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Correspondence |

“Nailing” the EvidenceResponse FREE TO VIEW

Greg S. Martin, MD, MSc, FCCP
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Affiliations: Emory University School of Medicine, Atlanta, GA,  Yale University School of Medicine, New Haven, CT

Correspondence to: Greg S. Martin, MD, MSc, FCCP, Assistant Professor of Medicine, Pulmonary, Allergy and Critical Care, Emory University School of Medicine, 49 Jesse Hill Jr Dr SE, Atlanta, GA 30303; e-mail: greg_marten@emory.edu



Chest. 2007;132(6):2055-2056. doi:10.1378/chest.07-1393
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Published online

Dr. Gomez and colleagues1deserve praise for a well- conducted laboratory investigation of the effects of endogenous albumin on acid-base balance and tolerance of acidosis. However, the accompanying editorial by Dr. Kaplan,2 entitled “Another Nail in Albumin’s Coffin,” is misleading and deserves comment. The title and text of the editorial imply that clinical treatment with exogenous albumin is without benefit and should be abandoned. Drawing these conclusions from the study by Gomez et al,1 which examined the effects of hypercapnia on acid-base status, nitric oxide balance, and BP in rodents with normal albumin, hypoalbuminemia, or analbuminemia is beyond the limits of this focused preclinical investigation. The assumption that these results may apply to humans requires testing, and we cannot advocate changing clinical practice based on such data.

A consensus statement3of the clinical use of albumin and other colloid solutions in critically ill patients exists to guide the appropriate use of these agents, and neither that document nor the cited reference4 in the editorial espouse the use of any colloid for modulating acid-base balance. Having never seen albumin administered to patients solely for buffering acidosis, it seems unlikely that even additional human data, as suggested by Dr. Kaplan, would alter current prescribing practices for this drug. However, it is equally incorrect to consider that the results of the study by Gomez et al1 may inform clinical practice and should prompt clinicians to discontinue their appropriate use of albumin. In the absence of clinical evidence in favor of or against the use of albumin, we should consider whether our nails are sealing a coffin or erecting a barrier to real evidence.

The author has no conflict of interest to disclose.

The author has no conflicts of interest to disclose.

Gomez, J, Gunnerson, K, Song, M, et al (2007) Effects of hypercapnia on blood pressure in hypoalbuminemic and nagase analbuminemic rats.Chest131,1295-1300. [PubMed] [CrossRef]
 
Kaplan, LJ Another nail in albumin’s coffin.Chest2007;131,1276-1277. [PubMed]
 
The American Thoracic Society Colloid Working Group.. Evidence-based colloid use in the critically ill: American Thoracic Society consensus statement.Am J Respir Crit Care Med2004;170,1247-1259. [PubMed]
 
Hemmila, MR, Napolitano, LM Severe respiratory failure: advanced treatment options.Crit Care Med2006;34(9 suppl),S278-S290
 
To the Editor:

I received Dr. Martin’s letter1with great enthusiasm, as it indeed underscores the visceral reaction that often accompanies colloid therapy. I agree that one would not abandon albumin solely on the basis of Dr. Gomez’s well-done and elegant study. However, I would advocate caution when selecting colloid therapy for plasma volume expansion (PVE) or acid-base management. Albumin offers no advantage over other colloid therapies for PVE. The results from the oft-touted SAFE trial2 declared that albumin was as safe as normal saline solution for PVE in the critically ill. Recall that normal saline solution PVE often creates hyperchloremic metabolic acidosis: an undesirable consequence of PVE, and one that may be decidedly “un-SAFE” with a preexisting acidosis.

Albumin therapy is frequently advocated based on the following: (1) colloid expansion efficiency, (2) the desire to increase colloid oncotic pressure, (3) protein carriage of protein-bound therapeutic agents, and (4) restoring diminished plasma buffer capacity. Colloid (vs crystalloid) efficiency is well accepted, but radiolabeled albumin studies34 document poor plasma retention with the capillary leak syndrome. Protein carriage is one putative mechanism behind enhanced urine flow when combining albumin and furosemide, an observation that does not well correlate with outcome benefit and confuses the effects of increased albumin concentration with reduction in plasma volume.5There is one trial6 of patients with spontaneous bacterial peritonitis in which albumin plus an antibiotic provided an outcome advantage compared to antibiotic therapy alone. The benefit was presumed to be related to PVE and reduction in acute kidney injury, but not enhanced protein carriage.6Raising colloid oncotic pressure with albumin has not provided a durable survival advantage, instead leaving more questions regarding mortality risk, cost, and safety than are answered.7 Thus, one is left with active management of the plasma buffer capacity that is partly mediated by the net negative charge of albumin in an aqueous milieu.

Dr. Gomez’s study is key in understanding that the presumed buffering role of albumin in the setting of CO2 clearance abnormalities is far less important than presumed because the analbuminemic animals fared equally well as those with normal or reduced albumin; no albumin supplementation was part of this study. Moreover, the reader should recall that US medicine went through a period when albumin was not available; no untoward events were noted that could be ascribed to the inability to provide exogenous albumin to the critically ill. Therefore, one may reasonably conclude that Dr. Gomez’s data are indeed placing another nail in albumin’s coffin—it simply is not the last nail.

References
Martin, GS Nailing the evidence.Chest2007;132,000-000
 
Finfer, S, Bellomo, R, Boyce, N, et al SAFE Study Investigators: a comparison of albumin and saline for fluid resuscitation in the intensive care unit.N Engl J Med2004;350,2247-2256. [PubMed] [CrossRef]
 
Wallace, JL, Steel, G, Whittle, BJ Gastrointestinal plasma leakage in endotoxic shock: inhibition by prostaglandin E2 and by a platelet-activating factor antagonist.Can J Physiol Pharmacol1987;65,1428-1432. [PubMed]
 
Akerstrom, G, Lisander, B Tissue extravasation of albumin from intra-abdominal trauma in rats.Acta Anaesthesiol Scand1991;35,257-261. [PubMed]
 
Elwell, RJ, Spencer, AP, Eisele, G Combined furosemide and human albumin treatment for diuretic-resistant edema.Ann Pharmacother2003;37,695-700. [PubMed]
 
Sort, P, Navasa, M, Arroyo, V, et al Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis.N Engl J Med1999;341,403-409. [PubMed]
 
Webb, AR The appropriate role of colloids in managing fluid imbalance: a critical review of recent meta-analytic findings.Crit Care (London)2000;4(suppl 2),S26-S32
 

Figures

Tables

References

Gomez, J, Gunnerson, K, Song, M, et al (2007) Effects of hypercapnia on blood pressure in hypoalbuminemic and nagase analbuminemic rats.Chest131,1295-1300. [PubMed] [CrossRef]
 
Kaplan, LJ Another nail in albumin’s coffin.Chest2007;131,1276-1277. [PubMed]
 
The American Thoracic Society Colloid Working Group.. Evidence-based colloid use in the critically ill: American Thoracic Society consensus statement.Am J Respir Crit Care Med2004;170,1247-1259. [PubMed]
 
Hemmila, MR, Napolitano, LM Severe respiratory failure: advanced treatment options.Crit Care Med2006;34(9 suppl),S278-S290
 
Martin, GS Nailing the evidence.Chest2007;132,000-000
 
Finfer, S, Bellomo, R, Boyce, N, et al SAFE Study Investigators: a comparison of albumin and saline for fluid resuscitation in the intensive care unit.N Engl J Med2004;350,2247-2256. [PubMed] [CrossRef]
 
Wallace, JL, Steel, G, Whittle, BJ Gastrointestinal plasma leakage in endotoxic shock: inhibition by prostaglandin E2 and by a platelet-activating factor antagonist.Can J Physiol Pharmacol1987;65,1428-1432. [PubMed]
 
Akerstrom, G, Lisander, B Tissue extravasation of albumin from intra-abdominal trauma in rats.Acta Anaesthesiol Scand1991;35,257-261. [PubMed]
 
Elwell, RJ, Spencer, AP, Eisele, G Combined furosemide and human albumin treatment for diuretic-resistant edema.Ann Pharmacother2003;37,695-700. [PubMed]
 
Sort, P, Navasa, M, Arroyo, V, et al Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis.N Engl J Med1999;341,403-409. [PubMed]
 
Webb, AR The appropriate role of colloids in managing fluid imbalance: a critical review of recent meta-analytic findings.Crit Care (London)2000;4(suppl 2),S26-S32
 
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