive agents plays an important role in maintaining organ perfusion. Numerous randomized, controlled trials (RCTs) have been conducted to compare mortality and morbidity with different vasoactive agents in critically ill patients with septic shock. Norepinephrine has emerged as the vasopressor of choice for most patients. A meta-analysis of 43 trials that assessed 17 vasopressors and inotropes showed that a combination of norepinephrine and dobutamine was associated with the lowest mortality, whereas dopamine was associated with the highest risk of arrythmia. Norepinephrine is recommended as the first-line vasoactive agent for septic shock because of its ease of use, rapid onset of action, and low cost. The target mean arterial pressure (MAP) is 60–65 mm Hg for most outcomes, although a target of 80–85 mm Hg decreased the risk of progressing to AKI stage 3 and requiring renal replacement therapy. Epinephrine stimulates β1-, β2-, and α1-adrenergic receptors, thereby increasing cardiac output and MAP. Compared with norepinephrine, epinephrine causes more adverse events, including mesenteric ischemia, tachyarrythmias, and lactic acidosis. Low-dose dopamine, often defined as <5 μg/kg per minute, was previously thought to increase renal perfusion by activating vasodilatory dopamine receptors in the renal circulation. However, human studies have not shown any renal benefits for this strategy in the setting of septic shock, and there are risks associated with this medication, including an increased risk of cardiac arrhythmias and greater mortality in patients with cardiogenic shock. Dobutamine is an inotrope that stimulates β1- and β2-adrenergic receptors. This agent increases cardiac output, which is usually high in the setting of septic shock, and acts as a vasodilator. Dobutamine alone would not be appropriate for this patient. Dobutamine in combination with norepinephrine has been effective in some trials. Vasopressin, which induces vasoconstriction via a non-adrenergic pathway, can be added to norepinephrine in refractory cases.

Why each option

A.
Correct. Norepinephrine is the first-line vasopressor for fluid-refractory septic shock, with fewer arrhythmias than dopamine and a MAP target of about 65.
B.
Epinephrine raises MAP but causes more tachyarrhythmias, lactic acidosis and mesenteric ischemia than norepinephrine and is reserved as a second-line agent.
C.
Dobutamine is an inotrope and vasodilator that would worsen hypotension alone; it is added to norepinephrine only for persistent hypoperfusion with low cardiac output.
D.
Dopamine carries a higher arrhythmia risk than norepinephrine, and low-dose renal dopamine has shown no kidney benefit in septic shock.

Reference: Evans L, Crit Care Med 2021 (Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2021); De Backer D, N Engl J Med 2010 (SOAP II: dopamine versus norepinephrine in shock); Asfar P, N Engl J Med 2014 (SEPSISPAM)

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