HPE Human albumin handbook | Page 23

hepatocytes ( 9 – 14g / day ) but is not stored in the liver but secreted directly into the blood of the sinusoidal space . Its half-life is approximately 17 – 19 days . Normal plasma albumin concentration is 35 – 50g / l ( about 140g / 50kg body weight ) and is the main determinant of plasma colloid osmotic pressure , maintaining 70 – 80 % of effective plasma colloid osmotic pressure . In addition , albumin has many other physiological functions , including effects on oxidation , substance transport and metabolism , immune conditioning and anticoagulation . More importantly , in recent years , it has been found that integration of albumin with endothelial glycocalyx coating components is crucial for structural and functional integrity of the vascular endothelial barrier . ^{7 , 8}

Human albumin has long been used in fluid resuscitation for critically ill patients . Its effects on osmotic pressure lead to blood volume expansion . The use of albumin in critically ill patients has been questioned because it was thought to possibly increase mortality , but a subsequent large-scale RCT proved its safety . ⁹ The SAFE trial was a prospective , multicentre , randomised , double-blind controlled trial that compared 4 % albumin with physiological saline in 6997 critically ill ICU patients . ¹⁰ It was found that there was no significant difference in the 28-day mortality of ICU patients with 4 % albumin or physiological saline . Subgroup analysis of the SAFE trial revealed that the use of albumin in patients with sepsis may reduce mortality .

The ALBIOS trial was a multicentre , open-label trial , including 1818 patients with severe sepsis in 100 ICUs who were randomised to receive 20 % albumin + crystalloid or crystalloid alone . ¹¹ In the albumin group , target concentration for serum albumin was ≥30g / l . There was no significant difference in the overall 28-day all-cause mortality , but the mortality of patients with septic shock at the time of enrollment decreased ; the mean arterial pressure in the albumin group was higher than that of the crystalloid group during the first 7 days ( p = 0.03 ), net liquid balance was more toward negative ( p < 0.001 ) and the vasoconstrictor / positive inotropic drug was discontinued earlier ( p < 0.007 ). Meta-analysis of five studies in patients with sepsis showed that albumin in severe sepsis tended to reduce the 90-day mortality rate ( odds ratio ( OR ): 0.88 ; 95 % CI 0.76 – 1.01 ; p = 0.08 ) but significantly reduced the 90-day mortality rate in patients with septic shock ( OR : 0.81 ; 95 % CI 0.67 – 0.97 ; p = 0.03 ). ¹² In addition , the use of albumin in patients with septic shock had a protective effect on renal function . ¹³

During fluid resuscitation , it is a clinical dilemma as to how to properly meet the demand of adequate resuscitation while minimising cumulative infusion volume to avoid fluid overload . The SWIPE trial using human serum albumin of high concentration ( 20 %) for human serum albumin resuscitation provides good evidence . ¹⁴ The patients included in the trial were adults with haemodynamic instability within 48 hours of admission and requiring intravenous infusion . They were randomised to receive 20 % albumin or low-concentration ( 4 % or 5 %) infusion . Compared with 4 – 5 % albumin , the 20 % albumin group had significant reductions in both 48-h cumulative resuscitation fluid volume and cumulative fluid balance .

Due to the shortage and high price of albumin , researchers have been committed to the development of other plasma amplifying agents . Three semi-synthetic colloidal liquids have been used in practical clinical applications : gelatins , prepared through the hydrolysis of bovine collagen , dextrans , obtained by bacterial biosynthesis , and HES solutions synthesised from corn or soybean starch as raw materials . Several large-scale clinical studies have investigated the safety of HES for resuscitation of patients with sepsis , such as the VISEP , CRYSTMAS , 6S , and CHEST trials , suggesting that there are many safety hazards associated with HES including increased risk of acute kidney injury ( AKI ), increased demand for renal replacement therapy ( RRT ), and higher mortality . ^{15 – 18} Subsequent meta-analysis also confirmed the association between HES , AKI and mortality . ¹⁹ Another study suggested that gelatin increased the risks of allergies , mortality , renal failure and bleeding , and dextran also increased the risks of allergic reactions and bleeding . ²⁰ Current guidelines and consensus oppose the use of HES , gelatin and dextran in critically ill patients , especially in those with sepsis . ^{1 , 6 , 21}

Balanced or non-balanced crystalloids ? According to whether the electrolyte composition of the solution is close to the level in plasma , crystalloids are divided into two categories : balanced and non-balanced . Commonly used balanced crystalloids include lactated Ringer ’ s solution , Hartmann ’ s solution and Plasmalyte ; non-balanced crystalloid refers to physiological saline ( 0.9 % sodium chloride ) ( Table 1 ). In recent

TABLE 1

Comparison of components in plasma and commonly used resuscitation fluids

Fluid Sodium Potassium Calcium Magnesium Chloride Acetate Lactate Gluconate Bicarbonate

Plasma 135 – 145 4.5 – 5.0 2.2 – 2.6 0.8 – 1.0 94 – 111 1 – 2 23 – 27

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