Summary

for people ages 18 years and up (full criteria)
healthy people welcome
at Fresno, California
study started
estimated completion:
Amir Fathi

Description

Summary

Malnutrition is a serious problem in patients undergoing major surgeries and has a direct association with increased morbidity, mortality, length of stay (LOS), increased readmissions and cost of care. Studies suggest several advantages of supplementation with protein or specific amino acids in malnourished patients. Dietary leucine or its metabolite β-hydroxy β-methylbutyrate (HMB) can improve skeletal muscle mass and function by increasing transcriptional level of protein synthase, while other high protein or amino acids like Glutamine or Arginine supplements only provide protein-amino acids pool for patients while body`s preferred fuel during metabolic stress is endogens protein, rather than exogenous diet. In this study the investigators seek to achieve two distinct goals: 1. Determine the patients' nutritional status before and after major surgeries by baseline and subsequent nutritional assessments, according to ASPEN's criteria. In addition, the investigators were going to use indirect calorimetry to determine the Resting Energy Expenditure (REE) in different phases of pre- and postoperative periods. The investigators also propose to compare different serum protein markers and their ratios in order to correlate them with ASPEN's criteria for nutritional status quantification. In Summary, three discrete tools including ASPEN's criteria, indirect calorimetry, and serum biomarkers are going to be used in conjunction with each other to delineate the patients' nutritional status in various pre- and post-operative periods. 2. Patients undergoing major surgeries were supplemented with high protein with ß-hydroxy ß-methylbutyrate (HMB) (Ensure, Envile) or HMB only as a control, in order to improve their nutritional status and improve postoperative outcomes. The investigators looked for depict meaningful improvements in surgical outcomes by nutritional supplementation with or without HMB.

Official Title

Effects of Nutritional Preconditioning on the Nutritional Status of Patients Undergoing Major General Surgeries and Subsequent Operative Outcomes

Details

Background and Significance:

The concept of malnutrition and its' effects on the outcomes of surgical patients was first reported in 1936. A study revealed that malnourished patients going through ulcer surgery had a 33 percent mortality rate when compared with 3.5 percent in well-nourished individuals. According to the American Society of Parenteral and Enteral Nutrition (ASPEN) guidelines, malnutrition is defined as 'an acute, subacute or chronic state of nutrition, in which varying degrees of overnutrition or undernutrition with or without inflammatory activity have led to a change in body composition and diminished function'.

Acute malnutrition is present in 25 to 54% of hospitalized patients at admission. Malnutrition has a direct association with increased morbidity, mortality, length of stay (LOS), increased readmissions and cost of care. A prospective study of 500 patients, including 200 surgical patients, demonstrated that patients lost an average of 5.4 percent of their body weight during their hospital stay. Also, the stress of surgery or trauma creates a hypermetabolic state with an increased Basal Metabolic Rate (BMR) while raising protein and energy requirements.

Furthermore, during illness, the metabolic demand, as well as recovery time, are increased. This situation could increase the risk of malnutrition or shift it from at risk of malnutrition to mild to moderate or even severe cases, resulting in a further increase in subsequent recovery time. The aforementioned condition is more evident in major surgical candidates because of metabolic stress leading to a general lack of desire to eat, malaise, fatigue and oftentimes depression interrupting normal eating processes and food intake while disturbing digestion and absorption. This condition results in skeletal muscle loss and usage of internal amino acids for endogenous glucose production (Gluconeogenesis). With the loss of skeletal muscle, protein and energy availability is lowered throughout the body. Muscle loss is also associated with delayed recovery from illness after surgery, slow wound healing and higher healthcare costs.

Measuring metabolic demand Given the increased caloric demand in a hypermetabolic state, the patient requires increased energy. Determining the exact amount of energy required has proven to be a moving target. Indirect calorimetry (IC), which is based on measurements of oxygen and carbon dioxide production (see attachment), has been shown to be the gold standard for Resting Energy Expenditure (REE) measurement in critically ill patients. However, this method is often underutilized due to staff shortage, equipment costs, and lack of knowledge and interpretation. Instead, predictive equations, such as the Mifflin St. Jeor, are used when other more precise methods, such as IC, are not available. These predictive equations are less precise, as they may not account for the increased demand due to the hypermetabolic state of the patient undergoing major surgeries, whose metabolic demand can increase as much as 150-200% above the Resting Energy Expenditure (REE). Therefore, the risk of inadequate energy intake is increased in these patients.

Screening and diagnosis of malnutrition

A number of well-known tools such as the Mini Nutrition Assessment (MNA), Graz Malnutrition Screening (GMS), Malnutrition Universal Screening Tool (MUST), Malnutrition Screening Tool (MST) and Subjective Global Assessment (SGA) are available to identify malnutrition. Although these tools have been validated, they can be limiting as they are self-directed and malnourished patients rarely receive adequate nutritional assessment and treatment prior to surgery. Instead, a recent expert consensus suggests that a diagnosis of malnutrition requires that the patient exhibit two or more of the six Parenteral and Enteral Nutrition`s (ASPEN) criteria for the diagnosis of malnutrition:

  • Insufficient energy intake
  • Weight loss
  • Loss of muscle mass
  • Loss of subcutaneous fat
  • Localized or generalized fluid accumulation that may sometimes mask weight loss
  • Diminished functional status as measured by hand grip strength Additionally, serum proteins such as albumin, prealbumin (PAB) and C-Reactive Protein (CRP) have been widely used by physicians as a marker for nutritional status. They provide a quantitative measure to indirectly evaluate malnutrition and its severity in patients undergoing surgery. Because of the overlap of malnutrition with chronic and acute inflammation, it can be challenging to predict, as well as identify, malnutrition. Acute inflammation seen in many chronic diseases could lead to hypermetabolism, rendering the patient in a hypercatabolic state.

Malnutrition intervention Available data demonstrates that early nutrition intervention, such as adequate energy and protein to prevent loss of skeletal muscle, weight and subcutaneous fat, can reduce complication rates, length of hospital stay (LOS), readmission rates, mortality, and cost of care in malnourished patients undergoing major surgeries such as gastrointestinal (GI) surgeries.

Studies suggest dietary leucine or its metabolite β-hydroxy β-methylbutyrate (HMB) can improve skeletal muscle mass and function, as well as whole-body health and well-being of animals and humans.

Supplementation with HMB has been extensively studied in elder patients and athletes. He X and colleagues displayed that the effect of HMB is through increasing gene expression of peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α), which is a master regulator of mitochondrial metabolism (See HMB information sheet, attached). However, no study has verified the effect of HMB on patients undergoing major surgeries.

HMB has been widely used in several over-the-counter products and supplements to improve muscle function and increase lean body mass. One supplement containing HMB is Ensure Enlive. This supplement is listed as the Abbott Company's most advanced nutrition shake and contains high protein plus HMB. This supplement is designed to help reconstruct muscles from the inside, with an all-in-one blend to support muscle, bone, heart immune, and digestive tract health. It is specifically designed to help patients undergoing metabolic stress including severe illness, injury, and surgery (See Ensure Enlive information sheet, attached).

The advantage of combining HMB with high protein nutrition supplement (Ensure Enlive) could translate to the theory that, HMB is executed by increasing transcriptional level of protein synthase, while other high protein or amino acids like Glutamine or Arginine supplements only provide protein-amino acids pool for patients while body's preferred fuel during metabolic stress is endogenous protein, rather than exogenous diet.

Hypotheses:

The investigators hypothesize that patients receiving high protein nutritional supplementation with HMB (Ensure Enlive) will have meaningful improvements in surgical outcomes rather than if they receive HMB only. Also, by comparing different methods of malnutrition designation, the investigators are hypothesizing that by conduction of this study, the investigators will have a better understanding of malnutrition and its consequences in the Central Valley of California. Furthermore, the investigators are planning to improve patient outcomes and significantly reduce the health care costs of the Valley by proper nutritional supplementation.

Specific Aims:

  1. Determine patients' nutritional status before and after major surgeries by baseline and subsequent nutritional assessments
  2. Determine the Resting Energy Expenditure (REE) in different phases of pre- and postoperative periods using indirect calorimetry
  3. Determine if at-risk for malnutrition is a major growing problem in the Central Valley for patients undergoing major surgeries due to lack of screening tools by monitoring and evaluating the Academy of Nutrition and Dietetics and the ASPEN recommendations for diagnostic characteristics for adults at risk for malnutrition in routine clinical practice including:
  4. Insufficient energy intake
  5. Weight Loss
  6. Loss of muscle mass
  7. Loss of subcutaneous fat
  8. Localized or generalized fluid accumulation that may sometimes mask weight loss
  9. Diminished functional status as measured by hand grip strength The presence of two or more are necessary for the diagnosis of at risk for malnutrition
  10. Compare serum protein markers and their ratios in order to correlate them with ASPEN's and The Academy criteria for nutritional status quantification
  11. Demonstrate the important role of leucine or its metabolite β-hydroxy β-methylbutyrate (HMB) supplementation with or without high protein nutrition supplement in patients undergoing major surgeries.
  12. Also, this is a unique opportunity for Fresno State Food Science and Nutrition, Nutrition and Dietetic undergraduate students to develop their skills and experience in clinical practice and research. In this study, our undergraduate students will initiate a full nutrition assessment analysis including all the 5 domains including client history (CH), Anthropometric Measurements (AD), biochemical data, medical tests, and procedures (BD), nutrition-focused/physical findings (PD) and Food/Nutrition-Related History (FH), nutrition education session and also check the 6 criteria for malnutrition, under the guidance of the researchers and registered dietitians, with the use of intact protocols and standards of comparison.

Keywords

Major Abdominal/GI Surgery HMB: β-hydroxy β-methylbutyrate MNA: Mini Nutrition Assessment GMS: Graz Malnutrition Screening MUST: Malnutrition Universal Screening Tool MST: Malnutrition Screening Tool SGA: Subjective Global Assessment REE: Resting Energy Expenditure IC: Indirect calorimetry HMB Protein and HMB HMB only

Eligibility

You can join if…

Open to people ages 18 years and up

  • Dr. Amir Fathi as attending surgeon
  • Adult patients (age >18) undergoing major abdominal and GI surgeries
  • Patients at risk for malnutrition based on the ASPEN and The Academy malnutrition criteria

You CAN'T join if...

  • Pediatric patients
  • Patients undergoing chemotherapy or radiation
  • Patients with a pacemaker (unable to conduct BIA)
  • Patients unable to successfully complete the IC
  • Patients with known allergies to products (Ensure Enlive, HMB)
  • Patients that are unable to comply with all requirements
  • Vegan patients
  • Pregnant patients
  • Prisoners

Location

  • Community Regional Medical Center not yet accepting patients
    Fresno California 93721 United States

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
ID
NCT03692507
Phase
Phase 1
Lead Scientist
Amir Fathi
Study Type
Interventional
Last Updated