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Central European Journal of Clinical Research Volume 2, Issue 1, Pages 48-50 DOI: 10.2478/cejcr-2019-0007

REVIEW

Refeeding syndrome relevance for critically ill patients

María Bermúdez López1 1 Servicio Anestesiología, Reanimación y Terapéutica del Dolor. Hospital Universitario Lucus Augusti. Lugo. 27003. España.

Correspondence to: María Bermúdez López, Servicio Anestesiología, Reanimación y Terapéutica del Dolor. Hospital Universitario Lucus Augusti. E-mail:[email protected]

Conflicts of interests Nothing to declare

Acknowledgment None

Funding: This research did not receive any specific grant from funding agencies in the public, commercial or not-for profit sectors.

Keywords: refeeding syndrome, , , nutritional support, .

These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. Central Eur J Clin Res 2019;2(1):48-50 ______Received: 05.03.2019, Accepted: 30.03.2019, Published: 10.04.2019

Copyright © 2018 Central European Journal of Clinical Research. This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. It is essential to know that the high morbidity and mortality can be reduced by ear- ABSTRACT ly diagnosis and taking appropriate measures. Therefore, to be aware of this metabolic con- Refeeding Syndrome (RFS) is a poten- dition in critically ill patients is necessary for its tial life-threatening complication of the nutrition- prevention, recognition, and treatment. Despite al therapy in the replenishment phase after peri- many pathophysiological aspects of RFS re- od of . This not very known syndrome main unclear it is highly relevant to identify in- may be a life-threatening metabolic condition dividuals at risk and avoid the development of due to rapid, inadequate nutritional support in RFS in the ICU. We insist on the need of elec- malnourished catabolic patients. The intake of trolyte especially during the first 72 food and therefore the switch from a catabolic hours of initiation of nutritional support. Patients to an anabolic is most considered at risk may benefit from hypocaloric or restricted etiological mechanism. The main biochemical caloric intake for at least 48h resulting in lower feature of RFS is hypophosphatemia and low long-term mortality. levels of and . Lack of RFS is common among critically ill pa- vitamins, especially vitamin B1 or thiamine is tients. But the potential risk of RFS is poorly often present and involves severe clinical com- known. Future quality studies may help to as- plications. 48 Refeeding syndrome relevance for critically ill patients sessment of RFS risk and optimize and stan- its relevance in critical illness remains unclear. dardize the RFS management. Recent literature shows that RFS is Refeeding syndrome (RFS) is a poten- common among critically ill patients [1][3]. But, tially fatal acute metabolic derangement that can whereas the awareness of malnutrition in the result in morbidity and mortality [1]. RFS is a po- UCI is well established, the potential risk of RFS tential life-threatening complication of the nutri- is much less known. Screening for RFS risk is tional therapy in the replenishment phase after not commonly done. Even when malnutrition is period of starvation [2]. From a pathophysiolog- present, the risk of RFS is usually neglected or ical point of view, the intake of food and there- overlooked among hospitalized patients [2][12]. fore the switch from a catabolic to an anabolic Concerning hospital stay and death the metabolism is the main etiological mechanism. heterogeneous results in the different studies By the start of the nutritional therapy, the makes it difficult to establish a direct correlation concentration of glucose increases causing hy- between RFS and long-term outcomes [13][14]. perglycemia and stimulates anabolic processes However, there is evidence that early diagno- [2]. The increased secretion causes the sis and adequate treatment may lead to better intracellular uptake of phosphate. In fact, the overall survival [1]. For this reason, it is highly main biochemical feature of RFS is hypophos- relevant to identify individuals at risk and avoid phatemia; and this abnormality is commonly en- the development of RFS in the ICU. countered during critical illness [3](4). Most com- According to the guidelines of the Na- monly used definitions are based on hypophos- tional Institute for Health and Care Excellence phatemia [1]. The hypophosphatemia is usually the risk factors for RFS are: low BMI and/or un- accompanied by low concentrations of intentional within the last 6 months, magnesium and potassium [1][2][5]. Rio et al. a negligible food intake for more than 5 days, used a so-called three-facet criteria design to low electrolyte (phosphate, potassium, mag- confirm the diagnosis of RFS unequivocally [6]. nesium) levels prior to nutritional support, poor These criteria comprised disturbed electrolyte absorptive capacity, catabolism and chronic al- balances, acute peripheral edema or circulatory coholism [15]. Friedli N. et al. describe other risk fluid overload combined with disturbances in or- factors as age (>70 years), low (pre)albumin or gan function. Despite the exact pathophysiology insulin-like growth factor, overfeeding, intrave- of RFS remains unclear, mostly occurs because nous glucose infusion before nutritional support, of the intracellular shift of glucose and electro- or scoring at least 3 points on the nutritional risk lytes (phosphate, potassium, magnesium) oc- screening [10]. cur, and their blood levels may drop severely However, as common risk factors fail provoking severe complications [7][8]. to identify RFS patients, regular phosphate and The hormonal and metabolic changes other electrolyte monitoring can be recommend- that occur in this syndrome are complex and ed at least once daily, in particular during the first may cause serious clinical complications [4]. 72h after the initiation of nutritional support [1]. , lipid and glucose are dis- In the review of Boot R. et al. it is recommended turbed, and a lack of vitamins, especially vita- that if occurs a marked drop of phosphate lev- min B1 (thiamine) occurs [2]. Thiamine deficien- els (>0.16 mmol/l) from normal levels within 72h cy thus may lead to Wernicke’s encephalopathy of commencement of feeding, that feature may or cardiovascular disorders with water retention select patients that benefit from hypocaloric or [9]. Symptoms such as , peripheral restricted caloric intake for at least 48h result- edema, respiratory insufficiency, fluid imbalance ing in lower long-term mortality [1]. Friedli N. et and neurologic disorders can occur [2][10]. If not al. suggests an interesting and detailed recom- treated, these disturbances can lead to severe mendations for the nutritional management ac- negative effects, from multiorganic dysfunction cording to all risk categories ( minor, high and to death [7][8]. very high risk) of developing RFS, including to- RFS can be defined as the biochemi- tal caloric intake, fluid therapy, sodium restric- cal abnormalities and physical sings that occurs tion, thiamine and supplement [10]. when a patient with vitamin and -energy Given the small number of randomized studies malnutrition is incaustiously fed (whether enter- the evidence is low; however, caloric restriction ally or parenterally) [11]. The lack of a proper for several days and gradual increase of caloric uniform definition complicates diagnosis and re- intake over days is recommendable [3]. search of RFS. Besides this, there is no clear Whereas if the RFS is yet established correlations between risk factors proposed by and diagnosed Boot R. et al. recommend as international guidelines and the occurrence of treatment strategy: electrolyte supplementation RFS in ICU patients [3]. For this reason RFS and (phosphate, magnesium, potassium); glucose

49 Refeeding syndrome relevance for critically ill patients monitoring to prevent hypoglycemia and hyper- 5. Schuetz P, Laviano A, Friedli N, Crook M, glycemia; intravenous insulin administration in Stanga Z, Kressig RW, et al. Management case of hyperglycemia; correction of fluid over- and prevention of refeeding syndrome in load if necessary; thiamine supplementation at medical inpatients: An evidence-based and a minimum dose of 100 mg daily, for at least consensus-supported algorithm. Nutrition. 7–10 days; restriction of total caloric intake to 2017;47:13–20. a maximum of 500kcal/24h during the first 48h 6. Rio A, Whelan K, Goff L, Reidlinger DP, after the diagnosis of refeeding hypophospha- Smeeton N. Occurrence of refeeding syn- temia and refeeding syndrome; gradually ad- drome in adults started on artificial nutrition vance feeding after 48h of caloric restriction in support: prospective cohort study. BMJ daily steps of 25% of the target until the nutrition Open. 2013 Jan 1;3(1):e002173. target is reached [1]. 7. Crook M., Hally V, Panteli J. The impor- It is essential to include the amount of tance of the refeeding syndrome. Nutrition. non nutritional calories from propofol, citrate (re- 2001 Jul 1;17(7–8):632–7. nal replacement therapy) and intravenous car- 8. Stanga Z, Brunner A, Leuenberger M, bohydrate solutions in total caloric intake calcu- Grimble RF, Shenkin A, Allison SP, et al. lations, because these may be even higher than Nutrition in clinical practice—the refeeding the proposed cutoff for caloric restriction [16]. syndrome: illustrative cases and guidelines In regard to elderly patients it is known for prevention and treatment. Eur J Clin that aging is often linked to frailty and poor nutri- Nutr. 2008 Jun 15;62(6):687–94. tional status. Aubry E. et al. alert about the high 9. Boateng AA, Sriram K, Meguid MM, Crook risk for RFS in that kind of patients and recom- M. Refeeding syndrome: Treatment con- mend an early identification of patients and risk siderations based on collective analysis and a refeeding start at a low level of energy re- of literature case reports. Nutrition. 2010 placement [2]. As frailty is a reversible process Feb;26(2):156–67. and can be positively influenced by adequate 10. Friedli N, Stanga Z, Sobotka L, Culkin A, nutritional support it is essential to optimize the Kondrup J, Laviano A, et al. Revisiting the nutritional therapy, especially in that population. refeeding syndrome: Results of a system- As conclusion, awareness of refeeding atic review. Nutrition. 2017 Mar;35:151–60. syndrome and identification of patients at risk is 11. Walmsley RS. Refeeding syndrome: crucial as the condition is preventable and the Screening, incidence, and treatment during metabolic complications are avoidable [4]. De- . J Gastroenterol Hepa- spite the paucity of published guidance on the tol. 2013;28(S4):113–7. practical details of how refeeding patients at risk, 12. Pourhassan M, Cuvelier I, Gehrke I, Mar- most of authors recommend start at 10 kcal/kg/ burger C, Modreker MK, Volkert D, et al. day, increasing to full needs over a minimum of Risk factors of refeeding syndrome in mal- 4 days, with supplementation of thiamine, for at nourished older hospitalized patients. Clin least 10 days, and regular phosphate and mag- Nutr. 2018 Aug 1;37(4):1354–9. nesium monitoring [11][15]. 13. Olthof LE, Koekkoek WACK, van Setten C, Kars JCN, van Blokland D, van Zanten References ARH. Impact of caloric intake in critically ill patients with, and without, refeeding syn- 1. Boot R, Koekkoek KWAC, van Zanten drome: A retrospective study. Clin Nutr. ARH. Refeeding syndrome. Curr Opin Crit 2018 Oct 1;37(5):1609–17. Care. 2018 Aug;24(4):235–40. 14. Coşkun R, Gündoğan K, Baldane S, Güven 2. Aubry E, Friedli N, Schuetz P, Stanga Z. M, Sungur M. Refeeding hypophospha- Refeeding syndrome in the frail elderly temia: a potentially fatal danger in the population: prevention, diagnosis and man- . Turkish J Med Sci. agement. Clin Exp Gastroenterol. 2018 Ju- 2014;44(3):369–74. l;Volume 11:255–64. 15. Overview | Nutrition support for adults: oral 3. Koekkoek WAC, Van Zanten ARH. Is re- nutrition support, enteral tube feeding and feeding syndrome relevant for critically ill parenteral nutrition | Guidance | NICE. patients? Curr Opin Clin Nutr Metab Care. 16. Bousie E, van Blokland D, Lammers HJW, 2018 Mar;21(2):130–7. van Zanten ARH. Relevance of non-nutri- 4. Mehanna HM, Moledina J, Travis J. Refeed- tional calories in mechanically ventilated ing syndrome: what it is, and how to prevent critically ill patients. Eur J Clin Nutr. 2016 and treat it. Bmj. 2008;336(7659):1495–8. Dec 14;70(12):1443–50.

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