Slide 1. Nutritional support in trauma and critically ill patients on itself is quite an extensive topic and has gained a greater deal of popularity in recent years.
Slide 2. Trauma victims, such as this gentleman, who sustained a stab wound to the chest and the abdomen can sometimes develop a Multiple Organ system Failure (MOF) that make them prone to malnutrition and the consequences of malnutrition.
Slide 3. Furthermore, there is a special group of patients who require great deal of nutritional support are especially burn victims such as this one depicted in this picture.
Slide 4. Nutrition support in Renal and Pulmonary Failure and ARDS (Acute Respiratory Distress Syndrome) is another topics that certainly have gained big popularity recently. This patient that is seen in this slide is a patient who has sustained rupture of the diaphragm and migration of the liver into the chest and as a consequence of that he doubled-up in acute respiratory distress syndrome (ARDS).
Slide 5. What are we really talking about and what's involved in this topic is the response of injury to injury and infection the role of Cytokines control over nutrition and metabolism, biology of nutrient substrates and enteral and parental feeds.
Slide 6. However, the three major questions that really need to be answered in this complex topic is timing of feeding and initiation of feeding, early versus late, composition of nutrient substrates and how do we feed. So basically, when do we feed, what will you feed and how do we feed?
Slide 7. It is important to know who is really in control over nutrition and metabolism of patients. Is there a sight to cytokines, are there hormones or perhaps genes or other factors that are yet unknown.
Slide 8. Regardless of that, the goals of nutrition support and nutrition maintained to be or are natural balances, to preserve and cover visceral proteins to reduce morbidity, reduce mortality and shorten hospital stay.
Slide 9. It is typical to see these patients in a great deal of metabolic de arrangements. However there is a picture of these patients in which it is somewhat clearly defined. Injury results in oxidation of body protein and fat increased hydration of fat-free body mass and about five liters on an average. One-fifth of the divided store of protein is lost mostly during ten days and two-thirds of this is from the skeletal muscle. This is associated with increased energy expenditure and oxygen consumption. These are data from Monk et.al. That was published in the Annals of Surgery in 1996.
Slide 10. The profile however, of a patient who develop a multiple system organ failure include hyperglycemia with increased gluconeogenesis and intolerance of infused glucose; decreased effect of insulin; increased lactate and pyruvate levels. But then progressively increasing beta-hydroxybutyrate and decreased AKBR with increased triglycerides and free fatty acids (FFA).
Slide 11. Furthermore, progressive ability of used glucose would increase levels of proline, methionine, glutamic acid and ornithine. Furthermore, this is associated with increased branch-chain amino acids (BCAA) and reduced protein synthesis increased albumin metabolism and increased peripheral protein metabolism.
Slide 12. Some of the role of some cytokines in critically ill patients as a whole, well this is not exactly clearly defined because they are not classical endocrine hormones, their paracrine effect which is direct cell to cell communication, that is a cascade. What is it - autocrine? A symbol is their own production. While when it is endocrine this is the time when cytokines are in excess or spill over into the system and circulation.
Slide 13. Protein and amino acids metabolism particularly with patients is characterized by muscle metabolism; increased urinary nitrogen excretion; increased excretion of 3-methylhystedine; increased total protein degradation; reduced protein synthesis and redistribution of amino acids such as glutamine. All of these basically lead to a state of negative nitrogen balance that has significant consequences in the patient's status, patient metabolism and prognosis.
Slide 14. One special theme has been branch-chain amino acids in critically ill patients. While it is clear that branch-chain amino acids do stimulate insulin secretion; there are skeletal muscle fuel and they render nitrogen balance positive. They certainly are very useful in hepatic coma although they do not change the prognosis of liver failure and encephalopathy and so far there have been some conflicting results in the use of branch-chain amino acids in critical instances.
Slide 15. Another amino acid that has been quite useful and has gained a great deal of popularity recently is key precursor of urea cycle. This conditional essential amino acid, it does promote growth and it is insulinogenic and has been shown clearly to be immuno-trophic to promote immuno-trophic effects and is decreased following injury.
Slide 16. The arginine well known in medical practice. It is a part of the diet are another part of micronutrient world that is being used quite a bit in nutrition support.
Slide 17. The patient who has undergone renal transplant and they were not being fed orally required significantly less amount of immune suppressing medications because they have basically been on a nucleotide free diets and when these patients were started on regular diets they simply required more anti-immune medications. Nucleotide free diets diminish certain t-cell mediated immune response; then decreased survival from S. Aureus and C. Albicans and all these effects are reversed with RNA supplementing.
Slide 18. As a result, nucleotides have called as conditional requirements.
Slide 19. For the liver injuries. Nucleotides clearly prevent ethionine-induced liver injury; it suppresses triglyceride accumulation; prevents increase of hepatic enzymes and decrease of liver ATP(Adenosinetriphosphatase) have been shown in hepatectomy rats to improve nitrogen balance even if the animals have undergone a 70 per cent hepatectomy when these animals were fed with TPN (Total Parenteral Nutrition) and nucleotides had reduced histologic injuries from galactosamine.
Slide 20. So the rationale for diets with nucleotides is to repair, repair of the injured intestinal mucous; increased DNA and protein content; increased maltase activity; increase the height of the villas, realign and certainly to improve the proliferation activity and improve results.
Slide 21. One very interesting and important topic in nutritional support is certainly the lipids and the lipid metabolism. In this case the consequences of lipid metabolism in sepsis are increased peripheral lipolysis and hepatic triglyceride synthesis, the fact that mobilization exceeds oxidation are density lipoproteins (VLDL) and triglyceride (TAG) synthesis increases; very low density lipoprotein (VLDL) clearance is decreased is as a result liver than is unable to maintain balance between free fatty acid uptake and triglycerides. Consequently the liver gets enlarged as fat accumulation causes hepatomegaly.
Slide 22. Lipid emulsions are typically rich in linoleic acid; they are converted to arachidonic acid and incorporated into tissue phospholipids where injury phospholipase A2 releases arachidonic acid from tissue phospholipids.
Slide 23. There are advantages, however, in using lipid emulsion as a therapy in nutritional support. They are with high-energy content, they low osmolarity; nitrogen stays in effect; and no carbon dioxide will evolve and subject may be given enterally or parenterally.
Slide 24. Disadvantages on the other hand, they may cause increase in triglycerides; increase of non-esterified free fatty acids (NEFA) levels; arrhythmias; it has suppressive affect on the reticuloendothelial system; and depresses or may depress myocardial function and has been shown that in patient that were fed with high lipid diets had caused increased mortality.
Slide 25. This is some of what appeared recently in the General Trauma and there were 60 patients on TPN that were started on the fifth day post-operatively or post-injury and were divided into two groups, the no-fat TPN group and the standard TPN group.
Slide 26. In the group of people who were on parenteral nutrition and where they were fed with fewer calories per kilograms during the program for twenty-four hours, 25 per cent lipids and 1.5 gram of protein per kilogram per day. The results were the following: lipid group had increased infection rate, they had prolonged intensive care unit and hospital stay, they had prolonged pulmonary failure, very severe or more severe acute respiratory distress syndrome and a depressed t-cell function.
Slide 27. The glucose metabolism substance is certainly, it's very important in order for us to achieve the optimal nutritional support so we have to know exactly how and what is happening with the glucose, hyperglycemia is certainly an early sign of sepsis and those should be identified early. Hypoglycemia on the other hand is a sign of advanced disease. The whole glucose metabolism is basically dose dependent on a tumor necrosis factor (TNF) and IL-1 marked increase of body use tumor necrosis factor or IL1 or interleukin stimulus of gluconeogenesis from alanine.
Slide 28. The other question comes when to start feeding. The answer is clear, as soon as possible, however there are a few questions that have not been resolved entirely. The main one is how early is early?
Slide 29. We, as a general rule, we attempt to resuscitate the patient first and then feed him. However, if the resuscitation takes longer and the patient is to be under vasopressors then administering enteral nutritional support is clearly a big NO and one should not feed an under-resuscitated gut. However, if this process continues to be prolonged, the resuscitation is somewhat difficult, the patient continues to be in a sick condition and requires invasive measures then parenteral nutritional support should be started.
Slide 30. The third question that we have is how to feed these patients? Well, it is clear that we can use the gut then we should think to use them. However, the nutrition support shouldn't be provided to all patients at all times with all diseases and this can be accomplished enterally parenterally.
Slide 31. This is a slide that somewhat explains why the nutrition support should be attempted to be performed or delivered enterally by enteral feeding. On the right side is a picture of the villa or the villas that has been normal or is a normal slide and the middle is a picture of the villi that has been atrophied with starvation or parenteral nutrition. While on the left is the slide where it shows the villa to be restored to its length after the internal nutrition. So, its basically the nutrition support provided internally maintained gastroenteric function, blocked the hypermetabolism response to injury and it may prevent bacterial translocation, although this is not enterally elucidated this is clearly supports and enhances immune system especially if we use immune enhancing feeding.
Slide 32. In 1993, the Annals of Surgery published a meta-analysis of eight prospective randomized trials with trauma in high-risk surgical patients. They had 111 patients that were fed with a tubal enteral nutrition and 112 were on total parenteral nutrition. The results were the following septic complications from the group that were fed by a total enteral were 18 while the patient with the total parenteral nutrition had a significant number of complications, 35 percent with a p-value 0.01 but one can clinically encounter patients with the lowest rate of complications patients.
Slide 33. They concluded that early enteral feeding compared with parenteral feeding reduces post-operative septic complications.
Slide 34. So just to reiterate one more time, the internal feeding however has complications and in our practice we do not feed patients who are in shock; who have a severe illness; who have severe diarrhea; high output fistula; multiple fistulas or severe acute pancreatitis as well as a patient who have very great prognosis.
Slide 35. How should we deliver the enteral nutrition support? We can do that through the gastric route through the duodenum, or the jejunum itself. The gastric feeding certainly makes a great deal of sense however it is not without complications and it is sometimes difficult to achieve the goal.
Slide 36. In the study published by the Critical Care Medicine in 1998 examined 7 patients with thoracic or thoracic-neurologic injuries that were studied with antroduodenal manometry during fasting and feeding while on a ventilator, weaning from and after they were extubated. The motility data were compared with 9 volunteers.
Slide 37. During the fasting state under the sedation of morphine the migrating motor complex in a patient who was significantly short, the p-value of 0.001 with 32.0 versus anything 101.0 minute.
Slide 38. The observed motility patterns suggests that early administration of internal feeding might be more effective into duodenum or jejunum than into the stomach in mechanically ventilated patients.
Slide 39. This is a patient who I had eluted initially to and who has an acute respiratory distress problem. Now the respiratory failure and nutritional support into this very high-risk patient had certainly achieved some milestones in development and the way we treat and feed these patients.
Slide 40. Now, the rationale for low carbohydrate and high fat diets in these patients has to do with increased CO2 production when one feeds them with high carbohydrate diet and certainly they have a higher RQ (ventilation/perfusion) ratio and it is more difficult to wean them from respirator.
Slide 41. In a prospective randomized double blind study of 146 patients the specialized nutrition support in these patients showed that reduction in neutrophil recruitment; improved oxidation, decreased ventilatory time from 11 versus 16 days with significant pee value. These patients developed less multiple organ system failure and have decreased length of stay in ICU (Intensive Care Unit).
Slide 42. Now, these patients were fed with a special enteral diet that is very rich in nucleotides and arginine and other immune enhancing nutrients. Immune enhancing formulas have certainly proliferated in the recent years and are being used more and more in our practice.
Slide 43. In fact, in a study published in 1995 showed the impact that is one of the immune enhancing diets was well tolerated and was safe and had lower mortality rate more than was expected in these group of patients with shortened hospital stays from 11 ½ days these patients were fed with an impacted lower infection rate and it was clearly shown that the most benefits were seen in septic and severely critically ill patients.
Slide 44. In 1995, most of the center of randomized control study was reported where 296 surgical patients were divided into isonitrogenous diet 158 and 168 of them were fed with immune enhancing diet.
Slide 45. The concluded from the study that early enteral feeding is safe and is associated with significant benefits especially in septic patients.
Slide 46. Another study was published in 1996 in which they had 35 patients who were severely injured patients, 17 of them were terribly immune-aid and 18 of them were on the isonitrogenous diet. 18 of the patients served as control and they were not fed.
Slide 47. Major infections rate was significantly less in the group that were fed with immune-aid only 6 percent on the isonitrogenous diet the complication rate was 41 percent while the control group had 58 percent rate of infection.
Slide 48. More recently, 398 medical and surgical patients who were studied, 193 were fed with enteral immunonutrition and 197 were control. 101 patients or 50 of them were fed with immune enhancing diets and 51 were control who were successful in achieving early internal nutrition whereby they received more than 2.5 liters within 72 hours.
Slide 49. In this study, immune enhancing diet had actually a higher APACHE II score and ir respectful of this of an immune enhancing diet patient showed significant reduction in mechanical ventilation time and intensive care unit stay, hospital length of stay and duration of systemic inflammatory response syndrome.
Slide 50. In patients who tolerated early internal nutrition and were fed with immune enhancing formula, there was a significant reduction of their requirement for mechanical ventilation with an associated significant reduction in post-randomization hospital length of stay.
Slide 51. More recently, meta-analysis of the immune-endo diet trough showed that 14 prospective randomized clinical trials used intact protein arginine, RNA Omega 3, Omega 6 fatty acids, 13 of at least 14 studies reported improved clinical outcome with reduced complication rate, rate of infections and hospital stay.
Slide 52. Of these 14 prospective randomized clinical trials were included 12 Type A, 5 patients they were burned, GI surgery or gastrointestinal surgery, HIV positive patients, trauma, sepsis and they were a mixed medical and surgical group of patients. Certainly with a variety of formulas were used and they all had somewhat similar results and although mortality was not affected significantly the results were favorable only in patients receiving early critical amount of enteral feeds.
Slide 53. The main question arise, are these immune enhancing drugs simply too expensive to use in massively in outpatients at this time. Well, prospective randomized double blind multi center studies showed that early feeding with Impact is actually cost effective.
Slide 54. 77 patients were given impact or immune enhancing diet and 77 out of these were given isonitrogenous diets. Early internal feeding with Impact was associated with significant cost reduction and lower late post-operative complications.
Slide 55. More recently, Annals of Surgery published a meta-analysis of 11 randomized controlled clinical trials of early nutritional support in more than 1,000 patients. These were critically ill and cancer patients that were fed with Immune-AID.
Slide 56. It was concluded from this study that nutritional support supplemented with arginine, glutamine, branch-chain amino acids (BCAA), nucleotides and Omega-3 fatty acids results in significant reduction of infections complications , and overall hospital stays in critically ill and patients with gastrointestinal cancer.
Slide 57. In recent years a great deal of information and questions have arise, the main one being is total parenteral nutrition really immunosuppressive. Well, one has to understand that a clinical trial for nutrition as is given today massively in most of the hospitals of the world it contains basically sugar, proteins and lipids. So, we do not have, as of now, in our practice use of multiple diets and arginine and glutamine and other immune enhancing micronutrients in the total parenteral nutrition formulas. So yes, total parenteral nutrition I think is immuno-suppressive if its mis administered, if it is misgiven to patients. If it causes hypoglycemia and the sugars are not controlled well, yes, it is immuno-suppressive if there is no nucleotides, there is no arginine and certainly it is immuno-suppressive if it is given for most of the calories are given us.
Slide 58. And the case is very clear; we are making total parenteral nutrition iatrogenic immuno-suppressive nutritional therapy.
Slide 59. One may think, how would the ideal formulation be in order to be immune enhancing and perhaps tolerable for the patients. Well, it should be very high in proteins and especially branch-chain amino acids; should be very high in arginine, glutamine and nucleotides, Omega-3 fatty acids but no Omega-6 fatty acids. Should be high in Taurine, high in trace elements and in vitamins, especially vitamin C, E (?) and
Slide 60. Should be clearly inexpensive, should be easy to be administered, should be tolerable by patients and preferentially should be given by mouth but however, should be able to be used enterally or parenterally.
Slide 61. Currently, the way we practice our nutritional support we try to give 25 kilocalories per kilogram per day or at least 80 percent of the requirements, 30 to 70 percent of them as glucose, which is approximately 2 to 5 grams per kilogram per day. We try to give at least 1.5 to 2 grams per kilogram of protein per day and often we use branch-chain amino acids. One should not hesitate to use high doses of vitamins, minerals and trace elements and reduce or restrict the calories from fat to 15 to 30 percent.
Slide 62. To conclude, nutrition support should really be considered as vital and one of the most important therapies that we give to patients. However, it should be considered as Dr. Stanley J. Dudrick said "A decision to initiate and to maintain adequate nutrition support via TPN should be based upon the achievement of the specific, definable and realistic goal for each patient and each condition. It should always be borne in mind that the ultimate aim of the technique is to prolong meaningful life and not merely to prolong an active process of individual death."