Malayappa Jeevanandam

Influence of total parenteral nutrition on fuel utilization in injury and sepsis.

Total parenteral nutrition with hypertonic glucose/AA solutions given to eighteen nutritionally depleted patients resulted in a rise in the respiratory quotient (RQ) from 0.83 to 1.05 (p less than .001), while oxygen consumption (VO2) increased only 3%. Excess glucose in depleted patients was converted to fat as evidenced by an RQ greater than 1.0. Administration of a similar glucose load to fourteen hypermetabolic patients (injury/infection) resulted in a rise in RQ from 0.76 to 0.90 while VO2 increased 29% (p less than .001) In hypermetabolic patients, even with administration of glucose in quantities above energy expenditure, there was still ongoing utilization of fat for energy, resulting in a RQ significantly less than 1.0. Excess glucose under these circumstances is apparently converted to glycogen while fat stores are utilized to partially meet energy needs. Septic and injuried man seems to preferentially utilize endogenous fat as an energy source. Administration of a large glucose load to hypermetabolic patients does not totally suppress the net fat oxidation as it does in depleted patients. Rather there is an increase in VO2, continuing oxidation of fat and apparently an increase in the conversion of glucose to glycogen.

Influence of increasing carbohydrate intake on glucose kinetics in injured patients.

The metabolic and hormonal effect of glucose loads, ranging from 125 to 504 g/70 kg/day, were studied in severely injured patients. There was little or no correlation of glucose intake with nitrogen balance, plasma glucose, fatty acid concentrations, or epinephrine excretion. Increased norepinephrine excretion correlated with and may have resulted from increased glucose intake. Serum glucagon concentrations averaged 320 pg/ml and were not depressed by glucose intake. Insulin concentrations rose with glucose intake but were low for the level of plasma glucose. Glucose oxidation and non-oxidative metabolism, including glycogen deposition, correlated well with glucose intake. Gluconcogenesis from alanine was much higher than normal but was completely suppressed at very high intakes. The data imply that cycling of glucose, with glycerol, glycogen, or both, increased with increasing glucose intake.

Effect of helicopter transport of trauma victims on survival in an urban trauma center

This paper reports a retrospective analysis of patients with serious yet substantially survivable injuries represented by ISS scores from 20 to 39 and whether or not survival was influenced by the use of helicopters. A review of 606 of these patients with blunt trauma was performed for the period from 1983 through 1986. When the group was evaluated there were 451 patients in the ISS cohort of 20-29 and 155 in the 30-39 group. The mean age was 30.5 years and 76% were males. A total of 259 patients were transported by ambulance and 347 by helicopter. Characteristics of the two groups were similar. The mean TS was 12.7 for ambulance and 12.1 for helicopter patients. Mean GCS was 10.4 in the ambulance group and 9.6 for helicopter patients. Overall the mortality for ambulance transported patients was 13% compared to 18% for the helicopter group. We conclude that there is no survival advantage in the helicopter transported group in an urban area with a sophisticated prehospital care system. Patients of rural origin deserve further study.

Effects of hypercaloric glucose infusion on lipid metabolism in injury and sepsis.

UNLABELLED Lipolysis was studied by measuring glycerol turnover (GTO) in injured and infected patients. GTO was elevated two to three times the normal values in five injured and four infected patients during D5W infusion. No correlation was found between GTO and plasma glycerol concentration in the two patient groups. GTO showed similar levels when measured during TPN in five injured and three infected patients. During TPN, plasma FFA levels remained unchanged in injured but decreased by 48% in septic patients. B-OH butyrate concentrations were high during D5W and dropped in both groups during TPN. Norepinephrine urinary output was high in both groups during D5W and TPN. CONCLUSIONS 1) GTO was elevated two to three times the normal range in injury and infection; plasma glycerol concentration was not related to GTO. 2) In face of high catecholamine output, the insulin response to TPN did not inhibit TG breakdown but did decrease plasma ketone body concentrations.

Enhancement of protein synthesis efficiency in parenterally fed trauma victims by adjuvant recombinant human growth hormone.

In the early catabolic phase of severe injury, conventional nutritional support is inadequate to reverse negative nitrogen balance and an anabolic stimulus may be beneficial. The utilization efficiency of body energy sources after injury could be improved by adjuvant recombinant human growth hormone (rhGH) therapy. We measured the protein kinetic response to exogenous rhGH in trauma patients fed parenterally (TPN). Severely injured (mean ISS, 31 +/- 2), highly catabolic (mean nitrogen loss, 19 +/- 2 g/day), and hypermetabolic (mean BEE/REE, 1.41 +/- 0.05), adult (mean age, 46 +/- 5 years), multiple trauma victims (n = 20, 17 men/3 women) were investigated. Rates of whole-body protein kinetics (turnover [WBPT], synthesis [WBPS], breakdown [WBPB], and protein synthesis efficiency [PSE]--the fraction of nitrogen turnover utilized for protein synthesis) were measured using a primed-constant infusion of 18N glycine 48 to 60 hours after injury when the patients were receiving only maintenance fluids without calories or nitrogen. The patients were then fed glucose-based TPN (1.1 x REE; 250 mg N/kg/day) and randomized to receive or not to receive rhGH. Group H (n = 10) received daily rhGH (0.15 mg/kg/day, Somatropin, Genentech, Inc.) intramuscularly at 8 am and group C (n = 10) received only the vehicle of infusion. Protein kinetic measurements were repeated at the end of 7 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulsatile nature of growth hormone levels in critically ill trauma victims

BACKGROUND Circulating growth hormone (GH) levels in normal persons fluctuate widely because of pulsatile GH secretion. It is not known whether this pulsatile nature and rhythmicity exist in severe injury. These data become necessary to decide the timing of supplementary GH administration for its optimal utilization. The purpose of this study was to investigate the GH circadian variation with respect to that of insulin-like growth factor-1 (IGF-1), insulin, C-peptide, and cortisol in the early flow phase of injury. METHODS Plasma GH, IGF-1, insulin, C-peptide, and cortisol levels were measured at 1-hour intervals during 24 hours (8 AM to 8 AM) in 10 severely injured adults with multiple trauma during the early catabolic flow phase 24 to 48 hours after injury, when patients received maintenance fluids without calories or nitrogen. RESULTS The 24-hour integrated GH concentration is not different from either 12-hour mean diurnal or 12-hour mean nocturnal or mean 8 AM GH concentration. Pulsatile GH bursts persist in injured patients during both day and night. Pulsatile bursts do not exist for IGF-1, insulin, and C-peptide. The plasma levels of cortisol show time-dependent daily maximum and minimum levels. CONCLUSIONS Pulsatile GH bursts persist in injured patients but less frequently than seen in normal persons. The time of bolus administration of GH to augment the anabolic GH action in patients with trauma does not matter; however, for convenience morning administration may be preferable for patients in the intensive care unit.

Reprioritization of liver protein synthesis resulting from recombinant human growth hormone supplementation in parenterally fed trauma patients: the effect of growth hormone on the acute-phase response.

BACKGROUND One of the major components of the metabolic response to severe trauma is the alteration in concentrations of a large number of plasma proteins referred to as acute-phase proteins (APP). The principle mediators of these liver-synthesized APP are mainly the cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). METHODS We have measured the plasma levels of IL-6, TNF alpha, and 20 APP in 24 adult, severely injured, hypermetabolic and highly catabolic patients with multiple injuries within 48-60 hours after injury, when they were receiving maintenance fluids without calories or nitrogen, and subsequently during 7 days of total parenteral nutrition with (n = 12) or without (n = 12) recombinant human growth hormone supplementation (rhGH, 0.15 mg/kg/d). RESULTS Baseline positive APP due to severe trauma include C-reactive protein (CRP), alpha-1 antichymotrypsin, alpha-1 acid glycoprotein, alpha-1 antitrypsin, fibronectin, and factor B. Negative APP include IgG, IgM, complement-3, prealbumin, transferrin, ceruloplasmin, and albumin. Except for CRP, alpha-1 antichymotrypsin, and albumin, all the APP levels increase during 7 days of nutritional support. Plasma levels of cytokines IL-6 and TNF-alpha, although initially markedly increased after injury, decrease with parenteral refeeding. There is a linear correlation between CRP and IL-6 levels and also between the transport proteins prealbumin and transferrin. Trauma-induced increases in CRP and IL-6 levels decreased with nutrition alone, but did not change with rhGH supplementation. An immunosuppressed state of injury is evident from the decreased immunoglobulin levels (IgG, IgM, IgA) in the trauma patients. Total parenteral nutrition alone increases the immunoglobulin levels to normal. However, with adjuvant rhGH, only IgA levels are normalized. CONCLUSIONS Adjuvant rhGH therapy does not attenuate the reprioritization of acute liver protein synthesis and results in only limited restoration of host defenses. The clinical implications of these findings await further study.

Influence of parenteral nutrition on rates of net substrate oxidation in severe trauma patients.

Optimal nutritional support should use a patients energy expenditure as a guide for administering sufficient but not excessive caloric intake. Eight patients requiring parenteral nutrition were evaluated, using indirect calorimetry measurements, to determine the nutritional influence on the rates of substrate utilization in the critical period of catabolic illness due to accidental trauma. Five days of total parenteral nutrition, providing calories to match the measured basal resting energy expenditure and N to replace the initial urinary losses a) shifted the RQ from 0.74 +/- 0.03 to 0.81 +/- 0.03, b) improved but could not reverse negative N balance, c) decreased net fat oxidation, d) increased carbohydrate and protein oxidation, e) elevated daily norepinephrine and epinephrine excretion rates, and f) attained positive energy balance. The results suggest that positive energy balance could be achieved in trauma patients by providing total energy intake matching their basal measured energy expenditure plus 7% to 10% for activity energy expenditure. To prevent further loss of lean body mass, an N intake of 350 mg/kg.day was needed in these catabolic ICU patients.

Substrate fuel kinetics in enterally fed traumapatients supplemented with ornithine alpha ketoglutarate

BACKGROUND Ornithine-alpha-ketoglutarate (OKG) is a promising anticatabolic agent and the mechanisms of its potential use in trauma patients are not clearly understood. AIM To determine the altered whole-body protein, lipid and glucose substrate kinetics in trauma victims in the early flow-phase of injury when they were fed enterally with or without OKG. METHODS Fourteen adult, multiple trauma patients who were highly catabolic and hypermetabolic were studied. Whole-body protein ((15)N glycine), fat (2 stage glycerol infusion) and glucose ((3H)glucose) kinetics (t/o) and plasma parameters were measured (A) within 48-60 h after injury before starting nutritional support and then (B) after 4 days of enteral feeding. Group A (n=7, control) received a defined enteral formula (Two Cal HN, 1.4 times BEE calories) and Group B (n=7, OKG) received same isonitrogenous diet replacing 2.62gN/d from the enteral diet by OKG-N (20g OKG/d). RESULTS (Mean+/-SEM): Protein turnover is significantly (P<==0.05) increased in OKG treated patients (4.68+/-0. 15 vs 3.90+/-0.23, gP/kg/day) and glycerol turnover is decreased (0. 87+/-0.16 vs 1.46+/-0.16, micro mole/kg/min). Glucose turnover is not changed. Significant (P<== 0.05) increases in circulating plasma levels of hormones (insulin, 44.2+/-8.4 vs 15.7+/-5.0 ulU/ml, growth hormone 1.68+/-0.33 vs 0.92+/-0.16, ng/ml and IGF-1, 106+/-13 vs 75+/-18, ng/ml) and free amino acids (glutamine, 383+/-20 vs 306+/-25, Proline, 203+/-18 vs 146+/-13 and ornithine, 164+/-27 vs 49+/-5 micro mole/l) are found in OKG treated patients, compared to non OKG patients. CONCLUSION Increased hormone secretion due to OKG and the rapid interaction between the metabolites of OKG at the intermediary metabolism level may be responsible for altered substrate fuel kinetics.

Release of proinflammatory cytokines by mitogen-stimulated peripheral blood mononuclear cells from critically III multiple-trauma victims☆☆☆

This study investigated the alterations in circulating proinflammatory cytokines and cytokine production by peripheral blood mononuclear cells (PBMCs) in response to lipopolysaccharide (LPS) or phytohemagglutinin (PHA) after severe trauma. Plasma and PBMCs were collected from 17 severely injured trauma patients and 10 healthy subjects. Plasma was stored at -80 degrees C and analyzed for cytokines. Isolated PBMCs from each subject were stimulated with LPS or PHA and incubated at 5% CO2 for 24 hours. Supernatants were collected and analyzed for cytokines. There was no significant change in the plasma concentration of free TNF-alpha and IL-1beta between healthy subjects and trauma patients. Plasma IL-6, total TNF-alpha, and total IL-1beta were significantly increased in severely traumatized patients compared with healthy control subjects. PBMCs from trauma patients produced higher levels of TNF-alpha in response to LPS but it showed no significant change in IL-1beta and IL-6 production in response to PHA or LPS in comparison to PBMCs from control subjects. We conclude that severe trauma results in a significant increase in plasma proinflammatory cytokine IL-6. Free TNF-alpha and IL-1beta in plasma remain at levels comparable to those in uninjured controls, while plasma free IL-6 levels in trauma patients remain high. Serious injury is associated with an enhanced production of TNF-alpha by PBMCs stimulated with LPS.