State of Shock: Contemporary Vasopressor and Inotrope Use in Cardiogenic Shock

Abstract

Cardiogenic shock is characterized by tissue hypoxia caused by circulatory failure arising from inadequate cardiac output. In addition to treating the pathologic process causing impaired cardiac function, prompt hemodynamic support is essential to reduce the risk of developing multiorgan dysfunction and to preserve cellular metabolism. Pharmacologic therapy with the use of vasopressors and inotropes is a key component of this treatment strategy, improving perfusion by increasing cardiac output, altering systemic vascular resistance, or both, while allowing time and hemodynamic stability to treat the underlying disease process implicated in the development of cardiogenic shock. Despite the use of mechanical circulatory support recently garnering significant interest, pharmacologic hemodynamic support remains a cornerstone of cardiogenic shock management, with over 90% of patients receiving at least 1 vasoactive agent. This review aims to describe the pharmacology and hemodynamic effects of current pharmacotherapies and provide a practical approach to their use, while highlighting important future research directions.

Keywords: cardiogenic; inotrope; mechanical circulatory support; shock; vasopressor.

Figure 1. Graphical representation of the intracellular signaling cascade following activation of the G‐protein coupled β₁‐adrenergic receptor in cardiac tissue.

Mediated through the stimulatory (Gs) component of the β₁‐adrenergic receptor, activation of the adenyl cyclase pathway occurs with a resulting increase in cAMP (cyclic adenosine monophosphate) and subsequent increased intracellular calcium cycling. The altered calcium handling results in a positive chronotropic response, increased myocardial contractility, and lusitropy. PLB indicates phospholamban; RyR, ryanodine receptor; SERCA, sarco/endoplasmic reticulum Ca²⁺ ATPase; and SR, sarcoplasmic reticulum.

Figure 2. Intracellular signaling within vascular smooth muscle following the activation of α₁‐adrenergic, vasopressin‐1, β₂‐adrenergic, and ATP‐sensitive potassium channel receptors.

Stimulation of the α₁‐adrenergic or vasopressin‐1 receptors causes activation of the Gq (G‐protein) subunit, resulting in downstream stimulation of the phospholipase C signaling pathway. Phospholipase C in turn activates inositol 1, 4, 5‐triphosphate (IP3) leading to Ca²⁺ release from the sarcoplasmic reticulum (SR), resulting in vasoconstriction. Conversely, β₂‐receptor stimulation activates the inhibitory G‐protein (Gi) subunit causing vasodilatation through increased cAMP (cyclic adenosine monophosphase) activation and resulting phospholamban‐mediated Ca²⁺ uptake into the SR. Similarly, activation of the ATP‐sensitive potassium channel causes potassium influx that hyperpolarizes voltage‐dependent Ca²⁺ channels, reducing intracellular Ca²⁺ and vasomotor tone. AMP indicates adenosine monophosphate; DAG, diacylglycerol; PDE3, phosphodiesterase 3; and PLB, phospholamban.

Figure 3. Summary of key cardiac societal guideline recommendations for the use of vasoactive medications in cardiogenic shock.

ESC HF, 2021 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure; ACC/AHA HF, 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure; ESC STEMI, 2017 ESC Guidelines for the Management of Acute Myocardial Infarction in Patients Presenting with ST‐Segment–Elevation; AHA CS, Contemporary Management of Cardiogenic Shock: A Scientific Statement from the American Heart Association; AHA AMI‐CS, Invasive Management of Acute Myocardial Infarction Complicated by Cardiogenic Shock: A Scientific Statement from the American Heart Association. ACC indicates American College of Cardiology; AHA, American Heart Association; AMI, acute myocardial infarction; CS, cardiogenic shock; ESC, European Society of Cardiology; HF, heart failure; HFSA, Heart Failure Society of America; and STEMI, ST‐segment–elevation myocardial infarction.

Figure 4. A stepwise approach to the use of vasoactive medications for the management of cardiogenic shock.

MAP indicates mean arterial pressure; and MCS, mechanical circulatory support.