Intensive Care Med
https://doi.org/10.1007/s00134-022-06795-x
CORRESPONDENCE
What’s wrong with the ten myths
about albumin: three layers for an indisputable
dispute
Khalil Chaïbi1,2, Stephane Gaudry1,2, Didier Dreyfuss2,3,4 and Thomas Edward Woodcock5*
© 2022 Springer-Verlag GmbH Germany, part of Springer Nature
The review by Joannidis et  al. [1] on Human Albu-
min Solution (HAS) and its use in intensive care poses
problems.
The form
Numerous articles and textbooks showed that financial
conflicts of interest (COIs) undermine scientific integrity
and accuracy of reviews and guidelines [2]. Two authors
declared fees from a company marketing HAS and this
reporting is appreciable. Although disclosure is neces-
sary, it is insufficient to protect against bias as clearly
stated by a former editor of the New England Journal of
Medicine [3]. Several major Journals have banned edito-
rials and guidelines by persons with COIs.
The surface
In myth #2, it is stated that albumin is more effective for
intravascular volume expansion than saline based on the
SAFE study. The difference in fluid volume administra-
tion between the two groups was only 300 mL/day dur-
ing the first 3 days. The total of fluid volume received by
critically ill patients may be more than 4000 mL by day.
With $232 for 1  L of 5% albumin (versus $2.32 for 1 L
of saline), each milliliter seems then a bit expensive. In
myth #3, it is stated that HAS administration prevents
acute kidney injury in “specific settings”. Evidence does
*Correspondence: thos.woodcock@gmail.com
5
FluidPhysiology.Org, Stockbridge, Hampshire, UK
Full author information is available at the end of the article
Didier Dreyfuss and Thomas Edward Woodcock contributed equally to
this work.
 
not support this assertion, but only low-grade (III) expert
opinion. Authors finally acknowledge that a large rand-
omized controlled trial (ALBIOS) did not confirm this
utterance. Putative effectiveness of albumin during sep-
sis is far from proven. In the ALBIOS study, no difference
in mortality of patients with sepsis (more than 60% with
shock) was observed. Post-hoc subgroup analysis sug-
gested that patients with septic shock may benefit from
albumin infusion. There is no published large randomised
controlled trial (RCT) on septic shock that showed a ben-
efit of albumin. In this context, the lack of publication of
the EARRS study (funded by industry) with nearly 800
patients included and no survival benefit observed with
HAS infusion is noteworthy [4]. Failure to publish results
is a form of scientific misconduct according to the Inter-
national Committee of Medical Journal Editors (ICMJE)
recommendations.
The substance
The extended Starling principle explains disappointing
trial outcomes for biophysical osmotic pressure therapy
with albumin. In myth #1, authors stated in the subhead-
ing that albumin does not leak from the intravascular
space into the interstitial compartment and therefore
does not contribute to oedema formation. Afterwards,
they admit a leakage from the intravascular space (Fig-
ure S1 in the publication). The arguments are exactly
the same as those presented in a paper in German by the
same authors and not quoted [5]. The authors claim that
it is a myth that albumin contributes to oedema, because
“albumin re-enters the bloodstream via the lymphatic
system at a rate similar to TER and does not remain in
the interstitium”. This assertion ignores the large pore
transport of albumin in inflammatory states and the
 Fig. 1  Layers of the endothelial barrier and transendothelial Starling forces. ESL endothelial surface layer, ECM extracellular matrix. The Starling
forces are capillary pressure Pc, interstitial pressure Pi, plasma colloid osmotic pressure πp and subglycocalyx colloid osmotic pressure πg. Plasma
water is filtered by the ESL and glycocalyx (small pores) before it passes paracellularly through tight junction breaks to the interendothelial cleft con-
taining intercellular adhesion molecules. Albumin is transported by large pore pathways such as the caveolae shown here

reabsorption of solvent to venular blood in lymph nodes, Publisher’s Note

a recognised exception to the no-reabsorption rule, cre-
ating a protein-rich effluent lymph to be pumped to the
great veins (Fig.  1). A more detailed demonstration is
provided in the Electronic Supplementary Material.
Supplementary Information
The online version contains supplementary material available at https://​doi.​
org/​10.​1007/​s00134-​022-​06795-x.
Author details
1
 Service de Réanimation Médico‑Chirurgicale, AP-HP, Hôpital Avicenne, 125
rue de Stalingrad, 93000 Bobigny, France. 2 French National Institute of Health
and Medical Research (INSERM), UMR_S1155, CORAKID, Hôpital Tenon,
Sorbonne Université, 75020 Paris, France. 3 Service de Médecine Intensive
Réanimation, Hôpital Louis Mourier, Colombes, France. 4 Université de Paris,
Paris, France. 5 FluidPhysiology.Org, Stockbridge, Hampshire, UK.
Declarations
Conflicts of interest
Authors declare no conflict of interest.
Springer Nature remains neutral with regard to jurisdictional claims in pub-
lished maps and institutional affiliations.
Received: 7 May 2022 Accepted: 1 June 2022
References
1. Joannidis M, Wiedermann CJ, Ostermann M (2022) Ten myths about albu-
min. Intensive Care Med. https://​doi.​org/​10.​1007/​s00134-​022-​06655-8
2. Emanuel EJ, Grady CC, Crouch RA et al (2008) The Oxford textbook of
clinical research ethics. Oxford University Press, Oxford
3. Angell M (2000) Is academic medicine for sale? N Engl J Med 342:1516–
1518. https://​doi.​org/​10.​1056/​NEJM2​00005​18342​2009
4. Efficacy and tolerance of hyperoncotic albumin administration in septic
shock patients: the earss study | Cochrane Library. https://​doi.​org/​10.​
1002/​centr​al/​CN-​01035​404/​full. Accessed 16 Apr 2022
5. Mayerhöfer T, Wiedermann CJ, Joannidis M (2021) Einsatz von albumin.
Med Klin Intensivmed Notfmed 116:655–664. https://​doi.​org/​10.​1007/​
s00063-​021-​00875-4