Volume expander
A volume expander is a type of intravenous fluid therapy administered to restore or maintain blood volume in the circulatory system, often in response to conditions such as hypovolemia, hemorrhage, or shock.[1] These solutions work by increasing intravascular volume through osmotic pressure or by directly replacing lost fluids, thereby supporting blood pressure and organ perfusion without relying on blood transfusions.[2] Volume expanders are broadly classified into two main categories: crystalloids and colloids. Crystalloids, such as normal saline (0.9% sodium chloride) or lactated Ringer's solution, are aqueous solutions of electrolytes and small molecules that distribute across body fluid compartments, providing rapid but short-lived volume expansion.[2] Colloids contain larger molecules that remain primarily in the intravascular space longer due to their oncotic properties. Examples include albumin and dextrans, which can provide sustained volume support, while synthetic colloids such as hydroxyethyl starches (e.g., hetastarch) and gelatins are generally avoided in critical care due to risks of kidney injury, bleeding, and increased mortality.[3][4] As of 2025, major clinical guidelines recommend balanced crystalloids as first-line for initial resuscitation due to their availability, lower cost, and favorable safety profile, with colloids like albumin reserved for specific cases such as septic shock unresponsive to crystalloids; hydroxyethyl starches are not recommended.[5][6] Volume expanders are employed in scenarios like surgical blood loss, trauma, sepsis, or dehydration to prevent circulatory collapse and improve tissue oxygenation.[1] Potential risks include fluid overload, electrolyte imbalances, and allergic reactions, necessitating careful monitoring during administration.[1]Overview
Definition
A volume expander is a type of intravenous fluid therapy administered to restore or maintain intravascular volume in patients experiencing hypovolemia, a condition characterized by reduced blood volume that can lead to circulatory instability.[1] These solutions are essential in clinical settings to support hemodynamic stability by rapidly increasing circulating blood volume, thereby improving tissue perfusion without directly addressing underlying causes of fluid loss.[7] Unlike blood transfusions, which replenish both fluid volume and oxygen-carrying capacity through the delivery of red blood cells and hemoglobin, volume expanders focus solely on volume replacement and do not contribute to oxygen transport in the bloodstream.[8] This distinction makes volume expanders suitable for initial resuscitation in scenarios where oxygen delivery is not immediately compromised, but they may require supplementation with blood products if significant anemia or hemorrhage persists.[9] Volume expanders are broadly classified into two categories: crystalloids, which are electrolyte-based solutions that mimic plasma composition and distribute across fluid compartments, and colloids, which contain larger molecules such as proteins or starches that exert oncotic pressure to retain fluid primarily within the vascular space.[6] This classification guides their selection based on the desired duration and distribution of volume expansion in therapeutic protocols.[1]Clinical indications
Volume expanders are primarily indicated for the management of hypovolemic shock, a condition characterized by significant reduction in intravascular volume leading to inadequate tissue perfusion. This includes scenarios such as acute hemorrhage from trauma or surgery, severe dehydration due to gastroenteritis or excessive fluid loss, and extensive burns causing capillary leakage and plasma extravasation.[10][11][12] In perioperative settings, volume expanders support fluid management to maintain hemodynamic stability during and after surgery, particularly in major abdominal or cardiac procedures where intraoperative blood loss or third-space fluid shifts occur.[13] For sepsis and septic shock, guidelines recommend initial resuscitation with volume expanders to restore intravascular volume and improve organ perfusion, with the Surviving Sepsis Campaign advocating at least 30 mL/kg of intravenous crystalloid within the first three hours for patients with sepsis-induced hypoperfusion.[5] Secondary indications encompass anaphylaxis, where profound vasodilation necessitates rapid volume replacement to counteract hypotension and support cardiac output.[14] Volume expanders also play a role in trauma resuscitation protocols for hemorrhagic shock, aiming to stabilize circulation prior to definitive hemostasis.[15] Additionally, they are used for ongoing volume maintenance in critically ill patients to prevent hypovolemia and sustain perfusion in intensive care settings.[16]Physiological basis
Fluid compartments and distribution
The human body maintains fluid balance across distinct compartments, with total body water comprising approximately 60% of body weight in adults. The intracellular fluid (ICF) accounts for about two-thirds of total body water, residing within cells and supporting cellular functions such as metabolism and ion transport. The extracellular fluid (ECF), making up the remaining one-third, is further subdivided into the intravascular compartment (plasma, approximately 25% of ECF) and the interstitial space (the remainder, including fluid surrounding cells). This distribution ensures that plasma, which circulates in blood vessels, facilitates nutrient delivery and waste removal, while interstitial fluid provides a medium for exchange between blood and tissues.[17] Fluid movement between the intravascular and interstitial compartments is primarily governed by Starling forces, which dictate the filtration and reabsorption of fluid across capillary walls. Capillary hydrostatic pressure pushes fluid out of the vessel into the interstitium, while plasma oncotic pressure, exerted by proteins like albumin, draws fluid back in. Interstitial hydrostatic and oncotic pressures oppose these forces, and capillary permeability influences the ease of fluid passage, with the reflection coefficient quantifying how impermeable the endothelium is to solutes. These forces maintain equilibrium under normal conditions, preventing excessive fluid shifts that could lead to edema or hypovolemia.[18] Volume expanders interact with these compartments based on their composition, affecting initial distribution kinetics. Crystalloids, being small-molecule solutions, rapidly distribute throughout the entire extracellular space, with only about one-third of the infused volume remaining in the plasma due to equilibration with the interstitial fluid.[19] In contrast, colloids, with larger molecules, primarily remain in the intravascular compartment initially, providing more sustained plasma volume expansion by enhancing oncotic pressure. This foundational distribution underpins their role in restoring circulatory volume, as detailed in subsequent physiological mechanisms.[20]Mechanism of action
Volume expanders function by rapidly increasing intravascular volume in states of hypovolemia, thereby enhancing venous return to the heart and preload according to the Frank-Starling mechanism, which in turn boosts cardiac output.[21] This augmented cardiac output supports mean arterial pressure restoration, typically targeting values above 65 mm Hg in critically ill patients, and improves overall tissue perfusion by ensuring adequate oxygen delivery to organs.[21] In the context of fluid compartments, these agents primarily target the intravascular space to counteract the loss of circulating volume while minimizing excessive shifts to the interstitial compartment.[22] Crystalloids achieve volume expansion through the provision of electrolyte solutions that closely mimic plasma composition, thereby maintaining ionic balance and preventing disruptions in cellular function.[22] However, due to their ability to freely diffuse across capillary membranes, only about 20-30% of infused crystalloid volume remains intravascularly after 30 minutes, with the rest distributing to the extracellular space, resulting in a short duration of effect.[23] In contrast, colloids exert their effects via elevated colloid osmotic pressure generated by large molecules such as proteins or starches, which retain fluid within the vascular compartment by opposing hydrostatic forces and preventing excessive fluid leakage into the interstitium.[24] This oncotic mechanism allows for more efficient and sustained plasma volume expansion, with durations extending up to 16-24 hours depending on the specific colloid, such as albumin solutions.[24]Types
Crystalloids
Crystalloid volume expanders are electrolyte solutions composed of small molecules, such as mineral salts and other water-soluble ions, that freely cross capillary membranes and distribute across extracellular fluid compartments.[22] These solutions are isotonic to human plasma and primarily function to expand intravascular volume while maintaining electrolyte balance, without causing significant shifts in intracellular fluid.[22] Unlike colloids, which contain larger molecules that remain predominantly intravascular, crystalloids rapidly equilibrate between intravascular and interstitial spaces.[25] Common examples of crystalloid solutions include normal saline, lactated Ringer's, and Plasma-Lyte, each formulated to mimic aspects of plasma composition for volume resuscitation. Normal saline (0.9% NaCl) contains 154 mEq/L of sodium and 154 mEq/L of chloride, making it a simple isotonic solution for fluid and sodium replacement.[22] Lactated Ringer's solution provides a more balanced electrolyte profile, with 130 mEq/L sodium, 109 mEq/L chloride, 28 mEq/L lactate (as a bicarbonate precursor), 4 mEq/L potassium, and 1.5–3 mEq/L calcium.[26] Plasma-Lyte, another balanced option, includes 140 mEq/L sodium, 98 mEq/L chloride, 27 mEq/L acetate, 23 mEq/L gluconate, 5 mEq/L potassium, and 3 mEq/L magnesium, using acetate and gluconate as buffers to closely approximate physiological pH.[27] Crystalloids offer key advantages as volume expanders, including their low cost, widespread availability, ease of storage and administration, and ability to provide immediate resuscitation without the risks associated with blood products.[25] However, their small molecular size leads to rapid extravascular distribution, with only about 20–25% of the infused volume remaining in the intravascular space after 30 minutes, potentially requiring larger volumes for sustained expansion.[28] Additionally, repeated use of normal saline can cause hyperchloremic metabolic acidosis due to its supraphysiological chloride content.[22] In clinical practice, crystalloids are often used for initial fluid boluses in hypovolemic shock, with a typical dose of 20 mL/kg administered over the first 30 minutes to rapidly restore perfusion, followed by reassessment.[22]| Solution | Sodium (mEq/L) | Chloride (mEq/L) | Other Key Electrolytes/Buffers (mEq/L) |
|---|---|---|---|
| Normal Saline | 154 | 154 | None |
| Lactated Ringer's | 130 | 109 | Lactate 28, Potassium 4, Calcium 1.5–3 |
| Plasma-Lyte | 140 | 98 | Acetate 27, Gluconate 23, Potassium 5, Magnesium 3 |
Colloids
Colloid volume expanders are solutions containing large molecules, such as proteins or starches, that exert oncotic pressure to retain fluid within the intravascular space, thereby providing more sustained volume expansion compared to crystalloids.[24] These colloids have high molecular weights, typically ranging from 30,000 to 670,000 Daltons or more, which limits their diffusion across capillary walls and promotes prolonged persistence in the bloodstream.[24] Common examples include human albumin solutions, derived from human plasma, available as 5% (iso-oncotic) or 25% (hyperoncotic) preparations, where the protein concentration mimics or exceeds normal plasma levels to restore oncotic pressure.[29] Hydroxyethyl starch (HES) solutions, such as hetastarch 6% in saline, consist of synthetic starch polymers modified with hydroxyethyl groups with a weight-average molecular weight of approximately 670,000 Daltons (range 550,000–800,000).[30] Gelatin-based colloids, like succinylated gelatin (e.g., Gelofusine 4%), are modified bovine collagen derivatives with an average molecular weight of 30,000 Daltons, suspended in an electrolyte solution containing sodium and chloride.[31] Synthetic dextrans, such as dextran 70 at 6% concentration with a molecular weight of 70,000 Daltons, were historically used but are now less common due to associated risks.[32] Albumin plays a natural role in plasma by contributing approximately 80% of the oncotic pressure that maintains intravascular fluid volume.[24] Colloids offer advantages such as longer duration of volume expansion, often lasting several hours, which can be beneficial in hypovolemia from surgery, trauma, or burns.[24] However, they carry disadvantages including higher costs—particularly for albumin—risk of allergic or anaphylactoid reactions across types, and potential renal toxicity with HES, which has been linked to acute kidney injury in critically ill patients. As of 2025, HES use is restricted or contraindicated in critically ill patients with sepsis or renal issues, though recent trials support safety in perioperative settings.[29][33][34]Administration and monitoring
Methods of administration
Volume expanders are primarily administered via intravenous infusion to ensure direct delivery into the vascular system. This can be achieved through peripheral intravenous lines, which are suitable for most crystalloid solutions in stable patients, or central venous catheters, which are preferred for hypertonic or viscous colloid solutions to minimize risks such as phlebitis or extravasation.[22][35] Administration methods include bolus injections for rapid volume expansion in acute settings like hypovolemic shock, where fluids are delivered quickly to restore hemodynamic stability, and continuous infusions for sustained volume support in perioperative or critical care scenarios. Bolus administration allows for faster intravascular expansion compared to slower infusions, though the choice depends on clinical context.[36][13] Essential equipment includes intravenous catheters for access and infusion pumps to regulate flow rates precisely, preventing overload or under-delivery. These pumps are particularly useful for controlled administration in non-emergent cases. Volume expanders like crystalloids are generally compatible with blood products when using normal saline as a carrier, but certain colloids require separate lines to avoid hemolysis or clotting.[37][35] In emergencies requiring rapid infusion, such as trauma resuscitation, pressure bags can be applied around the fluid bag to accelerate delivery by increasing pressure, often achieving rates up to 500 mL/min. Additionally, warming fluids to near body temperature using inline warmers is recommended during large-volume infusions to prevent hypothermia, especially in perioperative or hypothermic patients.[38][39]Dosage and monitoring
The administration of volume expanders follows goal-directed principles, where initial boluses are titrated based on hemodynamic response to optimize perfusion while minimizing risks of overload. For crystalloids, such as lactated Ringer's solution or normal saline, at least 30 mL/kg of ideal body weight is recommended in adults with hypovolemia or shock, within the first 3 hours with initial boluses administered rapidly based on response.[22][5] In contrast, colloids like albumin require lower volumes for equivalent expansion due to their oncotic properties; typical dosing is 5-10 mL/kg as a bolus, often reserved for cases where crystalloids alone are insufficient.[40] Subsequent doses are adjusted dynamically, assessing response after each bolus rather than using fixed volumes, to align with patient-specific needs in conditions like sepsis or hemorrhage.[13] Monitoring during volume expander therapy focuses on parameters that reflect organ perfusion and fluid status to guide ongoing administration. Vital signs, including blood pressure and heart rate, are tracked continuously to detect improvements in hemodynamic stability.[41] Urine output serves as a key indicator of renal perfusion, with a target of greater than 0.5 mL/kg/hour signaling adequate resuscitation.[40] Additional measures include dynamic parameters such as passive leg raise testing or stroke volume variation to assess fluid responsiveness, and serum lactate levels, which should decrease toward normal (<2 mmol/L) as tissue oxygenation improves.[5][42] Adjustments to dosing are made by titrating fluids to predefined endpoints, such as achieving a mean arterial pressure (MAP) of at least 65 mmHg, while vigilantly avoiding fluid overload through regular reassessment of these parameters.[5] If response is inadequate after initial boluses, advanced monitoring like stroke volume variation may inform further decisions, but therapy halts once endpoints are met or signs of overload emerge.[43] This approach ensures personalized resuscitation, particularly in critical care settings.[13]Adverse effects and contraindications
Common adverse effects
Volume expanders, whether crystalloid or colloid, can lead to general mild adverse effects such as chills and headache, reported in postmarketing surveillance data.[44] These symptoms are typically transient and resolve without intervention, often linked to infusion-related responses.[45] Crystalloid solutions commonly cause fluid overload, particularly with large-volume infusions exceeding 2-3 liters in patients with compromised cardiac or renal function, leading to symptoms like peripheral edema and dyspnea.[22] Normal saline (0.9% NaCl) administration may result in hypernatremia due to its sodium content of 154 mEq/L, which exceeds plasma levels, especially in resuscitation scenarios.[46] In contrast, 5% dextrose in water (D5W) can induce dilutional hyponatremia by providing free water after dextrose metabolism, with an incidence of 15-30% in hospitalized children receiving hypotonic maintenance fluids.[47] Colloid volume expanders are associated with mild allergic reactions, including rash and itching, occurring in approximately 0.003-0.1% of infusions depending on the agent—lowest with albumin (~0.01%) and higher with dextrans (~0.03%).[48] Nausea and fever are also reported in postmarketing experiences with hydroxyethyl starch solutions.[44] These effects are generally self-limiting and more frequent with synthetic colloids than human-derived ones.Contraindications and precautions
Volume expanders, whether crystalloids or colloids, are contraindicated in patients with fluid overload, such as those with congestive heart failure or pulmonary edema, to prevent exacerbation of cardiac or respiratory compromise.[22] Severe electrolyte disorders, including hyperkalemia or hyponatremia requiring rapid correction, also represent absolute contraindications, particularly for solutions containing potassium like lactated Ringer's or hypertonic saline, due to risks of worsening imbalances or central pontine myelinolysis.[22] Relative contraindications include hypersensitivity or allergy to components of the expander; for instance, dextran solutions should be avoided in patients with known allergies to dextrans or in those with active bleeding disorders, as they can interfere with platelet function and coagulation.[32] Hydroxyethyl starch (HES) colloids are relatively contraindicated in renal impairment, given their association with acute kidney injury.[49] Precautions are essential when administering volume expanders to elderly patients or those with renal dysfunction, necessitating close monitoring of fluid status, electrolytes, and renal function to avoid overload or organ stress.[22] In the European Union, HES solutions have been restricted since 2013 due to evidence of increased kidney risks, with additional risk minimization measures adopted in 2018, limiting their use to specific non-critical scenarios with vigilant oversight.[49] Albumin, while generally safer, requires caution in patients with severe anemia or renal insufficiency to mitigate potential volume overload.[29]Comparisons and guidelines
Efficacy and safety comparisons
Comparisons of efficacy between crystalloids and colloids in volume expansion reveal that colloids often require smaller infusion volumes to achieve hemodynamic stability due to their oncotic properties, which promote greater intravascular retention.[50] However, large randomized controlled trials (RCTs) and meta-analyses have consistently shown no significant mortality benefit for colloids over crystalloids in critically ill patients requiring fluid resuscitation.[51][52] For instance, the Saline versus Albumin Fluid Evaluation (SAFE) trial, involving 6,997 intensive care unit patients, found that 4% albumin and normal saline resulted in similar 28-day mortality rates (20.9% vs. 21.1%), despite albumin's theoretical advantages in volume efficiency.[51] Regarding safety, crystalloids such as normal saline are substantially cheaper and more widely available, with average costs under 1 USD per 100 mL across international settings, compared to colloids averaging 59 USD per 100 mL.[53] A key risk with large-volume crystalloid administration is hyperchloremic metabolic acidosis, arising from the high chloride content in solutions like 0.9% saline, which can impair renal function and acid-base balance.[22] In contrast, colloids carry a higher risk of anaphylactoid reactions, particularly with gelatin-based colloids.[54] Additionally, hydroxyethyl starch (HES) colloids have been linked to increased renal harm, including acute kidney injury and need for renal replacement therapy, as evidenced by the VISEP trial and subsequent meta-analyses.[55][56] The following table summarizes key comparative aspects, drawing from RCTs such as SAFE and VISEP:| Aspect | Crystalloids | Colloids |
|---|---|---|
| Intravascular Retention Time | Short half-life (20–40 minutes); up to 50% volume shifts extravascular within 30 minutes[57][58] | Longer retention (2–3 hours); nearly full volume retained intravascularly after 1 hour[50][59] |
| Cost (per 100 mL) | <1 USD[53] | ~59 USD (varies by type, e.g., higher for albumin and HES)[53] |
| Key Risks | Hyperchloremic metabolic acidosis with large volumes; potential renal vasoconstriction[22] | Anaphylaxis (particularly for gelatins); HES-associated acute kidney injury and mortality increase (risk ratio 1.09 for death)[54][56][55] |