MANAGEMENT AND PREVENTION OF REFEEDING SYNDROME IN INPATIENTS: A PRACTICAL APPROACH
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1 MANAGEMENT AND PREVENTION OF REFEEDING SYNDROME IN INPATIENTS: A PRACTICAL APPROACH Prof. Zeno Stanga, MD Nutritional Medicine Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism - University Hospital of Bern - Switzerland
2 Submitted to Nutrition
3 Definition of the refeeding syndrome ( RFS ) POTENTIALLY LIFE-THREATENING METABOLIC CONDITION ASSOCIATED WITH low-serum electrolyte and vitamin concentrations fluid imbalance sodium-retention disturbance of organ function resulting from over-rapid or unbalanced refeeding of a severe malnourished catabolic patient NICE. Clin. Guid / Crook MA. Nutrition 2014 / Stanga Z et al. Eur J Clin Nutr 2008
4 Diagnosis during nutritional therapy SHIFT IN ELECTROLYTES WITHIN 72 HOURS AFTER START OF NUTRITIONAL THERAPY Decrease of PO 4 from baseline >30% or below <0.6 mmol/l Any two other electrolyte shifts below normal range Mg <0.75 mmol/l, PO 4 <0.80 mmol/l, K <3.5 mmol/l YES ASSOCIATED WITH CLINICAL SYMPTOMS? NO IMMINENT RFS YES MANIFEST RFS
5 Diagnosis during nutritional therapy SHIFT IN ELECTROLYTES WITHIN 72 HOURS AFTER START OF NUTRITIONAL THERAPY Decrease of PO 4 from baseline >30% or below <0.6 mmol/l Any two other electrolyte shifts below normal range Mg <0.75 mmol/l, PO 4 <0.80 mmol/l, K <3.5 mmol/l YES ASSOCIATED WITH CLINICAL SYMPTOMS? NO IMMINENT RFS YES MANIFEST RFS
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7 Reference Initial energy/day Proteins Fluids/day Vitamins (before/during) Solomon et al. JPEN 1990 Dewar et al. Clinical Nutrition 2001 Crook et al. Nutrition 2001 / 2010 Nutrition 2014 Kraft et al. Nutr Clin Pract 2005 NICE Guidelines 2006 Stanga et al. Eur J Clin Nutr 2008 Nutrition 2014 / kcal/kg g 20 kcal/kg 10 kcal/kg high risk: 5 kcal/kg 50-60% CHO, 15-25% fat 20-30% g ml/kg, 0 fluid balance 7.5 kcal/kg _ <1 L/d 10 kcal/kg high risk: 5 kcal/kg kcal/kg high risk: 5 kcal/kg 50-60% CHO, 30-40% fat _ 15-20% 0 fluid balance ml/kg, 0 fluid balance Stroud et al. Gut kcal/kg Royal College of Psychiatrists 2005 MARSIPAN (RCP) 2014 Mehanna et al. BMJ 2008 ESPEN Blue Book 2012 thiamine IV or PO for 2 d thiamine 300 mg IV, than 100 mg daily during refeeding. In addition Vit B12, Vit B6 and folate thiamine mg IV or 100 mg PO for 5-7 d & multivitamin mg thiamine PO for 10 d & multivitamin for 10 days mg thiamine IV or PO for 3 d & multivitamin for 10 days thiamine and B vitamins IV for 3 days kcal/kg _ kcal/kg high risk: 5-10 kcal/kg 10 kcal/kg high risk: 5 kcal/kg kcal/kg high risk: 5 kcal/kg 50-60% CHO, 30-40% fat _ max ml/kg thiamine PO 4x/d for 7-10 days _ 15-20% carefully fluid repletion ml/kg, 0 fluid balance mg thiamine PO for 10 d & multivitamin for 10 days mg thiamine IV or PO for 3 d & multivitamin for 10 days
8 Reference Initial energy/day Proteins Fluids/day Vitamins (before/during) Solomon et al. JPEN 1990 Dewar et al. Clinical Nutrition 2001 Crook et al. Nutrition 2001 / 2010 Nutrition 2014 Kraft et al. Nutr Clin Pract 2005 NICE Guidelines 2006 Stanga et al. Eur J Clin Nutr 2008 Nutrition 2014 / kcal/kg g 20 kcal/kg 10 kcal/kg high risk: 5 kcal/kg 50-60% CHO, 15-25% fat 20-30% g ml/kg, 0 fluid balance 7.5 kcal/kg _ <1 L/d 10 kcal/kg high risk: 5 kcal/kg kcal/kg high risk: 5 kcal/kg 50-60% CHO, 30-40% fat _ 15-20% 0 fluid balance ml/kg, 0 fluid balance Stroud et al. Gut kcal/kg Royal College of Psychiatrists 2005 MARSIPAN (RCP) 2014 Mehanna et al. BMJ 2008 ESPEN Blue Book 2012 thiamine IV or PO for 2 d Thiamine 300 mg IV, than 100 mg daily during refeeding. In addition Vit B12, Vit B6 and folate thiamine mg IV or 100 mg PO for 5-7 d & multivitamin mg thiamine PO for 10 d & multivitamin for 10 days mg thiamine IV or PO for 3 d & multivitamin for 10 days thiamine and B vitamins IV for 3 days kcal/kg _ kcal/kg high risk: 5-10 kcal/kg 10 kcal/kg high risk: 5 kcal/kg kcal/kg high risk: 5 kcal/kg 50-60% CHO, 30-40% fat _ max ml/kg thiamine PO 4x/d for 7-10 days _ 15-20% carefully fluid repletion ml/kg, 0 fluid balance mg thiamine PO for 10 d & multivitamin for 10 days mg thiamine IV or PO for 3 d & multivitamin for 10 days
9 Screening for nutritional risk & screening for the risk Assess hydration status & check electrolytes (K, Mg, PO 4, Na, Ca) Stratification of the risk according to risk factors NO RISK LOW RISK HIGH RISK VERY HIGH RISK
10 Criteria for determination of patients at risk MAJOR RISK FACTORS (A) BMI < 16 kg/m2 Unintentional weight loss > 15% in the preceding 3-6 months Very little or no nutritional intake for > 10 days Low levels of serum Mg, PO 4 or K prior to feed MINOR RISK FACTORS (B) BMI < 18.5 kg/m2 Unintentional weight loss > 10% in the preceding 3-6 months Very little or no nutritional intake for > 5 days History of alcool or drug abuse NICE: National Institute for Health and Clinical Excellence. 2006
11 Criteria for determination of patients at risk MAJOR RISK FACTORS (A) BMI < 16 kg/m2 Unintentional weight loss > 15% in the preceding 3-6 months Very little or no nutritional intake for > 10 days Low levels of serum Mg, PO 4 or K prior to feed MINOR RISK FACTORS (B) BMI < 18.5 kg/m2 Unintentional weight loss > 10% in the preceding 3-6 months Very little or no nutritional intake for > 5 days History of alcool or drug abuse RISK BY PATIENT S CATEGORY Hunger strike, eating disorders, chronic severe dieting After bariatric surgery, short bowel syndrome Oncology patients and fraily elderly (chronic debilitating disease) NICE: National Institute for Health and Clinical Excellence. 2006
12 Criteria for determination of patients at risk MAJOR RISK FACTORS (A) BMI < 16 kg/m2 Unintentional weight loss > 15% in the preceding 3-6 months Very little or no nutritional intake for > 10 days Low levels of serum Mg, PO 4 or K prior to feed MINOR RISK FACTORS (B) BMI < 18.5 kg/m2 Unintentional weight loss > 10% in the preceding 3-6 months Very little or no nutritional intake for > 5 days History of alcool or drug abuse RISK BY PATIENT S CATEGORY Hunger strike, eating disorders, chronic severe dieting After bariatric surgery, short bowel syndrome Oncology patients and fraily elderly (chronic debilitating disease) NICE: National Institute for Health and Clinical Excellence. 2006
13 Screening for nutritional risk & screening for the risk Assess hydration status & check electrolytes (K, Mg, PO 4, Na, Ca) Stratification of the risk according to risk factors NO RISK LOW RISK HIGH RISK VERY HIGH RISK Correct the existing deficit of dehydration and replace previous or ongoing abnormal fluid losses Nutritional support and fluids maintenance according to the standard of care Preventive measures: electrolytes repletion, thiamine substitution (at least 30 min. before refeeding) NICE. Clin. Guid / Crook MA. Nutrition 2014 / Stanga Z et al. Eur J Clin Nutr 2008
14 Predictors Prospective cohort study 243 patients starting EE oder PE 133 at risk Predictors (sensitivity 67%, specificity 80%) Poor intake for >10 days Weight loss of >15% Low plasma magnesium (< 0.7 mmol/l; p = 0.021) STARVATION is the most reliable predictor Rio A et al. BMJ Open 2013
15 Preventive measures CORRECT ELECTROLYTES LEVELS AND EVALUATE EMPIRICAL SUPPLEMENTATION BEFORE FEEDING IS INITIATED Supplement electrolytes prophylactically (unless pre-feeding plasma levels are high) in very high risk patients. Amounts depend on patient size and plasma concentrations, but usual daily requirements (man of 70 kg) are: K Mg PO mmol/kg/d mmol/kg/d mmol/kg/d GIVE mg THIAMINE I.V. OR ORALLY BEFORE FEEDING NICE. Clin. Guid / Crook MA. Nutrition 2014 / Stanga Z et al. Eur J Clin Nutr 2008
16 Screening for nutritional risk & screening for the risk Assess hydration status & check electrolytes (K, Mg, PO 4, Na, Ca) Stratification of the risk according to risk factors NO RISK LOW RISK HIGH RISK VERY HIGH RISK Correct the existing deficit of dehydration and replace previous or ongoing abnormal fluid losses Nutritional support and fluids maintenance according to the standard of care Preventive measures: electrolytes repletion, thiamine substitution (at least 30 min. before refeeding) Nutritional support Fluids maintenance Give micronutrients Nutritional support Fluids maintenance Give micronutrients Nutritional support Fluids maintenance Give micronutrients NICE. Clin. Guid / Crook MA. Nutrition 2014 / Stanga Z et al. Eur J Clin Nutr 2008
17 Nutritional & fluid management LOW RISK DAYS NUTRITIONAL SUPPORT by all routes kcal/kg/d 4 30 kcal/kg/d 5 full requirements * * I suggest to use individually clinical judgement in decision how slow / fast nutrition support should proceed to full target in the refeeding period FLUID AND SODIUM BALANCE Fluids to maintain zero balance, approx ml/kg/d No restriction in salt intake
18 Nutritional & fluid management LOW RISK DAYS NUTRITIONAL SUPPORT by all routes kcal/kg/d 4 30 kcal/kg/d 5 full requirements * * I suggest to use individually clinical judgement in decision how slow / fast nutrition support should proceed to full target in the refeeding period FLUID AND SODIUM BALANCE Fluids to maintain zero balance, approx ml/kg/d No restriction in salt intake
19 Screening for nutritional risk & screening for the risk Assess hydration status & check electrolytes (K, Mg, PO 4, Na, Ca) Stratification of the risk according to risk factors NO RISK LOW RISK HIGH RISK VERY HIGH RISK Correct the existing deficit of dehydration and replace previous or ongoing abnormal fluid losses Nutritional support and fluids maintenance according to the standard of care Preventive measures: electrolytes repletion, thiamine substitution (at least 30 min. before refeeding) Nutritional support Fluids maintenance Give micronutrients Nutritional support Fluids maintenance Give micronutrients Nutritional support Fluids maintenance Give micronutrients NICE. Clin. Guid / Crook MA. Nutrition 2014 / Stanga Z et al. Eur J Clin Nutr 2008
20 Nutritional & fluid management HIGH RISK DAYS NUTRITIONAL SUPPORT by all routes kcal/kg/d kcal/kg/d 6 30 kcal/kg/d 7 full requirements * * I suggest to use individually clinical judgement in decision how slow / fast nutrition support should proceed to full target in the refeeding period FLUID AND SODIUM BALANCE Fluids to maintain zero balance, D ml/kg/d, > D ml/kg/d Salt: restrict Na to <1 mmol/kg/d D1-7
21 Distribution of infused solutions 40 % 15 % 5 % Intracellular volume (ICV) Extracellular volume (ECV) Interstitial fluid Intravascular fluid 5% Glucose 0.9% NaCl Colloids LOBO DN et al. 2013, ISBN
22 Distribution of infused solutions 40 % 15 % 5 % Intracellular volume (ICV) Extracellular volume (ECV) Interstitial fluid Intravascular fluid 5% Glucose 0.9% NaCl Colloids LOBO DN et al. 2013, ISBN
23 Cristalloid solutions for fluid maintenance INFUSION ( 1000 ml ) Na (mmol) Cl (mmol) K (mmol) Glucose (g) 0g NaCl Lactate (mmol) Glocose 5% g NaCl 3g NaCl 1.8g NaCl Glucosaline 1: Glucosaline 2: Glucosaline 4: g NaCl Saline 0.9% g NaCl Ringer s lactate g NaCl Hartmann s LOBO DN et al. 2013, ISBN
24 Nutritional & fluid management HIGH RISK DAYS NUTRITIONAL SUPPORT by all routes kcal/kg/d kcal/kg/d 6 30 kcal/kg/d 7 full requirements * * I suggest to use individually clinical judgement in decision how slow / fast nutrition support should proceed to full target in the refeeding period FLUID AND SODIUM BALANCE Fluids to maintain zero balance, D ml/kg/d, > D ml/kg/d Salt: restrict Na to <1 mmol/kg/d D1-7
25 Screening for nutritional risk & screening for the risk Assess hydration status & check electrolytes (K, Mg, PO 4, Na, Ca) Stratification of the risk according to risk factors NO RISK LOW RISK HIGH RISK VERY HIGH RISK Correct the existing deficit of dehydration and replace previous or ongoing abnormal fluid losses Nutritional support and fluids maintenance according to the standard of care Preventive measures: electrolytes repletion, thiamine substitution (at least 30 min. before refeeding) Nutritional support Fluids maintenance Give micronutrients Nutritional support Fluids maintenance Give micronutrients Nutritional support Fluids maintenance Give micronutrients NICE. Clin. Guid / Crook MA. Nutrition 2014 / Stanga Z et al. Eur J Clin Nutr 2008
26 Nutritional & fluid management VERY HIGH RISK DAYS NUTRITIONAL SUPPORT by all routes kcal/kg/d kcal/kg/d kcal/kg/d 10 full requirements * * I suggest to use individually clinical judgement in decision how slow / fast nutrition support should proceed to full target in the refeeding period FLUID AND SODIUM BALANCE Fluids to maintain zero balance, D ml/kg/d, D ml/kg/d, > D ml/kg/d Salt: restrict Na to <1 mmol/kg/d D1-10
27 Nutritional & fluid management VERY HIGH RISK DAYS NUTRITIONAL SUPPORT by all routes kcal/kg/d kcal/kg/d kcal/kg/d 10 full requirements * * I suggest to use individually clinical judgement in decision how slow / fast nutrition support should proceed to full target in the refeeding period FLUID AND SODIUM BALANCE Fluids to maintain zero balance, D ml/kg/d, D ml/kg/d, > D ml/kg/d Salt: restrict Na to <1 mmol/kg/d D1-10
28 Screening for nutritional risk & screening for the risk Assess hydration status & check electrolytes (K, Mg, PO 4, Na, Ca) Stratification of the risk according to risk factors NO RISK LOW RISK HIGH RISK VERY HIGH RISK Correct the existing deficit of dehydration and replace previous or ongoing abnormal fluid losses Nutritional support and fluids maintenance according to the standard of care Preventive measures: electrolytes repletion, thiamine substitution (at least 30 min. before refeeding) Nutritional support Fluids maintenace Give micronutrients Nutritional support Fluids maintenance Give micronutrients Nutritional support Fluids maintenace Give micronutrients Clinical and laboratory monitoring, management of complications NICE. Clin. Guid / Crook MA. Nutrition 2014 / Stanga Z et al. Eur J Clin Nutr 2008
29 Monitoring Body weight (or fluid balance) Vital signs blood pressure, pulse rate, respiratory rate, oxygen sat. Clinical examination hydration state, oedema, cardiopulmonary state Lab serum-parameters PO 4, K, Mg, Na, Ca, glucose, urea, creatinine DAY 1-3 monitor daily DAY 4-6 monitor every 2 nd day DAY 7-10 monitor 1-2x weekly Crook MA. Nutrition 2009 / Stanga Z et al. Eur J Clin Nutr 2008
30 Monitoring Body weight (or fluid balance) Vital signs blood pressure, pulse rate, respiratory rate, oxygen sat. Clinical examination hydration state, oedema, cardiopulmonary state Lab serum-parameters PO 4, K, Mg, Na, Ca, glucose, urea, creatinine DAY 1-3 monitor daily DAY 4-6 monitor every 2 nd day DAY 7-10 monitor 1-2x weekly Crook MA. Nutrition 2009 / Stanga Z et al. Eur J Clin Nutr 2008
31 Electrolyte deficiency and replacement POTASSIUM REPLETION S-POTASSIUM Mild deficit mmol/l Moderate deficit mmol/l Severe deficit < 2.5 mmol/l RECOMMENDATION FOR REPLETION oral replacement with 20 mmol (as KCl or other formularies) OR i.v. replacement with 20 mmol KCl over 4-8 h check K levels the next day i.v. replacement with mmol KCl over 4-8 h check K levels after 8 hours if not normal levels, give further 20 mmol KCL i.v. replacement with 40 mmol KCl over 4-8 h check K levels after 8 hours if not normal levels, give further 40 mmol KCL Gennari FJ. NEJM 1998 / Boateng AA et al. Nutrition 2010 / ESPEN Blue Book 2011 Marinella MA et al. Int J Clin Pract 2008 / Stanga Z et al. Eur J Clin Nutr 2008
32 Electrolyte deficiency and replacement MAGNESIUM REPLETION S-MAGNESIUM Mild to moderate deficit mmol/l RECOMMENDATION FOR REPLETION oral replacement with mmol Mg-chlorid or Mg-citrat or Mg-L-aspartat oral Mg should be given in divided doses to minimise diarrhoea (absorption process is saturated at about 5-10 mmol Mg) Severe deficit < 0.5 mmol/l i.v. replacement with mmol MgSO 4 (4-6 g) over 4-8 h reassess every 8-12 h Brannan GB et al. J Clin Invest 1976 / Boateng AA et al. Nutrition 2010 / ESPEN Blue Book 2011 Weisinger JR et al. Lancet 1998 / Stanga Z et al. Eur J Clin Nutr 2008
33 Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, University Hospital, Bern, Switzerland Zeno Stanga PENSA 2017 Manila Electrolyte deficiency and replacement MAGNESIUM REPLETION S-MAGNESIUM RECOMMENDATION FOR REPLETION Mild to moderate deficit mmol/l oral replacement with mmol Mg-chlorid or Mg-citrat or Mg-L-aspartat oral Mg should be given in divided doses to minimise diarrhoea (absorption process is saturated at about 5-10 mmol Mg) Severe deficit < 0.5 mmol/l i.v. replacement with mmol MgSO4 (4-6 g) over 4-8 h reassess every 8-12 h Brannan GB et al. J Clin Invest 1976 / Boateng AA et al. Nutrition 2010 / ESPEN Blue Book 2011 Weisinger JR et al. Lancet 1998 / Stanga Z et al. Eur J Clin Nutr 2008
34 Electrolyte deficiency and replacement PHOSPHATE REPLETION S-PHOSPHATE Mild deficit mmol/l Moderate deficit mmol/l Severe deficit < 0.32 mmol/l RECOMMENDATION FOR REPLETION oral replacement with 0.3 mmol/kg/d PO 4 (divided doses to minimise diarrhoea) OR i.v. replacement with 0.3 mmol/kg/d PO 4 (as K 3 PO 4 or Na 3 PO 4 ) over 8-12 h check PO 4 levels next day i.v. replacement with 0.6 mmol/kg/d PO 4 (as K 3 PO 4 or Na 3 PO 4 ) over 8-12 h check PO 4 levels after 8-12h and repeat infusion if necessary (max. of 50 mmol PO 4 in 24 h). same replacement therapy as above (moderate deficit) Thatte L et al. Am J Med 1995 / Crook MA. Nutrition 2009 / Stanga Z et al. Eur J Clin Nutr 2008
35 Energy ( kcal ) S-PO 4 ( mmol/l ) Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, University Hospital, Bern, Switzerland Zeno Stanga PENSA 2017 Manila (13 ICUs) Enrollment: 72h after start feeding (EE/PE) & PO 4, 1:1 rand., stratification by PO 4 > 0.32 vs 0.32 mmol/l and BMI < 18 vs 18 kg/m 2 n = 170 Standard care n = 169 Hypocaloric management Energy intake / d ( mean) Lowest daily s-phosphates PO 4 -substitution i.v. ( mmol ) Days Days Doig GS et al. Lancet Respir Med 2015
36 Survival ( % ) Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, University Hospital, Bern, Switzerland Zeno Stanga PENSA 2017 Manila Overall survival time 91% p = % Survival time ( days ) Doig GS et al. Lancet Respir Med 2015
37 Pending questions To date only low quality evidence exists... Too cautious energy step up? so far conflicting statements possible start feeding higher energy / CHO in hospital? Build-up of full food intake within 3-4 days? reduction of the catabolic phase Do we have to give electrolytes in a prophylactic way? prevention is better than cure Reliable predictors? How important is the clinical examination?
38 The big challenge
39 Take home message
40 UNIVERSITY HOSPITAL OF BERN - SWITZERLAND
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