Nutritional Support: Macronutrient Formulation (Assessment of Energy and Substrate Requirements)

I. Statement of the Problem

Provision of adequate calories and protein to the hypermetabolic injured patient is of paramount importance in achieving optimal outcomes for these patients. Failure to meet caloric requirements leads to erosion of lean body mass and subsequent negative nitrogen balance as the body attempts to provide sufficient energy and nitrogen to carry out vital functions. Conversely, overzealous nutritional support is associated with derangements in hepatic, pulmonary, and immunologic function and may lead to outcomes nearly as detrimental to the injured patient as malnutrition.

II. Process

A. Identification of References

References were identified from a computerized search of the National Library of Medicine for English language citations between 1973 and 2000. Keywords included: nutritional support, trauma, critically injured, head injury, spinal cord injury, paraplegia, quadriplegia, burns, energy expenditure, energy intake, enteral, parenteral, dietary proteins, dietary fats, dietary carbohydrates, protein, carbohydrate, fat, lipid, requirements, and nutrition. Studies involving laboratory animals were excluded from our review, as were studies where the patient population was exclusively or predominantly pediatric so as to avoid the effect of growth and maturation of the patient on energy and substrate requirements. The bibliographies of the selected references were reviewed for relevant articles not found in the computerized search. Literature reviews, case reports, and editorials were excluded. Seventy-three articles were identified.

B. Quality of the References

The quality assessment instrument applied to the references was developed by the Brain Trauma Foundation and subsequently adopted by the EAST Practice Management Guidelines Committee. Articles were classified as Class I, II, or III according to the following definitions (one article was classified as Class I and Class II):

Class I: A prospective, randomized clinical trial. Eighteen articles were chosen and analyzed.

Class II: A prospective, non-comparative clinical study or a retrospective analysis based on reliable data. Forty-two articles were chosen and analyzed.

Class III: A retrospective case series or database review. Thirteen articles were chosen and analyzed.

III. Recommendations

A. Level 1

There appears to be no advantage to the routine use of calorimetry to determine the caloric requirements of burn patients.

B. Level II

1. For moderately to severely injured patients (ISS 25-30), energy requirements are estimated to be 25-30 total kcal/kg/day or 120% to 140% of predicted BEE (per Harris-Benedict equation).
2. There appears to be no consistent relationship between ISS and measured resting energy expenditure (MREE) in trauma patients.
3. For patients with severe head injury (GCS score <8), energy requirements may be met by replacing 140% of MREE (~30 total kcal/kg/day) in non-pharmacologically paralyzed patients and 100% of MREE (~25 kcal/kg/day) in paralyzed patients.
4. Within the first 2 weeks after spinal cord injury, nutritional support should be delivered at 20-22 total kcal/kg/day (55% to 90% of predicted BEE by Harris-Benedict equation) for quadriplegics and 22-24 total kcal/kg/day (80% to 90% of predicted BEE by Harris-Benedict equation) for paraplegics.
5. For patients with burns exceeding 20% to 30% TBSA, initial caloric requirements may be estimated by several available formulas.
6. The Curreri formula (25 kcal/kg + 40kcal/TBSA burn) overestimates caloric needs of the burn patient (as estimated by calorimetry) by 25% to 50%.
7. The Harris-Benedict formula underestimates the caloric needs of the burn patient (as estimated by calorimetry) by 25% to 50%.
8. In patients with burns exceeding 50% TBSA, TPN supplementation of enteral feedings to achieve Curreri-predicted caloric requirements is associated with higher mortality and aberrations in T-cell function.
9. Caloric requirements for major burns fluctuate during the hospital course but appear to follow a biphasic course with energy expenditure declining as the burn wound closes. Therefore, direct measurement of energy expenditure via calorimetry once or twice weekly may be of benefit in adjusting caloric support throughout the hospital course.
10. Intraoperative enteral feeding of the burn patient is safe and efficacious, leads to fewer interruptions in the enteral feeding regimen, and, therefore, more successful attainment of calorie and protein goals.
11. Approximately 1.25 grams of protein per kg body weight per day is appropriate for most injured patients.
12. Up to 2 grams of protein per kg body weight per day is appropriate for severely burned patients.
13. In the burn patient, energy as carbohydrate may be provided at a rate of up to 5 mg/kg/min (~25 kcal/kg/day); exceeding this limit may predispose patients to the metabolic complications associated with overfeeding. In the non-burn trauma patient, even this rate of carbohydrate delivery may be excessive.
14. Intravenous lipid or fat intake should be carefully monitored and maintained at <30 percent of total calories. Zero fat or minimal fat administration to burned or traumatically injured patients during the acute phase of injury may minimize the susceptibility to infection and decrease length of stay.
15. Proteins, fat, and carbohydrate requirements do not appear to vary significantly according to the route of administration, either enterally or parenterally.
16. Fat or carbohydrate requirements do not appear to vary significantly according to the type of injury, i.e., burned versus traumatically injured.

C. Level III

1. Provision of excess calories to trauma patients may induce hyperglycemia, excess CO2 production, fluid/electrolyte abnormalities, lipogenesis, and hepatic steatosis.
2. Energy requirements for patients with less than 20% to 30% TBSA burns are similar to those of patients without cutaneous burns.
3. Protein requirements in burn patients and in those with severe CNS injuries may be significantly greater than anticipated, up to 2.2 grams/kg body weight per day. However, the ability to achieve positive nitrogen balance in a given patient varies according to the phase of injury. Provision of large protein loads to elderly patients or to those with compromised hepatic, renal, or pulmonary function may lead to deleterious outcomes.

IV. Scientific Foundation

Calorie requirements of trauma patients have been debated for years. The gold standard for determining the caloric needs of patients with traumatic injuries is to measure their energy expenditure with indirect calorimetry. By measuring oxygen consumption (VO₂) and carbon dioxide production (VCO₂) via indirect calorimetry, resting energy expenditure can be calculated using the abbreviated Weir equation: REE = [3.9 (VO₂) + 1.1 (VCO₂] x 1.44. Despite the availability of this technology, there have been few prospective, randomized clinical trials conducted specifically to determine the optimal number of calories for this patient population. The best study to date that has addressed this issue with Class I evidence compared the effect of three different parenteral nutrition regimens (hypercaloric, isocaloric, hypocaloric) on protein catabolism and nitrogen loss when protein administration was fixed at 1.7 g/kg/day.^[1] Caloric needs were provided at 125% of measured resting energy expenditure (MREE) in the hypercaloric group, 100% of MREE in the isocaloric group, and 75% of MREE in the hypocaloric group. The mean ISS was 27 for all three groups, and patients with burn, spinal cord, or isolated head injuries were excluded from study enrollment. Despite significant differences in caloric provision, no significant differences were observed in nitrogen balance, 3-methylhistidine excretion, or visceral protein status among the groups. The mean MREE was approximately 28 kcal/kg/day for all patients on day 4 of the study. However, 80% (24/30) of the patients were sedated with fentanyl, and 7% (2/30) of the patients were pharmacologically paralyzed. Both of these treatment interventions have been associated with a hypometabolic response in neurologically injured patients. The only additional Class I evidence available is derived from a trial comparing the metabolic effects of a carbohydrate-based diet with a fat-based diet in critically ill patients with infections or trauma.^[2] Only 2 of 12 patients were identified as having traumatic injuries. The mean MREE was approximately 26 kcal/kg/day for patients while receiving the different nutritional regimens. Demographic data describing the severity of illness or injury of the patients were not provided in the study.

Several methods have been used to estimate energy requirements of patients with traumatic injuries as an alternative to measuring actual energy requirements with indirect calorimetry. These include calculating basal energy expenditure with the Harris-Benedict energy equation (HBEE), multiplying the HBEE by an activity factor and a stress factor depending on the type of injury (i.e., blunt trauma, skeletal trauma, head trauma) and using 25 kcal/kg/day. A number of clinical trials have evaluated the accuracy of these predictive methods for estimating MREE in trauma patients. The MREE of trauma patients has been variously reported to be approximately 26 kcal/kg/day (range, 21-32 kcal/kg/day), 33 kcal/kg/day (postabsorptive state [range, 25-41 kcal/kg/day]), 37 kcal/kg/day (while receiving parenteral nutrition [range, 29-46 kcal/kg/day]), 38-48 kcal/kg/day (requiring insulin in TPN), and HBEE x 1.2 (activity factor) x

1.75 (stress factor).^[3-6] One recent study noted a biphasic metabolic response to injury, with total energy expenditure (TEE) peaking during the second post-injury week at 59 kcal/kg/day, compared with only 31 kcal/kg/day during the first post-injury week.^[7] Furthermore, these studies have attempted to identify a relationship between MREE and scoring systems used to evaluate the severity of disease and injury. Although some investigators ^{[8] [9]} have found no correlation (r=-0.042) between MREE and injury severity score (ISS), others^[4] have reported a relatively high correlation between ISS and MREE/kg (r=0.84).

Head and spinal cord injury patients represent a subset of trauma patients with unique metabolic requirements. Most clinical trials report hypermetabolism in head-injured patients with an average increase of 40% above that predicted with HBEE.^[10] The increases in energy expenditure are related to the increased oxygen consumption caused by the stress hormone flow in response to brain injury and may further be increased by hyperventilation, fever, seizures, and posturing. Patients with decerebrate or decorticate posturing have demonstrated elevations in energy expenditure at 200% to 250% of predicted energy expenditure.^[11] Pharmacologic treatments have also been shown to dramatically impact energy expenditure.^[10] High-dose barbiturates have been used to control increased intracranial pressures refractory to standard therapy. However, barbiturate therapy can decrease energy expenditure by as much as 40% below that predicted with HBEE.^[12] Other pharmacologic interventions, such as neuromuscular blockade with pancuronium bromide, have reduced energy expenditure by 42% below predicted energy expenditure with HBEE.^[11]

In contrast to trauma and head injury patients, spinal cord injury patients exhibit a decrease in energy expenditure. Within the first 3 weeks following spinal cord injury, metabolic rates 94% (range, 55% to 129%) of those predicted by HBEE have been observed.^[13] An inverse relationship has been identified between the location of injury and energy expenditure. Thus, the higher the lesion, the lower the energy expenditure measurement. Nutrition support recommendations for quadriplegics are 20% to 40% below HBEE (20-22 kcal/kg/day) and 10% to 20% below HBEE for paraplegics. Recognizing the hypometabolic response in spinal cord injury patients is important because overfeeding can have adverse effects. Providing calories in excess of energy expenditure in any patient can cause: (1) impaired glucose control, (2) suppression of chemotactic/phagocytic actions of monocytes due to hyperglycemia, (3) respiratory dysfunction from excessive CO2 production, (4) lipogenesis, and (5) hepatic steatosis.

Energy requirements in the burn patient are difficult to determine because many factors impact this calculation. Early studies demonstrated a relationship between the percentage of TBSA burned and energy requirements in these patients as determined by indirect or direct calorimetry. Wilmore^[14]was the first to document this relationship in his study of 20 patients with burns ranging from 7% to 84% TBSA. He further noted that this hypermetabolism appeared to be mediated by catecholamines and appeared to plateau at 60% TBSA. During that same year Curreri,^[15] in a prospective study of 9 patients, derived a formula, now bearing his name, relating energy expenditure to preburn weight and the percent TBSA burned. Although subsequent studies have shown that this formula frequently overestimates actual energy requirements, it remains one of the most, if not the most, commonly used method to determine energy requirements of patients in burn centers in the United States today.^[16]

Since the Curreri study, many formulas have been proposed as more accurate predictors of caloric requirements of the burned patient. The formulas tend to fall into two broad categories, formulas which include a factor for TBSA burned and those which do not. The majority of formulas in this latter category are based on calculations of basal energy expenditure (BEE) as determined by the Harris-Benedict equation, which takes into account patient age, sex, height, and weight. To the BEE are multiplied factors for the degree of stress (injury) and for the level of patient activity to arrive at an estimate for the patient’s overall caloric requirement. Many studies have compared the Curreri formula with formulas based on the Harris-Benedict­derived BEE. Turner and colleagues^[17]completed such a prospective study in 35 patients with second- and third-degree burns ranging between 10% and 75% TBSA and concluded that the Harris-Benedict-derived BEE underestimated actual energy expenditure by 23%, while the Curreri formula overestimated energy expenditure by 58%. Long and coworkers^[18] measured energy expenditure in 39 critically ill patients and in 20 normal volunteers, finding that energy expenditure in burned patients exceeded that predicted by the Harris-Benedict equation by 132%. They suggested that the Harris-Benedict equation be multiplied by a stress factor as well as an activity factor to arrive at a more accurate estimation of caloric requirements. In fact, the values for stress and activity factors, which he proposed nearly 20 years ago, are still widely employed today.

However, even with these correction factors, Harris-Benedict predictions seem to perform no better than the Curreri formula. In a prospective study of 21 patients with between 21% and 81% TBSA burns, the Curreri formula overestimated actual energy expenditure by 25% to 36%, while the Harris-Benedict predictions modified by stress and activity factors, overestimated actual energy expenditure by 32% to 39%.^[19] Other Harris-Benedict-derived formulas have attempted to simplify matters by simply multiplying the Harris-Benedict-derived BEE by either 1.5^[20] or by a factor of 2.^[21]Each of these authors claim superiority over Curreri­based predictions which, as indicated above, seem to consistently overestimate actual energy expenditure as determined by indirect calorimetry.

The other major category of energy-predicting formulas in burn patients includes those which, like the Curreri formula, are based on the patient’s TBSA and/or TBSA burned. Both Xie^[22] and Allard^[23]have compared their TBSA-based formulas with the Curreri formula and claim superior results, though the overall number of patients studied is quite small.

Despite the many published studies which claim superiority of a particular formula over the Curreri Formula in the prediction of energy requirements in burn patients, the Curreri Formula remains the most commonly used despite its well-documented propensity to overestimate energy requirements.^[16] One would suspect, therefore, that actual determination of energy expenditure by indirect calorimetry, might be the most accurate and commonly used method of determining caloric requirements of burned patients. However, in an interesting study documenting actual burn practices in North American burn centers, Williamson^[16] noted that indirect calorimetry is infrequently carried out on a routine basis, being used only occasionally or for research purposes only. More importantly, there appear to be no differences in patient outcome when calories are provided on the basis of direct measurement of energy expenditure or on the basis of a mathematical formula. In a prospective randomized study of 49 patients, patients received feedings based on the Curreri formula or on indirect calorimetry-determined energy expenditure. Despite the significant difference in the number of calories prescribed to each group, the actual number of calories received by each group were the same, and there were no differences in clinical outcomes or complications.^[24] An important finding in this study was the discrepancy between the number of calories prescribed and the number of calories delivered to these burn patients. Regardless of whether the Curreri formula is used or the BEE is multiplied by an activity factor and/or a stress factor, it is frequently difficult, if not impossible, for a patient to ingest this number of calories. Indeed, in Ireton's study mentioned above,^[20] patients received a caloric intake of only 81% of the calculated Curreri-predicted caloric requirement. Thus, it is perhaps advantageous that many of these formulas overestimate caloric need to compensate for the less-than-prescribed caloric load that these patients actually receive.

At the same time, however, it seems unwise to attempt to achieve these high caloric loads by supplementing enteral nutrition with TPN. In a prospective randomized study of 39 patients with TBSA burns exceeding 50%, Herndon et al.^[25] demonstrated a significantly higher mortality and greater depressions in T-helper/suppressor ratios in patients receiving TPN.

Thus, the available data support the use of some formula to determine the initial caloric requirements of burned patients, recognizing that formulas may over-estimate a patient’s actual caloric need and that it is unlikely that the entire caloric load can be delivered. One common reason for the inability to deliver the prescribed caloric load in burn patients is the need to interrupt the tube feeding regimen for frequent debridement and grafting in the operating room. The Williamson survey^[16] documents that most patients in North American burn centers are kept NPO for at least 6 to 8 hours before surgery. Jenkins,^[26] however, demonstrated the feasibility and safety of continuing enteral feedings throughout operative procedures in a very select group of burn patients with enteral access established beyond the pylorus and airway access established via an endotracheal tube or tracheostomy. These investigators demonstrated significant caloric deficits and an increased incidence of wound infection in the unfed group compared with the group that underwent intraoperative enteral feeding.

Finally, it should be mentioned that the caloric requirements of the burn patient fluctuate over the course of burn wound healing due to closure of the burn wound and other undetermined factors. Saffle and colleagues^[27] demonstrated the biphasic character of measured energy expenditures in burn patients. Energy expenditures actually rise from the time of admission through the 10th to 20th post-burn day and then decline thereafter but remain elevated at the time of discharge. This observation was confirmed by Cunningham^[21] as well as by Ruten,^[28] who noted a trend toward decreased energy expenditures with excision and coverage of the burn wound. Ireton-Jones,^[29]however, was unable to identify a relationship between the percent of burn wound remaining open and the measured energy expenditure. Even in the absence of a demonstrated relationship between the percent of burn wound remaining open and energy expenditure, the caloric needs of the burn patient fluctuate from day to day depending on other factors such as temperature, activity level, degree of anxiety, pain control, ventilator dependency, caloric intake, the presence or absence of sepsis, and other yet-to-be defined factors. Therefore, providing the same caloric requirement over time runs the risk of overfeeding or underfeeding the burned patient. This has led some authors to recommend the use of indirect calorimetry to determine actual caloric requirements on a weekly or twice-weekly basis.^{[19] [30] [31]}

At this time, there are insufficient data and on protein, fat, and carbohydrate requirements in traumatically injured or burned patients to provide any Level One recommendations. One major problem is the difficulty identifying specific groups of patients for study. For this reason, guidelines can only be applied broadly to patients within these two general categories. Another issue is that the current focus of nutrition and metabolic support has necessarily changed. The state of the art is such that we are less concerned with how to provide adequate quantities of macronutrients. The bulk of available evidence suggests that, with the exception of the risk of overfeeding, we currently provide patients with sufficient calories and protein to avoid the detrimental effects of malnutrition. Our attention has shifted toward manipulating a patient’s physiological and biochemical environment to his or her advantage through the administration of specific nutrients, growth factors, or other agents, often in pharmacological doses.

A few Class I reports, randomized, prospective and adequately controlled trials, have presented “convincingly justifiable” data. However, in these instances, either the number of patients studied was too small or the particular population investigated was too specialized to warrant inclusion in this practice management guideline.

Protein requirements were largely established by reports from the early 1980s that presented dose ranges believed to be appropriate. Most of these reports are Class II studies.^{[6] [32-35]} More recent publications have confirmed these dose ranges based on extensive research conducted by a leading investigator,^{[36] [37]} studies of protein requirements using state-of-the-art measurements of body composition,^[38] measurements of substrate metabolism and energy requirements,^[39] or expert opinions based on reviews of available literature.^{[40] [41]}

The focus of other investigations has not been on specific protein requirements, but these studies provide a reference point for the range of protein intakes that appear to be efficacious.^{[2] [42-45]}Variations in protein requirements as a function of time after burn or injury have been acknowledged illustrating that current recommendations are only estimates of average need.^[46]

The question of whether the contribution from protein should or should not be included in calculations of total caloric intake has not been specifically addressed. However, the preponderance of evidence available from detailed studies of actual energy expenditure^{[21] [47]} or nutrient utilization,^{[48] [49]} reviews of published reports,^[50] or prospective trials^{[51] [52]} suggest that the majority of calories should be administered as carbohydrate. Although the exact percentage of total calories needed as fat is unknown, consensus opinion suggests that 30% or less is sufficient under most circumstances. This conclusion does not obviate the need to modify carbohydrate administration to minimize CO2 production in selected instances,^{[47] [49] [50]} but the specific range under which these modifications should occur has not been established. Some reports, though not all,^[53] especially the Class I report by Battistella,^[54] suggest that minimizing fat intake or altering the type of fat administered^[55-57] may decrease morbidity and improve outcome or favorably alter metabolic profiles.

A few reports suggest that the specific macronutrients administered^{[56] [58]} or the use of growth factors^{[45] [59-61]} may favorably influence metabolic responses. However, recent preliminary reports suggest that the use of growth hormone for this purpose in critically ill patients may be associated with deleterious outcomes.

V. Summary

Multiple formulas provide an estimate of an individual patient’s energy and substrate needs. While many of these provide accurate estimates, many do not and can lead to overfeeding with all of its inherent complications. It is best to remember that these formulas provide at best only an estimate of an individual patient’s initial energy and substrate needs, and that these requirements will vary throughout the course of illness and recovery. Ongoing assessment of the appropriateness of nutritional support is crucial in avoiding under- and over-feeding.

VI. Future Investigation

It is unlikely that there is an ideal energy or substrate formula that will perform better than those currently in use. However, more reliable and easier-to-use means of measuring energy expenditure and substrate use would have significant advantages over the current state of technology with indirect calorimetry. Identification of these markers of metabolism will help in assessing a patient’s initial requirements and will help the clinician modify nutritional support throughout the course of illness and recovery. It is unlikely that prospective, randomized, double-blinded controlled trials will study the effects of the administration of different quantities of protein, fat, or carbohydrate. Our present health care environment requires a clearer delineation of the indications for nutritional or metabolic support and for unequivocal demonstrations of efficacy with regard to decreasing costs and improving outcomes. Important issues that should be examined include: 1) the nature of injury and its time course, with the goal of minimizing the effects of nutritional, especially parenteral, interventions; 2) the effects of macronutrients administration on cellular biology and organ function during critical illness; and 3) the identification of groups of patients who will benefit from the administration of specific nutrients or growth factors, who needs them, what kind, and when?

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Tables

Assessment of Energy and Substrate Requirements for the Trauma Patient

Table 1: Energy Requirements in Trauma Patients

Assessment of Energy and Substrate Requirements for the Trauma Patient

Table 2. Energy Requirements in Burn Patients

Assessment of Energy and Substrate Requirements for the Trauma Patient

Table 3. Macronutrient Requirements in Trauma And Burn Patients

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