1. Program Information

2. Nutritional Support in the ICU
Sandra L Schoepfel MS RD RN CNSD
Karl D Pilson MD
Suresh Agarwal MD FACS
Boston Medical Center
Boston, MA
This is a course lecture that will discuss the delivery and obstacles faced with providing nutrition support in the ICU setting. Evidenced based literature reviewed explores the benefits of early enteral feedings, glycemic control in the ICU, the benefits of immunonutrition, consequences of malnutrition, enteral feeding formulations, and assessing the nutritional needs of the critically ill patient, including feeding guidelines for the morbidly obese population.

3. Rationale for Nutrition Support
Limit catabolism – hypercatabolic state is driven by the underlying disease process and is not reversed by nutrition alone
Offset muscle wasting and starvation induced immune depletion – loss of 1% per day lean body mass = 2% per day skeletal muscle
Substrate for healing and preserve immune function
Increase survival
Nutritional therapy in the ICU is at best “supportive” – cannot reverse hypermetabolism
We know that nutrition support is a vital component of medical care. There are several rationales favoring nutrition support. For one, it can limit catabolism. We know that nutritional support cannot prevent the catabolism associated with critical illness, but it can at least attenuate the process. It can offset muscle wasting and starvation along with preserving immune function and improving wound healing. Nutritional support doesn’t necessarily reverse the hypermetabolism effects of critically ill patients so we look to nutritional therapy as a supportive measure in this population.

4. Goals of Nutritional Support In The ICU
Early intervention (after resuscitation)
Ensure adequate enteral access
Support the metabolic response to injury and infection (bone marrow, acute phase proteins, wound healing)
Correct fluid, metabolic and acid/base abnormalities
Avoid overfeeding and hyperglycemia
? reduce ventilator dependency
When thinking about why we want to feed our patients in the ICU, we must concentrate on the goals of why we should feed these patients. Concentration should be placed on early intervention and early feedings once deemed medically feasible. Usually once adequate resuscitation efforts have been made and enteral access is available, begin feeding as soon as possible. Providing early nutrition can support the metabolic responses to injury and infection as well as helping to correct fluid, metabolic and acid / base abnormalities. Keep in mind that once feeding is initiated, the clinician should monitor the patient for hyperglycemia, metabolic abnormalities, and nutrient adequacy, wound healing and any clinical signs of improvement. It is always a goal to help reduce ICU length of stay, decrease infectious complications and aim to decrease ventilator days.

5. Achieving Nutritional Goals in the ICU is Difficult
1 year survey of ICU Nutritional Practice:
3526 record feeding days were evaluated
Desired intake was only achieved 52% of days
Ideal protein intake achieved in 54%
Ideal energy intake achieved in 66%
Ideal volume intake achieved in 75% of patients
Binnekade JM. Crit Care Jun;9(3):R216-25
Despite our best intentions to meet the goals of nutrition support in the ICU, we are often faced with ways to maximally achieve such goals. For example, this was a study that was used to evaluate the daily feeding practice of enterally fed patients in an intensive care unit and to study the impact of preset factors in reaching predefined optimal nutritional goals. The feeding practice of all ICU patients receiving enteral nutrition for at least 48 hours was recorded during a 1-year period. Actual intake was expressed as the percentage of the prescribed volume of formula and success was defined as 90% or more. Prescribed volume or optimal intake was guided by a protocol but adjusted to individual patient condition by the intensivist. The potential barriers to the success of feeding were assessed by multivariate analysis. Regarding the results, 403 eligible patients had a total of 3,526 records of feeding days. The desired intake was successful in 52% (1,842 of 3,526) of feeding days. The percentage of successful feeding days increased from 39% (124 of 316) on day 1 to 51% (112 of 218) on day 5. Average ideal protein intake was 54% energy intake was 66% and volume intake 75%. The conclusions of this study showed that the records revealed an unsatisfactory feeding process. A better use of relative successful volume intake, namely increasing the energy and protein density, could enhance the nutritional yield. Factors such as an improper use of tubes and feeding intolerance were related to failure. Meticulous recording of intake and interfering factors helps to uncover inadequacies in ICU feeding practice.

6. Baseline Patient Assessment
No “single” test can be used as a completely reliable indicator of nutritional status
Evaluation of weight loss and previous nutrient intake before admission
Level of disease severity
Presence of comorbid conditions
Function of the gastrointestinal tract
Evaluation of biochemical indices
Measurement of body mass index
The nutritional status of the critically ill at the time of presentation to the ICU is variable. Many patients who suffer from a burn or trauma injury generally have been well-nourished up to the injury. On the other hand, patients with liver, renal or other chronic disease who become critically ill often are previously malnourished. A thorough history that includes a review of previous medical condition, recent weight loss or gain, dietary habits, gastrointestinal tract function, and medication is essential for assessing nutritional status. The clinician should gather as much historical and clinical data as efficiently possible for the practice setting. In most settings, nutrition assessment follows a process of screening for nutritional risk. With that said, there is no single test that can be used as a completely reliable indicator of nutritional status, but collectively, multiple data parameters, as listed in this slide, can be clinically gathered and utilized.

7. Nutritional Assessment – A Difficult Task in the ICU
Medical, surgical and dietary history may be hard to obtain
Physical assessment may be confounded by volume resuscitation (surgery, burn, trauma, infection)
Problems with Nutritional Assessment in ICU Patients
Parameter Invalidation
Weight (BMI) Edema, fluids, diuretics
Anthropometrics Edema, observer variability
Albumin, Pre-Albumin Infection, inflammation, injury, renal failure
Nitrogen Balance Drainage tubes, wounds, renal failure
We know that there is an inextricable relationship between nutritional status and severity of disease. Alteration in metabolism and physiology caused by inflammatory mediators associated with severe illness and trauma accelerate loss of lean body mass, alter hepatic protein metabolism, increase energy expenditure, cause fluid compartment shifts, cause anorexia, and ultimately organ dysfunction and failure. All of these alterations mandate consideration in the provision of nutrition support, but may be difficult in obtaining when trying to nutritionally assess patients in an ICU setting. Here are some of the specific nutritional assessment parameters typically utilized when conducting a nutritional assessment. Their validity is in question however, because of edema, fluid shifts, hemodynamic instability, drainage tubes, wounds, renal or hepatic failure and severity of injury.

8. Factors That Increase Nutritional Risk
Involuntary loss or gain of > 10% of usual BW within 6 months or > 5% of usual BW in 1 month, or a weight of 20% over or under ideal BW
Presence of chronic disease
Increased metabolic requirements
Altered nutrient schedules (TF’s, PN) because of recent surgery, illness
Impaired ability to ingest or absorb food adequately for > 7 days
While conducting a nutritional assessment as a clinician you should be screening patients for malnutrition concurrently. The ability to identify risk factors associated with an increased risk for malnutrition sooner than later is paramount so that patients can begin early nutritional intervention sooner. A factor to closely monitor is the weight loss history of the patient. Has there been an involuntary loss or gain of weight that is >10% of their usual body weight within 6 months or >5% of usual body weight in 1 month or is a patient’s weight ~20% over or under their ideal body weight? Comparison of a patient’s current weight to their usual weight is generally more useful than comparing current weight to an “ideal” or desirable weight. It is also important to establish whether weight loss was intentional, related to an eating disorder, or unintended. In the ICU we know that body weight is affected by fluid shifts and accumulation caused by inflammation. In addition, resuscitation and diuretic therapy also conceal real changes in body weight. Clinicians must consider all the factors that can affect weight among hospitalized ICU patients to interpret changes in weight accurately. Other risk factors that would increase a patient’s nutritional risk would be to see if the patient had any impaired ability to ingest or absorb food that lasted longer than 1 week, if there were any indications for having increased metabolic requirements such as burns or multiple trauma, if the patient had to rely on alternate modes of nutrition such as TF’s or TPN and to assess the patient’s past medical and surgical history. Any of these factors could pose as a potential risk for developing malnutrition in a patient.

9. Malnutrition
Recent surveys suggest that 33-53% of hospitalized patients suffer from moderate to severe malnutrition
Souba W. N. Eng J Med 1997;336-41
Atalay BG. JPEN 2008 Jul-Aug;32(4):454
Delgado AF. Clinics 2008;63(3):357
Assume some degree of malnutrition exists or will develop in all patients
In the ICU: Malnutrition contributes to respiratory weakness, failure to wean from the ventilator, increased morbidity, mortality and hospital costs
In critically ill patients, malnutrition is associated with impaired immune function, impaired ventilatory drive, and weakened respiratory muscles, leading to prolonged ventilatory dependence and increased infectious morbidity and mortality. It has been estimated that between 33-53% of hospitalized patients suffer from moderate to severe malnutrition and as high as 40% in the intensive care unit. Malnutrition occurs when net nutrient intake is less than needed requirements resulting in a loss of body mass and depletion of blood components. Disease and nutrition interact so that disease in turn may cause secondary malnutrition or malnutrition may adversely influence the underlying disease. The assessment of nutritional status is of clinical importance which should be able to predict whether the individual would have increased morbidity and mortality in the absence of nutritional support.

10. Protein Markers in the ICU
Traditional protein markers (albumin, prealbumin, transferrin, retinol binding protein) and may also be a reflection of the acute phase response and do not accurately represent nutritional status
Improvement in hepatic protein levels indicate recovery, although not necessarily nutritional recovery
The serum transport proteins, albumin, transferrin, thyroxin-binding prealbumin, and retinol-binding protein, have been used to assess nutritional status, specifically protein nutrition. Despite considerable published information to the contrary, these protein have been assumed to reflect a reservoir of protein in conditions of adequate nutrition and a deficit of protein in condition of inadequate nutrition. However, there are not directly linked to nutrition deprivation and should not be relied on as indicators of nutritional status or recovery. In fact, inflammatory metabolism causes a 25% decrease in the synthesis of these four proteins, which is why they have recently been referred to as negative acute phase proteins. In addition to altering hepatic synthesis, inflammation causes capillary leak of serum proteins and with subsequent resuscitation intravascular concentrations are reduced. There is an important indirect relationship with these proteins and nutritional status – they indicate inflammatory metabolism, which contributes to lean body muscle, and also cause anorexia. Decreased albumin level correlate with poor clinical outcomes, increased length of stay, increased risk for complications, and death. Unfortunately, many past clinical studies that have correlated serum levels of negative acute phase proteins to malnutrition did not account for the contribution of inflammation and erroneously assumed that low serum protein levels are caused by malnutrition as opposed to inflammatory mediators.

11. Stimuli for Stress Response
Loss of blood volume
Emotion/pain/fear
Temperature
Infection
Tissue injury
There are many factors that are known to trigger the stress response such as pain, blood loss or tissue injury. This state is characterized by the release of several counter-regulatory hormones which in sum lead to a general reduction in lean body mass. Cortisol, released from the adrenal glands stimulates glycogenolysis and gluconeogenesis as well as muscle proteolysis. Cortisol also causes a generalized peripheral insulin resistance in skeletal muscle limiting glucose uptake and making more available for critical demands elsewhere. Catecholamines released from the adrenals induce hepatic glycogenolysis and gluconeogenesis and reduce the secretion of insulin from the pancreas. Although insulin levels are increased overall there is a lower insulin to glucose ratio which inhibits the normal anabolic effects of insulin reducing protein synthesis, glycogenesis and lipogenesis. The response to injury also causes the release of glucagon which increases gluconeogenesis, glycolysis and lipolysis. The release of arginine vasopressin increases glycogenolysis and gluconeogenesis as well as fluid retention through both sodium dependent and sodium independent mechanisms. The role of AVP in vasoconstriction is well established and is the basis for its use in the treatment of shock where endocrine failure is suspected. There is a release of amino acids from skeletal muscle after injury and as much as 70% of these are alanine and glutamine though these represent a much smaller amount of the amino acids in muscle tissue. These amino acids are utilized in gluconeogenesis by the muscle. Glucagon, cortisol and catecholamines all increase lipolysis which occurs despite an overall increase in plasma insulin levels. Glycogen stores are rapidly depleted in the stressed state and the primary fuels for gluconeogenesis are from fat and a lesser contribution from amino acids.

12. Goals of Stress Response
Maintain energy substrates (GLUCOSE)
Maintain oxygen delivery
Minimize further injury...
The overall goals of the stress response serve to supply glucose for cellular respiration but much of this occurs at the expense of muscle catabolism. Attempts to reverse this through support and pharmacologic means have failed universally and in the support of the critically injured patient, we attempt to limit the catabolic response.

13. The various endocrine responses to injury are illustrated here and are chiefly controlled by the hypothalamus. The pancreas releases glucagon and although the ratio of insulin to glucose is decreased the overall insulin level is not. The cardiac response is dramatic and is chiefly catecholamine driven. ADH and aldosterone serve to conserve volume and it should be noted that ADH may conserve volume through a sodium independent mechanism.
Greenfield 1997

14. Response to Stress/Injury
Neurohormonal - "Counterregulatory hormones"
Glucagon
Epinephrine
Glucocorticoids
Inflammatory mediators
IL-1, IL-2, IL-6
TNF-a
IFN-g
In addition to the neurohumoral counter regulatory hormones discussed above there are numerous inflammatory mediators involved in the stress response. Tumor necrosis factor (TNF), increases metabolic rate, produces fever and tachycardia. Interlukin-1 stimulates ACTH and induces its effect on gluconeogenesis. Interlukin-2 inhibits catecholamine induced lipolysis. Following injury, levels of interlukin-6 are elevated which induces the drastic increase in acute phase protein production in the liver including C-reactive protein. There are many other humoral mediators involved in the stress response and this remains an active area of investigation.

15. Metabolic Response During Sepsis – Carbohydrate Metabolism
Pro-inflammatory cytokines potentiate the release of catabolic hormones (glucagon, catecholamines, and cortisol) stimulating glycogenolysis and gluconeogenesis to mobilize glucose
Following the onset of sepsis, glycogen stores are depleted within hours, and endogenous lipid and protein become the major source of oxidative energy substrate
As sepsis progresses, reduced splanchic blood flow and severe hepatic dysfunction eventually lead to hypoglycemia and decreased glucose production
The next several slides will review the macronutrient metabolic responses during sepsis, the first being carbohydrate metabolism. With carbohydrate metabolism, pro-inflammatory cytokines potentiate the release of catabolic hormones, glucagon, catecholamines, and cortisol, stimulating glycogenolysis and gluconeogenesis to mobilize glucose. Following the onset of sepsis, glycogen stores are depleted within hours, and endogenous lipid and protein become the major source of oxidative energy substrate. As sepsis progresses, reduced splanchic blood flow and severe hepatic dysfunction eventually lead to hypoglycemia and decreased glucose production.

16. Metabolic Response During Sepsis Protein Metabolism
Amino acids released from skeletal muscle breakdown, connective tissue, and unstimulated gut are shunted to the liver, where they are used in gluconeogenesis and for the synthesis of acute-phase reactants
The ureagenesis rate is increased, as well as the synthesis rates of creatinine, uric acid, and ammonia – all get excreted in the urine
In an unfed, stressed patient, up to 250 g of lean body mass will be broken down each day
The nitrogen loss of severe sepsis complicating recovery from trauma may exceed 30g/d
Adequate nutrition support will not completely ablate the catabolic effects and response
With protein metabolism, amino acids released from skeletal muscle breakdown, connective tissue, and unstimulated gut are shunted to the liver, where they are used in gluconeogenesis and for the synthesis of acute-phase reactants. The ureagenesis rate is then increased, as well as the synthesis rates of creatinine, uric acid, and ammonia, all of which get excreted in the urine. If you have an unfed, stressed patient, up to 250 g of lean body mass will be broken down each day and the nitrogen loss of severe sepsis complicating recovery from trauma may exceed 30g/d. Providing adequate nutrition support will not completely ablate the catabolic effects and response

17. This slide illustrates the pituitary stimulation adrenal release of cortisol with the release of glutamine and alanine from skeletal muscle generating a circulating pool of these amino acids. The hepatic generation of glucose and acute phase reactants is shown as is the feedback loop with the leukotrienes stimulating ACTH secretion.
Greenfield 1997

18. Metabolic Response During Sepsis Lipid Metabolism
Lipolysis under catecholamine regulation
In early sepsis, catabolic hormones outweigh the effects of anabolic hormones such as insulin and result in the breakdown of stored triglycerides to glycerol and free fatty acids affecting intracellular transport metabolism
Sepsis impairs ketogenesis and the activity of lipoprotein lipase is suppressed
Hyperlipidemia, hyperglycemia, hyperlactatemia, and high levels of circulating β-hydroxybutyrate often are present in severe sepsis
With lipid metabolism, lipolysis occurs under catecholamine regulation and in early sepsis, catabolic hormones outweigh the effects of anabolic hormones such as insulin and result in the breakdown of stored triglycerides to glycerol and free fatty acids affecting intracellular transport metabolism. Sepsis impairs ketogenesis and the activity of lipoprotein lipase is suppressed while Hyperlipidemia, hyperglycemia, hyperlactatemia, and high levels of circulating β-hydroxybutyrate often are present in severe sepsis

19. Metabolic Needs - How Much?
Assessment of metabolic rate is an integral part of the nutrition care of the ICU patient
Validity of multiple equations in this population has not been systematically evaluated
Metabolic rate can be gauged by 3 methods:
Indirect calorimetry (“gold standard”)
Pulmonary artery catheter measurements using the Fick equation VO²=cardiac output X 10 (CaO²-CvO²) where VO² is oxygen consumption in mL/min, cardiac output is in L/min, CaO² is concentration of oxygen in arterial blood (mL/dL), and CvO² is concentration of oxygen in mixed venous blood (mL/dL)
Can be estimated using several predictive equations based on body size, degree of injury/illness, or degree of inflammatory response
Given the limitations on the availability of indirect calorimetery, predictive equations are the mainstay of energy expenditure assessment in the ICU
There are many methods of determining metabolic needs all of which have their limitations. Most centers use a predictive equation and add a stress factor though there is much inaccuracy with this method. Progressive improvement in a patient’s condition and the absence of metabolic problems such as hyperglycemia and hyperuricemia with adequate feeding is the ideal result. The gold standard for assessing the needs of the ICU patient remains indirect calorimetry, however given the limitation on the availability of this method, predictive equations are the mainstay of energy expenditure assessment in the ICU.

20. Ideal Body Weight (IBW) The Hamwi Method
Adult females
100 lb (45kg) for the first 60 inches (152 cm) + 5 lbs (2.3 kg) for every inch > 60
Ex: Ht. 5’4” (165.1 cm) = IBW of 120 lb or 54.5 kg)
Adult males
106 lb (48 kg) for the first 60 inches (152 cm) = 6 lbs (2.7 kg for every inch > 60
Ex: Ht. 5’10” (180.3 cm) = IBW of 166 lb or 75.4 kg)
When trying to determine whether a patient is overweight or underweight, the Hamwi method calculates an ideal body weight of an individual in the context of a normal population as illustrated on this slide. For both equations, a range of plus or minus 10% is recommended to adjust for large or small frame sizes. The ideal body weight is used to compare to usual body weight, percent ideal body weight, and percent usual body weight.

21. Evaluation of Body Weight Data
Body Mass Index (BMI) - a weight-stature index, is use both as a measure of obesity and malnutrition.
BMI = Weight (kg) ÷ Height² (m²)
Interpretation of BMI:
18.5 – 25 Normal weight
Overweight
Obesity grade I
Obesity II
≥40 Obesity grade III
Protein-energy malnutrition grade I
Protein-energy malnutrition grade II
<16 Protein-energy malnutrition grade III
Individual variation is large so patients should not be misclassified as undernourished or obese using BMI alone
Ideal body weight is typically used concurrently with body mass index (BMI) which is a weight-stature index used as a measure of obesity and malnutrition status. Although the correlation between BMI and total body fat is relatively strong, individual variation is large, and some patients can be misclassified as undernourished or obese using BMI alone. It is important to remember that an obese patient can be protein malnourished and a low BMI does not always indicate malnourishment. A comprehensive approach to nutrition assessment as a clinician is when BMI is best used in conjunction with a good patient history and a review of their general physiologic status.

22. Goal Calculations - Harris-Benedict Equation
Estimates Basal Energy Expenditure (BEE):
Male BEE = 66 + (13.7 x Wt) + (5 x Ht) - (6.8 x age)
Female BEE = (9.6 x Wt) + (1.8 x Ht) - (4.7 x age)
Weight (Wt) in kilograms; Height (Ht) in centimeters
BEE X Stress Factor (see below); this prediction method can overestimate or underestimate true resting metabolic rate and may be too unreliable for clinical use in the ICU
Conditions
Energy Requirement
~ Kcal/kg/day
~Protein gm/kg/day
Elective Surgery
x BEE
25-30
Multiple Trauma
x BEE
25-35
Sepsis/Peritonitis
1.5 x BEE
Massive Burns >50% TBSA
x BEE
35-40
In 1919, Harris and Benedict published their classic studies of metabolic rate. Indirect calorimetry was measured in 136 normal adult men and 103 normal adult women and from this data, caloric requirements were derived. Though the equation was first thought to estimate basal metabolic demands, it is now thought to estimate resting energy requirements. Although these equations remain among the most commonly employed calculation methods for determining resting metabolic rate, they do not represent the body weight and height, age or racial diversity of the current generations because the data were collected nearly a century ago. The Harris-Benedict equation often uses stress factors to determine additional energy requirements added to the resting metabolic rate. These can be compared to the common use of calories per kilogram which is commonly used to assess energy needs of patients. Additionally, common protein requirements based on injury, presence of wounds, stress response, sepsis and nutritional status etc are provided as a means to use when calculating calories per kg.

23. Goal Calculations – Ireton-Jones Equation 1992 vs 1997 Version
Developed for intubated patients
RMR=(W x 5) – (A x 10) + (S x 281) + (T x 292) + (B x 851) for total calorie prescription where:
A=age
W=wt in kg
S=sex (1=male, 0=female)
T=trauma (1=yes, 0=no)
B=burns (1= yes, 0 = no)
(This is the 1992 version)
The corrected 1997 version of this equation does not perform as well as the 1992 version and is not recommended for use
There is some feeling that the Harris-Benedict equation may overestimate caloric requirements resulting in overfeeding. The Ireton-Jones equation was developed as an alternate because it does not get so rapidly inflated in a caloric sense related to stress factors commonly used with the Harris-Benedict equation.

24. Goal Calculations – Critically Obese
Permissive underfeeding or hypocaloric feeding is recommended
CALORIES: When BMI is >30 provide kcal/kg ACTUAL body weight/day or kcal/kg ideal body weight per day
PROTEIN: When BMI is ≥ 30-40, provide ≥2.0 g/kg/ideal body weight per day and if BMI is ≥40, provide ≥2.5 g/kg ideal body weight per day
Choban PS. Nutr Clin Pract. 2005;20:
With the increasing incidence of morbid obesity and the evolution of bariatric surgery, more obese hospitalized patients are being seen. Severe obesity adversely affects patient care in the ICU and increases risk of comorbidities like insulin resistance, sepsis, infections, deep venous thrombosis, and organ failure. To reduce these potential complications, strategies of hypocaloric nutrition have been advocated for obese patients. Achieving some degree of weight loss may increase insulin sensitivity, improve nursing care, and reduce risk of comorbidities. Providing 60%-70% of caloric requirements promotes steady weight loss, while infusing protein at a dose of g/kg ideal body weigh per day should approximate protein requirements and neutral nitrogen balance, allowing for adequate wound healing. A retrospective study by Choban and Dickerson indicated that provision of protein at a dose of 2.0 g/kg ideal body weight per day is insufficient for achieving neutral nitrogen balance when the BMI is > 40. Use of BMI and ideal body weight is recommended over use of adjusted body weight.

25. Nitrogen Balance
Used to reflect the balance between exogenous nitrogen intake and renal removal of nitrogen-containing compounds through stool, urine, skin, fistulas, wounds, etc.
Measurement of nitrogen balance is most accurate in patient who receive a defined nutrient intake such as is in the case in those receiving enteral or parenteral nutrition
Urea nitrogen urine concentration increases dramatically in the sickest of patients reflecting catabolism of protein associated with systemic inflammation
Nitrogen balance can be estimated in patients by a 24 hour urine. It is used to reflect the balance between exogenous nitrogen intake and renal removal of nitrogen-containing compounds through stool, urine, skin, fistulas, wounds, etc. The measurement of nitrogen balance is most accurate in patient who receive a defined nutrient intake such as is in the case in those receiving enteral or parenteral nutrition. It is known that urea nitrogen urine concentration increases dramatically in the sickest of patients reflecting catabolism of protein associated with systemic inflammation.

26. It is important to take into account other potential sources of protein loss such as wound drainage or excessive stool losses. This is a diagram to depict the various total body stores of protein and sources of protein loss.
Greenfield 1997

27. Calculating Nitrogen Balance
There are several versions of the nitrogen balance calculation. The major differences are in estimation of the insensible losses of nitrogen which vary from 1.5 grams to 5 grams or more. Unfortunately this is difficult to calculate so settling on a standardized approach in an institution should be encouraged. The presence of thoracostomy tubes, naso-gastric tubes, drains and drainage on dressings can be a particular problem in establishing an accurate idea of a patient’s nitrogen balance. There is a gram of nitrogen for every 6.25 grams of protein on average so protein intake is divided by 6.25 to calculate nitrogen intake. Insensible losses are presumed to run between 3-4 grams daily. Ideally a positive nitrogen between 5-10 grams should be achieved.
UUN excretion may differ from 3 to 5 grams

28. Problems With UUN
UUN will be invalid if creatinine clearance is <50 mL/min
One cannot assume that moving nitrogen in a positive direction always means that protein catabolism has decreased, particularly in inflammatory (disease and trauma) conditions
Valid 24-hour urine collections are difficult to obtain
Alterations in renal function frequently occur in patient with inflammatory metabolism, making standard nitrogen balance calculations inaccurate
Urine urea nitrogen can be difficult to collect and is most reliably done with a Foley catheter in place. Renal insufficiency is common in patients who have critical illness which may make the urinary nitrogen excretion inaccurate. Additionally it should be noted that a positive nitrogen balance does not mean that the catabolic state has ended.

29. Metabolic Cart / Indirect Calorimetry
Measurement of O2 consumption (VO2) and CO2 production (VCO2) by a metabolic cart to allow for a Measured Resting Energy Expenditure (MREE) and Respiratory Quotient (RQ) (VCO2/VO2)
RQ or respiratory quotient interpretation
starvation/underfeeding
desired range/mixed fuel utilization
carbohydrate metabolism
1.0+ overfeeding / lipogenesis
The use of a metabolic cart to perform indirect calorimetry and establish a patient’s respiratory quotient is thought to be the gold standard in assessing the adequacy of caloric needs. RQ is defined as CO2 produced divided by O2 consumed. Carbohydrates produce 1 mole of CO2 for every mole of O2 consumed thus the RQ for their metabolism is The metabolism of fatty acids results in the generation of a glycerol moiety thus they generate the production of 0.71 moles of CO2 for each mole of O2 consumed giving an RQ of 0.71 for pure fatty acid metabolism. Protein metabolism results in an RQ of During the hypermetabolic state the RQ is usually between 0.8 and 0.85 compared to an RQ of in the state of starvation. Normal diets usually result in an RQ around 0.8 indicating a mixed fuel source.

30. Clinical Indications for Indirect Calorimetry
Factors causing predictive equations to be inaccurate (ARDS, large open wounds or burns, MSOF, sepsis, SIRS, ascites, multiple trauma, use of paralytic or barbiturate agents, and malnutrition with altered body composition like obesity or limb amputations)
When patients fail to respond to nutrition support based on predictive equations during their clinical course (poor wound healing, failure to wean from vent and protein malnutrition) despite “adequate” support
To evaluate whether under- or overfeeding is contributing to metabolic and respiratory derangements in ICU patients
Indirect calorimetry is useful in the evaluation of critically ill patients when there is a continuing decline in nutritional indicators or physical signs of worsening nutritional status despite presumably adequate caloric intake. Patients with large volume losses from drainage such as entero-cutaneous fistulas, patients having difficulty weaning from the vent, multiple trauma, thermal burns, and morbid obesity are a few candidates appropriate for indirect calorimetry.

31. Technical Factors Decreasing Indirect Calorimetry Accuracy
Mechanical ventilation with FIO² ≥ 60
Mechanical ventilation with Positive End Expiratory Pressure (PEEP) >12 cm H2O
Leak in the sampling system
Moisture in the system can affect the oxygen analyzer
Inability to collect all expired gases (leaking CT’s or broncho-pleural fistula)
Supplemental O2 in spontaneously breathing patient
Dialysis or continuous renal replacement therapy in progress
Errors in calibration of indirect calorimeter
Wooley JA. Nutr Clin Pract. 2003;18:
Indirect calorimetry only provides a snap shot of a patients caloric requirements and cannot be performed when PEEP is high or on patients whose FiO2 is greater than 60%. Anything that would limit the return of CO2 such as an air leak in a thoracostomy tube will limit the accuracy. Additionally when the calorimetrry is performed it is done for short periods and an average is calculated for many measurements with extreme outliers excluded from the calculation while the patient remains in a steady state. There tends to be significant variation in the calculations. Indirect calorimetry can be performed in non-intubated patients with the use of a hood but there is some inherent inaccuracy in this method.

32. Enteral vs. Parenteral?
Several studies have compared each mode of therapy
Traditionally it’s been said: “Enteral is BETTER” and “If the gut works, use it”
Earlier studies did not adjust for “overfeeding” and various rates of hyperglycemia increasing infectious complications
Earlier meta-analyses failed to show benefit of TPN over EN
PN use safer today with NST availability and tighter glucose control decreasing overall infectious complications
Bistrian BR. Crit Care Med 2006;34:
The enteral route of nutritional support is preferred but conclusive studies showing a clear advantage remain elusive. Moore et al. showed a clear reduction in septic complications including pulmonary infections with enteral feeding vs. parenteral. It is widely accepted that atrophy of the intestinal epithelium which occurs rapidly with cessation of enteral feeding may lead to translocation of bacterial products leading to cytokine release from Kupfer cells in the liver and a worsening of the inflammatory state. Following injury there is a reprioritization in the production of pre-albumin, albumin and transferrin by the liver toward production of acute phase proteins. With recovery this reverses. Moore et al. showed that with enteral feeding this process was blunted confirming a decrease in the septic response.

33. Enteral vs. Parenteral? Use the GI tract whenever possible
Contraindications to GI feeds
Bowel obstruction / prolonged ileus > 7 day
High output fistula > 500 mL/d
Bowel ischemia
Intractable vomiting or diarrhea
Severe GI bleeding
Conditions precluding feeding tube placement (i.e. esophageal tumor or tear)
Acute exacerbation of IBD with PO intolerance (malnutrition + bowel rest > 7 days)
Failure of high risk, hypermetabolic patient to tolerate TF trials
The enteral route of nutritional support is preferred but conclusive studies showing a clear advantage remain elusive. Moore et al. showed a clear reduction in septic complications including pulmonary infections with enteral feeding vs. parenteral. It is widely accepted that atrophy of the intestinal epithelium which occurs rapidly with cessation of enteral feeding may lead to translocation of bacterial products leading to cytokine release from Kupfer cells in the liver and a worsening of the inflammatory state. Following injury there is a reprioritization in the production of pre-albumin, albumin and transferrin by the liver toward production of acute phase proteins. With recovery this reverses. Moore et al. showed that with enteral feeding this process was blunted confirming a decrease in the septic response.

34. ICU Enternal Feeding Algorithm
This is an example of a nutrition support protocol used in our SICU. It is imperative to always use the gut when you can. The best determinants of gut function are clinical signs i.e. bowel movements, absence of distension, absence of tympany, hunger etc. Bowel sounds require an interface between fluid and gas in the bowel and may not be present in patients who are tube fed thus are an unreliable indicator of bowel function. Patients with high NGT output can often be fed with the use of a post-pyloric tube if there is no suspicion of obstruction. Post-pyloric feeding may also be useful in patients with pancreatitis if they are stable as this may result in less stimulation of the pancreas and fewer septic complications.

35. Nutrition Support Protocol For Mechanically Vented Patients
Developed by multidisciplinary team approach
Timing of enteral nutrition
Identify high risk patients
Identify malnourished patients
Progression to minimal enteral nutrition goals (80%)
Monitor gastric residuals
Use of prokinetic agents or surgically placed jejeunal tubes with gastric intolerance
Mackensiz SL. JPEN 2005;29(2):74-80
Despite increasing understanding of the mechanisms underlying peristalsis the development of a good prokinetic medication remains elusive. Dopamine is known to have inhibitory effects in the intestine and is present in large quantities. Metaclopramide acts by antagonizing the inhibitory effect of dopamine on the myenteric motor neurons. Primary motility in the gut is under the control of acetylcholine. Cholinesterase inhibitors such as neostigmine have dramatic effects on motility particularly in the colon. The cardiovascular side effects of these drugs limit their utility i.e. profound bradycardia. Motilin is a 22 amino acid peptide found in gastrointestinal M-cells as well as in some enterochromafin cells in the upper small bowel. The macrolide antibiotics such as erythromycin, clarithromycin and azithromycin are motilin analogs and are useful in IV or Po form.

36. Results of Nutrition Support Protocol in Mechanically Vented Patients
Percentage of patients receiving 80% of nutritional goals rose from 20% to 60% (p<0.001)
Goal achieved in just 5 days
TPN use declined from 13% to 1.6% (p<0.02)
Significant increase in delivered calories
No data on the effect on outcome
Mackensiz SL. JPEN 2005;29(2):74-80
Many institutions including ours have found that the development of a multidisciplinary team approach to nutritional support have been able to drastically reduce the number of patients achieving their nutritional goals in a timely fashion. The drastic reduction on patients requiring parenteral nutrition results in fewer septic complications from central catheter infections and an overall reduction in costs. The current emphasis on hospital reimbursement based on outcomes and the avoidance of preventable complications necessitate this approach to nutritional support.

37. Early Nutritional Support in the Mechanically Vented Patient
4,049 ventilated (>2 days) patients were studied
2,537 (63%) labeled “Early Feeding” (<48 hours)
1,512 (37%) labeled “Late Feeding Group”
Patients with contraindication to enteral diet were excluded
Control for disease severity using separate models with:
APACHE II, SAPS II, MPM-0
Retrospective multi-institutional study
Artinian V, et al; Chest 2006;129(4):
The study discussed by Artinian et al evaluated the effect of early enteral feeding, within 2 days vs. late feeding in 4,049 ventilated hospital patients.

38. Effect of Early Feeding in Ventilated Patients
Outcomes
Early
Late Feeding
p Value
ICU Mortality
18.10%
21.40%
0.01
Hospital Mortality
28.70%
33.90%
0.001
ICU Length of Stay
10.9 ± 8.1
10.2± 7.7 NS
Survival (vented over 30 days)
~58%
~52%
The size of this study is impressive and the investigators were able to show a significant reduction in ICU mortality, 18.1% vs. 21.4% as well as overall hospital mortality 28.7% vs. 33.5% with P values of 0.01 and respectively.
Three separate models were used, APACHE II, SAPS II and Chronic Health Evaluation II. In all models early enteral feeding was associated with an approximately 20% reduction in ICU mortality and a 25% decrease in overall hospital mortality.
Artinian V, et al; Chest 2006;129(4):

39. Timing of Enteral Feeds
Many studies claim benefits to early EN
Meta-analysis that looked at 27 randomized, prospective studies
Early EN had lower infections (RR 0.45)
Early EN had shorter LOS (2.2 days)
Marik PE, Zaloga GP. Crit Care Med. 2001;29:
One of the seminal papers on early nutritional support was written by Marik and Zaloga. In this meta-analysis 27 randomized prospective studies were looked at. Early enteral nutrition again was shown to lead to lower rates of infection and shorter lengths of stay.

40. How Nutrition Support Goals Have Shifted in the ICU
Goals have become more focused on “nutrition therapy”
Attempt to attenuate the metabolic response to stress
Prevent oxidative cellular injury
Modulate the immune response
Aim for early enteral nutrition, appropriate macronutrient and micronutrient delivery and meticulous glycemic control
The goals of nutritional support have evolved somewhat. Reversing the catabolic response to injury remains a significant goal in critical care. Nutritional support alone is unlikely to achieve this and in fact it may not be achievable or perhaps even desirable. Support should focus providing available substrate and minimizing catabolism in the injured patient. In the last ten years there has been increasing emphasis on the use of anti-oxidants and immune modulators in nutritional support.

41. Where to start?! Determine number of calories needed
Use predetermined “feeding weight” whether actual, ideal, adjusted or usual body weight first
Utilize predictive equations, indirect calorimetry
Determine normal or increased protein needs
Severity of injury, presence of wounds, fistulas, burns
Determine if contraindication to fats
Sepsis, hemodynamic instability, hypertriglyceridemia
Determine fluid needs
Determine mode of nutrition => use the GI tract whenever feasible
Protein needs in the critically ill vary widely and it is extremely important to take into account the type of injury. The needs of a burn patient are very different from those of a patient with a community acquired pneumonia. In parenteral nutrition there is a changing opinion on the use of fats. Fats have been shown to be immunosuppressive and some have recommended administering only essential fatty acids. The use of Omega-3 fatty acids in an intravenous form is thought to be immunostimulatory, unfortunately they are not yet available in the United States.

42. ICU Nutrition Guidelines
Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition: Executive Summary
Robert G. Martindale, MD, PhD; Stephen A. McClave, MD; Vincent W. Vanek, MD; Mary McCarthy, RN, PhD;Pamela Roberts, MD; Beth Taylor, RD; Juan B. Ochoa, MD; Lena Napolitano, MD; GailCresci, RD; American College of Critical Care Medicine; and the A.S.P.E.N. Board of Directors
Crit Care Med 2009;37(5):
JPEN 2009;33(3):
Guidelines developed that provided recommendations supported by review and analysis of the pertinent available current literature up to May 2008, by other national and international guidelines, and by the blend of expert opinion and clinical practicality. A grading system was used to help determine the level of evidence to support these recommendations.
These guidelines were developed to offer basic recommendations that are supported by review and analysis of the pertinent available current literature, by other national and international guidelines, and by the blend of expert opinion and clinical practicality. Whenever possible, these factors were taken into account and the grade of statement reflects the power of the data. It was emphasized that these practice guideline were not intended to be used as absolute requirements and that the use of these practice guidelines did not in any way project or guarantee any specific benefit towards outcome or survival.

43. Grading System Used for the Guidelines
Grade of recommendation
A. Supported by at least two level I investigations
B. Supported by one level I investigation
C. Supported by level II investigations only
D. Supported by at least two level III investigations
E. Supported by level IV or level V evidence
Level of evidence
Large, randomized trials with clear-cut results; low risk of false-positive (alpha) error or false-negative (beta) error
Small, randomized trials with uncertain results; moderate to high risk of false-positive (alpha) and/or false-negative (beta) error
A list of guideline recommendations was compiled by the experts on the guidelines committee for the 2 societies (SCCM and ASPEN), each of which represented clinically applicable definitive statements of care or specific action statements. A grading system was then used to help determine the level of evidence to support these recommendations. Significant controversies in interpretation of the literature were resolved by consensus of opinion of the committee members, which in some cases let to a downgrade of the recommendation.

44. Grading System Used for the Guidelines
Nonrandomized, contemporaneous controls
Nonrandomized, historical controls
Case series, uncontrolled studies, and expert opinion
Large studies warranting level I evidence were defined as those with 100 patients or those which fulfilled end
point criteria predetermined by power analysis. Meta-analyses were used to organize information and to draw
conclusions about overall treatment effect from multiple studies on a particular subject. The grade of
recommendation, however, was based on the level of evidence of the individual studies.
Dellinger RP. Crit Care Med. 2004;32(11)(suppl):S446
A list of guideline recommendations was compiled by the experts on the guidelines committee for the 2 societies (SCCM and ASPEN), each of which represented clinically applicable definitive statements of care or specific action statements. A grading system was then used to help determine the level of evidence to support these recommendations. Significant controversies in interpretation of the literature were resolved by consensus of opinion of the committee members, which in some cases let to a downgrade of the recommendation.

45. “Guidelines”: Enteral Feeding
Enteral Nutrition (EN) is the preferred route of feeding over parenteral nutrition (PN) (Grade B)
EN should be started early within the first hours following admission (Grade C) and feedings should be advanced toward goal over the next hours (Grade E)
EN should be withheld until the patient is fully resuscitated and/or hemodynamically stable (Grade E)
Neither presence nor absence of bowel sounds, flatus, and stool is required for the initiation of EN (Grade B)
Either gastric or small bowel feeding is acceptable (Grade C)
The next several slides outline some of the highlights in regards to enteral and parenteral nutrition. The strongest guidelines for enteral nutrition revealed that enteral nutrition was the preferred route of feeding over parenteral nutrition and that in the ICU population, neither the presence nor absence of bowel sounds nor evidence of passage of flatus and stool is required for the initiation of enteral feeding.

46. “Guidelines”: When to Use Parenteral Nutrition
If early EN is not feasible or available over the first 7 days following admission to the ICU, no nutrition support (standard therapy) should be provided (Grade C)
If there is evidence of protein-calorie malnutrition at admission and EN is not feasible, it is appropriate to initiate PN as soon as possible following admission and adequate resuscitation (Grade C)
If a patient is expected to undergo major upper GI surgery and EN is not feasible, provide PN when:
Patient is malnourished. Initiate PN 5-7 days preoperatively and continue into the postoperative period (Grade B)
The duration of therapy is anticipated to be ≥ 7 days (Grade B)
The most controversial of the parenteral nutrition guidelines were these 2 guidelines – “If early EN is not feasible or available over the first 7 days following admission to the ICU, no nutrition support (standard therapy) should be provided”. The second of these is “In the patient who was previously healthy prior to critical illness with no evidence of protein-calorie malnutrition, use of PN should be reserved and initiated only after the first 7 days of hospitalization when enteral nutrition is not available”. Although the literature cited recommends withholding PN for days, the guidelines committee expressed concern that continuing to provide standard therapy, which was no nutrition support therapy, beyond 7 days would lead to deterioration of nutrition status and adverse effect on clinical outcome

47. “Guidelines”: Dosing of Enteral Feeding
The target goal of EN (defined by energy requirements) should be determined and clearly identified at the time of initiation of nutrition support therapy (Grade C)
Efforts to provide > 50%-65% of goal calories should be made to achieve the clinical benefit of EN over the first week of hospitalization (Grade C)
Initiating supplemental PN before 7-10 days when unable to meet energy requirements with EN alone does not improve outcome and may be detrimental to the patient (Grade C)
In patients with BMI <30, protein requirements should be in the range of g/kg/d actual body weight (Grade E)
Critically ill obese patients with BMI >30, give kcal/kg actual body weight/day or kcal/kg IBW/d. Protein should be provided in a range of ≥2.0 g/kg IBW/d for BMI and ≥2.5 g/kg IBW/d for BMI ≥40 (Grade D)
When discussing guidelines for the dosing of enteral feeding the target goal of EN (defined by energy requirements) should be determined and clearly identified at the time of initiation of nutrition support therapy. Efforts to provide > 50%-65% of goal calories should be made to achieve the clinical benefit of EN over the first week of hospitalization Initiating supplemental PN before 7-10 days when unable to meet energy requirements with EN alone does not improve outcome and may be detrimental to the patient. These guidelines were all classified as a grade C.

48. “Guidelines”: Selection of Appropriate Enteral Formula
Immune-modulating formulations containing arginine, glutamine, nucleic acid, omega-3 fatty acids and antioxidants should be used for major elective surgery, trauma, burns, head and neck cancer, and critically ill patients on vents. Be cautious with severe sepsis for SICU patients (Grade A) and MICU patients (Grade B).
Patients with ARDS and severe acute lung injury should receive a formula containing an anti-inflammatory lipid profile containing omega-3 fish oils, borage oil and antioxidants (Grade A)
The strongest of guidelines came along the lines of immunonutrition where immune-modulating formulations containing arginine, glutamine, nucleic acid, omega-3 fatty acids and antioxidants should be used for major elective surgery, trauma, burns, head and neck cancer, and critically ill patients on vents. Caution was advised with severe sepsis for SICU patients receiving a grade A and MICU patients that got a grade B. It was also recommended that patients with ARDS and severe acute lung injury should receive a formula containing an anti-inflammatory lipid profile containing omega-3 fish oils, borage oil and antioxidants. This recommendation received a grade A.

49. What is Immunonutrition (IMN)?
The term given to describe special enteral feeds containing:
Arginine
Omega-3 fatty acids
Nucleotides
+ / - Glutamine
Antioxidants
The concept that certain nutrients become conditionally essential during times of stress and that other nutrients such as Omega-6 fatty acids may enhance the inflammatory response in a negative way has led to the concept of immunonutrition.

50. Organs of the Immune System
The GI tract is an organ with significant immune function. Peyer’s patches are important in immune surveillance in the lumen of the GI tract. They are composed of B-cells in germinal centers and T-cells in zones between the follicles and are covered by M cells which sample antigen directly and deliver it to antigen presenting cells thereby stimulating B-cells and memory cells. These cells then pass to mesenteric lymph nodes where the immune response becomes amplified.

51. Immunonutrition
Glutamine – Most abundant AA in plasma and skeletal muscle; non-essential, but may be conditionally essential during catabolic stress. Has shown to be of benefit in burn, and trauma patients, but evidence is lacking in other critically ill patients.
Arginine – conditionally essential amino acid thought to enhance the depressed immune responses associated with trauma, sepsis, or malnutrition.
Nucleotides – precursor of DNA and RNA that are necessary for most cell functions, including protein synthesis. Demands during catabolic stress may exceed production.
Omega-3 FA’s – “fish oil” with beneficial effects in septic patients, including modulating of leukocyte function and regulation of cytokine release through nuclear signaling and gene expression. The enhance the production of prostaglandin derivatives which play a role in accelerating the resolution of the pro-inflammatory state. IV omega-3 fatty acids are currently unavailable in parenteral emulsions in the United States.
Antioxidants – thought to be of some benefit in severely stressed and septic patients, but exact amounts and combinations have yet to be determined for this population
Immune enhancing diets are increasingly popular. Glutamine production is increased in stress and intracellular concentrations decrease. Glutamine is an important substrate for various immune cells and is the primary fuel for the enterocyte. Arginine acts as a promoter for proliferating T-cells after stimulation by mitogens or cytokines in vitro. Arginine increases natural killer cell cytotoxicity, specific cytolytic T-cell activity and macrophage tumor cytotoxicity. Arginine has a positive effect on wound healing, stimulates growth hormone release and is a precursor for nitric oxide production. Omega-3 fatty acids can be used as an energy source and can replace Omega-6 fatty acids which are known to inhibit natural killer cell activity. Numerous studies have shown that supplementation with these nutrients has led to a reduction in wound infections, decreased lengths of stay, reduction in infections overall, improved glucose tolerance and a decreased incidence of multiple organ failure. Animal studies have shown that supplementation with RNA improves survival. Nucleotide deprivation suppresses T-cell function and reduces IL-2 production.

52. What Is An Appropriate Gastric Residual Volume (GRV)?
Threshold level of GRV tolerated by clinicians is of great debate!
No clinical significance of GRV < 200 ml
Stomach is a “distensible container” in which GRV measurements don’t account for
Aspiration of TF’s is associated with a low morbidity and an even lower mortality risk
Patients with high GRV >400 ml or who demonstrate GI intolerance => consider NJT
Gastric residual volumes are of limited utility and often do not reflect gastric emptying and overall GI tract function. Several studies have shown no significance to residuals greater than 400cc’s. Despite this data many clinicians remain uncomfortable feeding when there are significant gastric residuals. If there is no evidence of obstruction a nasoenteric feeding tube is a good strategy.

53. EN Associated Bowel Necrosis
Considered a very RARE complication < 1%
Most often reported with SB feeds
Exact cause is unclear - ? related to  mucosal perfusion, underlying bowel injury, excessive vasoconstriction or bacterial toxins
No prospective randomized studies for TF’s w/ hypotension
Intestinal ischemia is a dreaded complication of enteral nutritional support. When the GI tract is fed mesenteric blood flow may increase by a factor of ten. If there are stenotic areas due to atherosclerotic disease or vasoconstriction from the use of vasopressors demand may exceed supply in these vessels. This is hypothesized to account for cases of bowel ischemia. Post-prandial abdominal pain and weight loss in a patient at risk for atherosclerosis should raise a clinician’s suspicion for chronic mesenteric ischemia.

54. Hemodynamic Instability
High risk guidelines for a hypoperfused GI tract:
FiO2 >60
PEEP >5
Mean Arterial Pressure ≤ 75 mmHg
? high dose pressors
Levophed >8 mcg/min
Neosynephrine >40 mcg/min
Dopamine >15 mcg/kg/min
There is significant controversy surrounding the incidence of GI ischemia in patients without underlying vascular disease but there are case reports in patients on high dose vasopressors. It may be prudent to decrease or even discontinue enteral feeding in patients on significant doses of these medications or in patients with a significant lactic acidosis. Many patients in these clinical situations have limited GI function and are often not candidates for enteral nutrition.

55. Recommendations For Feeding The Hypotensive Patient
Hold feeds in hypotension:
Initiating pressor therapy
Increasing dose of pressors
Adding a second or third agent
Lactic acidosis
OK to feed in hypotension on pressors:
Stable (24-48 hrs) or  ing doses
MAP ≥75 mm/hg
Avoid fiber; stomach may be better than SB
Hold feeds (on pressors) for any sign of intolerance:
NG output increases
New abdominal pain
Abdominal distention
Cessation of flatus, stool
These are some standard clinical situations where enteral feedings may need to be reduced or discontinued. It should again be noted that there are no absolutes here and there is no substitution for good clinical judgment and an abdominal examination.

56. Refeeding Syndrome
Metabolic response caused by either enteral or parenteral nutrition
Shift from stored body fat to CHO as primary fuel after prolonged NPO status
Feeding causes insulin levels to rise creating intracellular movement of electrolytes
Mg, K, PO4 levels may fall; can lead to arrhythmias, respiratory and cardiac failure, and death
Prevention and therapy:
Correct electrolyte abnormalities BEFORE initiating nutrition support, avoid overfeeding, and provide appropriate vitamin supplementation
The rapid induction of the anabolic state in severely malnourished patients may have dire consequences and is known as the refeeding syndrome. Generation of ATP can lead to rapid decreases in the intracellular ions magnesium, phosphorus and potassium. If the patient is not ventilated profound respiratory muscle weakness can occur in addition to cardiac failure. When patients at risk for this nutrition should be started slowly and concentrations of these ions should be checked frequently.

57. Basic Parenteral Nutrition Calculations
Amino Acids 4 kcal / g
Dextrose kcal / g
Fat kcals / g
10% Lipids kcal / mL
20% Lipids 2 kcal / mL
30% Lipids 3 kcal / mL
These are the basic parenteral nutrition calculations needed to calculate macronutrient grams and determine ultimate total calories.

58. Basic Parenteral Nutrition Calculations
Amino Acids 4%
Dextrose 15%
Lipids 2%
Total Volume mL
Grams AA = 4 grams X 2000 mL = 80 g X 4 kcal/g = 320 kcal
100 mL
Grams CHO = 15 grams X 2000 mL = 300 g X 3.4 kcal/g = 1020 kcal
Grams Lipid = 2 grams X 2000 mL = 40 g X 10 kcal/g = 400 kcal
TOTAL CALORIES = 1740
This slide depicts an example of determining the amount of grams and calories from a TPN solution. Some institutions use percents as their final macronutrient solution, but the use of grams is desired and recommended as a standard by ASPEN. To convert to percent you would take the number of grams and divide by the total volume. In this example, 80 grams protein divided by 2000 is 4%, 300 grams carbohydrate divided by 2000 is 15% and 40 grams lipid divided by 2000 is 2%. The final solution would read 2000 mL D15%/ 4% amino acids and 2% lipid.

59. Parenteral Nutrition Formulation Additives
Vitamins
Folate, Thiamine, Vitamin C, Zinc, Vitamin B12
Trace Elements
Chromium, Copper, Zinc, Manganese, Selenium, Iron
Electrolytes
Usually in the form of NaCl, NaAc, NaPO4, KCL, KAc, KPO4, MgSO4, CaGluc
Miscellaneous
H2 blockers, Heparin, Insulin, Glutamine
This is a list of additional additives that are compatible with TPN which are often added on a daily basis. Additional additives desired to be added to the TPN bag must be cleared by pharmacy to ensure it meets compatibility requirements. This holds true with hanging TPN - nothing should piggyback the TPN bag or tubing except for IV intralipids.

60. When Initiating PN Therapy
CHO* - Start conservatively with grams of dextrose per day advancing only when electrolytes and blood sugars are stable and repleted.
Protein* - Amino acids should be limited initially to gm/kg feeding weight due to their potential “refeeding effects“.
Lipids** – Limit to ~1 gm/kg/d. Soy-based lipids have been shown to be immunosuppressive with proinflammatory characteristics so may have some benefit to withhold lipids or use with caution for the first 7 days in the ICU. Keep in mind that Propofol, is lipid based, and provides 1.1 kcal/mL.
*Patients should be monitored closely for refeeding syndrome for the first week of PN therapy.
**Essential Fatty Acid Deficiency (EFAD) may develop when no source of fatty acid is supplied for > 14 days. Minimum lipid requirements to prevent EFAD is 500 mL of a 20% fat emulsion (100 grams) over 24 hours given once a week
When initiating PN therapy start conservatively with grams of dextrose per day advancing only when electrolytes and blood sugars are stable and repleted. Amino acids should be limited initially to gm/kg feeding weight due to their potential “refeeding effects“ and lipids should be limited to ~1 gm/kg/d. Keep in mind that Propofol, is lipid based, and provides 1.1 kcal/mL and should be considered when assessing lipid intake. Lipids have also been shown to be immunosuppressive with proinflammatory characteristics so there may be some benefit to withholding lipids or to use with caution for the first 7 days in the ICU. Always monitor patients for refeeding syndrome especially if they are malnourished or have been NPO for an extended period of time prior to feeding.

61. Overfeeding Consequences - 1
Azotemia – Patients >65 years and patients given >2 gm/kg protein are at risk.
Fat-overload syndrome – Recommended maximum is 1 gm lipid/kg/d. Infuse IV lipid slowly over 24 hours.
Hepatic steatosis – Patients receiving chronic high-carbohydrate, very low fat TPN are at risk.
Hypercapnia – Makes weaning difficult.
Hyperglycemia – Increases risk of infection. Intake should not exceed 5 mg CHO/kg/min (4 mg/kg/min for diabetics).
A mention of the consequences to overfeeding are worthy of mentioning because “more is not always better”. These are potential causes of overfeeding whether it’s with utilizing enteral or parenteral nutrition. Probably the most common consequence is hyperglycemia which greatly increases the risk of infection.

62. Overfeeding Consequences - 2
Hypertonic dehydration – Can be caused by high-protein formula with inadequate fluid provision.
Hypertriglyceridemia – Propofol, high TPN lipid loads, and sepsis increase the risk. If the patient is hypertriglyceridemic, decrease lipid to an amount to prevent EFAD and monitor.
Hypertriglyceridemia is another common consequence to overfeeding especially with the frequency of the use of Propofol in the ICU setting. Monitoring frequent triglycerides is recommended. Also to prevent essential fatty acid deficiency (EFAD), typically grams of lipid is recommended per week.

63. Consequences of Overfeeding-3
Metabolic acidosis – Patients receiving low ratios of energy to nitrogen are at risk. Acidosis can cause muscle catabolism and negative nitrogen balance.
Refeeding syndrome – Common in malnourished patients or those held NPO prior to initiation of feeding. Start feedings conservatively, advance gradually, and monitor Mg, Ph, and K closely.
Refeeding syndrome, as previously explained, is a serious condition therefore, patients need to be monitored closely to prevent this syndrome from occurring especially within the first week of nutritional therapy.

64. Intensive Insulin Therapy in the Critically Ill
PRCT, SICU ventilated pts (n=1548)
Intensive insulin therapy (BG mg/dl) versus SSI (BG>215 mg/dl)
Results
  5 day ICU stay (10 vs 20%)
 Hospital mortality x 34%
 Blood infections x 46%
 ARF requiring therapy x 41%
Van den Berghe G, et al. N. Engl J Med 001;345:
Intensive insulin therapy has become an area of controversy in the last several years. In 2001 Van den Bergh et al. published a study of 1548 patients comparing standard vs. intensive insulin therapy where blood glucose levels were maintained between 80 and 110 while in the ICU and between 180 and 200 after discharge from the ICU. This was compared to treating levels of greater than 215 with a sliding scale.

65. Intensive Glycemic Control and Survival in SICU Patients
100 96 92 88 84 80
Intensive treatment
Conventional treatment
Survival in ICU (%)
In-Hospital Survival (%)
A Days After Admission
B Days After Admission
42.5% reduction in mortality with intensive treatment; P<.04
34% reduction in mortality with intensive treatment; P<.01
ONLY REACHED SIGNIFICANCE for patients in the SICU for
5 days or longer
This study showed improved survival, shorter ICU stays, fewer infections and a decreased incidence of acute renal failure.
Van den Berghe G et al. N Engl J Med. 2001;345:

66. Not so NICE (study) to follow
Hypothesis: There is no difference in the relative risk of death between patient assigned a glucose range of 4.5 – 6.0 mmol/L ( mg/dl) and those assigned a glucose range of 10.0 mmol/L, or less (180 mg/dl, or less). The primary end point would be defined as death from any cause within 90 days after randomization.
International multi-center
6104 ICU patients were randomized
Conventional insulin group (n = 3054 assigned => 3010 after 90 days)
Maintain mg/dL
Intensive insulin group (n = 3050 assigned => 3012 after 90 days)
Maintain < 180 mg/dL
The NICE-SUGAR Study Investigators. N Engl J Med 2009;360:
The NICE-SUGAR trial is a more recent study from This study was a randomized controlled trial of 6104 patients half of whom had a blood glucose target of between 81 and 108 and the other half a target of 180 or less.

67. NICE-SUGAR RESULTS No difference Severe hypoglycemia 90-day mortality
The NICE study showed no difference in ICU length of stay, hospital length of stay, days on the ventilator or need for renal replacement therapy. There was a significant incidence of severe hypoglycemia in the intensive therapy group combined with an increase in mortality of 27.5% vs 24.9% in the conventionally treated group.
No difference
ICU LOS
Hospital LOS
Ventilator days
Renal replacement therapy
Severe hypoglycemia
Conventional insulin group 0.5%
Intensive insulin group 6.8%
90-day mortality
 in conventional insulin group

68. Insulin Study Discrepancies
Van den Berghe
Majority PN
Did not account exact amount of EN
Majority CV surgery
NICE-SUGAR
> 70% nutrition received from EN
Larger sample size
Mixed medical / surgical
This is just a brief overview of the studies discrepancies and their pitfalls.

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70. Nutrition

71. References
Pasquel FJ, Spiegelman R, McCauley M, et al. Hyperglycemia during total parenteral nutrition: An important marker of poor outcome and mortality in hospitalized patients. Diabetes Care. 2010;33:
McClave SA, Martindale RG, Vanek VW, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient:: Society of Critical Care Medicine (SCCM) and American society for Parenteral and Enteral Nutrition (ASPEN). JPEN. 2009;33:
The NICE-SUGAR Study Investigators. N. Engl J Med. 2009;360:
Sungurtekin H, Sungurtekin U, Oner O, Okke D. Nutrition assessment in critically ill patients. Nutr Clin Pract. 2008;23:

72. References
Atalay BG, Yagmur C, Nursal TZ, et al. Use of subjective global assessment and clinical outcomes in critically ill geriatric patients receiving nutrition support. JPEN. 2008;32:
Delgado AF, Okay TS, Leone C, et al. Hospital malnutrition and inflammatory response in critically ill children and adolescents admitted to a tertiary intensive care unit. Clinics. 2008;63(3)
Bistrian BR, McCowen KC. Nutritional and metabolic support in the adult intensive care unit: Key controversies. Crit Care Med. 2006;34:
Artinian V, Krayem H, DiGiovine B. Effects of early enteral feeding on the outcome of critically ill mechanically ventilated medical patients. Chest. 2006;129:

73. References
Pontes-Arruda A, Aragao AM, Albuquerque JD. Effects of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock. Crit Care Med. 2006;34:
Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006;354:
Binnekade JM, Tepaske R, Bruynzeel P, et al. Daily enteral feeding practice on the ICU: attainment of goal and interfering factors. Crit Care. 2005;9:R218-R225.
Mackenzie SL, Zygun DA, Whitmore BL, et al. Implementation of a nutrition support protocol increases the proportion of mechanically ventilated patients reaching enteral nutrition targets in the adult intensive care unit. JPEN. 2005;29:74-80.

74. References
Kieft H, Roos A, Bindels A, et al. Clinical outcome of an immune enhancing diet in a heterogeneous intensive care population. Intensive Care Med. 2005;31:
McClave SA, et al. Poor validity of residual volumes as a marker for risk of aspiration in critically ill patients. Crit Care Med. 2005;33;
Choban PS, Dickerson RN. Morbid obesity and nutrition support: is bigger different? Nutr Clin Pract. 2005;20:
Dellinger RP, Carlet JM, Masur H, et al; Surviving Sepsis Campaign Management Guideline Committee. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32:

75. References
McClave SA, Chank WK. Feeding the hypotensive patient: does enteral feeding precipitate or protect against ischemic bowel? Nutr Clin Pract. 2003;18:
Montejo JC, Zarazaga A , Lopez-Martinez J, et al. Immunonutrition in the intensive care unit: a systematic review and consensus statement. Clin Nutr. 2003;22:
Wooley, JA, Sax HC. Indirect Calorimetry; Applications to Practice. Nutr Clin Pract. 2003;18:

76. References
Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patient. New Engl J Med. 2001;345:
Marik PE, Zaloga GP. Early enteral nutrition in acutely ill patients: a systematic review. Crit Care Med. 2001;29:
Souba WW, Austen WG. Nutrition and metabolism. In: Greenfield LJ, Mulholland MW, Oldham KT, et al. Surgery: Scientific Principles and Practice. 2nd ed. New York, NY: Lippincott-Raven; 1997.
Souba WW. Nutritional Support. N. Engl J Med. 1997;336:41-48.