Sociedade Portuguesa de Cuidados Intensivos guidelines for stress ulcer prophylaxis in the intensive care unit

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. 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