Re B as Te In ensi a. 2019
Sociedade Po uguesa de Cuidados In ensi os
guidelines o s ess ulce p ophylaxis in he
in ensi e ca e uni
SPECIAL ARTICLE
INTRODUCTION
S ess ulce ‑ ela ed gas oin es inal bleeding is a po en ial complica ion o
c i ical illness, o which he pa hophysiology is complex. Sys emic hemodynamic
and local al e a ions esul in gas ic mucosal blood low impai men wi h
subsequen ischemic mucosal inju y. Howe e , he c ucial ac o o he
de elopmen o ulce a ion and gas ic bleeding is he high gas ic in aluminal
acidi y, which is po en ia ed by as ing.(1) This p o ides he a ionale o he use
o acid‑supp essi e d ugs o pha macological p ophylaxis.(2)
Endoscopically e iden uppe gas oin es inal lesions may be ound in up
o 90% o c i ically ill pa ien s wi hin 3 days o admission;(3) less han 50% o
pa ien s will ha e occul bleeding (de ined as guaiac‑posi i e gas ic aspi a e o
guaiac‑posi i e s ool) and app oxima ely 5%(4,5) will ha e o e bleeding (de ined
as hema emesis, bloody gas ic aspi a e, melena, o hema ochezia). Howe e ,
his does no necessa ily ansla e in o clinically signi ican gas oin es inal
bleeding (defined as o e bleeding in he p esence o hypo ension, achyca dia
o o hos asis, a d op in hemoglobin o > 2g/dL, o he need o su ge y),(6)
whose incidence seems o ha e dec eased o e he yea s. In s udies published
be o e 1999, he incidence o clinically signi ican gas oin es inal bleeding
was be ween 2% and 6% in pa ien s no ecei ing p ophylaxis.(6) Howe e ,
in s udies published since 2001, he incidence has been epo ed o ange
be ween 0.1% and 4% wi h o wi hou p ophylaxis,(7) which is ela ed o be e
João João Mendes1, Má io Jo ge Sil a2,
Luís Sil a Miguel3, Ma ia Albe ina Gonçal es1,
Ma ia João Oli ei a4, Ca a ina da Luz Oli ei a5,
João Gou eia1
1. Sociedade Po uguesa de Cuidados
In ensi os - Lisboa, Po ugal.
2. Gas oen e ology Depa men , Cen o
Hospi ala de Lisboa Cen al E.P.E. - Lisboa,
Po ugal.
3. Cen e o E idence Based Medicine,
Faculdade de Medicina, Uni e sidade de Lisboa -
Lisboa, Po ugal.
4. Pha macy Depa men , Hospi al P o . Dou o
Fe nando da Fonseca E.P.E. - Amado a, Po ugal.
5. Associação Po uguesa de Fa macêu icos
Hospi ala es - Lisboa, Po ugal.
C i ically ill pa ien s a e a isk
o de eloping s ess ulce s in he
uppe diges i e ac . Agen s ha
supp ess gas ic acid a e commonly
p esc ibed o educe he incidence o
clinically impo an s ess ulce ‑ ela ed
gas oin es inal bleeding. Howe e ,
he indisc imina e use o s ess ulce
p ophylaxis in all pa ien s admi ed o
he in ensi e ca e uni is no wa an ed
and can ha e po en ial ad e se clinical
Con lic s o in e es : None.
Submi ed on May 21, 2018
Accep ed on Sep embe 8, 2018
Co esponding au ho :
João João Mendes
Sociedade Po uguesa de Cuidados In ensi os
R. Rod igo da Fonseca 204, 1070-196
Lisboa
E-mail: [email p o ec ed]
Responsible edi o : Flá ia Ribei o Machado
Di e izes da Sociedade Po uguesa de Cuidados In ensi os pa a
p o ilaxia da úlce a de es esse na unidade de e apia in ensi a
ABSTRACT
Keywo ds: S ess, psychological;
Pep ic ulce ; P ophylaxis; In ensi e ca e
uni s
e ec s and cos implica ions. The p esen
guidelines om he Sociedade Po uguesa
de Cuidados In ensi os summa izes he
cu en e idence and gi es six clinical
s a emen s and an algo i hm aiming o
p o ide a s anda dized p esc ibing policy
o he use o s ess ulce p ophylaxis in
he in ensi e ca e uni .
DOI: 10.5935/0103-507X.20190002
This is an open access a icle unde he CC BY license h ps://c ea i ecommons.o g/licenses/by/4.0/).
Sociedade Po uguesa de Cuidados In ensi os guidelines o s ess ulce p ophylaxis in he in ensi e ca e uni 13
Re B as Te In ensi a. 2019
o e all c i ical ca e, including he inc eased use o ea ly
en e al eeding. This, along wi h conce ns ela ed o he
epo ed inc easing equency o in ec ious complica ions
(nosocomial pneumonia and Clos idium di icile
in ec ions),(8,9) has challenged he adi ional co ne s one
o pha macological p ophylaxis wi h agen s ha supp ess
gas ic acid o s ess ulce p ophylaxis.(10)
This guideline om he Sociedade Po uguesa de
Cuidados In ensi os aims o summa ize cu en e idence
and gi e clinical ecommenda ions o he use o s ess
ulce p ophylaxis in he in ensi e ca e uni (ICU) o
p o ide a s anda dized p esc ibing policy and a oid
injudicious use.
METHODOLOGY
A mul idisciplina y ask o ce was assembled. The ask
o ce comp ised physicians (specialis s in gas oen e ology
and in ensi e ca e medicine), nu ses, pha macis s and
economis s wi h special in e es and expe ise in s ess
ulce p ophylaxis and/o e idence‑based medicine. All
membe s o he ask o ce decla ed ha no con lic o
in e es in luenced he de elopmen o he guidelines.
Task o ce membe s pa icipa ed in a discussion ia
e‑mail, and six clinical ques ions we e buil o e idence
e alua ion. Each wo king membe ook cha ge o one
clinical ques ion and buil sea ch que ies in he PICO
(Pa icipan s, In e en ions, Compa isons, and Ou comes)
o ma .(11) The a ailabili y o a Coch ane e iew(12) ele an
o he clinical ques ions was con i med by sea ching he
Coch ane Da abase o Sys ema ic Re iews. A u he
complemen a y li e a u e sea ch o PubMed® was
pe o med. T ial da a iden i ied by he sea ch s a egies
we e conside ed o ep esen he bes ‑quali y e idence. The
G ading o Recommenda ions Assessmen , De elopmen ,
and E alua ion (GRADE) sys em p inciples(13) was used
o assess he quali y o e idence om high o e y low and
o de e mine he s eng h o ecommenda ions.
Finally, he ask o ce de e mined he di ec ion
( o o agains ) and s eng h (s ong o weak) o he
ecommenda ions using a wo‑ ound (sel ‑adminis e ed
ques ionnai e wi h no mee ings among he pa icipan s)
simple Delphi me hod.(14) This was done acco ding
o he GRADE sys em and conside ed he ollowing
ac o s: e idence quali y, ce ain y in he balance be ween
ad an ages and disad an ages, ce ain y o simila i y in
alues and p e e ences, and esou ce implica ions. A i ing
a a consensus equi ed an a e age le el o ag eemen o
≥ 80%. When he ag eemen le el was < 80%, u he
discussions and o ing we e conduc ed.
A s ong ecommenda ion was wo ded as “we
ecommend” and a weak ecommenda ion as “we sugges ”.
The key ecommenda ions we e p esen ed a he
annual symposium o he Sociedade Po uguesa de
Cuidados In ensi os in Opo o and discussed by he panel
and audience membe s.
STATEMENTS
S a emen 1
We ecommend main aining (o ini ia ing) agen s
ha supp ess gas ic acid (namely, p o on‑pump
inhibi o s) in pa ien s wi h compelling indica ions o
acid supp ession. S ong ecommenda ion, mode a e
quali y o e idence.
Ra ional
Se e al clinical si ua ions equi e gas ic acid
supp ession (namely, p o on‑pump inhibi o s), and
indica ions should be espec ed, bo h in he ambula o y
and hospi al (including in ensi e ca e) se ings.
Pa ien s wi h compelling indica ions include he
ollowing:
‑ Known pep ic ulce disease in he healing phase
and main enance phase in selec ed ci cums ances
[> 50 yea s old; mul iple como bidi ies; pe sis en
symp oms; NSAID‑nega i e and Helicobac e
pylo i‑nega i e ulce s; need o con inue NSAID
o ailu e o e adica e Helicobac e pylo i; ulce s
complica ed a he ou se ; and gian (> 2cm),
e ac o y o ecu en ulce s].(15)
‑ T ea men o Helicobac e pylo i in ec ion.(16)
‑ Zollinge ‑Ellison synd ome and o he
hype sec e o y condi ions.(17)
‑ Gas oesophageal e lux disease and acid‑ ela ed
complica ions (i.e., e osi e esophagi is o pep ic
s ic u e)(18) and Ba e ’s esophagus.(19)
‑ Eosinophilic esophagi is.(20)
‑ Dual an ipla ele he apy o concomi an
an icoagulan he apy.(21)
14 Mendes JJ, Sil a MJ, Miguel LS, Gonçal es MA, Oli ei a MJ, Oli ei a CL, e al.
Re B as Te In ensi a. 2019
O he app o ed indica ions (which should be discussed
on a case‑by‑case basis) include he ollowing:
‑ Unin es iga ed dyspepsia(22) and epigas ic pain
synd ome.(23)
App o ed indica ions may a y wi h speci ic acid
supp essan s, and he e o e labeling indica ions should be
conside ed.
S a emen 2
We ecommend p ophylaxis wi h agen s ha supp ess
gas ic acid a he han no p ophylaxis in pa ien s who
ha e one majo isk ac o o wo mino isk ac o s o
s ess ulce a ion.
complica ions. This me analysis has been c i icized, and a
numbe o la ge phase‑III ials compa ing pha macological
p ophylaxis and placebos a e unde way. Thei esul s and
subsequen upda ed me a‑analyses a e expec ed o p o ide
impo an , mo e ele an da a on he balance be ween he
bene i s and ha ms o s ess ulce p ophylaxis.(27)
Impo an ly, he incidence o s ess ulce ‑ ela ed
gas oin es inal bleeding is no equally sha ed ac oss he
spec um o pa ien s admi ed o in ensi e ca e, and
ce ain pa ien s appea mo e a isk o bleeding.
A la ge mul icen e p ospec i e coho s udy(4) iden i ied
coagulopa hy (de ined as a pla ele coun < 50,000/m3, an
in e na ional no malized a io g ea e han 1.5, o a pa ial
h omboplas in ime g ea e han 2 imes he con ol alue)
and espi a o y ailu e (de ined as he need o mechanical
en ila ion o a leas 48 hou s) as majo isk ac o s
o clinically signi ican gas oin es inal bleeding. The
obus ness o hese isk ac o s has been con i med in a
leas one addi ional small obse a ional s udy.(28)
Olde s udies ha e been c i icized because clinical
p ac ice has unde gone majo changes(10) in he las
20 yea s, which ha e educed he incidence o s ess
ulce ‑ ela ed gas oin es inal bleeding. Mo eo e , in line
wi h wha was p e iously desc ibed, a ecen explo a o y
andomized clinical ial(29) compa ing pha macologic
p ophylaxis (wi h p o on‑pump inhibi o s) and a
placebo in mechanically en ila ed c i ically ill pa ien s
an icipa ed o ecei e en e al nu i ion did no show any
bene i (o ha m) o acid supp ession. Because his was a
easibili y ial, no i m e idence could be in e ed, and
he inal conclusion was ha i is possible o adminis e
pha macologic p ophylaxis p omp ly a e commencing
mechanical en ila ion.
Pa ien s wi h auma ic b ain inju y (Glasgow
Coma Scale sco e ≤ 8), auma ic spinal co d inju y,
o bu n inju y (> 35% o he body su ace a ea) ha e
been ou inely excluded om hese s udies because o a
p esumed high‑ isk o s ess ulce ‑ ela ed gas oin es inal
bleeding mos likely media ed h ough neu ological
pa hways.(30) Ne e heless, small andomized con olled
ials(31‑33) wi h di e en acid supp ession egimens
ha e demons a ed signi ican p o ec ion om s ess
ulce ‑ ela ed gas oin es inal bleeding in hese high‑ isk
popula ions.
Majo isk ac o :
- Coagulopa hy (de ined as a pla ele coun < 50,000/m3, an In e na ional
No malized Ra io (INR) g ea e han 1.5, o a pa ial h omboplas in ime
g ea e han 2 imes he con ol alue).
- Respi a o y ailu e (de ined as he need o mechanical en ila ion o a leas
48 hou s).
- T auma ic b ain inju y (Glasgow Coma Scale sco e ≤8), auma ic spinal co d
inju y, o bu n inju y (>35% o he body su ace a ea).
- Sepsis (acu e change in o al Sequen ial O gan Failu e Assessmen - SOFA
sco e ≥ 2 poin s consequen o in ec ion).
Mino isk ac o s:
- Acu e o ch onic enal ailu e (needing in e mi en o con inuous enal
eplacemen he apy).
- Shock (de ined as con inuous in usion wi h asop esso s o ino opes, mean
a e ial blood p essu e below 70mmHg o plasma lac a e le el equal o o
g ea e han 4mmol/L).
- Ch onic hepa ic ailu e (de ined as ci hosis p o en by biopsy, his o y o
a iceal bleeding o hepa ic encephalopa hy).
- Glucoco icoid he apy (≥ 250mg hyd oco isone equi alen pe day).
- Mul iple auma wi h an inju y se e i y sco e ≥ 16.
S ong ecommenda ion, low quali y o e idence.
Ra ional
Me a‑analysis and sys ema ic e iews(6,24,25) ha e
consis en ly shown ha agen s ha supp ess gas ic acid
(namely, his amine‑2‑ ecep o an agonis s and/o p o on‑
pump inhibi o s) a e supe io o placebos in educing
he isk o clinically signi ican gas oin es inal bleeding.
Howe e , a ecen me a‑analysis(26) sugges ed ha
in pa ien s ecei ing en e al eeding, pha macologic
p ophylaxis o s ess ulce s is no bene icial, and combined
in e en ions may e en inc ease he isk o some in ec ious
Sociedade Po uguesa de Cuidados In ensi os guidelines o s ess ulce p ophylaxis in he in ensi e ca e uni 15
Re B as Te In ensi a. 2019
No s udy has been pe o med speci ically o sepsis;
howe e , s ess ulce p ophylaxis has been an in eg al
pa o he ca e o sep ic pa ien s and is ecommended
by cu en guidelines.(34) This makes sense ega ding he
new sepsis de ini ions(35) in which he in ec ion‑ ela ed
dys egula ed hos esponse has o be associa ed wi h a
se e e (li e‑ h ea ening) o gan dys unc ion (iden i ied as
an acu e change in o al SOFA sco e ≥ 2 poin s), and hus
includes mul iple isk ac o s.
The e idence suppo ing o he mino isk ac o s o
s ess ulce ‑ ela ed gas oin es inal bleeding is weak as
a esul o a high isk o sys ema ic and andom e o s.
Howe e , an inc easing numbe o isk ac o s is associa ed
wi h an inc eased isk o bleeding,(36) and in e na ional
guidelines ecommended s ess ulce p ophylaxis o
pa ien s wi h wo o mo e isk ac o s.(37) In he o iginal
desc ip ion o s ess‑ulce bleeding, hypo ension
(alongside sepsis and espi a o y ailu e) was associa ed
wi h s ess‑ ela ed mucosal damage.(38) A ecen incep ion
coho s udy iden i ied he p esence o h ee o mo e
como bidi ies (including glucoco icoid he apy),
p eexis ing li e disease, enal ailu e (wi h use o enal
eplacemen he apy), and coexis ing o acu e coagulopa hy
and highe SOFA‑sco e, as signi ican isk ac o s o
s ess‑ulce bleeding a e mul i a ia e analysis.(39) In
ano he la ge coho s udy,(40) acu e kidney inju y (assessed
by maximum se um c ea inine le el) was independen ly
associa ed wi h an inc eased isk o gas oin es inal
bleeding in pa ien s mechanically en ila ed o mo e han
48 hou s. Addi ionally, a small p ospec i e andomized
ial(33) demons a ed independen signi icance o he
inju y se e i y sco e.
S a emen 3
We ecommend he use o a p o on‑pump inhibi o
when p ophylaxis wi h agen s ha supp ess gas ic acid
is indica ed. S ong ecommenda ion, low quali y o
e idence.
Ra ional
The choice o he pha macological p ophylaxis agen
should ake in o accoun ac o s ela ed o e ec i eness,
ad e se e ec s and cos .
Suc al a e, a mucosa‑p o ec i e agen , alone has
adi ionally been conside ed in e io o his amine‑
2‑ ecep o an agonis s o s ess ulce p ophylaxis.(6,41)
While his has been challenged in a ecen me a‑analysis
o andomized con olled ials,(42) he esul s ha e been
c i icized because o signi ican he e ogenei y be ween
s udies, o which only h ee had clinically signi ican
gas oin es inal bleeding as a epo ed ou come.(43)
The e icacy o p o on‑pump inhibi o s and his amine‑
2‑ ecep o an agonis s in p e en ing s ess‑ulce bleeding
in c i ically ill pa ien s has been compa ed in se e al
andomized con ol ials and me a‑analyses.(25,44‑48) The
mos ecen and comple e me a‑analyses o andomized
con olled ials(25,44) consis en ly demons a ed ha
p o on‑pump inhibi o s we e mo e e ec i e han
his amine‑2‑ ecep o an agonis s a educing clinically
signi ican gas oin es inal bleeding, al hough his was no
accompanied by a educ ion in ICU mo ali y o leng h o
s ay. The obus ness o hese conclusions is limi ed by he
ial me hodologies, di e ences be ween lowe and highe
quali y ials, spa se da a and possible publica ion bias. An
ongoing clus e ‑ andomized c osso e ial [Aus alian and
New Zealand In ensi e Ca e Socie y Clinical T ials G oup
(ANZICS CTG): s udy numbe 1415‑01] is compa ing
p o on‑pump inhibi o s and his amine‑2‑ ecep o
an agonis s, and he esul s a e expec ed o p o ide mo e
ele an da a.(27)
The e a e mul iple pha macoeconomic analyses(49‑51)
ocused on he compa ison be ween his amine‑2‑
ecep o an agonis s and p o on pump inhibi o s o he
p ophylaxis o s ess ulce ela ed gas oin es inal bleeding.
The esul s a e con adic o y, mainly due o he use o
di e en clinical inpu s, and he e is no s ong e idence
ega ding which is he mos e ec i e al e na i e. Da a om
he mos ecen me a‑analysis o clinical ials indica e
ha p o on pump inhibi o s should be used. Howe e ,
i one elies on a p opensi y sco e‑ma ched obse a ional
coho s udy, his amine‑2‑ ecep o an agonis s a e he
p e e ed op ion.(51) The only clea conclusion is ha , as
he cos o p ophylaxis is small when compa ed o he
cos s o complica ions, he mos e ec i e al e na i e will
cons i u e a dominan al e na i e.(51)
Al hough he quali y o e idence is subop imal,
p o on‑pump inhibi o s ha e been he p e e ed egimen
16 Mendes JJ, Sil a MJ, Miguel LS, Gonçal es MA, Oli ei a MJ, Oli ei a CL, e al.
Re B as Te In ensi a. 2019
in in ensi e ca e uni s ac oss Eu ope, he Uni ed S a es
and Canada.(52,53) I is acknowledged ha he published
li e a u e on his issue de i es om he e ogeneous
popula ions o c i ically ill pa ien s who may di e
om he popula ions a isk iden i ied by he p e ious
ecommenda ion.
Addi ionally, he expec ed ad e se e ec s o p o on‑
pump inhibi o s a e a conce n and mus be aken in o
accoun . A coho s udy(54) p o ided e idence o an
inc ease in pneumonia wi h p o on‑pump inhibi o use;
howe e , his s udy was ela ed only o ca diac su ge y
pa ien s, and con idence in e als we e wide. Small
andomized ials (29,55) and a case–con ol s udy showed an
inc eased adjus ed isk o Clos idium di icile in ec ions
du ing ea men wi h p o on‑pump inhibi o s, bu his
was mo e ela ed o he du a ion o exposu e.(56)
Ul ima ely, he desi able consequences o s ess ulce
p ophylaxis wi h p o on‑pump inhibi o s a e expec ed
o ou weigh he undesi able consequences among he
popula ion a isk.
S a emen 4
We make no ecommenda ion ega ding speci ic
p o on‑pump inhibi o egimens.
Ra ional
The ideal d ug egimen should be e ec i e in educing
he isk o ulce a ion, wi h a low po en ial o ad e se
e ec s and d ug in e ac ions and pha macokine ic
cha ac e is ics ha acili a e i s use in pa ien s wi h o gan
dys unc ion; i should also be cos ‑e ec i e.
The e is no di ec compa ison be ween di e en
p o on‑pump inhibi o ‑based egimens (including d ug,
dosing, ou e o adminis a ion and galenic o mula ion),
and he e ogenei y ac oss s udies (compa ing p o on‑pump
inhibi o s o o he egimens) impai s he compa ison o
e ec s be ween he indi idual p o on‑pump inhibi o
egimens es ed o da e. An a p io i de ined subg oup
analysis o a leas one me a‑analysis sugges s ha he ou e
o adminis a ion (en e al e sus in a enous) and dosing
(once e sus wice a day) do no a ec he esul s.(43,45)
In ela ion o he ou e o adminis a ion, mul iple
ac o s (e.g., asop esso use, al e ed gas ic emp ying
and mo ili y, eeding ube and nu ien in e ac ions)
may in luence en e al abso p ion in c i ically ill pa ien s,
and he in a enous ou e is gene ally p e e ed.(57) This
is dispu ed by a s udy showing ha , despi e a lowe
bioa ailabili y, en e al lansop azole supp essed acid in
in ensi e ca e uni pa ien s be e han he in a enous
o mula ion.(58) Howe e , his has no been con i med
by u he s udies, and lansop azole equi es a complex
and labo ‑in ensi e galenic o mula ion o eeding ube
adminis a ion.
Due o i s sa e y in (a leas mode a e) o gan
dys unc ion, lowe p obabili y o d ug‑d ug in e ac ions,
and a ailable o mula ions, in a enous pan op azole
(40mg qd) may be a easonable choice.(59) Howe e , he
de ini i e choice o he speci ic p o on‑pump inhibi o
egimen should be based on indi idual pa ien and
medical alues, expe ience, p oduc labeling, cos ‑bene i
analyses, an icipa ed isks o d ug‑d ug in e ac ions and
ad e se e ec s.
S a emen 5
We sugges using his amine‑2‑ ecep o an agonis s in
pa ien s wi h Clos idium di icile in ec ion and indica ions
o s ess ulce p ophylaxis. Weak ecommenda ion, e y
low quali y o e idence.
Ra ional
Accumula ing e idence sugges s ha he use o agen s
ha supp ess gas ic acid may inc ease he equency
o in ec ious complica ions.(8,9,60) The mos ecen and
comp ehensi e me a‑analysis(61) ound ha he apy wi h
agen s ha supp ess gas ic acid was associa ed wi h a
signi ican isk o Clos idium di icile in ec ions bu ha
he isk was lowe o his amine‑2‑ ecep o an agonis s
han wi h p o on‑pump inhibi o s.
In he c i ically ill popula ion, he inc eased isk o
Clos idium di icile in ec ions is s ill con o e sial because
me a‑analysis is weak in de ec ing a modes inc ease in
hese e en s.(62) Ne e heless, he isk o Clos idium
di icile in ec ions emains highe in pa ien s ecei ing
p o on‑pump inhibi o s compa ed wi h pa ien s
ecei ing his amine‑2‑ ecep o an agonis s.(8) Mo eo e ,
obse a ional s udies(63,64) ha e shown ha con inued
p o on‑pump inhibi o use du ing inciden Clos idium
di icile in ec ions inc eases he isk o ecu ence.

Sociedade Po uguesa de Cuidados In ensi os guidelines o s ess ulce p ophylaxis in he in ensi e ca e uni 17
Re B as Te In ensi a. 2019
Based on a ailable da a and gi en he signi ican
disease bu den and mo ali y associa ed wi h Clos idium
di icile in ec ions, p o on‑pump inhibi o s should be
a oided, and his amine‑2‑ ecep o an agonis s should
be he p e e ed he apy when s ess ulce p ophylaxis is
indica ed.(62)
S a emen 6
We ecommend s opping p ophylaxis wi h agen s
ha supp ess gas ic acid when isk ac o s a e no longe
p esen and he pa ien is ecei ing en e al nu i ion.
S ong ecommenda ion, low quali y o e idence.
Ra ional
Acid supp essan s a e inapp op ia ely con inued
in a la ge p opo ion o pa ien s a e he esolu ion o
isk ac o s and e en a e in ensi e ca e uni o hospi al
discha ge, hus ex ending he po en ial isks and cos s
associa ed wi h s ess ulce p ophylaxis beyond he
in ensi e ca e uni .(65) This is in ag eemen wi h s udies
ha ha e concluded ha 88.5% o s ess ulce p ophylaxis
in nonin ensi e ca e uni pa ien s is inapp op ia e(66) and
ha a ela i ely es ic i e s ess ulce p ophylaxis p og am
no only educes inapp op ia e use wi hou inc easing he
a es o hospi al‑ ela ed gas oin es inal bleeding bu also
esul s in an es ima ed annualized cos sa ings o mo e
han US$ 200.000.(67)
As p e iously desc ibed,(26) he e is some e idence
o sugges ha in pa ien s ecei ing en e al eeding,
pha macologic s ess ulce p ophylaxis is no bene icial,
and combined in e en ions may e en inc ease he
isk o some in ec ious complica ions. Howe e , he
e idence is s ill insu icien o jus i y wi hholding s ess
ulce p ophylaxis om pa ien s who a e a high isk o
gas oin es inal bleeding. I is su icien ly compelling o
suppo he cessa ion o p ophylaxis when isk ac o s
a e no longe p esen and he pa ien is ecei ing en e al
nu i ion.
Pa ien s should hus be e alua ed daily du ing
mul idisciplina y ca e ounds o he con inued need
o p ophylaxis, and once he pa ien is ecei ing en e al
nu i ion and isk ac o s a e no longe p esen , s ess
ulce p ophylaxis should be discon inued. This s a egy
will educe he o e use and unnecessa y con inua ion o
agen s ha supp ess gas ic acid upon discha ge and in
he ou pa ien se ing.(68) As one o he mo e common
indica ions o s ess ulce p ophylaxis is mechanical
en ila ion, ex uba ion is c ucial o iden i y and possibly
discon inue acid supp ession he apy.(62)
Gene al algo i hm
The gene al algo i hm o he p ophylaxis o s ess ulce
bleeding in he in ensi e ca e uni is p esen ed in igu e 1.
Pa ien s wi h compelling indica ions o acid supp ession
should ha e an acid‑supp essi e egimen in acco dance
wi h he indica ion (S a emen 1). Then, he isk o
bleeding should be conside ed in each pa ien ; he use o
s ess ulce p ophylaxis is app op ia e o hose wi h high
isk. Pa ien s a low isk should no s a (o discon inue
i p e iously ini ia ed) s ess ulce p ophylaxis (S a emen
2). When a s ess ulce p ophylaxis is ecommended, he
use o a p o on‑pump inhibi o is indica ed (S a emen
3) wi h no speci ic ecommended egimen (S a emen 4).
The excep ion is cases o Clos idium di icile in ec ion,
o which his amine‑2‑ ecep o an agonis s a e p e e ed
(S a emen 5). Once he pa ien is ecei ing en e al
nu i ion and isk ac o s a e no longe p esen , s ess
ulce p ophylaxis should be discon inued (S a emen 6).
Table 1 compa es he di e en a ailable p o on‑pump
inhibi o ‑ and his amine‑2‑ ecep o an agonis ‑based
egimens.
The au ho s sugges ha he p ac ices ecommended in
his guideline a e con inuously e alua ed and moni o ed
and ha his guideline is upda ed as new e idence becomes
a ailable.
18 Mendes JJ, Sil a MJ, Miguel LS, Gonçal es MA, Oli ei a MJ, Oli ei a CL, e al.
Re B as Te In ensi a. 2019
Figu e 1 - Algo i hm o p ophylaxis o s ess ulce bleeding in he in ensi e ca e uni . * I Clos idium di icile in ec ion and indica ions o s ess ulce p ophylaxis a o his amine-
2- ecep o an agonis s. INR - In e na ional No malized Ra io; aPPT - ac i a ed pa ial h omboplas in ime; SOFA - Sequen ial O gan Failu e Assessmen .
Table 1 - Compa ison o he di e en a ailable p o on-pump inhibi o - and his amine-2- ecep o an agonis -based egimens
D ug Pha maceu ical
o mula ion Dosing Dosing and ou e o
adminis a ion Recons i u ion and adminis a ion Dose adjus men
Rele an
majo
pha macological
in e ac ions (g ade
1 - 2 impac )
Pan op azole Powde o injec ion
solu ion
40mg qd In a enous Recons i u e 40mg wi h 10cc o 0.9%
NaCl and adminis e o 2 minu es (i
necessa y dilu e in 100cc o 0.9% NaCl
o 5% dex ose in H2O)
Hepa ic ailu e
(mode a e o se e e)
Azoles*
Re e se p o ease
inhibi o s†
Gas o esis an able O al* –
Omep azole Powde o injec ion
solu ion
40mg qd In a enous Recons i u e 40mg wi h 5cc o 0.9%
NaCl and adminis e o 20 - 30 minu es
(i necessa y dilu e in 100cc o 0.9%
NaCl o 5% dex ose in H2O)
Hepa ic ailu e
(mode a e o se e e)
Azoles†
Re e se p o ease
inhibi o s†
Clopidog el‡
Gas o esis an
capsule
O al –
Endogas ic o
endojejunal eeding
ube
Open capsules, dispe se he con en in
40mL o non-ca bona ed wa e , shake
igo ously and allow o s and o 2
minu es (un il hick)
Con inue...
Sociedade Po uguesa de Cuidados In ensi os guidelines o s ess ulce p ophylaxis in he in ensi e ca e uni 19
Re B as Te In ensi a. 2019
* No da a on en e al adminis a ion; conside al e na i e d ugs; † conside al e na i e d ugs; ‡ conside subs i u ion by pan op azole. NaCl - sodium ch o ide.
D ug Pha maceu ical
o mula ion Dosing Dosing and ou e o
adminis a ion Recons i u ion and adminis a ion Dose adjus men
Rele an
majo
pha macological
in e ac ions (g ade
1 - 2 impac )
Lansop ozole Gas o esis an
capsule
30mg qd O al – Hepa ic ailu e
(mode a e o se e e)
Azoles†
Re e se p o ease
inhibi o s†
Endogas ic o
endojejunal eeding
ube
Open capsules and dispe se he con en
in 40mL o (o ange o apple) juice
O odispe sible able O al –
Endogas ic o
endojejunal eeding
ube
Dispe se in 10mL o non-ca bona ed
wa e
Esomep azole
40mg i. . qd
Powde o injec ion
solu ion
40mg qd In a enous Hepa ic ailu e
(mode a e o se e e)
Azoles†
Re e se p o ease
inhibi o s†
Clopidog el‡
Gas o esis an
capsule
O al –
Endogas ic o
endojejunal eeding
ube
Open capsules, dispe se he g anules in
40mL o non-ca bona ed wa e
Gas o esis an able O al –
Rani idine Powde o injec ion
solu ion
50mg id In a enous Recons i u e 50mg wi h 20cc o 0.9%
NaCl and adminis e o 5 minu es
Con inuous pe usion: a e a 50mg bolus
(see abo e), dilu e 150mg o 250cc
o 0.9% NaCl o 5% dex ose in H2O in
pe usion a 10.4cc/hou
Renal ailu e (clea ance
< 50mL/min/m2)
Azoles†
Coa ed able 150mg qd O al –
Endogas ic o
endojejunal eeding
ube
G ind able s and educe o powde ,
and dispe se he con en in 40mL o
non-ca bona ed wa e
... con inua ion
O pacien e c í ico co e isco de desen ol e úlce as de
es esse do a o gas in es inal. An iácidos e an iulce osos de
di e en es classes são equen emen e p esc i os pa a eduzi a
incidência de hemo agia gas in es inal clinicamen e signi ica‑
i a associada à úlce a de es esse. No en an o, o uso indisc imi‑
nado des e ipo de p o ilaxia em odos os pacien es admi idos a
unidades de e apia in ensi a não só não se jus i ica, como em
po enciais e ei os ad e sos e implicações de cus o. As p esen es
di e izes da Sociedade Po uguesa de Cuidados In ensi os e‑
sume a e idência a ual e o nece seis a i mações clínicas e um
algo i mo com o obje i o de o nece uma polí ica pad onizada
pa a p esc ição de p o ilaxia da úlce a es esse em unidades de
e apia in ensi a.
RESUMO
Desc i o es: Es esse psicológico; Úlce a pép ica; P o ilaxia;
Unidades de e apia in ensi a
20 Mendes JJ, Sil a MJ, Miguel LS, Gonçal es MA, Oli ei a MJ, Oli ei a CL, e al.
Re B as Te In ensi a. 2019
REFERENCES
1. Fenne y MB. Pa hophysiology o he uppe gas oin es inal ac in
he c i ically ill pa ien : a ionale o he he apeu ic bene i s o acid
supp ession. C i Ca e Med. 2002;30(6 Suppl):S351-5.
2. Cook D, Guya G. P ophylaxis agains Uppe Gas oin es inal Bleeding in
Hospi alized Pa ien s. N Engl J Med. 2018;378(26):2506-16.
3. Eddles on JM, Pea son RC, Holland J, Too h JA, Voh a A, Do an BH.
P ospec i e endoscopic s udy o s ess e osions and ulce s in c i ically
ill adul pa ien s ea ed wi h ei he suc al a e o placebo. C i Ca e Med.
1994;22(12):1949-54.
4. Cook DJ, Fulle HD, Guya GH, Ma shall JC, Leasa D, Hall R, e al. Risk
ac o s o gas oin es inal bleeding in c i ically ill pa ien s. Canadian
C i ical Ca e T ials G oup. N Engl J Med. 1994;330(6):377-81.
5. Goldin GF, Peu a DA. S ess- ela ed mucosal damage. Wha o do o no o
do. Gas oin es Endosc Clin N Am. 1996;6(3):505-26.
6. Cook DJ, Ree e BK, Guya GH, Heyland DK, G i i h LE, Buckingham L, e
al. S ess ulce p ophylaxis in c i ically ill pa ien s. Resol ing disco dan
me a-analyses. JAMA. 1996;275(4):308-14.
7. Faisy C, Gue o E, Diehl JL, I imo ici E, Fagon JY. Clinically signi ican
gas oin es inal bleeding in c i ically ill pa ien s wi h and wi hou s ess-
ulce p ophylaxis. In ensi e Ca e Med. 2003;29(8):1306-13.
8. MacLa en R, Reynolds PM, Allen RR. His amine-2 ecep o an agonis s
s p o on pump inhibi o s on gas oin es inal ac hemo hage and
in ec ious complica ions in he in ensi e ca e uni . JAMA In e n Med.
2014;174(4):564-74.
9. Moayyedi P, Leon iadis GI. The isks o PPI he apy. Na Re Gas oen e ol
Hepa ol. 2012;9(3):132-9.
10. Buendgens L, Tacke F. Do we s ill need pha macological s ess ulce
p ophylaxis a he ICU? J Tho ac Dis. 2017;9(11):4201-4.
11. Guya GH, Oxman AD, Kunz R, A kins D, B ozek J, Vis G, e al. GRADE
guidelines: 2. F aming he ques ion and deciding on impo an ou comes.
J Clin Epidemiol.
12. Toews I, Geo ge AT, Pe e JV, Ki ubaka an R, Fon es LE, Ezekiel JP,
e al. In e en ions o p e en ing uppe gas oin es inal bleeding in
people admi ed o in ensi e ca e uni s. Coch ane Da abase Sys Re .
2018;6:CD008687.
13. Guya GH, Oxman AD, Vis GE, Kunz R, Falck-Y e Y, Alonso-Coello P,
Schünemann HJ; GRADE Wo king G oup. GRADE: an eme ging consensus
on a ing quali y o e idence and s eng h o ecommenda ions. BMJ.
2008;336(7650):924-6.
14. Boulkedid R, Abdoul H, Lous au M, Sibony O, Albe i C. Using and epo ing
he Delphi me hod o selec ing heal hca e quali y indica o s: a sys ema ic
e iew. PLoS One. 2011;6(6):e20476.
15. S and DS, Kim D, Peu a DA. 25 yea s o p o on pump inhibi o s: a
comp ehensi e e iew. Gu Li e . 2017;11(1):27-37.
16. Chey WD, Leon iadis GI, Howden CW, Moss SF. ACG Clinical Guideline:
ea men o Helicobac e pylo i in ec ion. Am J Gas oen e ol.
2017;112(2):212-39. E a um in: Am J Gas oen e ol. 2018;113(7):1102.
17. Jensen RT, Cadio G, B andi ML, de He de WW, Kal sas G, Kommino h
P, Scoazec JY, Salaza R, Sau ane A, Kianmanesh R, Ba celona
Consensus Con e ence pa icipan s. ENETS Consensus Guidelines o
he managemen o pa ien s wi h diges i e neu oendoc ine neoplasms:
unc ional panc ea ic endoc ine umo synd omes. Neu oendoc inology.
2012;95(2):98-119.
18. Ka z PO, Ge son LB, Vela MF. Guidelines o he diagnosis and managemen
o gas oesophageal e lux disease. Am J Gas oen e ol. 2013;108(3):308-
28; quiz 329. E a um in Am J Gas oen e ol. 2013;108(10):1672.
19. Shaheen NJ, Falk GW, Iye PG, Ge son LB; Ame ican College o
Gas oen e ology. ACG Clinical Guideline: Diagnosis and Managemen o
Ba e ’s Esophagus. Am J Gas oen e ol. 2016;111(1):30-50; quiz 51.
E a um in: Am J Gas oen e ol. 2016;111(7):1077.
20. Lucendo AJ, Molina-In an e J, A ias Á, on A nim U, B edenoo d AJ,
Bussmann C, e al. Guidelines on eosinophilic esophagi is: e idence-based
s a emen s and ecommenda ions o diagnosis and managemen in
child en and adul s. Uni ed Eu opean Gas oen e ol J. 2017;5(3):335-58.
21. Bha DL, Scheiman J, Ab aham NS, An man EM, Chan FK, Fu be g CD,
Johnson DA, Maha ey KW, Quigley EM; Ame ican College o Ca diology
Founda ion Task Fo ce on Clinical Expe Consensus Documen s.
ACCF/ACG/AHA 2008 expe consensus documen on educing he
gas oin es inal isks o an ipla ele he apy and NSAID use: a epo o he
Ame ican College o Ca diology Founda ion Task Fo ce on Clinical Expe
Consensus Documen s. Ci cula ion. 2008;118(18):1894-909. E a um in:
Ci cula ion. 2010;122(8):e438.
22. Talley NJ, Vakil N; P ac ice Pa ame e s Commi ee o he Ame ican College
o Gas oen e ology. Guidelines o he managemen o dyspepsia. Am J
Gas oen e ol. 2005;100(10):2324-37.
23. S anghellini V, Chan FK, Hasle WL, Malagelada JR, Suzuki H, Tack J, e al.
Gas oduodenal diso de s. Gas oen e ology. 2016;150(6):1380-92.
24. Ma ik PE, Vasu T, Hi ani A, Pachinbu a an M. S ess ulce p ophylaxis in
he new millennium: a sys ema ic e iew and me a-analysis. C i Ca e
Med. 2010;38(11):2222-8.
25. Alhazzani W, Alshamsi F, Belley-Co e E, Heels-Ansdell D, B igna dello-
Pe e sen R, Alqu aini M, e al. E icacy and sa e y o s ess ulce
p ophylaxis in c i ically ill pa ien s: a ne wo k me a-analysis o andomized
ials. In ensi e Ca e Med. 2018;44(1):1-11. E a um in: In ensi e Ca e
Med. 2017 Dec 11.
26. Huang HB, Jiang W, Wang CY, Qin HY, Du B. S ess ulce p ophylaxis in
in ensi e ca e uni pa ien s ecei ing en e al nu i ion: a sys ema ic e iew
and me a-analysis. C i Ca e. 2018;22(1):20.
27. Ma ke S, K ag M, Molle MH. Wha ’s new wi h s ess ulce p ophylaxis in
he ICU? In ensi e Ca e Med. 2017;43(8):1132-4.
28. Schus e DP, Rowley H, Feins ein S, McGue MK, Zucke man GR. P ospec i e
e alua ion o he isk o uppe gas oin es inal bleeding a e admission o a
medical in ensi e ca e uni . Am J Med. 1984;76(4):623-30.
29. Sel ande an SP, Summe s MJ, Finnis ME, Plumme MP, Ali Abdelhamid Y,
Ande son MB, e al. Pan op azole o placebo o s ess ulce p ophylaxis
(POP-UP): andomized double-blind explo a o y s udy. C i Ca e Med.
2016;44(10):1842-50.
30. Schi me CM, Ko nblu h J, Heilman CB, Bha dwaj A. Gas oin es inal
p ophylaxis in neu oc i ical ca e. Neu oc i Ca e. 2012;16(1):184-93.
31. Bu gess P, La son GM, Da idson P, B own J, Me z CA. E ec o ani idine
on in agas ic pH and s ess- ela ed uppe gas oin es inal bleeding in
pa ien s wi h se e e head inju y. Dig Dis Sci. 1995;40(3):645-50.
32. Me z CA, Li ings on DH, Smi h JS, La son GM, Wilson TH. Impac o
mul iple isk ac o s and ani idine p ophylaxis on he de elopmen o
s ess- ela ed uppe gas oin es inal bleeding: a p ospec i e, mul icen e ,
double-blind, andomized ial. The Rani idine Head Inju y S udy G oup. C i
Ca e Med. 1993;21(12):1844-9.
33. Fabian TC, Bouche BA, C oce MA, Kuhl DA, Janning SW, Co ey BC,
e al. Pneumonia and s ess ulce a ion in se e ely inju ed pa ien s. A
p ospec i e e alua ion o he e ec s o s ess ulce p ophylaxis. A ch
Su g. 1993;128(2):185-91; discussion 191-2.
34. Rhodes A, E ans LE, Alhazzani W, Le y MM, An onelli M, Fe e R, e al.
Su i ing Sepsis Campaign: In e na ional Guidelines o Managemen o
Sepsis and Sep ic Shock: 2016. C i Ca e Med. 2017;45(3):486-552.
35. Singe M, Deu schman CS, Seymou CW, Shanka -Ha i M, Annane D,
Baue M, e al. The Thi d In e na ional Consensus De ini ions o Sepsis
and Sep ic Shock (Sepsis-3). JAMA. 2016;315(8):801-10.
36. Has ings PR, Skillman JJ, Bushnell LS, Silen W. An acid i a ion in he
p e en ion o acu e gas oin es inal bleeding: a con olled, andomized
ial in 100 c i ically ill pa ien s. N Engl J Med. 1978;298(19):1041-5.