Correspondence
Beta-Blockade and Severe Burns
N Engl J Med 2002; 346:707-708February 28, 2002
- Article
To the Editor:
Herndon et al. (Oct. 25 issue)1 report that propranolol attenuates hypermetabolism and reverses muscle-protein catabolism in patients with severe burns. However, these conclusions must be critically examined, because the findings may be attributable to overfeeding. Patients in both groups received approximately 2000 kcal per day (57 and 70 kcal per kilogram of body weight in the control and propranolol groups, respectively). Both groups had a positive energy balance, with measured energy expenditures of 1670 and 1321 kcal per day, respectively, at two weeks, but the propranolol group had a daily caloric balance that was greater than that in the control group by approximately 210 kcal.
Increased carbohydrate intake improves nitrogen balance2 and skeletal-muscle balance.3 Beta-blockade, by reducing energy expenditure, would lead to a more positive energy balance and a more positive nitrogen balance if energy intake is maintained. The high energy expenditure in the control group is partly due to overfeeding through increases in lipogenesis4 and stimulation of catecholamine secretion by carbohydrates.5
The respiratory quotient at two weeks in the patients in the study by Herndon et al. was 0.9, indicating the absence of a steady state. Overfeeding with carbohydrates requires a nonoxidative pathway. Net lipogenesis produces a respiratory quotient above 1.0. Because the respiratory quotient in the current study was below 1.0, excess carbohydrate was used for glycogen repletion without consequence to the respiratory quotient, but with a limited capacity for glycogen storage. Since the carbohydrate balance was greater in the propranolol group than in the control group, so was the rate of glycogen repletion, measured as lean tissue by dual-energy x-ray absorptiometry and whole-body potassium scanning. As a result, values for lean tissue would be higher in the propranolol group than in the control group, without necessarily indicating increases in protein.
We question whether the results reported by Herndon et al. have implications for a wide variety of patients, such as adults with trauma or patients undergoing general surgery, since hypercaloric feeding to this degree is no longer practiced.
5 ReferencesJustin A. Maykel, M.D.
Sassan Pazirandeh, M.D.
Bruce R. Bistrian, M.D., Ph.D.
Harvard Medical School, Boston, MA 02115
bbistria@caregroup.harvard. edu 1
Herndon DN ,Hart DW ,Wolf SE ,Chinkes DL ,Wolfe RR . Reversal of catabolism by beta-blockade after severe burns. N Engl J Med 2001;345:1223-1229
Full Text | Web of Science | Medline2
Long JM III ,Wilmore DW ,Mason AD Jr ,Pruitt BA Jr . Effect of carbohydrate and fat intake on nitrogen excretion during total intravenous feeding. Ann Surg 1977;185:417-422
CrossRef | Web of Science | Medline3
Hart DW ,Wolf SE ,Zhang XJ , et al. Efficacy of a high-carbohydrate diet in catabolic illness. Crit Care Med 2001;29:1318-1324
CrossRef | Web of Science | Medline4
Schwarz JM ,Chiolero R ,Revelly JP , et al. Effects of enteral carbohydrates on de novo lipogenesis in critically ill patients. Am J Clin Nutr 2000;72:940-945
Web of Science | Medline5
Landsberg L ,Young JB . Insulin-mediated glucose metabolism in the relationship between dietary intake and sympathetic nervous system activity. Int J Obes 1985;9:Suppl 2:63-68
Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Dr. Maykel and his group suggest that the results we demonstrated with propranolol treatment were due to carbohydrate overfeeding, resulting in a net gain of lean mass through accrual of muscle glycogen, not muscle protein. We recognize the limitations of the methods used to measure lean mass in critically ill patients (dual-energy x-ray absorptiometry and total-body potassium counting), and we acknowledge that if muscle glycogen concentrations increase, the resulting increase in intracellular water could be mistakenly interpreted as an increase in protein (lean muscle) mass.
In this study, feeding was based on a formula devised to maintain total body weight during hospitalization.1 Patients in the control group actually received 1918±346 kcal per day, and those in the propranolol group received 1996± 215 kcal per day (P=0.83). However, propranolol treatment did reduce energy expenditure. It is conceivable that carbohydrate calories not used for energy expenditure might have been stored as muscle glycogen, but we emphasize that in addition to changes in lean mass measured by dual-energy x-ray absorptiometry and total-body potassium counting, increased net synthesis of muscle protein was measured in association with propranolol treatment by stable-isotope kinetic techniques performed independently. Thus, three independent methods yielded data that suggest that there was accrual of lean mass and protein in the severely burned children given propranolol.
In reply to the contention that muscle glycogen increased with propranolol treatment: We have now measured muscle glycogen concentrations in samples obtained from patients in both groups at their second isotopic study. We found no significant difference in muscle glycogen concentrations between patients in the control group and those in the propranolol group (mean ±SE, 16.9±2.1 and 15.8±1.6 mg of glucose per gram of muscle, respectively), further supporting our stated conclusions.
Perhaps the feeding regimen described in our article should be practiced more commonly in other populations. In fact, we have found that burned patients who obtain fewer calories than would be provided in this regimen lose weight, and weight loss in burned patients has been associated with poor outcomes.2,3 Although we and others have shown no direct benefit in terms of protein kinetics with high caloric feedings in critically ill patients,4 we have demonstrated that body mass is preserved, albeit with an overall gain in fat mass.5 Abundant calories in conjunction with anabolic agents such as propranolol appear to increase muscle protein accrual in critically ill patients so that strength and the ability to rehabilitate are improved.
5 ReferencesSteven E. Wolf, M.D.
Robert R. Wolfe, Ph.D.
David N. Herndon, M.D.
University of Texas Medical Branch, Galveston, TX 77550
swolf@utmb.edu 1
Hildreth MA ,Herndon DN ,Desai MH ,Duke MA . Reassessing caloric requirements in pediatric burn patients. J Burn Care Rehabil 1988;9:616-618
CrossRef | Medline2
Windsor JA ,Hill GL . Weight loss with physiologic impairment: a basic indicator of surgical risk. Ann Surg 1988;207:290-296
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Bistrian BR ,Sherman M ,Blackburn GL ,Marshall R ,Shaw C . Cellular immunity in adult marasmus. Arch Intern Med 1977;137:1408-1411
CrossRef | Web of Science | Medline4
Wolfe RR ,Goodenough RD ,Burke JF ,Wolfe MH . Response of protein and urea kinetics in burn patients to different levels of protein intake. Ann Surg 1983;197:163-171
CrossRef | Web of Science | Medline5
Hart DW ,Wolf SE ,Herndon DN , et al. Energy expenditure and caloric balance after burn: increased feeding leads to fat rather than lean mass accretion. Ann Surg 2002;235:152-161
CrossRef | Web of Science | Medline
