In this issue of Indian Pediatrics,
Shahian and Moslehi(1) report that albumin given prior to exchange
transfusion in jaundiced but healthy term newborns is associated with
significantly lower post-procedure total serum unconjugated bilirubin
levels (TSB) and a reduced need for further treatment. Unfortunately, the
evidence presented does not support routine administration of albumin
prior to exchange transfusion because the actual amounts of bilirubin
removed by the procedure are not documented. The bilirubin removed by the
procedure is readily obtained by measuring the volume and bilirubin
content of the blood discarded during the procedure(2-4). Without these
critical data, the study does not prove causation (i.e. that albumin
administration was the cause of the difference in outcome).
The post-exchange transfusion or "rebound" TSB is not
an appropriate outcome metric for judging the efficiency of an exchange
transfusion, regardless of the pre-exchange TSB(3). The amount of
bilirubin removed (the efficiency of the procedure) depends primarily on
how much pre-exchange bilirubin has accumulated in both the extravascular
and vascular compartments (the miscible bilirubin pool). Extravascular
bilirubin moves into the vascular compartment during the procedure and the
degree to which this impacts the post-exchange TSB therefore depends on
both the pre-exchange extravascular and vascular bilirubin levels(3).
Variability in vascular bilirubin-albumin binding confounds the
relationship between TSB and the extravascular bilirubin level(5), and
there is no guarantee that the extravascular bilirubin levels were similar
in the two study groups despite similar pre-exchange TSB and
randomization. The albumin group was admitted on average a day earlier
than the controls (P<0.001) and may have accumulated less bilirubin
and had lower miscible bilirubin pools (better than average bilirubin-albumin
binding would account for the relatively higher TSB around 30 mg/dL in the
vascular space).
It is also difficult to reconcile the differences in
post-exchange TSB with the dose of albumin used in this study,
particularly since little difference in albumin concentrations was
documented between the study groups either before or after the procedure.
Assuming the controls had a plasma volume of 1.6 dL (0.50 dL/kg x 3.2 kg)
and a TSB of 30 mg/dL, the vascular bilirubin available for removal at the
beginning of the procedure is 48 mg. The post-exchange TSB of 21.4 mg/dL
indicates a net removal of about 15 mg of bilirubin (33% efficiency). If
albumin administration (1 g/kg) transiently increased the albumin from 3.5
to 4.0 g/dL and the plasma volume by 10%(3,6), the maximum pre-exchange
vascular bilirubin available for removal would increase to about 62 mg (30
mg/dL × (4.0/3.5) × 1.8 dL), a 29% increase. In order to obtain a
post-exchange TSB of 14.4 mg/dL, about 40 mg of bilirubin would need to be
removed (65% efficiency, a 167% increase in bilirubin removed). This is
far beyond the typical efficiency of exchange transfusions(3) and requires
documentation with the actual amount of bilirubin removed by the
procedure, if we are to conclude that albumin administration augmented
bilirubin removal to this degree.
Odell, in 1959, verified the hypothesis that vascular
bilirubin-albumin binding would cause a shift of bilirubin from the
extravascular to intravascular compartment following albumin
administration(7). Subsequent studies showed that albumin administration
improved the efficiency of exchange transfusion, as measured by the
bilirubin removed (not the post-exchange TSB), by up to about 40%(2- 4,6).
While albumin may improve the efficiency of exchange transfusion, the
improvement has not been overly profound and routine clinical use is not
justified by this study. We are also reminded once again that vascular
bilirubin-albumin binding limits the use of TSB as an indicator of the
size of the miscible bilirubin pool, the magnitude of the ongoing
bilirubin production/excretion mismatch, and the overall risk of bilirubin
toxicity(5).
Funding: None.
Competing interests: None stated.
References
1. Shahian M, Moslehi MA. Effect of albumin
administration prior to exchange transfusion in term neonates with
hyperbilirubinemia: a randomized controlled trial. Indian Pediatr 2010;
47: 241-244.
2. Odell GB, Cohen SN, Gordes EH. Administration of
albumin in the management of hyperbilirubinemia by exchange transfusions.
Pediatrics 1962; 30: 613-621.
3. Valaes T. Bilirubin distribution and dynamics of
bilirubin removal by exchange transfusion. Acta Paediatr Scand 1963; 52 (suppl
1149): 1-117.
4. Comley A, Wood B. Albumin administration in exchange
transfusion for hyperbilirubinemia. Arch Dis Child 1968; 43: 151-154.
5. Ahlfors CE, Wennberg RP, Ostrow JD, Tiribelli C.
Unbound (free) bilirubin (bf): improving the paradigm for evaluating
neonatal jaundice. Clin Chem 2009; 55: 1288-1299.
6. Wood B, Comley A, Sherwell J. Effect of additional
albumin administration during exchange transfusion on plasma
albumin-binding capacity. Arch Dis Child 1970; 45: 69-52.
7. Odell GB. The dissociation of bilirubin from albumin and its
clinical implications. J Pediatr 1959; 55: 268-279.
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