Use of a lipid containing medium chain triglycerides in patients receiving TPN: a randomized prospective trial

Lipid emulsions which contain long chain triglycerides (LCTs) provide a valuable energy source for patients requiring total parenteral nutrition (TPN). We have investigated the use of a new lipid emulsion containing both long and medium chain triglycerides (MCTs) in a randomized prospective trial. Sixty patients received TPN including 500 ml of either 20 per cent Lipofundin S (LCT) or Lipofundin 10 per cent MCT/10 per cent LCT for at least 6 days. Patients with renal or hepatic impairment, or major trauma, were excluded from the study. The MCT/LCT emulsion was found to be as safe and as effective a source of calories as LCT but the differences in metabolic parameters did not differ significantly between the two groups of patients. A lipid emulsion containing MCTs may have important advantages for seriously ill patients, but appears to have no obvious advantages for the majority of patients receiving TPN who are not severely stressed.     

Nitrogen balance during total parenteral nutrition: glucose vs. fat.

Nitrogen balance and energy expenditure were measured in 18 traumatized and/or septic patients and five depleted patients during different dietary conditions. Total parenteral nutrition (TPN) was given with nonprotein energy entirely as hypertonic glucose solutions (glucose system) or as half glucose-half intravenous fat emulsion (lipid system). In acutely ill patients, the change from 5% dextrose to TPN resulted in a prompt improvement of nitrogen balance to maintenance levels. There were no significant differences between patients given the glucose or lipid system. The five depleted patients were given the lipid and glucose systems alternately for a total of 19 one-week periods. A highly positive N balance, 80 mg N/kg . day, was attained on both diets. There was no significant difference between diets and no period of adaptation after switching from one diet to the other. On comparable intravenous diets, the acutely ill patients had higher plasma concentrations of glucose, glycerol, triglycerides, insulin, and glucagon than did the depleted patients. The study shows that the nitrogen-sparing effects of the lipid and the glucose systems are similar in moderately traumatized or infected as well as in malnourished patients. Factors other than nitrogen balance are of greater importance when choosing between the lipid and the glucose system for intravenous support.     

Fat metabolism during total parenteral nutrition: a biochemical and ultra-structural study

Background : Before the introduction of Intralipid in 1961, the incidence of adverse reactions to intravenous fat emulsions was quite common. Concurrent with hyperlipidaemia, multiple organ dysfunction could occur, but the most prominent symptoms were high fever and anaemia, and the reaction was called “the fat overloading syndrome”. Although the reports are quite rare today the reaction does still appear, and we have observed that some patients develop severe fever during or after incidental retention of exogenous fat in the blood during total parenteral nutrition (TPN). The pathophysiological background to these adverse reactions, as well as the final destiny and the effects of the retained exogenous fat particles, are largely unknown. These questions initiated the present study, which focuses on two factors of importance for the clearance of infused fat from the circulation: the lipoprotein lipase (LPL) system and the reticluloendo-thelial system. Methods : An introductory analysis of the clinical course of a head-injured patient suffering from fat intolerance during TPN implied that observed adverse reactions could be due to influence on macrophages by retained exogenous fat particles. Results : During infusion of lipid emulsions, cholesterol and phospholipids accumulated in non-high-density lipoproteins, while high-density lipoproteins were enriched in triglycerides. Triglycerides also accumulated in hepatic tissue, and the activity of hepatic lipase decreased. Although lipoprotein lipase activity in the heart was up-regulated and serum levels of triglycerides were normal, suggesting that the total elimination rate of triglycerides was not impaired, ultra-structural investigations indicated that Kupffer cells were involved in clearing exogenous lipids from the blood during the infusion of long-chain triglycerides. Furthermore, the Kupffer cells were activated, according to morphological criteria. When high doses of fat were given intravenously, the Kupffer cells were grossly distended by fat vacuoles, and serum levels of lactate dehydrogenase increased. During treatment with fat emulsions containing medium-chain triglycerides and long-chain triglycerides in equal amounts, the alterations in lipid transport were less pronounced, and signs of Kupffer cell activation were weaker than during infusion with long-chain triglycerides only. Conclusion : The experimental studies showed that infusion of exogenous fat particles interfered with the regulation of lipid transport, and there were signs of increased demands on various aspects of lipid metabolism. Although the capacity of the LPL was sufficient in most situations in healthy rats, the Kupffer cells seemed to be involved in the clearance of exogenous lipids. The present investigations identified one factor, LCT fat emulsion, which was necessary for the appearance of fat vacuoles in the Kupffer cells during TPN. To some extent, the experimental findings may be related to clinical observations of a head-injured patient who developed signs of acute, severe macrophage activation with haemophago-cytosis during and after accumulation of exogenous fat in the blood after treatment with intravenous fat emulsions. The condition was considered to be a consequence of impaired lipid elimination and altered macrophage function during clearance of fat from the blood, a consideration supported by the morphological changes of rat Kupffer cells after TPN in the present study.     

A randomized prospective trial of amphotericin B lipid emulsion versus dextrose colloidal solution in critically ill patients.

BACKGROUND: Amphotericin B is the agent of choice for most invasive fungal infections in critically ill patients. It is associated with at least a 50% incidence of nephrotoxicity, despite prophylactic measures such as sodium loading. Newer formulations of amphotericin B are available but are costly and have unknown bioavailability in critically ill patients. Previous trials in neutropenic and critically ill patients have demonstrated that mixing amphotericin B with 20% lipid solution (Intralipid; Clintec Nutrition, Deerfield, III) may decrease nephrotoxicity. METHODS: In this randomized, prospective clinical trial, patients with positive fungal blood cultures, tracheal/sputum cultures or peritoneal cavity cultures were randomized to receive either 0.5 mg/kg per day of amphotericin B dextrose or 1.0 mg/kg per day of amphotericin B lipid emulsion. Duration of therapy was determined by the primary care team. Weekly 24-hour creatinine clearance was measured until 2 weeks after amphotericin B therapy was completed. RESULTS: The two groups were similar based on age, white blood cell count, serum creatinine, and creatinine clearance at the beginning of therapy. The group receiving amphotericin B lipid emulsion had significantly less decrease in creatinine clearance compared with controls, despite receiving significantly more amphotericin B. CONCLUSION: Amphotericin B lipid emulsion can be given at a higher total cumulative dose than amphotericin B dextrose with less nephrotoxicity.     

Parenteral nutrition in ventilated patients with chronic obstructive pulmonary disease: long chain vs medium chain triglycerides

AIM: The aim of this study was to assess the usefulness of a lipid formulation containing a physical mixture of medium (MCT) and long chain triglycerides (LCT) compared with a long chain triglycerides emulsion in patients affected by chronic obstructive pulmonary disease with acute respiratory failure. METHODS: Twenty-four patients requiring mechanical ventilation were randomly selected in 2 groups and received total parenteral nutrition. Twelve patients received a MCT/LCT emulsion (50:50), the others used a 100% LCT emulsion. Nutritional status, metabolic rate, time of ventilatory support and weaning were evaluated. RESULTS: Both groups showed an improvement of all nutritional parameters evaluated; oxygen uptake, carbon dioxide output and respiratory gas exchange ratio were similar in both groups. The duration of mechanical ventilation was not significantly different; however, the time of weaning in the MCT/LCT group was significantly shorter. The longer weaning time in the LCT group patients could be related to vasoactive intermediates deriving from long chain fatty acids. The T-cell subsets, which were evaluated for both groups, showed a significant decrease of T helper-T suppressor ratio in the LCT group. CONCLUSION: MCT/LCT emulsion is an effective lipid supplementation and should be considered the therapy of choice in COPD patients; however, the relationship between lipid emulsions administered and length of weaning requires further investigations.     

The effects of prostaglandin E1 on non-pulmonary organ function during clinical acute respiratory failure. The Prostaglandin E1 Study Group.

The effects of prostaglandin E1 (PGE1) on non-pulmonary vital organs in critically ill patients are not well defined. This study evaluated the role of exogenous PGE1 in systemic homeostasis during the adult respiratory distress syndrome (ARDS). Indicators of end-organ function were analyzed retrospectively in 146 septic or post-trauma patients with ARDS who received PGE1 (30/ng/kg/min) or placebo IV for up to 7 days in a randomized, double-blind clinical trial. Hemodynamic variables and serum levels of creatinine, bilirubin, and SGOT, platelet count, and changes in the white blood cell count were measured daily. Our results indicate that mean arterial pressure, pulmonary artery pressure, and systemic and pulmonary vascular resistance indices were significantly lower in the PGE1 group versus the placebo-treated group. Cardiac index, stroke index, and oxygen delivery index were significantly increased in the PGE1 group. Serum bilirubin and SGOT were decreased significantly among PGE1-treated patients compared with placebo-treated patients, while the white blood cell count increased more significantly from baseline values with PGE1 treatment. Intergroup differences in platelet count and serum creatinine levels were not statistically significant. The results indicate that PGE1 improves cardiovascular performance, hepatic function, and leukocyte availability during clinical ARDS. Prostaglandin E1 did not affect platelet counts and renal function in this study.     

Role of lipid control in diabetic nephropathy

Patients with diabetic nephropathy are known to be associated with many lipoprotein abnormalities, including higher plasma levels of very low-density lipoprotein, low-density lipoprotein and triglycerides, and lower levels of high-density lipoprotein. Many studies have reported that lipids may induce both glomerular and tubulointerstitial injury through mediators such as cytokines, reactive oxygen species, chemokines, and through hemodynamic changes. Clinical studies in patients with diabetic nephropathy showed that lipid control can be associated with an additional effect of reduction in proteinuria. Experimental studies demonstrated that lipid-lowering agents exerted a certain degree of renoprotection, through both indirect effects from lipid lowering and a direct effect on cell protection. Therefore, lipid control appears to be important in the prevention and treatment of diabetic nephropathy. Diabetic nephropathy has become the leading cause of end-stage renal failure in many countries, including Taiwan. One of the major risk factors for the development and progression of diabetic nephropathy is dyslipidemia. In this paper we will review the role of lipid in mediating renal injury and the beneficial effects of lipid control in diabetic nephropathy.     

The Relationships Among Serum Lipid Levels,Adiposity, And Depressive Symptomatology In Persons Aging With Spinal Cord Injury

Abstract

Background: Cardiovascular disease (CVD) appears to occur prematurely in persons with spinal cord injury (SCI). Stress may play a significant role in the development of CVD. Depression is the most common form of stress complicating the care of persons with SCI.

Methods: In 188 persons with SCI, 46% with tetraplegia and 54% with paraplegia, the relationship between depression and the serum lipid profile was studied. Depression was measured by the Older Adult Health and Mood Questionnaire (OAHMQ) for persons with disability. Total cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol and triglycerides were measured; body mass index (BMI) was computed and percent body fat was determined by dual-energy x-ray absorptiometry (DXA).

Results: Depression and level of SCI were found to have significant interactive effects on serum lipid levels. Serum total and LDL cholesterol, as well as triglycerides, were all higher among persons with paraplegia who were depressed compared to those who were not depressed. This was not found in persons with tetraplegia. Inverse relationships were evident between serum triglycerides and HDL cholesterol levels. Persons with paraplegia who were depressed had significantly more adiposity than those not depressed. BMI correlated directly with serum triglycerides and indirectly with serum HDL cholesterol.

Conclusion: Depression appears to be a strong determinant of adverse lipid profiles in patients with paraplegia. The association between depression and adiposity in these patients compounds the risk for cardiovascular disease.     

ICU nephrology: the implications of cardiovascular alterations in the acutely ill

Cardiovascular alterations are common in critically ill patients and can have important implications for multiple organ systems, including the kidney. Restoring and maintaining adequate hemodynamic status in such patients is crucial to ensure sufficient oxygen availability to tissues and organs so that they can function optimally. In this text, we will return to the basic physiology of cardiac output and its components so that we can better understand the effects of cardiovascular alterations in critically ill patients, and how best to treat them.     

The relationships among serum lipid levels, adiposity, and depressive symptomatology in persons aging with spinal cord injury

BACKGROUND: Cardiovascular disease (CVD) appears to occur prematurely in persons with spinal cord injury (SCI). Stress may play a significant role in the development of CVD. Depression is the most common form of stress complicating the care of persons with SCI. METHODS: In 188 persons with SCI, 46% with tetraplegia and 54% with paraplegia, the relationship between depression and the serum lipid profile was studied. Depression was measured by the Older Adult Health and Mood Questionnaire (OAHMQ) for persons with disability. Total cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol and triglycerides were measured; body mass index (BMI) was computed and percent body fat was determined by dual-energy x-ray absorptiometry (DXA). RESULTS: Depression and level of SCI were found to have significant interactive effects on serum lipid levels. Serum total and LDL cholesterol, as well as triglycerides, were all higher among persons with paraplegia who were depressed compared to those who were not depressed. This was not found in persons with tetraplegia. Inverse relationships were evident between serum triglycerides and HDL cholesterol levels. Persons with paraplegia who were depressed had significantly more adiposity than those not depressed. BMI correlated directly with serum triglycerides and indirectly with serum HDL cholesterol. CONCLUSION: Depression appears to be a strong determinant of adverse lipid profiles in patients with paraplegia. association between depression and adiposity in these patients compounds the risk for cardiovascular disease.     

Evaluation of the Pneupac Ventipac portable ventilator in critically ill patients

We assessed adequacy of ventilation in 20 critically ill patients with multiple organ failure using a Pneupac Ventipac portable ventilator and the effects on patients' haemodynamic stability. Baseline data were recorded over 15 min for a range of respiratory, haemodynamic and oxygen transport variables during ventilation with a standard intensive care ventilator (Engstr?m Erica). Patients were then ventilated for 40 min using the portable ventilator. Finally, they were ventilated for a further 40 min using the standard intensive care ventilator. Heart rate, arterial and pulmonary artery pressures were recorded at 5-min intervals throughout the study period. Cardiac index and other haemodynamic data derived from a pulmonary artery catheter were recorded at 20-min intervals. Blood gas analysis was performed and oxygen transport data (oxygen delivery, oxygen consumption and physiological shunt) were calculated at the end of each of the three periods of ventilation. In general, no significant adverse effects of ventilation using the portable ventilator were observed for any of the variables studied. Arterial PO(2) increased significantly during ventilation with the portable ventilator, reflecting the use of a higher inspired oxygen fraction during this part of the study. Oxygen consumption decreased significantly in one patient during ventilation by the portable ventilator although none of the other variables measured in this patient was altered. We conclude that ventilation of critically ill patients using the Pneupac Ventipac portable ventilator was safe, satisfactory and associated with minimal adverse effects on respiratory, haemodynamic and oxygen transport variables.     

Effects of inotropes on human leucocyte numbers, neutrophil function and lymphocyte subtypes

We have investigated the effects of inotropes with different adrenergic receptor specificity on differential white cell count, lymphocyte subtypes and neutrophil function in healthy volunteers. Six healthy, male volunteers were enrolled into this randomized, placebo-controlled pilot study. Each volunteer was studied on four separate occasions during a 2-h infusion of various agents, and for 2 h after stopping the infusion. The agents investigated were adrenaline 0.1 microgram kg-1 min-1, dobutamine 5 micrograms kg-1 min-1, dopexamine 2 micrograms kg-1 min-1 and 5% glucose 0.5 ml kg-1 h-1. Venous blood was sampled at 0, 30, 120 and 240 min. Haemodynamic monitoring was continued throughout the study. Full blood count, white cell differential count and enumeration of lymphocyte subtypes were performed. Neutrophil function tests included chemoluminescence, and assessment of neutrophil chemotaxis, phagocytosis and adhesion. The Wilcoxon signed rank test was used to compare differences between placebo and active drugs at each time compared with baseline. There was a significant increase in white cell count, lymphocyte count and neutrophil count with adrenaline, and a small but significant decrease in these variables with dobutamine and dopexamine. These changes were also apparent for absolute CD3+, CD4+ and CD8+ lymphocyte counts. Neutrophil respiratory burst in response to f-methionyl-leucyl-phenylalanine increased significantly only with adrenaline at 30 min (P = 0.046). There were no other significant changes in tests of neutrophil function. Infusion of inotropes was associated with changes in white cell numbers, lymphocyte subtypes and neutrophil respiratory burst. In healthy volunteers, adrenaline had effects different from those of dobutamine and dopexamine. The clinical relevance of such effects requires further investigation in critically ill patients.      

Octreotide therapy for chylous ascites in a chronic dialysis patient

Chylous ascites, a rare complication in patients receiving continuous peritoneal dialysis, often presents with turbid dialysate. This characteristic makes it frequently confused with peritonitis. Conservative treatments including bowel rest and dietary intervention with medium chain triglycerides are advised by many authors in the literature. However, this approach usually takes a long time before the lymphorrhagia are eventually resolved. Here, a case of chylous ascites that was successfully treated with subcutaneous octreotide, a somatostatin analogue, is reported. By shortening the bowel rest period, this treatment avoids the nutritional and immunological adverse effects. A series of peritoneal equilibrium tests were performed after administration of octreotide and the results showed that octreotide did not alter the peritoneal function in the short term. Therefore, subcutaneous octreotide administration is a safe and effective therapy in peritoneal dialysis patient with chylous ascites.     

允许性低氧血症理论与实践研究进展

背景 允许性低氧血症是指对于难治性低氧的危重患者在相对较低的氧饱和度的情况下,通过优化心输出量（cardiac output,CO）,部分代偿呼吸功能,维持正常氧供（delivery of oxygen,DO2）,减少机械通气对肺部和全身的损害。目的 对目前允许性低氧血症理论与实践进展综述,为进一步的研究与讨论提供基础。内容 阐述允许性低氧血症的基本概念、起源、理论基础、研究进展及临床实践可能需要关注的问题。 趋向 理论上允许性低氧血症能够改善危重患者的临床预后,但仍需更多的临床实验来证明其在危重患者呼吸管理中的有效性和安全性。     

Adipose tissue fibrosis

The increasing prevalence of obesity causes a major interest in white adipose tissue biology. Adipose tissue cells are surrounded by extracellular matrix proteins whose composition and remodeling is of crucial importance for cell function. The expansion of adipose tissue in obesity is linked to an inappropriate supply with oxygen and hypoxia development. Subsequent activation of hypoxia inducible factor 1 (HIF-1) inhibits preadipocyte differentiation and initiates adipose tissue fibrosis. Thereby adipose tissue growth is limited and excess triglycerides are stored in ectopic tissues. Stressed adipocytes and hypoxia contribute to immune cell immigration and activation which further aggravates adipose tissue fibrosis. There is substantial evidence that adipose tissue fibrosis is linked to metabolic dysfunction, both in rodent models and in the clinical setting. Peroxisome proliferator activated receptor gamma agonists and adiponectin both reduce adipose tissue fibrosis, inflammation and insulin resistance. Current knowledge suggests that antifibrotic drugs, increasing adipose tissue oxygen supply or HIF-1 antagonists will improve adipose tissue function and thereby ameliorate metabolic diseases.     

Effects of physiologic albumin and hespan levels on hepatocytes in vitro

BACKGROUND: Although albumin and hydroxyethyl starch (HES) are routinely used in critically ill, hypoalbuminemic patients, no studies have tested the effect of supplemental albumin and HES on hepatocyte function. METHODS: In this study, the effects of these agents were evaluated by using stable, rat hepatocyte cultures in a collagen sandwich configuration. Hepatocyte synthesis of albumin, urea, and intracellular triglycerides was monitored in Dulbecco's modified Eagle medium (supplemented with fetal bovine serum, hydrocortisone, L-proline, gentamycin, and insulin) without supplemental colloid (control cultures) and with supplemental 2% bovine serum albumin (BSA), 4% BSA, 2% HES, or 4% HES. RESULTS: The albumin secretion in control cultures rose from 31.03 microg/day per 10(6) cells on day 3 to 154.17 microg/day per 10(6) cells by day 12 and remained constant. In contrast, the level of albumin synthesis in the 2% and 4% BSA groups rose from significantly higher initial values (p < 0.05) of 71.25 microg/day per 10(6) cells and 73.27 microg/day per 10(6) cells, respectively, to 127.61 microg/day per 10(6) cells and 107.95 microg/day per 10(6) cells by day 7, then declined rapidly to 58.98 microg/day per 10(6) cells and 41.28 microg/day per 10(6) cells by day 12 when cell disruption was present. HES also reduced albumin synthesis. The urea genesis in the control groups and in the treatment groups was found to be comparable throughout the study. The BSA supplemented groups accumulated large amounts of intracellular lipid droplets during the experiment. The intracellular triglycerides analysis found the 4% BSA group to be significantly (p < 0.05) higher than the 4% HES. CONCLUSION: BSA, added to a collagen sandwich hepatocyte preparation, causes reduced hepatocyte synthesis by day 8, probably a result of intracellular triglyceride accumulation, whereas HES reduces synthesis through unidentified mechanisms.     

Lipid composition of the tissues of human knee joints. II. Synovial fluid in trauma

Synovial fluid was aspirated from the knees of 125 patients and lipid profiles were determined. The patients had knee injuries with or without fracture of bone; these lipid profiles were compared with "controls" (synovial fluid obtained at surgery from patients that did not have a knee injury). Floating lipid droplets were observed in some of the synovial fluid from patients with fractures. These lipid droplets could be separated as a well-defined supernatant layer after a few minutes of centrifugation (100 X g). This layer was found to consist mostly of triglycerides. The synovial fluid from patients with fracture and those with only soft-tissue trauma showed increases in total lipids and triglyceride content but had lower phospholipids when compared with nontraumatized knees. Phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, sphingomyelin, cholesterol, monoglycerides, diglycerides, triglycerides, and free fatty acids were present in all synovial fluids assayed. The large amount of triglycerides in the synovial fluid in many cases may be a good indicator of marrow leakage. Because the soft tissue surrounding the knee is also rich in triglycerides, a low phospholipid level in some cases may be an even better indicator of marrow leakage.     

Direct Assessments of the Antioxidant Effects of Propofol Medium Chain Triglyceride/Long Chain Triglyceride on the Brain of Stroke-prone Spontaneously Hypertensive Rats Using Electron Spin Resonance Spectroscopy

Background: Antioxidant anesthetics such as propofol (2,6-diisopropylphenol) directly inhibit lipid peroxidation via the generation of reactive oxygen species. Currently, there are no other studies regarding the direct effects of propofol medium chain triglyceride/long chain triglyceride (MCT/LCT) on reactive oxygen species generation or in experimental models of reactive oxygen species-induced oxidative stress in the brain.

Methods: The authors investigated the effects of propofol MCT/LCT on reactive oxygen species (hydroxyl radical or superoxide) by electron spin resonance spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide. The effects of propofol MCT/LCT on oxidative stress in the brain of Wistar-Kyoto rats or stroke-prone spontaneously hypertensive rats were investigated by using an in vivo L-band electron spin resonance system to monitor the decay rate of 3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl as a nitroxyl spin probe.

Results: These studies provided direct evidence that propofol MCT/LCT inhibited hydroxyl radical generation, but not superoxide generation. Regarding the hydroxyl radical from the Fenton system, it is likely to be due to the scavenging effects of vehicle. Anesthesia with propofol MCT/LCT reduced the degree of the high oxidative stress in the brain of stroke-prone spontaneously hypertensive rats.     

Patterns of injury and white cell response in critically ill trauma patients who present with leucopenia

The outcome of critically ill trauma patients who presented to the intensive care unit with leucopenia (total peripheral white cell count < 4 x 10(9)/1) was studied prospectively with respect to the total white cell and neutrophil response. A total of 105 patients, of whom 30 were leucopenic, were admitted to the ICU during a 4-month period. The prevalence of leucopenia was significantly higher in patients with gunshot wounds (P < 0.05) and hollow visceral intra-abdominal injury (P < 0.001). Eight (27%) of the leucopenic patients died. No significant difference was found in initial mean total white cell or neutrophil count, or in the differential percentages, between survivors and non-survivors. The total peripheral white cell count increased significantly in survivors compared with non-survivors (P < 0.001), and significant differences were found in absolute neutrophil counts and differential percentages by days 5 and 10 (counts P = 0.01, P < 0.02; differentials P < 0.01, P < 0.01). These results suggest that granulocyte colony-stimulating factor may have a role in the treatment of trauma patients with persistent neutropenia following intra-abdominal hollow visceral injury.