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Correspondence |

Severe Sepsis and Septic ShockResponse: Should Blood Be Transfused To Raise Mixed Venous Oxygen Saturation? FREE TO VIEW

Vinayak Jha, MD; Guillermo Gutierrez, MD, PhD, FCCP
Author and Funding Information

Affiliations: George Washington University, Washington, DC,  Henry Ford Hospital, Detroit, MI

Correspondence to: Vinayak Jha, MD, George Washington University, 2150 Pennsylvania Ave, Suite 5–425, Washington, DC 20037; email: vjha@mfa.gwu.edu



Chest. 2007;131(4):1267-1269. doi:10.1378/chest.06-2891
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We share the sentiments expressed by Otero et al1 (November 2006) regarding the importance of reducing mortality from severe sepsis, and applaud their efforts to develop early intervention strategies. While agreeing on the salutary effects of early and vigorous fluid resuscitation, we question the focus on mixed venous oxygen saturation (Svo2) as a centerpiece of the early goal-directed therapy (EGDT) algorithm. Specifically, we add a cautionary note against using blood transfusions to raise Svo2 > 70%.

In the study by Rivers et al,2 basal hematocrit was almost 35% in both groups, which would argue against transfusion. However, 64.1% of the EGDT subjects received transfusions. This we believe was the consequence of two interacting factors related to the study itself. Firstly, the larger volume of IV fluids received in the EGDT group caused greater hemodilution. Secondly, the intervention protocol dictated Svo2 > 70%. According to the Fick principle, Svo2 varies directly with arterial oxygen saturation, cardiac output, and hemoglobin concentration and inversely with oxygen consumption. Hemodilution-induced decreases in hemoglobin concentration would have had a depressing effect on Svo2. Since blood transfusion is the most energy-efficient way to raise Svo2, more so than the administration of dobutamine, which increases both cardiac output and oxygen consumption, it is not surprising that transfusion became the workhorse with which to achieve Svo2 > 70%. The unanswered issue is whether a transfusion-induced increase in Svo2 is tantamount to improved cellular oxygen utilization. We think not.

Otero et al1 assert that transfusions had a “physiologic effect.” Indeed they did, but that effect was the expected increase in Svo2, not necessarily improved cellular bioenergetics. Transfusion at similar hemoglobin concentrations has been found not to increase tissue oxygen utilization in septic patients,3or in trauma patients.4In addition to these physiologic considerations, the large-scale clinical trials5 suggesting harm associated with transfusions remain concerning.

The authors have no conflicts of interest to disclose.

Dr. Otero has received a research grant from Biosite, Inc., which ran the assays cited in the abstract reference 9. Dr. Rivers has spoken on behalf of Edwards Lifesciences and donates his honorarium to the research fund.

Otero, RM, Nguyen, B, Huang, DT, et al (2006) Early goal-directed therapy in severe sepsis and septic shock revisited.Chest130,1579-1595. [PubMed] [CrossRef]
 
Rivers, E, Nguyen, B, Havstad, S, et al Early goal-directed therapy in the treatment of severe sepsis and septic shock.N Engl J Med2001;345,1368-1377. [PubMed]
 
Fernandes, CJ, Jr, Akamine, N, De Marco, FV, et al Red blood cell transfusion does not increase oxygen consumption in critically ill septic patients.Crit Care2001;5,362-367. [PubMed]
 
Shah, DJ, Gottlieb, ME, Rahm, RL, et al Failure of red blood cell transfusion to increase oxygen transport or mixed venous PO2in injured patients.J Trauma1982;22,741-746. [PubMed]
 
Vincent, JL, Baron, JF, Reinhart, K, et al Anemia and blood transfusion in critically ill patients.JAMA2002;288,1499-1507. [PubMed]
 
To the Editor:

We would like to thank Drs. Jha and Gutierrez for emphasizing the importance of evaluating more than a single parameter, such as central venous oxygen saturation (Scvo2), as the centerpiece of decisions regarding resuscitation of patients with severe sepsis, especially in the use of transfusion therapy.

Our recent article in CHEST (November 2006)1was aimed at elucidating the rationale behind the stratified treatment strategy of early goal-directed therapy (EGDT).2 EGDT includes optimization of preload, afterload, arterial oxygen content, and subsequently contractility using a serial sequence of end points that incorporates Scvo2 among other important end points.

Although it is true that Scvo2 alone cannot be used as the only indicator of oxygen delivery, patients in the control and treatment arms were also monitored with serial assessments of various metabolic parameters including repeated measurements of lactate and base deficit. Although oxygen extraction ratios were not calculated in the original study, one can conceive that the improvement in Scvo2 in combination with the decrease in lactate level may signify an improvement in the imbalance between systemic oxygen demands and delivery.

As Dr. Jha points out, the baseline hematocrit was not the basis for transfusing a patient 3 h into the resuscitation. It was a uniform observation that the volume provided during the resuscitative course decreased the hematocrit by 30% at 3 h. The hematocrit value in the presence of a decreased Scvo2 and an increased lactate level signifies supply dependency and inadequate oxygen delivery. This has pathologic consequences in patients with cardiopulmonary comorbidities.35

Dr. Jha also indicated that the Fick equation suggests a direct correlation between oxygen consumption and arterial oxygen content. Previous studies68 are inconsistent on whether RBC transfusion increases tissue oxygen utilization. These studies reflect the presence of patients who were in the later stages of ICU admissions and who did not have the same degree of global tissue hypoxia as the patients in the EGDT study.2 If one concedes that the resolution of hypoperfusion at a local tissue level is clinically suggested by an increase in lactate clearance, as seen in the EGDT arm, then it logically proceeds that there must be improved perfusion at a cellular level.9While animal and human data indicate deranged rheologic characteristics of RBCs in the setting of sepsis,10which may impair microcirculatory flow,11 the outcome implications of these findings remain to be determined in this specific patient population.

One must remember that every component of EGDT has been part of critical care management for > 25 years. The relative contribution of each of these components is difficult to fully quantify, but the absolute consistent benefit of mortality reduction is the most important end point until we come up with something better.

References
Otero, R, Nguyen, H, Huang, D, et al Early goal directed therapy in severe sepsis and septic shock revisited.Chest2006;130,1579-1595. [PubMed] [CrossRef]
 
Rivers, EP, Nguyen, HB, Havstad, S, et al Early goal directed therapy in the treatment of severe sepsis and septic shock.N Engl J Med2001;345,1368-1377. [PubMed]
 
Corwin, HL, Gettinger, A, Pearl, RG, et al The CRIT Study: anemia and blood transfusion in the critically ill; current practice in the United States.Crit Care Med2004;32,39-52. [PubMed]
 
Jones, JG, Holland, BM, Wardrop, CAJ Total circulating red cells versus hematocrit as a primary descriptor of oxygen transport by the blood.Br J Haematol1990;76,228-232
 
Cordts, PR, La Morte, WW, Fisher, JB, et al Poor predictive value of hematocrit and hemodynamic parameters for erythrocyte deficits after extensive elective vascular operations.Surg Gynecol Obstet1992;175,243-248. [PubMed]
 
Silverman, H, Tuma, P Gastric tonometry in patients with sepsis: effects of dobutamine and packed red blood cell transfusions.Chest1992;102,184-188. [PubMed]
 
Marik, PE, Sibbald, W Effect of stored-blood transfusion on oxygen delivery in patients with sepsis.JAMA1993;269,3024-3029. [PubMed]
 
Robbins, JM, Keating, K, Orlando, R, et al Effects of blood transfusion on oxygen delivery and consumption in critically ill surgical patients.Contemp Surg1993;43,281-285
 
Otero, R, Rivers, E, Loomba, M The association of early lactate clearance with inflammatory biomarkers in severe sepsis and septic shock [abstract]Crit Care2006;10(suppl),P83
 
Piagnerelli, M, Zouaoui Boudjeltia, K, Vanhaeverbeek, M, et al Red blood cell rheology in sepsis.Intensive Care Med2003;29,1052-1071. [PubMed]
 
Desai, S, Manji, M Minimum haemoglobin in intensive care.Trauma2004;6,187-191
 

Figures

Tables

References

Otero, RM, Nguyen, B, Huang, DT, et al (2006) Early goal-directed therapy in severe sepsis and septic shock revisited.Chest130,1579-1595. [PubMed] [CrossRef]
 
Rivers, E, Nguyen, B, Havstad, S, et al Early goal-directed therapy in the treatment of severe sepsis and septic shock.N Engl J Med2001;345,1368-1377. [PubMed]
 
Fernandes, CJ, Jr, Akamine, N, De Marco, FV, et al Red blood cell transfusion does not increase oxygen consumption in critically ill septic patients.Crit Care2001;5,362-367. [PubMed]
 
Shah, DJ, Gottlieb, ME, Rahm, RL, et al Failure of red blood cell transfusion to increase oxygen transport or mixed venous PO2in injured patients.J Trauma1982;22,741-746. [PubMed]
 
Vincent, JL, Baron, JF, Reinhart, K, et al Anemia and blood transfusion in critically ill patients.JAMA2002;288,1499-1507. [PubMed]
 
Otero, R, Nguyen, H, Huang, D, et al Early goal directed therapy in severe sepsis and septic shock revisited.Chest2006;130,1579-1595. [PubMed] [CrossRef]
 
Rivers, EP, Nguyen, HB, Havstad, S, et al Early goal directed therapy in the treatment of severe sepsis and septic shock.N Engl J Med2001;345,1368-1377. [PubMed]
 
Corwin, HL, Gettinger, A, Pearl, RG, et al The CRIT Study: anemia and blood transfusion in the critically ill; current practice in the United States.Crit Care Med2004;32,39-52. [PubMed]
 
Jones, JG, Holland, BM, Wardrop, CAJ Total circulating red cells versus hematocrit as a primary descriptor of oxygen transport by the blood.Br J Haematol1990;76,228-232
 
Cordts, PR, La Morte, WW, Fisher, JB, et al Poor predictive value of hematocrit and hemodynamic parameters for erythrocyte deficits after extensive elective vascular operations.Surg Gynecol Obstet1992;175,243-248. [PubMed]
 
Silverman, H, Tuma, P Gastric tonometry in patients with sepsis: effects of dobutamine and packed red blood cell transfusions.Chest1992;102,184-188. [PubMed]
 
Marik, PE, Sibbald, W Effect of stored-blood transfusion on oxygen delivery in patients with sepsis.JAMA1993;269,3024-3029. [PubMed]
 
Robbins, JM, Keating, K, Orlando, R, et al Effects of blood transfusion on oxygen delivery and consumption in critically ill surgical patients.Contemp Surg1993;43,281-285
 
Otero, R, Rivers, E, Loomba, M The association of early lactate clearance with inflammatory biomarkers in severe sepsis and septic shock [abstract]Crit Care2006;10(suppl),P83
 
Piagnerelli, M, Zouaoui Boudjeltia, K, Vanhaeverbeek, M, et al Red blood cell rheology in sepsis.Intensive Care Med2003;29,1052-1071. [PubMed]
 
Desai, S, Manji, M Minimum haemoglobin in intensive care.Trauma2004;6,187-191
 
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