Albumin is one of the most important proteins in the body. Its physiological functions are numerous, including transport of proteins for many elements (e.g., hormones, drugs); free radical scavenging; maintenance of the oncotic pressure (albumin is responsible for 70–80% of the oncotic pressure); anti-apoptotic effects; and anticoagulant and anti-thrombotic, acid-base buffering, and anti-inflammatory properties. Albumin is a small molecule (66 kDa) synthesized by the liver. Hepatic onco-receptors regulate its synthesis. The usual quoted volume of distribution is 30% intravascular and 70% extravascular, but the transcapillary rate is very slow, as it can take several days for albumin to move across the endothelial membrane. After albumin infusion to healthy patients, 90% is still intravascular after 2 hours, and 25% after 2 days. However, that transcapillary flux can be increased up to 13 times in critical illness (e.g., infection, shock, burns). Moreover, albumin's half-life (8.2 days in dogs) is inversely dependent on its concentration, with hypoalbuminemia increasing its half-life.

Hypoalbuminemia, defined as a serum albumin of less than 3.0 g/dL, is common and has a prevalence between 10–25% in a regular canine population, and probably higher in critically ill dogs and cats. The cause of hypoalbuminemia is multifactorial. Although commonly quoted, decreased production of albumin by the liver should not lead to acute hypoalbuminemia, due to albumin's long half-life being inversely concentration dependent. Therefore, increased loss or more likely destruction during antioxidative processes are the main contributors to hypoalbuminemia, and albumin has been called the 'sacrificial lamb' of inflammation.

It is well documented that hypoalbuminemia carries a worse prognosis in critically ill humans. Each 1.0 g/dL decrease in albumin increases the odds of mortality by 137% and morbidity by 89%. This is also documented in veterinary medicine. Although hypoalbuminemia is a risk factor for death and worsening illness, the link between albumin replacement and improved outcome continues to be debated. In humans, there is evidence that albumin replacement does not improve mortality for perioperative patients, in heterogeneous ICU populations, or in trauma patients. Albumin transfusion is contraindicated in traumatic brain injury patients. Potential indications for albumin transfusion in humans are burns and severe sepsis/septic shock.

The use of HSA (25%, or 250 mg/mL, or 0.25 g/mL) is an attractive solution to replenish albumin using lower volume, although cost of HSA is still high. However, there is only 80% homology between CSA and HSA. However, species differences in the genetic amino acid sequence, molecular weight, net charge, and isoelectric set point of albumin are thought to contribute to antigenicity with the potential to develop adverse immediate and delayed hypersensitivity reactions in some dogs. Therefore, transfusion of HSA to dogs will result in the production of anti-HSA antibodies within 10 days of HSA infusion, peaking at 3 weeks after administration, and possibly leading to acute anaphylactic reaction and death of HSA-transfused dogs re-exposed to HSA. Moreover, approximately 8–10% of dogs have naturally occurring anti-HSA antibodies, so may develop an acute anaphylactic reaction during their first HSA transfusion. There are several reports on clinical use of HSA in dogs, but concerns about immunization and acute (type I) and delayed (type III) hypersensitivity reactions limit its use, and using HSA multiple times in a patient is strictly contraindicated. Also, it is documented that approximately 7% of critically ill dogs receiving HSA will have serious complications. There have been reports of hypersensitivity reactions in normal dogs as well as critically ill dogs receiving 25% HSA as well as HSA diluted to a 5% solution. Finally, deaths have been reported in critically ill dogs with type III hypersensitivity after receiving 25% HSA. Therefore, clinicians must carefully weigh risks/benefits in individual patients before use. Despite those findings, several prospective or retrospective studies have been published since 2005, including reports on maintenance or increase of serum albumin, COP or blood pressure.

Dosage of albumin in veterinary references usually use a specific formula to calculate the amount of albumin to be given. That amount (in grams) is based on the formula "10 × desired delta albumin × weight (kg) × 0.3", but the origin of that formula points to albumin replacement using total parenteral nutrition in the 1980s and is not used in people, where a fixed or targeted dose per day is used. A review of the literature indicates that the amount of albumin given per day in dogs and cats ranges from 0.5 to 2.5 grams/kg/day. As noted earlier, most human studies investigating albumin use for critically ill patients use a fixed dose of albumin, ranging from 0.2–1 gram/kg/day.

Alternatives to human serum albumin include canine-specific albumin (CSA) or albumin contained in fresh frozen plasma (FFP) or cryo-poor plasma (CPP). The albumin content of FFP is relatively low, around 2.9 and 3.2 g/dL, respectively, corresponding to 2.9 and 3.2% albumin, respectively. The use of CPP as an albumin replacement fluid, given as a CRI, has been published in veterinary medicine. The volume for 1 gram of albumin is 4 mL for 25% HSA, 20 mL for 5% HSA and CSA, and approximately 33 mL for FFP or CCP. The price of 1 gram of albumin is $6.2 for HSA, $43 for CSA, $20 for CCP, and approximately $40 for FFP, depending on the service provider.

References

1.  Rozga, J., Piątek, T. and Małkowski, P. Human albumin: old, new, and emerging applications. Ann. Transplant. Q. Pol. Transplant. Soc. 18, 205–217 (2013).

2.  Boldt, J. Use of albumin: an update. Br. J. Anaesth. 104, 276–284 (2010).

3.  Belinskaia, D. A. et al. The universal soldier: enzymatic and non-enzymatic antioxidant functions of serum albumin. Antioxid. Basel Switz. 9, (2020).

4.  Vincent, J.-L. Relevance of albumin in modern critical care medicine. Best Pract. Res. Clin. Anaesthesiol. 23, 183–191 (2009).

5.  Roux, F., Deswarte, A. and Deschamps, J. Prognostic value of preoperative serum albumin level in canine and feline gastro-intestinal surgery: 150 cases (2009–2012). J Vet Emerg Crit Care. 23, S17 (2013).

6.  SAFE Study Investigators et al. Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis. Intensive Care Med. 37, 86–96 (2011).

7.  Roberts, I., Blackhall, K., Alderson, P., Bunn, F. and Schierhout, G. Human albumin solution for resuscitation and volume expansion in critically ill patients. Cochrane Database Syst. Rev. CD001208 (2011) doi:10.1002/14651858.CD001208.pub4.

8.  Caironi, P. et al. Albumin replacement in patients with severe sepsis or septic shock. N. Engl. J. Med. 370, 1412–1421 (2014).

9.  Francis, A. H. et al. Adverse reactions suggestive of type III hypersensitivity in six healthy dogs given human albumin. J. Am. Vet. Med. Assoc. 230, 873–879 (2007).

10.  Mazzaferro, E. M. and Edwards, T. Update on albumin therapy in critical illness. Vet. Clin. North Am. Small Anim. Pract. 50, 1289–1305 (2020).

11.  Adamantos, S., Chan, D. L., Goggs, R. and Humm, K. Risk of immunologic reactions to human serum albumin solutions. J. Small Anim. Pract. 50, 206 (2009).

12.  Trow, A. V., Rozanski, E. A., Delaforcade, A. M. and Chan, D. L. Evaluation of use of human albumin in critically ill dogs: 73 cases (2003–2006). J. Am. Vet. Med. Assoc. 233, 607–612 (2008).

13.  Viganó, F., Perissinotto, L. and Bosco, V. R. F. Administration of 5% human serum albumin in critically ill small animal patients with hypoalbuminemia: 418 dogs and 170 cats (1994–2008). J. Vet. Emerg. Crit. Care San Antonio Tex. 2001 20, 237–243 (2010).

14.  Mathews, K. A. The therapeutic use of 25% human serum albumin in critically ill dogs and cats. Vet. Clin. North Am. Small Anim. Pract. 38, 595–605, xi–xii (2008).

15.  Brown, R. O., Bradley, J. E. and Luther, R. W. Response of serum albumin concentrations to albumin supplementation during central total parenteral nutrition. Clin. Pharm. 6, 222–226 (1987).