Clinical Information

Transfus Med Hemother 2016;43:223–232 Received: January 12, 2016

DOI: 10.1159/000446043 Accepted: January 12, 2016
Published online: May 3, 2016

Cross-Sectional Guidelines for Therapy with Blood

Components and Plasma Derivatives: Chapter 5 Human
Albumin – Revised
Executive Committee of the German Medical Association on the Recommendation of the
Scientific Advisory Board

Summary 5.2 Active Constituents

Chapter 5 ‘Human Albumin’ that was suspended on
January 10, 2011 has been completed and updated in Human albumin solutions are manufactured as hypooncotic
the present version. (4%), isooncotic (5%) or hyperoncotic (20% or 25%) infusion solu-
tions. The effective component is human albumin with a molecular
weight of around 66 kDa consisting of 584 amino acids of known
sequence. Albumin preparations intended for clinical use contain
5 Human Albumin monomers and may contain also dimers and, in small amounts,
polymers of albumin. Because of variable electrolyte concentra-
5.1 Preparation tions contained in albumin preparations, it is required to monitor
the balance of water and electrolyte, especially when administering
Human albumin is prepared from human pool plasma by large amounts. According to the European Pharmacopoeia, a max-
alcoholic precipitation [15]. For pathogen inactivation albumin is imum content of 10% polymers and aggregates is permitted.
pasteurized for at least 10 h at +60 ° C (see also European Pharma-
 

copoeia).
5.3 Physiological Properties and Function
5.1.1 Quality Criteria
Human albumin solutions for transfusion are obtained from The reference concentration of albumin in plasma ranges be-
human plasma proteins as sterile preparations which, according to tween 33 and 52 g/l. Albumin is synthesized exclusively in the liver.
the monograph ‘Human Albumin Solutions’ of the European The normal rate of albumin synthesis is approximately 0.2 g/kg
Pharmacopoeia, must contain a minimum of 95% albumin. Aside body weight/day. Extravascular colloid osmotic pressure (COP) in
from human albumin, preparations currently available have a so- the liver is considered to be the factor regulating albumin synthe-
dium concentration between 87 and 160 mmol/l and a potassium sis. Albumin synthesis may be suppressed by an exogenous supply
concentration below 2 mmol/l. Up to 19.3 mmol/l sodium oc- of substances affecting COP, i.e. natural or synthetic colloids [18].
tanoate and up to 17.4 mmol/l acetyltryptophan are added as stabi- A lasting normalization in albumin concentration can only be
lizers. All albumin preparations currently available contain less achieved by suitable nutrition therapy.
than 200 μg/l of aluminum. Under physiological conditions a steady state exists between al-
Albumin solutions do not contain isoagglutinins or blood group bumin synthesis and metabolism. The amount of albumin metabo-
substances and can thus be administered independent of the recipi- lized daily is proportional to the plasma concentration, i.e. a fixed
ent’s blood group. They do not contain oxygen carriers, coagula- percentage of approximately 10% of plasma albumin content is
tion factors or antibodies. Based on the manufacturing process and metabolized per day [61, 65]. Its half-life changes inversely propor-
the pathogen inactivation involved, albumin preparations are con- tionately to the plasma albumin concentration; i.e., a decreased al-
sidered to carry no risk of transmitting infections. bumin content results in increasing its half-life, whereas increasing
albumin concentrations cause the metabolic rate to increase by up
to 50%. The neonatal Fc receptor FcRn (also called Brambell recep-

© 2016 S. Karger GmbH, Freiburg Bundesärztekammer

1660–3796/16/0433–0223$39.50/0 Dezernat 6 – Wissenschaft, Forschung und Ethik
Fax +49 761 4 52 07 14 Herbert-Lewin-Platz 1, 10623 Berlin, Germany
[email protected] Accessible online at: [email protected]
www.karger.com www.karger.com/tmh
tor) is responsible for this homeostatic regulation of albumin as 5.4 Storage, Shelf Life, Packaging Sizes
well as for that of serum IgG, both of which have the longest half-
life of all serum proteins with 19–23 days [9, 52]. It is a membrane Human albumin preparations can be stored protected from
molecule, similar to the MHC class I molecule, on endothelial and light and at room temperature, although storage temperature for
intestinal epithelium cells that binds human albumin and IgG at human albumin solutions should not exceed 25 ° C. Therefore, it is
 

different positions, continuously taking them up into pinocytotic not possible to administer pre-warmed solutions.
vesicles in order to protect both serum proteins from rapid degra- Human albumin solutions can be administered by a peripheral
dation [72]. The pinocytotic vesicles containing albumin bound to or central venous line and are well tolerated. No daily maximum
FcRn are released either into the extravascular space through tran- permissible dose is specified for human albumin. However, con-
scytosis or back into the circulation [4]. Because of the limited centration and dose should be adjusted to the individual needs of
binding capacity of FcRn, the unbound amount of molecules in- the patient. It is licensed in Germany as 4%, 5%, 20% or 25% solu-
creases with increasing serum concentration of albumin, and ac- tions in ampoules, polyethylene bags, or glass bottles.
cordingly their catabolic rate, increases exponentially [51].
The distribution of albumin in the human body is adequately
described by a two-compartment model where about 40% is taken 5.5 Indications
up by the intravascular and about 60% by the extravascular space
[61, 73, 83]. The balance between plasma and interstitial space is Clinical application of albumin derives from its physiological
established at varying rates with respect to the two subcompart- functions. Possible areas of application are:
ments of the extravascular albumin pool [103]. The total exchange (1) hypovolemia,
rate between intra- and extravascular volume amounts to approxi- (2) hypoalbuminemia,
mately 5% of the intravascular albumin content per hour (so-called (3) other areas of application.
transcapillary escape rate). The transcapillary escape rate of albu-
min is increased in arterial hypertension, myxedema, burns, liver 5.5.1 Therapy of Hypovolemia
cirrhosis and diabetic microangiopathy [74, 75]. Possible areas of application of human albumin for the purpose
The physiological function of albumin can be summarized as of volume replacement are presented below, according to the re-
follows: spective specific underlying circumstances.
(1) volume effect (colloid oncotic effect),
(2) transport function. 5.5.1.1 Acute Volume Replacement during the Perioperative
Phase
Volume Effect (COP) There are three Cochrane analyses [10, 76, 113] and two system-
Albumin has a high capacity for binding water (approximately atic reviews [46, 110] on the application of albumin as volume re-
18 ml/g), an intravasal residence time of approximately 4 h presup- placement during the perioperative phase, investigating the effect
posing physiological capillary permeability [103] as well as an in of albumin as compared to a crystalloid or any other colloid vol-
vivo half-life of approximately 18–21 days [61, 65, 103]. At equal ume substitute. Regarding mortality neither benefit nor harm was
concentrations the oncotic effect of albumin is about 2.5 times shown when using human albumin.
greater than that of globulins which have an average molecular For the application of hyperoncotic albumin (20%), a benefit re-
weight of around 170 kDa [53]. Although albumin comprises only garding morbidity (renal function, formation of gastrointestinal
about 50–60% of the total protein content of plasma, it is responsi- edema) was reported in one review [46].
ble for about 80% of intravascular COP.
• Human albumin is not recommended as substitute in hypovole-
Transport Function mia or for increased hemodynamic stability of adult patients in
Because of its high net charge albumin possesses excellent bind- the perioperative phase, unless therapeutic alternatives have
ing capacities, among other things for water, calcium, sodium and been exhausted (1 B).
trace elements. Albumin is also an important transport protein for
fatty acids, bilirubin and hormones as well as for many drugs. Al- 5.5.1.2 Acute Volume Replacement in Intensive-Care Patients
though these transport qualities are of physiological and pharma- without Sepsis
cological importance, there is at best a reasonable therapeutic indi- For an assessment of using human albumin as substitute in hy-
cation for administering HA for binding of bilirubin and thus re- povolemia or for hemodynamic stabilization of adult nonseptic in-
duction of the need for phototherapy and exchange transfusion in tensive-care patients, the following references were incorporated in
neonates with severe hyperbilirubinemia [45, 66, 96]. the evaluation: [14, 19, 24, 25, 28, 36, 56, 78, 81, 82, 93, 95, 104, 105,
109, 110, 112]. The meta-analyses of the Cochrane Collaboration
[81, 82] are referred to in the following.
The consensus statement of the ESICM task force of 2012 [81]
and the meta-analysis of the Cochrane Collaboration of 2011 [82]

224 Transfus Med Hemother 2016;43:223–232 Executive Committee of the German Medical 

Association on the Recommendation of the 
Scientific Advisory Board et al.
show no benefit regarding mortality for the therapy using human group analysis of trauma patients enrolled in the SAFE trial are re-
albumin as compared to using crystalloid or colloid solutions. ferred to for assessment [27].
Neither the S3-Guideline nor the meta-analysis of the Cochrane
• Human albumin is not recommended as substitute in hypo- Collaboration of 2011 [82] showed a survival benefit for trauma pa-
volemia or for hemodynamic stabilization of adult nonseptic in- tients treated with albumin (consistent results based on three pro-
tensive-care patients, unless therapeutic alternatives have been spective randomized trauma trials and one quasi-randomized trial).
exhausted (1 A). This is supported by the fact that the mortality rate of the
trauma patients enrolled in the SAFE trial and treated with albu-
5.5.1.3 Acute Volume Replacement in Intensive-Care Patients min for hemodynamic stabilization tended to increase (13.6 vs.
with Sepsis 10.0%; p = 0.06). In this trial hypooncotic human albumin (4%)
The German S2k guideline of 2010 [86] recommends using al- was used that is not commonly used in Germany. Systematic re-
bumin as volume substitute in patients with severe sepsis or septic views [27, 32, 95, 100] also consistently find no survival benefit for
shock as an expert recommendation. The guideline of the Surviv- patients treated with albumin. However, the systematic reviews
ing Sepsis Campaign of 2013 gives a very weak recommendation (2 and meta-analyses by Groeneveld et al. [36], Heier et al. [43], Vin-
C) for using human albumin in patients with severe sepsis or septic cent et al. [110], and Wilkes et al. [115] did not strictly discriminate
shock who continue to require infusions to maintain adequate in group allocation between trauma and surgical patients; there-
mean arterial pressure [20]. Recent meta-analyses have reached di- fore, a bias cannot be ruled out in the end.
verging results: Delaney et al. [19] show a benefit for the use of al-
bumin for hemodynamic stabilization of patients with sepsis (OR • The administration of human albumin for increased hemody-
0.82; 95% CI 0.67–1.0; p = 0.047). Two recently published prospec- namic stability of patients with traumatic injury is not recom-
tive randomized trials showed no benefit regarding lower mortality mended (1 B).
for patients treated with albumin compared to patients treated with
crystalloid solutions [5, 11]. 5.5.1.6 Acute Volume Replacement in Pregnant Women
Because of the ambiguous data situation [5, 19, 20, 86] on There are only few reports on any kind of volume substitution
whether the treatment of patients with sepsis, severe sepsis, and (including human albumin) in pregnant women. Severe hypovolemia
septic shock with human albumin for hemodynamic stabilization is during pregnancy (e.g. in the context of surgical intervention) is a
superior to that using other infusion solutions, no recommenda- possible indication for albumin administration. There are hardly any
tion is given here. data on albumin use for correcting hypovolemia during delivery (e.g.
during Cesarean delivery) and for preventing hypotension in con-
5.5.1.4 Acute Volume Replacement in Burn Patients nection with performing a spinal anesthesia [16, 63]. In comparison,
Regarding the use of albumin and other colloid solutions for administration of synthetic colloid volume substitutes or crystalloid
acute volume replacement in severely burned patients, several sys- solutions is better documented in the literature [7, 16, 55]. In case
tematic reviews from the Cochrane database as well as randomized synthetic colloids are contraindicated or the maximum limit of a col-
clinical trials show no effect on the mortality rate compared to loid dose has been exceeded, albumin can be considered.
treatment with crystalloid solutions [10, 42, 76, 82, 110].
• The administration of human albumin for volume replacement
• The administration of human albumin for increased hemody- in the context of a Cesarean delivery is not recommended (2 C).
namic stability of burn patients is not recommended during the • The administration of human albumin for preventing hypoten-
first 24 h (1 A). sion during spinal anesthesia in the context of a Cesarean deliv-
ery is not recommended (2 B).
Based on published data, the relevance of using albumin for
long-term treatment in burn patients as substitute in hypoalbu- 5.5.1.7 Volume Replacement in Cardiac Surgery
minemia cannot be assessed conclusively [42, 110]. The prophylac- Regarding the correction of hypovolemia and for hemodynamic
tic use of albumin for maintaining physiological serum albumin stabilization in cardiac surgery as well as for pump priming of the
levels showed no effect on mortality or morbidity [34, 35, 49]. cardiopulmonary bypass, the S3-Guideline for Intensive Care in
Cardiac Surgery Patients ‘Hemodynamic Monitoring and Cardio-
• In the further course of treatment of burn patients administra- vascular Circulation’ [89] was incorporated in the evaluation, along
tion of human albumin may be considered (2 B). with the following individual studies: [33, 75 99]. All of these inves-
tigated the effect of albumin- versus non-albumin-based priming of
5.5.1.5 Acute Volume Replacement in Trauma Patients the cardiopulmonary bypass on the outcome of cardiac surgery pa-
Along with the S3-Guideline on Treatment of Patients with Se- tients, like decrease of platelets, weight gain, blood loss etc., whereas
vere and Multiple Injuries [88], the following publications have mortality was only considered in the analysis by Himpe [44].
been included in the assessment of hemodynamic stabilization of The S3-Guideline for Intensive Care in Cardiac Surgery Patients
trauma patients: [27, 32, 66, 95, 100]. In addition, data of a sub- recommends using synthetic colloid solutions as well as human al-

Cross-Sectional Guidelines for Therapy with Transfus Med Hemother 2016;43:223–232 225
Blood Components and Plasma Derivatives:
Chapter 5 Human Albumin – Revised
bumin solutions for hemodynamic stabilization even though no when used for perioperative volume replacement in neonates and
better outcome in patients has been demonstrated for human albu- older children [41, 102].
min (grade of evidence D, grade of recommendation 0). A signifi- In hypotensive neonates the effects of human albumin versus
cant benefit has been shown when using human albumin (4–5%) those of synthetic colloid or crystalloid solutions are inconsistent
for pump priming of the cardiopulmonary bypass (reduced drop in [57, 59, 71]. In dehydrated neonates with enteritis, there is no ben-
platelets and lower blood loss; one study reported a lower mortality efit in using human albumin compared to isotonic saline [40].
rate). Because of the date of the studies cited this usually concerned No benefit has been shown when using human albumin in infants
hydroxyethyl starch (HES) preparations with higher molecular and older children with severe infections or septic shock [2, 60].
weight which were compared with human albumin [44, 85, 114]. The use of human albumin in preterm neonates with hypoalbu-
In a recent meta-analysis, also including HES preparations with minemia [47] and in neonate jaundice [66] also remains controver-
lower molecular weight, the use of synthetic colloid solutions re- sial. There is a need for further trials covering different age brack-
sulted in increased blood loss and a higher rate of reoperation and ets to improve the data situation regarding therapeutic success and
transfusion [69]. adverse effects [47].

• Human albumin solution (5%) can be used for correction of hy- • The use of human albumin for volume replacement in preterm
povolemia and for hemodynamic stabilization in cardiac surgery and term neonates as well as in older children cannot be assessed
as well as for pump priming of the cardiopulmonary bypass (2 B). conclusively in comparison to other crystalloid and colloid solu-
tions, and therefore human albumin should only be used if ther-
5.5.1.8 Acute Volume Replacement in Patients with Risk of apeutic alternatives have been exhausted (2 A).
Bleeding and Patients with Manifest Bleeding due to
Coagulopathy 5.5.1.11 Volume Replacement in Therapeutic Plasmapheresis
In patients with altered coagulation (e.g. polytrauma, patients Administration of human albumin is indicated for volume re-
with sepsis, or in patients in whom coagulation disorders are an- placement with albumin in therapeutic plasmapheresis. However,
ticipated, e.g. cardiac surgery patients with extracorporeal circula- there are no large comparative trials involving other substances for
tion) the application of albumin is possible since no substance-spe- volume replacement that would document a benefit [54, 58, 64].
cific alterations regarding coagulation have been reported for
human albumin use. However, the administration of large amounts • Human albumin could be administered in order to balance
of albumin can also cause a dilutional coagulopathy [116]. volume withdrawal in plasmapheresis (2 C).

5.5.1.9 Acute Volume Replacement in Hepatic Surgery (e.g. 5.5.2 Therapy of Hypoalbuminemia
Liver Transplantation) Albumin is the protein with the highest concentration in plasma
Patients undergoing hepatic surgery (including transplantation) and primarily responsible for maintaining the COP. Therefore
frequently have previous liver damage possibly including a coagula- normalization or increase of COP has been considered as a possi-
tion disorder. Additional coagulopathy occurs during the anhepatic ble indication for administration of albumin solutions.
and postreperfusion stages of liver transplantation. The main cause of
this is assumed to be a rapidly increasing plasma level of the tissue- 5.5.2.1 Pathophysiology
type plasminogen activator which is caused by lacking hepatic clear- Compensation of hypoalbuminemia is considered to be an es-
ance on the one hand and by release from ischemically damaged en- sential indication for administration especially of highly concen-
dothelium of the donor liver on the other hand [22, 50, 77]. Coagu- trated albumin preparations. In human plasma albumin concentra-
lopathy may be aggravated by intraoperative hypothermia, hypocalce- tion ranges around 33–52 g/l and amounts to approximately 60% of
mia, and thrombocytopenia [37]. Accordingly, this group of patients the total plasma proteins (60–80 g/l). Around 30–40% of the re-
is especially at risk during further compromise of hemostasis. placeable albumin pool is located in the plasma compartment (ap-
Large-scale prospective trials comparing various strategies of proximately 120 g in around 3 l of plasma volume) [39]. Concentra-
volume substitution in hepatic surgery are lacking. There is also a tion in the tissue spaces is considerably lower (approximately 14 g/l;
lack of unambiguous data from controlled, randomized trials in- 160 g in 10–12 l of interstitial volume). Under normal conditions
vestigating the significance of substitution by albumin in major the liver produces around 0.2 g/kg body weight/day albumin, cor-
liver surgery, e.g. of extended liver tumors. Thus the present data responding to around 15 g/day in a man weighing 70 kg. The fore-
situation does not allow any further assessment of using human al- most factor in monitoring the production of albumin is apparently
bumin for volume replacement in hepatic surgery. COP in the region of the extravascular space of the liver. In sepsis,
infection, trauma or mental strain, the albumin level decreases (ap-
5.5.1.10 Acute Volume Replacement in Neonates and Older proximately 10–15 g/l during 3–7 days). Albumin synthesis is also
Children reduced under these circumstances, but with a half-life of around
While the number of studies is limited, the effects of human al- 20 days this cannot explain the rapid drop in serum albumin con-
bumin versus those of synthetic colloid solutions are comparable centration. The most significant cause of the reduced albumin level

226 Transfus Med Hemother 2016;43:223–232 Executive Committee of the German Medical 

Association on the Recommendation of the 
Scientific Advisory Board et al.
is apparently redistribution and/or catabolism. Particularly in pa- • Human albumin shall not be used exclusively for compensating
tients with sepsis, an increased vascular permeability (capillary leak) hypoalbuminemia in intensive-care patients without any addi-
plays an important role in developing hypoalbuminemia [29]. tional indication (1 B).
Following transfusion of human albumin, its distribution within
the extravascular compartment is complete after 7–10 days. Ap- 5.5.2.3 Therapy of Hypoalbuminemia in Undernutrition,
proximately 10% of transfused albumin migrates from the intra- Malnutrition and Enteropathies/Malabsorption Syndrome
vascular space within 2 h [75], and 75% of transfused albumin is In clinical practice no benefit is shown for the administration of
distributed into the extravascular space after 2 days [39]. In par- albumin in undernutrition, malnutrition, and enteropathies/mal-
ticular clinical pictures (e.g. in sepsis) this distribution process absorption syndrome. Because of the composition of amino acids
happens far more rapidly. In this connection capillary permeability with a low ratio of some essential amino acids (tryptophan, me-
of albumin can increase 13-fold compared to its normal level [13]. thionine and isoleucine) as well as its long biological half-life of
around 19–21 days, albumin is principally unsuitable for paren-
5.5.2.2 Therapy of Hypoalbuminemia in Intensive-Care Patients teral nutrition [17, 67, 118].
Hypoalbuminemia is a predictor of increased mortality and
morbidity [38, 109]. However, it has not been investigated compre- • Administration of human albumin in undernutrition, malnutri-
hensively or documented well whether compensation of hypoalbu- tion, enteropathies and malabsorption syndrome shall not be
minemia shows benefits regarding morbidity or mortality com- given (1 B).
pared to an expectant treatment. At present, due to an insufficient
data situation, no answer is possible regarding any benefit on the 5.5.2.4 Therapy of Hypoalbuminemia in Liver Cirrhosis
outcome, particularly for infants [47]. As an individual parameter, hypoalbuminemia per se is no con-
For compensation of hypoalbuminemia in adult intensive-care firmed indication for substitution in patients with established liver
patients the data situation is more substantial, although any assess- cirrhosis and ascites.
ment is doubtful because of the small group size in the trials in- Three clinical situations are described below where transfusion
cluded in the meta-analysis [115]. None of the four trials included with human albumin as volume replacement or an albumin substi-
could show a survival benefit for the patients treated with albumin, tution can be indicated:
with groups of between 15 and 116 patients (184 of which received (1) spontaneous bacterial peritonitis
albumin and 173 of which were in the control group). The com- (2) hepatorenal syndrome
bined relative risk for death during the observation period was 1.59 (3) post paracentesis.
(95% CI 0.91–2.78) to the disfavor of albumin.
Another meta-analysis of randomized clinical trials focusing on 5.5.2.4.1 Spontaneous Bacterial Peritonitis
the morbidity endpoint arrives at a different assessment from the one Even without sepsis, spontaneous bacterial peritonitis (SBP) can
above regarding the use of human albumin in children and adults. lead to an impaired circulatory function and end in a type 1 hepatore-
Complications (combined endpoint: one or more complications in a nal syndrome (HRS) with a high mortality rate. A single randomized
patient) tended to occur less frequently after application of human controlled trial involving patients with SBP and simultaneously ele-
albumin, with an OR of 0.81 (95% CI 0.41–1.60) [109]. Even if focus- vated levels of serum bilirubin and creatinine showed that patients
ing on randomized trials of adult patients who either received albu- developed type 1 HRS less frequently (10 vs. 30%) if they received
min in the context of parenteral nutrition or because of lowered lev- human albumin in addition to their antibiotics therapy. The dose was
els of albumin in plasma, this tendency towards a lower rate of com- 1.5 g/kg body weight at the time of SBP diagnosis (day 1) and 1 g/kg
plications, also in another systematic review by the same authors body weight on day 3 after SBP diagnosis. Particularly patients with
[110], could be regarded as weak indication of a beneficial effect in serum bilirubin levels > 4 mg/dl and creatinine > 1 mg/dl profited
individual cases and based on an underlying pathology. However, from human albumin infusions [101]. In contrast toHES, albumin
these results must be interpreted with utmost caution in view of the seems to improve circulatory function [26]. A meta-analysis showed
considerable heterogeneity of data, given the overall small group that the incidence of renal impairment could be significantly lowered
sizes (15–116 patients per group), a small total number of patients for by the use of albumin, and the mortality rate was significantly im-
each cohort analyzed (199 patients received albumin and 188 patients proved. This effect has also been proven in patients with a serum bili-
were in the control groups) as well as the quasi-retrospective ap- rubin level < 4 mg/dl and normal levels of creatinine [23, 91].
proach (classification of the occurring complications) with an OR of
0.92 (95% CI 0.77–1.08). For the time being, on no account does this • Administration of human albumin (1.5 g/kg body weight on day
permit to draw the conclusion that it is generally recommended to 1 and 1 g/kg body weight on day 3) shall be carried out in patients
use human albumin for preventing complications. with liver cirrhosis and SBP (1 B).
Moreover, it is doubtful which albumin level can still be consid-
ered to be tolerable and whether there is a ‘critical’ threshold in 5.5.2.4.2 Hepatorenal Syndrome
hypoalbuminemia starting from which there is a benefit in admin- The HRS is defined as renal failure in patients with advanced
istering human albumin. liver disease without evidence of a renal cause [6]. HRS is subdi-

Cross-Sectional Guidelines for Therapy with Transfus Med Hemother 2016;43:223–232 227
Blood Components and Plasma Derivatives:
Chapter 5 Human Albumin – Revised
vided into a rapidly progressing type 1 and type 2 with moderate ume replacement substances after paracentesis < 5 l. There are only
renal impairment. Type 2 HRS can turn into type 1 HRS. data on patient subgroups from other trials. However, the patient
Various randomized controlled and partly blinded trials have numbers are very small, and the trials were not designed for these
investigated albumin alone and in combination with terlipressin. subgroups [31, 100].
Most patients had type 1 HRS. In the treatment arm terlipressin + Based on the trial data available, no unambiguous recommen-
albumin, all trials showed a significant improvement of renal func- dation can be given. The S3-guidelines do not consider the use of
tion and short-term survival. In contrast, infusion of albumin albumin to be indicated and give no recommendation [87]. In case
alone only rarely led to an improvement of renal function [62, 70, volume substitution using colloid solutions is indicated, the EASL
92, 99]. Two meta-analyses reviewed the data of these reports and guidelines recommend using albumin rather than synthetic col-
confirmed the results [33, 90]. loids because the latter may have adverse effects on coagulation
Regarding dosage, the S3-guidelines recommend an albumin and renal function [23].
dose of 1 g/kg body weight (maximum 100 g) on day 1, followed by
20–40 g/day, and a terlipressin dose of 2–4 mg/day up to a maxi- • Following paracentesis with a volume of ascitic fluid ˰ 5 l, vol-
mum of 8–12 mg/day. The European guidelines give no dosage ume replacement with human albumin (6–8 g/l of ascitic fluid)
recommendation for albumin and for terlipressin 1 mg as bolus shall be performed (1 A).
every 4–6 h up to a maximum of 2 mg every 4 h. The treatment
should be continued for at least 3 days and for patients without There are no large randomized controlled trials investigating
decrease in serum creatinine for up to 14 days [23, 87]. the long-term effect of albumin in cirrhotic patients with the first
There are fewer data on the therapy of type 2 HRS. The combi- occurrence of ascites. There are two small randomized trials com-
nation of terlipressin and albumin is effective in 60–70% of type 2 paring albumin in combination with diuretics versus diuretics
HRS patients. However, clinical benefit is not proven unambigu- alone [1, 30]. One of these trials demonstrated a benefit in the al-
ously. bumin group regarding hospital stay, a less frequent recurrence of
There are insufficient data on other vasoconstrictors that were ascites and lower rates of hospital readmission due to ascites [30].
investigated for therapy of HRS or compared to terlipressin. Two The other trial reported also a lower mortality rate in the albumin
randomized, non-blinded trials with low patient numbers (N = group [1]. Another trial that admittedly involved only 13 patients
22/40) suggested that noradrenaline might have an equivalent ther- could showed no benefit [12]. A retrospective trial investigating 19
apeutic effectiveness in treating HRS [3, 97]. The lack of large ran- patients perceived a benefit in albumin therapy to maintain diure-
domized controlled trials makes an unambiguous recommenda- sis in cirrhotic patients with contraindications against a transjugu-
tion impossible. lar intrahepatic portosystemic shunt [107].
It is not indicated to administer albumin regularly in the first
• In patients with liver cirrhosis and type 1 HRS the treatment with occurrence of ascites in liver cirrhosis patients [87].
human albumin shall be combined with terlipressin (1 B).
5.5.2.5 Therapy of Hypoalbuminemia in Nephrotic Syndrome
5.5.2.4.3 Post-Paracentesis In nephrotic syndrome albumin is lost via the kidneys. Com-
A large-volume paracentesis in patients with liver cirrhosis can pensation of the resulting hypoalbuminemia is not reasonable be-
lead to circulatory alterations. This disorder, called post-paracente- cause the transfused albumin is soon eliminated again to the great-
sis circulatory dysfunction in the literature, frequently leads to est extent.
rapid ascites recurrence [98]. Also water retention develops with
dilution hyponatremia, and the disorder can lead to a HRS [32]. In • In cases of nephrotic syndrome human albumin shall not be given
addition, there may be a further increase in the portal pressure by (1 C+).
vasoconstrictive stimulation [84]. These pathological alterations
increase the mortality rate in patients with liver cirrhosis [31]. 5.5.2.6 Therapy of Hypoalbuminemia in Premature Infants
In controlled trials administration of albumin to treat large-vol- Hypoalbuminemia is a frequent occurrence in preterm neonates
ume paracentesis (>5 l) led to an increased hemodynamic stability because of reduced synthesis, increased catabolism, increased loss
[31, 32, 80, 106]. Some randomized controlled trials compared al- or distribution disorder between the intra- and extravascular space.
bumin to synthetic colloids. Albumin was superior regarding pre- Although there is no well-defined critical threshold, human albu-
vention of post-paracentesis circulatory dysfunction. There was no min is frequently substituted. There is a lack of randomized dou-
survival benefit [31, 68, 100]. ble-blind trials. Efficacy and safety of human albumin replacement
A meta-analysis involving 17 randomized trials (n = 1,225 pa- in preterm neonates with hypoalbuminemia are doubtful [47].
tients) comparing albumin to synthetic colloids could demonstrate
that administration of human albumin significantly lowered the 5.5.3 Other Applications of Albumin
mortality risk after large-volume paracentesis [8]. In addition to increasing COP and the volume-stabilizing effect
There are as yet no large randomized controlled trials investi- associated with this, numerous other features are assigned to albu-
gating the effect of albumin, crystalloid solutions or synthetic vol- min that exceed its function for volume substitution [21, 55].

228 Transfus Med Hemother 2016;43:223–232 Executive Committee of the German Medical 

Association on the Recommendation of the 
Scientific Advisory Board et al.
 5.5.3.1 Albumin in Patients with Ovarian Hyperstimulation 5.6 Adverse Reactions
Syndrome
Further potential indications concern the prevention and ther- In general, human albumin is tolerated well. No substance-spe-
apy of a severe ovarian hyperstimulation syndrome [117], despite cific, clinically relevant alterations in the coagulation capacity or
the fact that the data situation is quite controversial and that two alterations in organ function (e.g. renal function) due to albumin
additional systematic reviews could prove no or at most a marginal therapy have been reported. There is also no risk of retention of
effect on the incidence rate of ovarian hyperstimulation syndrome albumin. Although albumin is prepared from plasma pooled from
[48, 108]. Furthermore, deleterious effects (e.g. on the pregnancy numerous donors, albumin preparations per se are considered to
rate) are discussed [48]. be non-immunogenic. Nevertheless, in rare cases slight reactions
can occur after human albumin administration, like flush, urti-
• Human albumin can be used as a colloid volume substitute for caria, elevated temperature, and nausea. Generally, such reactions
the prevention and therapy of a severe ovarian hyperstimulation resolve rapidly after the infusion is administered more slowly or
syndrome in those cases in which other interventions are contra- discontinued. In singular cases an anaphylactic shock can develop.
indicated (2 B). In this case the infusion must be discontinued immediately and a
suitable shock therapy started.
5.5.3.2 Albumin Improving Transport Capacity for Drugs An investigation of the safety of human albumin application
Albumin serves as a transport protein for many substances (e.g. showed that in approximately 112 million units of human albumin
bilirubin, drugs). It is doubtful whether in the case of hypoalbu- administered worldwide adverse reactions directly associated with
minemia there may also be an increase in the ‘free’ unbound (bio- albumin were an extremely rare event [111]; from 1998 to 2000
logically active) fraction of drugs (e.g. coumarin derivatives). Since alone approximately 107 units of 40 g each were administered.
an increase in the free fraction of a substance is most often fol- A study compared approximately 7,000 critically ill patients who
lowed by a more rapid metabolism or an increased elimination of either received 4% human albumin or crystalloid solutions (SAFE
this substance, no critical increase in the concentration of the free study [27]). No serious adverse reactions were reported for the human
substance in plasma is to be anticipated in the case of low levels of albumin group in comparison to the crystalloid solution group.
albumin. There is no risk of acute toxic effects resulting from hy- Hyperoncotic albumin solutions as well as synthetic colloid so-
poalbuminemia because of rapid migration of the unbound frac- lutions can cause renal failure in patients with shock [94]. There-
tion of drugs from the intravascular to the extravascular space so fore, attention must be paid to sufficient hydration.
that a (low-level) balance is reached. At present, no assessment is
possible regarding the question whether albumin use is clinically
beneficial in patients with hypoalbuminemia in view of the non- 5.7 Absolute and Relative Contraindications
oncotic properties.
The only substance-specific contraindication for albumin is an
5.5.3.3 Albumin as Free Radical Scavenger and for Binding established allergy against human albumin. As any albumin infu-
Toxic Substances sion (e.g. to compensate hypovolemia) simultaneously causes in-
Physiologically, albumin is assumed to serve as free radical scav- creased intravascular volume, any hypervolemic state is to be con-
enger and is able to bind toxic substances (e.g. free fatty acids). sidered a contraindication. Special caution is necessary in patients
Therefore, albumin seems to be indicated in particular in patients with severely restricted cardiac function.
with sepsis because toxic oxygen radicals play a role in pathogene- As is true for all volume substitutes, the following contraindica-
sis and maintenance of sepsis [79]. Allegedly albumin can also bind tions apply also to human albumin in general:
toxins in large-scale burns. Therefore, albumin solutions could (1) congestive heart failure,
have a beneficial effect in these patients. However, to date there are (2) pulmonary edema,
no confirmed factual data on the benefit of human albumin ther- (3) hypocoagulopathy due to dilution.
apy regarding morbidity or mortality in humans. The current
AWMF guidelines regarding sepsis do not recommend using
5.8 Documentation
human albumin in this regard [86].
In severe cases of neonatal jaundice, human albumin therapy
The product type, batch number and recipient of human albu-
can contribute to a decrease of unconjugated serum bilirubin, to-
min must be documented in writing in accordance with section 14
gether with phototherapy and exchange transfusion [66].
of the German Transfusion Act (Transfusionsgesetz; TFG).

5.5.3.4 Albumin for Hemodilution in Neonates with

Polycythemia
Appendix
In neonatal polycythemia there is no difference in using human
albumin and crystalloid solutions regarding a blood-thinning effect The appendix is available at http://content.karger.com/ProdukteDB/
in the context of hemodilution. produkte.asp?doi=446043.

Cross-Sectional Guidelines for Therapy with Transfus Med Hemother 2016;43:223–232 229
Blood Components and Plasma Derivatives:
Chapter 5 Human Albumin – Revised
 References
1 Ahn HJ, Yang M, Gwak MS, et al: Coagulation and bi- 20 Dellinger RP, Levy MM, Rhodes A, et al: Surviving 40 Han JJ, Yim HE, Lee JH, et al: Albumin versus normal
ochemical effects of balanced salt-based high molecu- sepsis campaign: international guidelines for manage- saline for dehydrated term infants with metabolic acido-
lar weight vs saline-based low molecular weight hy- ment of severe sepsis and septic shock: 2012. Crit Care sis due to acute diarrhea. J Perinatol 2009; 29: 444–447.
droxyethyl starch solutions during the anhepatic pe- Med 2013; 41: 580–637. 41 Hanart C, Khalife M, De Villé A, et al: Perioperative
riod of liver transplantation. Anaesthesia 2008; 63: 21 Dykes PW: A study of the effects of albumin infusions volume replacement in children undergoing cardiac
235–242. in patients with cirrhosis of the liver. Q J Med 1961; 30: surgery: albumin versus hydroxyethyl starch 130/0.4.
2 Akech S, Ledermann H, Maitland K: Choice of fluids 297–327. Crit Care Med 2009; 37: 696–701.
for resuscitation in children with severe infection and 22 Dzik WH, Arkin CF, Jenkins RL, Stump DC: Fibrinol- 42 Haynes GR, Navickis RJ, Wilkes MM: Albumin ad-
shock: systematic review. BMJ 2010; 341:c4416. ysis during liver transplantation in humans: role of tis- ministration – what is the evidence of clinical benefit?
3 Alessandria C, Ottobrelli A, Debernardi-Venon W, et sue-type plasminogen activator. Blood 1988; 71: 1090– A systematic review of randomized controlled trials.
al: Noradrenalin vs terlipressin in patients with hepa- 1095. Eur J Anaesthesiol 2003; 20: 771–793.
torenal syndrome: a prospective, randomized, un- 23 European Association for the Study of the Liver: EASL 43 Heier HE, Bugge W, Hjelmeland K, Søreide E, Sørlie
blinded, pilot study. J Hepatol 2007; 47: 499–505. clinical practice guidelines on the management of as- D, Håheim LL: Transfusion vs. alternative treatment
4 Andersen JT, Sandlie I: The versatile MHC class I-re- cites, spontaneous bacterial peritonitis, and hepatore- modalities in acute bleeding: a systematic review. Acta
lated FcRn protects IgG and albumin from degrada- nal syndrome in cirrhosis. J Hepatol 2010; 53: 397–417. Anaesthesiol Scand 2006; 50: 920–931.
tion: Implications for development of new diagnostics 24 Fan E, Stewart TE: Albumin in critical care: SAFE, but 44 Himpe D: Colloids versus crystalloids as priming
and therapeutics. Drug Metab Pharmakokinet 2009; 24: worth its salt? Crit Care 2004; 8: 297–299. solutions for cardiopulmonary bypass: a meta-analysis
318–332. 25 Ferguson ND, Stewart TE, Etchells EE: Human albu- of prospective, randomized clinical trials. Acta Anaes-
5 Annane D, Siami S, Jaber S, et al; CRISTAL Investiga- min administration in critically ill patients. Intensive thesiol Belg 2003; 54: 207–215.
tors: Effects of fluid resuscitation with colloids vs crys- Care Med 1999; 25: 323–325. 45 Hosono S, Ohno T, Kimono H, et al: Effects of albu-
talloids on mortality in critically ill patients presenting 26 Fernandez J, Monteagudo J, Bargallo X, et al: A rand- min infusion therapy on total and unbound bilirubin
with hypovolemic shock. The CRISTAL randomized omized unblinded pilot study comparing albumin ver- values in term infants with intensive phototherapy.
trial. JAMA 2013; 310: 1809–1817. sus hydroxyethyl starch in spontaneous bacterial peri- Pediatr Int 2001; 43: 8–11.
6 Arroyo V, Ginés P, Gerbes AL, et al: Definition and tonitis. Hepatology 2005; 42: 627–634. 46 Jacob M, Chappell D, Conzen P, Wilkes MM, Becker
diagnostic criteria of refractory ascites and hepatorenal 27 Finfer S, Bellomo R, Boyce N, French J, Myburgh J, BF, Rehm M: Small-volume resuscitation with hyper-
syndrome in cirrhosis. Hepatology 1996; 23: 164–176. Norton R; SAFE Study Investigators: A comparison of oncotic albumin: a systematic review of randomized
7 Banerjee A, Stocche RM, Angle P, Halpern SH: Preload albumin and saline for fluid resuscitation in the inten- clinical trials. Crit Care 2008; 12:R34.
or coload for spinal anesthesia for elective Cesarean sive care unit. N Engl J Med 2004; 350: 2247–2256. 47 Jardine LA, Jenkins-Manning S, Davies MW: Albumin
delivery: a meta-analysis. Can J Anaesth 2010; 57:24–31. 28 Finfer S, Bellomo R, McEvoy S, et al: Effect of baseline infusion for low serum albumin in preterm newborn
8 Bernardi M, Caraceni P, Navickis RJ, Wilkes MM: Al- serum albumin concentration on outcome of resuscita- infants. Cochrane Database Syst Rev 2004; 3:CD004208.
bumin infusion in patients undergoing large-volume tion with albumin or saline in patients in intensive care 48 Jee BC, Suh CS, Kim YB, et al. Administration of intra-
paracentesis: A meta-analysis of randomized trials. units: analysis of data from the saline versus albumin venous albumin around the time of oocyte retrieval
Hepatology 2012; 55: 1172–1181. fluid evaluation (SAFE) study. BMJ 2006; 333: 1044. reduces pregnancy rate without preventing ovarian
9 Brambell FW, Hemmings WA, Morris IG: A theoreti- 29 Fleck A, Raines G, Hawker F, et al: Increased vascular hyperstimulation syndrome: a systematic review and
cal model of gamma-globulin catabolism. Nature 1964; permeability. Major cause of hypoalbuminaemia in meta-analysis. Gynecol Obstet Invest 2010; 70: 47–54.
203: 1352–1354. disease and injury. Lancet 1985;i:781–784. 49 Jelenko C III, Williams JB, Wheeler ML, et al: Studies
10 Bunn F, Trivedi D, Ashraf S: Colloid solutions for fluid 30 Gentilini P, Casini-Raggi V, diFiori G, et al: Albumin in shock and resuscitation, I: use of a hypertonic, albu-
resuscitation. Cochrane Database Syst Rev 2011; improves the response to diuretics in patients with cir- min-containing, fluid demand regimen (HALFD) in
3:CD001319. rhosis and ascites: results of a randomized, controlled resuscitation. Crit Care Med 1979; 7: 157–167.
11 Caironi P, Tognoni G, Masson S, et al; for the ALBIOS trial. J Hepatol 1999; 30: 639–645. 50 Kang YG, Martin DJ, Marquez J, et al: Intraoperative
Study Investigators: Albumin replacement in patients 31 Gines A, Fernandez-Esparrach G, Monescillo A, et al: changes in blood coagulation and thrombelastographic
with severe sepsis or septic shock. N Engl J Med 2014; Randomized trial comparing albumin, dextran 70, and monitoring in liver transplantation. Anesth Analg
370: 1412–1421. polygeline in cirrhotic patients with ascites treated by 1985; 61: 888–896.
12 Chalasani N, Gorski JC, Horlander JC Sr, Craven R, paracentesis. Gastroenterology 1996; 111: 1002–1010. 51 Kim J, Hayton WL, Robinson JM, Anderson CL: Ki-
Hoen H, Maya J: Effects of albumin/furosemide mix- 32 Ginès P, Tito L, Arroyo V, et al: Randomized compara- netics of FcRn-mediated recycling of IgG and albumin
tures on responses to furosemide in hypoalbuminemic tive study of therapeutic paracentesis with and without in human: pathophysiology and therapeutic implica-
patients. J Am Soc Nephrol 2001; 12: 1010–1016. intravenous albumin in cirrhosis. Gastroenterology tions using a simplified mechanism-based model. Clin
13 Chien S, Sinclair DG, Dellenback J, et al: Effect of en- 1988; 94: 1493–1502. Immunol 2007; 122: 146–155.
dotoxin on capillary permeability to macromolecules. 33 Gluud LL, Christensen K, Christensen E, Krag A: Sys- 52 Kuo TT, Aveson VG: Neonatal Fc receptor and IgG-
Am J Physiol 1964; 207: 518–522. tematic review of randomized trials on vasoconstrictor based therapeutics. MAbs 2011; 3: 422–430.
14 Cochrane Injuries Group Albumin Reviewers: Human drugs for hepatorenal syndrome. Hepatology 2010; 51: 53 Ladegaard-Pedersen HJ: Plasma volume and plasma
albumin administration in critically ill patients: sys- 576–584. colloid osmotic pressure. Scand J Clin Lab Invest 1969;
tematic review of randomised controlled trials. BMJ 34 Goodwin CW, Dorethy J, Lam V, Pruitt BA Jr. Rand- 23: 153–158.
1998; 317: 235–240. omized trial of efficacy of crystalloid and colloid resus- 54 Lasky LC, Finnerty EP, Genis L, Polesky HF: Protein
15 Cohn EJ, Oncley JL, Strong LE, et al: Chemical, clinical citation on hemodynamic response and lung water and colloid osmotic pressure changes with albumin
and immunologic studies on the products of human following thermal injury. Ann Surg 1983; 197: 520–531. and/or saline replacement during plasma exchange.
plasma fractionation. I. The characterization of the 35 Greenhalgh DG, Housinger TA, Kagan RJ, et al: Main- Transfusion 1984; 24: 256–259.
protein fractions of human plasma. J Clin Invest 1944; tenance of serum albumin levels in pediatric burn pa- 55 Li L, Zhang Y, Tan Y, Xu S: Colloid or crystalloid solu-
23: 417. tients: a prospective, randomized trial. J Trauma 1995; tion on maternal and neonatal hemodynamics for ce-
16 Cyna AM, Andrew M, Emmett RS, Middleton P, Sim- 39: 67–73. sarean section: a meta-analysis of randomized con-
mons SW: Techniques for preventing hypotension 36 Groeneveld AB, Navickis RJ, Wilkes MM: Update on trolled trials. J Obstet Gynaecol Res 2013; 39: 932–941.
during spinal anaesthesia for caesarean section. the comparative safety of colloids: a systematic review 56 Liberati A, Moja L, Moschetti I, Gensini GF, Gusinu R:
Cochrane Database Syst Rev 2006; 4:CD002251. of clinical studies. Ann Surg 2011; 253: 470–483. Human albumin solution for resuscitation and volume
17 D’Angio RG: Is there a role for albumin administration 37 Groenland HN, Porte RJ, Metselaar HJ: Liver trans- expansion in critically ill patients. Intern Emerg Med
in nutrition support? Ann Pharmacother 1994; 28: plantation and risk of bleeding. Curr Opin Organ 2006; 1: 243–245.
478–482. Transplant 2007; 12: 287–293. 57 Liet JM, Kuster A, Denizot S, et al: Effects of hydroxy-
18 de Jonge E, Levi M: Effects of different plasma substi- 38 Gupta D, Lis CG: Pretreatment serum albumin as a ethyl starch on cardiac output in hypotensive neonates:
tutes on blood coagulation: a comparative review. Crit predictor of cancer survival: a systematic review of the a comparison with isotonic saline and 5% albumin.
Care Med 2001; 29: 1261–1267. epidemiological literature. Nutr J 2010; 9: 69. Acta Paediatr 2006; 95: 555–560.
19 Delaney AP, Dan A, McCaffrey J, Finfer S: The role of 39 Guthrie RD Jr, Hines C Jr: Use of intravenous albumin
albumin as a resuscitation fluid for patients with sep- in the critically ill patient. Am Coll Gastroenterology
sis: a systematic review and meta-analysis. Crit Care 1991; 86: 255–263.
Med 2011; 39: 386–391.

230 Transfus Med Hemother 2016;43:223–232 Executive Committee of the German Medical 

Association on the Recommendation of the 
Scientific Advisory Board et al.
58 Liumbruno GM, Bennardello F, Lattanzio A, Piccoli P, 79 Quinlan GJ, Mumby S, Martin GS, Bernard GR, Gut- 96 Shahian M, Moslehi MA: Effect of albumin adminis-
Rossettias G; Italian Society of Transfusion Medicine teridge JM, Evans TW: Albumin influences total tration prior exchange transfusion in term neonates
and Immunohaematology (SIMTI): Recommendations plasma antioxidant capacity favorably in patients with with hyperbilirubinemia – a randomized controlled
for the use of albumin and immunoglobulins. Blood acute lung injury. Crit Care Med 2004; 32: 755–759. trial. Indian Pediatr 2010; 47: 241–244.
Transfus 2009; 7: 216–234. 80 Quintero E, Ginès P, Arroyo V, et al: Paracentesis ver- 97 Sharma P, Kumar A, Sharma BC, Sarin SK: An open
59 Lynch SK, Mullett MD, Graeber JE, et al: A compari- sus diuretics in the treatment of cirrhotics with tense label, pilot, randomized controlled trial of noradrena-
son of albumin-bolus therapy versus normal saline- ascites. Lancet 1985; 16: 611–612. line versus terlipressin in the treatment of type 1 hepa-
bolus therapy for hypotension in neonates. J Perinatol 81 Reinhart K, Perner A, Sprung CL, et al: Consensus torenal syndrome and predictors of response. Am J
2008; 28: 29–33. statement of the ESICM task force on colloid volume Gastroenterol 2008; 103: 1689–1697.
60 Maitland K, Kiguli S, Opoka RO, et al: Mortality after therapy in critically ill patients. Intensive Care Med 98 Solà R, Vila MC, Andreu M, et al: Total paracentesis
fluid bolus in African children with severe infection. N 2012; 38: 368–383. with dextran 40 vs. diuretics in the treatment of ascites
Engl J Med 2011; 364: 2483–2495. 82 Roberts I, Blackhall K, Alderson P, Bunn F, Schierhout in cirrhosis: a randomized controlled study. J Hepatol
61 Margarson MP, Soni N: Serum albumin: touchstone or G: Human albumin solution for resuscitation and vol- 1994; 20: 282–288.
totem? Anaesthesia 1998; 53: 789–803. ume expansion in critically ill patients. Cochrane Data- 99 Solanki P, Chawla A, Garg R, Gupta R, Jain M, Sarin
62 Martin-Llahi M, Pepin MN, Guevara M, et al: Terli- base Syst Rev 2011; 11:CD001208. SK: Beneficial effects of terlipressin in hepatorenal syn-
pressin and albumin vs albumin in patients with cir- 83 Rossign N: Intra- and extravascular distribution of drome: a prospective, randomized placebo-controlled
rhosis and hepatorenal syndrome: a randomized study. albumin and immunoglobulin in man. Lymphology clinical trial. J Gastroenterol Hepatol 2003; 18: 152–156.
Gastroenterology 2008; 134: 1352–1359. 1978; 11: 138–142. 100 Sola-Vera J, Minana J, Ricart E, et al: Randomized trial
63 Mathru M, Rao TL, Kartha RK, Shanmugham M, 84 Ruiz del Arbol L, Monescillo A, Jiménez W, Garcia- comparing albumin and saline in the prevention of
Jacobs HK: Intravenous albumin administration for Plaza A, Arroyo V, Rodes J: Paracentesis-induced cir- paracentesis-induced circulatory dysfunction in cir-
prevention of spinal hypotension during cesarean sec- culatory dysfunction: mechanism and effect on hepatic rhotic patients with ascites. Hepatology 2003; 37: 1147–
tion. Anesth Analg 1980; 9: 655–658. hemodynamics in cirrhosis. Gastroenterology 1997; 1153.
64 McLeod BC: Plasma and plasma derivatives in thera- 113: 579–586. 101 Sort P, Navasa M, Arroyo V, et al: Effects of intrave-
peutic plasmapheresis. Transfusion 2012; 52(suppl 85 Russell JA, Navickis RJ, Wilkes MM: Albumin versus nous albumin on renal impairment and mortality in
1):38–44. crystalloid for pump priming in cardiac surgery: meta- patients with cirrhosis and spontaneous bacterial peri-
65 Mendez CM, McClain CJ, Marsano LS: Albumin ther- analysis of controlled trials. J Cardiothorac Vasc An- tonitis. N Engl J Med 1999; 342: 403–409.
apy in clinical practice. Nutr Clin Pract 2005; 20: 314– esth 2004; 18: 429–437. 102 Standl T, Lochbuehler H, Galli C, et al: HES 130/0.4
320. 86 S2k-Leitlinie Prävention, Diagnose, Therapie und (Voluven®) or human albumin in children younger
66 Mitra S, Samanta M, Sarkar M, et al: Pre-exchange 5% Nachsorge der Sepsis. AWMF Register No. 079/001 than 2 yr undergoing non-cardiac surgery. A prospec-
albumin infusion in low birth weight neonates with in- www.awmf.org/uploads/tx_szleitlinien/079–001l_S2k_ tive, randomized, open label, multicenter trial. Eur J
tensive phototherapy failure – a randomized con- Sepsis_2010-abgelaufen.pdf (under revision, last re- Anaesthesiol 2008; 25: 437–445.
trolled trial. J Trop Pediatr 2011; 57: 217–221. trieved July 27, 2015) 103 Standl T: Albumin; in Boldt J (ed): Volumenersatzthe-
67 Mobarhan S: The role of albumin in nutritional sup- 87 German S3-Guideline Ascites, Spontaneous Bacterial rapie. Stuttgart, Thieme, 2001, pp 39–61.
port. J Am Coll Nutr 1988; 7;445–452. peritonitis, Hepatorenal Syndrome (in German). 104 Subcommittee of the Victorian Drug Usage: Human
68 Moreau R, Valla DC, Durand-Zaleski I, et al: Compari- AWMF Register No. 021/017 www.awmf.org/uploads/ albumin solutions: consensus statements for use in se-
son of outcome in patients with cirrhosis and ascites tx_szleitlinien/021–017l_S3_Aszites_2011.pdf (last re- lected clinical situations. Advisory Committee. Med J
following treatment with albumin or a synthetic col- trieved July 27, 2015). Aust 1992; 157: 340–343.
loid: a randomised controlled pilot trail. Liver Int 2006; 88 German S3-Guideline on Treatment of Patients with 105 Thomas-Rueddel DO, Vlasakov V, Reinhart K, et al:
26: 46–54. Severe and Multiple Injuries. AWMF Register No. Safety of gelatin for volume resuscitation – a system-
69 Navickis RJ, Haynes GR, Wilkes MM: Effect of hy- 012/019e. .www.awmf.org/fileadmin/user_upload/ atic review and meta-analysis. Intensive Care Med
droxyethyl starch on bleeding after cardiopulmonary Leitlinien/012_D_Ges_fuer_Unfallchirurgie/012–019e_ 2012; 38: 1134–1142.
bypass: a meta-analysis of randomized trials. J Thorac S3_Severe_and_Multiple_Injuries_2015–01.pdf (last 106 Tito L, Ginès P, Arroyo V, et al: Total paracentesis as-
Cardiovasc Surg 2012; 144: 223–230. retrieved July 27, 2015) sociated with intravenous albumin management of
70 Neri S, Pulvirenti D, Malaguarnera M, et al: Terlipres- 89 S3-Leitlinie zur intensivmedizinischen Versorgung patients with cirrhosis and ascites. Gastroenterology
sin and albumin in patients with cirrhosis and type I herzchirurgischer Patienten, Hämodynamisches Mo- 1990; 98: 146–151.
hepatorenal syndrome. Dig Dis Sci 2008; 53: 830–835. nitoring und Herz-Kreislauf-Therapie. AWMF Regis- 107 Trotter J, Pieramici E, Everson GT: Chronic albumin
71 Oca MJ, Nelson M, Donn SM: Randomized trial of ter No. 001/016 www.awmf.org/uploads/tx_szleitlinien/ infusions to achieve diuresis in patients with ascites
normal saline versus 5% albumin for the treatment of 001–016l_S3_Intensivmedizinische_Versorgung_herz- who are not candidates for transjugular intrahepatic
neonatal hypotension. J Perinatol 2003; 23: 473–476. chirurgischer_Patienten_2010-gelabelt.pdf (under revi- portosystemic shunt (TIPS). Dig Dis Sci 2005; 50:1356–
72 Oganesyan V, Damschroder MM, Cook KE, et al: sion, last retrieved July 27, 2015) 1360.
Structural insights into neonatal Fc receptor-based re- 90 Sagi SV, Mittal S, Kasturi KS, Sood GK: Terlipressin 108 Venetis CA, Kolibianakis EM, Toulis KA, Goulis DG,
cycling mechanisms. J Biol Chem 2014;289:7812–7824. therapy for reversal of type 1 hepatorenal syndrome: A Papadimas I, Tarlatzis BC: Intravenous albumin ad-
73 Oratz M, Rothschild MA, Schreiber SS: Effect of dex- meta-analysis of randomized controlled trials. J Gas- ministration for the prevention of severe ovarian hy-
tran infusions on protein synthesis by hepatic micro- troenterol Hepatol 2010; 25: 880–885. perstimulation syndrome: a systematic review and
somes. Am J Physiol 1970; 218: 1108–1112. 91 Salerno F, Navickis RJ, Wilkes MM: Albumin infusion metaanalysis. Fertil Steril 2011; 95: 188–196.
74 Parving HH, Ranek L, Lassen NA: Increased transcap- improves outcomes of patients with spontaneous bac- 109 Vincent JL, Dubois MJ, Navickis RJ, Wilkes MM: Hy-
illary escape rate of albumin in patients with cirrhosis terial peritonitis: a meta-analysis of randomized trials. poalbuminemia in acute illness: is there a rationale for
of the liver. Scand J Clin Lab Invest 1977; 37: 643–648. Clin Gastroenterol Hepatol 2013; 11: 123–130.e1. intervention? A meta-analysis of cohort studies and
75 Parving HH, Rossing N: Simultaneous determination 92 Sanyal AJ, Boyer T, Garcia-Tsao G, et al: A rand- controlled trials. Ann Surg 2003; 237: 319–334.
of the transcapillary escape rate of albumin and IgG in omized, prospective, double-blind, placebo-controlled 110 Vincent JL, Navickis RJ, Wilkes MM: Morbidity in
normal and long-term juvenile diabetic subjects. Scand trial of terlipressin for type 1 hepatorenal syndrome. hospitalized patients receiving human albumin: a
J Clin Lab Invest 1973; 32: 239–244. Gastroenterology 2008; 134: 1360–1368. meta-analysis of randomized, controlled trials. Crit
76 Perel P, Roberts I: Colloids versus crystalloids for fluid 93 Saw MM, Chandler B, Ho KM: Benefits and risks of Care Med 2004; 32: 2029–2038.
resuscitation in critically ill patients. Cochrane Data- using gelatin solution as a plasma expander for periop- 111 Vincent JL, Wilkes MM, Navickis RJ: Safety of human
base Syst Rev 2011; 3:CD000567. erative and critically ill patients: a meta-analysis. albumin – serious adverse events reported worldwide
77 Porte RJ, Bontempo FA, Knot EAR, Lewis JH, Kang Anaesth Intensive Care 2012; 40: 17–32. in 1998–2000. Br J Anaesth 2003; 91: 625–630.
YG, Starzl TE: Systemic effects of tissue plasminogen 94 Schortgen F, Girou E, Deye N, Brochard L; CRYCO 112 Webb AR: The appropriate role of colloids in manag-
activator-associated fibrinolysis and its relation to Study Group: The risk associated with hyperoncotic ing fluid imbalance: a critical review of recent meta-
thrombin generation in orthotopic liver transplanta- colloids in patients with shock. Intensive Care Med analytic findings. Crit Care 2000; 4(suppl 2):26–32.
tion. Transplantation 1989; 47: 978–984. 2008; 34: 2157–2168. 113 Whatling PJ: Intravenous fluids for abdominal aortic
78 Pulimood TB, Park GR: Debate: albumin administra- 95 Schrier RW: Fluid administration in critically ill pa- surgery. Cochrane Database Syst Rev 2000;3:CD000991.
tion should be avoided in the critically ill. Crit Care tients with acute kidney injury. Clin J Am Soc Nephrol
2000; 4: 151–155. 2010; 5: 733–739.

Cross-Sectional Guidelines for Therapy with Transfus Med Hemother 2016;43:223–232 231
Blood Components and Plasma Derivatives:
Chapter 5 Human Albumin – Revised
114 Wilkes MM, Navickis RJ, Sibbald WJ: Albumin versus 116 Winstedt D, Hanna J, Schött U: Albumin-induced co- 118 Yuan XY, Zhang CH, He YL, et al: Is albumin adminis-
hydroxyethyl starch in cardiopulmonary bypass sur- agulopathy is less severe and more effectively reversed tration beneficial in early stage of postoperative hy-
gery: a meta-analysis of postoperative bleeding. Ann with fibrinogen concentrate than is synthetic colloid- poalbuminemia following gastrointestinal surgery? A
Thorac Surg 2001; 72: 527–533. induced coagulopathy. Scand J Clin Lab Invest 2013; prospective randomized controlled trial. Am J Surg
115 Wilkes MM, Navickis RJ: Patient survival after human 73: 161–169. 2008; 196: 751–755.
albumin administration – a meta-analysis of rand- 117 Youssef MA, Al-Inany HG, Evers JL, Aboulghar M:
omized controlled trials. Ann Intern Med 2001; 135: Intra-venous fluids for the prevention of severe ovar-
149–164. ian hyperstimulation syndrome. Cochrane Database
Syst Rev 2011; 2:CD001302.