Metabolic Hidrai de carbon 100g glicogen Proteine, lipoproteine Sinteza AG

Triacilglicerol VLDL

Oxidarea parial a AG la corpi cetonici Depozit de vitamine: A, D, E, K, Fe, Cu; glicogen

Excreie Bi, formarea ureei Imunologice: sinteza Ig Aciune fagocitic a celulelor Kupffer

Hematologice Hematopoieza fetal Rezervor de snge 450ml 30ml/g mobilizare n cazul hipovolemiei Antibacterian Filtrarea bacteriilor Degradarea endotoxinelor Cel Kupffer fagociteaz : bacterii, virusuri, endotoxine, complexe imune, albumina denaturat, trombin, complexe fibrin-fibrinogen, celule tumorale lizozomi

Biotransformarea medicamentelor
Reacii de faz I: oxidare, reducere, hidroliz- citocromul

P450, SRE neted unii produi nc activi farmacologic

Reacii de faz II: glucuronidare, sulfatare, acetilare

compui inactivi

Producia bilei: 1/5 concentrat din 1000ml/zi Electrolii Proteine + sinteza a 120-300mg/kgc/zi albumin T1/2 20 zile = marker slab al leziunilor acute hepatice Bi Sruri biliare din acizii biliari emulsificarea grsimilor alimentareabsorbia lipidelor Acizii biliari sintetizai n ficat (colic + dezoxicolic din colesterol) conjugai cu Gly i Taurina sruri biliare

Ureea Degradarea hepatic a aa amoniac NH3 = toxic >1g/ml uree eliminare 100g proteine alimentare 30g uree 1molecul uree 2molecule H+ 1000mMolH+/zi Creatina n ficat - sintetizat din Met, Gly, Arg n muchi fsforilare fosfocreatin, excreie urinar n rat ct

 autoreglare Fluxul prop direct cu pres

autoreglare

Relaie semireciproc

2mmHg

Rapid disfuncie sever hepatic Lipsa antecedentelor hepatice Evoluie spre encefalopatie n 8 spt Bi serice Coagulopatie sever A 4-a cauz de deces n SUA pt vrstele de 45-54 ani dup cancer, boli cardiace, accidente traumatice!

Hiperacut 0-7 zile Acut 8-28 zile Subacut 29 zile-12 sptmni

Infecii Toxice AFPL (acute fatty liver of pregnancy), HELLP (hemoliz, enzimelor hepatice, trombocitopenie) Ischemie/hipoxie Boli metabolice

Encefalopatie grad 1-4 Icter Hepatomegalie Ascita Stelue Semnele vitale: hTA, hiperventilaie, alterarea termoreglrii, EAB

 TQ Bi ALAT, ASAT (alaninaminotransferaz, aspartataminotransferaz) , LDH Tardiv deteriorare renal creatininei intox cu acetaminofen, ischemie hepatic

IgM hepatita A Atg de suprafa hepatita B, C IgM hepatita B core Anticorpi pt hepatita C, HCV-ARN prin testul PCR

Acetaminofenic

Non- acetaminofenic

pHa < 7,3 INR > 6.5 TQ > 100s Creatinina > 3,4 mg% Encefalopatie III, IV

INR > 3,5 TQ > 50 sec Creatinina > 3,4 mg% Icter preced cu > 7 zile instalarea encefalopatiei B >18mg% Vrsta < 10 ani, > 40 ani

Neurologice Cardiovasculare Respiratorii Discrazii sanguine Renale DAB (acidoz lactic), DHE ( PIC) Metabolice (hipoglicemie, hipofosfatemie) Infecioase

Msuri generale Complicaii: neurol, CV, Resp, Coag, Renale, DABHE, Infecii Regimul glucide, aa ramificai Aport hidric Sedarea Decontaminarea tubului digestiv, lactuloza Evitarea ulcerului de stress OLT

Insuficien hepatic fulminant acetaminofen Hepatite non A, non B Hepatita datorat halothanului, idiosincraziilor

Sepsa SDRA Edemul cerebral refractar

Instabilitatea hemodinamic Tulburrile psihice Vrsta naintat

HIV Neoplasmele Disfunciile cronice pulmonare, cardiace,renale semnificative

Ficatul bioartificial Dializa hepatic

Prometheus Mars (Molecular Adsorbents Recirculation

System)

SNC Sistem CV Sist pulmonar Sistem renal GI Hemocoagulare

SNC Rar edem cerebral Encefalopatie : NH3, Mn, alterarea transmiterii endogene i a mesagerilorGABA, glutamat, NO

CV
Stare hiperdinamic
DC i vasodilataie arteriolar 70% Substanele vasoactive scurtcircuiteaz

metabolismul hepatic normal

DSE dobutamine stress echocardiography-

stratificare preoperatorie a riscului !!! Dg HTP i boala valvular!

Sistemul pulmonar Boli pulmonare restrictive Shunturi intrapulmonare Anomalii V/Q HTP
Hipoxemia n absena ascitei sau a bolilor pulmonare intrinsece: sindrom hepatopulmonar!

Dg diferenial Echocardiografie cu contrast bule de aer pt definirea cauzei hipoxemiei la aerul ambiental. Shunt intrapulmonar bulele apar la 5- 6 bti cardiace dup injectare Defect V/Q bulele de aer sunt absorbite n plmn

Absena uneri cauze renale primare Proteinurie Hipovolemie Cauze hemodinamice de hipoperfuzie renal

HTP
PAPmedie > 25mmHg cu PCWP N RVS > 120dyne/s x cm-5

Tipic Na urinar <10mEq/l Excreia fracionat a Na < 1% Tratament: vasoconstrictoare

Amelioreaz vasodilataia splanhnic, nivelul

vasoconstrictoarelor endogene, amelioreaz debitul sanguin renal

Evitarea antib nefrotoxice!

Modificarea algoritmelor terapeutice Stratificarea riscului Evaluri prognostice

Precizie Acuratee ncredere, stabilitate Reducerea invazivitii Continuitate/Intermiten Pre acceptabil Uor de neles, deprins, manipulat

ALAT alaninaminotransferaza ASAT aspartat aminotransferaza GGT gama glutamil transpeptidaza Bilirubina conj + excreie Fosfataza alcalin (ficat,oase, intestin) Proteine, albumina Coagularea IP sintez NH3, Mn GABA, glutamat, NO Intermitente

albuminemia
Sensibilitate
Caracterizarea modelelor de injurie Msurtoare crud a funciilor de sintez

Afectat de : starea de nutriie Boli renale

TP exprim
capacitii de sintez absorbiei de vit K (obstr biliar, colestaz)

Enzimele hepatice Ex; Tasmar, Imuran Rec: monitorizarea nivelelor enzimatice naintea creterii dozelor, apoi la fiecare 2-4 sptmni 6 luni de terapie ...> 6 luni, monitorizare periodic !!! ntreuperea tratamentelor la creterea enzimelor hepatice > 2x limita superioar a normalului Coagularea Bi

Studiu austriac 40 000pts Disfuncie hepatic la internare 10-25% Dezvoltarea disfunciei hepatice n TI: 15%

Krenn Claus G, Bedside assessment of hepatic function and functional reserve the time has come for all!

Edem cerebral + HIC 80% Coagulopatie + alterarea contienei + ALAT, ASAT anterior

Setup Configuration

PICG0025 ICG-PULSION 25 mg PICG0050 ICG-PULSION 50 mg

PULSION LiMON

PC5000 LiMON

PC50150 LiMON reusable sensor for adults and infants

Non-invasive liver function monitoring

PV50100 LiMON disposable sensor for adults and infants PV50200 LiMON disposable sensor for neonates

Pulse Densitometry Based on Pulse Oximetry

CICG mg/l

ICG Dilution Curve Analysis

LEDs
805 nm & 905 nm

pulsatile805 nm non pulsatile805 nm pulsatile905 nm

calculation of half life time and elimination rate of ICG-PULSION

Sensor
CICG mg/l
40 30

non pulsatile905
nm

dynamically determined range for back extrapolation pulsatile905 nm non pulsatile905 nm pulsatile805 nm non pulsatile805 nm

20

CICG =
0 10 20 30 40 50

10

[s]

Parameters

Global liver function from elimination of ICG-PULSION: Plasma Disappearance Rate of ICG ICG Retention Rate after 15 min ICG Clearance Circulating Blood Volume Pulse oximetry Oxygen Saturation Heart Rate PDR (%/min) R15 (%) CB (ml/min) BV (ml)

The Plasma Disappearance Rate of ICGPULSION (PDR) is influenced by liver function and liver perfusion. Changes of ICG-PDR within a short period of time are reflecting liver respectively splanchnic perfusion, as the function of liver cells does not change rapidly. LiMON provides an easy, fast and noninvasive monitoring of liver and splanchnic perfusion.

SpO2 (%) HR (bpm)

Calculations and Normal Ranges

Fields of Clinical Application

Parameter PDR (%/min) R15 (%) CBI (ml/min/m2) BVI (ml/m2)

Calculation ln2/t1/2 100 CICG15m / CICG t=0 100 BV PDR / BSA [ICG]inj / CICG t=0 / BSA

Normal Range 18 25 0 10 500 750 2600 - 3200

All critically patients, especially those with sepsis, acute liver or multi-organ failure, and after multiple trauma Patients with chronically reduced hepatic function (hepatitis, liver cirrhosis) Evaluation of liver function in organ donors and recipients Monitoring of liver function during liver or abdominal surgery (resection, porto-caval shunt) Diagnosis and monitoring of congenital liver failure in children and neonates

Prognosis of Survival in ICU Patients Clear indicator of probability of survival in septic shock
(Survivors) (Non-survivors)

Value as Liver Function Test in Intensive Care Higher sensitivity and specificity than bilirubin
ICG-PDR 100 (>15.2) 80
Sensitivity [%]

BILIRUBIN

n= 336 p= 0.06

60

(>33.8)

40 20 0

Conclusion: Increase of reduced ICG elimination during the first 120 hours of septic shock predicts survival, whereas no change or even further decrease of ICG elimination predicts non-survival
Kimura S et al: Crit Care Med 2001

20

40

60

80

100

100-Specificity [%]

Sakka SG, Meier-Hellmann A: Yearbook of Intensive Care and Emergency Medicine, 2001

Liver Function in Organ Donors Clear borderline for transplantation suitability

Application After Liver Transplantation Clear borderline for probability of graft function

Wesslau C et al: Transplantology 1994

Jalan R et al: Transplantation 1994

Value as Liver Function Test in Liver Surgery Better correlation with prognosis than laboratory parameters in cirrhotic patients

Value as Liver Function Test in Liver Surgery Correlation between parenchymal cell volume and ICG elimination

Hemming AW et al: Am J Surg 1992

Hashimoto M and Watanabe G: J Surg Res 2000

Senzor de tip pens Orice acces venos sau periferic pentru injecia ICG Rezultatele la pat n 6-8 min Cuantific funcia hepatic + valoare prognostic Rezultatele nu depind de utilizator pn la 10 msurtori n 24 de ore numrul prelevrilor de snge Bolnavii critici G 80 -110mg/ morbiditatea mortalitatea utilizarea atb transfuziilor riscul polineuropatiei Prevenirea insufieinei renale acute
Van Den Berghe G, Wouters PJ, Weekers F et al, N Engl J Med 2001; 345: 1359-67

Van Den Berghe G ; Wouters PJ, Bouillon R et al: Crit Care Med 2003; 31: 359-66

Dovedit NCH
Kinsley JS, Mayo Clinic Proc 2004; 79:992-1000

Dovedit CCV
Outttara A, Lecomte P, Le Manach Y et al; Anesthesiology 2005; 103:687-94

1. 2. 3.

Primum nil nocere Administrarea adecvat de proteine 1g/kgc/zi Preferina enteral

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1.

Enteral Parenteral Mixt entro-parenteral

2. 3. 4. 5. 6. 7. 8. 9.

Evaluarea necesitii suportului nutritiv indiferent de calea de administrare Evaluarea cheltuielilor energetice bazale n Kcal/zi Evaluarea cheltuielilor energetice de reapus Evaluarea necesarului caloric Evaluarea necesarului proteic Evaluarea necesarului de calorii neproteice Aportul de insulin Necesarul de electrolii Necesarul de vitamine, minerale, oligoelemente

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Identificarea condioolor n care se impune suportul nutritiv: a. Anticiparea ntreruperii alimentaiei enterale 7-10zile b. Cnd reluarea precoce a alimentaiei enterale este recomandat: seps, politraumatisme c. Subnutriia persistent diagnosticat ca pierderea a cel puin 10% din G uzual

Brbai Ec Harris Benedict BEE (kcal/zi)= 66+13,7G+5h-6,8A A vrsta (ani) G greutatea h nlimea Femei BEE = 66,5 + 9,6G + 1,7h-4,7A Necesarul energetic : 850-950kcal/kgc/zi 20-30cal/kgc/zi

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Factorul de stress Operaii majore, fr complicaii Traumatisme moderate, peritonit medie Traumatisme severe, insuficien de organ Arsuri > 40% din suprafa
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Cal = REE x activitate x febr

1,0-1,1 1,25 1,3-1,6 2,0
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Activitatea muscular crete necesarul caloric cu 10-25% Febra crete necesarul caloric cu 510%/grad Celsius/zi

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1g N provine din 6,25g proteine uscate Necesarul zilnic proteic: 1g/kgc/zi Arsuri 3,5g/kgc/zi 1g N pentru 150kcal neproteice

Glucidele 60% din dieta zilnic 400-500g /zi 4-5mg/kgc/min Lipidele 3-30% din caloriile totale Raportul optim G/L: 70/30

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n nutriia parenteral total

Glicemia >150mg% Glicemia >200mg% Glicemia > 250mg%

10U Ins/250g glucide 20-25 U Ins/250g glucide 30-50U Ins/250g glucide

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Na+, K+, Cl-, Ca2+, Mg2+, acetat, fosfat n funcie de nivelele serice Na necesar zilnic 60-150mEq/zi K 30-100mEq/zi, max 40mEq/l Pierderile de Cl- (sond nazo-gastric) impun creterea aportului Pierderile crescute de Bicarbonat- (diaree, acidoz) acetat Ca 5-15mM/zi Mg 8-20mM/zi PO42- 12-25mM/zi

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Liposolubile: A,D,E,K risc de intoxicaie, depozitare n es adipoase Hidrosolubile: C, B (1,2,6,12- tiamina, riboflavina, piridoxina, cobalamina), niacina, acidul pantotenic, folatul, biotina pot fi administrate pn la de 10x doza zilnic.

Deficite
vit A, B, C, Zn mpiedic vindecarea plgilor Vit E distrofii musculare, neuropatie, encefalopatie la copii Zn- alcoolici, insuficiena pancreatic, malabsorbie, sindromul intestinului mic, fistule gastro-intestinale, insuficiena renal cu dializ, nefroze, arsuri, plgi extinse: ntrzirtrea vindecrii plgilor, dermatite, alopecie, reducerea imunitii, diaree, depresie- suplimentele zilnice: 50mg, maz 3 zile Intoxicaia cu Zn: flushing, transpiraii, tulburri de vedere, imunodepresie Se- miastenie, cardiomiopatie Fe - Suplimentele sunt rareori necesare

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Evaluare
Anamnez Examen fizic
Pierderi ponderale de 5% 1 lun 7,5% n 3 luni 10% n 6 luni

Markeri serici
Albumina T1/2 20 zile Transferina T1/2 8 zile

Imunodepresia limfocite < 1200/mmc (limfopenie)

Calorimetrie indirect Scop: asigurarea aportului adecvat, evitarea excesului Consumul de O2 (ml/min) = DC (l/min) x (CaO2 ml/min-CvO2 ml/min) VO2 normal: 250ml/min aprox 3,5ml/kgc/min Producia normal de CO2 (VCO2)= 200ml/min (2,6ml/kgc/min) Coeficientul respirator: RQ = VCO2/VO2 Glucide 1, Proteine 0,82; lipide 0,71;alimentaie mixt 0,85; cetoz 0,67-0,7; lipogenez 1,0-12

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Formule parenterale modificate:

renale: hidrocarburilor catabolismului proteic Necesar: 1-1,2 g proteine/kgc/zi hemodializ 1,2-1,5 g/kgc/zi dializa peritoneal Formule cu restricie hidric i coninut crescut de lipide 30-40%, glucide 60-70% Formule hepatice lipsite de aa aromatici, coninut crescut de aa ramificai

Majoritatea sol enterale: 1kcal/ml, fr lactoz Soluii elementale: aa cristalini, zaharuri simple, AG eseniali, hipertone Soluii de stress (Impact): aa ramificai, nu necesit dezaminare hepatic, pot fi utilizate direct Soluii hepatice (Hepatic aid): aa ramificai, metionin, aa aromatici (precursori de fali neurotransmitori) Renale (Nephro) aa eseniali, puine proteine Formule gastrice: tamponeaz pHul, sucralfat Sol pentru adm jejunal: diluate la , mai ales dac osmolalitatea > 300mOsm/kgc

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Caut toxina de Clostridium difficile: metronidazol, vancomicin Reducei viteza de administrare sau reducei osmolalitatea sol Caut sorbitolul din medicaie (sorbitolul: diaree) Kaopectat 30ml oral la 4 ore, Imodium n lipsa clostridium Teste specifice pt d]g malabsorbiei

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