Financial Interest Disclosure (over the past 24 months)

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1 : Across the Spectrum of Primary care Jan Greenwood, R.D. Nutrition Support Consultant The Basic Five Programs The opinions expressed in this presentation are that of the presenter and do not necessarily reflect those of Dietitians of Canada. Further, this presentation should not be reproduced in full or in part without the express written consent of the presenter. Les opinions exprimées dans cette présentation sont celles du présentateur ou de la présentatrice et ne reflètent pas nécessairement celles des Diététistes du Canada. Par ailleurs, cette présentation ne devrait pas être reproduite, que ce soit en partie ou dans son intégralité, sans le consentement écrit exprès du présentateur ou de la présentatrice. Financial Interest Disclosure (over the past 24 months) I receive financial support from Baxter for The Basic Five Parenteral Nutrition Programs. Abstract Refeeding syndrome (RFS) is not limited to hospital care or mode of feeding. No standard definition or treatment approach has been established by randomized clinical trials. Using case reviews, I will illustrate the cause and mechanisms of refeeding syndrome, and discuss the best available evidence and guidelines for the nutritional management of this condition. After this presentation, you should be able to analyze patient scenarios for refeeding syndrome risk factors in primary care and interpret the refeeding syndrome sequelae. Learning outcomes 1. Analyze patient scenarios for RFS risk factors in primary care. 2. Interpret the RFS sequelae. 3. Evaluate the literature for the best available evidence and guidelines for the nutritional management of RFS. Outline 1. Dietitian on the case 2. The history of refeeding syndrome 3. Starvation and refeeding - the pathophysiological mechanisms and clinical symptoms 4. A systematic review of the literature 5. An evidence-based and consensus-based approach to managing RFS. 6. Back to the case 7. Results of a BC province-wide RFS survey 1

2 Dietitian on the case #1 HPI: 73 y/o obtunded female. Day 6 post stroke. Receiving D5 1/2 NS at 50 ml/hr. Nutrition: BMI 18 kg/m 2. Previously eating well; no weight loss. Currently NPO 6 days. Relevant blood work: Serum phosphate, magnesium and potassium all within normal range. Dietitian on the case #2 HPI: 55 y/o male. Significant hx alcohol abuse. Receiving D5 1/2 NS at 50 ml/hr. Nutrition: BMI 17 kg/m 2. Unknown if any recent weight loss. Currently NPO for 2 days secondary to agitation and confusion. Relevant blood work: Serum phosphate, magnesium and potassium all within normal range. Dietitian on the case #3 HPI: 35 y/o male. Day 16 post-op GI surgery. Nutrition hx: BMI 30 kg/m 2. Prior to surgery eating well. Currently negligible intake 16 days. Other: Receiving D5 1/2 NS at 75 ml/hr. Relevant blood work: Serum phosphate, magnesium, potassium all within normal range following IV repletion. RFS History 1940 s Adverse consequences of refeeding malnourished individuals described in the 1940s. Intentional starvation and refeeding: The Minnesota experiment. Oral refeeding in previously health volunteers subjected to 6 months semi-starvation. Unintentional starvation and refeeding: Oral refeeding of semi-starved victims of WW11 Burger GCE, et al. Lancet 1945;246: Keys A, et al. The biology of human starvation, vols 1,2. Minneapolis, University of Minnesota Press, 1950 RFS History 1940 s Subjects who had experienced 6 months of starvation showed no evidence of cardiac dysfunction. During recovery phase (refeeding) the cardiovascular reserve was diminished and cardiac failure occurred in some. RFS History 1970 s and 1980 s 1972: Case reports of malnourished patients who experienced paresthesias, weakness and seizures 4-5 days after beginning PN. 1981: Case reports of malnourished patients who suffered an acute MI and sudden death; acute respiratory complications. Events arose 48 hrs post PN initiation. Serum phosphate was normal pre PN initiation but extremely low at the time of initial decompensation. Observations consistent in both refeeding groups. Burger GCE, et al. Lancet 1945;246: Keys A, et al. Vols 1,2. Minneapolis, University of Minnesota Press, 1950 Silvis SE, et al. Gastroenterology 1972;62: Weinsier RL, et al. Am J Clin Nutr 1980;34:

3 RFS History 1990 Extensive literature review in an attempt to clarify and broaden the understanding of RFS and make recommendations for its recognition and prevention. Data obtained using a computerized literature search, reviewing of major nutrition texts, and cross-checking references in identifying sources. Due to the lack of objective data, no attempt was made to analyze statistically or rank data. RFS History 1990 The RFS is best thought of broadly as the occurrence of severe fluid and electrolyte shifts (especially but not exclusively, phosphorus) and their associated complications in malnourished patients undergoing feeding either orally, enterally or parenterally. The optimal way to avoiding RFS with either enteral or parenteral nutrition is unknown. Clearly, research is needed to make refeeding more science than art. Outlined 8 recommendations to avoid the RFS. Solomon SM, et al. JPEN 1990;14:90-7 Solomon SM, et al. JPEN 1990;14:90-7. Recommendations to avoid the RFS 1 Be aware of the syndrome. 2 Recognize the patient at risk. 3 Carefully test for and correct electrolyte abnormalities before initiation nutrition support whether by the oral, enteral and parenteral route. 4 Judiciously restore circulatory volume, monitor pulse arte, and intake and output. 5 Increase caloric delivery slowly. 6 Administer vitamins routinely. 7 Carefully monitor the electrolytes over the 1 st week, including phosphorus, potassium, magnesium, glucose. 8 Here A little nutrition support is good, too much is lethal. Solomon SM, et al. JPEN 1990;14:90-7. RFS Today Friedli N, et al. Revisiting the refeeding syndrome: results of a systematic review. Nutrition 2017;35: A systematic review undertaken to find evidence-based answers to the following questions: RFS Clinical Symptoms Starvation and refeeding the physiological mechanism Slides do not display well on handout Variable, unpredictable, may occur without warning. Most symptoms will occur between 1 3 days after refeeding is initiated, although in some cases up to 5 days. May arise in apparently well-nourished individuals only after a short fast. A result of changes in serum electrolytes that affect cell membrane potential in nerve, cardiac, skeletal muscle cells. Khan LU, et al. Gastroenterol Res Pract. 2011;Epub 2010 Aug 25. Kraft MD, et al. Nutr Clin Prac 2005;20: Presier JC, et al. Crit Care 2015;19:35 3

4 Variable clinical picture reflects both the type and severity of the biochemical abnormality present. Mild electrolyte derangements - may be symptom free. Clinical Symptoms A result of changes in serum electrolytes that affect cell membrane potential in nerve, cardiac, skeletal muscle cells. Significant derangements - may develop respiratory insufficiency, cardiac failure, hypotension, arrhythmias, delirium, coma and death. If not identified and appropriate measures instituted, clinical deterioration may occur rapidly. Cardiac CHF Cardiomyopathy Cardiac arrhythmia Cardiac arrest Hematologic Hemolytic anemia Thrombocytopenia Leukocyte dysfunction Respiratory Failure Diaphragmatic muscle weakness Pulmonary edema Khan LU, et al. Gastroenterol Res Pract. 2011;Epub 2010 Aug 25. Kraft MD, et al. Nutr Clin Prac 2005;20: Presier JC, et al. Crit Care 2015;19:35 Clinical Symptoms A result of changes in serum electrolytes that affect cell membrane potential in nerve, cardiac, skeletal muscle cells. Metabolic Alkalosis / acidosis Glucose intolerance Hypernatremia Ketoacidosis GI Constipation Diarrhea Anorexia Paralytic ileus Renal Decreased ability to concentrate urine Clinical Symptoms Neurologic Weakness, paresthesia, altered mental state, seizure, ataxia, tremor, vertigo, tetany, rhabdomyolysis, myalgia. Friedli N, et al. Revisiting the refeeding syndrome: results of a systematic review. Nutrition 2017;35: Purpose: find evidence-based answers to the following questions 4

5 Two more common definitions noted: Of 45 studies, 38 reported a definition for RFS. Definitions heterogeneous - some studies relied on electrolyte disturbances with a cut off; others integrated medical parameters into the definition. Most studies had hypophosphatemia as a cut off or as a relative decrease from baseline as part of the definition. Friedli N, et al. Nutrition 2017;35: Electrolyte disturbances (K<2.5 mmol/l, PO4 <0.32 mmol/ L, Mg <0.5 mmol/l) AND clinical symptoms (peripheral edema, acute circulatory fluid overload) AND disturbance to organ function (respiratory failure, cardiac failure, or pulmonary edema). Drop of PO4 by >0.16 mmol/l to <0.65mmol/L accompanied by possible other electrolyte disturbances. Friedli N, et al. Nutrition 2017;35: Non-refeeding causes of hypophosphatemia Infections: sepsis, gram-negative bacteremia Malabsorption Alcoholism Glucose administration Diabetic ketoacidosis Metabolic or respiratory alkalosis Initiating mechanical ventilation / correction of respiratory acidosis Renal: rhabdomyolysis, hemodialysis, initiation of continuous renal replacement therapy, conditions resulting in renal tubular phosphate loss Medications: diuretics, phosphate binders, insulin, beta-antagonists, epinephrine, antacids, glucagon, bicarbonate, corticosteroids, etc. What are the definitions used for RFS? Varied McCray SF, et al. Practical Gastroenterology 2005;29:26-44 Skipper A. Nutr Clin Pract 2012;27:34-40 Purpose: find evidence-based answers to the following questions Incidence rates were impacted on by numerous study variables, particularly definition used. The more rigorous the definition the lower the incidence. Study Variables: RFS definition RFS diagnostic criteria Patient population Degree of malnutrition Malnutrition diagnostic criteria RFS protocol Friedli N, et al. Nutrition 2017;35: Reported incidence: 34% all ICU patients 10% anorexic patients - ICU 15% hospitalized patients 9.5% patients hospitalized for malnutrition from GI fistulae 48% severely malnourished patients being re-fed McCray SF, et al. Pract Gastroenterology

6 What is the incidence of RFS? Varied Purpose: find evidence-based answers to the following questions Eleven studies reported on the time point when RFS occurred. Commonly occurred within the first 72 h post nutrition start. Of the 11 studies, 7 used only hypophosphatemia as the RFS definition. Two studies using clinical symptoms for their definition for RFS reported a time of occurrence of RFS within 24 h and after 5 days. Some consensus among studies regarding the time point of RFS occurrence, namely within the first 72 h. It cannot be excluded that in certain patients a later development of the RFS can occur. When does RFS occur? Within 72 hrs but may occur later Purpose: find evidence-based answers to the following questions Only a few studies investigated the clinical consequences and therapeutic measures of RFS. Of those studies, there was a lack of association between RFS and adverse clinical outcomes, as well as preventive measures and improved out-comes. Only 1 RCT evaluated therapeutic approaches of RFS as the main outcome. Reported that kcal restriction was a suitable therapeutic measure for RFS in ICU patients. (Doig GS, et al. Lancet Respir Med 2015;3:943-52) Friedli N, et al. Nutrition 2017;35:

7 Is RFS associated with an adverse clinical outcome? Unknown Purpose: find evidence-based answers to the following questions Individuals at RFS Risk Low nutrient intake Prolonged hypocaloric feeding or fasting Chronic swallowing problems Anorexia nervosa Chronic alcoholism Depression in the elderly Patients with cancer Chronic infectious diseases During convalescence from catabolic illness Postoperative patients Diabetic hyperosmolar states Morbid obesity with profound weight loss Homelessness, social deprivation Idiosyncratic/eccentric diets Unintentional weight loss Loss >5% body weight in 1 mth Loss >7.5% body weight in 3 mths Loss >10% body weight in 6 mths Increased nutrient losses/decreased nutrient absorption Significant vomiting and/or diarrhoea Dysfunction or inflammation of the gastrointestinal tract Chronic pancreatitis Chronic antacid users Chronic high-dose diuretic users After bariatric surgery National Institute for Health and Clinical Excellence. Nutrition support in adults. Clinical guideline CG Stanga Z, et al. Eur J Clin Nutr 2008;62: A number of studies consistent with the NICE 2006 guidelines (BMI, unintentional weight loss, starvation, history of alcohol abuse and low and initial electrolyte concentrations) Some studies used other parameters (low albumin or prealbumin, high nutritional intake during refeeding, enteral feeding, etc.) What are the risk factors for RFS? The NICE 2006 guidelines seem to adequately reflect study findings but with some additional factors. 7

8 Purpose: find evidence-based answers to the following questions 6. What are therapeutic strategies to prevent or treat RFS? Different studies evaluated event strategies, mainly Provision of electrolytes: With a supplementation of electrolytes and vitamins, six studies found a reduced risk for RFS, where as three found no such effect. One study proposed monitoring of electrolytes where another did not show reduction in the risk for RFS. In two studies phosphate supplementation was provided to treat the signs and symptoms of RFS concluding these measures were helpful. 6. What are therapeutic strategies to prevent or treat RFS? Hypocaloric nutrition. Five studies showed a preventative effect of hypocaloric feeding whereas six did not. A recent RCT undertaken in critically ill identified that a caloric restriction driven by a protocol was an option for the treatment of RFS. (Doig GS, et al. Lancet Respir Med 2015;3:943-52). There was no correlation between criteria used to define RFS and effective preventative measures. What are the therapeutic strategies to prevent RFS? To be discussed. RFS Suggested Management Strategy Published opinion-based therapeutic strategies to prevent / treat RFS. Day Kcal intake 1 10 kcal/kg/day. Extreme: (BMI <14 kg/ m2 or no food >15 days) 5 kcal/kg/m2. Composition: Carb: 50 60% Pro: 15 20% Fat: 30 40% Supplements Prophylactic: PO4: mmol/kg/day. K: 1 3 mmol/kg/day. Mg: mmol/kg/day. Na: < 1 mmol/kg/day (restricted). IV fluids: restricted; maintain zero balance. IV thiamine and vitamin B complex 30 minutes prior to feeding. Khan LU, et al. Gastroenterol Res Pract 2011;Epub 2010 Aug 25 8

9 Day Kcal intake Supplements 2-4 Increase by 5 kcal/kg/day. If low or no tolerance, stop or keep minimal feeding regime. Check all biochemistry and correct any abnormality. Thiamine and vitamin B complex orally or IV until day 3. Monitor as required kcal/kg/day. Check electrolytes, renal and liver function and minerals. Fluid: maintain 0 balance. Consider iron supplement from day kcal/kg/day or increase to full requirements. Monitor as required. Khan LU, et al. Gastroenterol Res Pract 2011;Epub 2010 Aug 25 Clinical Monitoring Early identification of high risk patients BP and pulse rate Feeding rate Fluid intake and output Change in body weight Neurologic signs and symptoms Biochemical Monitoring Electrolyte levels Blood glucose levels Feeding rate ECG monitoring in severe cases Sources of energy (dextrose, propofol) Khan LU, et al. Gastroenterol Res Pract 2011;Epub 2010 Aug 25 RFS Suggested Management Strategy 5 Routinely administer vitamins / minerals, especially thiamine, for Anticipate patients at risk. 2 Initiate nutrition support, including total calories and fluids, slowly (~10 kcal/kg for severe cases; kcal/kg for others). 3 Check baseline electrolytes (especially phosphorus, potassium, magnesium) before initiating nutrition support; replace low levels promptly. 4 Monitor lytes every 8, 12 or 24 hours (depending on severity of RFS risk). Replace electrolytes as needed. If enteral replacement, consider scheduled dosing if levels continue to be low, such as 1-2 packets neutra- or Kphos q 6, 8 or 12 hours until phosphorus consistently remains > 2.0mg/dl (0.65 mmol/l). Decrease blood draws as soon as electrolytes stabilize. days. 6 Unless hemodynamically unstable, keep sodium-containing IV fluids to ~ 1 liter/day initially in severely malnourished patients such as those with anorexia nervosa who may have a component of cardiomyopathy. 7 Increase calories cautiously in a stepwise manner ( kcal every 2-3 days). Continue to monitor lytes as kcal increased. 8 Outline a plan for nutrition advancement (especially if patient is to be discharged before goal calories reached) to prevent the patient from remaining on a refeeding kcal level longer than necessary. McCray SF, et al. Practical Gastroenterology 2016;Sept:56-66 McCray SF, et al. Practical Gastroenterology 2016 RFS Suggested Management Strategy 1 Identify patients at risk for RFS prior to EN initiation. 2 Monitor fluid balance, daily weight, electrolyte status (e.g, potassium, magnesium, phosphorus), as well as other metabolic parameters (e.g, glucose) as needed based on patient s presenting clinical situation. Boullata JL, et al. JPEN 2017;41: Inadequate nutritional intake for >2 weeks Poorly controlled diabetes Cancer (before / during treatment) Anorexia nervosa Short bowel syndrome IBD Elderly, living alone Chronic infections (e.g, HIV) 3 Evaluate metabolic and nutrition parameters, and correct metabolic abnormalities or depleted electrolyte concentrations prior to the initiation of enteral feedings. 4 Initiate 25% of goal requirements on day 1 of EN. 5 Provide supplemental thiamin (IV or PO) with EN initiation. 6 Monitor serum potassium, phosphorus, magnesium, glucose following EN initiation; replace as needed. Boullata JL, et al. JPEN 2017;41:

10 Published evidence-based and consensus-supported therapeutic strategies to prevent / treat RFS. Friedli N, et al. Management and prevention of refeeding syndrome in medical inpatients: an evidencebased and consensus supported algorithm. Nutrition 2018;47: Risk Assessment (Friedli N, et al. Nutrition 2018) Minor risk factors BMI < 18.5 kg/m² Unintentional weight loss > 10% in the past 3-6 months Little or no nutritional intake for > 5 days History of alcohol abuse or drugs including insulin, chemotherapy, antacids, or diuretics Major risk factors BMI <16 kg/m² Unintentional weight loss >15% in the past 3-6 months Little or no nutritional intake for >10 days Low baseline levels of potassium phosphate or magnesium before feeding Specific patient populations at high-risk Careful assessment is recommended Hunger strike, chronic severe dieting History of bariatric surgery, short bowel syndrome Tumor patients, frail elderly patients with chronic debilitating disease 2. Prevention of RFS During Nutritional Therapy RFS risk stratification Low Risk 1 minor risk factor High Risk 1 major OR 2 minor risk factors Very High Risk BMI < 14kg/m 2 Weight loss >20% Starvation >15 days Preventative measures before/during nutritional therapy Careful restoration of fluid balance to avoid fluid overload. Depending on the risk, consider electrolyte substitution if lower than normal / in low normal range with daily adaption according to serum levels: mmol/kg/d potassium mmol/kg/d magnesium mmol/kg/d phosphate Preventative measures before/during nutritional therapy Depending on the risk, consider other measures: Use of thiamine ( mg on days 1-5). Multivitamins during days Replace specific deficiency of trace elements. Sodium restriction (<1 mmol/kg/d for days 1 7). 10

11 Fluids and Salt Fluids to maintain zero balance. Approx ml/ kg/d. No Na restriction Fluids to maintain zero balance. Days 1 3: ml/kg/ Restrict Na <1 mmol/ kg/d (days 1 7) Fluids to maintain zero balance. Days 1 3: ml/kg/d Days 4 6: ml/kg/d > Days 7: ml/kg/d Restrict Na <1 mmol/kg/d (days 1-10) Monitoring Low Risk High Risk Very High Risk Assessment of serum electrolytes daily up to day 3, then every 2 3 days. Daily clinical examination focusing on hydration status (1 2 time/day). Continuous monitoring of cardiac rhythm or electrocardiogram daily in very high risk RFS. 3. Reassessment and diagnosis of RFS during nutritional therapy (all categories) Shift in electrolytes within 72 hr after start of nutrition therapy: Decrease of PO4 from baseline greater than 30% or <0.6 mmol/l OR any two other electrolyte shifts below normal range (Mg <0.75 mmol/l, PO4 <0.80 mmol/l, K <3.5 mmol/l) No à No RFS No change of therapy algorithm. Substitution of lytes if they drop below reference range. Yes Associated with clinical symptoms? No Imminent RFS Start and/or adapt lytes substitution. Repeat assessment every 2 3 d. à Yes Manifest RFS Increase lytes substitution and treat conditions adequately. Adapt nutrition therapy as in High-Risk patients.repeat assessment daily. 3. Diagnosis of RFS No à No RFS No change of therapy algorithm. Substitution of lytes if they drop below reference range Yes Associated with clinical symptoms? No Imminent RFS Start and/or adapt lytes substitution. Repeat assessment every 2 3 d. à Yes Manifest RFS Increase lytes substitution and Treat conditions adequately. Adapt nutrition therapy as in High Risk patients. Repeat assessment daily. Clinical symptoms: Most common: tachycardia, tachypnea, edema Other possible signs: Cardiac: hyper/hypotension, CHF, cardiomyopathy, sudden death Pulmonary: Failure or ventilator dependency, pulmonary edema Neurologic: weakness, paresthesia, altered mental state, seizure, ataxia, tremor, vertigo, tetany, rhabdomyolysis, myalgia. Hematologic: platelet dysfunction, hemolytic anemia, leukocyte dysfunction GI: constipation, abdominal pain, diarrhea, anorexia, paralytic ileus Renal: decreased ability to concentrate urine Metabolic: alkalosis, glucose intolerance, hypernatremia, ketoacidosis, metabolic acidosis 11

12 Dietitian on the case #1 HPI: 73 y/o obtunded female. Day 6 post stroke. Receiving D5 1/2 NS at 50 ml/hr. Nutrition: BMI 18 kg/m 2. Previously eating well; no weight loss. Currently NPO 6 days. Relevant blood work: Serum phosphate, magnesium and potassium all within normal range. Dietitian on the case #2 HPI: 55 y/o male. Significant hx alcohol abuse. Receiving D5 1/2 NS at 50 ml/hr. Nutrition: BMI 17 kg/m 2. Unknown if any recent weight loss. Currently NPO for 2 days secondary to agitation and confusion. Relevant blood work: Serum phosphate, magnesium and potassium all within normal range. Dietitian on the case #3 HPI: 35 y/o male. Day 16 post-op GI surgery. Nutrition hx: BMI 30 kg/m 2. Prior to surgery eating well. Currently negligible intake 16 days. Other: Receiving D5 1/2 NS at 75 ml/hr. Results of a B.C. province-wide anonymous electronic survey on dietitians practices on the topic of RFS. Relevant blood work: Serum phosphate, magnesium, potassium all within normal range following IV repletion. References Keys A, Brozek J, Henschel A, et al. The biology of human starvation, vols 1,2. Minneapolis, University of Minnesota Press,1950. Burger GCE, Sandstead HR, Drummond J. Starvation in Western Holland: 1945.Lancet 1945;246: Khan L, Ahmed J, Khan S, Macfie J. Refeeding syndrome: a literature review. Gastroenterol Res Pract 2011; Article ID Boullata JL, Carrera A, Harvey L, et al. A.S.P.E.N. Safe practices for enteral nutrition therapy. JPEN 2017;41: Kraft MD, Btaiche IF, Sacks GS. Review of the refeeding syndrome. Nutr Clin Prac 2005;20: Crook MA, Hally V, Panteli JV. The importance of the refeeding syndrome. Nutrition 2001;17: McCray SF, Walker S, Parrish CR. Much ado about refeeding. Practical Doig GS, Simpson F, Heighes PT, et al, Refeeding Syndrome Trial Investigators Gastroenterology 2005;29(1): McCray SF, Parrish CR, et al. Practical Gastroenterology 2016;Sept:56 66 Group. Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomized, parallelgroup, multicenter, single-blind controlled trial. Lancet Respir Med 2015;3: National Institute for Health and Clinical Excellence. Nutrition support in adults. Clinical guideline CG Preiser JC, van Zanten AR, Berger MM, et al. Metabolic and nutritional support of Friedli N, Stanga Z, Sobotka L, et al. Revisiting the refeeding syndrome: results of a systematic review. Nutrition 2017;35: critically ill patients: consensus and controversies. Crit Care 2015;19:35. Rio A, Whelan K, Goff L, et al. Occurrence of refeeding syndrome Friedli N, Stanga Z, Culkin A, et al. Management and prevention of refeeding syndrome in medical inpatients: an evidence-based and consensus supported in adults started on artificial nutrition support: prospective cohort study. algorithm. Nutrition 2018;47: BMJ Open 2013;3:e doi: / bmjopen

13 Silvis SE, Paragas Jr, PD. Parasthesias, weakness, seizures, and hypophosphatemia in patients receiving hyperalimentation. Gastroenterology 1972;62: Skipper A. Refeeding syndrome or refeeding hypophosphatemia: a systematic review of cases. Nutr Clin Pract 2012;27: Solomon SM, Kirby DF. The refeeding syndrome: a review. JPEN 1990;14:90-7. Stanga Z, Brunner A, Leuenberger M, et al. Nutrition in clinical practice - the refeeding syndrome: illustrative cases and guidelines for prevention and treatment. Eur J Clin Nutr 2008;62: Weinsier RL, Krumdieck CL. Death resulting from overzealous total parenteral nutrition: the refeeding syndrome revisited. Am J Clin Nutr 1980;34: