Reversal of Vasodilatory Shock: Current Perspectives on Conventional, Rescue, and Emerging Vasoactive Agents for the Treatment of Shock

Jonathan H. Chow, MD; Ezeldeen Abuelkasem, MBBCh, MSc; Susan Sankova, MD; Reney A. Henderson, MD; Michael A. Mazzeffi, MD, MPH; Kenichi A. Tanaka, MD, MSc


Anesth Analg. 2019;130(1):15-30. 

In This Article

Abstract and Introduction


Understanding the different mechanisms of vasoconstrictors is crucial to their optimal application to clinically diverse shock states. We present a comprehensive review of conventional, rescue, and novel vasoactive agents including their pharmacology and evidence supporting their use in vasodilatory shock. The role of each drug in relation to the Surviving Sepsis Guidelines is discussed to provide a context of how each one fits into the algorithm for treating vasodilatory shock. Rescue agents can be utilized when conventional medications fail, although there are varying levels of evidence on their clinical effectiveness. In addition, novel agents for the treatment of vasodilatory shock have recently emerged such as ascorbic acid and angiotensin II. Ascorbic acid has been used with some success in vasoplegia and is currently undergoing a more rigorous evaluation of its utility. Angiotensin II (Ang-2) is the newest available vasopressor for the treatment of vasodilatory shock. In addition to its catecholamine-sparing properties, it has been shown to hold promising mortality benefits in certain subsets of critically ill patients.


There are several classes of shock that anesthesiologists and intensivists frequently encounter: distributive, cardiogenic, obstructive, and hypovolemic. Each class of shock has a unique etiology and thus a different treatment. An important distinction is that shock is a syndrome graded into 4 classes, while hypotension is a clinical sign of class III or IV shock.[1] Vasodilatory shock is the most common form and represents 68% of all shock in the intensive care unit (ICU).[2] Sepsis accounts for approximately 91% of vasodilatory shock cases.[2] Other forms of vasodilatory shock come in the form of burns, pancreatitis, anaphylaxis, and spinal cord injuries. In the operating room and labor and delivery suite, vasodilation is also frequently encountered after induction of general anesthesia and administration of neuraxial local anesthetics, and, thus, knowledge regarding this class of shock is highly relevant not just to intensivists, but also to anesthesiologists.

Because of its prevalence, the treatment of vasodilatory shock has largely relied on the Surviving Sepsis Guidelines, which are updated biannually. After procurement of blood cultures, establishment of source control, administration of broad-spectrum antibiotics, and rapid administration of crystalloids, the treatment of vasodilatory shock relies on pharmacological interventions to maintain adequate mean arterial pressure (MAP) >65 mm Hg.[3]

Treating hypotension is critical in preventing adverse outcomes. Walsh et al[4] demonstrated that, in patients undergoing noncardiac surgery, hypotension for a period of only 60 s resulted in increased odds of postoperative acute kidney injury (AKI; odds ratio [OR] = 1.2; 95% confidence interval [CI], 1.06–1.31). Similarly, hypotension for 6–10 minutes resulted in an increase in postoperative myocardial injury (OR = 1.47), and persistent hypotension for >20 minutes resulted in an increase in postoperative cardiac complications by almost 2 times.[4] Thus, rapid control of hypotension is critical to decrease morbidity. Several pharmacological interventions are available to rapidly treat hypotension due to vasodilation, all of which have different mechanisms and distribution of target receptors.

Given the increasing number of vasoactive agents, an updated review of their pharmacological properties should help clinicians better implement a vasopressor strategy according to the underlying condition. We aim to provide a narrative review on vasopressor pharmacology and clinical evidence for the most commonly used vasoconstrictors in vasodilatory shock (Figure 1).

Figure 1.

Chemical structure of vasoconstrictors. Structures created with MarvinSketch (ChemAxon, Ltd, Cambridge, MA).