Effect of exogenous albumin on the incidence of postoperative acute kidney injury in patients undergoing off-pump coronary artery bypass surgery with a preoperative albumin level of less than 4.0 g/dl

  • Lee EH, Kim WJ, Kim JY, Chin JH, Choi DK, Sim JY, et al.
  • Anesthesiology 2016;124(5):1001-11.

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:

  • AKI Network criteria – 14 patients (x%) in the albumin group versus 26 (y%) in the saline group (p=0.048)
  • KDIGO criteria – 18 patients (x%) in the albumin group versus 32 (y%) in the saline group (p=0.012).

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.

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References

Lee EH, Kim WJ, Kim JY, Chin JH, Choi DK, Sim JY, et al. Anesthesiology. 2016 May;124(5):1001-11.

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