J. Askanazi

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.

Muscle and plasma amino acids following injury. Influence of intercurrent infection.

The present study was undertaken to determine intracellular amino acid patterns in patients with multiple trauma, whether or not complicated by sepsis and during convalescence. A percutaneous muscle biopsy was performed three to four days following major accidental injury in ten patients and analyzed for muscle free amino acids. Venous blood was drawn at the time of the biopsy and analyzed for plasma free amino acids. Five patients developed sepsis and a repeat biopsy was performed on days 8 to 11. In five of the patients a biopsy was performed during the late convalescent period (anabolic phase). A marked depletion of nonessential amino acids in muscle occurred in both injury and sepsis due to a decrease (50%) in glutamine, which was equally marked in both states. The essential amino acids in muscle increased in injury. During sepsis, a further increase was observed with a return toward normal in the convalescent period. In injury, the most marked rise was in the branched-chain amino acids, phenylalanine, tryosine and methionine. With sepsis, a further rise in muscle branched-chain amino acids, phenylalanine and tryosine occurred, while plasma levels remain unchanged. During convalescence, muscle glutamine, arginine, histidine and plasma branched-chain amino acids were below normal, whereas muscle phenylalanine and methionine were elevated. The muscle free amino acid pattern observed after major trauma was essentially the same as earlier described following elective operation. This suggests a common response of intracellular amino acids irrespective of the degree of injury, and may indicate that the pump settings which regulate amino acid transport follow the “all or none” rule. The high intracellular levels of branched-chain amino acids in sepsis suggest that the energy deficit of this state is due to an impairment of substrate use rather than intracellular availability. The high concentrations of the aromatic amino acids and methionine may be due to altered liver function. During the late convalescent period (anabolic phase) the low levels of certain key amino acids suggests inadequate nutrition. The difficulties in nourishing the injured or septic patient are well recognized. The period following these catabolic states may be an important period for the application of an optimal, aggressive nutritional regimen.

Muscle and Plasma Amino Acids after Injury: Hypocaloric Glucose vs. Amino Acid Infusion

This study examines the effect of three different hypocaloric diets on the patterns of muscle and plasma amino acids in patients undergoing total hip replacement. Group I (seven patients) received 90 g/day of glucose, Group II (seven patients) received 70 g/day of amino acids, Group III (eight patients) received both 90 g of glucose and 70 grams of amino acids per day. Utilizing the percutaneous biopsy technique of Berg-ström, free amino acid patterns in muscle and plasma were analyzed pre- and postoperatively (day 4). The postoperative pattern of amino acids was characterized by elevated levels in muscle and plasma of the branched chain amino acids, phenylalanine, tyrosine and methionine. There was a marked decrease in muscle glutamine and smaller decreases in the basic amino acids in both muscle and plasma. Muscle:plasma concentration ratios increased for the neutral amino acids, decreased for glutamine and the basic amino acids and were unchanged for the acidic amino acids. The patterns seen after hip replacement are almost identical to those seen after colectomy or accidental injury. There was little effect of diet on amino acid concentrations in muscle. In plasma, concentrations of leucine, isoleucine valine and proline were higher in Group II in the absence of glucose intake, than in the other groups. Lysine was lower in Group I with no amino acid intake than in the other groups. Thus, there is a unique amino acid pattern associated with operative trauma which is relatively unaffected by hypocaloric, intravenous nutrition.

Intravenous fat emulsions and lung function: a review.

Numerous studies have reported varying degrees of apparent pulmonary dysfunction when iv fat emulsions (IVFE) are given. These changes have generally not been of sufficient magnitude to carry clinical significance. The lung dysfunction observed has been attributed to an associated hyperlipemia. Recent studies, however, suggest that the associated impairment in lung function is due to alterations in pulmonary vascular tone (which results in ventilation/perfusion inequalities) caused by an IVFE-related increase in prostaglandin (PG) production. The polyunsaturated fatty acids in the IVFE serve as precursors to the PGs. Due to the varied effects of PGs on inflammation and pulmonary vasomotor tone, infusion of IVFE could have profound physiologic and pharmacologic actions aside from the provision of lipid calories. In some circumstances, IVFE may, in fact, be beneficial to the lung via alterations in PG synthesis and surfactant production.

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

UNLABELLEDnLipolysis 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.nnnCONCLUSIONSn1) 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.

Effect of immediate postoperative nutritional support on length of hospitalization.

This study is a retrospective review of the effect of nutritional support on duration of hospitalization in patients undergoing radical cystectomy. Thirty-five patients were randomly assigned to receive either 5% dextrose (D5W) solution plus electrolytes or total parenteral nutrition (TPN) following operation. The assigned nutritional regimen was continued for 1 week after operation until oral intake resumed. If the patients receiving D5W remained incapable of oral intake after 1 week, TPN was instituted. The group receiving immediate postoperative TPN had a median duration of hospitalization of 17 days, while the median duration for the group receiving 5% dextrose solution was 24 days. All other patient characteristics, such as age, sex, stage/grade of tumor, and extent of preoperative radiotherapy, were similar in the two groups. These results demonstrate that immediate postoperative institution of nutritional support reduced hospitalization time following radical cystectomy. This indicates that the routine use of 5% dextrose as postoperative nutrition should be reevaluated.

The response to TPN. A form of nutritional assessment.

Malnutrition in surgical patients is associated with an increased incidence of postoperative mortality and morbidity. Preoperative nutritional support has been shown to be efficacious in reducing the incidence of these complications, although the postoperative complication rate in these patients continues to be greater than in their wellnourished counterparts. This study attempts to determine whether the postoperative course can be either influenced by or predicted from the preoperative response to nutritional support. Thirty-two patients with nutritional depletion who received an average of 1 week of total parenteral nutrition prior to a major abdominal operation were studied. These patients were followed for postoperative complications. Of the 16 patients who exhibited the characteristic response to early nutritional support, diuresis of the expanded extracellular fluid compartment with a resultant loss of weight (127.9 ± 5.7 to 124.6 ± 5.8 (SEM) lbs, p < .001) and rise in serum albumin (3.21 ± 0.14 to 3.46 ± 0.15 gms%, p < 0.001), only one developed a complication in the postoperative period. The other 16 patients did not exhibit this response. They retained additional fluid, gained weight (119.3 ± 8.1 to 121.3 ± 8.2 lbs, p < .025), and showed a decrease in serum albumin levels (3.14 ± 0.14 to 3.00 ± 0.14%), p < 0.01). Eight of these patients developed a total of 15 postoperative complications (p < 0.01). This study demonstrates that the response to preoperative TPN is an important factor in assessing operative risk and morbidity. The need to individualize preoperative nutritional support and the timing of surgical intervention is clearly demonstrated.

Muscle and plasma amino acids after injury: the role of inactivity.

This study is part of an investigation of whether injury is associated with a unique amino acid pattern in muscle and plasma using the total hip replacement as a model for injury. The role of inactivity is examined as a factor in producing the changes observed with injury and associated bed rest. Nineteen preoperative patients and 16 normal subjects received a muscle biopsy following an overnight fast. Blood for plasma amino acids was drawn at the time of the biopsy. Seven patients (Group I) were treated with 90 g/day of dextrose for the first four postoperative days following which a second biopsy was performed. Eight normals were placed on four days of strict bed rest. Four (Group II) received a regular diet and four (Group III) received 90 g of dextrose/day I.V. as the sole nutrient. Both Groups I and III showed increases in valine, leucine, and isoleucine in both muscle and plasma on the postoperative biopsy. The postoperative pattern differed from that observed in either group of normal subjects in that significant decreases occurred in muscle glutamine and histidine, plasma alanine, lysine and glycine. Phenylalanine, tyrosine, methionine and threonine were increased in muscle postoperatively while only phenylalanine was increased in either Group II or III of the normal subjects. Plasma phenylalanine increased in the patients while remaining unchanged in normal subjects. The pattern reported here for the patient group differs from that reported for other catabolic states (uremia, starvation, etc.), as well as inactivity with or without partial starvation. This study suggests that injury in the form of a total hip replacement is associated with a unique amino acid pattern of muscle and plasma which differs from that observed in other catabolic states. Bed rest plus partial starvation causes a pattern with certain similarities but cannot account for the postoperative changes observed.

Effect of injury and sepsis on high-energy phosphates in muscle and red cells.

Changes in muscle high-energy phosphates in varying degrees of resting hypermetabolism were studied. Eleven patients were investigated before and 4 days after total hip replacement. The postoperative results were compared with those seen in major traumas and sepsis. High-energy phosphates were not significantly changed in muscle after total hip replacement or moderate injury; muscle lactate and pyruvate increased. Increased degrees of hypermetabolism such as severe trauma and sepsis were associated with reduction of muscle ATP and PC; AMP, free CR, lactate, and pyruvate rose. Simultaneously determined levels of high-energy phosphates in red blood cells did not reflect muscle changes, confirming the need for continued direct tissue measurements. Alterations in the ATP--ADP--AMP system in the muscle cell suggest a low-energy charge following severe trauma especially if accompanied by sepsis. This would indicate a decreased capcity for biosynthetic reactions and production of storage compounds. Tissue high-energy phosphates and cellular energy levels thus may be the cellular expression of the catabolic state.

Changes in respiratory control induced by amino acid infusions.

We compared the metabolic and respiratory responses to a 4-h infusion of an amino acid solution consisting primarily of branched-chain amino acids (BCAA) to those after a standard amino acid solution in healthy subjects. Both the BCAA solution and the standard amino acid solution increased minute ventilation (mean increase 22%, p less than .001, and 18%, p less than .01, respectively), mean inspiratory flow (19%, p less than .01, and 19%, p less than .05) and oxygen consumption (9%, p less than .02, and 5%, NS). PaCO2 decreased (mean decrease 6%, p less than .01); there was a major increase in the ventilatory response to CO2 inhalation during administration of the BCAA solution but not the standard amino acid solution. Increased plasma norepinephrine concentration (mean increase 75%, p less than .001) during the infusion of the standard amino acid solution but not the BCAA solution suggested increased sympathetic activity. The results demonstrate augmented respiratory effects of amino acid infusions by BCAA enrichment, and a dissociation between the respiratory stimulation, metabolic rate, and sympathetic activity.