AKE-Dialog Parenterales Fett: Mehr als Energie Braucht ein Intensivpatient Fett? wilfred.druml@meduniwien.ac.at
Fett in der klinischen Ernährung ENERGIE - Substrate Energie Substrate Energie Speicher Funktionen 9 kcal/g 140.000 kcal STRUKTURELLE - Substrate BEACHTE Komponenten : Fett aller ist Zellmembranen mehr als Energie! (Membran-Funktionen, Signal-Transduktion) FUNKTIONELLE - Substrate Essentielle Fettsäuren Prekursoren von Lipid-Mediatorem (Eicosanoiden) Prekursoren von Resolvinen /Protektinen Vorstufen von Hormonen / Vitamin D Träger von fett-löslichen Vitaminen Endotoxin-Elimination Immunmodulation
Influence of parenteral nutrition on rates of net substrate oxydation in severe trauma patients Jeevanandam M et al. Crit Care Med 1990; 18: 467
Short-Term Energy Balance in Patients with Infections: Carbohydrate-Based vs Fat-Based Diets Schneeweiß B et al. Metabolism 1992; 41: 125-130 Intake, expenditure, and storage of major fuels for the carbohydrate based diet. Storage significantly different from zero p < 0.05
Short-Term Energy Balance in Patients with Infections: Carbohydrate-Based vs Fat-Based Diets Schneeweiß B et al. Metabolism 1992; 41: 125-130 Intake, expenditure, and storage of major fuels for the fat based diet. Storage significantly different from zero p < 0.05
Effects of isoenergetic glucose-based or lipid-based parenteral nutrition on glucose metabolism, de novo lipogenesis, and respiratory gas exchanges in critically ill patients Tappy L et al. Crit Care Med 1998; 26: 860-67 Fractional de novo lipogenesis during glucose-based total parenteral nutrition (TPN-glucose) or lipidbased total parenteral nutrition (TPN-lipid). *p <.002 vs. TPNlipid.
Effects of enteral carbohydrates on de novo lipogenesis in critically ill patients Schwarz MT et al. Am J Clin Nutr 2000; 72: 940-45 Fractional hepatic de novo lipogenesis (DNL) in patients receiving continuous enteral nutrition containing 28% (EN-28%), 53% (EN-53%), or 75% (EN-75%) of energy (100 BEE) as carbohydrate. * vs. fasted group, P < 0.05. # vs. EN-28% and EN- 45%, P < 0.05. = Leberverfettung unter Kohlenhydrat-reicher Ernährung!
Effects of isoenergetic glucose-based or lipid-based parenteral nutrition on glucose metabolism, de novo lipogenesis, and respiratory gas exchanges in critically ill patients Tappy L et al. Crit Care Med 1998; 26: 860-67 Respiratory oxygen (VO 2 ) and CO 2 (VCO 2 ) exchanges in the unfed state and after glucose-based total parenteral nutrition (TPN-G) or lipid-based total parenteral nutrition (TPN-L). *p <.02 vs. basal.
Effects of Different Regimes of Parenteral Nutrition on Respiratory Paramters in Patients Requiring Artificial Ventilation Buchmiller CE et al JPEN 1993; 17: 301-306 B1, B2, B3 = basal periods, G 1 = 100 % glucose (1.5 x BEE), GL = 50% glucose, 50% lipid (1.5 x BEE)
Nutritionally associated increased carbon dioxide production. Excess total calories vs high proportion of carbohydrate calories Talpers SS et al Chest 1992; 102: 551-68 CO 2 production (Vco2) in mechanically ventilated patients receiving isocaloric nutrition regimen with varying percentage of carbohydrates (A) and in patients receiving no nutrition (fasting), 1.0 x REE, 1.5 x REE, and 2.0 x REE.
Effect of low-calorie parenteral nutrition on the incidence and severity of hyperglycemia in surgical patients: A RCT Ahrends Christine et al. Crit Care Med 2005; 33: 2507 Average blood glucose during TPN. Glucose curves begin 4 hrs after administration of lowcalorie (20 non-prot kcal/kg/d = 26.6 kcal/kg/d) vs. standard-calorie TPN (30 non-prot kcal/kg/d= 37 kcal/kg/d)
Stoner HB et al. Brit J Surg 1983; 70: 332-35
The effect of sepsis on the oxidation of carbohydrate and fat Stoner HB et al. Brit J Surg 1983; 70: 332-35 The relationship between fat oxidation and sepsis score in 55 measurements on 27 patients receiving parenteral nutrition
Stoffwechsel bei Akut-Phasen- Reaktion/ SIRS / Postaggressionssyndrom grundsätzliche Störungen Proteinstoffwechsel Aktivierung der peripheren (muskulären) Proteolyse Stimulation der hepatische Proteinsynthese Kohlenhydratstoffwechsel Hemmung der peripheren (muskul.) Glukoseaufnahme Aktivierung der hepatischen Glukoneogenese Fettstoffwechsel Aktivierung der Lipolyse Steigerung der Fett-Oxydation
Glukose-Infusion unterdrückt nicht die erhöhte Lipolyse nach Abdominalchirurgie Schricker Th. et al. Nutrition 2001; 17: 85-90 Lipolysis rates (R a glycerol) in volunteers and patients in the fasted state and during glucose infusion. +P < 0.05 vs volunteers, *P < 0.05 vs fasted patients. R a, rate of appearance daher: persistierende Fett-Verwertung bei Akuterkrankungen!
Increased lipid utilization in weight losing and weight stable cancer patients Körber J et al Europ J Clin Nutr 1999; 53: 740-45 Lipid clearance rates after bolus injections (0.1 g/kg/ bw MCT/LCT vs LCT). * Significant vs controls (p < 0.05 or 0.01)
Fett in der klinischen Ernährung Fett-Elimination bei versch. Krankheiten Elimination normal oder beschleunigt Sepsis Robin 1983; Druml 98 Trauma Carpentier 1979 postoperativ Lindholm 1979 chron. Leberversagen Rössner 79, Druml 96 ICU Patient / MODS Lindholm 79, Druml 98 Tumor - Patient Körber 1999 Elimination verzögert chron. Nierenversagen Chan 1980 akutes Nierenversagen Druml 1983 hypodyname Sepsis Druml 1983
Increase in plasma triglycerides above basal concentrations during long-chain tiglyceride (LCT) and medium-chain triglyceride (MCT) infusions in control subjects and in patients with chronic hepatic failure (CHF). Fat elimination in chronic hepatic failure: long-chain vs medium-chain triglycerides Druml W. et al Am J clin Nutr 1995; 61: 812-17
Use of Intravenous Lipids in Critically Ill Patients with Sepsis without and with Hepatic Failure Druml W. et al Am J clin Nutr 1998; 22: 217-23 Increase in plasma triglycerides during infusion of a LCT lipid emulsion in 8 healthy subjects (Ctrl), 8 patients with sepsis (S) and 8 patients with sepsis and hepatic failure (S+L). # p < 0.05, p < 0.01 between Controls and patient groups
Fat Elimination in Acute Renal Failure : long-chain vs medium-chain triglycerides Druml W et al. Am J Clin Nutr 1992; 55: 468-472 Increase in plasma triglycerides above basal concentrations
Lipid Utilization in Acute Renal Failure Plasma triglycerides during infusion of 1 g/kg.b.w./day of a lipid emulsion in patients with acute renal failure
Effects of intravenous fat emulsions on lung function in patients with acute respiratory distress syndrome or sepsis Suchner Ulrich et al. Crit Care Med 2001; 29: 1569-74 6-keto-prostaglandin (PG)- F 1 /thromboxane (Tx)-B 2 ratio in arterial blood (A), pulmonary shunt (B), oxygen exchange ratio (C), and oxygenation index (D) before, during, and after rapid (left panel) or slow (right panel) fat infusion. dashed lines, severe sepsis; solid lines, ARDS. a p.05 6 hrs fat infusion vs. baseline; A p.05 ARDS vs sepsis
The Impact of Intravenous Fat Emulsion Administration in Acute Lung Injury Lekka ME et al. Am J Resp Crit Care Med 2004; 169: 638-44 BALF cells stained by Sudan Black B from a representative of ARDS-Lipid group. (A) Before and (B) after the parenteral administration of long-chain triglycerides/ medium-chain triglycerides (LCT/MCT) 3.5 mg/kg/min = 5 g kg/d
Liver Dysfunction and Energy Source : Results of a Randomized Clinical Trial Buchmiller CE et al JPEN 1993; 17: 301-306 TPN (LIP-CHO) 8.5% amino acids, 30% glucose, 40% of total calories from lipids; TPN (CHO) 8.5 % amino acids, 50 % dextrose, 7.5 % of total calories from lipids
Choline : A Conditionally Essential Nutrient for Humans Zeisel SH et al FASEB J 1991; 5: 2093-98 Serum alanine aminotransferase activity in humans ingesting a control or choline-deficient diet
Choline : A Conditionally Essential Nutrient for Humans Zeisel SH et al FASEB J 1991; 5: 2093-98 Plasma choline concentration in humans ingesting a control or choline-deficient diet
Impaired leukotriene C4 generation in granulocytes from protein-energy malnourished chronically ill elderly Cederholm T et al. J Intern Med 2000; 247: 715 Leukotriene C4 (LTC4) generation in granulocytes from malnourished chronically ill elderly (grey columns) and controls (white columns) after calcium ionophore A23187 stimulation at 0.2 and 1.0 μmol L 1. PEM, protein-energy malnutrition.
Essential Fatty Acid Deficiency During TPN Barr LH et al. Ann Surg 1981; 193: 304 Triene/ tetraene ratio during a fat free nutrition
Untersuchungen zum Fettstoffwechsel bei polytraumatisierten Patienten V. Hundelhausen B et al. Klin Ernähr 1982; 8: 206 Prozentualer Linolsäureanteil C 18/2 Phospholipidfettsäuren (oben) und Prozentualer Arachidonsäureanteil C 20/ 4 Phospholipidfettsäuren unter parenteraler Ernährung mit (---) und ohne Fettemulsion ( ) = erhöhter Bedarf an essentiellen Fettsäuren bei Akuterkrankungen
Chylomicrons alter the fate of endotoxin, decreasing tumor necrosis factor release and preventing death Harris HW et al. J Clin Invest 1993; 91: 1028-34
Triglyceride-rich lipoproteins prevent septic death in rats Read TE et al. J Experimental Med 1995; 182: 267-72 Survival of rats after CLE receiving i.v. either mesenteric lymph containing nascent chylomicrons (1 g triglyceride/kg), Intralipid (1 g triglyceride/kg), or normal saline every 4 h for 28 h. All deaths occurred during the first 72 h after CLP. * P ~0.03 vs controls at 96 h
Triglyceride-rich lipoproteins prevent septic death in rats Read TE et al. J Experimental Med 1995; 182: 267-72 Serum endotoxin (LPS) levels and Serum TNF levels after CLP.
Enteral Administration of High-Fat Nutrition Before and Directly After Hemorrhagic Shock Reduces Endotoxemia and Bacterial Translocation Luyer M et al. Ann Surg 2004; 239: 257-64 Circulating endotoxin at 24 hours after shock is significantly lower in the HS-HF group compared with both the HS-S group (*P = 0.005) and the HS-LF group ( P = 0.002).
Fett in der enteralen Ernährung Was wird verwendet? Standard- NDD : PUFA-reiche LCT-Fette Pflanzenöle (Sonnenblumen-; Soyabohnen-Öl etc.) Modifizierte - NDD : 50 % MCT (Kokosnuß-Öl) (Resporptionsstörungen, Pankreatitis etc.) Immunonutrition : Zusatz von Fischöl (ω-3-fa), oder y-linolensäure
Effect of enteral feeding with eicosapentaenoic acid, gammalinolenic acid, and antioxidants in patients with ARDS Gadek JE et al. Crit Care Med 1999; 27:1409-20 Mean number of 30-day ventilator-free days and ICU-free days. *Patients with eicosapentaenoic acid + gamma-linolenic acid (EPA + GLA) had 4.9 more ventilator-free days (p =.02) and 4.0 more ICU-free days (p =.01) compared with patients with control diet.
Effects of enteral feeding with eicosapentaenoic acid, γ-linolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock Pontes-Arruda A et al. Crit Care Med 2006; 34:2325 Survival curves during the 28-day period. Enteral feeding with eicosapentaenoic acid (EPA) and γ- linolenic acid (GLA) ( Opexa ) was associated with higher survival (p =.037).
KLINISCHE VORBEHALTE GEGEN DIE VERWENDUNG VON FETT IN DER PARENTERALEN ERNÄHRUNG Blockade des RES? Phagozytose der Partikel in Granulozyten? Beeinträchtigung der Immunkompetenz? Klinische Bedeutung des Creaming? Inkompatibilität mit anderen Nährstoffen? Beeinträchtigung der Blutgerinnung? Verminderung der Thrombozytenzahl? Induktion einer Pankreatitis? Beeinträchtigung der Leberfunktion? Behinderung des Gasaustausches? WD 2003
Efficacy of a high-carbohydrate diet in catabolic illness Hart DW et al. Crit Care Med 2001; 29: 2318-24 Model calculations of protein synthesis, protein breakdown, and net balance for children with burn injury. *p <.05; p <.01. High Carb = 82% Carb, 3% Fat, 14% potein; high fat = 44% (as enteral Intralipid)Carb, 42% fat, 14 % protein, PHE phenylalanine (study using enteral nutrition) hoch-kalorische Ernährung!!
A Prosprective, Randomized Trial of Intravenous Fat Emulsion Administration in Trauma Victims Requiring Total Parenteral Nutrition Battistella FD. et al. J Trauma 1997; 43: 52-59 Lipid No Lipid p Value (N = 30) (N = 27) Nonprot Cal. (kcal/kg/d) 28 + 2 21 + 2 0.0001 Calories as fat (%) 24 + 5 0 0.0001 Amino acids (g/kg/d) 1.6 + 0.2 1.6 + 0.1 0.41 Nitrogen balance (g/day) - 9 + 7-9 + 5 0.78 Patient days with glucose NUTRITIONAL PARAMETERS > 200 mg/dl 32 38 0.72 Total insulin (U) for 10 d 245 227 0.52 Nicht isokalorisch hyperkalorisch in der Lipid-Gruppe
A Prosprective, Randomized Trial of Intravenous Fat Emulsion Administration in Trauma Victims Requiring Total Parenteral Nutrition Battistella FD. et al. J Trauma 1997; 43: 52-59 Lipid No Lipid p Value (N = 30) (N = 27) CLINICAL OUTCOME Hospital length of stay (d) 39 + 24 27 + 16 0.03 ICU length of stay (d) 29 + 22 18 + 12 0.02 Days on mech. Ventilation 27 + 21 15 + 12 0.01 INFECTIOUS COMPLICATIONS Pneumonia (n) 22 13 0.05 Line sepsis (n) 13 5 0.04 Bacteriemia (n) 8 6 0.68 Abdominal abscess (n) 4 3 0.99 Mortality (n) 0 2 0.99 nicht isokalorisch hyperkalorisch in der Fettgruppe!
Does Delaying Early Intravenous Fat Emulsion during Parenteral Nutrition Reduce Infections during Critical Illness? Gerlach AT. et al. Surg Infect 2011; 12: 43-47 Retrospective review of two sequential periods
Bloodstream Infections in Patients Receiving Manufactured Parenteral Nutrition With vs Without Lipids: Is the Use of Lipids Really Deleterious? Pontes-Arruda A. et al. JPEN 2012 e-pub Adjusted probability of infection adjusted for gender, geographic region, hospital size, admission type, transfer status, additional dextrose, additional mineral/ electrolyte, days of PN, malnutrition, peritonitis, cirrhosis/ chronic liver failure, renal failure.
Hypocaloric total parenteral nutrition: effectiveness in prevention of hyperglycemia and infectious complications- a randomized trial McCowen KC. et al. Crit Care Med 2000; 28: 3606-11 Nitrogen balance measured after 5 days of TPN*p <.03 for the difference between the hypocaloric (= 14 kcal /kg/d, Fett-frei!) and control groups (= ca. 18 (Ziel 25) kcal/kg/d, 3-Kammer-Beutel).
KONTRAINDIKATIONEN GEGEN DIE VERWENDUNG VON FETT IN DER PARENTERALEN ERNÄHRUNG Hyperlipidämie Jede Art von Schock Störungen der Mikrozirkulation Diffuse intravaskuläre Gerinnug Schwere Acidose (ph<7.2) Hypoxämie Nicht aber Leberversagen Nierenversagen hyperdyname Sepsis Pankreatitis etc. Beachte : Nicht die Art er Erkrankung ist entscheidend dafür ob ein Patient Fett erhalten kann, sondern ob er/sie Fett tatsächlich verwerten kann! WD 2003
FETT in der klinischen Ernährung Grenzen für die Fettzufuhr : Triglyceride Arbiträre Empfehlung von allen internat. Gesellschaften: 350 450 (500) mg/dl Gefahren einer Hypertriglyceridämie: Fettspeicherung im Granulozyten Sequestrierung im RES Pankreatits Pneumonitis neurolog Komplikationen
The importance of clinical factors in parenteral nutrition-associated hypertriglyceridemia Llop J et al. Clin Nutr 2003; 22: 577-83 Clinical factors associated with PN hypertriglyceridemia
Effects of Fat Proportion to Glucose in Peripheral Parenteral Nutrition on Nutritional Status in Normal Rats Nakayama M. et al Nutrition Res 2000; 20: 1771-82 Body weight changes and cumulative nitrogen balance during PPN periods.
Praktische Hinweise für die Infusion von FETT in der TPE beachte die Kontraindikationen beachte die Dosierungsrichtlinien infundiere kontinuierlich (z.b. 18-24 h) (Vermeidung von Konzentrationsspitzen) überwache die Infusion (Plasma-Triglyceride, nicht Trübung!) reduziere bzw. beende Infusion bei Triglyceriden > 350 mg/dl (4 mmol/l) Merke : Eine verzögerte Elimination ist KEINE Kontraindikation zur Fettgabe : aber Dosisanpassung! WD 2003
Fett in der Ernährung von Intensivpatienten Statement Fett bildet eine obligatorische Komponente JEDER künstlichen Ernährung, und damit auch Bestandteil jeder parenteralen Nährlösung. wenn keine Kontraindikationen vorliegen In der enteralen Ernährung ist das akzeptiert, warum nicht in der parenteralen?
Fett nicht vergessen! Danke für die Aufmerksamkeit wilfred.druml@meduniwien.ac.at