CLINICAL NUTRITION CASE THE HAZARDS OF HYPERCALORIC NUTRITIONAL SUPPORT IN RESPIRATORY DISEASE This case illustrates the dangers of hypercaloric feeding in a patient with limited respiratory reserve, in this instance secondary to heart-lung transplantation. The patient’s postoperative course was complicated by repeated bouts of infection andlor rejection that resulted in intubation and ventilatory support. The excessive caloric and protein load given to the patient resulted in increased C 0 2 generation with subsequent inability to wean the patient off the ventilator. Recognition of the problem and appropriate decreases in substrate intake permitted extubation.
Nutritional management of the critically ill patient presents particular challenges. Difficulties arise because the traditional parameters used to assess and monitor nutritional status are often altered because of the concomitant inflammatory Furthermore, if the disease has had a protracted course prior to hospitalization, there may be compromise of the visceral and somatic protein stores in addition to those of fat and glycogen. These nutritional depletions, often considered the sequelae of a prolonged disease process, are caused by associated hypermetabolism, malaise, and/or anorexia. Apart from these chronic changes, dramatic and accelerated utilization of muscle and fat stores, or “autocannibalism,” characterizes the acute illness.‘ Thus, the combination of these two processes often blurs the targeting of accurate nutritional needs and, if estimations are excessive in either direction, may adversely affect patient outcome. When the respiratory system is involved, several additional factors, recently identified, should be taken into consideration. This case was prepared by Mark T. DeMeo, M.D., Assistant Professor of Medicine, Sohrab Mobarhen M.D., Associate Chief of Gastroenterology, and William Van De Graaff M.D., Assistant Professor of Medicine, of Loyola University Medical Center, 2160 South First Avenue, Maywood, I1 60153. 112 NUTRmoN REVIEWSNOL 49.NO QIAPRIL 1991
Previously, it had been felt that, because of their integral role in the survival of the organism, the diaphragm and other respiratory muscles were relatively spared during periods of starvation. However, it is now recognized that reductions in diaphragmatic muscle mass and thickness parallel changes in body weight. This subsequently has an adverse effect on diaphragmatic strength and endurance, which may contribute to ventilatory f a i l ~ r e . ~Further.~ more, the substrates used during nutritional support may have a profound effect on gas exchange and respiratory fatigue, especially in the compromised patient with limited pulmonary reserve. Carbohydrate infusion can cause respiratory embarrassment in at least two ways. The first is a function of the hypermetabolic state of the critically ill patient. When such patients receive large infusions of glucose, there is minimal reduction in net lipolysis, a marked increase in norepinephrine excretion and resting energy expenditure, and continued fat oxidation with no net lipogenesis. The result is a large increase in carbon dioxide (CO,) production and oxygen con~umption.~ In a second scenario, larger glucose loads, which can be metabolically utilized by a more stable host, may not be as efficiently utilized in a stressed patient even if that patient is “hypermetabolic.”* In this situation, net lipogenesis occurs with the resultant effect of produc-
tion of eight molecules of COP for each molecule of oxygen consumed, thereby increasing the respiratory quotient and even elevating it above 1. Both of these situations will lead to increased production of COP with a resultant increased respiratory burden. When this situation is superimposed on an already-compromised lung, respiratory distress may e n s ~ e . ~Burke . l ~ et al." determined that, in stressed patients, maximal oxidation of infused glucose occurred at a rate of 5 mg/kg/min. Attention to maintaining glucose loads at or below this rate may decrease or obviate the COP burden placed on the pulmonary system. Also, intravenous infusions of amino acids appear to increase ventilatory sensitivity to PaCO,. This in effect lowers the pulmonary set point for CO, further increasing the respiratory burden.12-13 Lipid infusions may also influence lung function, but through different mechanisms. These effects may result from difficulties clearing the fat globules but are more likely secondary t o the vasoactive effects of the generated prostaglandins and leukotrienes.14-15 Thus, the ability to manage these difficult patients successfully is complicated by the lack of reliable parameters to assess and follow patients so as to guide the amount of calories to give and determine the proportion of the various substrates to use. We report a case that exemplifies these problems and describes our experience.
Case Report Mr G.S. is a 39-year-old white male with a history of congenital ventriculoseptal defect with right-to-left intracardiac shunting of blood. This resulted in pulmonary hypertension and subsequent heart failure (Eisenmenger's syndrome). He presented to our university medical center for heart-lung transplantation. The transplant operation was performed on November 28, 1989 and, despite requiring a return to the operating room the following day because of internal bleeding, was considered successful. The patient's initial nutritional profile revealed a height of 180 cm and a weight of 68 kg (UW 70 kg. IBW 78 kg). His somatic protein status was judged to be mildly impaired and his
visceral protein status as manifest by an albumin of 4.8 g/dL and a total lymphocyte count of 1400 was considered adequate. By December 3. the patient was Started on a clear liquid diet and appeared to tolerate it well. However, soon thereafter he began the first in a long series of rejection episodes and/or complications of immune suppression. On December 1 1 the patient began having difficulties maintaining adequate oral food intake because of marked odynophagia. Subsequent endoscopy revealed vesicular lesions in the esophagus consistent with herpes simplex infection and the patient was started on gancyclovir as well as antibiotics for a presumed bacterial lung infection. By December 21 the patient's weight had dropped to 61.6 kg and his albumin was 2.5 g/dL. On January 1 1 , the patient had a respiratory arrest and was intubated, and on January 19 total parenteral nutrition (TPN) was started. At this time the patient weighed 58 kg with an albumin of 2.2 g/dL; the estimated basal energy expenditure was 1769 kcal. He was started on a solution supplying 2485 nonprotein calories (npc), consisting of 1485 carbohydrate calories and lo00 lipid calories, as well as 94 g protein. The patient continued on this formula until January 21, when the line was pulled because of a positive blood culture. Total parenteral nutrition was restarted four days later, this time providing 2566 npc and 115 g protein. A 24-hour urine urea nitrogen was obtained and nitrogen intake, calculated on January 30, showed a positive nitrogen balance at 1.4 g/day, but in spite of this value, the rate was increased to provide 2942 npc and 122 g protein. Before the rate of infusion was increased the patient underwent elective endotracheal intubation in preparation for a left thoracotomy, which was performed for persistent drainage from the previous incision. The service was initially able to wean the patient off the ventilator. However, because of increasing respiratory distress, the ventilator was reintubated on February 7. Out of concern about the lack of response of the visceral protein status, the rate of TPN infusion was again increased on February 9 to provide 3742 npc and 173 g protein. Two attempts to extubate the patient over the next seven days were unsuccessful, resulting in tracheostomy placement on February 20. Four days later the service noted a marked deterioration in respiratory status. This was attributed to an undocumented aspiration. Enteral feeding was also reinitiated and the combined nutritional intake .provided 3594 npc and 199 g protein. Within two weeks the protein delivery was inNUTRITION REVIEWSIVOL 49, NO QIAPRIL 1991 113
creased to provide 202 g along with 3056 npc (70% carbohydrate and 30% fat). On March 13 a UUN was positive at +8 but the formula continued to supply 3056 npc and 171 g protein. At this time the service was having great difficulty getting the patient off the respirator and ventilatory requirements were increasing. On March 29 a medical nutrition consult was ordered. Because of a previous study by Baker et al.,l6 which suggested that these critically ill patients are not usually hypermetabolic. we recommended an immediate decrease in the nonprotein caloric load to 2400 (70% as carbohydrate and 30% as fat) and the total protein to 110 g/day. Within 48 hours the patient had a marked reduction in his minute ventilation(Ve). Table 1 shows representative respiratory values for his hospital course. The patient's respiratory status slowly improved and on April 18 he was taken off mechanical ventilation. Enteral feedings were initiated and slowly advanced. Finally, on April 26 the tracheostomy was plugged and the patient was placed on 4 L of oxygen via nasal cannula. Total parenteral nutrition was also discontinued. The albumin had risen to 2.8 g/dL. The patient continued to improve slowly and on May 18 was discharged to home.
Discussion This case illustrates a variation on an already-recognized clinical observation, namely, the inability of a compromised respiratory system to eliminate increased amounts of CO,. In this case a heart-lung
TABLE 1 Effectsof Parented Infusion on Respiratory Parameters* TPN Event
March 27
KcaVday (npc) Rotein (g)
3060
RR
171 18
KO2
30
Compliance Ve
25
vt
18
lo00
A~ril4 2360 I02 15
33 28 II 730
TPN = total parcntcral nutrition; npc = nonprotein calories; 6 0 , = Icvcl of carbon dioxide (CO,) in the blood; compliance = cstitnation of chticity of lung; Vc = minute ventilation; Vt = tidol volume; S = spontaneous respiratory rate; RR = mechanical brcaths drlivcrcd by ventilator. 114 N U T R m RffIEWSIVroL 49.NO 4IAPRIL 1991
transplant provided the trigger for the repeated bouts of infection and/or rejection that plagued the patient during his hospital course and compromised his lung function. It is interesting to note that although the patient was classified preoperatively as mildly nutritionally depleted, the excessive calories he received parenterally during his hospitalization had little impact on his depressed visceral protein status. One of these values, the low serum albumin, was the impetus for increasing total calories and protein calories, yet its return to normal levels paralleled the resolution of the inflammatory processes rather than the amount of exogenous substrate provided. In fact, the provision of excessive total and protein calories was probably detrimental in this patient, as the mechanisms previously discussed in this paper might explain. Table 1 demonstrates the correlation between the excess intravenous calories/ protein and minute ventilation, an association previously reported by others.lo The left column is representative of the high minute ventilation required during the high CarbohydraWprotein load. The right column shows his respiratory response when the substrate load was decreased. The rapid reduction in minute ventilation during a period when he otherwise appeared stable and showed no significant change in his respiratory compliance can be best attributed to reduced CO, production. This case exemplifies most complications of TPN in a patient with a compromised respiratory status. Specifically, the excessive unutilized carbohydrate calories could have been converted to storage fat with subsequent COP liberation and/or these excess glucose calories in a hypermetabolic patient could further increase metabolic rate and CO, generation. In addition to the generation of more COO, increases in the metabolic rate brought about by hypercaloric infusions have been shown to increase ventilatory response to hypoxia and hyper~apnia.'~ This patient's respiratory reserve, alregdy compromised by infection and/or rejection, was unable to
accommodate the increased demand, which contributed to the difficulty in weaning him off the ventilator. In both normal subjects and patients, increased demand on the respiratory system often takes the form of increases in minute ventilation.lO In our patient, increases in Ve up to 20 L were seen while on the high-calorie diet. After reducing the caloric load, these values decreased to approximately 10-12 Umin. In fact, it was only after reduction of total caloric and protein intake that ventilatory support could be withdrawn. The high protein load, often in excess of 3 g/kg, did not change visceral and somatic protein status of our patient but probably contributed to an accelerated respiratory drive through increasing ventilatory response to COP in the blood.12.18The excessive protein delivered to the patient also contributed to the rising blood urea nitrogen (BUN) in this patient; and reduction of protein infusion correlated roughly with a decrease in those same levels. We believe that the clinical course of our patient strongly displays the dangers of providing high-calorie loads to critically ill patients. Recommendations for caloric intake based on visceral protein status in such patients must be made with caution. 1 . Dinarello CA. Interleukin-1 and the pathogenesis of the acute-phase response. N Engl J Med 1984;311:1413-18 2. Hasselgren P, Pedersen P, Sox HC. Current concepts of protein turnover and amino acid transport in liver and skeletal muscle during sepsis. Arch Surg 1988;123:992-9 3. Brown JM. C r o w MA. Harken AH. Cytokines and the surgeon. Surg Gynecol Obstet 1989;169: 568-75 4. Cerra FB. Siege1 JH, Coleman 8. et al. Septic autocannibalism. Ann. Surg. 1980;192:571-9 5. Arora NS. Rochester DE. Respiratory muscle
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
strength and maximal voluntary ventilation in undernourished patients. Am Rev Respir Dis 1982;126:5-8 Kelly SM. Rosa A, Field S,el al. lnspiratory muscle strength and body composition in patients receiving total parenteral nutrition. Am Rev Respir Dis 1984;130:33-7 Askanazi J. Rosenbaum SH. Hyman AL. el al. R e spiratory changes induced by the large glucose loads of total parenteral nutrition. JAMA 1980;243:1444-7 Vo NM. Woycaster M, Acutt RV. el al. Effects of postoperative carbohydrate overfeeding. Am Surg 1987;53:632-5 Askanazi J, Elwyn DH. Silverberg PA, el el. Respiratory distress secondary to a high carbohydrate load: a case report. Surgery 1980;87:596-8 Covelli HD, Black JW, Olsen MS, et al. Respiratory failure precipitated by high carbohydrate loads. Ann Int Med 1 9 8 1 ;95:579-81 Burke J. el el. Glucose requirements following burn injury. Ann Surg 1979;190:274-83 Weissman C, Askanazi J, Rosenbaum S. et al. Amino acids and respiration. Ann Int Med 1983; 98:41-4 Askanazi J, Weissman C. La Sala PA, el al. Effect of protein intake on ventilatory drive. Anesthesiology 1984;60:106-10 Hageman J. el al. lntralipid alterations in pulmonary prostaglandin metabolism and gas exchange. Crit Care Med 19833 1 :794-8 Askanazi J, el al. In: Kinney JM, Jeejeebhoy KN, Hill 0, eds. Respiratory diseases in nutrition and metabolism in patient care. Philadelphia, PA: WB Saunders. 1988 Baker JP, Detsky AS, Stewart S.et al. Randomized trial of total parenteral nutrition in critically ill patients: metabolic effects of varying glucose lipid ratios as the energy source. Gastroenterology 1984;87:53-9 Doekel R, Zwillich CW, Scoggin CH, el al. Clinical semistarvation: depression of hypoxic ventilatory response. N Engl J Med 1976295358-61 Askanazi J, Weissman C, Rosenbaum SH. et al. Nutrition and the respiratory system. Crit Care Med 1982;lO:lW-72
Nutritional management of the critically ill patient presents particular challenges. Difficulties arise because the traditional parameters used to assess and monitor nutritional status are often altered because of the concomitant inflammatory Furthermore, if the disease has had a protracted course prior to hospitalization, there may be compromise of the visceral and somatic protein stores in addition to those of fat and glycogen. These nutritional depletions, often considered the sequelae of a prolonged disease process, are caused by associated hypermetabolism, malaise, and/or anorexia. Apart from these chronic changes, dramatic and accelerated utilization of muscle and fat stores, or “autocannibalism,” characterizes the acute illness.‘ Thus, the combination of these two processes often blurs the targeting of accurate nutritional needs and, if estimations are excessive in either direction, may adversely affect patient outcome. When the respiratory system is involved, several additional factors, recently identified, should be taken into consideration. This case was prepared by Mark T. DeMeo, M.D., Assistant Professor of Medicine, Sohrab Mobarhen M.D., Associate Chief of Gastroenterology, and William Van De Graaff M.D., Assistant Professor of Medicine, of Loyola University Medical Center, 2160 South First Avenue, Maywood, I1 60153. 112 NUTRmoN REVIEWSNOL 49.NO QIAPRIL 1991
Previously, it had been felt that, because of their integral role in the survival of the organism, the diaphragm and other respiratory muscles were relatively spared during periods of starvation. However, it is now recognized that reductions in diaphragmatic muscle mass and thickness parallel changes in body weight. This subsequently has an adverse effect on diaphragmatic strength and endurance, which may contribute to ventilatory f a i l ~ r e . ~Further.~ more, the substrates used during nutritional support may have a profound effect on gas exchange and respiratory fatigue, especially in the compromised patient with limited pulmonary reserve. Carbohydrate infusion can cause respiratory embarrassment in at least two ways. The first is a function of the hypermetabolic state of the critically ill patient. When such patients receive large infusions of glucose, there is minimal reduction in net lipolysis, a marked increase in norepinephrine excretion and resting energy expenditure, and continued fat oxidation with no net lipogenesis. The result is a large increase in carbon dioxide (CO,) production and oxygen con~umption.~ In a second scenario, larger glucose loads, which can be metabolically utilized by a more stable host, may not be as efficiently utilized in a stressed patient even if that patient is “hypermetabolic.”* In this situation, net lipogenesis occurs with the resultant effect of produc-
tion of eight molecules of COP for each molecule of oxygen consumed, thereby increasing the respiratory quotient and even elevating it above 1. Both of these situations will lead to increased production of COP with a resultant increased respiratory burden. When this situation is superimposed on an already-compromised lung, respiratory distress may e n s ~ e . ~Burke . l ~ et al." determined that, in stressed patients, maximal oxidation of infused glucose occurred at a rate of 5 mg/kg/min. Attention to maintaining glucose loads at or below this rate may decrease or obviate the COP burden placed on the pulmonary system. Also, intravenous infusions of amino acids appear to increase ventilatory sensitivity to PaCO,. This in effect lowers the pulmonary set point for CO, further increasing the respiratory burden.12-13 Lipid infusions may also influence lung function, but through different mechanisms. These effects may result from difficulties clearing the fat globules but are more likely secondary t o the vasoactive effects of the generated prostaglandins and leukotrienes.14-15 Thus, the ability to manage these difficult patients successfully is complicated by the lack of reliable parameters to assess and follow patients so as to guide the amount of calories to give and determine the proportion of the various substrates to use. We report a case that exemplifies these problems and describes our experience.
Case Report Mr G.S. is a 39-year-old white male with a history of congenital ventriculoseptal defect with right-to-left intracardiac shunting of blood. This resulted in pulmonary hypertension and subsequent heart failure (Eisenmenger's syndrome). He presented to our university medical center for heart-lung transplantation. The transplant operation was performed on November 28, 1989 and, despite requiring a return to the operating room the following day because of internal bleeding, was considered successful. The patient's initial nutritional profile revealed a height of 180 cm and a weight of 68 kg (UW 70 kg. IBW 78 kg). His somatic protein status was judged to be mildly impaired and his
visceral protein status as manifest by an albumin of 4.8 g/dL and a total lymphocyte count of 1400 was considered adequate. By December 3. the patient was Started on a clear liquid diet and appeared to tolerate it well. However, soon thereafter he began the first in a long series of rejection episodes and/or complications of immune suppression. On December 1 1 the patient began having difficulties maintaining adequate oral food intake because of marked odynophagia. Subsequent endoscopy revealed vesicular lesions in the esophagus consistent with herpes simplex infection and the patient was started on gancyclovir as well as antibiotics for a presumed bacterial lung infection. By December 21 the patient's weight had dropped to 61.6 kg and his albumin was 2.5 g/dL. On January 1 1 , the patient had a respiratory arrest and was intubated, and on January 19 total parenteral nutrition (TPN) was started. At this time the patient weighed 58 kg with an albumin of 2.2 g/dL; the estimated basal energy expenditure was 1769 kcal. He was started on a solution supplying 2485 nonprotein calories (npc), consisting of 1485 carbohydrate calories and lo00 lipid calories, as well as 94 g protein. The patient continued on this formula until January 21, when the line was pulled because of a positive blood culture. Total parenteral nutrition was restarted four days later, this time providing 2566 npc and 115 g protein. A 24-hour urine urea nitrogen was obtained and nitrogen intake, calculated on January 30, showed a positive nitrogen balance at 1.4 g/day, but in spite of this value, the rate was increased to provide 2942 npc and 122 g protein. Before the rate of infusion was increased the patient underwent elective endotracheal intubation in preparation for a left thoracotomy, which was performed for persistent drainage from the previous incision. The service was initially able to wean the patient off the ventilator. However, because of increasing respiratory distress, the ventilator was reintubated on February 7. Out of concern about the lack of response of the visceral protein status, the rate of TPN infusion was again increased on February 9 to provide 3742 npc and 173 g protein. Two attempts to extubate the patient over the next seven days were unsuccessful, resulting in tracheostomy placement on February 20. Four days later the service noted a marked deterioration in respiratory status. This was attributed to an undocumented aspiration. Enteral feeding was also reinitiated and the combined nutritional intake .provided 3594 npc and 199 g protein. Within two weeks the protein delivery was inNUTRITION REVIEWSIVOL 49, NO QIAPRIL 1991 113
creased to provide 202 g along with 3056 npc (70% carbohydrate and 30% fat). On March 13 a UUN was positive at +8 but the formula continued to supply 3056 npc and 171 g protein. At this time the service was having great difficulty getting the patient off the respirator and ventilatory requirements were increasing. On March 29 a medical nutrition consult was ordered. Because of a previous study by Baker et al.,l6 which suggested that these critically ill patients are not usually hypermetabolic. we recommended an immediate decrease in the nonprotein caloric load to 2400 (70% as carbohydrate and 30% as fat) and the total protein to 110 g/day. Within 48 hours the patient had a marked reduction in his minute ventilation(Ve). Table 1 shows representative respiratory values for his hospital course. The patient's respiratory status slowly improved and on April 18 he was taken off mechanical ventilation. Enteral feedings were initiated and slowly advanced. Finally, on April 26 the tracheostomy was plugged and the patient was placed on 4 L of oxygen via nasal cannula. Total parenteral nutrition was also discontinued. The albumin had risen to 2.8 g/dL. The patient continued to improve slowly and on May 18 was discharged to home.
Discussion This case illustrates a variation on an already-recognized clinical observation, namely, the inability of a compromised respiratory system to eliminate increased amounts of CO,. In this case a heart-lung
TABLE 1 Effectsof Parented Infusion on Respiratory Parameters* TPN Event
March 27
KcaVday (npc) Rotein (g)
3060
RR
171 18
KO2
30
Compliance Ve
25
vt
18
lo00
A~ril4 2360 I02 15
33 28 II 730
TPN = total parcntcral nutrition; npc = nonprotein calories; 6 0 , = Icvcl of carbon dioxide (CO,) in the blood; compliance = cstitnation of chticity of lung; Vc = minute ventilation; Vt = tidol volume; S = spontaneous respiratory rate; RR = mechanical brcaths drlivcrcd by ventilator. 114 N U T R m RffIEWSIVroL 49.NO 4IAPRIL 1991
transplant provided the trigger for the repeated bouts of infection and/or rejection that plagued the patient during his hospital course and compromised his lung function. It is interesting to note that although the patient was classified preoperatively as mildly nutritionally depleted, the excessive calories he received parenterally during his hospitalization had little impact on his depressed visceral protein status. One of these values, the low serum albumin, was the impetus for increasing total calories and protein calories, yet its return to normal levels paralleled the resolution of the inflammatory processes rather than the amount of exogenous substrate provided. In fact, the provision of excessive total and protein calories was probably detrimental in this patient, as the mechanisms previously discussed in this paper might explain. Table 1 demonstrates the correlation between the excess intravenous calories/ protein and minute ventilation, an association previously reported by others.lo The left column is representative of the high minute ventilation required during the high CarbohydraWprotein load. The right column shows his respiratory response when the substrate load was decreased. The rapid reduction in minute ventilation during a period when he otherwise appeared stable and showed no significant change in his respiratory compliance can be best attributed to reduced CO, production. This case exemplifies most complications of TPN in a patient with a compromised respiratory status. Specifically, the excessive unutilized carbohydrate calories could have been converted to storage fat with subsequent COP liberation and/or these excess glucose calories in a hypermetabolic patient could further increase metabolic rate and CO, generation. In addition to the generation of more COO, increases in the metabolic rate brought about by hypercaloric infusions have been shown to increase ventilatory response to hypoxia and hyper~apnia.'~ This patient's respiratory reserve, alregdy compromised by infection and/or rejection, was unable to
accommodate the increased demand, which contributed to the difficulty in weaning him off the ventilator. In both normal subjects and patients, increased demand on the respiratory system often takes the form of increases in minute ventilation.lO In our patient, increases in Ve up to 20 L were seen while on the high-calorie diet. After reducing the caloric load, these values decreased to approximately 10-12 Umin. In fact, it was only after reduction of total caloric and protein intake that ventilatory support could be withdrawn. The high protein load, often in excess of 3 g/kg, did not change visceral and somatic protein status of our patient but probably contributed to an accelerated respiratory drive through increasing ventilatory response to COP in the blood.12.18The excessive protein delivered to the patient also contributed to the rising blood urea nitrogen (BUN) in this patient; and reduction of protein infusion correlated roughly with a decrease in those same levels. We believe that the clinical course of our patient strongly displays the dangers of providing high-calorie loads to critically ill patients. Recommendations for caloric intake based on visceral protein status in such patients must be made with caution. 1 . Dinarello CA. Interleukin-1 and the pathogenesis of the acute-phase response. N Engl J Med 1984;311:1413-18 2. Hasselgren P, Pedersen P, Sox HC. Current concepts of protein turnover and amino acid transport in liver and skeletal muscle during sepsis. Arch Surg 1988;123:992-9 3. Brown JM. C r o w MA. Harken AH. Cytokines and the surgeon. Surg Gynecol Obstet 1989;169: 568-75 4. Cerra FB. Siege1 JH, Coleman 8. et al. Septic autocannibalism. Ann. Surg. 1980;192:571-9 5. Arora NS. Rochester DE. Respiratory muscle
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
strength and maximal voluntary ventilation in undernourished patients. Am Rev Respir Dis 1982;126:5-8 Kelly SM. Rosa A, Field S,el al. lnspiratory muscle strength and body composition in patients receiving total parenteral nutrition. Am Rev Respir Dis 1984;130:33-7 Askanazi J. Rosenbaum SH. Hyman AL. el al. R e spiratory changes induced by the large glucose loads of total parenteral nutrition. JAMA 1980;243:1444-7 Vo NM. Woycaster M, Acutt RV. el al. Effects of postoperative carbohydrate overfeeding. Am Surg 1987;53:632-5 Askanazi J, Elwyn DH. Silverberg PA, el el. Respiratory distress secondary to a high carbohydrate load: a case report. Surgery 1980;87:596-8 Covelli HD, Black JW, Olsen MS, et al. Respiratory failure precipitated by high carbohydrate loads. Ann Int Med 1 9 8 1 ;95:579-81 Burke J. el el. Glucose requirements following burn injury. Ann Surg 1979;190:274-83 Weissman C, Askanazi J, Rosenbaum S. et al. Amino acids and respiration. Ann Int Med 1983; 98:41-4 Askanazi J, Weissman C. La Sala PA, el al. Effect of protein intake on ventilatory drive. Anesthesiology 1984;60:106-10 Hageman J. el al. lntralipid alterations in pulmonary prostaglandin metabolism and gas exchange. Crit Care Med 19833 1 :794-8 Askanazi J, el al. In: Kinney JM, Jeejeebhoy KN, Hill 0, eds. Respiratory diseases in nutrition and metabolism in patient care. Philadelphia, PA: WB Saunders. 1988 Baker JP, Detsky AS, Stewart S.et al. Randomized trial of total parenteral nutrition in critically ill patients: metabolic effects of varying glucose lipid ratios as the energy source. Gastroenterology 1984;87:53-9 Doekel R, Zwillich CW, Scoggin CH, el al. Clinical semistarvation: depression of hypoxic ventilatory response. N Engl J Med 1976295358-61 Askanazi J, Weissman C, Rosenbaum SH. et al. Nutrition and the respiratory system. Crit Care Med 1982;lO:lW-72
