What is the cause of hypotension in a patient with sepsis?

From the Guidelines

Hypotension in a patient with sepsis is primarily caused by the excessive release of pro-inflammatory cytokines, particularly interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-α), which trigger widespread vasodilation and increase vascular permeability, leading to decreased systemic vascular resistance and fluid leakage into tissues. The pathophysiology of sepsis-induced hypotension is complex and involves multiple mechanisms. Key factors include:

• Excessive release of pro-inflammatory cytokines, such as IL-1 and TNF-α, which stimulate nitric oxide production and lead to vasodilation 1
• Decreased systemic vascular resistance due to vasodilation, resulting in inadequate tissue perfusion despite potentially normal or elevated cardiac output 1
• Increased vascular permeability, causing fluid leakage into tissues and further contributing to hypotension 1
• Distributive shock, characterized by inadequate tissue perfusion despite normal or high cardiac output, is a common feature of early septic shock 1

In terms of management, the Surviving Sepsis Campaign guidelines recommend initial fluid resuscitation with 30 mL/kg of crystalloid within the first 3 hours, and the use of vasopressors, such as norepinephrine, to restore organ perfusion if fluid resuscitation fails to optimize blood flow 1. The goal of therapy is to restore a mean arterial pressure (MAP) of 65 mmHg, which is considered a good initial goal during hemodynamic support of patients with sepsis 1.

It is essential to note that the management of sepsis-induced hypotension requires a comprehensive approach, including early recognition, prompt administration of intravenous fluids, and the use of vasopressors as needed, with careful monitoring of clinical endpoints, such as mean arterial pressure, skin color, and capillary refill, mental status, or urinary output 1.

From the FDA Drug Label

For blood pressure control in certain acute hypotensive states (e.g., pheochromocytomectomy, sympathectomy, poliomyelitis, spinal anesthesia, myocardial infarction, septicemia, blood transfusion, and drug reactions)

The cause of hypotension in a patient with sepsis is septicemia 2.

From the Research

Causes of Hypotension in Sepsis

The cause of hypotension in a patient with sepsis is multifactorial. Some of the key factors include:

• Vasodilation, which can lead to a decrease in blood pressure 3, 4
• Cardiac dysfunction, including reduced cardiac output and depressed cardiomyocyte contractility 4, 5
• Release of pro-inflammatory mediators, such as tumour necrosis factor alpha, interleukin-beta, and nitric oxide, which can contribute to hypotension and shock 4, 6
• Changes in circulating volume, down-regulation of beta-adrenergic receptors, and impaired electromechanical coupling 4
• Mitochondrial derangement, which can lead to tissue injury and multi-organ failure 4

Role of Nitric Oxide in Sepsis

Nitric oxide (NO) plays a significant role in the development of hypotension in sepsis. The inducible form of NO synthase (iNOS) can produce excessive amounts of NO, leading to vasodilation and hypotension 6. However, the use of NO synthesis inhibitors has shown mixed results in improving hemodynamic variables and survival in septic patients 6.

Organ Dysfunction in Sepsis

Sepsis can lead to dysfunction in multiple organ systems, including:

• Cardiovascular dysfunction, characterized by vasodilation, reduced cardiac output, and hypotension/shock 3, 5
• Respiratory dysfunction, which may require mechanical ventilation 5
• Renal dysfunction, which is a frequent manifestation of sepsis 5
• Hematologic dysfunction, which can produce low platelets and abnormal leukocyte counts 5
• Hepatic dysfunction, which can manifest as elevated bilirubin and reduced production of essential proteins 5
• Neurologic dysfunction, which can result from local endothelial injury and systemic inflammation 5