Management of Refeeding Syndrome in Medical Inpatients
Abstract
:1. Introduction
2. Pathophysiology and Clinical Manifestations
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- Phosphate is an important electrolyte in the metabolism of macronutrients for both the energy production and transport processes. Phosphate is especially important in the refeeding phase, since glycolysis requires only phosphorylated glucose. Hypophosphatemia may cause several clinical manifestations, such as rhabdomyolysis, hemolysis, respiratory failure, and musculoskeletal disorders. Severe hypophosphatemia (<0.32 mmol/L) is considered a typical hallmark of RFS and in several studies is a central defining criterion [15,18].
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- Potassium and magnesium are also important intercellular cations. Severe hypokalemia (<2.5 mmol/L) and/or hypomagnesemia (<0.50 mmol/L) may trigger potentially lethal arrhythmia, neuromuscular dysfunctions such as paresis, rhabdomyolysis, confusion, and respiratory insufficiency [15].
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- Thiamine is an essential coenzyme in the metabolism of carbohydrates, allowing the conversion from glucose to adenosine triphosphate (ATP) via the Krebs cycle. When thiamine is lacking (human body stores last for approximately 14 days), glucose is converted to lactate, leading to metabolic acidosis. Thiamine deficiency may also lead to neurologic (Wernicke’s encephalopathy: dry beriberi) or cardiovascular disorders (wet beriberi) [15,16].
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- Sodium: The major influence on the serum sodium level during the refeeding phase is the shift of sodium out of the cell as the potassium is pumped back into the cell (sodium-potassium-ATPase pump). In addition, the increased insulin level in the early phase of refeeding leads to sodium retention in the kidneys. Sodium concentration subsequently increases, thus inducing water retention. Noradrenaline and angiotensin II are stimulated and lead to augmented peripheral resistance and vasoconstriction [21]. This may cause peripheral edema and heart failure.
3. Current Level of Evidence
4. Prevention
4.1. Nutritional Support Teams
4.2. Individual Risk Assessment
5. Diagnostic Procedure
6. Clinical Management
6.1. Macronutrients
6.2. Fluids
6.3. Micronutrients
7. Monitoring
8. Important Clinical Sequelae of Refeeding Syndrome and Management of Complications
9. Outlook
10. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Clinical Conditions | |
---|---|
- Malnourished, catabolic patients - Geriatric patients - Oncologic patients - Trauma patients - Critically ill patients - Hunger strikers or prolonged fasting - Short -bowel syndrome - Bariatric surgery - Anorexia nervosa - Cystic fibrosis | - Chronic wasting disease - Chronic pancreatitis - Chronic infectious disease - Inflammatory bowel syndrome - Liver cirrhosis - Patients with dysphagia - Patients with hemodialysis - Patients with chemotherapy - Patients with chronic alcoholism - Drug dependent patients |
Reference | Type of Study | Level of Evidence | Initial Energy/day | Proteins/day | Fluids/day | Vitamins (Before/During) |
---|---|---|---|---|---|---|
Solomon et al. 1990 [11] | Review | 4 | 20 kcal/kg | 1.2–1.5 g | NR | NR |
Dewar et al. 2000 [42] | Review, guidelines | 4 | 20 kcal/kg | NR | NR | Thiamine IV or PO for 2 days |
Crook et al. 2001 [8] | Review | 4 | 10 kcal/kg high risk: 5 kcal/kg 50–60% CHO, 15–25% fat | 20–30% 1.2–1.5 g | 20–30 mL/kg, 0 fluid balance | Thiamine 300 mg IV, than 100 mg daily during refeeding. In addition, Vit B12, Vit B6 and folate |
Stroud et al. 2003 [43] | Review | 4 | 10–20 kcal/kg | NR | NR | Thiamine and B vitamins IV for 3 days |
Kraft et al. 2005 [44] | Review, guidelines | 4 | 7.5 kcal/kg | NR | <1000 mL/day | Thiamine 50–100 mg IV or 100 mg PO for 5–7 days and multivitamin |
NICE 2006 [23] | Review, guidelines | 4 | 10 kcal/kg high risk: 5 kcal/kg | NR | 0 fluid balance | Thiamine 200–300 mg PO for 10 days and multivitamin for 10 days |
Stanga et al. 2008 [12] | Case series | 4 | 10–15 kcal/kg high risk: 5 kcal/kg 50–60% CHO, 30–40% fat | 15–20% | 20–30 mL/kg, 0 fluid balance | Thiamine 200–300 mg IV or PO for 3 days and multivitamin for 10 days |
Mehanna et al. 2008 [16] | Review | 4 | 10 kcal/kg high risk: 5 kcal/kg | NR | carefully fluid repletion | Thiamine 200–300 mg PO for 10 days and multivitamin for 10 days |
Boateng et al. 2010 [15] | Case series | 4 | 10 kcal/kg high risk: 5 kcal/kg 50–60% CHO, 15–25% fat | 20–30% 1.2–1.5 g | 20–30 mL/kg, 0 fluid balance | Thiamine 300 mg IV, then 100 mg daily during refeeding. In addition, Vit B12, Vit B6 and folate |
ESPEN 2019 [45] | Review, guidelines | 4 | 10–15 kcal/kg high risk: 5 kcal/kg 50–60% CHO, 30–40% fat | 15–20% | 20–30 mL/kg, 0 fluid balance | Thiamine 200–300 mg IV or PO for 3 days and multivitamin for 10 days |
Crook et al. 2014 [46] | Review | 4 | 10 kcal/kg high risk: 5 kcal/kg 50–60% CHO, 15–25% fat | 20–30% 1.2–1.5 g | 20–30 mL/kg, 0 fluid balance | Thiamine 300 mg IV, then 100 mg daily during refeeding. In addition, Vit B12, Vit B6 and folate |
Friedli et al. 2017 [20] | Systematic review | 3a | 10–15 kcal/kg high risk: 5 kcal/kg 50–60% CHO, 30–40% fat | 15–20% | 20–30 mL/kg, 0 fluid balance | Thiamine 200–300 mg IV or PO for 3 days and multivitamin for 10 days |
Friedli et al. 2018 [19] | Systematic review, consensus paper | 3a | 10–15 kcal/kg high risk: 5 kcal/kg 50–60% CHO, 30–40% fat | 15–20% | 20–30 mL/kg, 0 fluid balance | Thiamine 200–300 mg IV or PO for 3 days and multivitamin for 10 days |
Reference | Type of Study | Level of Evidence | N | Preventive Medication | Therapeutic Medication | Effectivity |
---|---|---|---|---|---|---|
Hofer et al. 2014 [25] | Retrospective study | 3b | 86 | Hypocaloric feeding, restricted fluid administration (0 fluid balance), thiamine 200–300 mg IV or PO for 3 days and multivitamin for 10 days, electrolyte supplementation (unless prefeeding serum levels are high): PO4 0.5–0.8 mmol/kg/day, K 1–2.2 mmol/kg/day, Mg 0.3–0.4 mmol/kg/day | Hypocaloric feeding, restricted fluid administration, electrolytes substitution according to the serum level | Yes |
Eichelberger et al. 2014 [47] | Retrospective study | 3b | 37 | Hypocaloric feeding, restricted fluid administration (0 fluid balance), thiamine 200–300 mg IV or PO for 3 days and multivitamin for 10 days, electrolyte supplementation (unless prefeeding serum levels are high): PO4 0.5–0.8 mmol/kg/day, K 1–2.2 mmol/kg/day, Mg 0.3–0.4 mmol/kg/day | Hypocaloric feeding, restricted fluid administration, electrolytes substitution according to the serum level | Yes |
Terlevich et al. 2003 [31] | Prospective study | 4 | 30 | NR | 50 mmol PO4 over 24h | Yes |
Gonzalez Aviva et al. 1996 [48] | Prospective study | 3b | 106 | PO4 supplementation | NR | Yes |
Marvin et al. 2008 [49] | Case control study | 3b | 140 | During the first 24 h slow PN regimen providing <70% of protein and calories but >12 mmol PO4 | NR | Yes |
Garber et al. 2011 [50] | Retrospective study | 4 | 40 | No effective preventive measures found | NR | No |
Coskun et al. 2014 [51] | Retrospective study | 4 | 117 | Lower energy intake | NR | No |
Doig et al. 2015 [52] | RCT | 1b | 339 | NR | Lower caloric intake | Yes |
Whitelaw et al. 2010 [53] | Retrospective study | 4 | 46 | Prophylactic administration of PO4, lower initial energy intake, monitoring of PO4 | Supplementation of PO4 | Yes |
Luque et al. 2007 [54] | Retrospective study | 4 | 11 | PO4 supplementation, thiamine 3.51 mg/d | NR | Yes |
Manning et al. 2014 [55] | Prospective study | 2b | 36 | Repeated electrolyte testing | NR | No |
Fan et al. 2004 [33] | Retrospective study | 4 | 158 | PO4 supplementation | NR | Yes, if PO4 <0.30 |
Gentile et al. 2010 [56] | Retrospective study | 4 | 33 | Prophylactic administration of PO4 and K, cautious nutritional rehabilitation | NR | Yes |
Vignaud et al. 2010 [38] | Retrospective study | 4 | 68 | For patients at risk for initial nutritional support 10 kcal/kg/day falling to as low as 5 kcal/kg/day | NR | Yes |
Chen et al. 2014 [57] | Retrospective study | 4 | 56 | Thiamine and multivitamin supplementation, 15 kcal/kg/day | NR | Yes |
Golden et al. 2013 [58] | Retrospective study | 4 | 310 | Lower caloric intake | NR | No |
Leclerc et al. 2013 [59] | Retrospective study | 4 | 29 | Hypocaloric feeding | NR | No |
Flesher et al. 2005 [60] | Retrospective study | 4 | 51 | Thiamine supplementation, cautious feeding | NR | No |
Rio et al. 2013 [28] | Prospective | 2b | 243 | Hypocaloric feeding | NR | No |
Potassium | Magnesium | Phosphate | |
---|---|---|---|
Mild deficiency | 3.1–3.5 mmol/L Oral replacement with 20 mmol (as KCl or other salts) OR i.v. replacement with 20 mmol KCl over 4 to 8 h. Check levels the next day. | 0.5–0.7 mmol/L Oral replacement with 10–15 mmol MgCl2 or Mg-citrate or Mg-L-aspartate Oral Mg should be given in divided doses to minimize diarrhea (absorption process is saturated at about 5–10 mmol Mg) | 0.61–0.8 mmol/L Oral replacement with 0.3 mmol/kg/day PO4 (divided doses to minimize diarrhea) OR i.v. replacement with 0.3 mmol/kg/day PO4 (as K3PO4 or Na3PO4) over 8–12 h. Check levels the next day. |
Moderate deficiency | 2.5–3.0 mmol/L i.v. replacement with 20–40 mmol KCl over 4–8 h. Check levels after 8 h; if not normal, give an additional 20 mmol KCl. | 0.32–0.6 mmol/L i.v. replacement with 0.6 mmol/kg/day PO4 (as K3PO4 or Na3PO4) over 8–12 h. Check levels after 8–12 h and repeat infusion if necessary (max. of 50 mmol PO4 in 24 h). | |
Severe deficiency | <2.5 mmol/L i.v. replacement with 40 mmol KCl over 4–8 h. Check levels after 8 h; if not normal, give an additional 40 mmol KCl. | <0.5 mmol/L i.v. replacement with 20–24 mmol MgSO4 (4–6 g) over 4–8 h. Reassess every 8 to 12 h. | <0.32 mmol/L Same replacement therapy as for moderate deficiency. |
System | Symptoms |
---|---|
Cardiovascular | Tachycardia Arrhythmias Hypotension Congestive heart failure Shock Edemas Sudden death |
Gastrointestinal | Maldigestion and malabsorption Vomiting Constipation Abdominal pain |
Musculoskeletal | Weakness Myalgia Rhabdomyolysis Osteomalacia |
Respiratory | Tachypnea Dyspnea Respiratory failure Ventilator dependency Diaphragm muscle weakness |
Neurologic | Anorexia Paresthesia Tremor Wernicke encephalopathy Korsakoff syndrome Ataxia Tetany Delirium Seizures Coma |
Metabolic | Hyperglycemia Metabolic alkalosis Metabolic acidosis Respiratory alkalosis Insulin resistance |
Hematologic | Thrombocytopenia Hemolysis Anemia Leukocyte dysfunction Decreased 2,3-DPG |
Renal | Acute tubular necrosis |
Hepatological | Acute liver failure |
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Reber, E.; Friedli, N.; Vasiloglou, M.F.; Schuetz, P.; Stanga, Z. Management of Refeeding Syndrome in Medical Inpatients. J. Clin. Med. 2019, 8, 2202. https://doi.org/10.3390/jcm8122202
Reber E, Friedli N, Vasiloglou MF, Schuetz P, Stanga Z. Management of Refeeding Syndrome in Medical Inpatients. Journal of Clinical Medicine. 2019; 8(12):2202. https://doi.org/10.3390/jcm8122202
Chicago/Turabian StyleReber, Emilie, Natalie Friedli, Maria F. Vasiloglou, Philipp Schuetz, and Zeno Stanga. 2019. "Management of Refeeding Syndrome in Medical Inpatients" Journal of Clinical Medicine 8, no. 12: 2202. https://doi.org/10.3390/jcm8122202