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Editorials: Point and Counterpoint |

Rebuttal From Dr Caironi FREE TO VIEW

Pietro Caironi, MD
Author and Funding Information

FINANCIAL/NONFINANCIAL DISCLOSURES: The author has reported to CHEST the following: P. C. has received lecture honoraria from Grifols, B. Braun, and Baxter.

CORRESPONDENCE TO: Pietro Caironi, MD, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Via F. Sforza 35, 20122, Milan, Italy


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;149(6):1370-1371. doi:10.1016/j.chest.2016.03.049
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I read with interest the arguments of my opponents. The questions posed are undoubtedly crucial. As I have originally foreseen, in my rebuttal, I will have to discuss the available data in more details.

First, does administration of albumin improve outcomes in severe sepsis or septic shock? I agree with my opponents that we do not yet have a definitive answer. Nonetheless, the actual data available firmly suggest a beneficial effect of albumin-containing solutions, particularly during shock. The post hoc analysis of the ALBIOS trial revealed a significant 6.3% absolute reduction in 90-day mortality associated with albumin replacement in patients with shock, which remained significant even after adjustments for baseline unbalances (P = .02). Such improvement in survival remained significant even after adjustments for clinically relevant variables, when considering patients with shock as defined with a broader definition. In addition, all the meta-analyses performed reported data in favor of a beneficial effect of albumin in patients with shock. A this point, two considerations merit our attention. First, the “signal” supporting a survival benefit of albumin administration appears to refer to patients with shock and not to those without shock. Second, we should not contrast a single P value against a biological plausibility of a hypothesis. Even the analysis mentioned by my opponents as not significant and reported in the ALBIOS trial (relative risk in the albumin group during shock of 0.88 [95% confidence interval, 0.77-1.01] after adjustments for clinically relevant variables, P = .07) does not necessarily confirm the null hypothesis of the trial. In contrast, it may indicate either that the outcome chosen to test the hypothesis (mortality) may be inappropriate and other clinically relevant outcomes should be tested, or that the beneficial effect of the treatment may have a greater extent (and less variability) in specific patient subcategories.

Second, does exogenous albumin cause harm? Albumin-containing solutions have nonphysiological characteristics due to albumin’s molecular conformation (which undergoes posttranscriptional modifications) and to the “solvent” included (as the relative high chloride content in 4% as opposed to 20% solutions). Moreover, because albumin is a weak acid in human plasma, its increased concentration causes per se a reduction in bicarbonate concentration, but a parallel increase in total plasma-buffering capacity. Overall, to determine whether such modifications have clinically relevant effects, we should rely on the evidence available. The only clinically relevant harm (ie, on the renal system) reported retrospectively in patients with shock receiving hyperoncotic albumin-containing solutions was never confirmed, as no effect on renal function was observed in our trial.

Third, is administration of albumin a cost-effective treatment? Few studies have analyzed this issue. Based on the estimates provided by my opponents, albumin replacement might add an extra cost of approximately $79 per day (with a median of 1,100 mL of 20% albumin as the total amount administered over the entire study period, and a median ICU length of stay of 9 days), which may be a reasonable cost. Indeed, the application of the SAFE protocol, which used a similar amount of albumin administered per day but a lower presumed reduction in mortality, indicated albumin infusion was cost-effective.

References

Coz Yataco A.O. .Flannery A.H. .Simpson S.Q. . Counterpoint: Should intravenous albumin be used for volume resuscitation in severe sepsis/septic shock? No. Chest. 2016;149:1368-1370 [PubMed]journal
 
Caironi P. .Tognoni G. .Masson S. .et al Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med. 2014;370:1412-1421 [PubMed]journal. [CrossRef] [PubMed]
 
Caironi P. .Gattinoni L. . Proposed benefits of albumin from the ALBIOS trial: a dose of insane belief. Crit Care. 2014;18:510- [PubMed]journal. [CrossRef] [PubMed]
 
Caironi P. .Langer T. .Gattinoni L. . Albumin in critically ill patients: the ideal colloid? Curr Opin Crit Care. 2015;21:302-308 [PubMed]journal. [CrossRef] [PubMed]
 
Baker M. . Statisticians issue warning over misuse of P values. Nature. 2016;531:151- [PubMed]journal. [CrossRef] [PubMed]
 
Langer T. .Ferrari M. .Zazzeron L. .et al Effects of intravenous solutions on acid-base equilibrium: from crystalloids to colloids and blood components. Anaesthesiol Intensive Ther. 2014;46:350-360 [PubMed]journal. [CrossRef] [PubMed]
 
Schortgen F. .Girou E. .Deye N. .et al The risk associated with hyperoncotic colloids in patients with shock. Intensive Care Med. 2008;34:2157-2168 [PubMed]journal. [CrossRef] [PubMed]
 
Guidet B. .Mosqueda G.J. .Priol G. .et al The COASST study: cost-effectiveness of albumin in severe sepsis and septic shock. J Crit Care. 2007;22:197-203 [PubMed]journal. [PubMed]
 

Figures

Tables

References

Coz Yataco A.O. .Flannery A.H. .Simpson S.Q. . Counterpoint: Should intravenous albumin be used for volume resuscitation in severe sepsis/septic shock? No. Chest. 2016;149:1368-1370 [PubMed]journal
 
Caironi P. .Tognoni G. .Masson S. .et al Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med. 2014;370:1412-1421 [PubMed]journal. [CrossRef] [PubMed]
 
Caironi P. .Gattinoni L. . Proposed benefits of albumin from the ALBIOS trial: a dose of insane belief. Crit Care. 2014;18:510- [PubMed]journal. [CrossRef] [PubMed]
 
Caironi P. .Langer T. .Gattinoni L. . Albumin in critically ill patients: the ideal colloid? Curr Opin Crit Care. 2015;21:302-308 [PubMed]journal. [CrossRef] [PubMed]
 
Baker M. . Statisticians issue warning over misuse of P values. Nature. 2016;531:151- [PubMed]journal. [CrossRef] [PubMed]
 
Langer T. .Ferrari M. .Zazzeron L. .et al Effects of intravenous solutions on acid-base equilibrium: from crystalloids to colloids and blood components. Anaesthesiol Intensive Ther. 2014;46:350-360 [PubMed]journal. [CrossRef] [PubMed]
 
Schortgen F. .Girou E. .Deye N. .et al The risk associated with hyperoncotic colloids in patients with shock. Intensive Care Med. 2008;34:2157-2168 [PubMed]journal. [CrossRef] [PubMed]
 
Guidet B. .Mosqueda G.J. .Priol G. .et al The COASST study: cost-effectiveness of albumin in severe sepsis and septic shock. J Crit Care. 2007;22:197-203 [PubMed]journal. [PubMed]
 
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