Acute and Chron|c L|ver Ia||ure

Iesse na|| MD

rofessor of Med|c|ne, Anesthes|a & Cr|nca| Care

Secnon Ch|ef, u|monary and Cr|nca| Care
Med|c|ne
Un|vers|ty of Ch|cago
Iacu|ty D|sc|osures
ur. Pall
recelves honorarla from Lhe ACC for Lhls course
and SLLk
recelves honorarla from Lhe A1S for SC1A
recelves honorarla from McCraw-Plll and 1aylor-
lrancls publlshlng
Learn|ng Cb[ecnves
Acute ||ver fa||ure
Dehne eno|og|es of InI
D|erennate between encepha|opathy and cerebra|
edema
Conduct a pre-transp|antanon eva|uanon
Descr|be transp|ant comp||canons |n the ICU
Chron|c ||ver fa||ure
Dehne pathophys|o|ogy of porta| hypertens|on
Adhere to genera| suppornve measures
Descr|be comp||canons of c|rrhos|s
S8 and secondary per|ton|ns
nepanc encepha|opathy
nepatorena| syndrome
Var|cea| hemorrhage
Acute L|ver Ia||ure
Dehn|nons
Acute nepanns:
Acute ||ver parenchyma| |n[ury from exposure to hepatotox|ns or
|nfecnous agents, such as v|ra| hepanns, tox|ns, a|coho|, or med|canons.

Acute L|ver Ia||ure:
Deve|opment of ||ver dysfuncnon |n the semng of severe acute hepanns.
Ieatures:
Iaund|ce
Coagu|opathy
Lncepha|opathy
1|m|ng:
Iu|m|nant (1rey and Dav|dson, 1970): w|th|n 8 weeks of the onset of
[aund|ce
hyperacute: [aund|ce to encepha|opathy |n 0 - 7 d
acute 7 - 28 d
subacute (S - 26 weeks).
Cuesuon 1: Whlch of Lhe followlng ls Lhe mosL
common cause of acuLe llver fallure?
A. Wllsons dlsease
8. Pepauus 8
C. Pepauus C
u. AceLamlnophen overdose
L. AuLolmmune hepauus
Lno|ogy of ALI
nlP SLudy Croup, PepaLology, Aprll 2008
Acetam|nophen 1ox|c|ty
Most common cause of acute ||ver fa||ure
Low therapeunc |ndex
As ||u|e as S grams can be tox|c
8ody s|ze |s |mportant
1reatment
Acnvated charcoa| |f < 4 hours s|nce nme of |ngesnon
Acety|cyste|ne (C or IV)
If above the ||ne on the kumack-Mauhew nomogram ||ne
If unknown nme of |ngesnon and |eve| > 10mcg]m|
If > 7.S gm |ngesnon and |eve| not ava||ab|e for > 8 hours
Suppornve care
Intubanon w|th stage III or IV encepha|opathy to prevent pneumon|a
IC mon|tor|ng |f |ntubated and awa|nng transp|ant
L|ver transp|ant
NAC: C or IV?
No conv|nc|ng ev|dence of |mproved outcome w|th IV
preparanon
Anaphy|acto|d reacnons ||ke|y more common w|th IV
adm|n|stranon (reported |nc|dence w|th IV drug S to 1S,
predom|nance of sk|n reacnons)
Deaths have been reported from these reacnons
Accord|ng|y, C route preferred, IV used on|y when gut
adm|n|stranon |s prec|uded
Se|ecnng anents for 1ransp|antanon
Ma[or cha||enge |n ALI |s to determ|ne those who
w||| recover w|th med|ca| treatment, those for whom
surgery |s fun|e, and those |n whom the r|sks of
surgery and ||fe|ong |mmunosuppress|on are [usnhed
erform the above w|th the best a||ocanon of organ
to panent (|n the US, 17 k pts on wa|nng ||st, S k
xp|ants]yr)
Cuesuon 2: Whlch of Lhe followlng seL of parameLers ls
used Lo calculaLe Lhe MLLu score?
A. LacLaLe, blllrubln, and albumln
8. LacLaLe, creaunlne, blllrubln
C. laLeleL counL, ln8, lvll
u. Creaunlne, blllrubln, ln8
L. 8lllrubln, level of encephalopaLhy, ln8

Mode| for Lndstage L|ver D|sease
MLLD Score = 10 (.9S7 * Cr + 1.12 * 1b||| + 1.12 (INk
+ .643))
What you shou|d know
Cr, 8|||, INk
Des|gned to a||ow UNCS to be more emc|ent and d|d so
8ased predom|nant|y on CLD but now more w|de|y app||ed
ICU Management of ALI
rophy|ax|s aga|nst UGI 8|eed: Ac|d suppress|on w|th n2 b|ocker, proton-
pump |nh|b|tor or mucosa| protecnon w|th sucra|fate.
Coagu|opathy: rophy|acnc use of coagu|anon factors to prevent b|eed|ng
events |s |neecnve and d|scouraged. 1he|r use can obscure ear|y s|gns
(|mprov|ng 1) of hepanc recovery.
Seps|s: Seps|s |s one of the |ead|ng causes of death |n these panents.
Iebr||e panents shou|d be pan-cu|tured and annb|onc therapy |nsntuted
ear|y.
nypog|ycem|a: Severe ||ver |n[ury marked|y d|srupts g|ucose homeostas|s
as the ||ver |s one of the ma|n stores of g|ycogen. Intravenous g|ucose
|nfus|ons are a ma|nstay of treatment.
Lncepha|opathy: 1he cause of encepha|opathy |n the semng of acute ||ver
fa||ure |s cerebra| edema. Any panent w|th grade II or h|gher
encepha|opathy shou|d be eva|uated for cerebra| edema (|mag|ng stud|es of
the bra|n and]or |ntracran|a| pressure mon|tor|ng)
Mechan|sms of Lncepha|opathy
Chron|c L|ver D|sease
Ammon|a, GA8A, G|utamate - G|utam|ne, 8enzod|azep|ne keceptors
1reatment w|th |actu|ose, neomyc|n, |ow-prote|n d|et
Acute L|ver Ia||ure
Cerebra| Ldema (poss|b|e ro|e for Nn
3
)
1reatment w|th IC mon|tor, mann|to|, d|a|ys|s, nC8 e|evanon, pressure
contro|, |nduced coma.
Deve|opment of Grade III encepha|opathy |s an om|nous s|gn,
pred|cnve of poor outcome
Grades of Lncepha|opathy
Grade 0: No a|teranon of menta| status
Grade I: Awake and respons|ve
M||d confus|on and d|sor|entanon
A|tered persona||ty
Aster|x|s may or may not be present

Grade II: Awake, but ag|tated
Increas|ng|y confused and d|sor|ented
na||uc|nanons

Grade III: Increas|ng suppress|on of menta| status
Stuporous but arousab|e to voca| or tacn|e snmu||
May requ|re endotrachea| tube for a|rway protecnon

Grade IV: Unrespons|ve to voca| or tacn|e snmu|anon
Lssenna||y comatose but w|th |ntact pup|||ary reexes
Usua||y sn|| w|thdraw to pa|nfu| snmu||
Cuesuon 3: WhaL ls Lrue abouL lnLracranlal
pressure and lC monlLors ln fulmlnanL
hepauc fallure?
A. arenchymal lnLracranlal pressure Lransducers are
preferred over subdural or epldural monlLors
8. lC monlLors should be placed regardless of ablllLy Lo
correcL coagulopaLhy
C. 1he lncrease ln lC ls reverslble by LreaLmenL wlLh
lacLulose
u. Cerebral perfuslon pressure (MA - lC) < 40 mmPg for
more Lhan 4 hours resulLs ln lrreverslble braln ln[ury
L. 1he lC should be measured Lwlce dally
IC Mon|tor|ng
|ace the Intracran|a| ressure (IC) Mon|tor |n the Lp|dura| Space
IC Mon|tor|ng
Shou|d be strong|y cons|dered when panents evo|ve from stage II
(ag|tated confus|on) to stage III (stuporous) encepha|opathy.
Ma|nta|n adequate p|ate|et count (> 60,000) w|th p|ate|et
transfus|ons and INk < 1.S w|th fresh frozen p|asma, |f necessary.
1reatment Gu|de||nes
Mann|to| |s used to contro| IC |n panents w|th |ntact rena| funcnon
or |n those on d|a|ys|s.
Mann|to| |s g|ven |n 0.S to 1.0 g]kg doses. Serum e|ectro|ytes,
g|ucose, and osmo|ar|ty shou|d be checked every 4 to 6 hours. If
IC e|evated, osmo|ar|ty < 310, and Na <14S, then g|ve mann|to|.
Mann|to| shou|d be he|d |f the panent has excess|ve serum
osmo|ar|ty or s|gn|hcant hypernatrem|a.
Pall, SchmldL & Wood
rlnclples of Crlucal Care,
2003
Acute a|coho||c hepanns
May noL exhlblL all Lhe feaLures of ALl
8apld onseL of [aundlce, fever, asclLes, and proxlmal
muscle loss
Llver Lyplcally large and Lender
AsparLaLe amlnoLransferases levels > 2x normal buL
rarely above 300 lu/ml, and AS1/AL1 Lyplcally > 2
nL!M 2009
nL!M 2011
174 pLs randomlzed
rednlsolone x 4 weeks
nAC x 3 days or noL

rlmary endpL 6 mos survlval noL dl
ShorL Lerm morLallLy lmproved

Less hepaLorenal syndrome and
lnfecuon ln nAC group
nL!M 2011
8elapse Lo drlnklng ln 3 pLs over Lwo year perlod
Causes of hyperammonem|a |n the
absence of hepatoce||u|ar |n[ury
Clay and Palllne, ChesL 2007 132:1368
Causes of hyperammonem|a |n the
absence of hepatoce||u|ar |n[ury
Clay and Palllne, ChesL 2007 132:1368
Causes of hyperammonem|a |n the
absence of hepatoce||u|ar |n[ury
L|ver 1ransp|antanon
Cr|ter|a for L|ver 1ransp|antanon
|n InI: k|ngs Co||ege Uk
Cr|ter|a for L|ver 1ransp|antanon
|n InI: k|ngs Co||ege Uk
MLLD Score for pred|cnng need for ||ver
transp|ant
L|ver 1ransp|antanon |n InI
551 Cases Referred
129 Met Tx Criteria 422 Did Not Meet Criteria
39 Tx 90 No Tx
72% 11% 93% Survival
!"##"$%& () *+,- .$/01#23$ 411536) 7831 9::;
Surv|va| of ALI vs CLD aher transp|ant
nlP SLudy Croup, PepaLology, Aprll 2008
Comp||canons of 1ransp|antanon


Are c|ose|y re|ated to:
- re-morb|d d|sease and cond|non
- 1ransp|ant procedure
- ke[ecnon of the grah or host
- Consequences of |mmunosupress|on
May be dlvlded lnLo:
- nonlnfecuous compllcauons
- lnfecuous compllcauons

Lar|y non-|nfecnous comp||canons
Pemorrhage
rlmary gra fallure- 1 Lo 3 (change wlLh uCu?)
Pepauc arLery Lhrombosls
Masslve llver necrosls
8lle leak
Pepauc abscesses
u/S dx
8lle leaks or sLrlcLures
AcuLe re[ecuon
4 -14 days posL LransplanL
lever, mlld elevauon Lransamlnases
Chron|c L|ver Ia||ure (Management of
the anent w|th C|rrhos|s)
Management of the anent w|th C|rrhos|s
Stab|e (un||sted) panent w|th ma[or new prob|em
(var|cea| hemorrhage, S8 and seps|s)
L|sted panent w|th deter|oranon
In e|ther case, cr|nca| care at nexus of hepato|ogy,
Ik, transp|ant surgery, GI endoscopy, etc
athophys|o|ogy of orta| nypertens|on
Norma||y 2]3 of hepanc ow |s porta| at |ow
res|stance (portocava| grad|ent 2-6 mm ng)
W|th hbros|s, br|dg|ng, grad|ent r|ses, porta| ow
reduced w|th co||atera| c|rcu|anon
Mass|ve sp|en|c d||anon, sequestranon
Asc|tes
nyperdynam|c system|c c|rcu|anon
Management of the anent w|th C|rrhos|s
n|gh r|sk of |nfecnon
Immune comprom|se
W|der range of organ|sms and pr|or hea|thcare contact
Ad[usted kk for hosp|ta||zanon re|ated to seps|s 2.6 for
c|rrhos|s, Akk for death 2.0
Most common s|te |s ur|ne, fo||owed by asc|tes, b|ood,
and resp|ratory tract
Management of the anent w|th C|rrhos|s
8acter|a| per|ton|ns
Any panent w|th fever or abdom|na| pa|n shou|d be
cons|dered for paracentes|s
D|snngu|sh|ng S8 from secondary per|ton|ns may be
d|mcu|t by exam
U]S Gu|dance for paracentes|s
U]S Gu|dance for paracentes|s
Management of the anent w|th C|rrhos|s
S8 Cu|ture neg
neutrocync
asc|tes
8acterasc|tes Secondary
per|ton|ns
Mn CounL
(cells/mm3)
>230 >230 <230 >>230
CulLure Slngle
organlsm
negauve Slngle
organlsm
Muluple
organlsms
roLeln usually low usually low usually low usually > 1g/
dl
LuP normal normal normal Plgh
Clucose normal normal normal Low
8epeaL para can be of use Lo deLermlne course of amblguous ndlngs
Management of S8]CNNA]8A
Most cases caused by gut ora but Strep or
Staph may occur
Cefotax|me a reasonab|e emp|r|c cho|ce
If outpanent qu|no|one prophy|ax|s |s be|ng
emp|oyed, w|der spectrum may be needed
kena| fa||ure common comp||canon (30-40)
and one study showed dramanc beneht (AkI
|nc|dence and surv|va|) from a|bum|n 1.S g]kg at
dx and 1 gm]kg on d 3 (NLIM 1999, 341:403)

Management of the anent w|th C|rrhos|s
nL]SL
rec|p|tants
Drugs
GIn
Infecnon
Dehydranon
L|ectro|yte d|sturbances
nepanc decompensanon
Inc prote|n |ntake
Urem|a
Ac|dos|s
ortosystem|c shunts
Management of the anent w|th C|rrhos|s
nS]SL
Auennon to a|rway
Lactu|ose
Standard rx
Sa|d to dec trans|t nme, b|nd n|trogenous tox|ns, a|ter
gut pn
Abx: metron|dazo|e, neomyc|n, r|fax|m|n
rob|oncs
Management of the anent w|th C|rrhos|s
nepatorena| syndrome
Imp||es exc|us|on of nephrotox|c drugs, seps|s, |ntr|ns|c
rena| d|sease, hypovo|em|a
Cccurs |n up to 39 of pts w|th c|rrhos|s > S years
Marker for poor outcome
Creann|ne overesnmates GIk |n these pts
Shou|d prompt cons|deranon for ||ver xp|ant |f other
cond|nons dont prec|ude th|s
Management of the anent w|th C|rrhos|s
nepatorena| syndrome
nkS 1ype I-rap|d progress|on of kI over 2 weeks or |ess
w|th a 2-fo|d |ncrease |n creann|ne or S0 reducnon |n
creann|ne c|earance
nkS 1ype II- deve|ops stread||y over months w|th a
creann|ne c|earnace |ess than 40 m|]m|n
Med|an surv|va| |s |ess than two weeks for 1ype I and |ess
than s|x months for 1ype II
Management of the anent w|th
C|rrhos|s
nepatorena| syndrome
kevers|ng ||ver damage or transp|ant reverse the
cond|non
No ro|e for dopam|ne, octreonde as s|ng|e agents
Con|cnng data for ter||press|n as s|ng|e agent
erhaps beneht from comb|ned therapy w|th
m|dodr|ne and octreonde
nepato|ogy 1999, 29:1690
D|g D|s Sc| 2007, S2:742
Management of the anent w|th
C|rrhos|s
nepatorena| syndrome
|asma expans|on w|th a|bum|n and paracentes|s |n
cr|nca||y ||| pts w|th tense asc|tes and hepatorena|
syndrome (Cr|t Care 2008 12:1-9
200 m| 20 a|bum|n fo||owed by |arge vo|ume
paracentes|s
Management of the anent w|th
C|rrhos|s
Management of the anent w|th
C|rrhos|s
J Hepatol 2012
S8 rophy|ax|s for the asc|nc c|rrhonc |n
the ICU
Morta||ty beneht shown |n panents
hosp|ta||zed w|th GIn
May beg|n w|th cehr|axone 1 g IV da||y,
sw|tch to noroxac|n 400 mg ora||y when
po begun

8a||oon 1amponade
8a||oon 1amponade
anent w||| need spectacu|ar access
1hree dev|ces
Sengstaken-8|akemore
M|nnesota
L|nton-Nach|as (|arge vo|ume gastr|c ba||oon on|y)
A|rway, a|rway, a|rway
Immob|||ze, |mmob|||ze, |mmob|||ze
|an b, p|an b, p|an b
Cctreonde
Long-acnng ana|og of somatostann
IV adm|n|stranon causes marked and rap|d
decrease |n porta| venous |now, porta| pressure,
and |ntravar|cea| pressure
Wh||e these eects are trans|ent b|eed|ng reducnon
and reduced r|sk of reb|eed|ng are susta|ned
1rans[ugu|ar Intrahepanc
orta|-System|c Shunt:
(1IS)
nas |arge|y rep|aced ear||er surg|ca| shunts
nemostas|s ach|eved |n 90 of pts
Comp||canons
M|sp|acement
SL (30)
nemo|ync anem|a (10)
1IS stenos|s (|ess w|th coated dev|ces)
Vegetanve |nfecnons (rare)
Acute cerebra| edema (very rare)
Ind|canons for 1IS:
Nat| D|g D|s Adv|sory 8oard
Acute b|eed|ng not successfu||y contro||ed w|th
med|ca| or endoscop|c therapy
anents refractory or |nto|erant to med|ca| or
endoscop|c therapy, w|th recurrent b|eed|ng
8|eed|ng from gastr|c var|ces?

!une 2010
LAkL USL CI 1IS IN A1ILN1S
kLSLN1ING WI1n VAkICLAL
8LLLDING
C class C or class 8 wlLh conunued bleedlng aL endoscopy known
Lo have hlgh fallure raLe
63 such pauenLs randomly asslgned aL 24 h Lo elLher 1lS wlLhln
72 h vs 1lS s rescue Lherapy
lollowed for 16 mos for rebleedlng or fallure Lo conLrol bleedlng
Management of the anent w|th C|rrhos|s
Cne po|nt 1wo po|nt 1hree po|nt
8lllrubln <2 2-3 >3
Albumln > 3.3 3.3-2.8 <2.8
ln8 < 1.7 1.7-2.3 >2.3
AsclLes AbsenL Mlld-Mod Severe/refracLory
LncephalopaLhy AbsenL l-ll lll-lv
C|ass A: S-6
C|ass 8: 7-9
C|ass C: 10-1S