Adaptation and re-feeding Hypokalemia Bone complications

Transcription

1 Adaptation and re-feeding Hypokalemia Bone complications René Klinkby Støving Odense University Hospital Denmark 10% 20% 30% 40% BMI 18.5 BMI 16.5 BMI 14.5 BMI 12.5 Willmore DW, The Metabolic Management of the critically ill, Plenum Medical Book Company 1977 Hunger strike Belfast 1981: 30 IRA prisoners IBW 10% 20% 30% 10 died days Mean weight loss 40% (BMI 12.5) Nutrition % 65% BMI 7.8 Katzman, J Adolesc Health 2012 Støving, Odense, Denmark

2 refeeding syndrome: pathophysiology BMJ Case Rep 2016 glucose cardiac atrophy insulin Na K Mg PO 4 fluid retention cardiac failure edema ascites ulcers hypoalbuminemia keep an eye on the phosphate fluctuation catabolic ADP anabolic ATP P Fung, MJA 2005 Hypophosphataemia (s-phosphate<0.5 mmol/l) hypo phosphatemia Clinical manifestations Hematologic: hemolysis, thrombocytopenia CNS: convulsions, delirium, coma Cardiac: cardiac failure, arrhythmias Muscles: rhabdomyolysis phosphate renal failure respiratory failure urinary phosphate excretion normal s-phosphate rhabdomyolysis Støving, Odense, Denmark

3 refeeding syndrome: pathophysiology refeeding syndrome: pathophysiology low carb diet? glucose low Na diet? cardiac atrophy carbamide diuresis tube feeding syndrome (protein intoxication) Na fluid retention cardiac failure oedema low carb high protein- and lipid insulin K Mg PO 4 insulin non-diabetic ketoacidosis initial energy level (Kcal/kg/day) n=42 mean BMI 13.2: normal diet n= 176 mean BMI 13.8: low-na diet bioelectrical impedance analysis Fat-Free Mass Intracellular water Extracellular water (edema) risk for edema may be reduced by low sodium diet the first 4 weeks? Rigaud Clin Nutr 2010 MARSIPAN guidelines: initial energy level risky BW 30 kg: MARSIPAN 10 Kcal/kg 20 Kcal/kg Specialized medical unit in Dijon: BMI<11 (n=41 out of 484) Day 2 10 according to NICE 1 Myocardial infarction: 2 Heart rate 10 (pacemaker): 1 Rigaud, Clin Nutr 2012 Støving, Odense, Denmark

4 start low advance slow Under-feeding syndrome Under-feeding syndrome Further drop in body weight. Masked by re-hydration, edema, constipation n=34 %MBMI 80±12 Garber, J Adolesc Health 2012 n= 56 MBMI 79% ± 1.5 High caloric start Low caloric start Wanted! RCT multicenter: high risk patients BMI<12 - Low carb vs normal carb - Low Na vs normal Na - Low energy vs full energy Primary outcome: survival Secondary outcome: hypophosphatemia Garber, J Adolesc Health 2013 case Purging vomiting laxatives diuretics Worried family in Western Jutland: 27 y daughter Admitted to the Nutrition Unit. Weight loss 30%/6 months: BMI kg/6 weeks Transfered to Psychiatric Unit Severe hypokalemia: substitution 6000 mg KCl Støving, Odense, Denmark

5 case purging cortisol cortisone plasma volume glomerular filtration rate glycyrrhizin Renin-Angiotensine-Aldosterone secondary hyperaldosteronism (high renin and aldosterone) Aldosterone mineralokortikoid receptor K case renin and aldosterone Purging: Elevated Licorice: Suppressed BMI Støving, Nutrition 2011 potassium mixture with licorice metabolic alkalosis vomiting K 0.4 HCl loss HCO 3 ph 0.1 renin - angiotensin - aldosterone Resp CO 2 chronic dehydration dangerous condition simple to treat Støving, Odense, Denmark

6 no fractures normal Vitamine D Osteoporosis? n=339 AN 10 y remission rates restrictive 55% purging 40% purging restrictive T 5.9 SD Støving, Psych Res 2012 areal Bone Mineral Density (BMD) g/cm 2 Bone mass - Fracture risk: strongly age dependent what is osteoporosis? WHO: 1. Low energy fracture in the spine or femur 2. BMD T< -2.5 SD postmenopausal women Fracture risk n= 3,388 person-yr 80 y 45 y Bone mass Hui, J Clin Invest 1988 adapted to chronic semi starvation mechanical load bone marrow fat auto cannibalism: cortisol IGF-1 estrogen leptin reversible BMD Young patients with anorexia nervosa: Osteoporosis cannot be defined solely by BMD Z< 2.5: below expected range for age completely different from normal nutritional state Støving, Odense, Denmark

7 n=25 AN women age y controls age- and height matched High Resolution peripheral Quantitative CT (HR-pQCT) cortical bone trabecular bone bone marrow fat Calcif Tissue Int 2017 weight bearing vs non-weight bearing bones AN n = 2149 (24,555 person years) Calcif Tissue Int 2017 IJED 2002 can fractures be prevented pharmacologically? Fractures in anorexia nervosa Relative risk: high Absolute risk: strongly age-dependent Estrogen Bisphosphonate Parathyroid hormone (PTH) Denosumab (monoclonal antibody) Støving, Odense, Denmark

8 RCT n=112 age y mean BMI cycles x 28 days Dropouts BMD (g/cm2) vs (NS) BMI +1.5 vs +1.1 (NS) no evidence for oral contraceptives J Adolesc Health 2006 J Adolesc Health 2006 RCT n=110 AN + 40 C 18 months age 16.5±0.2 y BMI 17.4 ± 0.1 (% IBW 84.6 ± 0.6) Misra, JBMR 2011 Misra, JBMR 2011 Transdermal estrogen replacement might be beneficial in adolescens with minor weight loss n= 32, 12 months mean age 17 y BMI 16.3 ± ±6.4% 3.5±4.6% Misra, JBMR 2011 Golden, JCEM 2005 Støving, Odense, Denmark

9 treatment 1 y n= 32 mean age 17 y BMI 16.3 ± 1.1 No evidence for bisphosphonates Strong evidence for weight gain Strongest determinant: BW+8.7 kg +3.6 kg Golden, JCEM 2005 Golden, JCEM 2005 bisphosphonates concern unique pharmacokinetic: stored in bone tissue for years released into the blood pass placenta n= 21 6 months Age 47 ± 2 BMI 17.1 ± 0.4 Fazeli, JCEM 2014 Case report: preliminary evidence for PTH in middle-aged women with mild underweight 29 y, 17-year history, BMI 15 heel bone fracture treated for 3 y well tolerated Fazeli, JCEM 2014 Jamieson, JAMA 2016 Støving, Odense, Denmark

10 Take Home Messages Aim not increase in BMD but fracture prevention. So far, only one evidence based treatment: High risk patients: start low advance slow is not urban legend In hypokalemia: avoid licorice Osteoporosis cannot be diagnosed solely by DXA Støving, Odense, Denmark