Vasopressin Therapy in Septic Shock

Catecholamine-resistant arterial hypotension associated with severe impairment of tissue oxygenation plays a pivotal role in the development of multiple organ failure (MOF) and is associated with increased mortality in septic shock [1]. Therefore, alternative, non-adrenergic treatment strategies are urgently warranted. During recent years, research has increasingly focused on the use of vasopressinergic agents, such as arginine vasopressin (AVP) and terlipressin. Contrary to adrenergic receptors, the sensitivity of vasopressin receptors increases in septic shock [2]. This phenomenon may be explained by autonomic insufficiency, baroreceptor dysfunction [3] and the relative deficiency of endogenous vasopressin that is linked to increased receptor expression and sensitivity [4]. Mechanisms of action further include stimulation of vasopressin 1a receptors (V1aR), inhibition of nitric oxide (NO) synthesis [5], inhibition of ATP-dependent potassium channels [6] and restoration of adrenergic receptor sensitivity [7]. As a consequence, low doses of vasopressin analogs have been shown to increase mean arterial pressure (MAP) in catecholamine-resistant septic shock in numerous experimental [8, 9] and clinical studies [10–13]. In addition, these studies demonstrated a significant reduction in catecholamine requirements and attenuated renal dysfunction in septic shock patients.