Albumin is a plasma-derived blood product. Albumin may be prescribed as a bolus dose, where a patient requires an Albumin infusion over a discrete period of time and the total dose is known.
A continuous infusion is sometimes used when a patient needs an Albumin infusion for an extended period of time and when the clinician does not know exactly when the infusion will cease. In this instance it should be prescribed as a regular administration e. Two clinicians must independently complete the patient and blood product identification check at the bedside. Record the batch number and expiry date of each bottled infused in the medical record.
Staff administering Albumin must also record the date, time and volume infused. Administer via a standard intravenous IV giving set. It does not require a transfusion filter. The manufacturer recommends that each bottle of Albumin is used immediately after opening the bottle as it does not contain antimicrobial preservative.
At RCH we allow the product to be administered within 6 hours of piercing the bottle. Temperature, heart rate, respiration rate, blood pressure and SpO2 should be recorded at baseline, hourly, at every change in bottle and upon completion.
More frequent observations as the clinical condition of the patient requires. It is well known that albumin has multiple physiological effects [ 3 ], including regulation of colloid osmotic pressure COP , binding and transportation of various substances for example, drugs, hormones within the blood, antioxidant properties, nitric oxide modulation and buffer capabilities, which may be of particular relevance in critically ill patients.
It is also well established that low serum albumin levels, a common occurrence in critically ill patients, are associated with worse outcomes [ 4 , 5 ]. There would therefore seem to be a good rationale for use of albumin infusions in critically ill patients.
However, albumin solutions also have limitations, including high costs relative to possible alternatives, notably crystalloids, and potential rare risks of transmission of microorganisms, anticoagulant, and allergic effects [ 6 — 8 ]. Because there are no definitive randomized controlled trials RCTs demonstrating an outcome benefit of albumin in heterogeneous groups of critically ill patients, routine administration of albumin for fluid resuscitation is not warranted in all patients, but there is evidence to support its use in some patient populations.
The purpose of this article is not to review in detail the multiple functions and roles of albumin or the many comparative studies and meta-analyses that have now been performed, although we will briefly summarize this information to provide some context.
Rather, we wish to provide some clear suggestions and guidance for albumin use based on the current available evidence and highlight important areas for future research. Albumin was one of the first human proteins to be isolated and extracted from plasma for clinical use.
First crystallized in , a preparation was made available for clinical use in the s [ 9 , 10 ]. Early successful use in multi-trauma and severely burned patients led to rapid expansion of the so-called human albumin program in the USA [ 11 ], and albumin use spread from the military setting to civilian hospitals and into regular use in operating and emergency rooms around the world.
The first commercially available preparations of intravenous human albumin solution were developed using the cold alcohol fractionation technique created by Edwin Joseph Cohn [ 9 , 11 ]. Later developments and refinements in extraction and processing have resulted in increasingly pure solutions [ 12 ]. In critically ill patients, particularly those with sepsis, the relationship between COP and the albumin concentration is complex, being influenced by altered permeability and increased transcapillary escape rates [ 14 , 15 ].
Moreover, improved understanding of the endothelial glyocalyx has altered our comprehension of the role of COP in fluid balance [ 16 ]. Numerous experimental studies have confirmed that the traditional understanding of an inwards-directed oncotic gradient between a protein-low interstitial space and a protein-rich plasma, as suggested by Ernest Starling more than years ago, is not correct; indeed, the interstitial compartment has high protein concentrations. A small space, situated on the luminal side of the endothelium beneath this protein sponge, is permanently cleared of passing protein molecules by a protein-low resting flux through small breaks in the intercellular junction strands towards the tissues [ 18 ].
Accordingly, an inwardly-directed oncotic force, quantitatively opposite to the hydrostatically driven fluid filtration, develops exclusively across the small space beneath the glycocalyx and the protein-loaded endothelial surface layer Figure 2. Schematic illustration of the current understanding of vascular barrier function within the high-pressure segment of the vascular system.
For explanation, see text. White arrows, hydrostatic pressure HP gradients towards the interstitial space; thick black arrow, inward directed oncotic force across the endothelial surface layer; thin black arrow, small flux of protein low ultrafiltrate. Current understanding of optimal vascular barrier function in the high-pressure segment of the vascular system includes an intact glycocalyx combined with a minimum concentration of plasma proteins [ 20 ].
Nevertheless, below a certain threshold, artificial substitutes such as starches or gelatin are not sufficient to form an endothelial surface layer with a resistance against pressure-dependent fluid and protein outflow comparable with albumin [ 21 , 23 ]. Albumin has many other properties in addition to its effects on intravascular volume, including transport and antioxidant activities, but their importance in health and disease are less well documented.
The antioxidant effects of albumin are, in brief, related to its ability to bind certain ligands, notably iron and copper, which reduces the availability of these compounds for pro-oxidant reactions, and are related to an exposed thiol group on the free cysteine residue, which acts as a free radical scavenger, able to interact with or trap reactive oxygen or nitrogen species, including nitric oxide, a key mediator in many conditions including sepsis [ 10 , 24 — 26 ].
In addition to the binding of iron and copper ions, albumin also transports multiple other endogenous and exogenous substances Figure 3 [ 13 ]. Changes in albumin concentrations and structure during critical illness can therefore potentially have marked effects on normal homeostasis and metabolism and on drug delivery and efficacy [ 10 , 27 ].
In a systematic review, Ulldemolins and colleagues reported that protein binding of antibacterials, including ceftriaxone, ertapenem, teicoplanin, and aztreonam, was frequently decreased in critically ill patients with hypoalbuminemia, notably with increased volume of distribution and drug clearance [ 27 ].
These changes could result in suboptimal treatment, particularly for time-dependent antibiotics, and may necessitate dose adjustment. Some of the key substances transported by albumin. The balance of acidic to basic residues on albumin makes it a weak acid in physiological concentrations [ 10 , 28 ], so that a decrease in albumin concentration increases the anion gap.
This passively increases bicarbonate concentration, and is therefore associated with development of metabolic alkalosis. Albumin also has anticoagulant effects similar to, but much less potent than, those of heparin, and inhibits platelet aggregation [ 29 ]. Finally, albumin can protect the microvasculature and mitigate increased vascular permeability via its antioxidant, anti-inflammatory effects, and anti-apoptotic effects [ 3 ]. Clearly there is much about the physiologic effects of albumin that is not yet well understood [ 8 ].
These effects are probably altered in various disease states, particularly those associated with oxidant stress such as sepsis, but whether and how these changes are involved in the pathogenesis of these conditions requires further elucidation. Although animal models suggested that albumin synthesis may be reduced in critical illness [ 33 ], synthesis appears to be increased in critically ill humans [ 34 ].
Importantly, whatever the underlying mechanisms, hypoalbuminemia is associated with worse outcomes including increased complications [ 5 , 35 — 38 ] and reduced short-term [ 5 , 39 — 43 ] and longer-term [ 42 , 44 ] survival in critically ill patients. There is therefore a clear association between the albumin level and the severity of the insult [ 45 ], but it remains uncertain whether the effect of hypoalbuminemia on outcome is a cause—effect relationship or whether hypoalbuminemia is rather a marker of serious disease.
Although albumin solutions were first introduced in the s, the first RCT of albumin administration was only published some 30 years later in Table 1. This early RCT, conducted in just 16 patients undergoing abdominal aortic surgery, compared the effects of intraoperative use of albumin solution with those of a sodium-rich fluid during surgery and showed that albumin infusion led to less extracellular fluid expansion [ 46 ].
Other relatively small studies followed, so that by the time the Cochrane meta-analysis [ 2 ] was published in the average sample size of the 32 included studies was just 46 patients. An Expert Working Party of the Committee on Safety of Medicines in the UK highlighted the thoughts of many in the medical community that there was an urgent need to conduct large multicenter RCTs to determine whether albumin administration did indeed worsen outcomes [ 48 ].
A subsequent meta-analysis that included 17 RCTs comparing albumin solutions with other fluids for fluid resuscitation in patients with sepsis reported that albumin use was associated with decreased mortality odds ratio, 0. Guidelines currently suggest grade 2C that albumin use should be considered as a resuscitation fluid in patients with severe sepsis, particularly if those patients are not responding to crystalloid infusion [ 59 , 60 ], based on data from the meta-analysis [ 58 ] and preliminary data from a multicenter study in France that suggested a nonsignificant reduction in mortality in patients with septic shock who received albumin [ 61 ].
In the SAFE trial, patients with traumatic brain injury treated with albumin had worse outcomes than saline-treated patients [ 55 ]. Using pattern mixture modeling, the probable mechanism for the increased mortality appeared to be albumin-induced increases in intracranial pressure [ 63 ].
The hypotonic and hypooncotic nature of the albumin solution used may also have played a role [ 64 ]. The effects of increasing albumin concentrations by giving exogenous albumin have also been investigated in the critically ill. There was also a beneficial effect on cumulative calorie intake during the first week, suggesting that albumin may have helped decrease intestinal edema.
The effects of albumin administration may also depend on the simultaneous use of diuretics to prevent an albumin infusion-induced increase in hydrostatic pressure, which may increase rather than decrease edema formation.
In Sort and colleagues published the results of a RCT in patients with cirrhosis and spontaneous bacterial peritonitis comparing treatment with intravenous cefotaxime or cefotaxime plus intravenous albumin for plasma volume expansion [ 52 ].
A more recent RCT reported beneficial effects of albumin plus antibiotic on renal and circulatory function in patients with cirrhosis and infections other than spontaneous bacterial peritonitis; treatment with albumin was an independent predictive factor of survival [ 69 ].
A meta-analysis of 16 RCTs also suggested that albumin use was associated with a significant reduction in mortality odds ratio, 0. Two small RCTs have also demonstrated improved renal function in patients with cirrhosis and hepatorenal syndrome treated with albumin and terlipressin [ 71 , 72 ]. Following the results of the SAFE study suggesting a benefit of albumin administration in patients with sepsis, several groups designed RCTs to further evaluate albumin use in this specific group of patients.
Of the 1, patients, Almost all patients had severe hypoalbuminemia at study inclusion. There were no significant differences in mortality rates between the two groups Having briefly reviewed the background to the albumin story so far, where are we left? Who, if anyone, should be given albumin?
Some answers will be provided from further analysis of the results from recent and ongoing studies, but in the meantime we believe there are six key questions that need answering. Initially considered largely as an acute resuscitation fluid for its beneficial short-term effects on COP and blood volume, recognition of the adverse outcomes associated with hypoalbuminemia and new knowledge about vascular barrier functioning has led to an increased interest in use of albumin solutions as a supplement to correct and maintain albumin levels.
Nevertheless, it is difficult to separate volume effects from the effects of maintenance of serum albumin — particularly in critically ill patients, many of whom are hypoalbuminemic and in whom it is difficult to clearly relate the timing of interventions to the onset of disease.
As a resuscitation fluid, the major benefit of albumin will be from its impact on COP, resulting in a short-term increase in intravascular volume. Efforts to substitute synthetic colloids for albumin as part of perioperative fluid therapy have not been very successful. Hydroxyethylstarch solutions can persist for long durations in the skin, the liver and, most importantly, the kidney [ 74 ], with a potential risk of renal failure and even increased mortality rates in septic patients [ 75 ].
Gelatin solutions have been less well studied, in part because they are not available in the United States, and their persistence is quite short. Nevertheless, hyperoncotic albumin may be a better choice if edema is already present [ 77 ], avoiding excessive sodium and chloride loads and their attendant complications [ 78 ].
Determining the ideal dose or volume of albumin that should be used is difficult. Different studies have used different doses, and perhaps the dose should be adjusted according to a target serum albumin concentration, as in the ALBIOS study [ 62 ]. The need to make decisions as to whether or not a particular patient should receive albumin based on their albumin level is related to whether the considered use is targeted as resuscitation or supplementation.
Most patients requiring resuscitation fluids in the ICU are hypoalbuminemic and, as mentioned earlier, the fluid will be given largely for its effects on COP — that is, limiting edema formation — provided that the hydrostatic pressure does not increase excessively. In such patients, monitoring the albumin concentration is probably of little value.
In more prolonged administration as supplementation, however, serum albumin levels may be a useful guide to ongoing needs, in combination with disease severity, hemodynamic status, and nutritional status; just as an arbitrary cutoff hemoglobin concentration should not be used to define absolute need for blood transfusion in all patients, so a specific serum albumin threshold for albumin administration is unlikely to be relevant to all.
Following the time course of albumin levels, especially in response to an albumin infusion, may be more valuable than a single albumin level, but optimal albumin levels during critical illness are not clearly defined. Currently available human albumin solutions are developed using various techniques, such that the various commercially available albumin solutions may differ in protein content and composition, binding capacity, metal ion content, antioxidant properties, charge, capacity to bind drugs, and so forth [ 80 , 81 ].
Oxford Academic. Cite Cite J. Select Format Select format. Abstract Human albumin HA is widely used for volume replacement or correction of hypoalbuminaemia. Open in new tab Download slide. Physiological functions of albumin in the plasma.
Human albumin solution for resuscitation and volume expansion in critically ill patients. Randomized comparative multicenter study of hydroxyethyl starch versus albumin as a plasma expander in cirrhotic patients with tense ascites treated with paracentesis. Google Scholar Crossref. Search ADS. Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide. Is albumin administration in hypoalbuminemic elderly cardiac surgery patients of benefit with regard to inflammation, endothelial activation, and long-term kidney function?
Fluid management in burn patients: results from a European survey—more questions than answers. The value of an albumin-based intravascular volume replacement strategy in elderly patients undergoing major abdominal surgery.
Anaesthetic management and outcome in right-lobe living liver-donor surgery. Google Scholar PubMed. Five percent albumin for adult burn shock resuscitation: lack of effect on daily multiple organ dysfunction score. Intraoperative hetastarch infusion impairs hemostasis after cardiac surgery operations.
International guidelines for management of severe sepsis and septic shock: Albumin administration improves organ function in critically ill hypoalbuminemic patients: a prospective, randomized, controlled, pilot study.
Effects of noradrenalin and albumin in patients with type 1 hepatorenal syndrome: a pilot study. Review article: albumin as a drug—biological effects of albumin unrelated to oncotic pressure. Paracentesis with dextran 70 vs. Results of a randomized study. A randomized unblinded pilot study comparing albumin versus hydroxyethyl starch in spontaneous bacterial peritonitis. A comparison of albumin and saline for fluid resuscitation in the intensive care unit.
Increased vascular permeability. Major cause of hypoalbuminaemia in disease and injury. Treatment of cirrhotic tense ascites with Dextran versus albumin associated with large volume paracentesis: a randomized controlled trial. Albumin improves the response to diuretics in patients with cirrhosis and ascites: results of a randomized, controlled trial. Randomized trial comparing albumin, dextran 70, and polygeline in cirrhotic patients with ascites treated by paracentesis.
Randomized comparative study of therapeutic paracentesis with and without intravenous albumin in cirrhosis. Con: starches are not preferable to albumin during cardiac surgery: a contrary opinion. Maintenance of serum albumin levels in pediatric burn patients: a prospective, randomized trial. Small-volume resuscitation with hyperoncotic albumin: a systematic review of randomized clinical trials. Does intraoperative hetastarch administration increase blood loss and transfusion requirements after cardiac surgery?
A randomized, controlled trial of furosemide with or without albumin in hypoproteinemic patients with acute lung injury. The management of ascites in cirrhosis: report on the consensus conference of the International Ascites Club. Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: a retrospective multicenter study. Comparison of outcome in patients with cirrhosis and ascites following treatment with albumin or a synthetic colloid: a randomised controlled pilot trial.
The impact of maintaining normal serum albumin level following living related liver transplantation: does serum albumin level affect the course?
A pilot study. Terlipressin therapy with and without albumin for patients with hepatorenal syndrome: results of a prospective, nonrandomized study. Increased transcapillary escape rate of albumin in patients with cirrhosis of the liver. Simultaneous determination of the transcapillary escape rate of albumin and IgG in normal and long-term juvenile diabetic subjects. Cardiovascular, renal, and neurohumoral responses to single large-volume paracentesis in patients with cirrhosis and diuretic-resistant ascites.
Dextran versus albumin as plasma expanders in cirrhotic patients with tense ascites treated with total paracentesis. Albumin influences total plasma antioxidant capacity favorably in patients with acute lung injury.
Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis: a consensus document. Long-term albumin infusion improves survival in patients with cirrhosis and ascites: an unblinded randomized trial.
Intra- und extravascular distribution of albumin and immunoglobulin in man. Saline or albumin for fluid resuscitation in patients with traumatic brain injury. Randomized comparative study of hemaccel vs. Volume expansion with albumin decreases mortality after coronary artery bypass graft surgery. Randomised controlled trial of colloid or crystalloid in hypotensive preterm infants. Beneficial effects of terlipressin in hepatorenal syndrome: a prospective, randomized placebo-controlled clinical trial.
Randomized trial comparing albumin and saline in the prevention of paracentesis-induced circulatory dysfunction in cirrhotic patients with ascites. Effects of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. A prospective, randomized, open label, multicentre trial. A comparison of 4. Evaluation of the appropriate use of albumin in adult and pediatric patients. Crystalloid or colloid fluid loading and pulmonary permeability, edema, and injury in septic and nonseptic critically ill patients with hypovolemia.
Hypoalbuminemia in acute illness: is there a rationale for intervention? A meta-analysis of cohort studies and controlled trials. Morbidity in hospitalized patients receiving human albumin: a meta-analysis of randomized, controlled trials.
Is albumin administration in the acutely ill associated with increased mortality? Results of the SOAP study. Safety of human albumin-serious adverse events reported worldwide in — Impact of intensive care unit ICU drug use on hospital costs: a descriptive analysis, with recommendations for optimizing ICU pharmacotherapy.
Patient survival after human albumin administration—a meta-analysis of randomized controlled trials. Albumin versus hydroxyethyl starch in cardiopulmonary bypass surgery: a meta-analysis of postoperative bleeding. Is albumin administration beneficial in early stage of postoperative hypoalbuminemia following gastrointestinal surgery?
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