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.
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?
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