Obligatory Negative Nitrogen Balance Following Spinal Cord Injury DONNA J. RODRIGUEZ, R.D., FREDERICK W. CLEVENGER, M.D., TURNER M. OSLER, M.D., GERALD B. DEMAREST, M.D., AND DONALD E. FRY, M.D. From the
Department of Surgery, University of New Mexico, and Food Albuquerque, New
and Nutrition Mexico
Seruices, University of New
Mexico
ABSTRACT. Obligatory nitrogen losses due to paralysis in the spinal cord-injured (SCI) patient prevent positive nitrogen balance (NB) regardless of the calorie and protein intakes. Ten patients with SCI and 20 controls with nonspinal cord injury (NSCI) matched for time, sex, age, and injury severity score (ISS) were admitted to our Level I trauma center. In both groups, total nutritional support was delivered within 72 hours of admission based on predicted energy expenditures (PEE Harris-Benedict equation x 1.2 x 1.6) and 2 g of protein/kg of ideal body weight (IBW). Subsequent changes in nutrient delivery were based on NB. No SCI patient established positive NB during the 7-week period following injury despite an average delivery of 2.4 g of protein/kg IBW and 120% of the PEE
at the time of peak
Ten thousand spinal cord injuries occur in the United States each year. The nutritional management of multi-
injuries (NSCI) matched for time, sex, severity score (ISS). Upon admission
=
with spinal cord injury (SCI) falls into two phases. Initially, one would anticipate elevations in energy expenditure and urinary nitrogen loss characteristic of all patients with traumatic insult.1,2 As the hypermetabolic phase resolves, these patients lapse into a chronic state of decreased metabolism characterized by obligatory loss of lean body mass and marked reduction in substrate utilization.3-5 Although the latter phase has been well described, the characteristics of the initial metabolic response to injury in SCI patients is a topic about which little has been written. We have found it impossible to establish positive nitrogen balance (NB) in patients acutely following SCI, despite near uniform ability to do so in other groups of severely injured patients. In an attempt to characterize the early metabolic response to SCI, we studied NB and metabolic requirements during periods of adequate calorie and nitrogen delivery in a group of SCI patients. We compared this group with a cohort of patients with multisystem trauma not involving the spinal cord (NSCI) matched for age, sex, and injury severity. This study was designed (1) to test the hypothesis that negative NB is obligatory in SCI patients and (2) to determine the profile of the metabolic response to SCI.
ply injured patients
Hospital,
negative NB (-10.5). In six SCI patients, an protein and 12% in delivered calories over a 1-week period effected no change in average NB (-7.4 us -6.8). Indirect calorimetry in five SCI patients average increase of 25% in delivered
showed that calorie intakes were 110% more than average measured energy expenditures. In contrast, 17 of 20 NCSI patients achieved positive NB within 3 weeks of admission. They required an average delivery of 2.3 g of protein/kg IBW and 110% of PEE to reach positive NB. These data demonstrate the phenomenon of obligatory negative NB acutely following SCI. Aggressive attempts to achieve positive NB in these patients will fail and result in overfeeding. ( Journal of Parenteral and Enteral Nutrition 15 :319-322, 1991) age, and injury to our Level I
trauma center, nutritional needs were calculated for each patient. Predicted energy expenditures (PEE) were esti-
mated from the Harris-Benedict equation (BEE) multiplied by 1.2 as the activity factor for bedrest, and 1.6 as the stress factor for trauma. Protein delivery was based on 2 g of protein/kg of ideal body weight (IBW) (male: 106 pounds for the first 5 feet plus 6 pounds for every inch taller; female: 100 pounds for the first 5 feet plus 5 pounds for every inch taller).6 Injury severity scores were assigned to each patient according to the method described by Baker et al.’°8 In both the spinal-cord injured and control groups, total nutritional support was delivered within 72 hours of admission. Enteral and/or parenteral nutrition support (depending on patient tolerance) was provided in amounts necessary to meet calculated calorie and protein needs. Subsequent changes in nutrient delivery were based on nitrogen balances and metabolic cart measurements. Calorie and protein intakes, types of formulas, and formula tolerances were recorded on a daily basis. Patient weights were not consistently obtained due to the inherent difficulties and inaccuracies in weighing these types of
patients. Twenty-four-hour urinary urea nitrogen were done on each patient only when calorie and protein intakes were meeting estimated needs, and repeated weekly or when dictated by clinical conditions. Aliquots of each 24-hour urine collection were assayed for their urea nitrogen contents by our standard enzymatic laboratory technique using the Beckman Astra (Beckman Instruments, Fullerton, CA). Nitrogen balances were then calculated using the following equation:’
METHODS
(UUN) collections
Ten patients with acute SCI were compared with 20 controls with multi-system trauma but no spinal cord
Reprints to: Frederick W. Clevenger, M.D., Department of Surgery. University of New Mexico Hospital, 2211 Lomas Blvd., N.E., Albuquerque, NM 87131.
319 Downloaded from pen.sagepub.com at East Carolina University on April 23, 2015
320
Indirect calorimetry was performed on both mechanically ventilated and spontaneously breathing patients with the Critical Care Monitor (CCM) metabolic cart (Medical Graphics Corporation, St. Paul, MN). Only those studies that had fluctuations in FI02 of less than 0.02% and that demonstrated steady state measurements were utilized. These metabolic cart studies were done weekly when possible, but were not performed if inspired oxygen concentrations exceeded 60%. RESULTS
The SCI group had
eight men (80%) and two women age of 48 years (range 25-83). Mean ISS in this group was 30 (range 24-41). The control group consisted of 16 men (80%) and four women (20%) with a mean age of 45 years (range 16-80) and a mean ISS of 26 (range 13-43). Comparison between groups is depicted in Table I. All patients were receiving at or (20%) with
a mean
above their calculated calorie and protein needs by the second week of hospitalization. At this point, all 10 patients were tolerating delivered nutrients without evidence of glucose intolerance, hypertriglyceridemia or azotemia. Thus, failure to deliver or tolerate adequate nutrients was not a factor in ability to accumulate nitrogen balance data. No SCI patient was able to achieve and maintain positive NB during the 7-week period following injury. Two SCI patients had positive NB limited to the early postinjury period (both +3 when meeting their estimated nutrient needs on day 4 postinjury). Both showed excessive urinary urea nitrogen excretions (>25 g of N/24 h) and severely negative NB on weeks 2 and 3 even when intakes were increased above previously measured adequate nutrient deliveries. Increases in calorie and protein intakes above needs measured by indirect calorimetry and/or initially estimated needs were attempted in all 10 patients to ensure that negative nitrogen balances were not due to unaccounted-for hypermetabolic states. Indirect calorimetry was performed in five patients during excessive nitrogen loss. In these patients, the average energy intake was 110% of measured needs. In six SCI patients, an increase of 25% in delivered protein and 12% in delivered calories effected no change in average NB (-7.4 us -6.8). Increases in protein and calorie delivery above calculated and measured needs were tolerated without hyperglycemia or hypertriglyceridemia in all 10 patients. Peak negative NB (mean of -10.5) occurred during the 3rd week postinjury despite an average calorie delivery of 120% of the PEE and 2.4 g of protein/kg
IBW. After the 3rd week, the pattern of nitrogen balances in our SCI patients became progressively less negative over the next 5 weeks. Positive NB was not achieved until 2 months following injury (Fig. 1). In order to determine if ability to achieve enteral nutrition was a factor in nitrogen equilibrium, we separated nitrogen balance by mode of support. All patients were on full enteral support by the end of the 3rd postinjury week. During the 2nd postinjury week, the average NB of patients on enteral support was -10.6 us -8.0 for those on parenteral. By week 3, patients on enteral nutrition had an average NB of -7.8 us -15 for the one patient on TPN who had nitrogen balance data. In the control group of 20 multi-system trauma patients, positive NB was reached by week 3 in 17. In this group, the approach of delivering calories and protein based on predicted needs (BEE x 1.2 x 1.6 and 2 g of protein/kg of IBW) was typically sufficient. The weekly mean nitrogen balances in this group did not show the consistently negative pattern that was documented in the SCI group (Fig. 2). When PEE and protein delivery were shown to be inadequate, subsequent increases in the nutritional regimens were successful in achieving positive nitrogen balances in all but three patients. These three patients were septic and two subsequently died of multiple organ failure. DISCUSSION
The long-term metabolic sequelae of SCI is well documented. Chronic paraplegia and quadriplegia are
FIG. 1. Average of all 24-hour nitrogen balances postinjury week for SCI patients.
as
compared
to
FIG. 2. Average of all 24-hour nitrogen balances postinjury week for NSCI patients.
as
compared
to
TABLE I
Comparison of demographics and injury severity
Downloaded from pen.sagepub.com at East Carolina University on April 23, 2015
321
marked by a reduction in energy expenditure of up to 6 7 ~ and progressive loss of lean body mass. Agarwal and
Associates’ studied 15 quadriplegics
an average of 9.2 and demonstrated after their cord spinal injury years marked reduction in measured energy expenditure (MEE) and suggested that delivery of calories based on the Harris-Benedict formula leads to overfeeding. Cox et al4 studied 22 SCI patients over 2 months after injury and demonstrated a need of 22.7 kcal/kg/d for quadriplegics and 27.9 kcal/kg/d for paraplegics (45 to 90% of recommended calories based on various formulae). Kearns et al5 studied five quadriplegics and demonstrated that when the Harris-Benedict equation was used, calculated expenditure exceeded measured expenditure by a factor of 1.5. Although the time frame of the study in relation to injury was not specified, these authors suggested delivery of 80% of estimated caloric needs. Studies of the acute metabolic response to SCI are few. Kaufman et all° measured calorie intake and NB in eight patients for 10 to 14 days following SCI. Although markedly negative nitrogen balances were observed during the study period, supplemental calories were not given, and patients took in only 38% of expected caloric needs during the study. It is not apparent how protein needs were estimated and if these needs were being met at the time of NB determinations. One might argue that, had energy and protein requirements been delivered at the level of predicted or measured needs, these patients might have attained positive NB.
Kolpek
alll compared urinary
urea nitrogen excrepatients with acute SCI to seven patients immediately following head trauma. Indirect calorimetry demonstrated marked reductions in MEE as compared to the Harris-Benedict PEE. However, no mention of the use of stress or activity factors (if any) was made by the authors. It is difficult to determine if protein intakes met estimated needs and what manipulations were made in response to negative NB by Kolpek et al.ll Nitrogen balance studies were reported for the first 3 weeks following injury and mirrored the results we have reported. In our study and that reported by Kolpek, peak negative NB was seen on week 3 despite adequate delivery of predicted and measured calories. We have found it impossible to establish positive NB acutely following SCI. We have hypothesized that negative NB is obligatory in these patients. Our data demonstrate this phenomenon in three ways. First, when given protein and calories adequate to meet predicted needs, SCI patients were in negative NB. When an increase in protein and calories was delivered, NB remained unchanged. Despite overfeeding as measured by indirect calorimetry, these patients remained in negative NB. The second argument in favor of this negative NB being &dquo;obligatory&dquo; is based on comparison of SCI patients to multi-system trauma patients without SCI (controls). Positive NB was obtained in all but three patients in the control group by the 3rd week after injury. Since ISSmatched controls were used, the differences we noticed in SCI patients can only be explained by the presence of SCI. The method of correlating ISS and NB has previously been used by Andrassy and Dubois. 12 Thirdly, the
et
tion and MEE in
seven
demonstration of obligatory negative NB was made dramatically by a tragic case (Fig. 3). We followed a 22year-old Hispanic women on the trauma service who suffered a closed head injury, blunt rupture of the thoracic aorta, and a lumbar spine fracture not associated with neurologic deficit. With aggressive delivery of protein and calories, the patient was in positive NB on week 2 following her injury. She then went to the operating room for stabilization of her lumbar spine and suffered perioperative spinal cord injury resulting in paraplegia. Immediately thereafter, she developed negative NB despite increases in previously adequate amounts of protein and calories (Fig. 2). The pattern of her nitrogen balances again began to parallel the overall pattern that was apparent in our other patients with acute SCI. The mechanism responsible for obligatory negative NB in acute SCI remains speculative. Studies on the effects of immobilization on metabolism date back to the work by Dietrick et ap3 in 1948. Four conscientious objectors were immobilized at bed rest in a pelvic girdle and leg casts for 6 to 7 weeks and studied on a metabolism ward. All four subjects showed an increase in nitrogen excretion and negative NB during immobilization. Interestingly, the delay in development of negative NB for up to 5 days was also observed in our patients in whom NB was measured early. More recently, Bunker et all’ described negative nitrogen balance in housebound elderly people whereas age-matched active individuals were in nitrogen equilibrium. The authors speculated that immobility led to wasting and breakdown of muscle protein causing the negative NB. Unfortunately, comparison of these studies with an acutely injured population is not justified. However, acute immobilization could at least contribute to the elevated early nitrogen excretion in paralyzed patients. Many authors have speculated that denervation atrophy may also play a role in this phenomenon. Certainly, loss of lean body mass following SCI is a progressive process that occurs over a prolonged period. 15 The hormonal milieu immediately following SCI has not been well studied. Depressed thyroid function has been described immediately following cord injury and could be relevant. 16 However, alterations in thyroxine activity are difficult to interpret in acutely injured patients. Tumor necrosis factor and Interleukin1 appear to be mediators of altered protein metabolism following injury.17,18 Comparison of these monokine lev-
FIG. 3. Weekly 24-hour nitrogen balance determinations for exemplary patient (see discussion). Arrow indicates the point following injury where patient suffered perioperative spinal cord injury.
Downloaded from pen.sagepub.com at East Carolina University on April 23, 2015
322 els in SCI and NSCI patients may prove informative. With the observation of &dquo;obligatory negative nitrogen balance&dquo; in patients acutely following SCI, we have adopted a new approach to nutritional support in these patients. Our initial regimen is based on 2 g of protein/ kg of IBW and calories predicted by BEE times an activity factor of 1.2 and a stress factor of 1.6. Further changes in caloric delivery are based on needs measured by indirect calorimetry. Protein delivery is kept constant in spite of the anticipated measurement of negative NB. Aggressive attempts to achieve positive NB in these patients will fail and result in overfeeding.
6. American Diabetic Association, American Dietetic Association: A Guide for Professionals: The Effective Application of Exchange Lists for Meal Planning. 1977, p 17 7. Baker SP, O’Neill B, Haddon W, et al: The injury severity score: A method for describing patients with multiple injuries and evaluating emergency care. J Trauma 14:187, 1974 8. Baker SP, O’Neill B: The injury severity score: An update. J Trauma 16:882, 1976 9. Mackenzie TA, Clark NG, Bistrian BR, et al: A simple method for estimation of nitrogen balance in hospitalized patients: A review and supporting data for a previously proposed technique. J Am Coll Nutr 4:575-581, 1985 10. Kaufman HH, Rowlands BJ, Stern DK, et al: General metabolism in patients with acute paraplegia and quadriplegia. Neurosurgery 11.
ACKNOWLEDGMENTS
The authors wish to express deep appreciation to Ms. Diane Robinson for her assistance in preparation of the
manuscript.
1. 2.
3. 4.
13:277-280, 1989 12.
13.
REFERENCES
Fry DE, Borzotta AP: Options in nutritional support of the surgical patient. Prob Gen Surg 4:427-440, 1987 Kinney JM, Duke JH Jr, Long CL, et al: Tissue fuel and weight loss after injury. J Clin Path 4:65-72, 1970 Agarwal N, Lee BY, Corcoran L, et al: Energy expenditure in quadriplegic patients (abstr). JPEN 8:98, 1984 Cox SA, Weiss SM, Posuniak EA, et al: Energy expenditure after spinal cord injury: An evaluation of stable rehabilitating patients.
J Trauma 25:419-423, 1985 5. Kearns PJ, Pipp TL, Quirk quadriplegics (abstr). JPEN
M, et al: Nutritional requirements in 6:577, 1982
16:309-313, 1985 Kolpek JH, Ott LG, Record KE, et al: Comparison of urinary urea nitrogen excretion and measured energy expenditure in spinal cord injury and nonsteroid-treated severe head trauma patients. JPEN
Andrassy RJ, Dubois T: Modified injury severity scale and concurrent steroid therapy: Independent correlates of negative nitrogen balance in pediatric trauma. J Pediatr Surg 20:799-802, 1985 Dietrick JE, Whedon GD, Shorr E: Effects of immobilization upon various metabolic and physiologic functions of normal men. Ann J
Med 4:3-36, 1948 14. Bunker VW, Lawson MS, Stansfield F, et al: Nitrogen balance studies in apparently healthy elderly people and those who are housebound. Br J Nutr 57:211-221, 1987 15. Greenway RM, Houser HP, Lindan O, et al: Long-term changes in gross body composition of paraplegic and quadriplegic patients. Paraplegia 7:301, 1970 16. Tator CH, VanderJagt RHC, Malkin A: The effect of acute spinal cord injury on thyroid function in the rat. Surg Neurol 18:64-68, 1982 17. Beutler B: The tumor necrosis factors: Cachectin and lymphotoxin. Hosp Pract 25:45-56, 1990 18. Fry DE, Polk HC (eds): Host defense and organ system failure, IN Trauma: Clinical Care and Pathophysiology. YearBook Medical Publishers, Inc, Chicago, 1987, pp 41-74
Downloaded from pen.sagepub.com at East Carolina University on April 23, 2015
Department of Surgery, University of New Mexico, and Food Albuquerque, New
and Nutrition Mexico
Seruices, University of New
Mexico
ABSTRACT. Obligatory nitrogen losses due to paralysis in the spinal cord-injured (SCI) patient prevent positive nitrogen balance (NB) regardless of the calorie and protein intakes. Ten patients with SCI and 20 controls with nonspinal cord injury (NSCI) matched for time, sex, age, and injury severity score (ISS) were admitted to our Level I trauma center. In both groups, total nutritional support was delivered within 72 hours of admission based on predicted energy expenditures (PEE Harris-Benedict equation x 1.2 x 1.6) and 2 g of protein/kg of ideal body weight (IBW). Subsequent changes in nutrient delivery were based on NB. No SCI patient established positive NB during the 7-week period following injury despite an average delivery of 2.4 g of protein/kg IBW and 120% of the PEE
at the time of peak
Ten thousand spinal cord injuries occur in the United States each year. The nutritional management of multi-
injuries (NSCI) matched for time, sex, severity score (ISS). Upon admission
=
with spinal cord injury (SCI) falls into two phases. Initially, one would anticipate elevations in energy expenditure and urinary nitrogen loss characteristic of all patients with traumatic insult.1,2 As the hypermetabolic phase resolves, these patients lapse into a chronic state of decreased metabolism characterized by obligatory loss of lean body mass and marked reduction in substrate utilization.3-5 Although the latter phase has been well described, the characteristics of the initial metabolic response to injury in SCI patients is a topic about which little has been written. We have found it impossible to establish positive nitrogen balance (NB) in patients acutely following SCI, despite near uniform ability to do so in other groups of severely injured patients. In an attempt to characterize the early metabolic response to SCI, we studied NB and metabolic requirements during periods of adequate calorie and nitrogen delivery in a group of SCI patients. We compared this group with a cohort of patients with multisystem trauma not involving the spinal cord (NSCI) matched for age, sex, and injury severity. This study was designed (1) to test the hypothesis that negative NB is obligatory in SCI patients and (2) to determine the profile of the metabolic response to SCI.
ply injured patients
Hospital,
negative NB (-10.5). In six SCI patients, an protein and 12% in delivered calories over a 1-week period effected no change in average NB (-7.4 us -6.8). Indirect calorimetry in five SCI patients average increase of 25% in delivered
showed that calorie intakes were 110% more than average measured energy expenditures. In contrast, 17 of 20 NCSI patients achieved positive NB within 3 weeks of admission. They required an average delivery of 2.3 g of protein/kg IBW and 110% of PEE to reach positive NB. These data demonstrate the phenomenon of obligatory negative NB acutely following SCI. Aggressive attempts to achieve positive NB in these patients will fail and result in overfeeding. ( Journal of Parenteral and Enteral Nutrition 15 :319-322, 1991) age, and injury to our Level I
trauma center, nutritional needs were calculated for each patient. Predicted energy expenditures (PEE) were esti-
mated from the Harris-Benedict equation (BEE) multiplied by 1.2 as the activity factor for bedrest, and 1.6 as the stress factor for trauma. Protein delivery was based on 2 g of protein/kg of ideal body weight (IBW) (male: 106 pounds for the first 5 feet plus 6 pounds for every inch taller; female: 100 pounds for the first 5 feet plus 5 pounds for every inch taller).6 Injury severity scores were assigned to each patient according to the method described by Baker et al.’°8 In both the spinal-cord injured and control groups, total nutritional support was delivered within 72 hours of admission. Enteral and/or parenteral nutrition support (depending on patient tolerance) was provided in amounts necessary to meet calculated calorie and protein needs. Subsequent changes in nutrient delivery were based on nitrogen balances and metabolic cart measurements. Calorie and protein intakes, types of formulas, and formula tolerances were recorded on a daily basis. Patient weights were not consistently obtained due to the inherent difficulties and inaccuracies in weighing these types of
patients. Twenty-four-hour urinary urea nitrogen were done on each patient only when calorie and protein intakes were meeting estimated needs, and repeated weekly or when dictated by clinical conditions. Aliquots of each 24-hour urine collection were assayed for their urea nitrogen contents by our standard enzymatic laboratory technique using the Beckman Astra (Beckman Instruments, Fullerton, CA). Nitrogen balances were then calculated using the following equation:’
METHODS
(UUN) collections
Ten patients with acute SCI were compared with 20 controls with multi-system trauma but no spinal cord
Reprints to: Frederick W. Clevenger, M.D., Department of Surgery. University of New Mexico Hospital, 2211 Lomas Blvd., N.E., Albuquerque, NM 87131.
319 Downloaded from pen.sagepub.com at East Carolina University on April 23, 2015
320
Indirect calorimetry was performed on both mechanically ventilated and spontaneously breathing patients with the Critical Care Monitor (CCM) metabolic cart (Medical Graphics Corporation, St. Paul, MN). Only those studies that had fluctuations in FI02 of less than 0.02% and that demonstrated steady state measurements were utilized. These metabolic cart studies were done weekly when possible, but were not performed if inspired oxygen concentrations exceeded 60%. RESULTS
The SCI group had
eight men (80%) and two women age of 48 years (range 25-83). Mean ISS in this group was 30 (range 24-41). The control group consisted of 16 men (80%) and four women (20%) with a mean age of 45 years (range 16-80) and a mean ISS of 26 (range 13-43). Comparison between groups is depicted in Table I. All patients were receiving at or (20%) with
a mean
above their calculated calorie and protein needs by the second week of hospitalization. At this point, all 10 patients were tolerating delivered nutrients without evidence of glucose intolerance, hypertriglyceridemia or azotemia. Thus, failure to deliver or tolerate adequate nutrients was not a factor in ability to accumulate nitrogen balance data. No SCI patient was able to achieve and maintain positive NB during the 7-week period following injury. Two SCI patients had positive NB limited to the early postinjury period (both +3 when meeting their estimated nutrient needs on day 4 postinjury). Both showed excessive urinary urea nitrogen excretions (>25 g of N/24 h) and severely negative NB on weeks 2 and 3 even when intakes were increased above previously measured adequate nutrient deliveries. Increases in calorie and protein intakes above needs measured by indirect calorimetry and/or initially estimated needs were attempted in all 10 patients to ensure that negative nitrogen balances were not due to unaccounted-for hypermetabolic states. Indirect calorimetry was performed in five patients during excessive nitrogen loss. In these patients, the average energy intake was 110% of measured needs. In six SCI patients, an increase of 25% in delivered protein and 12% in delivered calories effected no change in average NB (-7.4 us -6.8). Increases in protein and calorie delivery above calculated and measured needs were tolerated without hyperglycemia or hypertriglyceridemia in all 10 patients. Peak negative NB (mean of -10.5) occurred during the 3rd week postinjury despite an average calorie delivery of 120% of the PEE and 2.4 g of protein/kg
IBW. After the 3rd week, the pattern of nitrogen balances in our SCI patients became progressively less negative over the next 5 weeks. Positive NB was not achieved until 2 months following injury (Fig. 1). In order to determine if ability to achieve enteral nutrition was a factor in nitrogen equilibrium, we separated nitrogen balance by mode of support. All patients were on full enteral support by the end of the 3rd postinjury week. During the 2nd postinjury week, the average NB of patients on enteral support was -10.6 us -8.0 for those on parenteral. By week 3, patients on enteral nutrition had an average NB of -7.8 us -15 for the one patient on TPN who had nitrogen balance data. In the control group of 20 multi-system trauma patients, positive NB was reached by week 3 in 17. In this group, the approach of delivering calories and protein based on predicted needs (BEE x 1.2 x 1.6 and 2 g of protein/kg of IBW) was typically sufficient. The weekly mean nitrogen balances in this group did not show the consistently negative pattern that was documented in the SCI group (Fig. 2). When PEE and protein delivery were shown to be inadequate, subsequent increases in the nutritional regimens were successful in achieving positive nitrogen balances in all but three patients. These three patients were septic and two subsequently died of multiple organ failure. DISCUSSION
The long-term metabolic sequelae of SCI is well documented. Chronic paraplegia and quadriplegia are
FIG. 1. Average of all 24-hour nitrogen balances postinjury week for SCI patients.
as
compared
to
FIG. 2. Average of all 24-hour nitrogen balances postinjury week for NSCI patients.
as
compared
to
TABLE I
Comparison of demographics and injury severity
Downloaded from pen.sagepub.com at East Carolina University on April 23, 2015
321
marked by a reduction in energy expenditure of up to 6 7 ~ and progressive loss of lean body mass. Agarwal and
Associates’ studied 15 quadriplegics
an average of 9.2 and demonstrated after their cord spinal injury years marked reduction in measured energy expenditure (MEE) and suggested that delivery of calories based on the Harris-Benedict formula leads to overfeeding. Cox et al4 studied 22 SCI patients over 2 months after injury and demonstrated a need of 22.7 kcal/kg/d for quadriplegics and 27.9 kcal/kg/d for paraplegics (45 to 90% of recommended calories based on various formulae). Kearns et al5 studied five quadriplegics and demonstrated that when the Harris-Benedict equation was used, calculated expenditure exceeded measured expenditure by a factor of 1.5. Although the time frame of the study in relation to injury was not specified, these authors suggested delivery of 80% of estimated caloric needs. Studies of the acute metabolic response to SCI are few. Kaufman et all° measured calorie intake and NB in eight patients for 10 to 14 days following SCI. Although markedly negative nitrogen balances were observed during the study period, supplemental calories were not given, and patients took in only 38% of expected caloric needs during the study. It is not apparent how protein needs were estimated and if these needs were being met at the time of NB determinations. One might argue that, had energy and protein requirements been delivered at the level of predicted or measured needs, these patients might have attained positive NB.
Kolpek
alll compared urinary
urea nitrogen excrepatients with acute SCI to seven patients immediately following head trauma. Indirect calorimetry demonstrated marked reductions in MEE as compared to the Harris-Benedict PEE. However, no mention of the use of stress or activity factors (if any) was made by the authors. It is difficult to determine if protein intakes met estimated needs and what manipulations were made in response to negative NB by Kolpek et al.ll Nitrogen balance studies were reported for the first 3 weeks following injury and mirrored the results we have reported. In our study and that reported by Kolpek, peak negative NB was seen on week 3 despite adequate delivery of predicted and measured calories. We have found it impossible to establish positive NB acutely following SCI. We have hypothesized that negative NB is obligatory in these patients. Our data demonstrate this phenomenon in three ways. First, when given protein and calories adequate to meet predicted needs, SCI patients were in negative NB. When an increase in protein and calories was delivered, NB remained unchanged. Despite overfeeding as measured by indirect calorimetry, these patients remained in negative NB. The second argument in favor of this negative NB being &dquo;obligatory&dquo; is based on comparison of SCI patients to multi-system trauma patients without SCI (controls). Positive NB was obtained in all but three patients in the control group by the 3rd week after injury. Since ISSmatched controls were used, the differences we noticed in SCI patients can only be explained by the presence of SCI. The method of correlating ISS and NB has previously been used by Andrassy and Dubois. 12 Thirdly, the
et
tion and MEE in
seven
demonstration of obligatory negative NB was made dramatically by a tragic case (Fig. 3). We followed a 22year-old Hispanic women on the trauma service who suffered a closed head injury, blunt rupture of the thoracic aorta, and a lumbar spine fracture not associated with neurologic deficit. With aggressive delivery of protein and calories, the patient was in positive NB on week 2 following her injury. She then went to the operating room for stabilization of her lumbar spine and suffered perioperative spinal cord injury resulting in paraplegia. Immediately thereafter, she developed negative NB despite increases in previously adequate amounts of protein and calories (Fig. 2). The pattern of her nitrogen balances again began to parallel the overall pattern that was apparent in our other patients with acute SCI. The mechanism responsible for obligatory negative NB in acute SCI remains speculative. Studies on the effects of immobilization on metabolism date back to the work by Dietrick et ap3 in 1948. Four conscientious objectors were immobilized at bed rest in a pelvic girdle and leg casts for 6 to 7 weeks and studied on a metabolism ward. All four subjects showed an increase in nitrogen excretion and negative NB during immobilization. Interestingly, the delay in development of negative NB for up to 5 days was also observed in our patients in whom NB was measured early. More recently, Bunker et all’ described negative nitrogen balance in housebound elderly people whereas age-matched active individuals were in nitrogen equilibrium. The authors speculated that immobility led to wasting and breakdown of muscle protein causing the negative NB. Unfortunately, comparison of these studies with an acutely injured population is not justified. However, acute immobilization could at least contribute to the elevated early nitrogen excretion in paralyzed patients. Many authors have speculated that denervation atrophy may also play a role in this phenomenon. Certainly, loss of lean body mass following SCI is a progressive process that occurs over a prolonged period. 15 The hormonal milieu immediately following SCI has not been well studied. Depressed thyroid function has been described immediately following cord injury and could be relevant. 16 However, alterations in thyroxine activity are difficult to interpret in acutely injured patients. Tumor necrosis factor and Interleukin1 appear to be mediators of altered protein metabolism following injury.17,18 Comparison of these monokine lev-
FIG. 3. Weekly 24-hour nitrogen balance determinations for exemplary patient (see discussion). Arrow indicates the point following injury where patient suffered perioperative spinal cord injury.
Downloaded from pen.sagepub.com at East Carolina University on April 23, 2015
322 els in SCI and NSCI patients may prove informative. With the observation of &dquo;obligatory negative nitrogen balance&dquo; in patients acutely following SCI, we have adopted a new approach to nutritional support in these patients. Our initial regimen is based on 2 g of protein/ kg of IBW and calories predicted by BEE times an activity factor of 1.2 and a stress factor of 1.6. Further changes in caloric delivery are based on needs measured by indirect calorimetry. Protein delivery is kept constant in spite of the anticipated measurement of negative NB. Aggressive attempts to achieve positive NB in these patients will fail and result in overfeeding.
6. American Diabetic Association, American Dietetic Association: A Guide for Professionals: The Effective Application of Exchange Lists for Meal Planning. 1977, p 17 7. Baker SP, O’Neill B, Haddon W, et al: The injury severity score: A method for describing patients with multiple injuries and evaluating emergency care. J Trauma 14:187, 1974 8. Baker SP, O’Neill B: The injury severity score: An update. J Trauma 16:882, 1976 9. Mackenzie TA, Clark NG, Bistrian BR, et al: A simple method for estimation of nitrogen balance in hospitalized patients: A review and supporting data for a previously proposed technique. J Am Coll Nutr 4:575-581, 1985 10. Kaufman HH, Rowlands BJ, Stern DK, et al: General metabolism in patients with acute paraplegia and quadriplegia. Neurosurgery 11.
ACKNOWLEDGMENTS
The authors wish to express deep appreciation to Ms. Diane Robinson for her assistance in preparation of the
manuscript.
1. 2.
3. 4.
13:277-280, 1989 12.
13.
REFERENCES
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