What is vasoplegia?

What is Vasoplegia?

Vasoplegia is a pathological syndrome characterized by persistent low systemic vascular resistance (SVR) despite normal or elevated cardiac output, resulting in profound vasodilation and hypotension that is refractory to fluid resuscitation. 1, 2

Core Pathophysiology

Vasoplegia represents a state of pathological vasodilation where blood vessels lose their ability to maintain normal tone, leading to:

• Decreased systemic vascular resistance as the dominant hemodynamic feature 3, 2
• Normal or high cardiac index despite profound hypotension 1, 4
• Relative hypovolemia from abnormal distribution of blood flow in the microcirculation 3
• Hypotension refractory to both fluid resuscitation and standard-dose vasopressors 4

The condition is fundamentally different from other shock states because cardiac output is preserved or even elevated, yet perfusion pressure remains inadequate due to loss of vascular tone 2.

Clinical Contexts Where Vasoplegia Occurs

Vasoplegia manifests across multiple clinical scenarios:

Distributive Shock States

• Septic shock - the most common presentation 5, 3
• Pancreatitis 5, 3
• Burns and trauma 2, 3
• Anaphylactic shock 6

Post-Cardiac Surgery

• Post-cardiopulmonary bypass vasoplegia is increasingly recognized 1, 4
• Occurs in patients undergoing complex cardiac procedures 4
• Associated with surgical trauma and systemic inflammation 4

Other Critical Illness States

• Cardiogenic shock with concurrent vasodilation 6
• Hemorrhagic shock in advanced stages 6

Underlying Mechanisms

Multiple intrinsic and extrinsic pathways drive vasoplegic syndrome 2:

Intrinsic Vascular Mechanisms

• Excessive nitric oxide production causing smooth muscle relaxation 2, 6
• Prostanoid dysregulation 2
• Endothelin-1 pathway alterations 2
• Hydrogen sulfide overproduction 2
• Reactive oxygen species generation 2

Extrinsic Regulatory Dysfunction

• G protein-coupled receptor desensitization, particularly adrenoceptors and vasopressin receptors 6
• Critical illness-related corticosteroid insufficiency 6
• Catecholamine responsiveness impairment 2
• Vasopressin pathway dysfunction 2

Clinical Recognition

Vasoplegia should be suspected when hypotension persists despite adequate fluid resuscitation in the presence of warm extremities and normal or elevated cardiac output. 5, 3

Key diagnostic features include:

• Mean arterial pressure <65 mmHg despite vasopressor support 3
• Cardiac index normal (>2.5 L/min/m²) or elevated 1, 7
• Low systemic vascular resistance 1, 4
• Requirement for high-dose vasopressors to maintain perfusion pressure 4
• Elevated serum lactate indicating tissue hypoperfusion despite adequate cardiac output 3

Management Principles

First-Line Therapy

Norepinephrine is the recommended first-line vasopressor after adequate fluid resuscitation in distributive shock with vasoplegia 5, 3, 6

Second-Line and Adjunctive Agents

When hypotension persists on norepinephrine:

• Vasopressin (up to 0.03 units/min) should be added to reduce norepinephrine requirements 5, 3
• Vasopressin is likely the most effective first-line agent specifically in post-cardiac surgery vasoplegia 4

Rescue Therapies for Refractory Vasoplegia

• Methylene blue shows promise in restoring vascular tone 1, 4
• Hydroxocobalamin may be effective as alternative therapy 1, 4
• Angiotensin II substantially increases SVR without altering cardiac output 5, 1, 6
• Corticosteroids (hydrocortisone) for critical illness-related insufficiency 1

Management of Concurrent Myocardial Depression

Myocardial depression is common in septic shock, occurring in up to one-third of patients 3:

• Dobutamine can be added to norepinephrine when myocardial dysfunction is present 5, 3
• Epinephrine as a single agent is an alternative for combined inotropic and vasopressor support 5

Important Clinical Pitfalls

• Phenylephrine should be reserved for salvage therapy only in distributive shock with vasoplegia 5
• Dopamine is only recommended in hypotensive patients with bradycardia or low risk for tachycardia 5
• Routine use of inotropes without documented myocardial dysfunction has been associated with increased mortality 5
• Failure to exclude hypovolemia in patients requiring vasopressors through repeated volume assessments 5
• Epinephrine use alone (without norepinephrine) is associated with higher mortality in some contexts 5

Special Considerations

Target Mean Arterial Pressure

Target MAP of 65 mmHg is the standard goal, but should be individualized based on baseline blood pressure and comorbidities 3. In cardiogenic shock with vasoplegia, individualized MAP goals balance hypoperfusion risk against negative impacts on cardiac output 5.

Multimodal Approach

The therapeutic approach is evolving from standardized single-agent therapy to personalized multimodal treatment with combinations of vasopressors to limit adrenoceptor desensitization and sympathetic overactivation 6.