This meta-analysis examines whether the dosing of albumin affects outcomes in type 1 hepatorenal syndrome (HRS). Most studies to date have focussed on the vasopressor component of treatment, while this study extracted data from those studies to determine whether there was a response to increased levels of albumin. They were able to demonstrate a statistically significant association between patients who received more albumin overall and 30-day survival (HR 1.15; 95% CI 1.02–1.31; p=0.023).
Hepatorenal syndrome is a form of functional severe renal failure in patients with advanced liver cirrhosis; it is typically diagnosed by excluding other causes. There are two variants: type 1 disease has a fast onset and is treatable, although has a high mortality rate – average survival if disease is untreated is 11 days, and with treatment approximately half of affected patients will survive; type 2 disease has a more insidious onset and a median survival of 6 months. Treatment is with vasopressors and albumin infusion, with evidence demonstrating that the combined action provides better clinical outcomes versus monotherapy with either alone. To date, most studies have centred on the role of the vasopressor, testing different formulations and doses. Hard evidence is generally lacking regarding the optimisation of the albumin infusion however – prompting the authors to initiate this meta-analysis.
Studies which evaluated albumin infusion with vasopressors were identified; specifically, data were needed on HRS reversal and/or survival time. Unfortunately, there were no randomised trials suitable for inclusion, so only observational trials were included. Suitable papers were scrutinised to eliminate any redundant data included in multiple sources. Numerous data were extracted regarding therapy strategy and outcomes. The hypothesis to be tested was that outcomes of type 1 HRS vary significantly as a result of albumin dose. Potentially confounding factors were controlled for using a Cox proportional hazards regression model.
A total of 19 studies published between 1999 and 2012 met the inclusion criteria, comprising 574 patients in total – the median number of patients per study was 24. Baseline characteristics were consistently reported; age, serum creatinine, bilirubin and albumin, and mean arterial pressure; a diverse range of clinical criteria were also available for the analysis. HRS reversal was defined as correction to a serum creatinine of <1.5 mg/dL (132 µmol/L). The pooled data suggested the overall percentage attaining HRS reversal was 49.5% (95% CI 40.0–59.1%). Time of survival data were reported in 15 studies (n=377); pooled survival was 50.6% at 30 days (95% CI 45.5–56.3%). It was noted that increments of 100 g in cumulative albumin dose were associated with significantly increased survival (HR 1.15; 95% CI 1.02–1.31; p=0.023). An association was also noted for 10 g increments of daily albumin, although this did not reach statistical significance.
In their discussion, the authors highlight that this is the first clear data to discriminate between albumin doses. The outlook for survival in HRS has improved markedly, but there is still room for improvement with currently available therapies; a focus on optimisation of albumin dosing could improve outcomes further. The authors point to the homogenous definition for reversal of HRS as a strength of the study, alongside a robust sample size for those at risk of death. They were able to control for vasoconstrictor dose and type, treatment duration, baseline bloods as well as several other clinical factors. It was limited by not being designed from the start as a head-to-head comparison, and as such can only demonstrate an association rather than a causative relationship. It is remarked that longer survival may correspond to receiving more albumin overall, however survival was not associated with longer duration of treatment or larger cumulative doses of vasopressors. The survival benefits of albumin have been identified in a variety of settings related to severe liver disease – all suggesting it is a useful strategy for patients with decompensated cirrhosis. There were few adverse events identified that were attributed to albumin therapy.
This study does not provide a basis for a rework of clinical protocols, however it does suggest a relationship between the administration of albumin and increased survival that should be further investigated. The study forms the basis for further confirmatory trials to demonstrate whether causation exists. For a condition such as HRS with a high mortality rate, every percentage point that survival is increased has a substantial impact on patients, and optimisation of treatment is a key strategy to improving care.
Catch-up on the debate surrounding hydroxyethyl starch use as we take you on an interactive journey through its changing fortunes. Do you think current restrictions will be enough to change clinical practice?
This position paper from the Italian Association for the Study of the Liver (AISF) and the Italian Society of Transfusion Medicine and Immunohaematology (SIMTI) reviews the evidence for the use of albumin in several settings related to liver cirrhosis.
This paper presents a meta-analysis to determine the impact of resuscitation with albumin on the morbidity and mortality of adult burn patients.
This meta-analysis examines whether the dosing of albumin affects outcomes in type 1 hepatorenal syndrome (HRS).
This review article explores the relationship between low albumin levels and acute kidney injury (AKI).
This meta-analysis pooled data from three large randomised controlled trials to determine whether early goal-directed therapy (EGDT) was an effective intervention for managing septic shock.
This systematic review and meta-analysis looked at the different mortality rates of various intravenous fluids and fluid protocols when used for resuscitation in sepsis.
This Chinese randomised controlled study explores the impact that a goal-directed fluid restriction (GDFR) protocol had on outcomes during anaesthesia for brain surgery.
This review paper examines the role of albumin in chronic liver disease, assessing the evidence for its use in several key clinical areas.
This matched cohort study aimed to determine whether a goal-directed fluid therapy (GDFT) intervention, delivered intraoperatively, would reduce post-operative morbidity in patients undergoing hip revision surgery.
This study explored fluid prescribing practices in intensive care – providing a picture of how fluid resuscitation is being managed internationally.
This multicentre audit reviewed the records of 431 patients who had undergone major elective surgery. The authors sought to determine how well IV fluids were prescribed both intraoperatively and perioperatively when compared with current guidance.
This double-blinded, randomised controlled trial examined whether pre-operative administration of exogenous albumin affected rates of acute kidney injury (AKI).
This article is a review and summary of the current opinion of albumin in fluid management.
This retrospective, observational study used a propensity scoring system to match patients treated with saline with those given a balanced, calcium-free fluid.
A recent PRAC review has recommended suspension of marketing authorisations for HES solutions for infusion across the EU.
Following the European Medicines Agency’s (EMA) suspension of the marketing authorisations of hydroxyethyl starch (HES) solutions across the European Union (EMA, 2018), Roberts et al., have written an open letter addressed to the World Health Organization (WHO) Director General seeking support for the suspension of HES solutions and expanding it to a worldwide ban.
The Coordination Group for Mutual Recognition and Decentralised Procedures (CMDh) endorse the suspension of hydroxyethyl-starch (HES) solutions, due to serious risks of kidney injury and death in certain patient populations.
The hypothesis that hypertonic fluid has a dual physiological role, increasing circulatory volume while administering minimal volumes and muting the pro-inflammatory response to injury and illness, may be appealing, but is it superior to isotonic fluids in practice?
In this post-hoc, subgroup analysis (study 1) and prospective, single-centre nested cohort (study 2) from the SPLIT (0.9% saline vs. PL-148 for ICU fluid therapy) trial, the investigators hypothesised that patients receiving Plasma-Lyte 148 would require fewer blood products and have less post-operative bleeding than those receiving saline.
Acute kidney injury (AKI) affects one-fifth of major surgery patients, increasing the risk of long-term mortality. This review paper discusses recent study data, discussing the best methods for preventing postoperative AKI.
Guidelines to promote the early recovery of patients undergoing major surgery recommend a restrictive intravenous-fluid strategy for abdominal surgery. However, the supporting evidence is limited, and there is concern about impaired organ perfusion.
Cirrhosis of the liver is a leading cause of mortality. For patients with decompensated cirrhosis, long-term weekly human albumin administration can act as an effective disease-modifying treatment.
In 1896 Ernest Starling published his hypothesis for fluid exchange, whereby fluid exchange exists mainly in the capillaries through a process of plasma ultrafiltration across semipermeable membranes (Starling, 1896). But is this 19th century theory something of the past?
Long-term albumin treatment for ascites associated with cirrhosis has been debated in recent years, with mixed results reported for the treatment’s efficacy. In this non-randomised prospective study, Di Pascoli and colleagues question the benefits of long-term albumin in patients with liver cirrhosis and refractory ascites, focussing on survival and emergent hospitalisations. Could this be part of the solution to the ongoing challenge of ascites in cirrhosis?
The choice of fluid administered during cardiac surgery remains a debated topic, often focussed around colloid solutions containing albumin. Conflicting results from numerous studies have left questions over albumin safety and potential to be superior to crystalloids during surgery. Kingeter et al. hoped to achieve clarity on this controversial topic in a retrospective study of cardiac surgery outcomes over a 12-year period.
Patients admitted to intensive care are often haemodynamically unstable with fluid resuscitation therapy regularly used to overcome this. The use of small volume resuscitation with 20% albumin has historically been limited compared to standard fluid resuscitation with 4–5% albumin due to safety concerns, but could those concerns be misplaced? Read more about how the SWIPE trial has provided new insights into the possibilities of using small volume resuscitation within the ICU.