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A16 month old boy with stage IV neuroblastoma and hypoalbuminaemia presented with a left sided haemorrhagic pleural effusion. He subsequently developed generalised oedema. You wonder if there was a role of albumin infusion in correcting hypoalbuminaemia and colloid osmotic pressure (COP), in order to treat the extravasation of fluid into tissue spaces.
Structured clinical question
In critically ill children with low serum albumin [patient group] does giving albumin infusion [intervention] improve COP and hence morbidity and mortality [outcome]?
Search strategy and outcome
Secondary sources—Cochrane Library (Issue 4, 2000): “hypoalbuminaemia”, seven systematic reviews (one relevant). PubMed clinical queries; LIMIT to English: “albumin” AND “critical illness”—159 references (one meta-analysis of 55 studies, four of which dealt with hypoalbuminaemia); “colloid osmotic pressure” AND “critical illness”—four references (one relevant to question); “hypoalbuminaemia” AND “critical illness”—six references (one relevant to question). See table 1.
There is a paucity of data in children. However, in critically ill adults a decrease in serum albumin is associated with increased morbidity and mortality. This may represent a disease related alteration in hepatic synthetic function. Albumin contributes up to 80% of COP in healthy subjects; however, its contribution towards COP is only 17% in critically ill individuals (Blunt et al). In adults, the studies suggest that albumin administration has no effect on mortality. In addition, its contribution towards COP is questionable. In fact, there appears to be no significant difference in COP of survivors compared with non-survivors of critical illness. Taken together, this information suggests that low serum albumin may merely be a surrogate marker of disease severity rather than an indicator of low COP. Hence, when treating patients with hypoalbuminaemia, efforts must be focused on correcting the underlying disorder, rather than reversal of hypoalbuminaemia; or, alternatively, on measuring COP directly. There are no such studies in children, but in the systematic reviews the relation between mortality and albumin administration was similar to that described in adults.
We therefore speculate that in children with protracted or critical illness, such as seen in oncological or life threatening disease, the adult relation between albumin, COP, and outcome may also hold. However, this idea should be tested by prospective biochemical study.
▸ CLINICAL BOTTOM LINE
Little published research addresses the question of albumin use in oncological hypoalbuminaemia in children.
Critically ill adults with hypoalbuminaemia do not have better outcomes when treated with albumin.
Citation Study group Study type (level of evidence) Outcome Key results Comments
Mahlon and Navickis (2001) 55 randomised controlled trials comparing albumin therapy with other interventions Systematic review (level 1a) Relative risk of death Pooled relative risk for death was 1.11 (95% CI 0.95 to 1.28). Relative risk for death in hypoalbuminaemia group was 1.59 (95% CI 0.91 to 2.78). Overall, no effect of albumin on mortality detected Relative risk was lower in trials with blinding, mortality as end point, no crossover, and 100 or more patients. Only 5 trials dealt with patients with hypoalbuminaemia Alderson et al (2001) 30 randomised controlled trials comparing albumin with other interventions in critically ill patients Systematic review (level 1a) Mortality For hypoalbuminaemia relative risk of death was 1.69 (95% CI 1.07 to 2.67). Pooled relative risk of death with albumin was 1.68 (95% CI 1.26 to 2.23). The risk of death in the albumin treated group was higher than in the comparison group Large peer response (BMJ 1998;317:882, 1999;318:464, 1214). Small trial bias, lack of enough trials in the paediatric population and concerns over homogeneity through the trials Blunt et al (1998) 145 survivors and non-survivors of prolonged critical illness Retrospective review of practice (level 4) COP and mortality Non-survivors had significantly lower mean serum albumin compared with survivors; p<0.05. Albumin only contributed to 17% of the COP in critically ill patients. There was no relation between death and COP Adult pattern disease: one half of this population were postoperative patients, e.g. aortic aneurysm, gastrointestinal and renal patients Grundmann and Heistermann (1985) 220 patients on adult ITU randomised to receive albumin when COP fell <24 cm H2O (group 1) or COP <29 cm H2O (group 2) Prospective randomised controlled trial (level 1b) Postoperative complications, COP, duration of intensive care and mortality Albumin replacement did not influence the final outcome. The 95% CI of risk difference for mortality includes zero (-5.4%, -16.6 to 5.8%). The absolute risk increase of lower COP (<20 cm H2O) for mortality was 50.5% (95% CI 20.5 to 80.5%) Both groups received albumin. All patients were postoperative