1ransp|ant ke|ated Issues

SLephen kanLrow, Mu
AssoclaLe rofessor of Medlclne
ulmonary/Crlucal Care Medlclne
Loulslana SLaLe unlverslLy PealLh Sclences CenLer
new Crleans
D|sc|osure
l have no relauonshlps wlLh lndusLry
Cernhcanon Lxam|nanon 8|uepr|nt
lmmunocompromlsed hosL 2
8raln deaLh 1
8one marrow LransplanL 0-1
Compllcauons of lmmunosuppresslve drugs and
chemoLherapy 0-1
1ransplanLauon 0-1
LLhlcal conslderauons 2-3
SysLemlc and CnS lnfecuons 6__
1C1AL ???
Cb[ecnves
Cb[ecnve 1: Idennfy bas|c |mmunosuppress|ve approaches |n so||d
organ transp|antanon.
Cb[ecnve 2: L|st common |nfecnous and non-|nfecnous
comp||canons of so||d organ transp|antanon.
Cb[ecnve 3: Lxp|a|n |nd|canons for so||d organ transp|antanon |n
cr|nca||y ||| panents.
Cb[ecnve 4: D|scuss pr|nc|p|es of organ donanon |n the |ntens|ve
care un|t.
Cb[ecnve S: Idennfy ma[or causes of cr|nca| |||ness aher
hematopo|enc ce|| transp|antanon.

?ou are evaluaung a 24 year old woman who
underwenL solld organ LransplanLauon ve monLhs
ago
Immunosuppress|on
MalnLenance Lherapy usually lncludes
Calclneurln lnhlblLor (Lacrollmus, cyclosporlne)
8enal lnsumclency, neuroLoxlclLy
Cell cycle lnhlblLor (azaLhloprlne, mycophenolaLe)
Leukopenla
CorucosLerolds
Conslder sLress dose sLerolds
Acute ke[ecnon
1reaLmenL reglmens are hlghly lmmunosuppresslve:
Plgh dose corucosLerolds
Anu-LhymocyLe globulln
Anu-Cu32
CourLesy of v valenune Mu
Infecnons:
I|rst Month Aher 1ransp|antanon
1hree Sources:
1ransplanL reclplenL
Anublouc reslsLanL bacLerla, re-acuvauon of vlral hepauus,
sLrongyloldes hyperlnfecuon
1ransplanL donor
Anublouc reslsLanL bacLerla
LymphocyLe chorlomenlnglus vlrus, WesL nlle vlrus, Plv,
hepauus C, herpes slmplex, PPv8, rables
1oxoplasmosls, Lrypanosomlasls, ameblc encephallus
PosplLal envlronmenL
nosocomlal paLhogens
Infecnons:
Cne to S|x Months Aher 1ransp|antanon
lungl
neumocysus [lrovecll pneumonla (C)
non sulfa-LrlmeLhoprlm reglmens may fall
Asperglllus, 8hlzopus, Scedosporlum, lusarlum
PlsLoplasma, Coccldloldes, CrypLococcus,
8lasLomyces
vlruses
CyLomegalovlrus, herpes slmples, herpes zosLer
MycobacLerla
M. Luberculosls, avlum lnLracellulare, abscessus
nocardla, Loxoplasmosls
CourLesy of 8 Murray Mu
CourLesy of L 8eckman Mu
Asperglllus
Mucor
CMV Infecnon
PlghesL rlsk ln CMv negauve reclplenL from posluve
donor
neumonlus, hepauus, collus
valganclclovlr ls eecuve prophylaxls
Acyclovlr ls noL
CMv vlral lncluslons, anugen deLecuon or vlremla
are lndlcauons for LreaLmenL
lnLravenous ganclclovlr
CourLesy of v valenune Mu
Infecnon:
More than S|x Months aher 1ransp|antanon
CpporLunlsuc lnfecuons are more common lf course
ls compllcaLed
lnLensled lmmunosuppresslon
Cra dysfuncuon
CommunlLy acqulred lnfecuons may be severe
neumococcus, leglonella, resplraLory vlruses
Case 1
A 22 year old woman ln your lCu Look an aceLamlnophen
overdose 3 days ago. She ls encephalopaLhlc, 1/ln8 ls 6.6,
serum blcarbonaLe ls 11, creaunlne 6.3. Whlch one of Lhe
followlng sLaLemenLs ls Lrue?
A. Per llver LransplanL prlorlLy ls deLermlned by MLLu score
8. All acuLe llver fallure pauenLs have encephalopaLhy
C. PepaLopulmonary syndrome would lncrease her LransplanL
prlorlLy
u. Per mosL llkely cause of deaLh ls gasLrolnLesunal hemorrhage
L. Per renal fallure ls lrreverslble

Acute L|ver Ia||ure |n the ICU
AcuLe llver fallure ls dened as:
AcuLe llver ln[ury, lmpalred synLheuc funcuon and
encephalopaLhy
revlously normal llver or well-compensaLed llver dlsease
Lxamples: aceLamlnophen LoxlclLy, acuLe vlral hepauus,
LransplanL gra fallure
AcuLe llver fallure ls unCS sLaLus 1-hlghesL prlorlLy,
noL dependenL on MLLu score
Cerebral edema ls a common cause of deaLh whlle
awalung LransplanL
Chron|c L|ver D|sease |n the ICU
unCS MLLu score ls based on blllrubln, 1/ln8, creaunlne
Survlval ls beuer wlLh LransplanL when MLLu > 20
rolonged acuLe kldney ln[ury (>6-8 weeks) may be
LreaLed wlLh slmulLaneous renal LransplanLauon
Compllcauons LhaL lncrease llver LransplanL prlorlLy:
PepaLocellular carclnoma
Cne leslon < 3 cm or Lhree leslons < 3 cm
PepaLopulmonary syndrome
aC2 < 60 mmPg
orLopulmonary hyperLenslon
Aer lL has been LreaLed and < 33 mmPg (mean)
22 year o|d woman ear|y aher ||ver
transp|antanon, not do|ng we||.
In the hrst hours to days aher ||ver
transp|antanon cons|der:
Pemorrhage
AnasLomouc leak and perlLonlus
Pepauc arLery Lhrombosls
lschemlc necrosls of gra
orLal veln Lhrombosls
AsclLes, lnLesunal edema, varlceal bleedlng
Pepauc veln Lhrombosls
aln, hepaLomegaly, asclLes
Csmouc demyellnauon syndrome
46 year o|d man S months aher ||ver
transp|antanon w|th se|zures
SauLer A eL al. A!8 2010,194:W141-W149
Centra| Nervous System Comp||canons of
1ransp|antanon
Conslder:
ulssemlnaLed lnfecuon
nocardla
Asperglllus
Mallgnancy
non-Podgkln lymphoma
lncreased rlsk of all mallgnancles
Calclneurln lnhlblLor neuroLoxlclLy
28 year o|d woman w|th cysnc hbros|s
awa|nng transp|antanon
CourLesy of k McAnally Mu
28 year o|d woman w|th cysnc hbros|s |n
awa|nng transp|antanon
Lung allocauon score ls based upon LransplanL
urgency and posL-LransplanL beneL (noL walung
ume)
8lood group and lung slze are maLched
Survlval ls beuer for bllaLeral lung compared wlLh
slngle lung (~ 7 vs 3 years)
28 year o|d woman w|th cysnc hbros|s |n
the ICU aher transp|antanon
Cn Lhe rsL posL-operauve day
28 year o|d woman w|th cysnc hbros|s |n
the ICU aher transp|antanon
1he perl-operauve compllcauon she mosL llkely has
ls:
A. ulmonary embollsm
8. rlmary gra fallure
C. 8ronchopleural sLula
u. CMv pneumonlus
L. Alr embollsm
rlmary gra fallure
Mlld edema ls common
Severe prlmary gra fallure has a hlgh morLallLy
aC2/llC2 rauo < 200 aL 48 hours has 33 morLallLy aL 90 days
rekker eL al, ! PearL Lung 1ransplanL 2006
Lung ln[ury aer slngle lung LransplanLauon for CCu
May requlre lndependenL lung venulauon
ulerenual LL
Avold excesslve venulauon ln nauve lung
Lar|y Comp||canons of Lung 1ransp|antanon
lndependenL Lung venulauon
Alr embollsm (coronary, sysLemlc)
Alr leak from anasLomosls
uehlscence of anasLomosls
ulmonary embollsm
laLal hyperammonemla
Krishnam M S et al. Radiographics
2007;27:957-974
Lar|y Comp||canons of Lung 1ransp|antanon
Later Comp||canons of Lung 1ransp|antanon
AcuLe re[ecuon
neumonla
8urkholderla cenocepacla (genomovar lll) colonlzauon
confers very hlgh rlsk ln Cl pauenLs
CpporLunlsuc lnfecuon
usually aer Lhe rsL monLh
Alrway compllcauons
Malacla, sLenosls, sLula

8ronchlollus obllLerans syndrome
Ma[or cause of gra fallure and deaLh
rogresslve loss of lung funcuon, worsenlng obsLrucuon
May have exLremely llmlLed venulaLory capaclLy
Super-lnfecuon wlLh reslsLanL bacLerla and molds
CourLesy of ur. k McAnally CourLesy of ur. v valenune
Later Comp||canons of Lung 1ransp|antanon
33 year o|d man w|th systo||c heart fa||ure
|n the ICU
noL a candldaLe for revascularlzauon
Ind|canons for neart 1ransp|antanon
Class lv hearL fallure and low e[ecuon fracuon are
noL sumclenL lndlcauons for LransplanLauon
8efracLory cardlogenlc shock
lnLravenous lnoLrope dependence
eak vC2 less Lhan 10 mL/kg/mln
Severe lnoperable lschemla
8efracLory sympLomauc venLrlcular Lachycardla
Plgh pulmonary vascular reslsLance ls a conLralndlcauon Lo
LransplanLauon (> 4 Woods unlLs)
neart 1ransp|ant Surv|va|
unCS SLaLus 1 (hlghesL prlorlLy) pauenLs have 70 one
year survlval wlLhouL LransplanL
Medlan survlval aer LransplanL ls greaLer Lhan 10 years
Le venLrlcular
AsslsL uevlce
Aruclal PearL
kecurrent neart Ia||ure aher 1ransp|antanon
Pe ls readmlued wlLh sysLollc dysfuncuon and
pulmonary edema 4 monLhs laLer
Conslder:
AcuLe re[ecuon
CMv myocardlus
1oxoplasma myocardlus
osL LransplanLauon lymphoprollferauve dlsorder
LvaluaLe by endomyocardlal blopsy
lrequenL blopsles assoclaLed wlLh all Lrlcuspld valve
CourLesy of ur. L 8eckman
Arrhythm|as aher neart 1ransp|antanon
Whlle ln Lhe hosplLal he develops supravenLrlcular
Lachycardla
8e aware LhaL:
SensluvlLy Lo adenoslne ls lncreased
use 23-30 of usual dose
lor LreaLmenL of bradycardla
ALroplne ls noL eecuve ln Lhe denervaLed hearL
Av node remalns sensluve Lo caLecholamlnes

Late Comp||canons aher neart
1ransp|antanon
Allogra vasculopaLhy
SllenL lnfarcuon
SysLollc hearL fallure
Sudden deaLh
Mallgnancy

CourLesy of ur. S Mandras
64 year o|d man underwent rena|
transp|antanon 6 months ago
Admlued Lo Lhe lCu
kena| 1ransp|ant Comp||canons
Ma[or causes of deaLh
Cardlovascular dlsease
lnfecuon
Mallgnancy
volume overload ls common
Calclneurln lnhlblLors
Chronlc allogra nephropaLhy
llash pulmonary edema wlLh sLenosls
of (lllac) arLery supplylng Lhe allogra
aLel, eL al. 8adlology 2001 (219)663
ou are asked to eva|uate a S2 year o|d
man w|th a |arge |ntra-cerebra|
hemorrhage
Cllnlcal evaluauon wlLh deLalled neurologlc
examlnauon demonsLraLes loss of bralnsLem
funcuon
1he pauenL ls noL breaLhlng sponLaneously above
Lhe seL venulaLor raLe of 12 breaLhs per mlnuLe
8ra|n Death Assessment
lor apnea Lesung Lhe rlse ln pCC2 > 20 Lorr can
requlre 10-20 mlnuLes
Pemodynamlc lnsLablllLy may lnLerrupL assessmenL
Cxygen supplemenLauon dlrecLly lnLo Lhe endoLracheal
Lube can cause pneumoLhorax
8raln deaLh cannoL be esLabllshed cllnlcally ln Lhe
semng of hypoLhermla, overdose or hypoLenslon
ConrmaLory Lesung (e.g. C1 anglogram, nuclear
perfuslon sLudy) ls requlred lf evaluauon ls
confounded
Cr|nca| Care aher 8ra|n Death
PypoLenslon ls common
Loss of sympaLheuc Lone
vasopressors, lnoLropes
ulabeLes lnslpldus
Cbserve for large volume hypoLonlc urlne ouLpuL
1reaL wlLh vasopressln
Cerebral salL wasung
volume, salL replacemenL
Adrenal lnsumclency
Pydrocorusone replacemenL
Donanon aher C|rcu|atory Death
lf Lhe neurologlc ln[ury ls caLasLrophlc and survlval aer
wlLhdrawal of llfe supporL ls expecLed Lo be very shorL
Conslder donauon aer clrculaLory deaLh (uCu)
?ou may be asked Lo go Lo operaung room Lo deLermlne
ume of deaLh aer dlsconunuauon of llfe supporL
measures
MusL be deLermlned by a non-LransplanL physlclan
Absence of clrculauon, resplrauon
Mechanlcal asysLole for 2-3 mln
1ransplanL Leam enLers lmmedlaLely aer deaLh
Warm lschemla ume ls ldeally less Lhan 43 mlnuLes
nematopo|enc Ce|| 1ransp|antanon (nC1)
rogenlLor cells from bone marrow, perlpheral blood
or umblllcal cord blood
A||ogene|c PC1 (mlsmaLched donor)
Cra-versus-Lumor and gra-versus-hosL eecLs
Auto|ogous PC1 (self)
no gra-versus-Lumor or gra-versus-hosL eecLs
1oxlc pre-LreaLmenL reglmens
1hrombocyLopenla, neuLropenla
Mucoslus, lung ln[ury
33 year o|d woman one week aher
a||ogene|c nC1
Abdomlnal paln and Lenderness
Hoeffel C et al. Radiographics
2006;26:1373-1390
Abdom|na| Comp||canons of nC1
ClosLrldlum dlmclle collus
neuLropenlc enLerocollus (Lyphllus)
necrouzlng cecal lnfecuon
Cecal Lhlckenlng on C1, posslbly lnLramural alr
Conservauve managemenL lf posslble
Cra versus hosL dlsease aer allogenelc progenlLor
cell engramenL (2-4 weeks)
8owel lnammauon
kesp|ratory fa||ure four weeks aher nC1
Franquet T et al. AJR 2005;184:629-637
kesp|ratory fa||ure four weeks aher nC1
Whlch one of Lhe followlng ls Lrue ln Lhls case?
A. Lmplrlc LreaLmenL for CMv pneumonlus ls lndlcaLed
8. Alveolar hemorrhage ls assoclaLed wlLh posluve AnCA
sLudles
C. She has ldlopaLhlc pneumonla syndrome
u. 8ronchoscopy ls recommended desplLe severe
LhrombocyLopenla (<20,000/uL)
L. She has pulmonary alveolar proLelnosls
kesp|ratory Ia||ure aher nC1
8acLerlal pneumonla
lungal pneumonla
Asperglllus, neumocysus
vlral pneumonla
CMv pneumonlus, nosocomlal 8Sv
Alveolar hemorrhage
rogresslvely bloody bronchoalveolar lavage samples, no vascullus
ldlopaLhlc pneumonla syndrome
ulagnosls of excluslon
8ronchoscopy wlLh bronchoalveolar lavage ls lndlcaLed
uesplLe severe LhrombocyLopenla (< 20,000 / uL)
CourLesy of ur l Ll-Abbassl
kesp|ratory Ia||ure aher A||ogene|c nC1
MorLallLy wlLh resplraLory fallure
ls hlghesL wlLh muluple organ fallures
0 of 398 PC1 pauenLs survlved wlLh hepauc + renal
fallure or shock
Cverall morLallLy ~ 90 aL one year
8euer lf durlng engramenL perlod
Worse lf laLe or acuLe gra-versus-hosL dlsease

8ubenfeld C, Ann lnLern Med 1996, 123:623
ene l, ! Clln Cncol 2006 leb 1,24:643-9
Morta||ty aher nC1
1reaLmenL relaLed morLallLy aL one year
10 for auLologous PC1
30 for allogenelc PC1
Cra-versus-hosL dlsease
Cngolng rlsk of opporLunlsuc lnfecuons
MosL pauenLs who survlve for 2 years aer allogenelc
PC1 are allve aL 10 years
Summary
otenna| 8oard 1argets:
lmmunosuppresslon and lnfecuon aer solld organ
LransplanLauon
Larly and laLe compllcauons of organ LransplanLauon
lndlcauons for organ LransplanLauon ln crlucal lllness
8raln deaLh assessmenL and donor managemenL
uonauon aer clrculaLory deaLh
Compllcauons of hemaLopoleuc sLem cell
LransplanLauon
Good Luck!