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Applications of indirect calorimetry.

Indirect calorimetry should be considered a useful and practical adjunctive technology that can assist in the assessment and management of critically ill patients. Examples of applications of indirect calorimetry include nutritional assessments of metabolic status, evaluation of the oxygen cost of breathing during mechanical ventilatory support, and measurement of oxygen transport for the purpose of evaluating patient tolerance of therapies and effectiveness of therapeutic interventions. Multidisciplinary teamwork can make use of this technology to develop greater understanding of the metabolic needs of critically ill patients and to test interventions that advance evidence-based clinical practice in the care of these vulnerable patients.

Calorimetry, Indirect↗

Indirect calorimetry.

Indirect calorimetry is a method which allows the non-invasive measurement of energy expenditure and substrate utilization in humans. The procedure is described and the main equations to calculate energy expenditure and substrate utilization are presented. The limitations of the method include physiological effects, such as hyperventilation, and the influence of metabolic processes such as gluconeogenesis, ketogenesis and lipogenesis. The general principle is that intermediate processes do not influence overall conclusions, provided that the intermediate substrates which are formed do not accumulate within the body or are not excreted. Continuous measurements of metabolic rate and respiratory quotient using the ventilated hood system have been carried out during the last 5 years to study carbohydrate and lipid metabolism in lean subjects, in obese and diabetic patients. By using the euglycaemic insulin clamp technique or by giving oral glucose loads, it has been shown that the main effect of insulin on carbohydrate metabolism is to stimulate glucose storage. By raising plasma free fatty acid levels with a neutral fat infusion in lean subjects, both glucose oxidation and glucose storage were imparied during euglycaemic insulin clamps. Glucose storage was found to be markedly impaired in non-diabetic obese patients, during euglycaemic insulin clamps in the presence of elevated lipid oxidation. In obese diabetic patients, the impairment in glucose storage was more pronounced than in non-diabetic obese; this defect was particularly marked during euglycaemic insulin clamps, but it was also present after an oral glucose load. It is concluded that impairment of glucose storage is a major defect of glucose utilization in type II diabetes.

Blood Glucose↗

[Study of metabolism in critically ill patients by indirect calorimetry].

Indirect calorimetry was performed in 48 postsurgical critically ill patients including those with multiple organ failure. The patients were divided into two groups, organ failure group (OF group) and postsurgical control group (C group), according to the presence of postsurgical organ failure and severe infection. The following results were obtained. The ratio of energy expenditure to basal energy expenditure, reflecting a degree of hypermetabolism, was 1.44 +/- 0.38 in OF group and 1.26 +/- 0.23 in C group respectively. The change in respiratory quotient by caloric intake was greater in OF group than in C group, indicating that it is more important to maintain an adequate intake for the prevention of increased respiratory work and excess lipogenesis in OF group. When nitrogen intake as amino acids was sufficient (0.1-0.2 g/kg/day), nitrogen balance could be maintained around 0 by a caloric intake being equal to measured energy expenditure. A positive correlation was observed between arterial ketone body ratio reflecting energy charge in hepatocytes and respiratory quotient, indicating that in patients with impaired mitochondrial function in hepatocytes as shown by a decrease in ketone body ratio, glucose cannot be utilized effectively. These results let us conclude that calorimetry is indispensable in the management of critically ill patients and that adequate energy intake should be cautiously determined according to the calorimetry.

Calorimetry↗

Indirect calorimetry.

Indirect calorimetry can be a useful tool to define nutritional status, determine nutritional requirements, and assess response to nutritional interventions. Measurements of oxygen consumption and carbon dioxide production may be used to determine cardiac output and work of breathing, and estimate the components of minute ventilation. An understanding of the potential technical and physiological pitfalls is necessary to obtain meaningful and useful information.

Acid-Base Equilibrium↗

The theoretical bases of indirect calorimetry: a review.

Indirect calorimetry is the method by which the type and rate of substrate utilization, and energy metabolism are estimated in vivo starting from gas exchange measurements. This technique provides unique information, is noninvasive, and can be advantageously combined with other experimental methods to investigate numerous aspects of nutrient assimilation, thermogenesis, the energetics of physical exercise, and the pathogenesis of metabolic diseases. Since its use as a research tool in metabolism is growing, the theoretical bases of indirect calorimetry are here reviewed in a detailed and orderly fashion. Special cases, such as the occurrence of net lipid synthesis or gluconeogenesis, are formally considered with derivation of explicit stoichiometric equations. The limitations of indirect calorimetry, both theoretical and technical, are discussed in the context of circumstances of clinical interest in metabolism.

Adenosine Triphosphate↗

Using direct calorimetry to test the accuracy of indirect calorimetry in an ectotherm.

We previously demonstrated that the relationship between respiratory gas exchange and metabolic heat production is unexpectedly variable and that conventional approaches to estimating energy expenditure by indirect calorimetry can incorporate large errors. Prior studies, however, comparing direct and indirect calorimetry of animals focused only on endothermic organisms. Given that endothermy and ectothermy represent a fundamental dichotomy of animal energetics, in this analysis we explore how these contrasting physiologies correlate with the relationship between heat production and respiratory gas exchange. Simultaneous indirect and direct calorimetry in an ectotherm, the ball python (Python regius Shaw), revealed that the relationships between gas exchange and heat production were within 1% of those expected when analyses using indirect calorimetry were based on the assumption that the fasting animal catabolized only protein. This accuracy of indirect calorimetry contrasts sharply with our previous conclusions for three species of birds and mammals.

Animals↗

Indirect calorimetry: technical aspects.

Indirect calorimetry measures oxygen consumption and carbon dioxide production to calculate resting energy expenditure and respiratory quotient. The respiratory quotient can be determined from indirect calorimetry to determine substrate utilization and used to alter the patient's nutrition support regimen. All but one indirect calorimeter manufactured in the United States are open-circuit rather than closed-circuit systems.

Calorimetry, Indirect↗

Indirect calorimetry and nutritional problems in clinical practice.

Indirect calorimetry is a simple and affordable tool for measuring energy expenditure and for quantifying the utilization of macronutrients. Its use is becoming increasingly widespread, but it is necessary to know its methodological features and its theoretical and practical limitations. Indirect calorimetry measures the rate of resting energy expenditure (REE), the major component of the total daily energy expenditure. Thus, indirect calorimetry reliably estimates the individual energy needs. Coupling the measurement of body composition to that of REE expands the diagnostic potential of indirect calorimetry. Once the lean and fat compartments have been measured, it is possible to establish on the basis of REE whether an individual is hyper- or hypometabolic. The evaluation of substrate oxidation by indirect calorimetry is subject to more severe theoretical constraints, because certain metabolic assumptions must be made. The clinical applications are practically unlimited. In the critically ill, a major goal is to maintain energy balance during the hypermetabolic response following trauma. The REE measurement is valuable from the diagnostic standpoint, because it recognizes discrepancies from the expected time-course of hypermetabolism, for example signaling a potentially catastrophic hypometabolic response. REE is also indispensable for providing correct nutritional support because both hyper- and undernutrition lead to increased mortality. In young or elderly patients, in whom energy consumption may be very different from that predicted from equations based on anthropometric measures, indirect calorimetry is particularly useful.

Aging↗

Automated VO2max calibrator for open-circuit indirect calorimetry systems.

The complete calibration of indirect calorimetry systems involves simultaneous checks of gas analyzers, volume device, and software, and this requires a machine that can mimic accurately and precisely the ventilation and expired gases of an athlete. While previous calibrators have been built successfully, none have matched the ventilatory flows produced by athletes during high intensity exercise. A calibrator able to simulate high aerobic power (VO2max calibrator) was fabricated and tested against conventional indirect calorimetry systems that use chain-compensated gasometers to measure expired volume (VE systems) and calibrated electronic gas analyzers. The calibrator was also checked against a system that measures inspired volume (VI system) with a turbine ventilometer. The pooled data from both VE and VI systems for predicted VO2 ranging from 2.9 to 7.9 L.min-1 and ventilation ranging from 89 to 246 L.min-1 how that the absolute accuracy (bias) of values measured by conventional indirect calorimetry systems compared with those predicted by the calibrator was excellent. The bias was < 35 mL.min-1 for VO2 and carbon dioxide production, < 0.50 L.min-1 for ventilator (VE BTPS), -0.02% absolute for the percentage of expired O2 and +0.02% absolute for the percentage of expired CO2. Overall, the precision of the measured VO2, VCO2, and VE BTPS was approximately 1%. This VO2max calibrator is a versatile device that can be used for routine calibration of most indirect calorimetry systems that assess the ventilation and aerobic power of athletes.

Blood Gas Analysis↗

Indirect calorimetry: methodological and interpretative problems.

The technique of indirect calorimetry is now widely used to examine rates of energy production and substrate oxidation in humans. Although the basic principles of indirect calorimetry are well established, it is important to recognize that there are several potential pitfalls in the methodology and data interpretation that must be appreciated to properly understand and apply the results derived from this technique. In particular, one must recognize that the fundamental measurement provided by indirect calorimetry is the net disappearance rate of a substrate regardless of the metabolic interconversions that the substrate may undergo before its disappearance from its metabolic pool. Under most circumstances, direct oxidation represents the major route by which a substrate disappears from its metabolic pool, and the two terms are often used interchangeably. However, under conditions when rates of gluconeogenesis, ketogenesis, or lipogenesis are elevated, the presumed equivalence between oxidation and disappearance may no longer apply, even though the actual measurements derived from indirect calorimetry remain valid. When indirect calorimetry is combined with other in vivo metabolic techniques (e.g., the insulin clamp or radioisotope turnover methods) it can provide a powerful tool for noninvasively examining complex metabolic processes.

Body Temperature Regulation↗

Some mathematical and technical issues in the measurement and interpretation of open-circuit indirect calorimetry in small animals.

Indirect calorimetry is increasingly used to investigate why compounds or genetic manipulations affect body weight or composition in small animals. This review introduces the principles of indirect (primarily open-circuit) calorimetry and explains some common misunderstandings. It is not widely understood that in open-circuit systems in which carbon dioxide (CO2) is not removed from the air leaving the respiratory chamber, measurement of airflow out of the chamber and its oxygen (O2) content paradoxically allows a more reliable estimate of energy expenditure (EE) than of O2 consumption. If the CO2 content of the exiting air is also measured, both O2 consumption and CO2 production, and hence respiratory quotient (RQ), can be calculated. Respiratory quotient coupled with nitrogen excretion allows the calculation of the relative combustion of the macronutrients only if measurements are over a period where interconversions of macronutrients that alter their pool sizes can be ignored. Changes in rates of O2 consumption and CO2 production are not instantly reflected in changes in the concentrations of O2 and CO2 in the air leaving the respiratory chamber. Consequently, unless air-flow is high and chamber size is small, or rates of change of O2 and CO2 concentrations are included in the calculations, maxima and minima are underestimated and will appear later than their real times. It is widely appreciated that bigger animals with more body tissue will expend more energy than smaller animals. A major issue is how to compare animals correcting for such differences in body size. Comparison of the EE or O2 consumption per gram body weight of lean and obese animals is misleading because tissues vary in their energy requirements or in how they influence EE in other ways. Moreover, the contribution of fat to EE is lower than that of lean tissue. Use of metabolic mass for normalisation, based on interspecific scaling exponents (0.75 or 0.66), is similarly flawed. It is best to use analysis of covariance to determine the relationship of EE to body mass or fat-free mass within each group, and then test whether this relationship differs between groups.

Animals↗

Percent relative cumulative frequency analysis in indirect calorimetry: application to studies of transgenic mice.

Indirect calorimetry is commonly used in research and clinical settings to assess characteristics of energy expenditure. Respiration chambers in indirect calorimetry allow measurements over long periods of time (e.g., hours to days) and thus the collection of large sets of data. Current methods of data analysis usually involve the extraction of only a selected small proportion of data, most commonly the data that reflects resting metabolic rate. Here, we describe a simple quantitative approach for the analysis of large data sets that is capable of detecting small differences in energy metabolism. We refer to it as the percent relative cumulative frequency (PRCF) approach and have applied it to the study of uncoupling protein-1 (UCP1) deficient and control mice. The approach involves sorting data in ascending order, calculating their cumulative frequency, and expressing the frequencies in the form of percentile curves. Results demonstrate the sensitivity of the PRCF approach for analyses of oxygen consumption (.VO2) as well as respiratory exchange ratio data. Statistical comparisons of PRCF curves are based on the 50th percentile values and curve slopes (H values). The application of the PRCF approach revealed that energy expenditure in UCP1-deficient mice housed and studied at room temperature (24 degrees C) is on average 10% lower (p < 0.0001) than in littermate controls. The gradual acclimation of mice to 12 degrees C caused a near-doubling of .VO2 in both UCP1-deficient and control mice. At this lower environmental temperature, there were no differences in .VO2 between groups. The latter is likely due to augmented shivering thermogenesis in UCP1-deficient mice compared with controls. With the increased availability of murine models of metabolic disease, indirect calorimetry is increasingly used, and the PRCF approach provides a novel and powerful means for data analysis.

Acclimatization↗

Circulatory indirect calorimetry in the critically ill.

Circulatory indirect calorimetry (CIC) is a potentially useful method to assess the energy requirements of critically ill patients. Unlike respiratory indirect calorimetry (RIC), which measures oxygen utilization from inhaled and exhaled gases, CIC measures oxygen utilization from arterial and mixed venous blood. Twenty-two measurements in eight critically ill patients comparing RIC, CIC, and commonly used estimates of energy expenditure were performed. A significant correlation between RIC and CIC was identified (r = 0.831, p less than 0.001). Poor correlation was noted with either method and the commonly used estimates. CIC may be a useful tool in estimating energy expenditures in the critically ill.

Aged↗

Measured pulmonary oxygen consumption: difference between systemic oxygen uptake measured by the reverse Fick method and indirect calorimetry in cardiac surgery.

Measurement of oxygen uptake by indirect calorimetry was compared with the reverse Fick method in a series of patients undergoing cardiac surgery. Oxygen uptake measurements for indirect calorimetry were made using a calibrated measurement system utilizing the Haldane transformation in a simple semiclosed breathing system based upon a modified Bain circuit. Pulmonary blood flow for the reverse Fick method was measured using bolus thermodilution. The results were (mean [standard deviation]): indirect calorimetry 167[26] ml.min(-1), and reverse Fick 148[27] ml.min(-1). Indirect calorimetry overestimated the reverse Fick value by 11.3% (p < 0.001). These results are consistent with the findings of previous studies in similar patient groups and are explained by lung tissue oxygen consumption.

Aged↗

Indirect calorimetry: relevance to patient outcome.

Indirect calorimetry provides an important adjunctive monitor for the provision of nutrition support in the critically ill patient. Accuracy in determining caloric requirements may serve to optimize benefit from nutrition therapy and improve patient outcome. A number of strategies in nutrition management in the intensive care setting (eg, dosing of enteral nutrition, monitoring cumulative caloric balance, and deliberate but "permissive" underfeeding) necessitate the determination of a fairly specific goal for caloric provision. Inaccuracy leading to inappropriate under- or overfeeding may generate additional morbidity and adverse clinical consequences for patients already at high risk from hypermetabolic stress response to injury.

Calorimetry, Indirect↗

Reducing the time period of steady state does not affect the accuracy of energy expenditure measurements by indirect calorimetry.

Achievement of steady state during indirect calorimetry measurements of resting energy expenditure (REE) is necessary to reduce error and ensure accuracy in the measurement. Steady state is often defined as 5 consecutive min (5-min SS) during which oxygen consumption and carbon dioxide production vary by +/-10%. These criteria, however, are stringent and often difficult to satisfy. This study aimed to assess whether reducing the time period for steady state (4-min SS or 3-min SS) produced measurements of REE that were significantly different from 5-min SS. REE was measured with the use of open-circuit indirect calorimetry in 39 subjects, of whom only 21 (54%) met the 5-min SS criteria. In these 21 subjects, median biases in REE between 5-min SS and 4-min SS and between 5-min SS and 3-min SS were 0.1 and 0.01%, respectively. For individuals, 4-min SS measured REE within a clinically acceptable range of +/-2% of 5-min SS, whereas 3-min SS measured REE within a range of -2-3% of 5-min SS. Harris-Benedict prediction equations estimated REE for individuals within +/-20-30% of 5-min SS. Reducing the time period of steady state to 4 min produced measurements of REE for individuals that were within clinically acceptable, predetermined limits. The limits of agreement for 3-min SS fell outside the predefined limits of +/-2%; however, both 4-min SS and 3-min SS criteria greatly increased the proportion of subjects who satisfied steady state within smaller limits than would be achieved if relying on prediction equations.

Aged↗

Methodological evaluation of indirect calorimetry data in lean and obese rats.

1. The applicability of current indirect calorimetry formulae to the study of energy and substrate balances on obese rats has been evaluated. The energy consumption of series of 60-day rats of Wistar, lean and obese Zucker stock were studied by means of direct and indirect calorimetry, and by establishing their energy balance through measurement of food intake and retention. Calorimetric studies encompassed a 24 h period, with gas and heat output measurements every 2 or 5 min, respectively, for direct and indirect calorimetry. 2. The analysis of fat composition (diet, whole rat, and synthesized and oxidized fat) showed only small variations that had only a limited effect on the overall energy equation parameters. 3. A gap in the nitrogen balance, which represents a urinary N excretion lower than the actual protein oxidized, resulted in significant deviations in the estimation of carbohydrate and lipid oxidized when using the equations currently available for indirect calorimetry. 4. Analysis of the amino acid composition of diet and rat protein as well as of the portion actually oxidized, and correcting for the nitrogen gap allowed the establishment of a set of equations that gave better coincidence of the calculated data with the measured substrate balance. 5. The measured heat output of all rats was lower than the estimated values calculated by means of either indirect calorimetry of direct energy balance measurement; the difference corresponded to the energy lost in water evaporation, and was in the range of one-fifth of total energy produced in the three rat stocks. 6. Wistar rats showed a biphasic circadian rhythm of substrate utilization, with alternate lipid synthesis/degradation that reversed that of carbohydrate, concordant with nocturnal feeding habits. Zucker rats did not show this rhythm; obese rats synthesized large amounts of fat during most of the light period, consuming fat at the end of the dark period, which suggests more diurnal feeding habits. Lean Zucker rats showed a similar, but less marked pattern. 7. The results obtained indicate that lean and obese rats can be studied using the same indirect calorimetry formulae provided that there is an adequate measure of protein oxidation and the composition of diet does not differ.

Amino Acids↗

Indirect calorimetry as a guide to caloric replacement during total parenteral nutrition.

Fifty patients were studied by indirect calorimetry to assess caloric needs. Seventeen patients received total parenteral nutrition (TPN) in a fixed dose of 45 +/- 3 kcal/kg. Thirty-three patients were studied after acute injury. Indirect calorimetry and the basal energy expenditure equation (BEEE) were compared. In male patients receiving TPN, indirect calorimetry more closely approximated caloric needs than did the BEEE X 1.75. In female patients, the BEEE X 1.75, indirect calorimetry value, and calories infused were more equivalent, and positive nitrogen balance was consistently achieved. In thirty-three trauma patients, indirect calorimetry and the BEEE were compared. Indirect calorimetry consistently predicted higher caloric expenditure than did the BEEE X 1.75. In assessing caloric requirements in acutely catabolic patients, the BEEE X 1.75 appears to be inadequate. The BEEE does not take into account changes in temperature or degree of illness. Indirect calorimetry is easy to perform and gives more pointed information about the patient's caloric needs.

Adolescent↗