Das Refeeding-Syndrom – Eine Literaturübersicht

Zusammenfassung

Das Refeeding-Syndrom ist eine gefährliche, mitunter lebensbedrohliche Komplikation, die nach der Wiederaufnahme einer adäquaten Nahrungszufuhr bei mangelernährten und kachektischen Patienten entstehen kann. Die Entwicklung eines Refeeding-Syndroms wurde nach oraler, enteraler und parenteraler Ernährung beschrieben. Ein frühzeitiges Erkennen eines Refeeding-Syndroms ist für eine adäquate Therapie unumgänglich, jedoch leider aufgrund einer unzureichenden Kenntnis dieses Krankheitsbilds nicht regelhaft. Leitsymptom des Refeeding-Syndroms ist eine Hypophosphatämie. Häufig wird diese von weiteren Elektrolytentgleisungen sowie von Mangelzuständen an Vitaminen und Spurenelementen begleitet. Aufgrund einer Zufuhr an Kohlenhydraten sowie intravenöser Flüssigkeitsgabe kann es zu einer Hypervolämie mit Herzversagen kommen. Weitere Organfunktionsstörungen unterschiedlichen Schweregrads, die bis zum Tod führen können, sind beschrieben worden. Zur Prävention eines Refeeding-Syndroms ist eine frühzeitige Identifikation von Risikopatienten und eine initial niedrige Kalorienzufuhr, begleitet von regelmäßigen laborchemischen Kontrollen unter Nahrungsaufbau, empfehlenswert.

Methoden: Literaturrecherche mit den Begriffen „refeeding syndrome“ sowie „hypophosphataemia“ mit Einbeziehung der NICE-Leitlinien aus dem Jahre 2006.

Abstract

The refeeding syndrome is a dangerous condition, which may even lead to death. The syndrome occurs after re-establishment of adequate nutrition in malnourished and cachectic patients. More specifically its occurrence has been reported during oral, enteral and parenteral feeding. Early diagnosis is crucial for adequate and timely therapy. However, due to a lack of knowledge in the community this is not always achieved. The leading symptom is hypophosphatemia, often accompanied by electrolyte disturbances and vitamin and trace element deficiencies. Due to a concomitant administration of carbohydrates and intravenous fluid volume it may also lead to hypervolemia with cardiac failure. Compromise of other organ functions with a varying degree of severity, even leading to death, have been reported. The most efficient prevention of the refeeding syndrom is recommended by an early identification of patients at risk and the administration of an initially lower caloric nutrition accompanied by a tight and regularly scheduled observation of relevant laboratory parameters.

Methods: This literature research included the following terms: “refeeding syndrome” and “hypophosphataemia” including the 2006 guidelines from the National Institute for Health and Clinical Excellence (UK).

Schlüsselwörter

Refeeding - Hypophosphatämie - Hypomagnesinämie - Hypokaliämie - Thiamin - Kachexie

Key words

refeeding syndrome - hypophosphataemia - hypomagnesinaemie - hypokaliaemia - thiamine - cachexia

• Literatur

• 1 Schnitker MA, Mattman PE, Bliss TL. A clinical study of malnutrition in Japanese prisoners of war. Annals of internal medicine 1951; 35: 69-96
• 2 Crook MA, Hally V, Panteli JV. The importance of the refeeding syndrome. Nutrition (Burbank, Los Angeles County, Calif) 2001; 17: 632-637
• 3 Mehanna HM, Moledina J, Travis J. Refeeding syndrome: what it is, and how to prevent and treat it. BMJ (Clinical research ed) 2008; 336: 1495-1498
• 4 Skipper A. Refeeding syndrome or refeeding hypophosphatemia: a systematic review of cases. Nutr Clin Pract 2012; 27: 34-40
• 5 Khan LU, Ahmed J, Khan S et al. Refeeding syndrome: a literature review. Gastroenterology research and practice 2011; 2011 , Article ID 410971.
• 6 Marik PE, Bedigian MK. Refeeding hypophosphatemia in critically ill patients in an intensive care unit. A prospective study. Arch Surg 1996; 131: 1043-1047
• 7 Dewar H, Horvath R. Refeeding Syndrome:. Oxford Radcliffe Hospital NHS Trust; 2001
• 8 Solomon SM, Kirby DF. The refeeding syndrome: a review. Jpen 1990; 14: 90-97
• 9 Dewar H, Horvath R. Refeeding-Syndrome. In: Todorovic VE, Micklewright A, (eds.) A pocket guide to clinical Nutrition. British Dietetic Association; 2001
• 10 Crook MA, Panteli JV. The refeeding syndrome and hypophosphataemia in the elderly. Journal of internal medicine 2005; 257: 397-398
• 11 Fiaccadori E, Coffrini E, Fracchia C et al. Hypophosphatemia and phosphorus depletion in respiratory and peripheral muscles of patients with respiratory failure due to COPD. Chest 1994; 105: 1392-1398
• 12 Excellence NIfHaC. Nutrition support in adults. Clinical Guideline 32. In NICE Clinical Guidelines 2006
• 13 Cahill Jr GF. Starvation in man. The New England journal of medicine 1970; 282: 668-675
• 14 Cahill Jr GF, Herrera MG, Morgan AP et al. Hormone-fuel interrelationships during fasting. The Journal of clinical investigation 1966; 45: 1751-1769
• 15 Romijn JA, Godfried MH, Hommes MJ et al. Decreased glucose oxidation during short-term starvation. Metabolism: clinical and experimental 1990; 39: 525-530
• 16 Nesbakken R, Reinlie S. Magnesium and phosphorous: the electrolytes of energy metabolism. Acta anaesthesiologica Scandinavica 1985; 82: 60-64
• 17 Knochel JP. The pathophysiology and clinical characteristics of severe hypophosphatemia. Archives of internal medicine 1977; 137: 203-220
• 18 Hearing SD. Refeeding syndrome. BMJ 2004; 328: 908-909 (Clinical research ed)
• 19 Dietrich JW, Landgrafe G, Fotiadou EH. TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis. Journal of thyroid research 2012; 2012: 351864
• 20 Portnay GI, O'Brian JT, Bush J et al. The effect of starvation on the concentration and binding of thyroxine and triiodothyronine in serum and on the response to TRH. The Journal of clinical endocrinology and metabolism 1974; 39: 191-194
• 21 Rothenbuchner G, Loos U, Kiessling WR et al. The influence of total starvation on the pituitary-thyroid-axis in obese individuals. Acta Endocrinol Suppl (Copenh) 1973; 173: 144
• 22 Allon M, Copkney C. Albuterol and insulin for treatment of hyperkalemia in hemodialysis patients. Kidney international 1990; 38: 869-872
• 23 Campbell CH. The severe lacticacidosis of thiamine deficiency: acute pernicious or fulminating beriberi. Lancet 1984; 2: 446-449
• 24 Weisinger JR, Bellorin-Font E. Magnesium and phosphorus. Lancet 1998; 352: 391-396
• 25 Marino LP. The ICU Book. Lippincott Williams & Wilkins; 2008
• 26 Silva JE. Thermogenic mechanisms and their hormonal regulation. Physiological reviews 2006; 86: 435-464
• 27 van Marken LWD, Schrauwen P. Implications of nonshivering thermogenesis for energy balance regulation in humans. American journal of physiology 2011; 301: R285-R296
• 28 Wijers SL, Schrauwen P, Saris WH et al. Human skeletal muscle mitochondrial uncoupling is associated with cold induced adaptive thermogenesis. PloS one 2008; 3: e1777
• 29 Mitchell CS, Savage DB, Dufour S et al. Resistance to thyroid hormone is associated with raised energy expenditure, muscle mitochondrial uncoupling, and hyperphagia. The Journal of clinical investigation 2010; 120: 1345-1354
• 30 Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab 2007; 293: E444-E452
• 31 Golozoubova V, Hohtola E, Matthias A et al. Only UCP1 can mediate adaptive nonshivering thermogenesis in the cold. Faseb J 2001; 15: 2048-2050
• 32 Golozoubova V, Cannon B, Nedergaard J. UCP1 is essential for adaptive adrenergic nonshivering thermogenesis. Am J Physiol Endocrinol Metab 2006; 291: E350-E357
• 33 Salvatore D, Bartha T, Harney JW et al. Molecular biological and biochemical characterization of the human type 2 selenodeiodinase. Endocrinology 1996; 137: 3308-3315
• 34 Wijers SL, Schrauwen P, van Baak MA et al. Beta-adrenergic receptor blockade does not inhibit cold-induced thermogenesis in humans: possible involvement of brown adipose tissue. The Journal of clinical endocrinology and metabolism 2011; 96: E598-E605
• 35 Araujo RL, Andrade BM, da Silva ML et al. Tissue-specific deiodinase regulation during food restriction and low replacement dose of leptin in rats. Am J Physiol Endocrinol Metab 2009; 296: E1157-E1163
• 36 Bianco AC, Salvatore D, Gereben B et al. Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocrine reviews 2002; 23: 38-89
• 37 de Jesus LA, Carvalho SD, Ribeiro MO et al. The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. The Journal of clinical investigation 2001; 108: 1379-1385
• 38 Encke D, Ely M, Heldmaier G et al. Physiological approach to maturation of brown adipocytes in primary cell culture. Biochimica et biophysica acta 1997; 1357: 339-347
• 39 Coppola A, Liu ZW, Andrews ZB et al. A central thermogenic-like mechanism in feeding regulation: an interplay between arcuate nucleus T3 and UCP2. Cell metabolism 2007; 5: 21-33
• 40 Silva JE, Larsen PR. Hormonal regulation of iodothyronine 5'-deiodinase in rat brown adipose tissue. The American journal of physiology 1986; 251: E639-E643
• 41 Thomas C, Auwerx J, Schoonjans K. Bile acids and the membrane bile acid receptor TGR5--connecting nutrition and metabolism. Thyroid 2008; 18: 167-174
• 42 Dietrich JW. Thyreotoxische Krise [Thyroid storm]. Medizinische Klinik, Intensivmedizin und Notfallmedizin 2012; 107: 448-453
• 43 Falhammar H, Thoren M, Calissendorff J. Thyrotoxic periodic paralysis: clinical and molecular aspects. Endocrine 2012; 43: 274-284
• 44 Bugg NC, Jones JA. Hypophosphataemia. Pathophysiology, effects and management on the intensive care unit. Anaesthesia 1998; 53: 895-902
• 45 Stoff JS. Phosphate homeostasis and hypophosphatemia. The American journal of medicine 1982; 72: 489-495
• 46 Stryer L. Biochemistry. New York: W. H. Freeman and Company; 1995
• 47 Gourley DR. The role of adenosine triphosphate in the transport of phosphate in the human erythrocyte. Archives of biochemistry and biophysics 1952; 40: 1-12
• 48 King AL, Sica DA, Miller G et al. Severe hypophosphatemia in a general hospital population. Southern medical journal 1987; 80: 831-835
• 49 Marinella MA. Refeeding syndrome and hypophosphatemia. Journal of intensive care medicine 2005; 20: 155-159
• 50 Newman JH, Neff TA, Ziporin P. Acute respiratory failure associated with hypophosphatemia. The New England journal of medicine 1977; 296: 1101-1103
• 51 Agusti AG, Torres A, Estopa R et al. Hypophosphatemia as a cause of failed weaning: the importance of metabolic factors. Critical care medicine 1984; 12: 142-143
• 52 Brown GR, Greenwood JK. Drug- and nutrition-induced hypophosphatemia: mechanisms and relevance in the critically ill. The Annals of pharmacotherapy 1994; 28: 626-632
• 53 Dominguez JH, Gray RW, Lemann JJr. Dietary phosphate deprivation in women and men: effects on mineral and acid balances, parathyroid hormone and the metabolism of 25-OH-vitamin D. The Journal of clinical endocrinology and metabolism 1976; 43: 1056-1068
• 54 Brown RS. Extrarenal potassium homeostasis. Kidney international 1986; 30: 116-127
• 55 Sterns RH, Cox M, Feig PU et al. Internal potassium balance and the control of the plasma potassium concentration. Medicine 1981; 60: 339-354
• 56 Schaefer TJ, Wolford RW. Disorders of potassium. Emergency medicine clinics of North America 2005; 23: 723-747 , viii-ix
• 57 Whang R, Flink EB, Dyckner T et al. Magnesium depletion as a cause of refractory potassium repletion. Archives of internal medicine 1985; 145: 1686-1689
• 58 Berkelhammer C, Bear RA. A clinical approach to common electrolyte problems: 4. Hypomagnesemia. Canadian Medical Association journal 1985; 132: 360-368
• 59 Elin RJ. Assessment of magnesium status. Clinical chemistry 1987; 33: 1965-1970
• 60 Reinhart RA. Magnesium metabolism. A review with special reference to the relationship between intracellular content and serum levels. Archives of internal medicine 1988; 148: 2415-2420
• 61 Noronha JL, Matuschak GM. Magnesium in critical illness: metabolism, assessment, and treatment. Intensive care medicine 2002; 28: 667-679
• 62 McLean RM. Magnesium and its therapeutic uses: a review. The American journal of medicine 1994; 96: 63-76
• 63 Whang R. Magnesium deficiency: pathogenesis, prevalence, and clinical implications. The American journal of medicine 1987; 82: 24-29
• 64 Anast CS, Winnacker JL, Forte LR et al. Impaired release of parathyroid hormone in magnesium deficiency. The Journal of clinical endocrinology and metabolism 1976; 42: 707-717
• 65 Rude RK, Oldham SB, Singer FR. Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency. Clinical endocrinology 1976; 5: 209-224
• 66 Durr JA, Hoffman WH, Hensen J et al. Osmoregulation of vasopressin in diabetic ketoacidosis. The American journal of physiology 1990; 259: E723-E728
• 67 Hensen J. Hyponatremia. Deutsches Arzteblatt international 2010; 107: 709 ; author reply 710
• 68 Veverbrants E, Arky RA. Effects of fasting and refeeding. I. Studies on sodium, potassium and water excretion on a constant electrolyte and fluid intake. The Journal of clinical endocrinology and metabolism 1969; 29: 55-62
• 69 Gottdiener JS, Gross HA, Henry WL et al. Effects of self-induced starvation on cardiac size and function in anorexia nervosa. Circulation 1978; 58: 425-433
• 70 Heymsfield SB, Bethel RA, Ansley JD et al. Cardiac abnormalities in cachectic patients before and during nutritional repletion. American heart journal 1978; 95: 584-594
• 71 Huang YL, Fang CT, Tseng MC et al. Life-threatening refeeding syndrome in a severely malnourished anorexia nervosa patient. Journal of the Formosan Medical Association = Taiwan yi zhi 2001; 100: 343-346
• 72 Zauner C, Schneeweiss B, Kranz A et al. Resting energy expenditure in short-term starvation is increased as a result of an increase in serum norepinephrine. The American journal of clinical nutrition 2000; 71: 1511-1515
• 73 Deaths associated with thiamine-deficient total parenteral nutrition. MMWR Morb Mortal Wkly Rep 1989; 38: 43-46
• 74 Barrett TG, Forsyth JM, Nathavitharana KA et al. Potentially lethal thiamine deficiency complicating parenteral nutrition in children. Lancet 1993; 341: 901
• 75 Beard ME, Hatipov CS, Hamer JW. Acute onset of folate deficiency in patients under intensive care. Critical care medicine 1980; 8: 500-503
• 76 Koike H, Misu K, Hattori N et al. Postgastrectomy polyneuropathy with thiamine deficiency. Journal of neurology, neurosurgery, and psychiatry 2001; 71: 357-362
• 77 Oriot D, Wood C, Gottesman R et al. Severe lactic acidosis related to acute thiamine deficiency. Jpen 1991; 15: 105-109
• 78 Tan GH, Farnell GF, Hensrud DD et al. Acute Wernicke's encephalopathy attributable to pure dietary thiamine deficiency. Mayo Clinic proceedings 1994; 69: 849-850
• 79 Boni L, Kieckens L, Hendrikx A. An evaluation of a modified erythrocyte transketolase assay for assessing thiamine nutritional adequacy. Journal of nutritional science and vitaminology 1980; 26: 507-514
• 80 Dyckner T, Ek B, Nyhlin H et al. Aggravation of thiamine deficiency by magnesium depletion. A case report. Acta medica Scandinavica 1985; 218: 129-131
• 81 Ahmed S, Travis J, Mehanna H. Re-feeding syndrome in head and neck – prevention and management. Oral oncology 2011; 47: 792-796
• 82 Brooks MJ, Melnik G. The refeeding syndrome: an approach to understanding its complications and preventing its occurrence. Pharmacotherapy 1995; 15: 713-726
• 83 Klein CJ, Stanek GS, Wiles 3rd CE. Overfeeding macronutrients to critically ill adults: metabolic complications. Journal of the American Dietetic Association 1998; 98: 795-806
• 84 Maier-Dobersberger T, Lochs H. Enteral supplementation of phosphate does not prevent hypophosphatemia during refeeding of cachectic patients. Jpen 1994; 18: 182-184
• 85 Young IS, Neely RD, Lavery GG. Treatment of hypophosphataemia. Lancet 1993; 341: 374
• 86 Perreault MM, Ostrop NJ, Tierney MG. Efficacy and safety of intravenous phosphate replacement in critically ill patients. The Annals of pharmacotherapy 1997; 31: 683-688
• 87 Terlevich A, Hearing SD, Woltersdorf WW et al. Refeeding syndrome: effective and safe treatment with Phosphates Polyfusor. Alimentary pharmacology & therapeutics 2003; 17: 1325-1329