In septic shock, as well as other states of critical illness, patients tend to be vasopressin depleted [1]. The Surviving Sepsis Campaign 2021 Guidelines recommend using norepinephrine as the first-line agent over other vasopressors for adults with septic shock [2]. For such patients on norepinephrine with inadequate mean arterial pressure level, they suggest adding vasopressin instead of escalating the dose of norepinephrine [2]. A systematic review comparing vasopressin to norepinephrine as first-line vasopressors in septic shock revealed that patients in the vasopressin group had lower odds of renal replacement therapy [3]. That review also included the VANISH trial, which demonstrated similar findings; patients treated with vasopressin as opposed to norepinephrine had higher urine output, reduced serum creatinine, and a decreased need for dialysis following fluid resuscitation [3,4]. These benefits may be explained by vasopressin-induced vasoconstriction of renal efferent arterioles, which enhances the glomerular filtration rate [5]. Vasopressin had no effect on the blood pressure of healthy (not vasopressin depleted) individuals [1].

Vasopressin also shows benefits in cases of massive pulmonary embolism by raising systemic vascular resistance while simultaneously promoting pulmonary vasodilation and improving right ventricular afterload [5]. Increasing renal filtration and urine output reduces blood volume, which can be advantageous in pulmonary embolism where excess intravascular volume may be harmful and lead to worsening right ventricular failure [6].

This medication is also widely used for managing acute variceal bleeding. It is believed to induce splanchnic arteriolar vasoconstriction, which decreases portal inflow and pressure [7]. In cirrhotic patients with variceal bleeding, those treated with vasopressin had similar efficacy and mortality to those treated with octreotide [8].

Traditional teaching suggests that early administration of vasopressors in trauma may increase mortality due to elevated cardiac afterload, arrhythmias, and reduced tissue perfusion [5]. The later stages of hemorrhagic shock involve inhibition of the sympathetic response, resulting in lack of vasoconstriction, as in distributive shock due to catecholamine and/or vasopressin depletion [5]. Additionally, patients may be vasopressin depleted from continuous blood loss from the trauma itself [5]. A recent randomized controlled trial investigated whether vasopressin supplementation in trauma patients with hemorrhagic shock could reduce the need for blood transfusions [9]. Patients included in the study had received at least 6 units of packed red blood cells within 12 hours. The study found that, although continuous vasopressin infusion did not impact mortality, it was linked to a reduced need for blood product transfusion. The authors theorize that this may be due to increased vascular tone and promotion of platelet aggregation via V1 receptors, leading to enhanced hemostasis [5,9].

Despite its various uses, vasopressin should be avoided in specific scenarios. It induces splanchnic vasoconstriction, which can be detrimental for patients with mesenteric ischemia or those at risk of anastomotic breakdown [10]. It may also lead to cardiac and limb ischemia due to its vasoconstrictive properties [10]. These adverse effects were predominantly observed in patients receiving doses exceeding 0.04 units/min and when administered with other catecholamine vasopressors [10]. Vasopressin, unlike most other vasopressors, commonly is administered at a fixed dose of 0.03 units/min rather than being titrated to response [2]. In trials with vasopressin doses up to 0.06 units/min, negative side effects were observed [2]. Vasopressin should not be used peripherally as there is no antidote in the setting of extravasation [11]. The contraindications mentioned above are summarized in Table 2.

Although traditionally regarded as a secondary vasopressor, particularly in septic shock, vasopressin has a range of other indications. Using vasopressin as a primary vasopressor in certain conditions may improve patient survival and outcomes.