follow-up period was significantly lower in the study group ( p = 0.018 ); the 30-day medical cost of patients in the study group was significantly lower than that in the control group ( 1915 Euros vs . 4612 Euros , p = 0.004 ). In this study , in terms of preventing complications of liver cirrhosis , human albumin was more cost-effective than polygelatin . 22 Due to differences in medical cost in various countries , the results of economic evaluation in other countries are for reference only .
For the efficacy of long-term albumin treatment for ascites , a meta-analysis 21 showed that longterm albumin infusion combined with diuretics significantly reduced the recurrence rate of ascites ( RR = 0.11 ; 95 % CI : 0.06 – 0.20 ) and reduced rates of complications ( RR = 0.35 ; 95 % CI 0.18 – 0.69 ) and rate of readmission ( RR = 0.22 ; 95 % CI 0.12 – 0.42 ). Mortality rate between the two groups ( RR = 1.06 ; 95 % CI 0.58 – 1.92 ) was not statistically different . No albumin-related adverse reactions were found during the study . Owing to the small sample size , the quality of evidence was evaluated as lowquality according to GRADE . Factoring in the high cost of this treatment strategy also explains why long-term application of albumin infusion has not been recommended by guidelines from home and abroad . 23
Prevention of renal failure after SBP In SBP patients , effective blood volume and arterial blood pressure are significantly reduced , alongside renal perfusion , resulting in renal dysfunction . Approximately one-third of patients with SBP develop renal dysfunction , which is an independent predictor of death during hospitalisation . Several studies and meta-analysis 24 – 26 showed that cephalosporins combined with albumin infusion reduced the incidence of renal failure and in-hospital and three-month mortality after SBP . The albumin dose was 1.5g / kg on the day of diagnosis , and 1g / kg on the third day . Physicians in China believed that the dose was too high . In order to avoid excessive cardiac load caused by over-correction of circulating blood volume , it is recommended that the patient ’ s medication regimen should be individualised .
A preliminary study evaluated the effectiveness of lower albumin dose . 27 In this study , a group of patients with cirrhosis and SBP was treated with a reduced dose of albumin ( 1g / kg albumin on the day of diagnosis and 0.5g / kg on day 3 ). Among the group , 77 % were high-risk patients . In terms of preventing renal failure , it seemed to be as effective as the standard regimen . The in-hospital mortality ( 27 % vs 21 %) and three-month mortality ( 36 % vs 37 %) in patients receiving reduced-dose and standard-dose albumin were not statistically different .
A small study showed that SBP patients with a lower risk of kidney injury ( defined as bilirubin < 4mg / dl and serum creatinine < 1mg / dl ) did not die from renal dysfunction when being treated with antimicrobial therapy only . 28 Another retrospective study 29 showed the incidence of renal failure in patients with low-risk SBP ( urea < 11mmol / l / bilirubin < 68μmol / l or untreated human albumin ) and in-hospital and three-month mortality were significantly lower than in high-risk SBP patients ( urea > 11mmol / l / bilirubin > 68μmol / l or without albumin treatment by an attending physician ; incidence rates were 4.7 %, 3.1 % and 7 % vs 25.6 %, 38.2 %, and 47 %). Among high-risk SBP patients , the in-hospital mortality rate of those treated with albumin was lower than those treated with antimicrobials only ( 28.8 % vs 46.8 %) and had a higher survival rate at three months ( 62 % vs 45 %). Therefore , albumin can significantly improve the survival rate of high-risk SBP patients , but it does not seem to be essential for low-risk SBP patients .
Prevention of circulatory dysfunction after large volume paracentesis Guidelines from China and abroad recommend large volume paracentesis ( LVP ) as a second-line treatment for liver cirrhosis and ascites . 17 , 18 , 20 Most patients who receive LVP without plasma volume expansion develop post paracentesis circulatory dysfunction ( PPCD ). The most effective method to prevent PPCD is to administer plasma volume expander to offset the loss of effective blood volume . It was first demonstrated that infusion of albumin after paracentesis improved circulation and prevents PPCD in the 1980s . 30 Circulatory dysfunction is defined as elevation of plasma renin activity level by > 50 % within 4 – 6 days of paracentesis . The development of PPCD is associated with more frequent recurrence of ascites , dilutive hyponatraemia and renal dysfunction , readmission rates , and shorter survival . 30
A meta-analysis in patients with liver cirrhosis and ascites receiving LVP ( albumin 23 – 32g / l ) showed that , compared with other plasma volume expanders or vasopressin , human albumin treatment after LVP can reduce the incidence of PPCD , hyponatraemia and risk of death by 66 %, 42 %, and 36 %, respectively . 31 In the eligible trials included , the average amount of ascites aspired was more than 5l . There was no significant difference between those with 5.5 – 8.0l and > 8l aspired . In most of these studies , 8g albumin was given for each litre of ascites aspired while just a few studies gave 5g or 6g . There is only one randomised trial that compares standard dose albumin ( 8g / l upon aspiration , 35 patients ) and half-dose albumin ( 4g / l upon aspiration , 35 patients ) after LVP . 32 The incidence of PPCD , hyponatraemia , and renal failure was similar between the two groups ( 14 % vs 20 %, 9 % vs 6 %, and 0 % in both groups ). In six months of follow-up , there was no difference between the two groups in survival rate , the need for LVP , and recurrence rate of ascites . However , a small sample size reduced the quality of the study and the certainty of the conclusions .
HRS Type 1 HRS is a rapidly progressing acute renal failure that is secondary to inducing factors such as bacterial infection . Type 2 HRS occurs in patients with refractory ascites . Its progression to functional renal failure is slower than Type 1 HRS . The most effective treatment for Type 1 HRS is the combination of vasopressor and albumin to further
33 , 34 increase effective circulation volume . Randomised and non-randomised clinical studies 35 , 36 showed that the combined use of terlipressin and albumin improved renal function , whereas 40 %– 50 % of patients with Type 1 HRS can be completely reversed . In spite of prolonged survival between those whose renal function improved and those who did not , patients ’ overall survival rates were not significantly superior to those treated with albumin or placebo alone . 33 , 35 In addition , a meta-analysis by the Cochrane Network showed that terlipressin combined with albumin improved short-term survival . 37
The combination of albumin plus vasopressor demonstrates a dose – response relationship for treating hepatorenal syndrome . A meta-analysis evaluated the effect of different doses of albumin
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