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

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.