This double-blinded, randomised controlled trial examined whether pre-operative administration of exogenous albumin affected rates of acute kidney injury (AKI). The population studied were patients undergoing an off-pump coronary artery bypass who were hypoalbuminaemic. The results demonstrated a higher urine output intra-operatively, and a lower rate of AKI in those who received albumin. There were no significant differences in mortality or requirement of renal replacement therapy.
Post-operative AKI in bypass surgery is a common clinical problem that is associated with increased morbidity and mortality, and off-pump procedures mitigate some of the risk. Preventive measures would therefore be worth establishing. Albumin is the primary modulator of plasma oncotic pressure, but has a role in many other processes – it mops up toxic substances, both exogenous and endogenous, and scavenges free radicals. A previous study by the same authors showed that a pre-operative hypoalbuminaemic state (<4.0 g/dl [<40 g/l]) was associated with increased incidence of AKI. Although it is common practice, there is no reliable evidence to demonstrate that pre-operative correction of hypoalbuminaemia counters that risk, or to determine thresholds for treatment. It was for this purpose that the current study was undertaken.
Based in Korea, this was a prospective, randomised, double-blind superiority study. Patients planned for elective off-pump bypass surgery were approached for enrolment if they were found to have an albumin level below 4.0 g/dl (40 g/l) on their pre-operative blood measurements. Enrolled patients were randomised to receive either 100, 200 or 300 ml of 20% human albumin (dose determined by their initial albumin levels), or 100 ml of 0.9% saline at anaesthetic induction. Other surgical and anaesthetic factors were kept as similar as possible, and any patient with a post-operative serum albumin of <3.0 g/dl (30 g/l) was given albumin regardless of study arm. Repeat blood samples were taken at arrival in intensive care, at 6 hours post-op, at 1, 2 and 3 days, and at discharge, as well as whenever clinically necessary. The primary outcome was development of AKI, defined by either the Kidney Disease Improving Global Outcomes (KDIGO) or AKI Network criteria (both were assessed). Secondary outcomes included mortality, severe AKI and requirement for renal replacement therapy.
A total of 220 patients were randomised at a 1:1 ratio. Following exclusions for conversion to cardiopulmonary bypass or surgery cancellation, 203 patients were included in the final analysis (102 in the albumin group, 101 in the placebo group). There were no significant differences in demographics. All intra-operative characteristics were similar except for urine output, which was significantly increased in the albumin group (p=0.006), despite having the same median volumes of fluid infused. The median albumin levels pre-infusion were similar. At the 6 hours post-operative measurement, the albumin group had a non-significantly higher median level of 2.7 g/dl (range 2.4–2.9) versus 2.2 g/dl in the placebo group (range 2.0–2.4), while all subsequent levels post-operation were again similar between the groups.
Incidence of AKI was significantly higher in the non-albumin group by both criteria:
The rates were similar to those described following adjustment for diuretic use, or diuretic plus ACE inhibitor/alpha-2 blocker. No secondary outcomes met the threshold for statistical significance.
In their discussion, the authors suggest potential reasons for the difference in incidence of AKI. This study was not directed towards establishing a mechanism, but other studies were. They suggest that it may be as simple as an increase in circulating volume, with albumin acting as a volume expander – although its ligand-binding of nephrotoxic drugs or antioxidant properties may play a role. Comparable studies have not demonstrated the same effect with pre-operative albumin, although the administration times have not been as close to surgery. The authors also mention the lack of a significant difference in mortality and haemodialysis, and posit that this may be due to a limitation of the effect of albumin, but equally could represent the lack of power in the experimental design to explore these interactions. Other limitations of the study include the lack of applicability to patients with cardiac dysfunction (since they were excluded), the relatively small scale, and the possibility that the ‘positive’ finding of reduced AKI with albumin infusion may have represented a negative effect relating to chloride administration and its impact on the kidneys.
This study provides an answer to the clinical problem of hypoalbuminaemia and its increased risk of AKI. Certainly requiring more exploration, the prospect of reducing operative morbidity and potentially mortality is an interesting potential target.
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?
Lee EH, Kim WJ, Kim JY, Chin JH, Choi DK, Sim JY, et al. Anesthesiology. 2016 May;124(5):1001-11.
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.