Online Letters to the Editor 3. Sociedad Española de Medicina Preventiva Salud Pública e Higiene: Diapos Resultados EPINE 1990–2011. Available at: Accessed December 3, 2013 4. Almirante B, Limón E, Freixas N, et al: Laboratory-based surveillance of hospital-acquired catheter-related bloodstream infections in Catalonia. Results of the VINCat Program (2007–2010). Enferm Inf Microb Clin 2012; 30(Suppl 3):13–19 5. Pronovost PJ, Goeschel CA: Time to take health delivery research seriously. JAMA 2011; 306:310–311

This work was performed at Beth Israel Deaconess Medical Center. Dr. Bistrian consulted for Nestle (advises on major nutritional issues) and has stock options with Pronutria.

DOI: 10.1097/CCM.0000000000000233


Timing of Parenteral Nutrition Support To the Editor:


he effect of early versus late parenteral nutrition (PN) on muscle and adipose tissue in neurosurgical patients (1) presents interesting and valuable data about the potential role of CT scanning for assessing body composition. The increase in fat tissue/water with the much greater use of parenteral glucose in the early PN group would be expected to increase fat synthesis, since more than two thirds of parenteral glucose is not directly oxidized (2), and the insulin response to glucose has a very potent antinatriuretic and antidiuretic effect (3). This effect on water metabolism would be much greater in hydrated tissue such as muscle and much less in adipose tissue that has little water. Although one of the important goals for nutritional support is to maintain skeletal muscle function, particularly in the later stages of an extended illness where protein calorie malnutrition may be present, there is limited likelihood that meeting all nutritional requirements can prevent the early, severe loss of protein from the usually active leg muscles of a now completely immobilized, acute neurosurgical patient. Furthermore, the failure to detect a difference in skeletal muscle loss with the two feeding regimens may also reflect, in part, the very small difference in protein intake which I estimate to be about 200–250 g over the study period. With an estimated net protein utilization of less than 50% and muscle being about half of lean body mass, one would anticipate a less than 1–1.5% difference in muscle volume which would be hard to detect in this small number of patients. There are, however, other important benefits of early nutritional support that can be responsive to the better nitrogen balance that increased protein intake provides (4), such as improved tissue repair and immune response. For instance, it takes about 30 g of new protein synthesis just to maintain a WBC count of 20,000/mm3. However, in this study, this potential immunologic benefit would have been countered by the unusual dietary regimen of an initial 2 days of hypertonic dextrose without protein in the early PN group. Such feeding may have adverse immunologic consequences since hypertonic dextrose alone in substantial amounts critically lowers plasma branchedchain amino acid concentrations that in experimental animals reversibly impair cellular immunity (5). Thus, this study provides an excellent demonstration of a potentially valuable body composition technique for the critically ill, but it does not help to identify the optimal timing of nutritional support. Critical Care Medicine

Bruce R. Bistrian, MD, PhD, Division of Clinical Nutrition, Beth Israel Deaconess Medical Center, Boston, MA

1. Casaer MP, Langouche L, Coudyzer W, et al: Impact of Early Parenteral Nutrition on Muscle and Adipose Tissue Compartments During Critical Illness. Crit Care Med 2013; 41:2298–2309 2. Wolfe RR, O’Donnell TF Jr, Stone MD, et al: Investigation of factors determining the optimal glucose infusion rate in total parenteral nutrition. Metabolism 1980; 29:892–900 3. Rudman D, Millikan WJ, Richardson TJ, et al: Elemental balances during intravenous hyperalimentation of underweight adult subjects. J Clin Invest 1975; 55:94–104 4. Hoffer LJ, Bistrian BR: Appropriate protein provision in critical illness: A systematic and narrative review. Am J Clin Nutr 2012; 96: 591–600 5. Moldawer LL, Trerice MS, Flatt JP, et al: A protein sparing model in the rat during hypocaloric feeding: Factors determining preservation of visceral protein function. J Surg Res 1978; 25:424–432 DOI: 10.1097/CCM.0000000000000168

The authors reply:


e thank Bristrian (1) for kindly appreciating our assessment of body composition changes during critical illness through quantitative CT (qCT). This EPaNIC substudy, indeed, does not answer the clinical question when to start artificial feeding. This question has been addressed by three different high-quality randomized controlled trials (RCTs) including 6,317 patients, unanimously showing no immediate vital or delayed functional benefit with parenteral nutrition (PN) initiated before day 7 (early PN) in the ICU (2–4). The largest RCT even demonstrated net harm by early PN (2). Enhanced enteral nutrition during the first week in ICU, likewise, failed to provoke clinical benefit (5). The aim of the EPaNIC qCT substudy was to generate insight in the mechanisms of early PN’s failure. Early PN provoked a muscle composition shift toward water or fat, and it increased the volume of intramuscular adipose tissue. Therefore, as suggested by Bristrian (1), lipogenesis is more likely the underlying mechanism than water retention. Second, early PN failed to prevent muscle wasting, both early and late PN patients lost on average 7% of their initial muscle volume during the first week in ICU. Bristrian (1) suggests that this failure is partly due to the small difference in protein intake between the two patient groups. As he rightly estimated, supplementation of insufficient enteral nutrition with commercial all-in-one PN preparations resulted, after 1 week, in on average 270 g of additional protein administered to early PN patients. The cumulative protein intake did not correlate with muscle volume losses (r2 = 0.004; p = 0.82). Furthermore, 63% of the administered nitrogen with early PN in EPaNIC was eliminated via the urine (6). In addition, as The Nephro-Protective Trial-authors recently reported at European


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