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OBJECTIVE: To discuss certain important features of nutrition and metabolism in the intensive care unit. DATA SOURCE: Prospective clinical trials examining issues related to glucose control, immunonutrition, and comparison of enteral and parenteral nutrition. CONCLUSIONS: It remains unclear which glycemic threshold should be used in many patients for insulin initiation, but surgical patients receiving adequate nutrition should probably be treated to true normoglycemia. Immunonutrition may be beneficial in some populations, but the evidence does not justify its use in the intensive care unit. Contrary to popular belief, appropriately administered parenteral nutrition may provide similar or more benefit than enteral and clearly needs more widespread acceptance in cases where initiation of enteral nutrition is slow to start or is contraindicated. [ABSTRACT FROM AUTHOR]

Introduction: It appears that enteral nutrition is more likely to produce hypoglycemia during intensive insulin therapy than is total parenteral nutrition., Point of View: Although this consequence may in part be the result of frequent discontinuation of feeding or to variability of gastrointestinal absorption of nutrients, there are also distinct physiological differences between total parenteral nutrition and enteral nutrition that are more likely to be responsible, including much higher serum insulin responses to total parenteral nutrition than with enteral nutrition that approach submaximal response levels and direct appearance of administered glucose into the systemic circulation with total parenteral nutrition at rates that approximate usual postabsorptive rates and that avoid first-pass hepatic clearance., Conclusions: These factors may make total parenteral nutrition more efficacious, at least initially, with intensive insulin therapy and may justify setting a higher limit for glucose control when enteral feeding is principally used.

Objective: To discuss certain important features of nutrition and metabolism in the intensive care unit., Data Source: Prospective clinical trials examining issues related to glucose control, immunonutrition, and comparison of enteral and parenteral nutrition., Conclusions: It remains unclear which glycemic threshold should be used in many patients for insulin initiation, but surgical patients receiving adequate nutrition should probably be treated to true normoglycemia. Immunonutrition may be beneficial in some populations, but the evidence does not justify its use in the intensive care unit. Contrary to popular belief, appropriately administered parenteral nutrition may provide similar or more benefit than enteral and clearly needs more widespread acceptance in cases where initiation of enteral nutrition is slow to start or is contraindicated.

Objective: The aim of this study was to investigate whether hyperglycemia enhances the systemic inflammatory response and oxidative stress induced by endotoxin., Design: Laboratory investigation., Setting: University medical school., Subjects: Forty-one male Sprague-Dawley rats., Interventions: A hyperglycemic condition was produced in rats by glucose clamp for 3 hrs. Immediately on stopping the glucose infusion, animals received different doses of endotoxin injection (0, 0.2, or 1 mg/kg), and then blood glucose concentration was monitored over the ensuing 2 hrs. At the end of 2 hrs, levels of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, corticosterone, and alpha-1 acid glycoprotein were determined in serum, and malondialdehyde and total glutathione content were determined in the liver., Measurements and Main Results: Over the 2-hr period, blood glucose concentrations returned to normal in initially hyperglycemic rats. However, the levels of cytokines, corticosterone, and alpha-1 acid glycoprotein were significantly higher in these animals compared with nonhyperglycemic controls, demonstrating an extended effect of prior hyperglycemia on markers of systemic inflammation. With low-dose (0.2 mg/kg) but not high-dose (1 mg/kg) endotoxin administration, hyperglycemic animals had significantly higher levels of cytokines compared with controls, indicating that prior hyperglycemia can enhance the systemic inflammatory response to a moderate endotoxin dose, but that the maximum effects of endotoxin on production of inflammatory cytokines are not altered by transient high glucose exposure., Conclusions: Systemic inflammation persists for a period following hyperglycemia, and this can enhance the systemic inflammatory response to a subsequent moderate stress.

Purpose of Review: This review will address recent research in metabolism of essential fatty acids and their long chain derivatives. Our main focus will be the association between essential fatty acid status and various disease states, as well as the effects of supplementation with essential fatty acids or their derivatives on a number of clinical outcomes., Recent Findings: There have been several papers over the last few years that show links between supplementation with fish oil (n-3 polyunsaturated fatty acids) and cardiovascular disease. Recent data suggest that the use of fish oil (containing n-3 fatty acids) in a variety of disorders such as cystic fibrosis, coronary disease and in the prevention of sudden death is beneficial. Several papers show reductions in systemic markers of inflammation. More widespread use of essential fatty acid derivatives in infant formula can certainly be questioned on the basis of the recent data. Fewer benefits are seen with ingestion of the essential fatty acids themselves, likely related to limited conversion to their long chain derivatives in humans., Summary: Derivatives of essential fatty acids have the potential to modify a number of disease states, either ingested in greater quantities in the diet, or taken as supplements in the form of fish oil.

Objectives: Endotoxin-induced cytokines, such as interleukin-6, mediate systemic inflammatory responses through multiple cellular signaling pathways. Interleukin-6 is also responsible for the synthesis of acute phase proteins. Recent studies have shown that endotoxin can inhibit signal transducers and activators of transcription (STAT)-3 tyrosine phosphorylation in cultured cells, suggesting that this effect may limit the synthesis of acute phase proteins. The purpose of this study was to examine the effects of endotoxin on interleukin-6 activation of STATs and mitogen-activated protein (MAP) kinase pathways in rat liver in vivo., Design: Controlled laboratory study., Setting: Medical school laboratory., Subjects: Specific pathogen-free male Sprague Dawley rats., Interventions: Under anesthesia, interleukin-6 was injected into the portal vein of rats 4 hrs after the bolus intravenous administration of endotoxin (1 mg/kg) or saline. The effects of interleukin-6 on key intermediates in early steps of the interleukin-6 signaling pathway, including janus kinase-1, gp 130, the interleukin-6 receptor, STAT1, and STAT3, were examined in both saline and endotoxin-treated rats., Measurements and Main Results: In endotoxin-treated rats, there was significant inhibition of interleukin-6 activation of janus kinase-1, gp 130, the interleukin-6 receptor, STAT1, and STAT3. These signaling changes were associated with decreased tissue abundance of interleukin-6 receptors and STAT3. In contrast to its effects on the janus kinase/STAT pathways, interleukin-6 activation of MAP kinases (extracellular signal-regulated kinase-1, extracellular signal-regulated kinase-2, and p38) was unaffected by endotoxin., Conclusions: The pathway-specific inhibition of interleukin-6 signaling responses in the liver may be an important determinant of the pathophysiologic consequences of endotoxin exposure.

Objectives: To determine the effects of sustained, 3-day endotoxin infusion on early steps of the insulin-signaling pathway in rat liver and skeletal muscle in vivo; to examine insulin signaling in well-established acute endotoxin models of insulin resistance., Design: Prospective, controlled animal study., Setting: University research laboratory., Subjects: Male Sprague-Dawley rats: 24 in the 3-day endotoxin study, 22 in each acute endotoxin study., Interventions: In prolonged endotoxemia studies, endotoxin (1 mg.kg-1.24 hrs-1) was administered via jugular venous catheter for 74 hrs. Insulin was then injected, and liver and skeletal muscle were removed after 5 mins. In acute endotoxemia studies, an endotoxin bolus (1 mg/kg) was administered, and insulin-signaling responses were studied after 4 hrs., Measurements and Main Results: In liver of rats with sustained endotoxemia, there were significant decreases in insulin-stimulated tyrosine phosphorylation of insulin receptors (74%), insulin receptor substrate (IRS)-1 (74%), and IRS2 (53%); binding of the p85 subunit of phosphatidylinositide 3-kinase to IRS1 (80%); and IRS1-precipitable phosphatidylinositide 3-kinase activity (>90%). These findings were associated with significant reductions in abundance of insulin receptors (37%), IRS1 (60%), and IRS2 (23%). Signaling in skeletal muscle was similarly affected, with reduced IRS1 phosphorylation (49%), IRS1 abundance (50%), and binding of p85 to IRS1 (57%). Insulin signaling 4 hrs after endotoxin administration was not different from controls., Conclusions: Prolonged endotoxemia is associated with marked deficits in early steps of the insulin-signaling pathway, which are at least partly explained by reduced abundance of the insulin receptor and IRS proteins. Signaling defects were not evident 4 hrs after endotoxin administration under conditions of adequate nutrition, indicating that insulin resistance develops gradually, may require concomitant malnutrition, and is not reversed by the development of endotoxin tolerance.

Objectives: Because vasoactive eicosanoids derived from arachidonic acid present in immune cell phospholipids promote lung inflammation in critically ill patients, novel experimental diets containing eicosapentaenoic acid from fish oil and gamma-linolenic acid from borage oil have been designed to limit arachidonic acid metabolism. However, excess dietary eicosapentaenoic acid impairs superoxide formation and bacterial killing by immune cells. The present study determined whether short-term enteral feeding with diets enriched with either eicosapentaenoic acid alone or in combination with gamma-linolenic acid would modulate alveolar macrophage eicosanoid synthesis without compromising bactericidal function., Design: Prospective, randomized, controlled, blinded study., Setting: University medical center., Subjects: Adult male Sprague-Dawley rats., Interventions: Rats underwent surgical placement of a gastroduodenal feeding catheter and were randomly assigned to receive one of three high-fat (55.2% of total calories), low-carbohydrate diets containing isocaloric amounts of lipids for 4 days. The control diet was enriched with linoleic acid, whereas the two test diets were low in linoleic acid and enriched with either 5 mole % eicosapentaenoic acid alone or in combination with 5 mole % gamma-linolenic acid. Alveolar macrophages were then procured to assess phospholipid fatty acid composition, eicosanoid synthesis after stimulation with endotoxin, superoxide formation and phagocytosis by flow cytometry, and killing of Staphylococcus aureus, Measurements and Main Results: Alveolar macrophage levels of arachidonic acid were significantly (p < .01) lower and levels of eicosapentaenoic and dihomo-gamma-linolenic acids were higher after feeding the eicosapentaenoic and gamma-linolenic acid diet vs. the linoleic acid diet. Ratios of thromboxane B2,/B3, leukotriene B4/B5, and prostaglandin E2/E1 were reduced in the macrophages from rats given either the eicosapentaenoic acid or eicosapentaenoic acid with gamma-linolenic acid diet compared with ratios from rats given the linoleic acid diet. Macrophages from rats given the eicosapentaenoic with gamma-linolenic acid diet released 35% or 24% more prostaglandin E1 than macrophages from rats given either the linoleic acid or the eicosapentaenoic acid diet, respectively. Macrophage superoxide generation, phagocytosis of opsonized zymosan, and killing of S. aureus were similar irrespective of dietary treatment., Conclusion: Short-term enteral feeding with an eicosapentaenoic acid-enriched or eicosapentaenoic with gamma-linolenic acid-enriched diet rapidly modulated the fatty acid composition of alveolar macrophage phospholipids, promoted a shift toward formation of less inflammatory eicosanoids by stimulated macrophages, but did not impair alveolar macrophage bactericidal function relative to responses observed after feeding a linoleic acid diet.

Objective: This study was designed to identify the unique metabolic characteristics of patients undergoing cardiopulmonary bypass (CPB) surgery who require postoperative parenteral nutrition., Summary Background Data: Patients undergoing CPB surgery occasionally develop postoperative complications that result in the need for nutrition support. Although enteral nutrition is generally the preferred feeding route, symptomatic hyperlipasemia has been described in critically ill CPB patients receiving enteral nutrition proximal to the ligament of Treitz. In such instances, enteral feeding must be temporarily discontinued or severely curtailed, thereby necessitating the initiation of parenteral nutrition for full or partial support., Methods: The period from 1988 through 1993 during which time 4091 CPB procedures were performed was reviewed. Data were retrospectively collected on 208 (5%) of the patients who underwent CPB who developed postoperative complications that necessitated the initiation of parenteral nutrition (PN) support. A random sample of 79 patients who underwent CPB who did not require PN were selected as controls., Results: Patients requiring PN after CPB were significantly older and had a higher prevalence of diabetes and metabolic complications, specifically volume overload, hyponatremia, metabolic alkalosis, uremia, and hyperglycemia, than those patients who did not require PN after CPB. In addition, patients requiring PN after CPB were significantly more hypotensive and required more vasopressive drugs during the first 24 to 48 hours after surgery than control patients., Conclusions: In patients with postoperative complications after CPB, PN is often necessary to correct the metabolic characteristics of overhydration, hyponatremia, uremia, hyperglycemia, and alkalosis.

Objectives: The authors compared the safety, gastrointestinal tolerance, and clinical efficacy of feeding an enteral diet containing a fish oil/medium-chain triglyceride structured lipid (FOSL-HN) versus an isonitrogenous, isocaloric formula (O-HN) in patients undergoing major abdominal surgery for upper gastrointestinal malignancies., Summary Background Data: Previous studies suggest that feeding with n-3 fatty acids from fish oil can alter eicosanoid and cytokine production, yielding an improved immunocompetence and a reduced inflammatory response to injury. The use of n-3 fatty acids as a structured lipid can improve long-chain fatty acid absorption., Methods: This prospective, blinded, randomized trial was conducted in 50 adult patients who were jejunally fed either FOSL-HN or O-HN for 7 days. Serum chemistries, hematology, urinalysis, gastrointestinal complications, liver and renal function, plasma and erythrocyte fatty acid analysis, urinary prostaglandins, and outcome parameters were measured at baseline and on day 7. Comparisons were made in 18 and 17 evaluable patients based a priori on the ability to reach a tube feeding rate of 40 mL/hour., Results: Patients receiving FOSL-HN experienced no untoward side effects, significant incorporation of eicosapentaenoic acid into plasma and erythrocyte phospholipids, and a 50% decline in the total number of gastrointestinal complications and infections compared with patients given O-HN. The data strongly suggest improved liver and renal function during the postoperative period in the FOSL-HN group., Conclusion: Early enteral feeding with FOSL-HN was safe and well tolerated. Results suggest that the use of such a formula during the postoperative period may reduce the number of infections and gastrointestinal complications per patient, as well as improve renal and liver function through modulation of urinary prostaglandin levels. Additional clinical trials to fully quantify clinical benefits and optimize nutritional support with FOSL-HN should be undertaken.

Pressure support ventilation (PSV) is a new ventilator modality that augments spontaneous inspiratory pressure with selected levels of positive airway pressure. There is presently considerable interest in its use in the management of critically ill, ventilator-dependent patients. The optimal method for application has not yet been established. This study investigated the effects of PSV on the oxygen cost of breathing (OCOB), a clinically applicable technique for quantitating the work of breathing. The OCOB and other bedside variables of pulmonary function were measured during PSV in ventilator-dependent patients where weaning was limited by an inability to sustain respiratory work. Nine studies were performed in 8 patients in the surgical intensive care unit. The OCOB, tidal volume (VT), respiratory rate (RR), and minute ventilation (VE) were measured at various levels of pressure support. The OCOB was calculated from the difference in oxygen consumption (VO2) during mechanical and spontaneous ventilation both at CPAP and with PSV. With increasing levels of PSV, the OCOB was observed to steadily decrease from 22% to 8% (p < 0.001). There were also statistically significant increases in VT and decreases in RR. VE appeared not to be influenced. The results of this study suggest that the bedside measurement of the OCOB may be an accurate, simple, and reproducible method of titrating the level of applied pressure support in order to optimize respiratory work.

The extensive reduction of adenine nucleotides during preservation coupled with the loss of salvageable precursors during initial reflow may exacerbate recovery of adenine nucleotides in allograft liver following transplantation. The objective of this study was to assess whether provision of adenosine during reperfusion of rat liver stored for 20 hr in University of Wisconsin solution could enhance adenine nucleotide restoration. ATP and total adenine nucleotide content of livers perfused with an oxygenated Krebs/fluorocarbon solution containing 1 mM adenosine were restored to levels in vivo within 30 min of perfusion. Adenine nucleotide recovery in livers perfused without adenosine was only 65% of normal. Acute nutritional deprivation of the donor rats had no effect on adenine nucleotide restoration. These results indicate that a conditional deficiency of intracellular nucleotide precursors exists during initial reperfusion of liver subjected to extended storage in UW solution. Provision of supplemental adenosine to the allograft liver during initial reflow appears warranted to promote full and rapid restoration of adenine nucleotide content following extended preservation ex vivo.

The effect of 6 weeks dietary lipid manipulation on the acute physiologic response to 7-hour continuous endotoxin infusion in guinea pigs was examined. One diet was enriched with N-3 fatty acids, whereas the other contained N-6 fatty acids, primarily linoleic acid. Animals fed N-6 fatty acids developed significant lactic acidemia, microvascular muscle hypoperfusion, and pulmonary infiltrates in response to endotoxin infusion. N-3 fatty acid-fed animals demonstrated improved lactate levels, microvascular muscle perfusion, and lung morphology compared to N-6 fatty acid-fed animals after endotoxin infusion. There was no significant change in cardiac output, PaO2, or mean arterial blood pressure at the end of the endotoxin infusion in either group. Pretreatment with indomethacin, or BM 13505, a specific thromboxane A2 receptor blocker, ameliorated the development of metabolic acidosis in N-6 fatty acid-fed animals, demonstrating a role for prostanoids in the sequelae of endotoxemia. The ability of dietary pretreatment with N-3 fatty acids to influence favorably the physiologic response to endotoxin represents a novel nutrient-metabolic interaction with potential therapeutic implications.

Nutritional support of the malnourished patient can be lifesaving. However, the efficacy of total parenteral nutrition in this setting depends on: a) careful estimation of energy requirements, using the Harris-Benedict equation or indirect calorimetry; b) minimizing the fluid retention which invariably complicates refeeding in marasmus; c) adequate repletion of P, K, and Mg on a daily basis; and d) accurate assessment of the rate of weight regain.

The incidence and consequences of fluid overload in the surgical ICU (SICU) have not been well defined, but may influence length of stay, days requiring mechanical ventilation, and mortality. Forty-eight consecutive patients admitted to our SICU were prospectively monitored for acute changes in weight and its impact on clinical management and outcome. When defined as a gain greater than 10% from their preoperative or premorbid weight (or an approximately 20% increase in total body water), 40% of patients had fluid overload. Patients were divided into three groups: those who had gained less than or equal to 10%, those with a weight gain between 11% and 20%, and those with greater than 20% increase in weight. Significant differences were found with respect to vasopressor dependence, colloid administration, and mortality. When indexed by initial Acute Physiology and Chronic Health Evaluation (APACHE II) mortality prediction scores, all groups had similar degrees of illness. On average, presumably due to volume limitations, patients were inadequately nourished during 85% of their SICU stay. Our results suggest that the morbidity of fluid overload can be significant, and warrants a fresh look at the methods of intraoperative fluid resuscitation.

During the course of a critical illness, many patients become ventilator dependent. The standard assessment criteria are not always accurate in predicting potential for extubation. This investigation was designed to analyze whether the work of breathing (WOB) was a more reliable predictor of ventilator dependence. Twenty consecutive ventilator-dependent patients were prospectively studied. Nineteen required ventilator support for greater than 2 wk and all were considered ventilator dependent because of their inability to tolerate weaning trials. The oxygen consumption (VO2) and resting energy expenditure were measured using a metabolic gas monitor. Respiratory mechanics and arterial blood gas measurements were obtained, and the deadspace to tidal volume ratio (VD/VT) was calculated. The WOB was determined by the difference in VO2 between spontaneous and mechanical ventilation, and expressed as a percentage of VO2 during mechanical ventilation. Five of eight patients with a WOB less than 15% (mean 1.9) were extubated within 2 wk of study, while none of 12 patients with a WOB greater than or equal to 15% (mean 34) were able to be extubated in this period. The differences in the WOB between the two groups were statistically significant (p less than .01), while there was no significant difference in mechanics, PaCO2, VD/VT or measured resting energy expenditure. These data support the use of WOB determinations in evaluating extubation potential. Using a reference value for the WOB of 15%, this study had a sensitivity of 100% and a specificity of 80%. This proved to be of greater predictive value than traditional criteria.

Peritoneal dialysis is a relatively safe and effective form of therapy for acute renal failure (ARF). As dextrose in the dialysate provides the osmotic gradient to achieve fluid removal, frequent exchanges with dialysate containing high dextrose is occasionally used to achieve negative balance in fluid overloaded patients. It has previously been shown that dextrose absorption from the peritoneal cavity is significant. Using indirect calorimetry and analyzing the dialysate effluent for its dextrose concentration, we studied the effects of high dextrose-containing dialysate in five patients with ARF. Despite minimal intake of calories, all patients had an RQ greater than 1.0 consistent with net lipogenesis resulting from dextrose absorbed from the peritoneal cavity. Four of five patients absorbed greater than 500 g of dextrose over 24 h. As overfeeding could lead to hepatic steatosis, increased CO2 production with worsening of respiratory failure, and hyperglycemia, the risks of using high dextrose-containing dialysate fluids should be weighed carefully against potential benefits. When nutritional support is indicated in such patients, contribution of dextrose calories from dialysate fluid should be taken into account.

To determine the effect of infusing large quantities of BCAA on plasma amino acid concentrations, plasma amino acid profiles were measured in 18 stressed patients before and 48 to 96 hours after initiation of amino acid solutions enriched with or exclusively containing BCAA (15.6+, 50%, 100%). Plasma concentrations of BCAA were elevated in the 100% and 50% BCAA groups, but not in the 15.6% group. Methionine, glycine, and phenylalanine concentrations were increased in the 15.6% BCAA group: methionine and glycine were decreased in the 100% BCAA groups. In the 50% BCAA group, nonbranched-chain amino acids maintained baseline concentrations. The 50% solution best preserved nitrogen balance of the BCAA solutions. The plasma amino acid profiles of patients with maple syrup urine disease (BCAA levels 5 to 10 times normal) were compared to our patients receiving BCAA-enriched solutions. Although plasma BCAA levels were elevated in our patients, allo-isoleucine, alanine, and glutamine concentrations were normal; the amino acid abnormalities of maple syrup urine disease were not observed.

To define the risks associated with central venous catheterization for total parenteral nutrition (TPN) 3291 patient days of this therapy, delivered by an established nutrition support team, were evaluated. One hundred and seventy-five catheters placed in 104 patients were reviewed over an 18 month period. Positive cultures were reported on 11 cannulae for a 6.4% incidence of colonization; five catheters (2.8%) were considered septic. Pleural or mediastinal complications of subclavian or internal jugular venipuncture occurred in eight patients (4.8%). Misdirection of the catheter tip occurred in 11.5% of insertions. Five patients (4.8%) had clinically apparent thrombosis in the superior vena cava, innominate and/or subclavian veins during hospitalization; four others had evidence of thrombosis at autopsy examination, giving an incidence of 8.7% in the entire series. No death directly resulted from the use of this therapy. Compliance with a rigid protocol by an experienced team can allow safe and effective use of central venous catheters and parenteral nutrition therapy.

Correlation of hepatocellular adenine nucleotides in donor liver with clinical posttransplant outcome has recently been reported. Our earlier work with rats has shown that pretreatment of donors with glucose effectively retards hepatocellular ATP losses in livers preserved in Collins' II solution through potentiation of their glycolytic capacity. The primary substrate--i.e., endogenous or exogenous glucose--was not identified. The current study was undertaken to compare the relative efficacy of the University of Wisconsin (UW) solution, which is devoid of glucose, with Collins' II in the support of adenine nucleotides through anaerobic glycolysis in flush-preserved rat liver. Adult rats were either pretreated with 25% dextrose or fasted prior to liver harvesting and preservation in either UW or Collins' II. Adenine nucleotide degradation and lactate production during preservation were assessed. For a given dietary pretreatment, losses of ATP and adenylate energy charge and lactate production were similar for UW- and Collins' II-preserved livers. Donor pretreatment with dextrose resulted in significantly higher ex vivo liver ATP, energy charge, and lactate regardless of the preservation solution. Salvageable nucleotide degradates were increased significantly in UW livers, presumably through the effects of allopurinol. These results demonstrate that effective support of adenine nucleotides by glycolysis in flush-preserved liver is independent of the presence of exogenous glucose but dependent upon the nutritional status of the donor prior to liver procurement.

The oxygen consumption (VO2) of healthy volunteers and patients recovering from respiratory failure in the ICU was measured by indirect calorimetry during complete mechanical (VO2vent) and spontaneous (VO2wean) ventilation. The work of breathing was calculated as the difference in VO2 between spontaneous and mechanical ventilation and expressed as a percentage of VO2vent (% delta VO2). The average % delta VO2 for eight normal healthy volunteers was 3.7 +/- 1.8%, while it was 7.7 +/- 8.8% with the Bechman and Utah metabolic carts for patients recovering from ventilatory failure who were weaned successfully from respiratory support based on clinical criteria within 24 h of their metabolic study. In patients who were not weaned successfully, the average % delta VO2 measured was 24.7 +/- 12.3%. Indirect calorimetry is a relatively simple, reliable bedside technique for determining the oxygen cost of breathing. In our sample, the oxygen cost of breathing was a reliable predictor of weaning and extubation in patients recovering from respiratory failure. This measurement may be clinically useful in identifying the patient who cannot sustain spontaneous ventilation because of excessive respiratory work.

Five patients undergoing orthotopic liver transplantation were investigated for changes in acid-base homeostasis secondary to large volume transfusions. All patients developed a transient acidemia during the operative period, followed by alkalemia which persisted into the early postoperative period. The patients received an estimated mean of 750 mEq of citrate, which appeared to cause metabolic alkalosis. The biochemical basis underlying the regulation of citrate metabolism that may have led to the timing, extent, and duration of the subsequent metabolic alkalosis is presented. Finally, the time course for the development of metabolic alkalosis may be a potentially sensitive indicator of early allograft function.

Donor pretreatment with antilymphocyte serum (ALS) effectively prevents graft-versus-host disease (GVHD) in a unidirectional (parent-to-F1 hybrid) rat small bowel transplantation model. ALS must be administered prior to or at the time of transplantation, and the intraperitoneal route is more effective than subcutaneous administration. Donor pretreatment with ALS uniformly prevents GVHD without impairing subsequent allograft function as measured by absorption of dietary energy and nitrogen, weight gain, and bowel morphology. These rodent studies suggest that ALS treatment of donors as well as recipients in small bowel transplantation may be a highly effective, simple, and easily applicable method to prevent or ameliorate GVHD in human small bowel transplantation.

The effects of enteral feeding with safflower oil or a structured lipid (SL) derived from 60% medium-chain triglyceride (MCT) and 40% fish oil (MCT/fish oil) on protein and energy metabolism were compared in gastrostomy-fed burned rats (30% body surface area) by measuring oxygen consumption, carbon dioxide production, nitrogen balance, total liver protein, whole-body leucine kinetics, and rectus muscle and liver protein fractional synthetic rates (FSR, %/day). Male Sprague-Dawley rats (195 +/- 5g) received 50 ml/day of an enteral regimen containing 50 kcal, 2 g amino acids, and 40% nonprotein calories as lipid for three days. Protein kinetics were estimated by using a continuous L-[1-14C] leucine infusion technique on day 2. Thermally injured rats enterally fed MCT/fish oil yielded significantly higher daily and cumulative nitrogen balances (p less than or equal to 0.025) and rectus muscle (39%) FSR (p less than or equal to 0.05) when compared with safflower oil. MCT/fish oil showed a 22% decrease (p less than or equal to 0.005) in per cent flux oxidized and a 7% (p less than or equal to 0.05) decrease in total energy expenditure (TEE) versus safflower oil. A 15% increase in liver FSR was accompanied by a significant elevation (p less than or equal to 0.025) in total liver protein with MCT/fish oil. This novel SL shares the properties of other structured lipids in that it reduces the net protein catabolic effects of burn injury, in part, by influencing tissue protein synthetic rates. The reduction in TEE is unique to MCT/fish oil and may relate to the ability of fish oil to diminish the injury response.