The Eight Unanswered and Answered Questions about the Use of Vasopressors in Septic Shock

Septic shock is mainly characterized—in addition to hypovolemia—by vasoplegia as a consequence of a release of inflammatory mediators. Systemic vasodilatation due to depressed vascular tone results in arterial hypotension, which induces or worsens organ hypoperfusion. Accordingly, vasopressor therapy is mandatory to correct hypotension and to reverse organ perfusion due to hypotension. Currently, two vasopressors are recommended to be used, norepinephrine and vasopressin. Norepinephrine, an α(1)-agonist agent, is the first-line vasopressor. Vasopressin is suggested to be added to norepinephrine in cases of inadequate mean arterial pressure instead of escalating the doses of norepinephrine. However, some questions about the bedside use of these vasopressors remain. Some of these questions have been well answered, some of them not clearly addressed, and some others not yet answered. Regarding norepinephrine, we firstly reviewed the arguments in favor of the choice of norepinephrine as a first-line vasopressor. Secondly, we detailed the arguments found in the recent literature in favor of an early introduction of norepinephrine. Thirdly, we reviewed the literature referring to the issue of titrating the doses of norepinephrine using an individualized resuscitation target, and finally, we addressed the issue of escalation of doses in case of refractory shock, a remaining unanswered question. For vasopressin, we reviewed the rationale for adding vasopressin to norepinephrine. Then, we discussed the optimal time for vasopressin administration. Subsequently, we addressed the issue of the optimal vasopressin dose, and finally we discussed the best strategy to wean these two vasopressors when combined.