Bill Coleman

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, isoleucinc, 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.

Increased lipid fuel dependence in the critically ill septic patient.

The effect of sepsis in modifying post-surgical fuel utilization in critically ill patients was determined from 374 observations (246 septic [S] and 128 nonseptic [N] in 12 intubated ICU patients studied serially. Patients received TPN (values/24 hrs: Septic, N2, 9.1 +/- 2.2 gm; glucose, 543 +/- 211 kcal/m2, Nonseptic, N2, 8.3 +/- 3.6 gm; glucose, 550 +/- 346 kcal/m2). In some periods, intravenous lipid (L) was given to raise total caloric intake to 826 +/- 223 kcal/ 24 hr/m2. The VO2, VCO2, respiratory rate, minute volume, and blood gas levels were measured, and respiratory quotient (RQ) and metabolic rate (MR) computed. Statistics were performed by 2-way ANOVA and analysis of covariance. Without lipid, mean VCO2 for S (126 ml/min/m2) and N (128 ml/min/m2) were not significantly different, but VO2 in S (146 ml/min/m2) and N (132 ml/min/m2), and the RQ values S (0.88) and N (0.97), were different (p less than 0.0001). In 360 studies RQ was shown to be increased by the total caloric intake, but reduced in the presence of sepsis: RQ = 0.00014 (kcal/m2) - 0.09 (sepsis effect + 0.878 N = 360; r2 = 0.304; F2,357 = 78; p less than 0.0001; but both administered glucose and lipid calories contribute to the RQ in sepsis: RQ = 0.00017 (glucose kcal/m2) + 0.266 X 10(-3) (lipid kcal/m2) + 0.732 n = 114; r2 = 0.260; F2,111 = 19.5; p 0.0001. Sepsis increased VO2 with little change in VCO2, thus RQ fell, suggesting increased use of lipid fuels for oxidation. During hypercaloric lipid infusion in septic patients (SL) VO2 and VCO2 increased but VO2 was still greater, so RQ remained low (SL RQ = 0.89). As sepsis worsened VO2 remained high but VCO2 fell producing RQ less than 0.8, while plasma glucose levels were increased. These data suggest that septic patients are more dependent than nonseptics on lipid fuels for oxidative metabolism, and that IV lipids can be used to increase oxidative metabolism in sepsis at a time when glucose metabolism appears reduced.

Ventilation:perfusion maldistribution secondary to the hyperdynamic cardiovascular state as the major cause of increased pulmonary shunting in human sepsis.

Cardiovascular and respiratory parameters were obtained in 374 studies from 151 patients (64 septic or septic shock and 87 with nonseptic cardiogenic syndromes). Cardiac output and related measures, respiratory parameters, pulmonary blood volume (DV/m2), cardiac ejection fraction (EFx), left ventricular end-diastolic volume (LVEDV), peripheral resistance (TPR), pulmonary shunt (QS/QT), physiologic dead space (VD/VT) and mean ventilation perfusion ratios (VA/QT) were calculated. Both physiologic evaluation and multivariable statistical analyses of the data were performed. For a given level of (A-aO2 gradient/PaO2) septic patients have a higher QS/QT than cardiogenic patients. Hyperdynamic septic patients have a larger QS/QT, a greater VD/VT, and a lower VA/QT and TPR than cardiogenics. The decrease in VA/QT and the rise in VD/VT are strong functions of the increased EFx, which raises cardiac index (CI) and reduces LVEDV and the mean dispersion of pulmonary blood volume, thus causing hemodynamic redistribution of flow. QS/QT is mainly a direct function of the increase in CI which also tends to reverse the EFx-mediated rise in VD/VT. The role of the septic mediated decrease in TPR as a contributing pathologic feature and the use of volume infusion to raise LVEDV and VA/QT in high-CI septics with large QS/QT is discussed.

The effect on survival of critically ill and injured patients of an ICU teaching service organized about a computer-based physiologic CARE system.

Management of the critically ill or injured surgical patient requires the organization and integration of clinical, biochemical, and physiologic data to facilitate the continuity and consistency of physician decision-making. To study the influence of these factors on improving survival, the implementation of a system of metabolically and physiologically oriented ICU care, structured around a surgical teaching service, was monitored over 6 years. Key to the organization of patient care and resident teaching was the staged introduction into the ICU of a computer-based Clinical Assessment, Research, and Education (CARE) system. In its present configuration it permits interactive entry of clinical information, fluid intake and output data, biochemical, immunologic, and metabolic profiles, as related to the cardiorespiratory physiologic data. The patients cardiovascular and metabolic abnormalities can then be compared over time to prototype patterns obtained from previously studied patients. From this physiologic state time-course trajectory, the physician can infer pathophysiologic mechanisms and make the appropriate therapeutic decisions. The phased implementation of the CARE principles into a teaching ICU surgical service has been associated with a reduction of noncardiac surgical mortality from 18.8 to 10.5% from 1973 through 1978. Trauma mortality was reduced from 25 to 7.5%, and in surgical patients with complications of gastrointestinal disease, mortality dropped from 19.7 to 8.3%. The probability that the reduction in noncardiac surgical ICU mortality was a Linear Logistic function of the increase in CARE cardiovascular physiologic studies was significant at p

Inhibition of post-traumatic septic proteolysis and ureagenesis and stimulation of hepatic acute-phase protein production by branched-chain amino acid TPN.

Previous studies have shown that severe sepsis after major trauma results in the reprioritization of release of hepatic acute-phase proteins (APP). They suggest competition for leucine for nutritional utilization may be responsible. To test this hypothesis, a branched-chain enriched (46.6%) amino acid mixture (BCAA) was administered on a prospective randomized basis with standard TPN therapy to 16 septic post-trauma patients. After sepsis was diagnosed, a randomized therapy (control-TPN or BCAA-TPN) was given for 12 days, or until death occurred. Total calories and amino acid nitrogen (N) administered were not different in the two groups (t-test) and q 8 h (347 study periods) amino acid clearances, urinary urea nitrogen excretion, muscle proteolysis from 3-methyl-histidine (3-MH) excretion, and standard indices of sepsis severity and hepatic function were measured, as well as platelets (PLAT), leucocytes (WBC), albumin (ALB), and six acute-phase proteins: C-reactive protein (CRP), alpha-1-antitrypsin (A1TRIP), fibrinogen (FIBRIN), alpha-2-macroglobulin (AMACRO), ceruloplasmin (CERUL), and transferrin (TRANS). Using Scheffé analysis of all contrasts the data showed: BCAA resulted in a fall in 24-hour urea N excretion (24.0 to 20.0 gm/24 hr) and in proteolysis (138 to 126 gm/24 hr) (p less than 0.0001). Prestudy CRP levels were all elevated, but compared to control where APP reprioritization occurred, over the initial 10 days of therapy BCAA patients had a more rapid fall in CRP with a more rapid rise in FIBRIN, TRANS, CERUL, ALBUMIN, AMACRO, and A1TRIP (all p less than 0.0001) relative to CRP. Also, the sepsis-reduced clearances of glutamine and glutamate, alanine, and proline were increased (p less than 0.0001) during BCAA even though urea nitrogen production was reduced (p less than 0.0001). The increase in leucine clearance with BCAA-enriched TPN was positively correlated (r2 = 0.601; p less than 0.0001) with the increase in the sum of all APP and ALB and was also associated with an increase both in FIBRIN and in platelets (p less than 0.0001). The BCAA-related increase in FIBRIN (9.1 to 11.9 mg/ml) occurred at the same time as a fall in prothrombin time (p less than 0.0001). BCAA-enriched TPN reduced proteolysis and amino acid catabolism and appeared to increase the levels of the more rapidly appearing anti-inflammatory and nutritional hepatic APP and formed coagulation elements in post-traumatic sepsis.