Comment

Diana Bilton

4

Royal Brompton Hospital, Department of Respiratory Medicine, London SW3 6NP, UK [email protected]

5

I declare that I have no conflicts of interest. 1

2 3

Valery PC, Morris PS, Byrnes CA, et al. Long-term azithromycin for Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention Study): a multicentre, double-blind, randomised controlled trial. Lancet Respir Med 2013; published online Sept 17. http://dx.doi.org/10.1016/S22132600(13)70185-1. Steinfort DP, Brady S, Weisinger HS, Einsiedel L. Bronchiectasis in central Australia: a young face to an old disease. Respir Med 2008; 102: 574–78. Stocks J, Thia LP, Sonnappa S. Evaluation and use of childhood lung function tests in cystic fibrosis. Curr Opin Pulm Med 2012; 18: 602–08.

6

7

Serisier DJ, Martin ML, McGuckin MA, et al. Effect of long-term, low-dose erythromycin on pulmonary exacerbations among patients with noncystic fibrosis bronchiectasis: the BLESS randomised controlled trial. JAMA 2013; 309: 1260–67. Altenburg J, deGraaf CS, Stienstra Y, et al. Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: the BAT randomised controlled trial. JAMA 2013; 309: 1251–59. Wong C, Jayaram L, Karalus N, et al. Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo- controlled trial. Lancet 2012; 380: 660–67. Wilson R, Wells AU. Azithromycin in bronchiectasis: when should it be used? Lancet 2012; 380: 627–29.

Muscle weakness and nutrition in critical illness: matching nutrient supply and use

www.thelancet.com/respiratory Vol 1 October 2013

(43% vs 34%), although this difference was no longer significant at the last assessment (31% vs 26%). Recovery of muscle strength was faster in patients given late PN, who also had earlier discharge from the intensive-care unit. In a subset of 120 patients from whom muscle biopsy samples were taken, markers of autophagy were more expressed in those who received late PN rather than early PN, and in 58 patients with weakness a significant inverse association was identified between autophagy and the occurrence of weakness. Since autophagy is a survival mechanism that provides cells with alternative sources of substrates in cases of

Published Online September 10, 2013 http://dx.doi.org/10.1016/ S2213-2600(13)70148-6 This online publication has been corrected. The corrected version first appeared at thelancet.com/ respiratory on October 7, 2013 See Articles page 621

LTH NHS Trust/Science Photo Library

Intensive-care unit acquired muscle weakness is a major complication of critical illness. A quarter of patients awaking from prolonged sedation develop this complication, which is associated with prolonged mechanical ventilation and stay in the intensive-care unit, and increased mortality.1 The most common causes of this weakness are critical illness polyneuropathy and myopathy, but muscle atrophy also reduces muscle strength. In The Lancet Respiratory Medicine, Hermans and colleagues2 present a substudy of the Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC) study.3 A large randomised controlled trial in which 4640 patients were randomly assigned to receive parenteral macronutrient supplementation within 48 h of admission to the intensive-care unit (early parenteral nutrition; PN) or to late PN (8 days or later after admission), in accordance with European and North American guidelines. Patients given late PN were more likely to be discharged alive from the intensive-care unit within 8 days than patients given early PN, but intensive-care unit, hospital, and 90-day mortality was not different. The patients given late PN had shorter duration of mechanical ventilation and hospitalisation. In the present study of 600 patients, the largest cohort of critically ill patients assessed for weakness so far, weakness assessed within 9 days of randomisation was significantly more common in patients receiving early PN compared with those receiving late PN

589

Comment

nutrient deficit,4 the result is not easily interpreted. One would expect increased muscle proteolysis and hence declining muscle function and strength associated with enhanced autophagy. However, optimised recycling of proteins with elimination of toxic proteins and damaged cell organelles might improve cell functioning.5 The late-PN regimen can be thought of as a special model of caloric restriction. Stress resistance of cultured cells is improved by serum obtained from individuals submitted to caloric restriction, and diverse organisms, from yeast to mammals, live longer when exposed to this serum.6 The molecular mechanisms involved in this process include the promotion by nitric oxide of mitochondrial biogenesis with increased energy production7 and activation of autophagy in different tissues, especially in the skeletal muscle.8 Mitochondrial autophagy (so-called mitophagy), together with mitochondrial fission and fusion, is the quality control process that keeps the mitochondria fully functional, leading to elimination of damaged organelles.9 Therefore, one can speculate that the latePN-induced caloric restriction promotes mitochondrial mechanisms for repair or removal, thus creating better cellular conditions for effective muscle contraction and strength generation. The findings of Hermans and colleagues2 should be viewed as hypothesis generating, and need to be confirmed in future efficacy trials. First, muscle weakness during the acute stage of critical illness is difficult to assess with volition-dependent techniques, including the Medical Research Council score or dynamometry: these measurements are often affected by many factors not related to muscle physiology.10 Second, early PN adds a fluid load that might temporarily affect muscle performance in cases of a positive total fluid balance. This assumption is supported by other recent results of the same authors based on quantitative CT, showing increased amounts of water and lipid content in the skeletal muscle of patients receiving early PN.7 Finally, a third of participants in the intensive-care unit who were enrolled into the study were cardiac surgery patients who therefore have specific risks (ie, higher rates of atrial fibrillation and ventricular dysrhythmias), shorter average stay in the intensive-care unit, and lower mortality rates than general patients in these units. This might raise questions about the generalisability 590

of the clinical results to the total intensive-care-unit population, as well as the proposed pathophysiological mechanisms. In published series, mortality was increased in patients with intensive-care unit acquired muscle weakness.1 Strategies promoting a balanced equilibrium between mitochondrial biogenesis and autophagy might be of help in the early phase of critical illness. In future studies, outcome measures should include the appropriate assessment of the patient’s functional independence rather than simple muscle strength, because survivors of intensive-care units might have persistent functional limitations and physical disability after recovery of muscle strength.11 *Nicola Latronico, Enzo Nisoli, Matthias Eikermann Department of Anaesthesia and Critical Care Medicine, University of Brescia at Spedali Civili, Piazzale Ospedali Civili, 1, 25123 Brescia, Italy (NL); Centre for Study and Research on Obesity, Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy (EN); Department of Anaesthesia, Critical Care and Pain Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA (ME); and Klinik fuer Anaesthesiologie und Intensivmedizin, Essen-Duisburg University, Essen, Germany (ME) [email protected] We declare that we have no conflicts of interest. 1

2

3 4 5

6 7

8

9

10

11

Latronico N, Bolton CF. Critical illness polyneuropathy and myopathy: a major cause of muscle weakness and paralysis. Lancet Neurol 2011; 10: 931–41. Hermans G, Casaer MP, Clerckx B, et al. Effect of tolerating macronutrient deficit on the development of intensive-care unit acquired weakness: a subanalysis of the EPaNIC trial. Lancet Respir Med 2013; published online Sept 10. http://dx.doi.org/10.1016/S22132600(13)70183-8. Casaer MP, Mesotten D, Hermans G, et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med 2011; 365: 506–17. Hotchkiss RS, Strasser A, McDunn JE, Swanson PE. Cell death. N Engl J Med 2009; 361: 1570–83. Vanhorebeek I, Gunst J, Derde S, et al. Insufficient activation of autophagy allows cellular damage to accumulate in critically ill patients. J Clin Endocrinol Metab 2011; 96: E633–45. Guarente L. Mitochondria—a nexus for aging, calorie restriction, and sirtuins? Cell 2008; 132: 171–76. 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; published online July 15. DOI:10.1097/ CCM.0b013e31828cef02. Wohlgemuth SE, Seo AY, Marzetti E, Lees HA, Leeuwenburgh C. Skeletal muscle autophagy and apoptosis during aging: effects of calorie restriction and life-long exercise. Exp Gerontol 2010; 45: 138–48. Liesa M, Shirihai OS. Mitochondrial dynamics in the regulation of nutrient utilization and energy expenditure. Cell Metab 2013; 17: 491–506. Waak K, Zaremba S, Eikermann M. Muscle strength measurement in the intensive care unit: not everything that can be counted counts. J Crit Care 2013; 28: 96–98. Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet 2009; 373: 1874–82.

www.thelancet.com/respiratory Vol 1 October 2013

Muscle weakness and nutrition in critical illness: matching nutrient supply and use.

Muscle weakness and nutrition in critical illness: matching nutrient supply and use. - PDF Download Free
629KB Sizes 0 Downloads 0 Views