Alternatives to norepinephrine in septic shock: Which agents and when?

Vasopressors are the cornerstone of hemodynamic management in patients with septic shock. Norepinephrine is currently recommended as the first-line vasopressor in these patients. In addition to norepinephrine, there are many other potent vasopressors with specific properties and/or advantages that act on vessels through different pathways after activation of specific receptors; these could be of interest in patients with septic shock. Dopamine is no longer recommended in patients with septic shock because its use is associated with a higher rate of cardiac arrhythmias without any benefit in terms of mortality or organ dysfunction. Epinephrine is currently considered as a second-line vasopressor therapy, because of the higher rate of associated metabolic and cardiac adverse effects compared with norepinephrine; however, it may be considered in settings where norepinephrine is unavailable or in patients with refractory septic shock and myocardial dysfunction. Owing to its potential effects on mortality and renal function and its norepinephrine-sparing effect, vasopressin is recommended as second-line vasopressor therapy instead of norepinephrine dose escalation in patients with septic shock and persistent arterial hypotension. However, two synthetic analogs of vasopressin, namely, terlipressin and selepressin, have not yet been employed in the management of patients with septic shock, as their use is associated with a higher rate of digital ischemia. Finally, angiotensin Ⅱ also appears to be a promising vasopressor in patients with septic shock, especially in the most severe cases and/or in patients with acute kidney injury requiring renal replacement therapy. Nevertheless, due to limited evidence and concerns regarding safety (which remains unclear because of potential adverse effects related to its marked vasopressor activity), angiotensin Ⅱ is currently not recommended in patients with septic shock. Further studies are needed to better define the role of these vasopressors in the management of these patients.