After completing this chapter, the reader should be able to
Describe the current defining criteria and parameters for the diagnosis of malnutrition
Discuss the relevance and feasibility of laboratory tests that have been/are currently used in the assessment of a patient’s nutritional status based on the current definition of malnutrition
Determine whether specific laboratory tests in a patient’s profile provide valid and specific information regarding the patient’s nutritional status
Propose a patient-specific assessment plan for monitoring a patient’s nutritional status
Identifying patients who are at risk for malnutrition and continually monitoring a patient’s nutritional status are critical components of the comprehensive patient care plan. Research has confirmed that the presence of malnutrition consistently correlates with increased length of stay in the hospital and the intensive care unit (ICU), prolonged mechanical ventilation, increased risk for healthcare–associated infections and complications, delayed recovery from surgery, delayed wound healing, and increased mortality.1-7 Malnutrition is also associated with increased use of healthcare resources and increases healthcare costs.8 Implementation of optimal nutrition support therapy in a timely manner has been shown to improve patient outcomes and reduce costs to the healthcare system.9 The Joint Commission has established standards related to nutritional screening and assessment that are applicable to patients in all acute care and long–term care facilities.10
Understanding a patient’s nutritional status has a direct implication on the roles performed by pharmacists. A patient’s malnutrition risk and clinical conditions determine the needs and urgency for specialized nutrition support, such as enteral and parenteral nutrition. Use of specialized nutrition support has implications on patient safety, such as optimization of fluid and electrolyte balance, determining route and method of drug administration, and addressing drug compatibility concerns. Additionally, patients with malnutrition are at increased risk for falls and frailty. Altered body composition such as sarcopenia, dehydration, edema, and end organ dysfunction may alter pharmacokinetic and pharmacodynamic response to pharmacotherapy. Therefore, identifying malnourished patients or those who are at risk for malnutrition may help pharmacists adjust and optimize pharmacotherapeutic approaches and decisions that can improve patient safety and outcomes.
The perception and understanding of malnutrition have evolved over time. Historically, the term malnutrition is mostly associated with starvation and famine leading to kwashiorkor and marasmus. Kwashiorkor, sometimes known as edematous malnutrition, is a form of protein–calorie malnutrition most commonly associated with hunger and starvation. Patients typically present with loss of muscle and generalized edema and a large, protuberant belly. Marasmus is also a form of protein–calorie malnutrition. It generally presents with overall weight loss with severe muscle mass depletion without edema. The two conditions are not mutually exclusive because marasmus may progress to kwashiorkor in some patients. With changes in the global economy and landscape and improvements in agriculture, healthcare, education, living standards, and high–risk medical/surgical interventions, the presentation of malnutrition has expanded. The presentation of malnutrition in modern days may not be limited to a lack of access to food in general. Instead, malnutrition more commonly presents as nutrient imbalance, undernutrition, micronutrient abnormalities, obesity, cachexia, frailty, and sarcopenia.11 In particular, sarcopenia, or loss of muscle mass, is the current malnutrition–related research focus. Its prevalence is especially high among older adults, hospitalized patients, critically ill patients, and patients with cancer (Table 12-1).12 The evolving changes also challenge the existing clinical definition of malnutrition. According to the tenth revision of International Classification of Diseases (ICD) codes, the clinical features that fit the diagnosis of malnutrition are still limited (Table 12-2) and do not fully address the current understanding of the etiology and presentation of malnutrition.
Prevalence of Sarcopenia Among Patient Populations Based on Recent Clinical Studies
60–70 years old
≥ 80 years old
Adult patients admitted to medical and surgical floors
Adult patients admitted to the ICU
Patients with cancer
ICD-10 codes for Malnutrition
Unspecified severe protein-calorie malnutrition
Protein-calorie malnutrition of moderate and mild degree
Retarded development following protein-calorie malnutrition
Unspecified protein-calorie malnutrition
The current etiology–based disease definition accepted in the field of nutrition is that malnutrition is a syndrome that includes chronic starvation without inflammation (eg, anorexia nervosa or major depression with lack of interest in eating); chronic disease–associated malnutrition, when inflammation is chronic and of mild to moderate degree (eg, organ failure, pancreatic cancer, rheumatoid arthritis, or sarcopenic obesity); and acute disease or injury–associated malnutrition, when inflammation is acute and of severe degree (eg, major infection, burns, trauma, or closed head injury).11 Since 2016, a group of international researchers have come together and started a workgroup called Global Leadership Initiative on Malnutrition (GLIM). This group aims to develop a consensus–based framework to define, describe, and record the occurrence of malnutrition that would be applicable worldwide.13
Inflammation is an important component in the current/modern definition of malnutrition. Inflammation alters food intake, nutrition absorption, and/or assimilation and leads to altered body composition and impairs certain biological functions.14 Inflammation is a critical pathophysiological process that leads to or accelerates the loss of lean body mass and muscle size (ie, sarcopenia) and cellularity. Chronic inflammation may progress to severe functional loss, and increases morbidity and mortality. Therefore, identifying the presence and severity of inflammation is crucial to the screening, characterization, and assessment of malnutrition as well as developing a patient–specific therapeutic plan to reverse malnutrition and functional loss. It also affects what monitoring parameters, including laboratory surrogate markers, are more accurate and specific for monitoring progress and response toward nutritional interventions. Laboratory tests that are significantly impacted by inflammation may not accurately reflect a person’s nutritional status and, therefore, are unreliable nutritional markers.
Serum visceral protein concentrations, such as albumin, prealbumin, transferrin, and retinol binding protein, have been extensively used as laboratory markers for malnutrition since the 1970s.15,16 Each of these serum proteins has different physiologic characteristics (Table 12-3). However, the regulation, synthesis, and degradation of these serum proteins are all affected by other factors in addition to decreased nutrient intake. End organ dysfunction, specific nutrient deficiency, and inflammation all have a direct impact on the homeostasis of these compounds. With the current knowledge that malnutrition is associated with an inflammatory state, none of these visceral proteins is a sensitive or specific marker in the clinical assessment of a patient’s nutritional status and response to nutrition therapy. They should not be used for nutritional assessment. The history of each of the visceral proteins as a nutrition marker and their respective limitations are discussed next.
Summary of General Physiologic Functions and Serum Half-Lives of Visceral Proteins Used Historically as Nutrition Markers
VISCERAL PROTEIN AND NORMAL RANGE
SERUM HALF-LIFE (UNDER NORMAL PHYSIOLOGY)
FACTORS THAT AFFECT PLASMA CONCENTRATION
Maintaining oncotic pressure of plasma
Transporting a number of divalent cations (eg, calcium)
Transporting a number of peptide hormones and biological compounds
Serving as an antioxidant molecule
Transporting thyroxine in the plasma and across the blood–brain barrier
Serving as a carrier protein for retinol-binding protein
Transporting vitamin A, specifically retinol
Vitamin A status
Albumin is a major serum protein that is exclusively synthesized in the liver. Its primary functions include maintaining colloidal osmotic pressure for plasma, serving as the carrier and binding protein for many physiologic compounds (eg, bilirubin; long–chain fatty acids; divalent cations such as calcium, magnesium and zinc; bile acids; vitamin D; sex hormones; cortisol; thyroxine; and catecholamines) and drugs, maintaining acid–base balance for plasma, and providing important extracellular antioxidant function of the plasma to scavenge free radicals generated under normal physiology.17,18 The estimated total body albumin is ~280 g for an average adult, as determined by tracer method. Of the total albumin pool, ~40% is found in the intravascular space and the rest is distributed in the interstitial space of different vital organs, such as muscle, connective tissues, and skin. The average hepatic synthetic rate of albumin for a healthy adult is ~150 mg/kg/day (~10 to 15 g/day). The average total body turnover time is ~25 days.18,19 Under normal physiology, renal and gastrointestinal (GI) loss of albumin should be less than 6% and 10% of the total body albumin pool, respectively. The rest of the turnover mechanism is not fully understood. Some studies have suggested that albumin undergoes degradation in the extravascular compartment.20 When the synthetic and removal rate of albumin is at steady state, the serum albumin concentration is maintained between 3.5 and 4 g/dL.
With its hepatic origin and the early studies linking its serum changes with kwashiorkor, it has been assumed historically that serum albumin concentration reflects a person’s nutritional status given the liver is the primary organ for plasma protein synthesis.21,22 In 1977, it was first suggested by Blackburn et al that serum proteins, including albumin and transferrin, could be used as a marker of nutritional assessment for hospitalized patients.23 With a number of studies published shortly after that also demonstrating a correlation between serum albumin concentration and prognosis of hospitalized patients, serum albumin was widely suggested as a clinical marker of malnutrition. In their retrospective study involving 500 consecutively admitted patients, Seltzer and colleagues showed that patients with a serum albumin concentration <3.5 g/dL on admission had statistically significant higher complication rates (33% versus 7.3%) and mortality rates (0.8% versus 0%) for that hospital stay. Compared with patients with serum albumin >3.5 g/dL, those with hypoalbuminemia were associated with a 4–fold increase in complications and a 6–fold increase in deaths. When the data were further compared between surgical versus nonsurgical patients, hypoalbuminemia was associated with a 9.7 times higher mortality rate for nonsurgical patients. Based on their findings, the authors called for using serum albumin as an “instant nutritional assessment information” that should be used for every hospital admission.24 In the following year, a pivotal trial by Rheinhart et al showed a negative linear correlation between serum albumin concentration and 30–day mortality in 509 adult patients with hypoalbuminemia.25 The hospital mortality rate for those with albumin <2.1 g/dL was more than 10 times higher than for patients with albumin <3.4 g/dL. These findings paved the way in making serum albumin a routine laboratory test in assessing nutritional status of patients.
Contemporary research in clinical nutrition and metabolism has significantly increased our understanding of the pathophysiology of malnutrition and the physiological response to feeding. It is now clear that although serum albumin concentration may have a prognostic value in predicting survival, it is not a valid surrogate marker of total muscle mass or clinical response to feeding. Increased vascular permeability, changes in interstitial volume, and systemic inflammation can alter serum albumin concentration independent of liver function, nutrient intake, and nutrient utilization. Thus, it should not be used as a clinical marker for a patient’s nutritional status.15
Hypoalbuminemia is a common presentation in hospitalized patients, especially among individuals who are critically ill. Multiple factors may contribute to decreased serum albumin concentration. The most important driving factor is inflammation associated with an acute phase response. Acute phase response may occur in acute illnesses (eg, trauma, sepsis, pancreatitis) and ongoing, uncontrolled chronic diseases (eg, gout, heart failure, inflammatory bowel disease, autoimmune diseases). In both situations, it is associated with increased plasma and cellular concentrations of proinflammatory cytokines (eg, tumor necrosis factor, interleukin-6). The inflammatory process can also be confirmed by the presence of nonspecific surrogate markers of inflammation, such as an elevated C–reactive protein concentration in the plasma.
It is proposed that inflammation affects serum albumin in at least three different mechanisms: (1) increased capillary permeability and leak resulting in serum albumin leaving the intravascular compartment to the interstitium; (2) hepatic reprioritization of protein synthesis—a process in which the liver increases the synthesis of other proteins and compounds essential for host defense and survival over visceral proteins such as albumin and transferrin; (3) increased degradation to immediately increase the free concentrations of hormones, cytokines, and other vital peptides available in the plasma to promote healing and recovery of the body as well as be recycled after serving specific physiologic functions, such as oxidation, glycation, or binding of other highly reactive substances that may be harmful to cells and tissues.15,18,26-28 These mechanistic explanations are consistent with clinical observations. In fact, serum albumin concentration falls quickly shortly after injuries and acute illnesses. For example, in the pivotal study published by Rheinhart et al, the lowest serum albumin concentration was recorded in 48.9% of the patients within 1 week of hospital admission.25 In an ICU study with nine mild–to–moderate critically ill adults (mean APACHE II score 7.5) with hypoalbuminemia, feeding patients with parenteral nutrition at 35 to 40 kcal/kg/day with 1.2 to 1.6 g/kg/day of protein did not change the mean serum albumin concentration (2.0 g/dL to 2.1 g/dL) or extend the shortened serum half–life of albumin (9.1 days).29 Serum albumin concentration is inversely correlated with C–reactive protein concentration and remains low as long as plasma C–reactive protein concentration is elevated (Figure 12-1).30 These results indicate that although albumin consistently shows a positive correlation with survival, hypoalbuminemia is a more accurate reflection of the magnitude of systemic inflammation (and possibly severity of acute illnesses) experienced by a patient rather than a true, reliable surrogate marker of a patient’s nutritional status.
A related topic is whether serial serum albumin concentrations can be used to reliably assess a patient’s response to nutritional interventions and guide therapeutic changes to the nutrition support regimen. Despite the relatively small number of clinical studies, the results have failed to confirm a positive relationship. For example, Li et al showed that among older adults undergoing gastric cancer surgery, continuous feeding by either enteral or parenteral route at 30 kcal/kg/day for up to 7 days did not improve serum albumin concentration (3.4 versus 3.1 g/dL on days 1 and 7, respectively). The lack of improvement was likely due to the ongoing, uncontrolled systemic inflammation, as reflected by the continued increase in serum C–reactive protein concentration (2.9 to 11.6 mg/L on days 1 and 7, respectively).31 Yeh et al also showed that changes in serum albumin concentration did not correlate with the adequacy of nutrient delivery and clinical response to feeding in patients in the surgical ICU.32 Overall, serum albumin concentration has not been shown to be a sensitive marker of energy and protein intake adequacy, especially in hospitalized patients. Normalization of serum albumin concentration during the hospital stay or course of care may merely be a reflection of the resolution of inflammation (ie, optimal and positive response to the treatment of the current illness) and does not suggest an improvement of nutritional status or decreased need for nutrition intervention.
In summary, based on current knowledge and evidence, serum albumin concentration is significantly affected by inflammation. Hypoalbuminemia in patients is likely a reflection of ongoing and uncontrolled illness involving a heightened inflammatory state. Serum albumin concentration does not serve as a proxy measure of total body protein or total muscle mass and should not be used to assess nutritional status or guide nutritional intervention.
Prealbumin, also known as transthyretin, is another visceral serum protein that has been proposed as a useful laboratory marker for nutritional assessment. Prealbumin is also a hepatic plasma protein and is partly catabolized by the kidneys. Its primary functions include transport of thyroid hormones and retinol–binding protein both in the plasma and across the blood–brain barrier. It may also play a role in regulating epinephrine availability because it has binding affinity for this neuropeptide.33 Recently, it has also been found to be a major binding protein for β–amyloid (Aβ) peptide in the brain, suggesting its neuroprotective effect or as a potential treatment target for Alzheimer disease.34
The interest of using prealbumin as a nutrition marker can be traced back to the early 1970s. In 40 hospitalized children with protein–calorie malnutrition, serum prealbumin concentration was found to be depleted but quickly reversible upon dietary protein replenishment and with a much faster response rate than albumin.35 The higher degree of responsiveness in the normalization of serum concentration can be attributed to its shorter biological half–life of 2 days, compared with 20 days for albumin.36 In the following 30 years, numerous studies and conference proceedings have suggested and even emphasized the use of prealbumin as the preferred laboratory test to assess patient nutritional status and guide nutritional interventions.37,38
One of the major limitations of using prealbumin as a nutrition marker is that it is a negative acute phase reactant. It can be useful for estimating nutrition risk by identifying patients whose inflammatory state is heightened and can help determine whether these patients are at an increased risk of poor outcomes if nutritional intervention is not initiated. Because it is a visceral transport protein synthesized by the liver, however, it shares the same characteristics with albumin in response to stress and inflammatory response and thus is subject to the same limitations as a marker for nutritional status. Under acute stress conditions, the synthesis of prealbumin is abruptly depressed by a cytokine–directed hepatic reprioritization of metabolic and synthetic processes for plasma proteins as well as a redistribution of organ and tissue protein pools.15,33 Additionally, prealbumin concentrations may be increased in renal dysfunction, corticosteroid therapy, or dehydration. Studies have also shown that prealbumin concentration does not correlated with anthropometric assessment findings in patients with cancer and eating disorders.39,40
Regarding its role for monitoring nutrition interventions and guiding nutrient provision, serum prealbumin is also found to be inconsistent and unreliable as a nutrition marker. Although some studies have suggested that prealbumin is more sensitive than transferrin and albumin as an indicator of adequate nutritional provision, additional studies have showed that prealbumin more accurately reflects systemic inflammation rather than adequacy of calorie and protein provision.32,41-43Figure 12-2 summarizes the relationship between plasma concentration of prealbumin and high–sensitivity C–reactive protein over time for 36 adult patients in the medical ICU. It shows that while a patient is under a heightened inflammatory state on ICU admission, prealbumin concentration is suppressed. As the patient’s clinical status improved and C-reactive protein concentration dropped to <100 mg/L, prealbumin concentration increased significantly. However, as these patients experienced new clinical complications with C–reactive protein concentration rising once again, their prealbumin concentration also trended downward despite adequate caloric and protein provision through nutrition support (Figure 12-2).44
In summary, although prealbumin has been used and continues to be used as a laboratory marker for nutrition assessment and response to nutritional intervention, more recent knowledge and clinical data show that changes in its serum concentration are more likely related to system inflammation. Therefore, it should not be used to assess a patient’s nutritional status. Its role as a surrogate marker for response to feeding is highly questionable and requires further investigation.
Transferrin is another hepatic visceral protein with the primary function as a carrier protein for iron. Its expression is regulated by the iron status of the body, with increased expression in iron deficiency. Its use as a nutritional marker dates back in the 1970s. Its serum half–life is approximately 10 days, making it a more favorable serum marker than album.45 However, it is also a negative acute phase reactant, and its serum concentration is increased with renal failure, pregnancy, anemia, and dehydration. Abrupt reduction in serum transferrin concentration in critically ill patients is common and is caused by inflammation and reprioritization of hepatic protein synthesis. Given the confounders that affect its homeostasis, transferrin is an unreliable marker for nutrition assessment. Studies have also shown conflicting results regarding its change in serum concentration in response to nutritional interventions.46-49 Its use as a general malnutrition marker or as a marker for nutrition response is not recommended.
OTHER HISTORICAL LABORATORY MARKERS
Serum Retinol-Binding Protein
The use of retinol–binding protein as a laboratory marker to assess nutritional status was initially proposed by Ingenbleek and colleagues in 1975 in a study involving 37 children aged 18 to 30 months. All the patients in the study presented with protein–calorie malnutrition with clinical presentations including weight loss, growth failure, hair discoloration, skin lesions, diarrhea, and swollen limbs. Serial serum visceral protein concentrations were measured at baseline and weekly for 3 weeks after oral diet treatment was initiated. Serum viscera protein measured included albumin, transferrin, prealbumin, and retinol–binding protein. Retinol–binding protein was selected because it binds to prealbumin and has a short biologic half–life of approximately 12 hours. It theoretically offers a benefit over prealbumin and transferring by having a faster turnover rate in detecting responses to feeding. Investigators found that prealbumin and retinol–binding protein had the most pronounced decline in their plasma concentration at baseline. The serum recovery rate after dietary intervention was initiated was comparable between the two proteins. By day 22, plasma retinol–binding protein concentration was increased by 3- to 4–fold from baseline. The authors suggested that retinol–binding protein is a more sensitive marker than albumin and transferrin in assessing nutritional status.16
Despite its potential benefits over other visceral proteins, there are an insufficient number of high–quality validation studies to confirm the role of retinol–binding protein in nutritional assessment across different patient populations. Additionally, retinol–binding protein is affected by a patient’s vitamin A status and the presence of inflammation.50,51 Currently, retinol–binding protein concentration should be considered a component of a comprehensive assessment for vitamin A status rather than a general laboratory marker for nutritional assessment.
Total Lymphocyte Count
Total lymphocyte count has been used historically as a laboratory marker for nutritional assessment. Seltzer et al showed that an abnormal total lymphocyte count, defined as <1,500 cell/mm3 of absolute lymphocyte, was associated with 1.8–fold increase in complications and a 4–fold increase in mortality among 500 hospitalized patients.24 It is thought that malnutrition, especially protein–calorie malnutrition, may lead to decreased lymphocyte production by the body; however, this change is neither sensitive nor specific to malnutrition. Concomitant diseases and a severe stress reaction may also affect lymphocyte count and bone marrow response. Chronic deficiency in specific nutrients, such as hypocupremia from intestinal malabsorption, can also lead to lymphopenia. Although it continues to be used by some investigators as a marker of nutritional status, a consistent relationship between total lymphocyte count and malnutrition based on anthropometric assessment or validated nutrition screening tools is lacking.52,53 Total lymphocyte count responds slowly to the correction of the nutritional status, even in the absence of other factors. Therefore, it is neither an accurate nor a clinically reliable laboratory marker as a diagnostic tool for malnutrition for assessment of response to nutritional support.
Additional Laboratory Tests Used in Clinical Nutrition
Nitrogen Balance Study
Nitrogen balance study is intended to assess the adequacy of protein intake and is the most established and accepted clinical procedure and laboratory assessment for this purpose in current practice and clinical research. Amino acids are important building blocks for tissues and other vital cellular components, such as transport proteins and peptide hormones. Protein synthesis involves the incorporation of an amine group into carbon molecules. By measuring the rate of dietary nitrogen entering and leaving the body and calculating the difference in a defined period, it can help optimize nutritional provision, especially for daily protein, which can, in turn, help prevent malnutrition by preserving or increasing body cell mass. Nitrogen balance study is the technique used to optimize dietary nitrogen (thus protein) intake.
Nitrogen is primarily eliminated from the body in the urine and feces. Other minor sources of nitrogen loss include dermal loss and daily tissue turnover such as from hair, nails, and secretions.54 The nonurinary and fecal loss is generally considered negligible and clinically insignificant. Because most nitrogen loss is through the urine in the form of mostly urea but also as ammonium and creatinine, nitrogen balance study typically involves collecting 24–hour urine to quantify the urinary urea nitrogen (UUN). The following is the general equation to determine nitrogen balance:
In this equation, UUN is the directly measured value from a 24–hour urine collection. The +4 is added to account for fecal and other minor sources of nitrogen loss based on historical data. Daily dietary protein intake in grams per day is divided by 6.25 because the metabolically active proteins in the human body, as well as in most dietary proteins, generally contain 16% nitrogen by weight.55
Based on the setup of this equation, ideal candidates for accurate nitrogen balance study include patients whose total protein intake can be fully and accurately quantified, who are preferably receiving full enteral or parenteral feeding, who have normal renal function, and who are not experiencing excessive nonurinary nitrogen loss, such as through diarrhea, open wounds, or GI drainage. In patients with renal insufficiency, nitrogen kinetics can be evaluated by analyzing nitrogen content in the dialyzed fluid and the rate of change in serum blood urea nitrogen concentration.56-59 The details of determining nitrogen kinetics are beyond the scope of this chapter. In catabolic patients, the goal is the achieve a nitrogen balance of +2 or higher to facilitate anabolism.
Nitrogen balance studies are more commonly performed in the critical care setting, in which patients are likely receiving continuous nutritional support and an accurate timed urine sample collection is more feasible. Critically ill patients are in a severe inflammatory and catabolic state. Therefore, it is also important to meet their protein requirement to promote healing and recovery.
C–reactive protein is a pentameric protein synthesized by the liver. It is released in response to inflammation; thus, it is a nonspecific positive acute phase reactant. Plasma C–reactive protein concentration is elevated in both acute and chronic inflammatory responses. It has a serum half–life of 19 hours.60 Therefore, it can fluctuate throughout the course of a patient’s treatment and offer some information on whether the patient’s inflammatory state is worsening or improving. However, it must be interpreted according to patient–specific clinical context and presentation. No single value can be used to rule in or rule out a specific diagnosis or disease.
C–reactive protein is not a direct marker to reflect a patient’s nutritional status. However, because the current consensus is that the etiology of malnutrition includes inflammation, determining plasma C–reactive protein concentration can help clinicians determine if a patient is at risk for malnutrition and prioritize the need for nutritional intervention.11,13
WHAT ARE THE BEST APPROACHES TO ASSESS NUTRITION STATUS, DIAGNOSE MALNUTRITION, AND MONITOR NUTRITIONAL RESPONSE?
Based on the contemporary understanding and clinical definition of malnutrition, it appears that none of the laboratory tests historically or currently in use are sensitive markers for nutritional assessment and monitoring. Instead, changes in the serum concentrations of these visceral proteins reflect the magnitude of ongoing inflammation experienced by the patients. So, what are the optimal approaches in assessing nutritional status and response to nutritional interventions?
Malnutrition should be determined based on the presence of phenotypic or etiologic criteria. Phenotypic criteria include changes such as unintended weight loss of ≥5% within the past 6 months, lower body mass index (exact cutoff is being addressed by the GLIM workgroup and is likely to be region/demographic–specific), or reduced muscle mass as measured by validated body composition–measuring techniques, such as dual–energy absorptiometry, computed tomography, bioelectrical impedance analysis, magnetic resonance imaging, and ultrasound. Etiologic criteria include reduced food intake and the presence of systemic inflammation.8,61 Importantly, the presence and the severity of inflammation should be routinely evaluated because they help determine a patient’s malnutrition risk and prioritize the needs for nutritional intervention.
Ultimately, laboratory tests alone should not be used to replace a detailed nutritional assessment in determining a patient’s malnutrition risk. The purpose of a nutritional assessment is to gather relevant information to provide evidence for the nutrition diagnosis and aid in the development of a patient–specific nutrition intervention plan. Assessing nutritional status and monitoring for clinical response to nutritional intervention require the application of basic clinical skills, which include collecting a detailed patient’s history, performing physical examinations whenever possible, and using validated screening tools where applicable.62,63 Detailed history–taking is a critical component of nutritional screening, assessment, and ongoing monitoring. It is important to identify risk factors that would increase a patient’s malnutrition risk, such as inflammation, the use of certain medications (eg, corticosteroids, chemotherapeutics agents), and the presence of underlying medical, health, or social conditions (eg, loss of dentition, depression, chronic nausea, dry mouth, lack of access to food) that could impair food intake or nutrient use (Table 12-4). Performing simple and basic physical examination, such as determining fluid status, adiposity, weight changes, and symptoms associated with specific nutrient deficiencies can help identify at–risk patients and expedite nutritional intervention. Finally, the use of validated nutritional assessment tools, such as Mini Nutritional Assessment or Subjective Global Assessment, can provide a comprehensive evaluation of a patient’s malnutrition risk.
Factors Contributing to Increased Risk for Malnutrition in Patients
Changes in Body Composition
Unintentional weight loss
Moderate malnutrition: 5%–10% within 6 mo or 10%–20% beyond 6 mo
Severe malnutrition: >10% within 6 mo or >20% beyond 6 mo
High or low body mass index
Moderate malnutrition: <20 kg/m2 if <70 yr; <22 kg/m2 if ≥70 yr
Severe malnutrition: <18.5 kg/m2 if <70 yr; <20 kg/m2 if ≥70 yr
Changes in intake
Decreased or loss of appetite
Loss of smell or taste
Decreased food intake
Severe dry mouth
Inflammation (acute and/or chronic)
Chronic diseases not being controlled
Acute injuries and changes to the state of health
Significant decline or loss of visual acuity
Social and psychological factors
Loss of companionship (eg, partners, pet)
Drug-induced changes in intake or GI tract functions
Inflammation is an important component of malnutrition that can lead to loss of muscle mass, impair physiologic and body function, and negatively impact clinical outcomes. Although a number of laboratory tests, such as albumin, prealbumin, and transferrin, are routinely used as surrogate markers of nutritional status, they mostly reflect the state of inflammation the body is experiencing and are neither accurate nor specific for nutritional assessment. Nutritional assessment should be performed by using a multicomponent comprehensive evaluation that includes history–taking, physical examination, and the use of a validated nutrition assessment tool rather than relying on a laboratory test or tests in isolation.
Nancy M. is a 68-year-old woman admitted to the hospital for an aortic valve replacement and coronary artery bypass graft surgery. Her past medical history includes hypertension, type 2 diabetes mellitus, hypercholesterolemia, and chronic constipation. Her current medications include metformin, sitagliptin, simvastatin, fosinopril, and polyethylene glycol 3350.
Her height is 165 cm and weight is 89.4 kg. She has gained 2.5 kg in the last 2 weeks. Her vital signs on admission include blood pressure 110/85 mm Hg, heart rate 68 beats/min at regular rhythm, and a respiratory rate 12 breaths/min. Physical examination findings include +2 edema on both ankles and bilateral numbness in her thumb and first finger.
Her laboratory test results before surgery include a serum albumin concentration of 3.8 g/dL and a hemoglobin A1c concentration of 6.3%. All other laboratory values on the chemistry panel are within normal limits.
QUESTION: What is her malnutrition risk?
DISCUSSION: The fact that this patient is undergoing major cardiac surgery puts her at high risk for malnutrition. Cardiac surgery is a high-stress procedure. Underlying malnutrition is associated with increased postoperative mortality, especially in older adults. Fortunately, her chronic illnesses appear to be well controlled at this point. Additional history regarding her dietary habit, appetite, and approximate daily food intake should be obtained. Each of these independent factors affects her malnutrition risk.
Studies show that immediately after surgery, patients lose a substantial amount of muscle mass due to acute inflammation. The inflammation response will likely be reflected by an elevated C-reactive protein concentration and a decline in serum albumin concentration. Her nutritional status should be continually assessed by following daily intake, weight changes, and presence of any surgery-related complications. Serum albumin or prealbumin concentrations will not provide any patient-specific information regarding her ongoing nutritional status.
Carrie M., a 32-year-old woman, presents to the emergency department with 1-day history of severe epigastric pain, nausea, dizziness, and fever. She rates the pain as 8 out of 10. She reports three episodes of vomiting within the past 12 hours. Before presenting to the hospital, she was in her usual state of health. Laboratory values obtained from her routine health maintenance visit from 6 months ago show normal findings for her liver function tests, including serum albumin, serum chemistry, and complete blood count.
Her past medical history includes Crohn disease since age 17 years, resulting in an extensive history of small bowel resection. Her current GI anatomy includes approximately 300 cm of functional small intestine and an intact colon. She tolerates an oral diet and takes four small meals daily with an oral protein supplementation. She has mild chronic diarrhea, which is usually well-controlled by diet at two to three soft bowel movements per day, and she takes loperamide three times a day and clonidine twice a day.
On admission, her weight is 65.7 kg, which has decreased by 1.1 kg from baseline measured 6 months ago. Her body mass index is 20.7 kg/m2. Physical examination shows she has mild dehydration with no peripheral edema.
Pertinent laboratory findings are as follows:
Albumin, 2.8 g/dL
Prealbumin, 15 mg/dL
Amylase, 880 units/L
Lipase, 930 units/L
C-reactive protein, 49 mg/dL
The patient is diagnosed with acute pancreatitis and admitted to the hospital for further management. Intravenous (IV) fluids and pain medication are started immediately.
QUESTION: Based on her underlying medical condition, clinical presentation, and laboratory findings, including serum albumin and prealbumin concentrations upon admission, does the patient have severe malnutrition necessitating immediate initiation of parenteral nutrition?
DISCUSSION: Acute pancreatitis is a disease associated with acute inflammation and catabolism. This is reflected by the elevated C-reactive protein concentration, which is common among patients with acute pancreatitis. The inflammation causes an acute decline in serum albumin and prealbumin concentrations because they are negative acute phase reactants. Therefore, the current albumin and prealbumin concentrations do not reflect this patient’s nutritional status. Rather, these are additional markers besides C-reactive protein confirming the presence of acute inflammation.
The change of body weight from baseline is likely the result of dehydration. Along with acute pancreatitis, dehydration, vomiting, and fever are all independent factors associated with increased malnutrition risk. Therefore, this patient’s nutritional status and intake should be carefully monitored in the next 24 to 48 hours. Nutritional interventions with protein provision should be initiated as tolerated. However, because she was in her usual state of health before admission and tolerated an oral diet at baseline, parenteral nutrition is not indicated at this point. Enteral nutrition should be first attempted after controlling vomiting and abdominal pain. Postpyloric feeding tube placement is more likely to increase enteral feeding tolerance without aggravating pain. This should be attempted along with IV fluid rehydration and electrolyte replacement, which are consistent approaches with the current practice standards for acute pancreatitis. Consistent with the current practice standards, if she is unable to tolerate enteral feeding in the next 3 to 5 days, parenteral nutrition would be considered.64
Serum albumin and prealbumin will remain suppressed as long as C-reactive protein concentration is elevated. Therefore, albumin and prealbumin should not be used during this time as a marker of nutritional response. Instead, her response to enteral feeding should be based on daily caloric and protein intake, GI symptoms, pain control, and general well-being. Additional protein supplementation is likely necessary upon hospital discharge as she continues to regain her appetite and reestablish an oral diet that is tolerated by her underlying medical condition.
Frank K. is a 52-year-man who has systemic lupus erythematosus (SLE), hypertension, type 2 diabetes, chronic proteinuria, and chronic kidney disease (CKD) stage 5 and is currently receiving hemodialysis. The following laboratory results have been obtained as his dialysis care process:
Hemoglobin, 10.5 g/dL
Mean corpuscular volume, 77 fL
Red cell distribution width, 19.9%
Serum ferritin, 34 ng/mL
Transferrin, 382 mg/dL
Transferrin saturation, 28%
QUESTION: Based on this patient’s medical history and laboratory results, what are his risk factors for malnutrition?
DISCUSSION: This patient has anemia based on his hemoglobin concentration, an unsurprising finding due to CKD. The results of the iron study suggest that he has iron deficiency, which can increase serum transferrin concentration. This finding makes serum transferrin an unreliable marker for nutritional status in this patient.
Nutritional status cannot be reliably assessed using retinol-binding protein because it is increased in CKD. Additionally, it is not uncommon that chronic inflammation is present in patient’s CKD. Therefore, if his serum albumin concentration is below the normal range, it may be a reflection of uncontrolled systemic inflammation. This also makes hypoalbuminemia and hypo-prealbuminemia unreliable markers for malnutrition in CKD. Nutrition assessment for this patient should be based on a comprehensive clinical assessment using history, clinical findings, and a validated assessment tool.
This patient does have multiple risk factors for malnutrition, including SLE, hypertension, iron deficiency anemia, and CKD. SLE is associated with a chronic inflammatory state, which may have suppressive effect on appetite and oral intake. Along with proteinuria, this patient is at high risk for developing protein-calorie malnutrition. Therefore, his treatment plan must include suppressing chronic inflammation, reducing urinary protein loss, and optimizing calorie and protein intake. Ideally, in addition to body weight and oral intake monitoring, routine body composition assessment to prevent sarcopenia should be considered.
Josha T. is a 39-year-old man has been admitted to the hospital after being hit by a bus while riding his bicycle to work. His injuries include multiple fractured ribs and blunt abdominal injury. He undergoes surgery upon admission to the hospital and is found to have a small intestinal perforation. Postoperatively, he is transferred to the trauma/surgical ICU for recovery and supportive care.
Because of abdominal trauma, parenteral nutrition is started on postoperation day 2. The parenteral nutrition prescription provides 2,350 kcal (35 kcal/kg) with 120 g (1.8 g/kg) of protein per day.
His serum albumin concentration on admission is 3.5 g/dL. On the day parenteral nutrition is initiated, his serum albumin level is 3.1 g/dL. Five days after parenteral nutrition therapy, his serum albumin concentration is still 3.1 g/L and prealbumin is 18 mg/dL. The surgical team consults with the clinical nutrition team to optimize nutrient provision and delivery. At this point, there is still substantial drainage from his small intestine; therefore, enteral feeding is not a feasible option.
QUESTION: How should the clinical nutrition team optimize nutrient provision and delivery for this patient?
DISCUSSION: Traumatic injury is associated with a profound systemic inflammation. Therefore, continued hypoalbuminemia in this patient, despite receiving 120 g of protein per day, is due to continued, unsuppressed inflammation. It does not reflect the patient’s response to nutritional therapy. Neither serum albumin nor prealbumin should be used to determine the adequacy of nutritional intervention in this patient.
Because his renal function remains stable with an estimated glomerular filtration rate of 108 mL/min, the clinical nutrition team orders 24-hour urine collection for a nitrogen balance study. The next day, the clinical nutrition team assesses the result, which shows urine urea nitrogen output of 17.5 g in 24 hours. His blood urea nitrogen and serum creatinine concentrations remain stable at 19 mg/dL and 1.12 mg/dL, respectively. Under normal physiology with an assumed nonrenal nitrogen loss of 4 g/day, the total daily nitrogen output for this patient is approximately 21.5 g (17.5 g + 4 g). However, because he has continued fluid drainage from this small intestine, his actual nitrogen output is likely higher than 21.5 g/day. Based on his current parenteral nutrition prescription, his total nitrogen input is 120 g/6.25 g = 19.2 g. Therefore, he is currently in a negative nitrogen balance (at least −3 but probably higher).
In response to the nitrogen balance study, the clinical nutrition team suggests increasing the amino acid content from 120 to 150 g/day (equivalent to 24 g of nitrogen intake per day). In addition, indirect calorimetry is ordered to ensure that the patient is not overfed in total calories. The patient will continue to be monitored for vital signs, daily fluid and electrolyte balance, weight changes, ongoing inflammatory state, and clinical improvement. Repeat nitrogen balance study may be considered in a week if his clinical condition does not improve.
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