TY - JOUR
T1 - Reevaluation of the Role of Cellular Hypoxia and Bioenergetic Failure in Sepsis
AU - Hotchkiss, Richard S.
AU - Karl, Irene E.
N1 - Funding Information:
bytheEdwardMallinckrodt,Jr,Foundation,the AmericanMedicalAssociationEducationandRe¬ thesiology.search Fund, andthe American Society of Anes¬
PY - 1992/3/18
Y1 - 1992/3/18
N2 - Sepsis is frequently characterized by a number of metabolic abnormalities: increased plasma lactate concentration, metabolic acidosis, increased glycolysis, and an abnormal “delivery-dependent” oxygen consumption. Two hypotheses have been advanced to explain these metabolic abnormalities: (1) cellular hypoxia resulting from abnormal microcirculatory blood flow or (2) defect(s) in energy-producing metabolic pathways of cells. Results of our studies on rat muscle, liver, heart, brain, and plasma suggest that there is no evidence of bioenergetic failure in these septic tissues and that the increase in lactate production is not necessarily due to cellular hypoxia. The adequacy of cellular oxygenation and bioenergetics was verified using in vivo phosphorus 31 nuclear magnetic resonance spectroscopy, [18F]fluoromisonidazole, and microfluorometric enzymatic techniques. Findings from these studies as well as results from several clinical investigations indicate that neither hypothesis can adequately account for the metabolic features typical of sepsis and that the pathophysiology of sepsis awaits further clarification. These studies and important clinical implications are discussed.
AB - Sepsis is frequently characterized by a number of metabolic abnormalities: increased plasma lactate concentration, metabolic acidosis, increased glycolysis, and an abnormal “delivery-dependent” oxygen consumption. Two hypotheses have been advanced to explain these metabolic abnormalities: (1) cellular hypoxia resulting from abnormal microcirculatory blood flow or (2) defect(s) in energy-producing metabolic pathways of cells. Results of our studies on rat muscle, liver, heart, brain, and plasma suggest that there is no evidence of bioenergetic failure in these septic tissues and that the increase in lactate production is not necessarily due to cellular hypoxia. The adequacy of cellular oxygenation and bioenergetics was verified using in vivo phosphorus 31 nuclear magnetic resonance spectroscopy, [18F]fluoromisonidazole, and microfluorometric enzymatic techniques. Findings from these studies as well as results from several clinical investigations indicate that neither hypothesis can adequately account for the metabolic features typical of sepsis and that the pathophysiology of sepsis awaits further clarification. These studies and important clinical implications are discussed.
UR - http://www.scopus.com/inward/record.url?scp=0026602489&partnerID=8YFLogxK
U2 - 10.1001/jama.1992.03480110079038
DO - 10.1001/jama.1992.03480110079038
M3 - Article
C2 - 1538541
AN - SCOPUS:0026602489
SN - 0098-7484
VL - 267
SP - 1503
EP - 1510
JO - JAMA: The Journal of the American Medical Association
JF - JAMA: The Journal of the American Medical Association
IS - 11
ER -