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Editorials: Point and Counterpoint |

Rebuttal From Drs Coz Yataco, Flannery, and Simpson FREE TO VIEW

Angel O. Coz Yataco, MD, FCCP; Alexander H. Flannery, PharmD, BCPS; Steven Q. Simpson, MD, FCCP
Author and Funding Information

FINANCIAL/NONFINANCIAL DISCLOSURES: None declared.

CORRESPONDENCE TO: Angel O. Coz Yataco, MD, FCCP, University of Kentucky, KY Clinic, 740 S Limestone L-543, Lexington, KY 40536


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


Chest. 2016;149(6):1371-1372. doi:10.1016/j.chest.2016.03.051
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We agree with Dr Caironi that hypoalbuminemia, epiphenomenon or not, is associated with increased morbidity and mortality in critically ill patients. However, no study has shown that correcting hypoalbuminemia or using albumin in resuscitation alters these outcomes.

In the spirit of accepting our opponent’s challenge to debate the theory rather than the details of trial results, we keep our statistical concerns brief, as they have been outlined elsewhere. We agree that shock defines a well-characterized patient subset; however, subgroup analysis, even in a well-defined subpopulation, has the potential for selection bias and sampling error. It is plausible that data exploration in ALBIOS to identify a subgroup with a positive treatment effect resulted in an overestimation of albumin’s potential effect. Moreover, subgroup analysis (prespecified or post hoc) can lead to conclusions of false benefit arising from multiple testing. It would certainly not be the first time that biologically plausible treatments fail to show benefit when tested in critically ill patients. A study on albumin replacement in patients with septic shock found no significant mortality difference.

The biological plausibility discussion proposed by our opponent is incomplete and fails to justify the use of albumin in severe sepsis or septic shock, as it lists several potential mechanisms that have not been tested in these circumstances. First, the pleiotropic effects of albumin could be postulated to benefit patients in the short term but not exclusively in the long term, as suggested by the reduction in 90-day mortality. Why would albumin fail to show a 28-day mortality benefit and yet paradoxically affect 90-day mortality?

Second, the argument of increasing colloid osmotic pressure carries much more weight in the original Starling equation than in the revised Starling principle and glycocalyx model. In the latter, colloid osmotic pressure has no effect on transendothelial filtration rate in conditions of lower capillary pressures, where transcapillary flow approaches zero. Both crystalloids and colloids are retained in the intravascular space until the transcapillary pressure reaches a hydrostatic threshold. This concept, known as the “no absorption rule,” is proposed to explain the failure of colloids to improve clinical outcomes. If our opponent’s argument held true, then protocols limiting the use of albumin in ICUs should show a potential signal of harm. However, such protocols have been published from surgical ICUs and demonstrated no impact on ICU mortality or length of stay.

The cost-effectiveness analysis cited by our opponent needs to be evaluated carefully, given that it involves a hypothetical patient population, and the authors reported an important conflict of interest. Moreover, a recent study found that albumin use is associated with increase in cost but no mortality benefit.

In summary, we believe that the theoretical effects of albumin are not proven to produce beneficial clinical outcomes, and the conclusions drawn from recent trials could be affected by important statistical flaws. Given albumin’s high cost and lack of proven benefit, we stand in our position that it should not be used in severe sepsis and septic shock.

References

Caironi P. . Point: Should intravenous albumin be used for volume resuscitation in severe sepsis/septic shock? Yes. Chest. 2016;149:1365-1367 [PubMed]journal
 
Flannery A.H. .Kane S.P. .Coz-Yataco A.O. . A word of caution regarding proposed benefits of albumin from ALBIOS: a dose of healthy skepticism. Crit Care. 2014;18:509- [PubMed]journal. [CrossRef] [PubMed]
 
Wang R. .Lagakos S.W. .Ware J.H. .Hunter D.J. .Drazen J.M. . Statistics in medicine—reporting of subgroup analyses in clinical trials. N Engl J Med. 2007;357:2189-2194 [PubMed]journal. [CrossRef] [PubMed]
 
Charpentier J. .Mira J.P. . EARSS Study Group: Efficacy and tolerance of hyperoncotic albumin administration in septic shock patients: the EARSS study [abstract]. Intensive Care Med. 2011;37:S115-0438 [PubMed]journal
 
Woodcock T.E. .Woodcock T.M. . Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy. Br J Anaesth. 2012;108:384-394 [PubMed]journal. [CrossRef] [PubMed]
 
Charles A. .Purtill M. .Dickinson S. .et al Albumin use guidelines and outcome in a surgical intensive care unit. Arch Surg. 2008;143:935-939 [PubMed]journal. [CrossRef] [PubMed]
 
Farrugia A. .Bansal M. .Balboni S. .Kimber M.C. .Martin G.S. .Cassar J. . Choice of fluids in severe septic patients—a cost-effectiveness analysis informed by recent clinical trials. Rev Recent Clin Trials. 2014;9:21-30 [PubMed]journal. [CrossRef] [PubMed]
 
Raghunathan K. .Bonavia A. .Nathanson B.H. .et al Association between initial fluid choice and subsequent in-hospital mortality during the resuscitation of adults with septic shock. Anesthesiology. 2015;123:1385-1393 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Tables

References

Caironi P. . Point: Should intravenous albumin be used for volume resuscitation in severe sepsis/septic shock? Yes. Chest. 2016;149:1365-1367 [PubMed]journal
 
Flannery A.H. .Kane S.P. .Coz-Yataco A.O. . A word of caution regarding proposed benefits of albumin from ALBIOS: a dose of healthy skepticism. Crit Care. 2014;18:509- [PubMed]journal. [CrossRef] [PubMed]
 
Wang R. .Lagakos S.W. .Ware J.H. .Hunter D.J. .Drazen J.M. . Statistics in medicine—reporting of subgroup analyses in clinical trials. N Engl J Med. 2007;357:2189-2194 [PubMed]journal. [CrossRef] [PubMed]
 
Charpentier J. .Mira J.P. . EARSS Study Group: Efficacy and tolerance of hyperoncotic albumin administration in septic shock patients: the EARSS study [abstract]. Intensive Care Med. 2011;37:S115-0438 [PubMed]journal
 
Woodcock T.E. .Woodcock T.M. . Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy. Br J Anaesth. 2012;108:384-394 [PubMed]journal. [CrossRef] [PubMed]
 
Charles A. .Purtill M. .Dickinson S. .et al Albumin use guidelines and outcome in a surgical intensive care unit. Arch Surg. 2008;143:935-939 [PubMed]journal. [CrossRef] [PubMed]
 
Farrugia A. .Bansal M. .Balboni S. .Kimber M.C. .Martin G.S. .Cassar J. . Choice of fluids in severe septic patients—a cost-effectiveness analysis informed by recent clinical trials. Rev Recent Clin Trials. 2014;9:21-30 [PubMed]journal. [CrossRef] [PubMed]
 
Raghunathan K. .Bonavia A. .Nathanson B.H. .et al Association between initial fluid choice and subsequent in-hospital mortality during the resuscitation of adults with septic shock. Anesthesiology. 2015;123:1385-1393 [PubMed]journal. [CrossRef] [PubMed]
 
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