Understanding Pharmacology: What Medications Increase Preload?

October 11, 2025 •

4 min read

Cardiac preload, the stretch on ventricular muscle fibers at the end of diastole, is a primary determinant of stroke volume [1.8.1]. But in clinical settings like shock, what medications increase preload to improve cardiac output and tissue perfusion? [1.7.1]

Quick Summary

An overview of pharmacological agents that increase cardiac preload. This summary covers how intravenous fluids, blood products, and specific vasopressors with venoconstrictive properties enhance venous return to the heart.

Key Points

Definition: Preload is the stretch on cardiac muscle cells at the end of diastole, determined by ventricular filling and venous return [1.8.1].
Primary Methods: Preload is increased pharmacologically either by expanding intravascular volume with fluids or by enhancing venous return via venoconstriction [1.7.5, 1.5.6].
Fluid Resuscitation: Intravenous crystalloids (e.g., Normal Saline) and colloids (e.g., Albumin) directly increase the circulating volume, thereby raising preload [1.7.1, 1.4.4].
Vasopressor Effects: Vasopressors like norepinephrine and phenylephrine cause venoconstriction, which shifts blood from the periphery to the central circulation, increasing preload [1.6.3, 1.5.2].
Norepinephrine: As a mixed alpha- and beta-agonist, norepinephrine increases preload through potent venoconstriction and is a first-line agent in septic shock [1.3.2, 1.6.5].
Phenylephrine: This pure alpha-agonist increases preload by constricting capacitance veins, an effect particularly useful in states of vasodilation [1.5.4, 1.5.6].
Clinical Application: Increasing preload is crucial in treating hypovolemic and distributive shock, often starting with fluids and adding vasopressors if needed [1.3.2, 1.9.3].

Understanding Cardiac Preload

Cardiac preload is a fundamental concept in cardiovascular physiology, representing the degree of stretch experienced by the heart's ventricular muscle cells at the end of their filling phase (diastole) [1.8.1]. Often equated with left ventricular end-diastolic pressure (LVEDP), it is directly influenced by the volume of blood returning to the heart, a factor known as venous return [1.8.1, 1.8.4]. The relationship between preload and the force of the subsequent contraction is described by the Frank-Starling mechanism. This principle states that as preload increases (to a point), the stroke volume—the amount of blood pumped with each beat—also increases [1.8.5]. In clinical practice, manipulating preload is a key strategy for managing various hemodynamic states, from hypovolemic shock to heart failure [1.9.3]. Understanding which interventions increase this crucial parameter is vital for healthcare professionals.

Primary Methods for Increasing Preload

There are two main pharmacological strategies to increase cardiac preload: increasing the total circulating volume and increasing venous tone.

Increasing Circulating Volume: This is the most direct method and is achieved by administering intravenous (IV) fluids or blood products. This intervention aims to increase the total volume within the vascular system, which in turn enhances venous return to the heart [1.7.5].
Increasing Venous Tone (Venoconstriction): Certain medications, primarily in the vasopressor class, cause the veins to constrict. Since a significant portion of the body's blood volume resides in the venous system, this venoconstriction effectively reduces the capacity of these venous 'reservoirs' [1.5.6]. This action mobilizes blood from the peripheral circulation toward the central circulation, increasing venous return and thereby boosting preload without adding external volume [1.5.2, 1.6.3].

Increasing Circulating Volume: Fluids and Blood Products

Fluid resuscitation is a cornerstone of treatment for many forms of shock, with the primary goal of increasing stroke volume and cardiac output by augmenting preload [1.7.1].

Crystalloids Crystalloid solutions, such as Normal Saline (0.9% NaCl) and Lactated Ringer's, are the most commonly used fluids for volume resuscitation. They are salt and water solutions that increase intravascular volume. However, a significant portion of the administered crystalloid fluid quickly redistributes from the intravascular space into the interstitium, meaning only about 20% remains in circulation to directly affect preload long-term [1.4.1].

Colloids Colloids, such as albumin or synthetic starches, contain larger molecules that do not easily pass out of the vascular space [1.4.4]. This property allows them to remain in the circulation longer and expand the intravascular volume more efficiently than crystalloids. Some studies have shown colloids to be superior to crystalloids in preventing hypotension by maintaining preload, though they are more expensive and carry risks like allergic reactions [1.4.2, 1.4.4].

Modulating Venous Tone: Vasopressors with Venoconstrictive Effects

While often associated with increasing blood pressure by constricting arteries (increasing afterload), many vasopressors also have significant effects on the venous system, which can increase preload [1.3.1].

Norepinephrine Norepinephrine is a first-line vasopressor in conditions like septic shock [1.6.5]. It acts on both alpha-1 and beta-1 adrenergic receptors [1.3.2]. Its potent alpha-1 agonist activity causes strong arterial and venous vasoconstriction. This venoconstriction increases venous return, which in turn increases cardiac preload and cardiac output, particularly in patients who are 'preload-dependent' [1.6.1, 1.6.3].

Phenylephrine Phenylephrine is a pure alpha-1 adrenergic agonist, causing potent vasoconstriction in both arteries and veins [1.3.5]. By constricting venous capacitance vessels, it effectively squeezes blood from the peripheral venous system back toward the heart, an effect sometimes described as an "auto-transfusion" [1.5.2, 1.5.6]. In patients who are preload-dependent (i.e., their heart will respond to more volume with increased output), phenylephrine has been shown to increase cardiac preload and, consequently, cardiac output [1.5.4, 1.5.5].

Vasopressin Vasopressin acts on V1 receptors in vascular smooth muscle to cause vasoconstriction [1.3.4]. It also has a venoconstrictive effect that can contribute to an increase in preload [1.3.1]. It is often used as a secondary agent in vasodilatory shock, like sepsis [1.3.1].

Comparison of Medications that Increase Preload


Agent	Mechanism of Action	Primary Clinical Use	Key Considerations
IV Fluids (Crystalloids)	Increases total circulating blood volume [1.7.5].	Hypovolemia, initial resuscitation in shock [1.7.1].	Large volumes are needed as fluid redistributes to the interstitium [1.4.1]. Can lead to fluid overload.
IV Fluids (Colloids)	Increases plasma oncotic pressure, retaining fluid in the intravascular space more effectively than crystalloids [1.4.4].	Volume expansion, particularly studied in contexts like spinal anesthesia-induced hypotension [1.4.2].	More expensive than crystalloids; risk of anaphylactoid reactions and potential effects on renal function [1.4.1, 1.4.4].
Norepinephrine	Alpha-1 and beta-1 agonist. Causes potent venoconstriction, increasing venous return [1.3.2, 1.6.3].	First-line agent for most types of shock, especially septic shock [1.6.5].	Can increase heart rate and afterload, potentially increasing myocardial oxygen demand [1.3.5].
Phenylephrine	Pure alpha-1 agonist. Causes venoconstriction, recruiting unstressed volume into stressed volume [1.3.5, 1.5.6].	Used to treat hypotension, especially when caused by vasodilation (e.g., anesthesia-induced) [1.5.4].	May cause a reflex bradycardia (slowing of heart rate) due to the increase in blood pressure [1.3.1]. Effect on cardiac output is highly dependent on the patient's preload status [1.5.1].

Clinical Scenarios and Conclusion

The decision to increase preload depends on a careful assessment of the patient's hemodynamic status. In states of hypovolemic shock (e.g., from hemorrhage or dehydration) or distributive shock (e.g., from sepsis or anesthesia), increasing preload is a primary goal [1.3.2, 1.9.3]. Initially, this is almost always done with IV fluids [1.7.1]. If hypotension persists despite adequate fluid resuscitation, vasopressors like norepinephrine are added. These agents not only increase arterial pressure but also further augment preload through venoconstriction [1.6.1]. In certain situations, like anesthesia-induced vasodilation, a pure alpha-agonist like phenylephrine might be used to specifically target the loss of vascular tone and increase preload [1.5.4].

In conclusion, medications and interventions that increase preload work by either expanding the intravascular volume or by constricting the venous system to enhance venous return. The primary tools are intravenous fluids (crystalloids and colloids) and vasopressor medications such as norepinephrine and phenylephrine [1.3.1, 1.7.5]. The appropriate choice depends on the underlying clinical condition, the patient's volume status, and the desired hemodynamic outcome.

An authoritative outbound link on Vasopressors can be found at the EMCrit Project.

Frequently Asked Questions

The most direct way to increase cardiac preload is by administering intravenous (IV) fluids, such as crystalloids or colloids, which directly increase the total circulating blood volume [1.7.5].

Vasopressors like norepinephrine cause venoconstriction (constriction of the veins). This reduces the capacity of the venous system and pushes blood from the peripheral circulation towards the heart, increasing venous return and thereby increasing preload [1.6.3].

No. The effect of phenylephrine on cardiac output depends on the patient's volume status. In a preload-dependent patient (one who will benefit from more volume), phenylephrine can increase cardiac output by increasing preload. In a preload-independent patient, it may decrease cardiac output by increasing afterload [1.5.1].

Crystalloids (like Normal Saline) are salt solutions that distribute throughout the body's fluid compartments, with only about 20% remaining in the blood vessels [1.4.1]. Colloids (like albumin) have larger molecules that stay within the blood vessels longer, making them more efficient at expanding intravascular volume for a given amount infused [1.4.4].

Yes. In conditions like cardiogenic shock or fluid overload, increasing preload can worsen the condition by further straining the heart and leading to complications like pulmonary edema. Vasopressors also have side effects, including potentially reducing blood flow to vital organs if used excessively.

Not exactly. While increasing preload often leads to an increase in stroke volume and cardiac output, which in turn can raise blood pressure, they are distinct concepts. Blood pressure is the product of cardiac output and systemic vascular resistance (SVR). Vasopressors, for example, increase blood pressure by increasing SVR, but their effect on preload is a separate, additional mechanism [1.5.4].

Increasing preload is a primary therapeutic goal in both hypovolemic shock (caused by volume loss) and distributive shock (caused by widespread vasodilation, as seen in sepsis) [1.3.2].