Treating H ypoalbuminemia

Bobbi J. Conner, DVM

KEYWORDS
 Hypoalbuminemia  Hypoproteinemia  Albumin  Colloid osmotic pressure
 Edema

KEY POINTS
 Hypoalbuminemia is a common finding in critically ill veterinary patients and is associated
with poor outcomes in many diseases.
 Specific therapy to correct low serum albumin concentration is rarely indicated and treat-
ments are associated with high rates of adverse events.
 Treatment should focus on addressing the underlying disease leading to hypoalbumine-
mia. Nutritional supplementation should be considered in many cases.

Video content accompanies this article at http://www.vetsmall.theclinics.com.

INTRODUCTION

Hypoalbuminemia, typically defined as serum albumin concentration less than 3.0 g/dL
(30 g/L), is a common complication seen in critically ill dogs and cats. There is significant
interest in identifying, assessing, and treating hypoalbuminemia because it has clearly
been established as a marker for disease severity and is associated with poor outcomes
in many human and animal diseases.1–3 Unfortunately, although hypoalbuminemia may
reliably correlate with disease severity, measures to directly correct serum albumin
concentration have not led to improved outcomes in most situations and may even
be harmful in some cases. Adverse effects of hypoalbuminemia are generally not
seen until it becomes severe (<2.0 g/dL or 20 g/L).
Albumin is critical for maintenance of vascular integrity and colloid osmotic pres-
sure. It also plays important roles in metabolism, anticoagulation, acid-base regula-
tion, and antioxidation. In the blood, albumin is an important carrier for many
endogenous and exogenous substances, and alterations in serum albumin concentra-
tion may affect pharmacokinetics and pharmacodynamics of highly protein-bound
drugs. The functions of albumin should be taken into consideration when assessing
any patient with hypoalbuminemia and potential complications of decreased serum al-
bumin concentration should not be overlooked.

The author has nothing to disclose.

Emergency & Critical Care, University of Florida College of Veterinary Medicine, 2015 South-
west 16th Avenue, PO Box 100116, Gainesville, FL 32610, USA
E-mail address: [email protected]

Vet Clin Small Anim - (2016) -–-

http://dx.doi.org/10.1016/j.cvsm.2016.09.009 vetsmall.theclinics.com
0195-5616/16/ª 2016 Elsevier Inc. All rights reserved.
2 Conner

PATIENT EVALUATION OVERVIEW

Hypoalbuminemia is a consequence of many different disease processes (Box 1). As

such, patients with hypoalbuminemia present with a variety of clinical signs referable
to the underlying disease but a few findings should prompt the clinician to consider
low serum albumin concentration as a cause:
 Peripheral edema or pitting edema (Fig. 1)
 Ascites
 Pleural effusion.
These findings are not specific for hypoalbuminemia because fluid loss from the
intravascular space may be caused by several other problems (Fig. 2). However,
low serum albumin concentration as a cause or contributor should be ruled out.
Many, if not most, patients with hypoalbuminemia will not have any readily identifiable

Box 1
Diseases commonly associated with hypoalbuminemia

 Liver diseases
 Portosystemic shunts
 Hepatitis
 Cholangiohepatitis
 Hepatic lipidosis
 Hepatic neoplasia
 Cirrhosis
 Protein-losing enteropathies
 Inflammatory bowel disease
 Infectious enteropathies
- Parvoviral enteritis
- Panleukopenia virus
- Salmonellosis
- Parasitism
 Intestinal neoplasia
 Lymphangiectasia
 Food allergy
 Protein-losing nephropathies
 Glomerulonephritis
- Heartworm disease
- Tick-borne disease
- Bacterial pyelonephritis
- Lupus
- Neoplasia
- Feline leukemia virus
- Idiopathic
 Glomerulonephropathy
- Familial glomerulonephropathy
 Amyloidosis
 Inflammatory diseases, systemic inflammatory response syndrome (SIRS)
 Pancreatitis
 Peritonitis
 Pneumonia
 Sepsis
 Heat stroke
 Neoplasia
 Treating Hypoalbuminemia 3

Fig. 1. Pitting edema in a dog with tibial fracture and external fixation. Note how after
pressing on the edematous area (A) the indentation remains (B).

signs attributable to low oncotic pressure until hypoalbuminemia becomes severe

(generally < 2.0 g/dL [20 g/L]).

PHARMACOLOGIC TREATMENT OPTIONS

Most animals with hypoalbuminemia will not require specific therapy to address the
serum albumin concentration (Fig. 3). Patients with diseases that are identified and
treated appropriately will generally see improvements in serum albumin concentra-
tion relatively quickly (improvement may be seen within a few days). Patients with
protracted, chronic, or incurable diseases may develop clinical signs secondary to
low oncotic pressure and require therapies aimed specifically at addressing albumin
content within the body. Routine correction of serum albumin concentration should
be avoided. There are few studies in veterinary medicine on the use of products to
correct or improve hypoalbuminemia (Table 1). Routine use of albumin is no longer
recommended in people to treat hypoalbuminemia because of either increased risk

Fig. 2. Starling’s forces describe the movement of fluid across capillaries. Increased hydro-
static pressure or reduced oncotic pressure within the capillary will favor movement of fluid
out of the vasculature and promote edema. Altered vascular integrity seen with inflamma-
tion can lead to so-called leaky vessels and promote edema. In health, there is a net move-
ment of fluid out of the capillaries and the excess fluid is taken up into the lymphatic
system.
4 Conner

Fig. 3. Decision tree providing guidance for management of patients with

hypoalbuminemia.

of complications (including death in some studies) or lack of proven benefit in many

cases.4,5
Formula to determine amount of albumin needed to raise the serum albumin con-
centration to 2.0 g/dL (20 g/L) (target albumin concentration may be adjusted as
appropriate)

Albumin dose (in grams) 5 10  (2.0 g/dL, patient albumin g/dL)  body weight (kg)  0.3
Or
Albumin dose (in grams) 5 20 g/L, patient albumin g/L  body weight (kg)  0.3
 Treating Hypoalbuminemia 5

Table 1
Summary of evidence for albumin supplementation in veterinary medicine

Product
Study Evaluated Population Benefit? Comments
Francis et al,6 25% HSA 6 healthy dogs No Prospective: 2 healthy dogs
2007 given HSA died during this
prospective study
Cohn et al,7 25% HSA 9 healthy dogs No Prospective: frequent, severe
2007 reactions reported
Trow et al,1 25% HSA 73 critically Yes Retrospective: frequent
2008 ill dogs immediate reactions, some
delayed reactions, cause and
effect unclear; HSA
associated with increased
serum albumin
concentration and higher
serum albumin
concentration was
associated with survival
Viganó et al,8 5% HSA 418 sick dogs, Unclear Retrospective: no major
2010 170 sick cats adverse effects reported,
frequent minor reactions
Horowitz 25% HSA 39 dogs with No Retrospective: high mortality
et al,2 2015 septic overall, survival was
peritonitis, associated with higher serum
22 given HSA albumin concentration; no
association between HSA
administration and survival.
Craft & Powell,9 5% CSA 14 dogs with No Prospective: CSA transfusion
2012 septic increased serum albumin
peritonitis, concentration, no survival
7 given CSA benefit identified; CSA not
readily available
Snow et al,10 Fresh frozen 283 sick dogs, 25 No Retrospective: no difference in
2010 plasma sick cats albumin concentration seen
preplasma and postplasma
transfusion (dosage:
15–18 mL/kg)

Abbreviations: CSA, canine serum albumin; HSA, human serum albumin.

Once the decision has been made to transfuse an albumin-containing product,

careful monitoring must be used to identify transfusion reactions as quickly as
possible. Once an albumin-containing product (lyophilized human serum albumin,
lyophilized canine serum albumin, or fresh frozen plasma) is reconstituted or thawed,
it should be used within 4 to 6 hours to decrease the risk of contamination. Signs of an
adverse allergic reaction may include angioedema, urticarial, pruritus, or fever.
Anaphylactic reactions may cause tachypnea, collapse, or hypotension. Severe reac-
tions may be delayed by several days.

NONPHARMACOLOGIC TREATMENT OPTIONS

In addition to treatment of the underlying disease process, proper nutrition may be an

important component of therapy for patients with hypoalbuminemia and there is
6 Conner

Fig. 4. NE red rubber catheter used to provide supplemental nutrition.

increasing evidence to support early nutritional support for a variety of diseases in vet-
erinary medicine.11–13 In people and animals, evidence is mounting for the provision of
enteral feeding instead of or in addition to parenteral feeding whenever possible.13,14
Voluntary food intake is generally tried first. Appetite stimulants should be considered
in some patients (see Video 1).
Temporary feeding tubes, such as nasoesophageal (NE), nasogastric (NG), and
esophagostomy tubes (E-tubes), are relatively simple to place and are good options
for short-term (NE and NG tubes, Figs. 4 and 5) or longer-term (E-tubes) nutritional
support. NE and NG tubes can be placed without anesthesia and without sedation
in most patients. E-tubes can be placed with a brief anesthetic event or can be com-
bined with other procedures requiring anesthesia. Radiographs are arguably the
safest way to ensure placement is correct (Fig. 6), although many hospitals establish
their own safety protocols. The nutritional make-up of voluntary oral or supplemental
diets will vary depending on the underlying disease process and specific needs of the
patient.

TREATMENT COMPLICATIONS

Severe hypersensitivity reactions have been reported following treatment with human serum
albumin. Caution should be used when administering it or other transfusion products. Risk of a
delayed reaction is also potentially high. Milder reactions are also common.

Because albumin is an important carrier for many different types of drugs, some treat-
ments needed to address the underlying disease process may be affected by altered
pharmacokinetics and pharmacodynamics. For example, nonsteroidal anti-
inflammatory drugs (NSAIDs) are commonly 99% protein bound, which means that
if there is not enough albumin to bind the drug and only 98% is bound to albumin,
the free drug concentration will have doubled. This may be offset by increased renal
or hepatic clearance of the drug but could be a concern for patients with organ
 Treating Hypoalbuminemia 7

Fig. 5. NG feeding tube using commercially available feeding tube.

dysfunction. Even drugs that are not so highly bound to albumin may have altered drug
concentrations.

EVALUATION OF OUTCOME AND LONG-TERM RECOMMENDATIONS

Many diseases associated with hypoalbuminemia are treatable and, once the condi-
tion is controlled, serum albumin concentration is expected to return to normal. For
those conditions that are chronic and may be associated with long-term hypoalbumi-
nemia, including inflammatory bowel disease and familial glomerulopathy, aggressive
management of the condition is paramount. In refractory or end-stage cases, thera-
pies directed at symptom management may include albumin supplementation; how-
ever, no studies are available to prove efficacy. Clinicians should carefully weigh the
pros and cons of specific therapy to address complications of hypoalbuminemia,
and discuss the potential adverse effects and costs with pet owners.

Fig. 6. Right lateral radiograph showing positioning of an E-tube. Note the end of the tube
located caudal to the carina but proximal to the diaphragm. An endotracheal tube is in
place within the trachea.
8 Conner

SUMMARY

Although hypoalbuminemia is common in critically ill patients, clinicians should not

dwell on the measured serum albumin concentration or focus on correcting it. If a pa-
tient does not have clinical signs directly attributable to low serum albumin concentra-
tion (eg, edema, effusion), treatment with albumin-containing products is not likely to
be beneficial and may be harmful. Even when these clinical signs are present, it is not
clear that correcting serum albumin concentration will lead to improved outcomes, so
clinicians should carefully consider all treatment options. Although studies have not
clearly linked nutritional supplementation with improved serum albumin concentra-
tions, there is growing evidence that early provision of nutrition can lead to improved
outcomes in various diseases.

SUPPLEMENTARY DATA

Supplementary data related to this article can be found at http://dx.doi.org/10.1016/j.

cvsm.2016.09.009.

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 Treating Hypoalbuminemia 9

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