Expert consensus on the use of human serum albumin in critically ill patients

Abstract

Introduction Human serum albumin (HSA) is a non-glycosylated, negatively charged, single-chain polypeptide composed of 585 amino acid residues with a relative molecular mass of 66.438 kD. It is synthesized by the liver at a rate of approximately 200 mg·kg−1·day−1, with a half-life of 21 days, and subjected to catabolism in the muscles, liver, and kidneys at a rate of 4% per day.[1] Albumin, accounting for 60% of the total plasma protein, has various physiological functions,[2] such as maintaining 70% to 80% of effective plasma colloid osmotic pressure, coordinating vascular endothelial integrity, anti-oxidant and anti-inflammatory activities, maintaining the acid-base balance, and participating in the transport, distribution, and metabolism of a variety of endogenous and exogenous substances. The normal concentration of plasma albumin is 35 to 50 g/L. In clinical practice, hypoalbuminemia often occurs because of reduced albumin synthesis due to liver dysfunction, redistribution of serum albumin due to capillary leakage, or increased loss via the intestinal and renal routes. Hypoalbuminemia (defined as a serum albumin concentration less than 35 g/L) reportedly has an incidence of 24% to 87% in critically ill patients,[3] while severe hypoalbuminemia (a serum albumin concentration less than 25 g/L) has an incidence of 5.0–9.6%.[4] Hypoalbuminemia is an independent risk factor for increased short- and long-term mortality and an increased incidence of acute kidney injury (AKI) in patients with acute conditions such as trauma, cardiogenic shock, and sepsis.[5] A meta-analysis showed that for every 10 g/L decrease in the serum albumin concentration in critically ill patients, there was a 137% increase in in-hospital mortality, an 89% increase in the incidence of comorbidities, and a 72% increase in the length of hospital stay.[6] Hypoalbuminemia can also alter the pharmacokinetics of antibiotics, leading to either insufficient or excessively high blood concentrations, thereby resulting in treatment failure or excessive toxicity.[7] HSA is mainly used for fluid resuscitation and the treatment of hypoproteinemia in critically ill patients.[2] Existing studies have shown controversial results regarding whether the use of albumin in critically ill patients improves their clinical prognosis.[8] Albumin consumption varies greatly among countries,[9] and its inappropriate use is frequently seen, with 40% to 90% of reported HSA applications failing to follow clinical guidelines.[10] A tertiary hospital in China reported that hypoproteinemia was the most common indication for the use of HSA (35.6%); however, it was also used in 11.8% of patients with serum albumin concentrations more than 40 g/L. The reason for its use was not documented in 22% of cases.[11] In clinical practice, guidelines and consensus are lacking regarding the selection of HSA concentration, the timing of administration, dosage, and target concentration. Inappropriate use of HSA will cause adverse effects and increase medical costs inevitably, whereas guidance from clinical pharmacists or hospital standards can help reduce inappropriate HSA use by 30% and decrease medical costs without affecting patient prognosis.[12] To further strengthen the standardized application of HSA in critically ill patients and achieve optimal clinical outcomes, the Chinese Society of Critical Care Medicine convened a panel of relevant experts who reviewed and summarized data on the clinical use of HSA, outlined 11 relevant clinical problems, and formulated the “Expert Consensus on the Use of Human Serum Albumin in Critically Ill Patients” using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Application Scope of the Consensus This consensus is mainly intended to propose recommendations relevant to critically ill patients through establishment of clinical problems, literature search, and comprehensive analysis with respect to 11 aspects: sepsis and septic shock, hemorrhagic shock, cardiac surgery, surgery, acute trauma, acute liver and adverse effects of HSA This consensus mainly as a for and clinical pharmacists on HSA Development of the Consensus The was in for the “Expert Consensus on the Use of Human Serum Albumin in Critically Ill Patients” of experts in and experts in and on a to relevant the experts that HSA has used for fluid resuscitation and albumin in critically ill patients, regarding the and the in clinical and treatment as as the that it was and to an consensus and recommendations to the and standardized use of HSA in The the clinical to and experts to the clinical using the and is for and for literature and relevant studies for The was and to clinical to insufficient literature in The 11 to in the consensus on as as panel and A of experts in was with experts a in of the literature and and for a as as the of the of the relevant consensus In from was for and clinical of the as as with of the the and for in or with and on and further the of in 25 The recommendations and using the in of and This was to a of consensus the a literature and the in a to the the of the consensus by the of and the at the of The was through of with high of for consensus on the use of serum albumin in critically ill not not Recommendations for the Use of HSA in the of and is a in the resuscitation of patients with sepsis and septic shock, with and effective of plasma the of and of The guidelines as the resuscitation fluid and albumin as a resuscitation there are recommendations regarding the timing of administration, optimal concentration, or for the of albumin for fluid resuscitation in patients with In consensus the and recommendations HSA is as a resuscitation fluid for patients with sepsis and its use in fluid resuscitation in patients with septic reduce mortality HSA is a used resuscitation fluid in clinical practice, its in fluid resuscitation in patients with sepsis To have the of HSA in fluid resuscitation in patients with The Albumin Evaluation in patients who to 4% HSA or for fluid resuscitation and reported clinical for the A analysis of patients with severe sepsis a of mortality among patients HSA treatment The showed that the of HSA is to that of for and HSA use the of patients with severe In the Albumin patients with sepsis a with and a with and HSA The of the a analysis of patients with septic showed a decrease in mortality among patients with HSA the Albumin and the Albumin in resuscitation with HSA in patients with septic and showed in the of HSA for fluid resuscitation in patients with sepsis and reported that HSA resuscitation was not to resuscitation in patients with sepsis to mortality among patients with severe sepsis and septic In the studies that the of HSA is to that of for resuscitation in patients with and its use reduce the mortality of patients with septic in patients with septic of HSA has the optimal timing of HSA fluid resuscitation in patients with A of is for fluid resuscitation by the sepsis on the and the the guidelines with HSA of are for patients with septic 70% to 80% of plasma colloid osmotic is by and of albumin of with 10 of albumin the by 200 In the and albumin was of In the HSA was of the that HSA of in patients with septic shock, resuscitation using HSA the not It that the patients with septic in the patients, the of is for clinical regarding the timing of HSA resuscitation in patients with the guidelines and clinical practice, the that albumin to septic patients who resuscitation with and that as failure to a of or the of at a rate of or in at and a capillary in albumin the patient has a or cardiogenic or and or HSA can used for fluid resuscitation in patients with sepsis have not the and of concentrations of HSA for fluid resuscitation in patients with in or and or HSA have used as resuscitation and adverse have that and HSA are in patients with concentrations of HSA used in 4% albumin was used in the and and albumin was used in the not HSA A meta-analysis of patients in clinical that there was in the rate or of resuscitation fluid patients with sepsis who and HSA on the results of the is that and HSA can used for fluid resuscitation in patients with HSA can in patients with sepsis serum albumin g/L or more and are In a comprehensive meta-analysis of critically ill patients from hypoalbuminemia was as an using The results showed that for every 10 g/L decrease in the serum albumin concentration, the length of hospital incidence of comorbidities, and mortality rate increased by and A meta-analysis of on hypoalbuminemia in critically ill patients showed that the incidence of was reduced in patients with serum albumin concentrations of more than g/L albumin A of critically ill also showed that hypoalbuminemia at was an independent of A of patients with sepsis showed that albumin with mortality risk in patients with In the the mortality was in patients with severe sepsis with a serum albumin of less than g/L at the of using with a high rate in patients with HSA is for pharmacokinetics and used in patients with sepsis to in the and with albumin accounting for 60% of plasma such as and have high of and Hypoalbuminemia the of and rate of The rate of to albumin is to Hypoalbuminemia patients with have and of than The rate of is 90% to In critically ill patients, the of is than that in The rate of is to with severe sepsis have and of than patients with sepsis are with with high with albumin is to pharmacokinetics and Recommendations for the use of HSA in patients with hemorrhagic In patients with hemorrhagic shock, severe and can to resulting in cardiac and of blood is for the treatment of hemorrhagic The on of and the use of and as fluid for hemorrhagic In the guidelines the use of for fluid resuscitation because studies have shown that to the of patients with hemorrhagic shock, and in there is for whether albumin used as a colloid for fluid resuscitation in patients with hemorrhagic The use of HSA as a fluid for resuscitation in patients with hemorrhagic with is not a albumin is the for maintaining blood and osmotic In studies have shown that of HSA, in with hemorrhagic can increase and reduce The showed that 4% HSA or normal was used for fluid resuscitation and the target was the in the normal was than that in the albumin that albumin has for the of blood was in mortality the albumin and normal that HSA not an normal with respect to patient In a analysis of patients by that HSA not an resuscitation in the mortality of patients with hemorrhagic results also in the for the of the Critically Ill in studies on the of various and on have that decrease and factor and and albumin was not to in This a of albumin for fluid resuscitation in patients with hemorrhagic shock, has not in HSA is for patients with hemorrhagic in has to and hypoalbuminemia patients with hemorrhagic in has the loss of blood is to redistribution of and insufficient to In increased capillary by and for a of plasma can and the of In a of increased capillary due to the of HSA was than that of a colloid fluid resuscitation in patients the total capillary and In HSA has anti-oxidant effects and the of the vascular to the endothelial hemorrhagic and endothelial showed that HSA has a on the kidneys in critically ill HSA is for patients with hemorrhagic in has to and Recommendations for the Use of HSA in to blood blood of increased capillary and injury by it is common for patients to and hypoproteinemia of cardiac fluid is to such HSA is for fluid resuscitation in patients with cardiac HSA is used as a for patients with serum albumin and fluid resuscitation In a of patients cardiac surgery, HSA, or was at a of 50 the The results showed that the total fluid in the HSA was than that in the and In a meta-analysis of patients from clinical to albumin increased blood loss by blood by plasma by and by In a patients from the for was for patients who HSA and and patients who a on the of or the cardiac The results that to using using HSA in with reduced the in-hospital mortality and is with a in cardiac and can to increased and such as renal A patients cardiac with serum albumin of less than 40 g/L showed that the of HSA in patients with serum albumin of less than 40 g/L increased The incidence of in the albumin was than that in the and the risk of was reduced by there was in the incidence of severe the A was in the Consensus of the in on clinical that the use of HSA the of cardiac can thereby the for fluid In patients with hypoalbuminemia of less than 40 g/L) cardiac surgery, the use of HSA has effects on the Recommendations for the Use of HSA in Critically Ill are often in a with and In to a with the of and it can increase vascular and capillary while the plasma albumin concentration is hypoproteinemia is often in critically ill patients of albumin in critically ill patients the of is to for the risk of and in the and In a patients showed that a decrease of 10 g/L or more in the serum albumin concentration on the was with a increase in the risk of can used to patients at high risk of albumin in critically ill patients are with A patients that the serum albumin was an independent risk factor for the of albumin can reduce the of A total of patients in a the and The serum albumin was to an independent risk factor of albumin also to A patients who and that of albumin in the for Critically ill patients a and a failure analysis that serum albumin was a risk factor for failure in critically ill patients A meta-analysis of studies showed that the mortality increased by 137% for every 10 g/L in the serum albumin In a of critically ill patients who to the and patients the and analysis that hypoalbuminemia was an independent risk factor for in-hospital mortality of in risk and the of optimal HSA is for fluid resuscitation in critically ill patients with hypoalbuminemia the of patients albumin treatment and on whether albumin at serum albumin concentrations g/L. Albumin was to in critically ill patients with hypoalbuminemia to the A patients with liver from to in patients who acute kidney to liver and and albumin the to whether to and albumin (a was as a decrease of in serum concentration from the and a and a and patients in of the renal patients without who liver the used as a to The of renal in the was to than that in the and the incidence of kidney at liver was in the than that in the analysis that to and albumin was an independent of renal at whereas the risk not increase in to and albumin in patients with the for renal liver and the risk of renal failure In patients with liver who in liver with the fluid resuscitation plasma and blood and the fluid resuscitation 10 of and with the fluid resuscitation fluid resuscitation with albumin in the of liver was to the risk of HSA is for critically ill patients the serum albumin is and albumin g/L A of liver at a hospital and patients and g/L and g/L on the albumin on in the albumin g/L to have of than patients in the g/L Albumin can for patients surgery, in critically ill and A of patients that maintaining g/L the is in fluid intestinal clinical and Recommendations for the Use of HSA in with injury injury and are by high of mortality and is the treatment for acute resuscitation and and as a factor of HSA has used for a in the treatment of patients with In the that maintaining normal colloid osmotic by of HSA and of reduce This has greatly the clinical use of HSA, whether albumin can the of injury is HSA is not as the for fluid resuscitation in patients with acute injury guidelines and consensus the use of for fluid it is not to the results of clinical on fluid resuscitation in critically ill patients with acute because the of patients with acute injury in such studies is analysis of the showed a and mortality rate with 4% albumin to the in showed that the use of albumin was with a data analysis of the that the use of HSA at a of not was with an increased incidence of and in A in and a of patients with in that the use of HSA was with to In a in in patients with showed that HSA on the of was with of at The of HSA in and and through is HSA is not as the for fluid resuscitation in patients with acute HSA is for use in patients with and In reported that using albumin with for in of in less in and patients showed a or to the In reported patients with who HSA or 40 and increase in and a decrease in in the in patients with whereas in was A in that with albumin and in with HSA in the of to The use of HSA for in patients with injury is not HSA is in clinical practice, are more whether it can decrease the In reported a of the patients who there was a increase in and more in the HSA with normal was the there are studies on whether albumin used to reduce and the of studies are not to the of HSA on studies the with the with HSA are as is more relevant and has more on the the use of HSA to reduce in patients with injury is not Recommendations for the Use of HSA in with often severe blood loss and fluid loss and of fluid HSA is a and of HSA can the blood by 25 HSA can used for resuscitation and of the and of HSA for fluid resuscitation in patients The use of HSA for fluid resuscitation in patients is not have studies on the use of HSA for fluid resuscitation in patients as the guidelines for the use of HSA, and that for patients with hemorrhagic in the of is and HSA are In the critically ill patients, patients, and with 4% HSA and and in a analysis of patients, was in the and mortality the the HSA a mortality the mortality of the patients with injury In a of of patients with injury or Albumin for in with the mortality rate in the HSA was than that in the normal The results of the showed that HSA is as as normal as a resuscitation fluid for patients, its use to adverse in patients with The of the Society of Care Medicine on in Critically Ill Patients” also not the use of HSA for fluid resuscitation in patients with the critically ill patients, patients, who a resuscitation and a colloid resuscitation The that there was in the mortality the the colloid a mortality rate than the It is that the resuscitation in the HSA, and The resuscitation of the HSA was not and to further patients often from hypoalbuminemia due to blood capillary leakage, and the serum albumin is less than 10 the mortality to The for the Use of Albumin, and and the for Human Albumin that HSA can used in patients with severe hypoalbuminemia with serum albumin of g/L or patients with whether an exogenous of HSA can the of patients with hypoalbuminemia is an to HSA can used for patients with severe hypoalbuminemia and A on the data from the that critically ill patients in the patients, mortality resuscitation using HSA or normal of the serum albumin concentration or 25 In a a total of and patients from The results showed that HSA not mortality it help colloid osmotic more than intestinal and cardiac in and patients, was for the HSA can used for patients with severe hypoalbuminemia and Recommendations for the Use of HSA in with patients, with or severe fluid resuscitation the have and regarding the of resuscitation for HSA, a consensus on whether colloid resuscitation is and of colloid resuscitation is more The resuscitation with and is for patients with severe in the is the and albumin is an in of insufficient plasma In the among patients with severe capillary and the fluid of the blood resulting in reduced blood concentration and fluid the of the fluid is of and resuscitation with and the of in not a consensus on a and fluid for resuscitation of patients, the most used resuscitation is per to is effective in and due to The use of in resuscitation The use of of resuscitation the plasma concentration, further fluid and the of in blood the use of or to plasma reduce as are more with the the by the of a of studies have that have clinical in patients used of and increase the clinical studies have that colloid fluid resuscitation using HSA, and high molecular such as and can reduce the resuscitation fluid incidence of patient pressure, and and increase the of from In the of patients and an of HSA at a of and to plasma plasma albumin and osmotic The was to the in plasma and osmotic a of HSA to patients and and to the capillary of albumin and The results showed that the a HSA the plasma was by was to the was more than that of The of capillary albumin in the patients and and to and per of the The of plasma in the and HSA was an effective at and there was patients and In most use with plasma HSA to of resuscitation in patients with severe data on in patients are and the studies such as and The colloid resuscitation used in clinical of using plasma is on and there is to that plasma resuscitation is to albumin there is in the of of HSA can help blood it can cause and HSA is with and the rate to of HSA is in the of the of HSA is not In HSA in is used for resuscitation to HSA can used in patients with severe the of A analysis 40 patients to the the injury showed that the resuscitation the was per is than the using the and the rate It also that HSA can used for fluid resuscitation and for the of In and have that HSA can reduce the of fluid in patients in the of in with the and the with HSA and It showed that the use of HSA the of injury was with mortality, a of and less patients with serum albumin concentrations g/L with HSA A in patients with the is by capillary loss of serum and an increased risk of the serum albumin concentration is less than the patient with HSA at a concentration of more than in to the and the of with high to the of capillary in the of severe and the of a of patients a decrease in plasma and colloid osmotic pressure, resulting in the treatment in mainly to plasma colloid osmotic and HSA or in the of while HSA Recommendations for the use of HSA in In patients with acute the of the can the of to the The of and of can to and reduced whether albumin can the of patients with HSA is for patients with and hypoproteinemia to to have the effects of and In the of increased capillary leakage, the of colloid increase and the use of and is to the increased incidence of renal injury and in patients with To effects of studies have to the use of HSA in and meta-analysis the effects on HSA treatment not the mortality of patients with and effects on that HSA treatment the in patients with hypoproteinemia at albumin albumin and albumin was in the patients with HSA and with 10 the of relevant studies and insufficient of clinical are to the Recommendations for HSA Use in the Critically Ill with Critically ill patients with by as and and or failure are often to for and as as for liver A meta-analysis of that the mortality, in-hospital mortality, and mortality of patients and and synthesis of albumin and with increased of mortality among the clinical use of HSA for serum albumin in patients, recommendations are Critically ill patients with severe are to with albumin is the optimal treatment for with and HSA and The albumin for the treatment of in patients with an patients with that with the patients with medical treatment the risk of was by and the was by in the patients with albumin was by albumin A meta-analysis by with patients showed that the incidence of and mortality by and with albumin a meta-analysis by in 21 with patients without showed that the rate was not by albumin results also in the by and The the of to the of controversial in the meta-analysis to with was with and was with albumin use reduce mortality the are in the albumin in critically ill patients with and can reduce the risk of decrease the incidence of and the HSA with is for patients is common among patients with and the incidence is to 80% to with high The of serum and mortality in patients by HSA with A patients with that of patients with albumin and and of patients with albumin was as serum at at In in patients with the and the treatment A by a total of patients from with that mortality was by albumin and than with albumin In meta-analysis with patients from that the rate was in the patients with albumin and with albumin or with and rate was as in serum or serum of however, was in the and mortality A meta-analysis that 25 with a total of patients reported that a rate was in the patients with albumin and treatment than that with and treatment or with albumin and however, there was in of albumin with is to patients by The risk of in patients by albumin A that a in the incidence of and mortality was in the albumin treatment with the treatment in patients with Recommendations for the Use of HSA in Critically Ill on has an for in patients with severe failure in a critically ill patients on and HSA in the data from with the are HSA not to the of to or HSA was to the of in the to the and it was as an in patients with the and is that the is a and that a to the of such as in the the of albumin on the not and the albumin as it is by a also as the using or have in clinical the of HSA to the has a on blood long-term and on is The use of HSA and is for patients fluid resuscitation The of and have has resulting in capillary and loss and The of or in the of and cause an insufficient blood in the and blood fluid resuscitation in the of is Consensus on fluid resuscitation is patients with a fluid at that fluid resuscitation with a of HSA and to a in-hospital rate than fluid resuscitation with and that the fluid resuscitation of HSA the in-hospital rate with an of and an of The analysis that more to patients with and Recommendations for the of of HSA and of the adverse effects of HSA are a from adverse effects of are of patients such as and the rate is reduced or the is In and fluid are also common the of on the and the clinical In the of albumin and the and to the incidence of HSA for fluid resuscitation in A of patients with that patients who fluid resuscitation with HSA a risk of than patients who not shown in that patients fluid resuscitation for shock, resuscitation with HSA was with adverse renal A meta-analysis of clinical patients showed in the incidence of patients with sepsis fluid resuscitation with and fluid resuscitation with In HSA has in clinical the of its to colloid osmotic pressure, and its to and the concentration of it is used in critically ill patients the clinical of HSA in the controversial because of the and in on the analysis of the consensus a total of 25 recommendations on to use HSA in critically ill studies to on of critically ill patients are most to from the of HSA and that are of clinical by of from the the with on critically ill patients, it will to further the molecular and physiological the effects of albumin as as the of its such studies the the of the and of and whether concentrations of HSA have effects on clinical This was by the of and the and of