What Instead of Plasma Can Be Used as a Replacement Fluid?

Millions of intravenous fluid units are administered annually for volume resuscitation and procedures like therapeutic plasma exchange [1.7.5]. When donor plasma isn't used, what instead of plasma can be used as a replacement fluid? The main alternatives fall into two categories: crystalloids and colloids [1.3.1, 1.4.5].

Quick Summary

An in-depth review of the fluids used as alternatives to plasma. This content covers the two main classes, crystalloids and colloids, comparing their specific types, uses, mechanisms, and risks.

Key Points

• Two Main Classes: The primary alternatives to plasma are crystalloids (e.g., normal saline, Lactated Ringer's) and colloids (e.g., albumin, starches) [1.4.2].

• Crystalloid Action: Crystalloids contain small molecules that move easily out of blood vessels, requiring larger volumes to be infused for effective blood volume expansion [1.2.2, 1.3.6].

• Colloid Advantage: Colloids have large molecules that stay in the bloodstream longer, making them more efficient volume expanders by maintaining osmotic pressure [1.3.2, 1.3.3].

• Albumin's Role: 5% Albumin is the most common colloid replacement fluid for many therapeutic plasma exchange (TPE) procedures due to its excellent safety profile and effectiveness [1.5.5, 1.9.4].

• Synthetic Colloid Risks: Synthetic colloids like hydroxyethyl starches (HES) and dextrans are now rarely used due to significant risks, including kidney injury, allergic reactions, and bleeding problems [1.3.1, 1.6.1].

• Balanced is Often Better: Balanced crystalloids like Lactated Ringer's and Plasma-Lyte are increasingly preferred over normal saline to avoid the risk of acid-base imbalances [1.7.2, 1.7.5].

• No Universal Substitute: The choice of a plasma replacement fluid is a complex clinical decision that depends on the patient's underlying disease, organ function, and the specific goals of treatment [1.9.1, 1.9.3].

Understanding Plasma and the Need for Replacement

Blood plasma is the liquid component of blood that holds blood cells in suspension. It is critical for maintaining oncotic pressure, which keeps fluid within the blood vessels, and for transporting proteins, hormones, and nutrients [1.5.4]. In certain medical situations, such as therapeutic plasma exchange (TPE), major trauma, or severe burns, a patient's plasma must be removed or is lost, necessitating a replacement fluid to maintain circulatory volume and stability [1.2.2, 1.8.5].

While fresh frozen plasma (FFP) can be used, it carries risks of allergic reactions and viral transmission and has logistical challenges like needing to be ABO-type matched and thawed before use [1.5.4, 1.5.5]. For these reasons, and especially in procedures like TPE where the primary goal is to remove harmful substances like autoantibodies, alternative replacement fluids are often preferred [1.5.4]. The choice of fluid depends on the clinical context, patient condition, and the specific therapeutic goal [1.9.1].

The Primary Alternatives: Crystalloids vs. Colloids

The fundamental choice for a plasma replacement fluid is between crystalloids and colloids. The main difference lies in the size of the molecules they contain, which dictates how they behave in the body [1.3.2, 1.4.5].

• Crystalloids are solutions of small molecules (like salts and dextrose) dissolved in water. These small molecules can easily pass from the bloodstream into the surrounding tissues [1.4.3, 1.4.5]. Because they distribute throughout the extracellular fluid space, larger volumes are needed to expand the intravascular (in-vessel) volume effectively [1.2.2, 1.3.5].
• Colloids contain large molecules (like proteins or starches) that do not easily cross capillary walls [1.3.2, 1.4.5]. This property helps them remain in the intravascular space for longer, making them more potent volume expanders by maintaining colloid osmotic pressure [1.3.3, 1.3.6].

A Deep Dive into Crystalloid Solutions

Crystalloids are often used as a first-line treatment for fluid resuscitation due to their low cost and wide availability [1.2.3]. The most common types include:

• Normal Saline (0.9% NaCl): This isotonic solution has a salt concentration similar to the blood [1.4.2]. It is widely used for fluid resuscitation and is the only fluid compatible with blood transfusions [1.4.1, 1.4.3]. However, administration of large volumes can lead to hyperchloremic metabolic acidosis, a condition where the blood becomes too acidic due to high chloride levels [1.4.2, 1.7.3].
• Balanced Salt Solutions: These fluids, such as Lactated Ringer's (LR) and Plasma-Lyte, have an electrolyte composition closer to that of human plasma [1.7.3]. They are often preferred because they reduce the risk of acid-base disturbances seen with normal saline [1.7.1, 1.7.2]. However, LR contains lactate, which can be problematic in patients with severe liver failure, and may also contain calcium, which can interact with other medications or blood products [1.4.2, 1.4.6].
• Hypertonic Saline (e.g., 3% NaCl): This solution has a higher salt concentration than blood. It works by drawing fluid from the tissues into the bloodstream, making it a powerful tool for rapidly increasing intravascular volume or reducing brain swelling (cerebral edema) [1.4.1, 1.4.6]. It must be used with extreme caution due to risks of severe electrolyte imbalances [1.4.1].

Exploring Colloid Solutions

Colloids are categorized as natural or synthetic. They are more effective at expanding plasma volume per unit infused compared to crystalloids but are also more expensive and carry their own set of risks [1.3.1, 1.3.4].

Natural Colloids

• Albumin (5% and 25%): Human serum albumin is the most common natural colloid and the standard replacement fluid for many TPE procedures [1.5.5, 1.9.4]. A 5% solution is iso-oncotic with plasma, meaning it maintains volume without causing major fluid shifts [1.5.4]. It is pasteurized to inactivate viruses and has a very low risk of allergic reactions [1.5.4, 1.5.5]. The primary drawbacks are its high cost and the fact that it is a human blood product, which some patients may refuse [1.3.1, 1.4.3]. Using albumin alone can also dilute coagulation factors, potentially increasing bleeding risk [1.8.2, 1.9.4].

Synthetic Colloids

Over the years, various artificial colloids have been developed, but many have fallen out of favor due to significant safety concerns [1.2.2, 1.3.1].

• Hydroxyethyl Starches (HES): Once widely used, HES products (hetastarch, pentastarch) are now restricted in many regions. Studies have linked them to an increased risk of acute kidney injury, coagulation problems, and even increased mortality in critically ill patients [1.3.1, 1.6.1, 1.6.3].
• Dextrans: These large sugar polymers are effective volume expanders but can interfere with blood cross-matching, impair coagulation, and cause rare but severe allergic reactions [1.2.2, 1.3.1]. Their use has significantly declined [1.2.2].
• Gelatins: Derived from bovine collagen, gelatins have a short duration of action and a notable risk of allergic reactions [1.2.2, 1.6.1]. They are not approved for use in the United States [1.3.1].

Comparison of Common Replacement Fluids

Fluid Type	Category	Primary Use	Key Advantage	Key Disadvantage/Risk
Normal Saline (0.9% NaCl)	Crystalloid	General fluid resuscitation, hyponatremia [1.4.1]	Inexpensive, widely available, compatible with blood products [1.2.3, 1.4.3]	Risk of hyperchloremic metabolic acidosis with large volumes [1.4.2, 1.7.3]
Lactated Ringer's	Crystalloid	Resuscitation for burns, trauma, surgery [1.4.1]	Balanced electrolyte profile, reduces acidosis risk compared to saline [1.7.1]	Contains lactate and calcium; may be unsuitable for liver failure or with certain drugs [1.4.6]
5% Albumin	Natural Colloid	TPE, volume expansion in liver disease, burns [1.4.3, 1.5.4]	Low risk of allergic reaction, long intravascular duration, virally inactivated [1.5.5]	High cost, derived from human blood, can dilute clotting factors [1.3.1, 1.8.2]
Hydroxyethyl Starch (HES)	Synthetic Colloid	(Historically) Rapid volume expansion [1.6.1]	Potent volume expander [1.2.1]	Associated with kidney injury, bleeding, and increased mortality; use is now restricted [1.3.1, 1.6.3]

Choosing the Right Fluid: A Clinical Decision

There is no single 'best' replacement fluid. The choice is a complex medical decision based on several factors [1.9.1, 1.9.3]:

1. The Clinical Indication: In TPE for thrombotic thrombocytopenic purpura (TTP), FFP is required because it replenishes a crucial enzyme that patients lack [1.5.4]. In contrast, for TPE in autoimmune conditions like myasthenia gravis, 5% albumin is the standard of care to remove antibodies without introducing new ones [1.5.5, 1.8.5]. For general resuscitation, balanced crystalloids are increasingly favored over normal saline [1.7.2, 1.7.5].
2. Patient-Specific Factors: Kidney and liver function are critical considerations. Patients with kidney failure are at higher risk from certain fluids, while those with liver failure cannot metabolize lactate from LR [1.7.3, 1.4.6]. Pre-existing bleeding disorders might also influence the choice away from fluids that impair coagulation [1.8.2].
3. Risk Profile: Each fluid carries potential complications. Crystalloids can cause edema, while colloids have been linked to more severe issues like anaphylaxis and renal failure [1.3.4]. Hypocalcemia (low calcium) is a common complication of TPE, often related to the citrate anticoagulant used, but can be influenced by the replacement fluid [1.8.2, 1.8.5].
4. Cost and Availability: Crystalloids are significantly cheaper than colloids, especially albumin, which is a major factor in clinical decision-making [1.2.3, 1.3.1].

Conclusion

The question of 'what instead of plasma can be used as a replacement fluid?' opens up a wide array of pharmacological options, primarily divided into crystalloids and colloids. While fresh frozen plasma has a specific role, alternatives like 5% albumin and balanced crystalloids are central to modern practice. The trend has moved away from synthetic colloids like HES due to significant safety concerns. Ultimately, the ideal choice is not universal; it is tailored to the specific disease, patient physiology, and the intended therapeutic outcome, balancing efficacy, safety, and cost.

An authoritative outbound link for further reading: Intravenous fluid therapy - Knowledge @ AMBOSS

Frequently Asked Questions

Is saline a good replacement for plasma?

Normal saline (a crystalloid) can be used to expand fluid volume but is not a direct replacement for plasma's proteins. It is often used for initial resuscitation, but balanced crystalloids or colloids like albumin are preferred in many situations to avoid side effects like metabolic acidosis [1.4.2, 1.7.2].

What is the main difference between a crystalloid and a colloid?

The main difference is molecular size. Crystalloids have small molecules that easily pass through capillary walls into the tissues, while colloids have large molecules that remain in the bloodstream, holding fluid in the vessels more effectively [1.3.2, 1.4.5].

Why is albumin used instead of plasma for some procedures?

5% albumin is often preferred for procedures like therapeutic plasma exchange because it is virally inactivated, does not need to be blood-type matched, and has a very low risk of allergic reactions compared to fresh frozen plasma (FFP) [1.5.4, 1.5.5].

What are the biggest risks with plasma replacement fluids?

Risks vary by fluid type. Large volumes of crystalloids can cause tissue swelling (edema). Synthetic colloids like HES are linked to kidney damage and bleeding [1.3.1, 1.6.3]. Allergic reactions can occur with FFP and synthetic colloids [1.8.2]. Dilution of clotting factors is a risk when using albumin [1.9.4].

What is therapeutic plasma exchange (TPE) and what fluid is used?

TPE is a procedure that removes a patient's plasma to get rid of harmful substances, like antibodies in autoimmune diseases. The replacement fluid is chosen based on the disease; 5% albumin is standard for many conditions, while fresh frozen plasma is required for others, like TTP [1.5.4, 1.8.5].

Are synthetic plasma substitutes like starches safe?

No, many synthetic colloids, particularly hydroxyethyl starches (HES), have been found to have significant safety risks. These include acute kidney injury, bleeding disorders, and increased mortality in critically ill patients, leading to major restrictions on their use [1.3.1, 1.6.1].

What makes a salt solution 'balanced'?

A balanced salt solution, like Lactated Ringer's or Plasma-Lyte, has an electrolyte concentration and pH that is much closer to that of human blood plasma compared to normal saline. This helps prevent the acid-base disturbances that can occur with large infusions of normal saline [1.7.3, 1.7.4].