What is the role of albumin in treating third spacing (edema)?

From the Guidelines

Albumin is not routinely recommended for treating third spacing (edema) due to its limited benefits and potential risks, and instead, treatment should focus on addressing the underlying cause of third spacing. The use of albumin in treating third spacing is a complex issue, and the evidence suggests that it should be reserved for specific situations. According to the most recent guideline from the International Collaboration for Transfusion Medicine Guidelines 1, albumin is administered in various clinical scenarios, including complications of cirrhosis, intradialytic hypotension, volume resuscitation, and priming of cardiopulmonary bypass circuit. However, the guideline emphasizes that the potential benefits and risks of albumin use should be carefully considered.

Some key points to consider when deciding whether to use albumin in treating third spacing include:

• The underlying cause of third spacing, such as sepsis, liver disease, or heart failure, should be addressed as the primary treatment approach.
• Crystalloid solutions like normal saline or lactated Ringer's are generally preferred as first-line fluid therapy for volume replacement.
• In specific situations like large-volume paracentesis (>5 liters) in cirrhotic patients, albumin (6-8 g per liter of ascites removed) may be beneficial to prevent post-paracentesis circulatory dysfunction, as recommended by the AGA clinical practice update 1.
• Albumin administration carries risks, including cost, allergic reactions, and potential disease transmission, as outlined in the guideline 1 and the AGA clinical practice update 1.
• The physiological rationale for limiting albumin use is that in most third spacing conditions, the problem isn't low albumin itself but increased capillary permeability, which allows albumin to leak into tissues, potentially worsening edema.

In summary, the use of albumin in treating third spacing should be individualized and based on the specific clinical scenario, with careful consideration of the potential benefits and risks. The most recent and highest quality evidence suggests that albumin should not be routinely used for treating third spacing, except in specific situations where its benefits outweigh the risks 1.

From the FDA Drug Label

When administered intravenously to an adequately hydrated subject, the oncotic (colloid osmotic) effect of 20 mL Plasbumin-25 is such that it will draw approximately a further 70 mL of fluid from the extravascular tissues into the circulation within 15 minutes,(1) thus increasing the total blood volume and reducing both hemoconcentration and whole blood viscosity Sequestration of Protein Rich Fluids(7) This occurs in such conditions as acute peritonitis, pancreatitis, mediastinitis, and extensive cellulitis. The magnitude of loss into the third space may require treatment of reduced volume or oncotic activity with an infusion of albumin Acute Nephrosis(2) Certain patients may not respond to cyclophosphamide or steroid therapy. The steroids may even aggravate the underlying edema In this situation a loop diuretic and 100 mL Plasbumin-25 repeated daily for 7 to 10 days may be helpful in controlling the edema and the patient may then respond to steroid treatment.

The role of albumin in treating third spacing (edema) is to:

• Increase the total blood volume and reduce hemoconcentration and whole blood viscosity by drawing fluid from the extravascular tissues into the circulation
• Treat reduced volume or oncotic activity in conditions such as acute peritonitis, pancreatitis, and extensive cellulitis
• Control edema in certain patients with acute nephrosis who do not respond to cyclophosphamide or steroid therapy, in combination with a loop diuretic 2, 2, 2. Key points:
• Albumin can help reduce edema by increasing oncotic pressure and drawing fluid into the circulation
• It is used to treat third spacing in conditions such as acute peritonitis and pancreatitis
• It can be used in combination with a loop diuretic to control edema in certain patients with acute nephrosis.

From the Research

Role of Albumin in Treating Third Spacing (Edema)

• Albumin plays a crucial role in treating third spacing (edema) by helping to maintain oncotic pressure and prevent fluid shift from the vascular space to the interstitial space 3, 4.
• The use of intravenous albumin solution has been shown to result in a lower net fluid balance compared with crystalloids, and smaller infusion volumes may be sufficient for hemodynamic stabilization when human albumin solutions are used 3.
• Hypoalbuminemia acts as an effect moderator in volume resuscitation and plasma expansion with albumin solution, and the volume effectiveness of intravenous human albumin solution in resuscitation appears to be greater when the serum albumin levels are low 3.
• The "interstitial washdown" mechanism, which involves the recruitment of albumin from the interstitial space to the plasma, may help to prevent edema formation and improve fluid removal during renal replacement therapy 5.

Comparison with Crystalloids

• The administration of iso-oncotic or hyper-oncotic albumin solutions in patients undergoing resuscitation does not have the reductions in fluid requirements anticipated from a traditional understanding of the oncotic actions of albumin 4.
• However, the use of albumin in combination with crystalloids has been shown to improve survival of critically ill patients, particularly when administered early in the course of treatment 6.
• The choice between crystalloid solution and colloidal solution, including albumin, remains a topic of debate, and the decision to use one over the other may depend on various factors, including the clinical scenario and physician preference 7.

Clinical Implications

• The use of albumin in treating third spacing (edema) may be beneficial in certain clinical scenarios, such as in patients with hypoalbuminemia or those undergoing renal replacement therapy 3, 5.
• However, the decision to use albumin should be based on individual patient needs and circumstances, and should take into account the potential benefits and risks of its use 4, 6.
• Further studies are needed to fully understand the role of albumin in treating third spacing (edema) and to determine the optimal approach to fluid resuscitation in critically ill patients 3, 6.