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Sepsis, Lactate, and Oxygen Supply DependenceSepsis, Lactate, and Oxygen Supply Dependence FREE TO VIEW

Constantine A. Manthous, MD, FCCP
Author and Funding Information

From the Bridgeport Hospital and Yale University School of Medicine.

Correspondence to: Constantine A. Manthous, MD, FCCP, Bridgeport Hospital and Yale University School of Medicine, 267 Grant St, Bridgeport, CT 06610; e-mail: pcmant@bpthosp.org


Financial/nonfinancial disclosures: The author has reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2012 American College of Chest Physicians


Chest. 2012;141(5):1361-1362. doi:10.1378/chest.11-3117
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To the Editor:

I read with great interest the Point/Counterpoint Editorials of Jones1,3 and Rivers et al2,4 in CHEST (December 2011). A central supposition of both, however, is that sepsis/septic shock is a condition in which oxygen consumption is dependent on oxygen delivery (Do2). Studies suggesting such were discounted in the 1990s as (measurement) artifact of mathematical coupling.5-7 Although nitric oxide-mediated microvascular dysregulation is certainly a feature of septic shock, data are not so conclusive that tissue-level Do2/oxygen consumption mismatch contributes to tissue dysoxia/hypoxia or lactic acidosis (LA). Nobody would argue that patients with severe hypotension during septic shock may have some LA resulting from hypoxia (when/if extraction fractions exceed around 60%),7 but LA often persists after resuscitation. And both debaters agree that generation of LA in sepsis is complex, if not completely understood.

What if LA is a marker of dysmetabolism more than tissue hypoxia in septic shock? Data from the 1980s may support such a concept.8,9 Then the underlying theoretical presumption for treating the macrocirculation using LA as a marker of “success” is ill founded. Even the landmark study by Rivers et al10 does not provide conclusive evidence that patients who received an intervention benefited because hypoxia was attenuated; with postresuscitation central vein saturations averaging 66% (control group) and 77% (intervention group), patients were nowhere near critical oxygen extraction (ie, central vein saturations of 40%).7 The intervention included a complex algorithm of titrated treatments, including fluids, vasoactive agents, inotropes, and blood, all designed to augment Do2. But the protocol also suggested that these patients were transferred to “the first available inpatient bed,” whereas control subjects were admitted “as soon as possible.” Time-to-transfer is not reported, but it is plausible that the observed differences resulted from (1) the Do2-driven interventions, (2) type 1 error (we are still awaiting confirmatory studies), (3) earlier transfer to units with better nursing ratios/proficiency, and/or (4) some other intervention bias.

Do not get me wrong: It would be foolhardy not to embrace earliest-possible administration of syndrome-targeted antibiotics, refilling of the circulation, and source drainage when necessary. It is only common sense. But the prevalent presumptions that outcomes are impacted by manipulation of Do2 (beyond rudimentary resuscitation), that central venous oxygen saturation (beyond very low values) can help guide therapy, and that LA fluxes are necessarily tied to Do2 in sepsis are not proven, at least not to my satisfaction. None of these theoretical nuances in any way reduces the importance of Dr Rivers’ work,10 which has driven health-care systems and clinicians to treat patients who are septic with the same vigilance and rigor brought to other treatment-time-sensitive illnesses.

Jones AE. Point: should lactate clearance be substituted for central venous oxygen saturation as goals of early severe sepsis and septic shock therapy? Yes. Chest. 2011;1406:1406-1408. [CrossRef] [PubMed]
 
Rivers EP, Elkin R, Cannon CM. Counterpoint: should lactate clearance be substituted for central venous oxygen saturation as goals of early severe sepsis and septic shock therapy? No. Chest. 2011;1406:1408-1413. [CrossRef] [PubMed]
 
Jones AE. Rebuttal from Dr. Jones. Chest. 2011;1406:1413-1415. [CrossRef]
 
Rivers EP, Elkin R, Cannon CM. Rebuttal from Dr Rivers et al. Chest. 2011;1406:1415-1419. [CrossRef]
 
Ronco JJ, Phang PT, Walley KR, Wiggs B, Fenwick JC, Russell JA. Oxygen consumption is independent of changes in oxygen delivery in severe adult respiratory distress syndrome. Am Rev Respir Dis. 1991;1436:1267-1273. [PubMed]
 
Manthous CA, Schumacker PT, Pohlman A, et al. Absence of supply dependence of oxygen consumption in patients with septic shock. J Crit Care. 1993;84:203-211. [CrossRef] [PubMed]
 
Ronco JJ, Fenwick JC, Tweeddale MG, et al. Identification of the critical oxygen delivery for anaerobic metabolism in critically ill septic and nonseptic humans. JAMA. 1993;27014:1724-1730. [CrossRef] [PubMed]
 
Hotchkiss RS, Karl IE. Reevaluation of the role of cellular hypoxia and bioenergetic failure in sepsis. JAMA. 1992;26711:1503-1510. [CrossRef] [PubMed]
 
Vary TC, Siegel JH, Nakatani T, Sato T, Aoyama H. Effect of sepsis on activity of pyruvate dehydrogenase complex in skeletal muscle and liver. Am J Physiol. 1986;2506 pt 1:E634-E640. [PubMed]
 
Rivers E, Nguyen B, Havstad S, et al; Early Goal-Directed Therapy Collaborative Group Early Goal-Directed Therapy Collaborative Group Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;34519:1368-1377. [CrossRef] [PubMed]
 

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References

Jones AE. Point: should lactate clearance be substituted for central venous oxygen saturation as goals of early severe sepsis and septic shock therapy? Yes. Chest. 2011;1406:1406-1408. [CrossRef] [PubMed]
 
Rivers EP, Elkin R, Cannon CM. Counterpoint: should lactate clearance be substituted for central venous oxygen saturation as goals of early severe sepsis and septic shock therapy? No. Chest. 2011;1406:1408-1413. [CrossRef] [PubMed]
 
Jones AE. Rebuttal from Dr. Jones. Chest. 2011;1406:1413-1415. [CrossRef]
 
Rivers EP, Elkin R, Cannon CM. Rebuttal from Dr Rivers et al. Chest. 2011;1406:1415-1419. [CrossRef]
 
Ronco JJ, Phang PT, Walley KR, Wiggs B, Fenwick JC, Russell JA. Oxygen consumption is independent of changes in oxygen delivery in severe adult respiratory distress syndrome. Am Rev Respir Dis. 1991;1436:1267-1273. [PubMed]
 
Manthous CA, Schumacker PT, Pohlman A, et al. Absence of supply dependence of oxygen consumption in patients with septic shock. J Crit Care. 1993;84:203-211. [CrossRef] [PubMed]
 
Ronco JJ, Fenwick JC, Tweeddale MG, et al. Identification of the critical oxygen delivery for anaerobic metabolism in critically ill septic and nonseptic humans. JAMA. 1993;27014:1724-1730. [CrossRef] [PubMed]
 
Hotchkiss RS, Karl IE. Reevaluation of the role of cellular hypoxia and bioenergetic failure in sepsis. JAMA. 1992;26711:1503-1510. [CrossRef] [PubMed]
 
Vary TC, Siegel JH, Nakatani T, Sato T, Aoyama H. Effect of sepsis on activity of pyruvate dehydrogenase complex in skeletal muscle and liver. Am J Physiol. 1986;2506 pt 1:E634-E640. [PubMed]
 
Rivers E, Nguyen B, Havstad S, et al; Early Goal-Directed Therapy Collaborative Group Early Goal-Directed Therapy Collaborative Group Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;34519:1368-1377. [CrossRef] [PubMed]
 
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