How does vasopressor use cause plasma depletion?

From the Guidelines

Vasopressors cause plasma depletion primarily through their effects on blood vessels and fluid distribution in the body, leading to increased vascular permeability and fluid leakage into the interstitial space. When vasopressors like norepinephrine, epinephrine, vasopressin, or phenylephrine are administered, they cause intense vasoconstriction by binding to alpha-adrenergic receptors on vascular smooth muscle 1. This vasoconstriction increases hydrostatic pressure within the capillaries, which forces fluid out of the intravascular space and into the interstitial space through a process called capillary leak. Additionally, vasopressors can damage the glycocalyx, a protective layer lining blood vessels that normally prevents fluid leakage. The increased vascular permeability allows plasma proteins like albumin to escape into the interstitial space, further drawing fluid out of the circulation through oncotic pressure changes. Some vasopressors also have direct effects on the kidneys, altering renal blood flow and potentially reducing plasma volume through changes in fluid excretion.

Key mechanisms of plasma depletion include:

• Increased vascular permeability due to vasoconstriction and glycocalyx damage
• Capillary leak and fluid shift into the interstitial space
• Oncotic pressure changes due to plasma protein leakage
• Direct effects on renal blood flow and fluid excretion

According to the most recent and highest quality study, the use of vasopressin, in particular, can lead to plasma depletion, but highly selective V1a agonists like selepressin may have a more favorable effect on minimizing vascular leak and preserving plasma protein concentration 1. This highlights the importance of careful selection and dosing of vasopressors to minimize adverse effects on plasma volume and fluid balance. The Surviving Sepsis Campaign guidelines recommend norepinephrine as the first-choice vasopressor, with vasopressin or epinephrine added as needed to achieve target blood pressure 1.

In clinical practice, it is essential to monitor patients receiving vasopressors closely for signs of plasma depletion and adjust fluid resuscitation and vasopressor therapy accordingly. This may involve frequent assessment of hemodynamic parameters, fluid balance, and laboratory markers of fluid status and organ perfusion. By prioritizing the prevention and management of plasma depletion, clinicians can optimize the use of vasopressors and improve patient outcomes in terms of morbidity, mortality, and quality of life.

From the FDA Drug Label

Prolonged administration of any potent vasopressor may result in plasma volume depletion which should be continuously corrected by appropriate fluid and electrolyte replacement therapy Vasopressor use can cause plasma depletion due to its potent vasoconstrictor action, leading to decreased blood flow and tissue perfusion. This can result in tissue hypoxia and lactic acidosis, and if not corrected, may cause hypotension when the vasopressor is discontinued, or lead to severe peripheral and visceral vasoconstriction. Key points to consider:

• Prolonged administration of vasopressors increases the risk of plasma depletion
• Appropriate fluid and electrolyte replacement therapy is necessary to correct plasma volume depletion 2

From the Research

Vasopressor Use and Plasma Depletion

• The relationship between vasopressor use and plasma depletion is not directly addressed in the provided studies 3, 4, 5, 6, 7.
• However, vasopressors are known to cause vasoconstriction, which can lead to decreased blood flow to certain areas of the body 4, 5.
• This decreased blood flow can potentially lead to organ ischemia and other complications, but the direct link to plasma depletion is not explicitly stated in the studies.
• Vasopressors are often used to treat shock and hypotension, and their effects on blood flow and organ perfusion are critical considerations in their use 3, 5.
• The studies suggest that the choice of vasopressor and its dose can have significant effects on patient outcomes, and that careful consideration of the patient's individual response is necessary 3, 5.
• Some vasopressors, such as norepinephrine, have been shown to have beneficial effects on renal perfusion and urine output in certain conditions, such as sepsis 6.
• However, the mechanisms underlying the effects of vasopressors on plasma volume and depletion are not fully understood and require further research.

Mechanisms of Vasopressor Action

• Vasopressors act on various receptors, including adrenergic and vasopressin receptors, to induce vasoconstriction and other effects 5, 7.
• The specific mechanisms of action of different vasopressors can vary, and their effects on the body can be complex and multifaceted 4, 7.
• The use of vasopressors in critically ill patients requires careful consideration of their potential benefits and risks, as well as the individual patient's response to treatment 3, 5.