Albumin in burn shock resuscitation: a meta-analysis of controlled clinical studies

  • Navickis RJ, Greenhalgh DG, Wilkes MM.
  • J Burn Care Res, 2016 May–June;37(3):e268–78.

This paper presents a meta-analysis to determine the impact of resuscitation with albumin on the morbidity and mortality of adult burn patients. It is a combination of randomised and non-randomised trials, examining data from 688 total patients. Analysis initially showed no significant improvement for albumin versus control. However, when two of the studies at most risk of bias were removed to reduce the heterogeneity of the data, albumin was found to reduce mortality and some measures of morbidity.

Fluid resuscitation is one of the cornerstones of treatment for acute burn care, however the optimal treatment modalities and rates of administration are not well investigated. Historically, burn treatments used colloids – predominantly derived from blood products – but this was challenged by the unacceptable rates of viral hepatitis transmission. The emphasis on sodium replacement led to crystalloids becoming predominant in the 1970s, and treatment regimens have remained largely unchanged since. Over time the recommended volumes used have slowly increased, and recognition of the nuances of fluid balance has brought the current paradigm into question. Excess fluid administration has been linked with higher complication rates; pneumonia, bacteraemia, respiratory distress syndrome, multi-organ failure and compartment syndrome (both abdominal and peripheral) are all increased with excessive fluid therapy. Albumin and fresh frozen plasma are being used routinely in an effort to reduce these effects, yet the evidence is not sufficient to provide a clear case.

The authors identified all controlled clinical studies comparing albumin and a crystalloid in adult burn patients. After exclusions, four randomised and four non-randomised trials were included for analysis. Statistical analysis was carried out following data extraction. Pooled odds ratios (OR) and 95% confidence intervals were calculated. Bias and heterogeneity of results were assessed.

The four randomised studies were generally of poor quality; three were over 30 years old and only one was multicentre. They were all small in size, rendering them vulnerable to chance imbalances despite randomisation. The non-randomised trials were of better quality, with dates ranging from 2007–2012, and they accounted for 81.2% of total patients. However, they were limited by their retrospective design.

Mortality data revealed 119 total deaths; inhalation injury was associated with a significantly worse prognosis – skewing the unadjusted OR for one of the trials. There was significant heterogeneity in the results, which may have been due to unadjusted excess baseline risk. In two of the studies the ORs for death with albumin treatment (4.12 and 5.76) were considerable outliers – the adjusted ORs for the other six trials were all in the range 0.23–0.50. When these outlier trials were excluded from the analysis, heterogeneity of results was abolished and a significant mortality benefit with albumin treatment demonstrated: OR 0.34, 95% CI 0.19–0.58 (p < 0.001).

The most common adverse events recorded were compartment syndrome (abdominal and peripheral), respiratory complications and renal dysfunction. The group treated with albumin had an 81% reduced risk of compartment syndrome (pooled OR: 0.19 [p < 0.001]), reflected equally in all studies. Although there was some improvement in other outcomes, only ‘gastrointestinal and central nervous system complications’ was statistically significant (relevant data were only recorded in one study).

In their discussion, the authors reiterate that the current evidence is limited at best, but their findings suggest there may be a mortality and morbidity benefit with albumin treatment. Burn mortality in general is at an all-time low, and more emphasis is being placed on reducing morbidity. It is this which has led to a resurgence of interest in albumin – as more fluid remaining in the intravascular space should reduce oedema, preventing compartment syndrome and the need for fasciotomy. The authors also discuss the current Cochrane meta-analysis of albumin use in critically injured patients, which suggested an increased mortality with albumin administration – they believe that the methodology and inclusions were not optimal.

It is clear that more study is needed in this field, and is difficult to draw any firm conclusions from this paper; however albumin treatment may demonstrate some benefit over crystalloid fluids in treating burns patients.

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