Septic autocannibalism. A failure of exogenous nutritional support.

Forty-six patients with surgical sepsis were studied prospectively until death or survival to evaluate the effect of exogenous metabolic support on the observed plasma substrate levels and on the differential endogenous utilization of branch chain amino acids. There were no effects of administered glucose or colloid load. The administered amino acid load had little effect on substrate levels in patients who died; but significantly effected the observed levels of glycine, isoleucine, and methionine in patients who survived. Evidence is presented which suggests that fatal sepsis is associated with an increased release of endogenous valine and isoleucine into plasma, as well as increased plasma levels of tyrosine, proline, and methionine. These abnormalities are highly correlated with the increased levels of plasma alanine and occur at a time when the nonsurviving septic patient manifests a tendency toward reduced oxygen consumption and abnormal vascular tone relations--the septic B state. These data are consistent with the hypothesis that increased muscle protein catabolism is occurring with a differential utilization of branch chain amino acids and increased use of leucine and isoleucine and reduced use of valine. This autocannibalism of muscle mass appears to be the source of the increased plasma alanine and is little influenced by administered amino acid support in the absence of control of the septic process.

Proline metabolism in sepsis, cirrhosis and general surgery. The peripheral energy deficit.

Proline metabolism was prospectively evaluated in patients with surgical sepsis, cirrhosis, and elective surgical procedures. Significant correlations were found in the septic patients. Proline levels were an excellent indicator of mortality and correlated positively with lactate levels. Lactate and proline were inversely related to total peripheral resistance and oxygen consumption. In septic patients who expired: the metabolites involved in the hepatic pathways of proline degradation were elevated in proportion to proline; lactate, glutamate and proline were directly related to pyruvate; lactate/pyruvate ratios were constant; proline, glutamate, ammonia, ornithine, lactate and pyruvate levels were inversely proportional to oxygen consumption and total peripheral resistance. The primary defects in sepsis seem to be metabolic; there are very strong correlations in time between physiology and metabolism; the metabolic abnormality seems to be a progressive energy-fuel deficit, possibly from a progressive inhibition of substrate entry into the Krebs cycle.

Correlations between metabolic and cardiopulmonary measurements in patients after trauma, general surgery, and sepsis.

Simultaneous longitudinal hormonometabolic-physiologic (cardiopulmonary) profiles were measured in 14 nonseptic trauma/general surgery (T/GS) patients and in ten patients with Gram-negative abdominal surgical sepsis. The physiologic state classification system was used as the frame of reference. There were no response differences between the T and GS groups: they had A State responses. The sepsis (S) patients initially had exaggerated A State responses with significant changes in glucose, fat, amino acid, and glucagon plasma levels relative to T/GS. The S patients who survived (four) demonstrated profiles as in T/GS. The S patients who expired (six) progressively evolved an unbalanced, hyperdynamic B State response with progressive elevations of glucose, lactate, aromatic and branched-chain amino acids and glucagon, and low ketone bodies. There is definite correlation over time between metabolic and physiologic responses; the physiologic responses reflect the metabolic responses; the metabolic responses are consistent with a peripheral energy-fuel deficit.