Vasopressor Strategies for Septic Shock in Surgical and Trauma Critical Care: A Systematic Review and Network Meta-analysis

adding epinephrine as a second agent, the order of vasopressor discontinuation, and sedation choices that modulate vasopressor needs. [10][11]1][12] Phenylephrine has also been contrasted with NE for initial support, 13 and translational work suggests NE can alter host IntroductIonSepsis-3 defines septic shock by vasopressor-dependent hypotension and elevated lactate despite adequate resuscitation, a state that portends the highest mortality within the sepsis spectrum. 1Contemporary guidance recommends NE as the preferred first-line vasopressor to restore perfusion pressure in adults. 2 Even so, excessive catecholamine exposure can drive tachyarrhythmias, disrupt the microcirculation, and trigger ischemia in vulnerable tissues-problems with amplified impact in surgical and trauma cohorts where anastomoses, flaps, stomas, and limb perfusion are central to outcomes. 3,4onadrenergic vasopressors offer a catecholamine-sparing strategy.AVP enhances vascular tone via V1 receptors and has been tested in large randomized trials, including vasopressin and septic shock trial (VASST) and the early-use, titrated VANISH study that also assessed kidney outcomes. 5,6TLP, a longer-acting vasopressin (AVP) analog with potent V1 agonism, has been compared with NE in a multicenter, double-blind infusion trial building on earlier hyperdynamic-shock experience. 7Other vasoactive options lie outside our core network but inform practice: selepressin, a selective V1A agonist, has been evaluated in septic shock 8 ; angiotensin II is used for refractory vasodilatory states. 9Strategy questions relevant to surgical intensivists include thresholds for 1,2,