Introduction
Medicine is a continuously evolving field of science, using state-of-the-art technologies and devices to provide patients with the best possible care in accordance with the latest standards. Current technology makes it possible to tailor treatment to individual patients, which is the core principle of personalized medicine. One area where technological progress has led to the development of new solutions is gastrointestinal failure, including acute intestinal failure (AIF), particularly the issue of determining caloric needs.
Parenteral nutrition (PN) is a modality of nutritional support indicated for patients with conditions such as short bowel syndrome or intestinal obstruction, as well as for individuals unable to ingest food orally or intolerant of enteral feeding. Additionally, PN may be employed to address nutritional deficiencies in preoperative patients to optimize surgical outcomes [1, 2]. In this context, an extremely important issue is the selection of patient groups requiring nutritional support [2]. However, given the severity of potential disease exacerbations, indirect calorimetry (IC) may be valuable as a screening tool to identify patients in need of nutritional support.
Malnutrition in hospitalized patients worsens prognosis and quality of life by increasing mortality, morbidity, and infection rates; extending hospital stays; reducing treatment effectiveness; and raising both readmission rates and healthcare costs. An estimated 20–50% of patients are malnourished upon hospital admission. Additionally, about one-third of patients with adequate nutritional status at admission develop malnutrition during their hospital stay [3].
Intestinal failure
Intestinal failure (IF) is defined as the inability to absorb the minimum required amounts of macronutrients, micronutrients, minerals, and vitamins due to impaired intestinal function [4]. IF is a challenging and debilitating condition, characterized by its complexity, as illustrated by the following points:
a) it took nearly four decades, i.e., from 1981 to 2020, to reach a consensus on its definitions and classification;
b) its causes are varied and complex;
c) the functional classification recognizes three distinct types of IF; and
d) its pathophysiological classification identifies five primary mechanisms [5].
The three types of intestinal failure are acute (AIF), prolonged acute, and chronic (CIF). CIF is defined as a persistent reduction in gut function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous support (IVS) is required to maintain health and/or growth in a metabolically stable patient [6]. AIF, on the other hand, is characterized by a decrease in gut function that falls below the threshold needed for adequate absorption of macronutrients, water, and electrolytes, necessitating parenteral nutrition [7]. Prolonged acute IF is an uncommon clinical condition in which acute deficiency is accompanied by septic and other complications [6] and is associated with poor prognosis [8]. Oterdoom et al. [8] emphasized that survival after total parenteral nutrition lasting over 6 months has not been recorded and that the procedure is an indicator of poor prognosis as late as 1.5 years after its use. It was also found that approximately 58% to 87% of patients aged 75 and older died within 730 days after starting nutrition via gastrostomy, nasogastric tube (NGT) feeding, or PN; and those with non-malignant conditions who received NGT feeding or PN had a worse 2-year prognosis [9]. Since both CIF and prolonged acute IF are relatively uncommon in internal medicine wards, this article focuses on the specific characteristics and challenges associated with AIF.
It is also important to distinguish between AIF and acute gastrointestinal injury (AGI). The European Society of Intensive Care Medicine (ESICM) defines AGI as the malfunctioning of the gastrointestinal tract in critically ill patients due to their acute illness. AGI is categorized into four grades, ranging from mild dysfunction to life-threatening conditions [10]. As important as it is clinically, this condition is not the focus of this article. AIF, on the other hand, is defined by the European Society for Clinical Nutrition and Metabolism (ESPEN) based on its duration and reversibility and classified into the following three types:
Type I: acute, short-term, and usually self-limiting;
Type II: a prolonged acute condition, often in severely ill patients, requiring multidisciplinary intervention;
Type III: a chronic condition necessitating long-term nutritional support.
A comparison between the two aforementioned conditions is presented in Table I [11].
Table I
Comparison of key features of acute gastrointestinal injury and acute intestinal failure
As AIF is a more specific condition, defined by the need for artificial nutrition, the article focuses on the needs of patients suffering from this type of insufficiency. It should be noted, however, that patients with sepsis receiving enteral nutrition are likely to be underfed, due to their poor gastrointestinal tolerance to liquids and feeds. Such a condition is associated with the development of a progressively increasing energy debt, representing the difference between energy need and intake, strongly correlated with complications and/or reduced survival [12]. They are, however, hardly ever patients typical for internal medicine wards.
Indirect calorimetry in gastrointestinal conditions leading to intestinal failure
Compared to other conditions, literature data on the application of IC in gastrointestinal diseases is very limited. For instance, although the study by Rattanachaiwong and Singer [13] was conducted on a highly diverse group of patients – including those after surgery, with cancer, the geriatric population, individuals with diabetes, sepsis, acute illnesses, multiple traumas, brain injuries, burns, renal failure, and obesity – the only gastrointestinal-related disease included was liver cirrhosis. The group with gastrointestinal failure, especially those hospitalized in internal medicine wards, was not sufficiently studied.
A group of gastrointestinal diseases that can lead to failure is inflammatory bowel diseases (IBD). Symptoms such as abdominal pain, nausea, rectal bleeding, and diarrhea can cause loss of appetite, reduced food intake, and – ultimately – deterioration of the nutritional status of the patient. Hence, dietary management in IBD focuses on maximizing the nutritional status, maintaining adequate food intake, and avoiding products that can exacerbate the symptoms. Nutritional interventions, e.g., enteral or parenteral nutrition, are important alternatives when oral feeding is impossible. It is thus crucial to identify those IBD patients who may require nutritional intervention, as optimizing the nutritional status is crucial in preventing long-term health consequences of malnutrition [14].
In critically ill patients, a variable degree of gastrointestinal failure is often observed, leading to enteral feeding intolerance in about 60% of cases. This condition is often evolutionary and usually resolves completely after 5–7 days. However, even during the resolution phase, several days of undernutrition are not uncommon, contributing to acute malnutrition and the resulting harmful consequences. Tolerance of partial or complete fasting varies depending on the patient’s nutritional status at admission, the presence of sarcopenia, and age. Additionally, partial intestinal failure can complicate the assessment of intestinal functional capacity, particularly in patients with short bowel syndrome. Hyperphagia can partially cover the nutritional needs, reducing the requirement for parenteral nutrition. Furthermore, frequent interruptions of enteral feeding often become problematic, making it difficult to deliver sufficient amounts of energy and proteins. In general, certain clinical situations pose a risk of malnutrition and may indicate the need for supplemental or total parenteral nutrition.
Clinical criteria have been proposed to identify situations where enteral nutrition is likely to fail. According to these, the introduction of parenteral nutrition or supplementary parenteral nutrition (SPN) should be based on an increasing deficit with a cumulative energy balance of –4000 kcal to -6000 kcal, or a cumulative protein deficit exceeding –300 g or remaining below 75%. It is important not to postpone the intervention until the indicated limits are exceeded, as such situations are associated with irreversible clinical consequences. In the case of diarrhea related to enteral feeding, it is recommended that the feeding dose should be reduced by 50% for a few days [2].
Another group of gastrointestinal disorders where nutritional intervention may be required is liver cirrhosis. Malnutrition is reported in 50 to 100% of patients with decompensated cirrhosis and in about 20% of patients with compensated cirrhosis [15]. This is the result of several factors:
a) Inadequate intake: reduced dietary intake can be associated with symptoms such as anorexia, nausea, cognitive changes related to hepatic encephalopathy, and abdominal bloating caused by ascites. A sodium-restricted diet and alcohol consumption can also contribute to reduced intake.
b) Malabsorption: poor absorption and abnormal digestion of nutrients can result from altered regulation of bile salt levels, bacterial overgrowth, altered gut motility, intestinal inflammation, and increased intestinal permeability.
c) Accelerated cachexia: the body utilizes fuels other than glucose (i.e., protein and lipids). Decreased urea synthesis and protein production in the liver lead to a general loss of protein, reduced intestinal protein absorption, and increased urinary nitrogen excretion.
d) Lack of physical activity: this can contribute to reduced muscle mass and the development of hepatic encephalopathy.
Additionally, determining the caloric needs based on factors such as body weight and/or its loss in cirrhotic patients is challenging and may prove less useful due to weight fluctuations related to fluid retention and diuretic treatment [15], particularly in the case of patients with decompensated cirrhosis.
Moreover, glycogen reserves in the liver decrease and can become depleted in patients with cirrhosis, leading to increased mobilization and utilization of fats and proteins as energy substrates. Therefore, the value of the respiratory quotient (RQ) – which is one of the parameters measured using indirect calorimetry – approaching 0.7 suggests the worsening of liver function, reflecting impaired glycogen synthesis and reduced hepatic glycogen reserves [13].
Indirect calorimetry – general characteristics of the method
A certain subpopulation of patients with gastrointestinal dysfunction requires treatment with total or supplemental parenteral nutrition. Currently, as far as methodology is concerned, the gold standard for determining energy expenditure is indirect calorimetry [16]. This method allows for individualized nutritional treatment based on measurements performed directly on the patient to be treated, rather than relying solely on mathematical methods such as equations or body weight calculations. Hence, IC is virtually the only method that can be used to establish the patient’s energy goals, as none of the existing predictive equations estimates energy expenditure accurately enough [17]. This approach helps reduce the risk of life-threatening complications associated with nutrient dosing, such as refeeding syndrome, parenteral nutrition-associated liver disease (PNALD), and hyperglycemia [18]. However, although clearly superior to predictive equations, IC has its own serious issues and limitations.
Indirect calorimetry is a relatively new non-invasive method for measuring resting energy expenditure (REE). It does not require active participation from the patient, the performance of complex tasks, or any invasive procedures such as blood draws, making it an optimal measurement method in its intended clinical contexts. This enhances the quality of patient care and can potentially reduce mortality in hospitalized patients. IC is based on non-invasive measurement of the volumes of inhaled and exhaled oxygen (O2) and carbon dioxide (CO2). The values of these parameters are obtained through measurements of gas dynamics and physics, inhalation, and the concentration and volume of exhaled gases. The fractions of O2 and CO2 gases are measured by determining the volume of exhaled gas using gas sensors and then converting these values into the volume of oxygen consumed (VO2) and carbon dioxide expelled (VCO2), expressed in milliliters per minute. These data are then used to calculate REE, expressed in kilocalories (kcal) or kilojoules (kJ) per day [19].
Monitoring the physiological and metabolic state of the patient, their response to illness, and their nutritional needs are important clinical tasks. Assessing REE is essential for ensuring proper daily nutritional requirements to avoid hyper- or hypocaloric and hyper/hypoproteic feeding, which lead to increased morbidity and mortality, particularly among critically ill patients [19]. The indications for indirect calorimetry, i.e., situations where it has the greatest diagnostic and clinical value, can be divided into the following three categories:
a) clinical conditions that significantly alter REE;
b) patients not responding to presumed adequate nutritional support;
c) situations requiring individualized and optimized nutritional support in intensive care units (ICUs) [19].
Recent advances in gas exchange measurements, such as continuous, real-time assessment of VO2 and VCO2 at the patient’s bedside and, if necessary, around-the-clock measurement, increase the chances of optimal nutritional adjustment. However, like any other method, indirect calorimetry has its disadvantages. It is thus crucial to understand its methodological foundations as well as theoretical and practical limitations. To avoid falsification of measurement results, the type of assessment being performed must also be considered, i.e., whether the patient is undergoing mechanical ventilation, breathing spontaneously, or exercising [19]. Moreover, despite the relatively long time that has passed since the development of the IC technology, the cost of the equipment remains high.
Due to the impossibility to accurately estimate resting metabolic rate (RMR)/REE using predictive equations and the fact that the current alternative consists of only one method, i.e., indirect calorimetry, the aim of this article is to present a critical review of literature data regarding the potential application of indirect calorimetry as a method for measuring REE in AIF, particularly in the context of internal medicine wards. The purpose of this study is to decide whether IC is a viable procedure especially in the context of AIF, taking into account both its accuracy and the fact that no alternative method exists at this point.
Methods
The study was conducted as a critical review of articles published in the period from 1997 to 2024 in the following databases: PubMed/Medline, EMBASE (Elsevier), Scopus, Web of Science, Google Scholar, and UpToDate. The review mainly focused on the current scientific consensus regarding the applicability of indirect calorimetry as a method for measuring REE in the context of AIF.
Results and discussion
Technical and methodological difficulties of indirect calorimetry and their significance in AIF
As mentioned, indirect calorimetry is widely recognized as a relatively simple, non-invasive diagnostic test that provides valuable information regarding caloric requirements. However, despite its straightforward procedure, the literature indicates several technical and methodological challenges that can impact its usefulness and the reliability of measurements.
The procedure for performing IC measurements involves several assumptions concerning the patient’s cooperation that may be difficult to meet for objective reasons stemming from their medical condition. Thus, the following procedure is followed when IC measurements are performed: patients undergoing indirect calorimetry should remain in a supine position for at least 30 min before the test to ensure that physical activity does not influence their REE. Additionally, there should be at least a 2-hour gap since the last meal (preferably, the test should be performed in the morning on an empty stomach) to avoid the thermogenesis associated with digestion, which can also skew the results. Furthermore, involuntary or deliberate movements during the test can significantly elevate the measurement results. Moreover, to avoid unreliable results, the environment in which calorimetry is conducted should be quiet and thermally neutral. In the context of conducting tests in general internal medicine wards, oxygen supplementation should not be used, in order to obtain the most accurate results. In addition, it is crucial to ensure the highest possible seal of the measurement hood to avoid leaks [20].
In this context, patients with AIF are particularly problematic as they are often characterized by unstable body temperature and variable pH levels due to CO2 accumulation or other causes, which can lead to incorrect calorimetry results. Therefore, periodic retesting or conducting measurements after the patient’s condition has stabilized is recommended. Obese patients are another specific case as they show significant differences in energy expenditure (EE) due to underlying diseases, varying body composition, and differing degrees of malnutrition. Body composition is a crucial modifier of EE since lean body mass constitutes the majority of EE [12].
The importance of repeated measurements in the context of monitoring nutritional needs
The ability to perform repeated measurements is crucial in cases of diseases with a dynamic course. In this context, one of the key features of indirect calorimetry, i.e., the possibility to obtain immediate results, is extremely useful. Measurements obtained in the early phase of a critical illness should be repeated within the next 24–48 h to capture the dynamic evolution of the disease. With other measurement methods, such repetition would be impossible due to the long data analysis time or unnecessary due to the unchanging nature of the data despite changes in the disease course. In contrast, the results of IC measurements are available immediately after the test, allowing for quick monitoring of changes [12].
Calorimetric measurements show significant changes with the progression of the disease, which can indirectly indicate its progression or remission. In the early phase of an acute illness, endogenous energy reserves cover most of the energy needs, while exogenous energy supplementation has only a marginal impact. During this period, additional nutrition may lead to a significant excess of energy intake and result in relative overfeeding, associated with harmful consequences [12]. For this reason, the use of indirect calorimetry during this particular period could help avoid overfeeding patients in the initial stages of the disease and detect the need for nutritional intervention at the appropriate time, provided that IC is used multiple times throughout the disease course.
Changes in feeding methods should be introduced no more than twice a week, based on trends in indirect calorimetry, urinary nitrogen levels, and clinical examination results [16]. Regarding the frequency of calorimetric assessments, authors indicate [2] that in cases of acute illnesses requiring ICU admission, energy expenditure may increase due to physiological changes such as fever, pain, muscle spasms, or elevated stress hormone levels. In this light, advances in ICU therapy over the past 20 years have been associated with a reduction in the amplitude of hypermetabolism, which persists – in a less pronounced form – for 1–2 weeks. Measurements should be repeated due to the fact that EE changes with evolving clinical conditions. In practice, the first measurement should occur between the third and fifth day of admission and should be repeated at least once a week.
The necessity for nutritional intervention is also connected with surgical procedures. Malnutrition results in increased morbidity through poor wound healing or higher post-operative infection rates. No universally accepted method exists to determine the difference between patients with mild and severe surgical stress. Interventions such as more effective pain control, temperature regulation, and anxiety management or optimization of ventilation can reduce measured caloric expenditure in patients under high stress after surgery, trauma, or burns. Such relationships as well as the difficulty in determining caloric needs can be encountered not only in surgical wards but also in internal medicine wards, where patients with varying degrees of gastrointestinal failure are admitted. Therefore, indirect calorimetry remains the most accurate method for estimating a patient’s caloric intake [1]. However, despite the undeniable usefulness of IC, its disadvantages include the long preparation time of the equipment, the high cost of purchase, the need for calibration, and the necessity to perform disinfection of the equipment [18], which are particularly relevant for staff of wards where the number of patients requiring parenteral nutrition is relatively low.
For surgical patients, the adequacy of their current nutritional support is best assessed based on the clinical course of the illness and wound healing. Combined with daily clinical assessment, analysis of total body mass trends, and the results of measurements and laboratory tests, indirect calorimetry can help evaluate the adequacy of nutritional support. The calculated energy balance can make it possible to determine whether it is in equilibrium, in deficit, or in excess. A cumulative energy deficit of 6,000 kcal is considered a critical threshold, as it is associated with poorer outcomes, such as longer hospital stays and increased mortality [2]. This is yet another example of a clinical issue necessitating the performance of multiple measurements to accurately determine the caloric needs of patients [16].
Determining REE – indirect calorimetry vs. predictive equations
The assessment of caloric demand in gastrointestinal failure, especially AIF, plays a very important diagnostic role. In recent years, it has become clear that both overnutrition and undernutrition can be harmful, which is why optimizing nutritional support tailored to the specific needs of patients is an extremely important task.
Indirect calorimetry was commercialized for medical use in the 1980s, but the complexity and high cost of the equipment have limited its applications in routine clinical practice over the past four decades. Despite such limitations, IC has become essential, for instance, in pediatric intensive care units (PICUs) [12]. The concept of REE is based on the assumption that the patient’s energy goal should match their energy expenditure. Indirect calorimetry is currently the only practical clinical method that enables the measurement of EE in hospitalized and ambulatory patients, making it possible for nutritional therapy/support to be tailored to their specific needs [21]. However, the widespread use of the method is hindered by the fact that the calorimeters currently available on the market are still too complex and expensive to be easily accessible in general hospitals [12].
To illustrate the point, among critically ill adults, although indirect calorimetry was indicated in half of the patients in IC units – due to lack of access to the equipment and the necessary skills of the personnel – measurements could only be taken in rare instances, indicating great demand for this type of assessment. This also exemplifies how the development of modern medicine focuses on diagnostic and treatment options becoming “tailored to the patient” [12].
Currently, the only alternative to IC is the aforementioned predictive equations. A number of predictive equations based on simple anthropometric measures have been proposed for clinical use. Some of them take into account gender, age, and minute ventilation as substitutes for EE measurement. Unfortunately, since REE cannot be accurately predicted using this method, indirect calorimetry has been proposed as a reliable means of assessment of the parameter in question. Numerous studies [21–25] have shown that – compared to IC – predictive equations are not sufficiently accurate, although some authors do in fact believe that indirect calorimetry is not a superior method [26, 27].
To illustrate the difficulties inherent in establishing nutritional needs of patients in serious conditions using either method, some examples are needed. For patients with acute vs. chronic diseases, the issue lies in their different metabolic characteristics, reflected in highly variable EE values. For instance, patients with chronic obstructive pulmonary disease (COPD) and cancer patients often exhibit elevated energy expenditure (EE), which can be easily underestimated when using predictive equations. Furthermore, critically ill patients with trauma or sepsis show dynamic changes in EE during different phases of their illness [12].
The ESPEN (European Society for Clinical Nutrition and Metabolism) recommendations – which suggest a dose of 20 kcal/kg/day as an equivalent of REE – and the Ireton-Jones predictive equation provide the best approximations of energy needs in the population of patients with intestinal failure. However, in the case of patients on home parenteral nutrition, feeding based on the results provided by these methods may result in a significant negative or positive energy balance. For this reason, indirect calorimetry is the preferred method for assessing REE [18, 21].
Due to the great diversity of both pathologies and treatment methods, there is no single predictive equation that is accurate for critical illness. McClave and Omer [28] reported that compared to measurements performed using indirect calorimetry, estimating energy expenditure based on predictive equations was inaccurate in almost 70% of critically ill patients, either overestimated or underestimated, which is a clinically unacceptable proportion. Moreover, studies have shown that predictive equations provided acceptable estimates for only half of the population of critically ill patients. In the case of indirect calorimetry, repeated REE measurements performed during the illness showed changing patterns, suggesting disease progression or improvement [13]. Moreover, in populations with extreme body mass index values (BMI < 16 kg/m2 and BMI > 40 kg/m2), IC was also the method of choice over predictive equations [18].
In general, studies [19, 22–24] have shown that it is very difficult to accurately estimate a patient’s RMR/REE using predictive equations. For this reason, indirect calorimetry constitutes an important tool for clinicians working with nutrition specialists and dietitians, which makes it possible to adequately determine the energy needs of patients with specific pathological conditions.
In general, IC is a method that allows estimated needs to be matched to actual energy expenditure, which is crucial in the management of critically ill patients, especially those who are obese or malnourished, and are at significant risk of damage to organs, including those comprising the gastrointestinal tract, due to being subjected to multiple medications and diagnostic-therapeutic procedures that significantly alter their metabolic state. The repeated use of indirect calorimetry in such clinical situations is necessary to determine treatment effectiveness, avoid harmful overfeeding or underfeeding, and reduce clinical morbidity and mortality associated with nutrition [21]. For this reason, the proper implementation of a multidisciplinary metabolic monitoring protocol as part of the overall nutritional assessment of the patient can contribute to both improved treatment outcomes and increased cost-effectiveness of patient care [29].
Nonetheless, significant drawbacks of IC include the high cost of the equipment and various methodological challenges that complicate its application. Furthermore, the limited accessibility of this method contributes to the relative inexperience of nutritional teams in its implementation, both within individual wards and across entire hospitals. This issue is especially relevant in wards where only a few patients require specialized nutritional management. Hence, it can be concluded that although the use of IC as a method of REE measurement in AIF patients is not without its merits, its usefulness is hampered by several serious methodological, practical, and financial issues that may be difficult to overcome.
Conclusions
Indirect calorimetry is a useful method for measuring REE, enabling the adjustment of nutrition for patients receiving oral, enteral, or parenteral feeding in accordance with their needs and capabilities. It is a relatively easy-to-apply method, well tolerated by patients, tailored for repeated measurements. However, the quality of measurements is influenced by many diverse and difficult-to-control factors. IC can be used to monitor the course of the disease and adjust the need for nutritional intervention based on the patient’s clinical situation, which is exceptionally important in predicting the course of AIF. However, the high cost of the equipment and various methodological issues that complicate the use of IC are its important disadvantages. Additionally, the limited availability of the method results in the relative inexperience of nutritional teams regarding its use, both in individual wards and entire hospitals. This is particularly important in wards where only a small number of patients require specialized nutritional management.
Moreover, the performed critical review of the literature also indicates that the diagnostic usefulness of indirect calorimetry requires further research, especially concerning AIF. As the available studies mainly focus on surgical and ICU settings, there is a pronounced lack of data on diseases treated by internal medicine. This presents a promising opportunity to study the topic of the applicability of indirect calorimetry specifically on internal medicine wards. Given that – in the context of general internal medicine wards – the assessment of patients in terms of their need for nutritional intervention is a sporadic task, it is reasonable to conclude that, given its current cost and various disadvantages, indirect calorimetry can be dispensed with.
The study has certain notable limitations. It primarily draws conclusions from a critical literature review without extensive clinical trials specifically in AIF patients in internal medicine wards. As a result, the findings may not fully capture the practical challenges and nuances of IC application across all patient demographics. Additionally, IC requires stringent conditions for accuracy – such as stable patient condition, movement restrictions, and thermally neutral environments – which can be challenging to maintain in a typical internal medicine setting, especially for critically ill patients. High equipment costs and the need for calibration and specialized personnel also present significant barriers to its routine use, limiting accessibility, particularly in resource-constrained settings. Combined with the de facto lack of alternative solutions, this makes it difficult to make accurate generalizations as to the actual usefulness of IC, which therefore often has to be decided on a case-by-case basis.
Moreover, the rapid metabolic fluctuations in AIF patients mean that single-point REE measurements may not fully represent their ongoing nutritional needs. While IC offers accuracy advantages over predictive equations, frequent retesting would be ideal to capture these changes, though this may not always be feasible due to practical constraints. This study also does not extensively compare IC with newer predictive models, highlighting the need for further research to confirm its advantages over alternative methods and to establish protocols that address these practical and economic challenges.
