Insuficiena hepatic

acut

Funciile ficatului
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

Funciile ficatului cont

Excreie Bi, formarea ureei

Imunologice:
sinteza Ig
Aciune fagocitic a celulelor Kupffer

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

Funciile ficatului cont

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

Funciile ficatului cont

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

Ficatul i rinichiul
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

Aportul de snge al acinului hepatic

Microcirculaia ficatului
autoreglare
Fluxul prop direct cu pres

autoreglare

Relaie semireciproc

2mmHg

Insuficiena hepatic acut

Definiie

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!

Insuficiena hepatic fulminant

Hiperacut 0-7 zile

Acut 8-28 zile
Subacut 29 zile-12 sptmni

Etiologie

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

Tablou clinic

Encefalopatie grad 1-4

Icter
Hepatomegalie
Ascita
Stelue
Semnele vitale: hTA, hiperventilaie, alterarea
termoreglrii, EAB

Ex paraclinice

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

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

Prognosticul advers al insuficienei

hepatice acute
Acetaminofenic

Non- acetaminofenic

pHa < 7,3

INR > 3,5

INR > 6.5

TQ > 100s
Creatinina > 3,4 mg%

TQ > 50 sec

Encefalopatie III, IV

Icter preced cu > 7 zile

instalarea encefalopatiei
B >18mg%

Creatinina > 3,4 mg%

Vrsta < 10 ani, > 40 ani

Complicaii

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

HIC in insuficienta hepatica acuta

Tratament

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

Indicaiile transplantului hepatic

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

Argumente de abinere

Sepsa
SDRA
Edemul cerebral refractar

Contraindicaii relative/absolute

Instabilitatea
hemodinamic
Tulburrile psihice
Vrsta naintat

HIV
Neoplasmele
Disfunciile cronice
pulmonare,
cardiace,renale
semnificative

Metode experimentale

Ficatul bioartificial

Dializa hepatic
Prometheus
Mars

(Molecular Adsorbents Recirculation

System)

Prometheus

Mars

Boala hepatic preterminal

end stage liver disease
SNC
Sistem CV
Sist pulmonar
Sistem renal
GI
Hemocoagulare

Boala hepatic preterminal

- cronic end stage liver disease
SNC
Rar edem cerebral
Encefalopatie : NH3, Mn, alterarea
transmiterii endogene i a mesagerilorGABA, glutamat, NO

Boala hepatic preterminal

- cronic end stage liver disease
CV

Stare hiperdinamic

DC i vasodilataie arteriolar 70%

Substanele vasoactive scurtcircuiteaz
metabolismul hepatic normal
DSE dobutamine stress echocardiographystratificare preoperatorie a riscului !!! Dg HTP i
boala valvular!

Boala hepatic preterminal

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

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

Sindrom hepatopulmonar

HTP

PAPmedie > 25mmHg cu PCWP N

RVS > 120dyne/s x cm-5

Sindromul hepato-renal

Absena unei cauze renale primare

Proteinurie
Hipovolemie
Cauze hemodinamice de hipoperfuzie renal

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!

Monitorizarea funciei hepatice

Motivaie

Modificarea algoritmelor terapeutice

Stratificarea riscului
Evaluri prognostice

Cererea

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

Ficatul - funcii

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

Caracterizarea modelelor de
injurie

Msurtoare crud a funciilor

de sintez

Sinteza

albuminemia
Sensibilitate
Afectat

de :

starea de nutriie
Boli renale

TP exprim

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

Monitorizarea tratamentelor
cronice
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

Disfuncia hepatic i TI
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!

Insuficiena hepatic fulminant

Edem cerebral + HIC 80%

Coagulopatie + alterarea contienei +

ALAT, ASAT anterior

Ficatul un necunoscut n tranziie?

PULSION LiMON

Non-invasive
liver function monitoring

Setup Configuration

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

PC5000 LiMON

PC50150 LiMON reusable sensor for adults and infants

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

Pulse Densitometry Based on Pulse Oximetry

LEDs

pulsatile805 nm

805 nm & 905 nm

non pulsatile805 nm

pulsatile905 nm

Sensor

non pulsatile905
nm

CICG mg/l
40

pulsatile905 nm

30

20

CICG =

10

non pulsatile905 nm
pulsatile805 nm
non pulsatile805 nm

0
0

10

20

30

40

50

[s]

ICG Dilution Curve Analysis

CICG mg/l

calculation of half life time and

elimination rate of ICG-PULSION

dynamically determined
range for back extrapolation

Parameters

Global liver function from elimination of ICG-PULSION:

Plasma Disappearance Rate of ICG

ICG Retention Rate after 15 min
ICG Clearance

PDR (%/min)
R15 (%)
CB (ml/min)

Circulating Blood Volume

BV (ml)

Pulse oximetry
Oxygen Saturation
Heart Rate

SpO2 (%)
HR (bpm)

Basics

The Plasma Disappearance Rate of

ICG-PULSION (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

non-invasive monitoring of liver and
splanchnic perfusion.

Calculations and Normal Ranges

Parameter

Calculation

Normal Range

PDR (%/min)

ln2/t1/2 100

18 25

R15 (%)

CICG15m / CICG t=0 100

0 10

CBI (ml/min/m2)

BV PDR / BSA

500 750

BVI (ml/m2)

[ICG]inj / CICG t=0 / BSA

2600 - 3200

Fields of Clinical Application

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)

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

Value as Liver Function Test in Intensive Care

Higher sensitivity and specificity than bilirubin
ICG-PDR

BILIRUBIN

100

n= 336
p= 0.06

(>15.2)

Sensitivity [%]

80
(>33.8)

60

40
20

0
0

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

Wesslau C et al: Transplantology 1994

Application After Liver Transplantation

Clear borderline for probability of graft function

Jalan R et al: Transplantation 1994

Value as Liver Function Test in Liver Surgery

Better correlation with prognosis than laboratory parameters
in cirrhotic patients

Hemming AW et al: Am J Surg 1992

Value as Liver Function Test in Liver Surgery

Correlation between parenchymal cell volume and ICG elimination

Hashimoto M and Watanabe G: J Surg Res 2000

Avantajele Pulsion Limon

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

Ficat
Metabolism nutriie controlul glicemiei
EHE - EAB

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