HUMAN ALBUMIN

SOLUTION GUIDE
July 2021
 BACKGROUND
Albumine: protein by the liver, circulates in plasma, distributed
only in the intravascular sapce. Is used in different clinical
setting to replace albumine deficiency caused by different
mechanisms:
 Decrease synthesis (liver cirrhosis)
 Increase loss (urinary loss, burn, GIT loss)
 Decrease intake (malnutrition)
 FUNCTION
1. Vascular function:
• Rugulating the osmotic pressure of plasma +++
• Maintaining micro vascular integrity:
 Direct protective: prevents apoptosis in cultured endothelial cells.
 Albumine is the most important source of sulfhydryl groups in the
circulation. Nitric oxide (NO) binds to these sulfhydryl to form a stable S-
nitrosothiol group, and is thus protected from repid degradation.
 Albumine slowed the onset and reduced the maximal intensity of the
vasodilatory response to NO. It is possible that albumine has a role in the
modulation of vascular tone in different vascular beds.
 FUNCTION
2. Transport:
• Binding of substances to albumine: carrier of variouse
hydrophobic substance in the blood such as:
 Medium-sized hydrophobic organic anions: long-chain fatty acids,
bilirubin, hematin.
 Metals: Ca2+, Magnesium, zinc, copper, and trace elements.
 Hormones: thyroxine, steroid hormones.
 Some drugs: salicylate (aspirine), phenytoin, digoxin, ceftriaxone,
lorazepam, diazepam, valproic acid (DPK), and warfarin.
 DRUG DESCRIPTION
Phenytoin Extensively bound to the albumin. For critically-ill
patients with hypoalbuminemia that are being treated
with phenytoin, there are dosing adjustments
available.
The Sheiner-Tozer equation assuming renal function is
not impaired.
Calcium Fluctuations in serum albumin will lead to variations
in measure Ca++. However, the perceived change in
Ca++ is not indicative of the actual concentration.
Total serum Ca++ will increase 0.8mg/dL for every
1g/dL rise in serum albumin, and will fall 0.8mg/dL for
every 1g/dL fall in serum albumin.
Salicylate In hypoalbuminemia, the ratio of free salicylate to
bound salicylate rises and the free salicylate might be
more active and thus more hepatotoxic even at
relatively low total serum salicylate levels.
Valproic Binds to albumin, with a dose-dependent free fraction
Acid of 10% to 30% that maybe higher in elderly patients.
The unbound free fraction increases in a linear fashion
as the dose and the serum concentration of VPA
increases.
CORRECTIVE ACTION
Assuming renal function is not impaired then Corrected
Phenytoin (mg/L) = Observed Phenytoin (mg/L) / (0.2 x
Albumin [g/dL] + 0.1).
If CrCl < 20mL/min then Corrected Phenytoin = Observed
Phenytoin Level / (0.1 x Albumin + 0.1).
There is a corrected calcium adjustment calculated using
the following formular: Corrected Calcium (mg/dL) =
measured total serum calcium (mg/dL) + 0.8 x [4 – serum
albumin (g/dL)].
In all patients with hypoalbuminemia of less then 3.5g/dL,
close monitoring the SGOT is advisable, especially if the
level of total serum Salicylate is 15mg/dL or higher.
The manufacturer recommends using caution when
interpreting total levels in patients with hepatic disease and
decreased albumin but provides no specific dosing
recommendations. Thus, when a patient has
hypoalbuminemia , Valproic Acid dosing should be based
on the free Valproic Acid level and the clinical picture.
 FUNCTION
3. Metabolic:
• Acid-base function:
 The presence of many charged residues on the albumin molecule and the
relative abundance of albumin in plasma mean that it can act as an effective
plasma buffer.
 At physiological pH, albumin has a net charge of negative 19. It is responsible
for about half of the normal anion gap. A reduction in plasma protein
concentration causes metabolic alkalosis.
 A decrease 1g/dL of serum albumin may increase standard bicarbonate by
3.4mmol/L, and reduce the anion gap by 3mmol/L.
 FUNCTION
3. Metabolic:
• Antioxydant function:
 It is involved in the scavenging of oxygen free radicals, which have been
implicated in the pathogenesis of the inflammatory disease. Physiologycal of
solutions of human serum Alb have been shown to inhibit the production of
oxygen free radicals by polymorph nuclear leukocytes. This may be related
to the abundance of sulfhydryl (-SH) groups on the Alb molecule.
• Anticoagulant effects:
 It has effects on blood coagulation. It seems to exert a heparin-like action
perhaps related to a similarity in the structures of the 2 molecules. Heparin
has negatively charged sulphate groups that binds to positively charged
groups on antithrombin III, thus exerting an anticoagulant effect. Serum Alb
has many negatively charged groups.
 PHARMACOLOGIC CATEGORY
• Blood produce derivative
• Plasma volume expander
• Colloid fluid
 MECHANISM OF ACTION
• Albumin is a highly soluble, globular protein, normally present in the
blood and constitutes 50% to 60% of the plasma protein, and 80% to
85% of the oncotic pressure.
• The albumin concentration in plasma in healthy humans ranges
between 33-52g/L (3.3-5.2g/dL).
• It is synthesized exclusively in the liver. The normal rate of albumin
synthesis is 0.2g/kg body weight / day.
 MECHANISM OF ACTION
• The distribution of albumin is adequately described by a two-
compartment model where about 40% is taken up by the
intravascular and 60% by the extravascular space.
• Exogenously administered albumin increase the oncotic pressure of
the intravascular system, pulling fluids from the interstitial space,
thereby decreasing edema and increasing the circulating blood
volume => reduces the concentration and viscosity of blood, and also
maintains cardiac output in shock.
 PHARMACOKINETICS
• It has a half-life of 15-20 days in the circulation, with a turn over of
approximately 15g/day.
• The balance between synthesis and breakdown is normally achieved
by feedback regulation.
• Elimination is predominantly intracellular and due to lysosome
proteases.
• In healthy subjects, less than 10% of infused albumin leaves the
intravascular compartment during the first 2h following infusion.
There is considerable individual variation in the effect on the plasma
volume.
 PHARMACOKINETICS
• In some patients the plasma volume can remain increased for some
hours. However, in critically ill patients, albumin can leak out of the
vascular space in substantial amounts at an unpredictable rate.
• The degree and duration of volume expansion depend on initial blood
volume. When administered to patients with diminished blood
volume, the effect of infused albumin may last for many hours,
however, the duration is much shorter in patients with normal blood
volume.
 CONCENTRATION
• Albumin (human) 20% is available in 50ml vial that contains 10g of
human albumin.
• In general, 5% albumin is intended to restore plasma volume while
the 20% albumin will raise oncotic pressure.
 PREPARATION
• Albumin solutions must not be diluted with water for injections as this
may cause hemolysis in recipients.
• Usual diluents are NS and D5W.
• For albumin 5% preparation: add a bottle of albumin 20% (50ml) to
150ml of NS to get 200ml solution of 5% albumin
[(10g/200ml) x 100 = 5%).
 ADMINISTRATION
1. Route:
• Intravenous route only.
2. Instructions:
• If large volumes are administered, the product should be warmed to room
temporature before use.
• Do not use with ethanol or protein hydrolysates, precipitation may form
hypoproteinemia.
3. Dose:
• According to the indication.
4. Rate:
• Infusion over 30-120min, not to exceed 5-10mL/min for 5% solution, 2mL/min
for 20% solution. Rapid infusion => vascular overload.
 ADMINISTRATION
5. Warnings and precaustions:
• The colloid-osmotic effect of human alb 200g/L is approximately 4 times that
of blood plasma. Therefore, when concentrated alb is administered, care
must be taken to assure adequate hydration of the patient. Patients should be
monitored carefully to guard against circulatory overload and hyper
hydration.
• Hypervolemia may occur if the dossage and infusion rate are not adjusted to
the patient’s circulatory situation. At the first clinical signs of cardiovasular
overload (headache, dyspnea, jugular vein congestion), or increase blood
pressure, raised venous pressure and pulmonary edema, the infusion is to be
stopped immediately.
 ADMINISTRATION
6. Monitoring Parameters:
• Monitor electrolytes
• Hb/Ht
• Urine output
• Monitor hemodynamic parameters (BP, HR, CVP, pulmonary artery occlusion
pressure and colloid-oncotic pressure).
 ADMINISTRATION
7. Advanced Practitioners Physical Assessment/Monitoring:
• Assess patient for hepatic or renal failure. Patient should be monitered closely
for pulmonary edema and cardiac failure (assess vital signs and central
venous pressure) during administration.
• Monitor frequently for hypovolemia or fluid overload.
• If fever, tachycardia, hypotension, or dyspnea occurs, infusion should be
stopped and prescriber notified.
 TRANSFUSION REACTION (Actual or
Suspected)
The following are common signs of a transfusion reaction in first 1-2
hours:
• Increase pulse
• Hives or itching / allergic reaction
• Temporature elevetion > 1℃
• Hypo/hypertension
• Chills
• Dyspnea / hypoxemia
 TRANSFUSION REACTION (Actual or
Suspected)
Management:
• STOP TRANSFUSION immediately
• Obtain vital signs (T, HR, BP, RR, SpO2) and document
• Appropriate treatment initiated (IV fluids for hypotension and IM adrenaline
for anaphylaxis)
• In case of shock, standard medical treatment for shock should be
implemented
• Report ADVERSE DRUG REACTION.