Economic impact of improving patient safety using Sugammadex for routine reversal of neuromuscular blockade in Spain

RESEARCH ARTICLE Open Access Economic impac o imp o ing pa ien sa e y using Sugammadex o ou ine e e sal o neu omuscula blockade in Spain J. Ma inez-Ubie o 1 , C. A agón- Benedí 2 , J. de Ped o 3 , L. Cea-Cal o 3 , A. Mo ell 4 , Y. Jiang 5 , S. Cedillo 6 , P. Ramí ez-Boix 3* and A. M. Pascual-Bellos a 1 Abs ac Backg ound: Neu omuscula blocking (NMB) agen s a e o en adminis e ed o acili a e acheal in uba ion and p e en pa ien mo emen du ing su gical p ocedu es equi ing he use o gene al anes he ics. Incomple e e e sal o NMB, can lead o esidual NMB, which can inc ease he isk o pos -ope a i e pulmona y complica ions. Sugammadex is indica ed o e e se neu omuscula blockade induced by ocu onium o ecu onium in adul s. The aim o his s udy is o es ima e he clinical and economic impac o in oducing sugammadex o ou ine e e sal o neu omuscula blockade (NMB) wi h ocu onium in Spain. Me hods: A decision analy ic model was cons uc ed e lec ing a se o p ocedu es using ocu onium ha esul ed in mode a e o deep NMB a he end o he p ocedu e. Two scena ios we e conside ed o 537,931 p ocedu es using NMB agen s in Spain in 2015: a scena io wi hou sugammadex e sus a scena io wi h sugammadex. Compa a o s included neos igmine (plus glycopy ola e) and no e e sal agen . The o al cos s o he heal hca e sys em we e es ima ed om he ne o cos s o e e sal agen s and o e all cos o se s ia educ ion in pos ope a i e pneumonias and a elec asis o which incidence a es we e based on a Spanish eal-wo ld e idence (RWE) s udy. The model ime ho izon was assumed o be one yea . Cos s we e exp essed in 2019 eu os (€) and es ima ed om he pe spec i e o a heal hca e sys em. One-way sensi i i y analysis was ca ied ou by a ying each pa ame e included in he model wi hin a ange o +/−50%. Resul s: The es ima ed budge impac o he in oduc ion o sugammadex o he ou ine e e sal o neu omuscula blockade in Spanish hospi als was a ne sa ing o €57.1 million annually. An inc ease in d ug acquisi ion cos s was o se by sa ings in pos -ope a i e pulmona y e en s, including 4806 pos -ope a i e pneumonias and 13,996 cases o a elec asis. The o al cos o complica ions a oided was €70.4 million. All pa ame e s included in he model we e es ed in sensi i i y analysis and we e a o able o he scena io wi h sugammadex. (Con inued on nex page) © The Au ho (s). 2021 Open Access This a icle is licensed unde a C ea i e Commons A ibu ion 4.0 In e na ional License, which pe mi s use, sha ing, adap a ion, dis ibu ion and ep oduc ion in any medium o o ma , as long as you gi e app op ia e c edi o he o iginal au ho (s) and he sou ce, p o ide a link o he C ea i e Commons licence, and indica e i changes we e made. The images o o he hi d pa y ma e ial in his a icle a e included in he a icle's C ea i e Commons licence, unless indica ed o he wise in a c edi line o he ma e ial. I ma e ial is no included in he a icle's C ea i e Commons licence and you in ended use is no pe mi ed by s a u o y egula ion o exceeds he pe mi ed use, you will need o ob ain pe mission di ec ly om he copy igh holde . To iew a copy o his licence, isi h p://c ea i ecommons.o g/licenses/by/4.0/. The C ea i e Commons Public Domain Dedica ion wai e (h p://c ea i ecommons.o g/publicdomain/ze o/1.0/) applies o he da a made a ailable in his a icle, unless o he wise s a ed in a c edi line o he da a. * Co espondence: [email p o ec ed] 3 MSD, Mad id, Spain Full lis o au ho in o ma ion is a ailable a he end o he a icle Ma inez-Ubie o e al. BMC Anes hesiology (2021) 21:55 h ps://doi.o g/10.1186/s12871-021-01248-2 (Con inued om p e ious page) Conclusions: This economic analysis shows ha sugammadex can po en ially lead o cos sa ings o he e e sal o ocu onium-induced mode a e o p o ound NMB compa ed o no e e sal and e e sal wi h neos igmine in he Spanish heal h ca e se ing. The economic model was based on da a ob ained om Spain and om assump ions om clinical p ac ice and may no be alid o o he coun ies. Keywo ds: Neu omuscula blocking agen s, Sugammadex, Economic impac , Spain, Sa e y, Su gical p ocedu es, Re e sal agen s Backg ound Neu omuscula blocking (NMB) agen s a e adminis e ed ou inely du ing su gical p ocedu es o p o ide muscle elaxa ion, acili a e he inse ion o an endo acheal ube, and p e en pa ien mo emen du ing su gical p o- cedu es equi ing use o gene al anes he ics [1]. When neu omuscula blockade is no longe needed o be main ained, pa ien s may ei he be allowed o spon- aneously eco e neu omuscula unc ion o be admin- is e ed a pha macological e e sal agen o mo e apid eco e y. Spon aneous e e sal is nei he apid no o p edic able du a ion, so equen ly, pa ien s may be in- ad e en ly ex uba ed while s ill expe iencing esidual neu omuscula blockage [2]. The ace ylcholines e ase inhibi o neos igmine is com- monly used o e e sal o mode a e neu omuscula blockade when a leas he second wi ch (T2) o a ain- o - ou (ToF) s imula ion is p esen . Reco e y o neu o- muscula unc ion using neos igmine is also no apid and i s du a ion may no be p edic able [3] which can lead o an ex uba ion o pa ien s while hey a e s ill ex- pe iencing esidual neu omuscula blockage, and, in consequence, he isk o pos -ope a i e pulmona y com- plica ions including hypoxemia, di icul y b ea hing and swallowing, uppe ai way p oblems, hype capnia, slu ed speech, blu ed ision and impai ed clinical eco e y a e su ge y [2–10]. This inc ease in pos ope a i e mo bidi y can lead o inc eased leng h o s ay in he pos -anes he ic eco e y uni s (PACU), an inc eased hospi al leng h o s ay, and, an inc ease in he needs and cos s o heal h se ices [4, 11,12]. In he pas yea s, new pha macological al e na i es o e e sal o neu omuscula blockade ha e been in o- duced. Sugammadex (B idion®, Me ck & Co., Inc., Kenil- wo h, NJ, USA) a modi ied gamma-cyclodex in, is a e e sal agen a ailable in Spain since 2009 and indi- ca ed o e e se neu omuscula blockade induced by he NMB agen s ocu onium o ecu onium in adul s [13]. In clinical ials, sugammadex has been shown o p o- duce much mo e apid and p edic able e e sal o neu omuscula block compa ed o neos igmine, in he absence o an i-musca inic side e ec s and, in ials whe e quan i a i e neu omuscula moni o ing was no equi ed, a s eep educ ion in he incidence o esidual NMB [11,14–17]. In ecen yea s, he numbe o na ional and in e - na ional s udies ha highligh he inc ease in complica- ions associa ed wi h esidual NMB has inc eased. The equency o esidual NMB anges be ween 24 and 32% acco ding o he mos ecen se ies, al hough i has been gene ally es ima ed be ween 6 and 80% depending on he scope o he e alua ion, placing i as he main com- plica ion in pa ien s unde going gene al anes hesia [5, 12,18–24]. The RECITE-US s udy es ima ed he bu den and asso- cia ed isk ac o s o esidual NMB du ing ou ine U.S. hospi al ca e. The esul s o his p ospec i e s udy showed ha 64.7% o he pa ien s had esidual NMB (TOF a io < 0.9%) despi e neos igmine adminis a ion [25]. A na ional le el, he e a e se e al obse a ional s ud- ies ha e alua e he incidence o esidual NMB in Spain [26,27]. A p ospec i e mul icen e s udy conduc ed in 26 Spanish hospi als ound ha 26,7% o a gene al su gi- cal popula ion in Spain showed esidual NMB in he Pos anes hesia Ca e Uni (PACU). Pa ien - ela ed and p ocedu e- ela ed ac o s such as emale gende , longe du a ion o su ge y, use o benzyl-isoquinolines o halo- gena ed anes hesic use, lack o in aope a i e neu omus- cula moni o ing, and use o neos igmine as e e sal agen o no pha macological e e sal we e mo e p e a- len in pa ien s showing esidual NMB in he immedia e pos ope a i e pe iod [26]. Ma inez-Ubie o e al. con- duc ed a p ospec i e obse a ional s udy o coho s o e alua e he incidence o Pos ope a i e Residual Cu a i- za ion (PORC) in he PACU and i is ela ion o he ype o muscle elaxan and e e sal agen used in 558 pa- ien s ope a ed unde gene al anes hesia. In his s udy, he incidence o esidual NMB was much lowe when he NMB and e e sal agen adminis e ed we e ocu o- nium/sugammadex (1.15%) han when i was cisa acu - ium/neos igmine (28.6%) o when no e e sal agen was used (34%) [27]. Cu en ly, e e sal o NMB con inues o be a sa e y issue, and so a , he s udies ela ed o e e sal o NMB a a na ional le el in Spain ha e ocused on pa hophysio- logical, clinical and epidemiological aspec s. The aim o Ma inez-Ubie o e al. BMC Anes hesiology (2021) 21:55 Page 2 o 10 his analysis is o es ima e he economic impac o in o- ducing sugammadex o ou ine e e sal o ocu onium- induced neu omuscula blockade in Spain. Me hods Model o e iew Me hodologically, a budge impac analysis makes i pos- sible o e alua e an icipa ed expendi u es o heal hca e sys ems planning o adop new in e en ions o in o- duce changes o he cu en clinical p ac ice [28]. We de eloped a budge impac model ha p ojec ed he ag- g ega ed annual ne economic impac o using sugam- madex ins ead o neos igmine o no e e sal agen in a p opo ion o p ocedu es we e ocu onium is adminis- e ed. The model was cons uc ed in Mic oso ® Excel® 2016 (Mic oso Co p., Redmond, WA, USA). We collec ed da a om in e na ional li e a u e and om o icial Spanish heal hca e da abases. Whe e he a ailable in o ma ion was insu icien , o da a om Spanish sou ces we e conside ed inaccu a e, es ima ions we e p o ided by an expe panel o Spanish esea che s. The budge impac analysis has been de eloped in ac- co dance wi h he P inciples o Good P ac ice o Budge Impac Analysis o he In e na ional Socie y o Pha ma- coeconomics and Ou comes Resea ch (ISPOR) [28]. Model desc ip ion This budge impac is based on a compa ison be ween wo hypo he ical scena ios: –The cu en scena io: which ep esen s a si ua ion whe e sugammadex is no a ailable o ou ine e e sal o NMB –The al e na i e scena io: whe e sugammadex is included as a e e sal agen in su gical p ocedu es wi h mode a e and deep NMB. Time ho izon The budge impac model p ojec ed he economic im- pac o he in oduc ion o sugammadex in Spain o e a one-yea ime ho izon. Pe spec i e The pe spec i e used in his analysis is he Spanish Na- ional Heal hca e Sys em which only conside di ec cos s. Pha macological cos o ocu onium and he e- e sal agen s (neos igmine/a opine and sugammadex) and di ec cos s o he clinical ou comes we e included in he model. P ocedu es Fi een ypes o su gical p ocedu es in which using NMB agen s is mo e equen we e included in he model: ap- pendec omies, he nia epai s, cholecys ec omies, colo ec al esec ions, gas ic su ge ies, in ac anial su - ge ies, spinal co d su ge ies, emu su ge ies, hip ac- u e epai s, knee ac u e epai s, b onchoscopies o la yngoscopies, ocal co d su ge ies, hy oid gland su - ge ies, p os a ec omies, hys e ec omies and oopho ec o- mies. Local da a om nea ly 93% o Spanish public and p i a e hospi als es ima ed ha he annual numbe o hese p ocedu es in 2015 was 733,876 [29] (Table 1). Ac- co ding o Olesnicky e al. [30] coho s udy, 73.3% o su gical p ocedu es would use a NMB agen du ing he su gical p ocedu e. The model di e en ia ed be ween mode a e NMB (in ou analysis de ined as TOF: 1 o 2 wi ches) and deep NMB (de ined as TOF = 0 and pos - e anic coun o 1 o 2). We assumed a spli o 80% p ocedu es wi h mode a e NMB and 20% p ocedu es wi h deep NMB. As he e was no li e a u e a ailable om Spain, his assump ion was made based on in e nal ma ke esea ch da a, ha was alida ed by expe s acco ding o hei hospi al clin- ical p ac ice. (Fig. 1). Re e sal agen s Rocu onium and cisa acu ium a e he neu omuscula blocking agen s included in he model, as ecu onium is no a ailable in ou coun y, ep esen ing mo e han 90% o he ma ke . Howe e , sugammadex is no indi- ca ed o e e se cisa acu ium-induced NMB [13]. The e o e, he model conside ed a p opo ion o in- s ances o cisa acu ium use which can be swi ched o ocu onium, pe mi ing he in oduc ion o sugamma- dex. I was assumed ha 50% o ins ances in which Table 1 Numbe o su gical p ocedu es ca ied ou in Spain (2015) Type o Numbe o su gical p ocedu es Appendec omies 44,593 He nia Repai s 70,618 Cholecys ec omies 72,483 Colo ec al esec ions 82,435 Gas ic su ge ies 123,401 In ac aneal su ge ies 20,411 Spinal co d su ge ies 49,069 Femu su ge ies 21,415 Hip ac u e epai s 42,120 Knee ac u e epai s 52,493 B onchoscopies/La yngoscopies 21,599 Vocal co d su ge ies 25,673 Thy oid gland su ge ies 21,945 P os ac e omies 31,332 His e ec omies and oopho ec omies 54,289 To al anual numbe 733,876 Ma inez-Ubie o e al. BMC Anes hesiology (2021) 21:55 Page 3 o 10 cisa acu ium was used we e swi ched o ocu onium in he al e na i e scena io using sugammadex as e e sal agen . Acco ding o he p ospec i e obse a ional s udy by Ma inez-Ubie o e al. [27], ocu onium was adminis- e ed in 64% o hose p ocedu es (Table 2). Due o lack o local da a di e en ia ing be ween mode a e and deep NMB, i was assumed he same agen dis ibu ion o bo h. In he cases whe e neos igmine was conside ed o e e sal i would be co-adminis e ed wi h he an i- musca inic agen a opine, so he model e lec ed he co-adminis a ion o hese wo agen s. Clinical pa ame e s The use o sugammadex and neos igmine has been associ- a ed wi h a isk educ ion o wo pulmona y complica ions (a elec asis and pos -ope a i e pneumonias). Acco ding o he da a a ailable when he analysis was pe o med, bo h complica ions we e conside ed as pos -ope a i e e en s o in e es o he p esen analysis [27,31]. In he case o he isk o pos -ope a i e pneumonia, he da a combined wo sou ces o in o ma ion: he Spanish obse a ional s udies [27,31] and a clinical ial [25].Thesame isko pos - ope a i e complica ions was assumed o bo h o mode a e and deep NMB; his poin was alida ed by he expe panel. P opo ion o isk o pos -ope a i e e en s wi h sugammadex o neos igmine/no e e sal a e p esen ed in Table 2. Cos s Lis p ices o NMB and e e sal agen s we e ob ained om Bo plus (2019) [32]. A 7.5% discoun was applied o d ug cos s acco ding o Spanish law [33]. D ug cos s o speci ic combina ions o NMB agen s, e e sal agen s and block dep hs a e summa ized in Table 2.To s anda dize he cos pe dose pe pa ien be ween di e - en NMB and e e sal agen s, an a e age pa ien weigh o 75 kg was assumed. The dose o sugammadex used o NMB e e sal was 4 mg/kg o deep NMB and 2 mg/ kg o mode a e NMB acco ding o he phase III clinical Fig. 1 Model s uc u e Table 2 Model clinical pa ame e s alues: base case Pa ame e Value Annual numbe o hospi al su gical p ocedu es 733,876 P ocedu es u ilizing an NMBA 73.3% Type o block Mode a e: 80% Deep: 20% Re e sal agen use (neos igmine) No e e sal agen : Re e sal agen : No e e sal agen : Re e sal agen : 68.0% 32.0% 68.0% 32.0% Ins ances wi h use o ocu onium 64.0% 43.5% 64.0% 43.5% Ins ances wi h use o cisa acu ium 25.0% 25.0% 25.0% 25.0% Ins ances wi h use o o he agen s 11.0% 31.5% 11.0% 31.5% P opo ion o ins ances whe e cisa acu ium swi ched o ocu onium 50.0% 50.0% 50.0% 50.0% Neos igmine / No e e sal agen Sugammadex Risk o pos -ope a i e a elec asis 7.3% 1.1% Risk o pos -ope a i e pneumonia 4.0% 1.9% Ma inez-Ubie o e al. BMC Anes hesiology (2021) 21:55 Page 4 o 10 ials desc ibed in he sugammadex label [13]. Vial was - age o any unused amoun was no conside ed. Cos s o pos -ope a i e a elec asis we e de i ed om he cos pe diagnosis- ela ed g oup (DRG) p o ided by he Spanish Minis y o Heal h o icial s a is ical si e [29]. In he case o pos -ope a i e pneumonia, he cos pe e en was e ie ed om egional a i s ex ac ed om eSalud da abase [34] (Table 3). Cos o pos - ope a i e complica ions we e in la ed o €2019. Follow- ing he In e na ional Socie y o Pha macoeconomics and Ou comes Resea ch (ISPOR) P inciples o Good P ac ice o budge impac analysis cos s we e no dis- coun ed due o he sho ime ho izon used. Cos o se s ob ained om educing pos -ope a i e pul- mona y e en s wi h sugammadex compa ed wi h neos ig- mine o no pha macological e e sal we e calcula ed by mul iplying he expec ed numbe o e en s (wi h/wi hou sugammadex) by he cos o each e en and calcula ing he di e ence be ween he wo scena ios (Fig. 2). Sensi i i y analysis De e minis ic sensi i i y analysis (DSA) was ca ied ou by a ying he ollowing pa ame e s included in he model wi hin a ange o +/−50%: p opo ion o p oce- du es using an NMB agen , isk o pos -ope a i e e en s, cos pe e en , p opo ion o cases when sugammadex is used in mode a e block and p opo ion o ins ances whe e cisa acu ium is swi ched o ocu onium, p opo - ion o ins ances ocu onium is used gi en each e e sal agen . Model ou pu s The esul s o he analysis a e p esen ed in wo le els: 1) a p ocedu e le el: budge impac o u ilizing sugammadex o a speci ic pa ien e sus neos igmine o non-pha macological e e sal o a single ope a ing oom p ocedu e 2) a na ional le el: agg ega e budge impac o using sugammadex e sus neos igmine o no pha macological e e sal o all p ocedu es o whom sugammadex could be used a na ional le el. Resul s A p ocedu e le el, he in oduc ion o sugammadex is p ojec ed o esul in o a ne sa ing o €249.82 pe p o- cedu e whe e his agen could be used (31.2% o he o al numbe o p ocedu es included). Conside ing he o al annual numbe o hospi al su gical p ocedu es, e- ga dless o sugammadex usage, he a e age ne sa ing pe p ocedu e p ojec ed was €73.88 (Table 4). A na ional le el, om he o al o 733,876 a ge p o- cedu es conside ed, sugammadex was used in 228,863 o hem (147,542 wi h ocu onium and no e e sal, and 81,321 ocu onium and neos igmine in he p io sce- na io). The es ima ed budge impac o he ou ine in oduc ion o sugammadex in Spanish hospi als was p ojec ed o a ne sa ing o €57.1 million annually (Table 5). An inc ease in d ug acquisi ion cos s was o - se by sa ings in pos -ope a i e pulmona y e en s in- cluding 4806 pos -ope a i e pneumonias ( educ ion o 52% compa ed o p io scena io) and 13,996 cases o Table 3 Model economic pa ame e s: base case Pha macological cos s Agen Dose D ug Cos Sou ce Sugammadex (mode a e block) a 2mg €51.34 Bo Plus Sugammadex (deep block) a 4mg €102.68 Bo Plus Neos igmine/A opine 0.5 mg/2 mg €0.46 Bo Plus Rocu onium 0.6 mg €1.80 Bo Plus Pos -ope a i e e en Cos Sou ce A elec asis €4999.40 DRG cos . MoH Pneumonia €4449.72 eSalud. Oblikue a An a e age pa ien weigh o 75 kg was assumed in es ima ing he cos pe dose, wi h ial was age o any unused amoun Fig. 2 Modeling o clinical cos o se s associa ed wi h sugammadex Use Ma inez-Ubie o e al. BMC Anes hesiology (2021) 21:55 Page 5 o 10 a elec asis ( educ ion o 84% compa ed o p io sce- na io). The o al cos o complica ions a oided was p o- jec ed o €70.4 million) (Table 6). Sensi i i y analysis All scena ios es ed in he de e minis ic sensi i i y ana- lysis we e a o able o he scena io whe e sugammadex was used (Fig. 3) esul ing in cos -sa ing s a egies. Ac- co ding o he sensi i i y analysis, he p opo ion o p o- cedu es using a NMB agen and he isk o pos - ope a i e a elec asis o pneumonia we e he pa ame e s wi h he g ea es impac on he esul s o he economic model. Discussion Se e al s udies showed ha sugammadex can educe he isk o esidual NMB, enhancing ope a ing oom e i- ciency [26,27]; howe e , ew s udies ha e assessed he economic impac o he imp o emen o sa e y ou comes ela ed o he use o sugammadex. In ou knowledge, his is he i s s udy o es ima e he economic impac o sugammadex based on Spanish eal-wo ld da a. The e is s ill a signi ican incidence o esidual NMB in he immedia e pos ope a i e pe iod. As i was p e i- ously men ioned, di e en s udies desc ibed no pha ma- cological e e sal, o e e sal wi h neos igmine as a p ocedu e- ela ed ac o mo e p e alen in pa ien s wi h pulmona y complica ions in PACU [26,27]. Fu he - mo e, an inc ease numbe o a elec asis and pneumo- nias was ound in pa ien s who p esen ed esidual NMB in he immedia e pos ope a i e pe iod and we e e e sed wi h neos igmine o spon aneously [22,23, 35]. Also, he la es s udy o Capellini e al. [36]e al- ua ed h ough ul asound scan he con ac ion and diaph agma ic mo emen o pa ien s e e sed wi h neos igmine e sus pa ien s wi h sugammadex. This s udy concluded ha in pa ien s e e sed wi h neo- s igmine, comple e eco e y o basal diaph agm unc- ion is poo e compa ed o pa ien s e e sed wi h sugammadex. This e idence s ays in line wi h o he s udies whe e he incidence o pos ope a i e esidual neu omuscula blockade was assessed by TOF and whe e he incidence o a elec asis was highe (7.61%) when e e sed wi h neos igmine compa ed o pa ien s who we e adminis- e ed sugammadex (1.15%) [27,31]. The e o e, i is c ucial o unde s and he impo ance o ou ine use o e e sal agen s o a oid he occu ence o complica ions associa ed wi h he neu omuscula blocking d ugs esul ing in a cos -e ec i e s a egy [37–39]. In 2010, wo economic analyses assessed he e i- ciency o e e sal agen s. The s udy ca ied ou by Mandim el al [40] showed ha he cos pe minu e o he e e sal wi h sugammadex ($8.34) was lowe compa ed o neos igmine ($104.86). On he o he hand, in he UK, Pa on e al. [41] conduc ed a sys- ema ic e iew o andomized con olled ials o sugammadex compa ed wi h neos igmine and an eco- nomic assessmen o sugammadex o he e e sal o mode a e o deep NMB was pe o med. The s udy concluded ha he educ ion in eco e y ime associ- a ed wi h sugammadex e sus neos igmine was 23.37 Table 4 P ocedu e-le el ne budge impac Block Dep h A Re e sal P io NMBA & Re e sal Agen P io Scena io D ug Cos s Al e na i e Scena io (incl. sugammadex) D ug Cos s To al Cos O se s F om Clinical E en s A oided Ne Cos Sa ings Mode a e Rocu onium + No e e sal €1.80 €53.14 €307.61 -€256.27 Mode a e Rocu onium + Neos igmine €2.27 €53.14 €307.61 -€256.73 Deep Rocu onium + No e e sal €1.80 €104.48 €307.61 -€204.93 A e age pe p ocedu e using Sugammadex €1.97 €59.76 €307.61 -€249.82 A e age ac oss all su gical p ocedu es ( ega dless o sugammadex usage) €0.58 €17.67 €90.97 -€73.88 Table 5 Annual coun y-le el ne budge impac Block Dep h A Re e sal P io NMBA & Re e sal Agen P io Scena io D ug Cos s Al e na i e Scena io (incl. sugammadex) D ug Cos s To al Cos O se s F om Clinical E en s A oided Ne Cos Sa ings Mode a e Rocu onium + No e e sal €212,903 €6,272,453 €36,308,198 -€30,248,647 Mode a e Rocu onium + Neos igmine €184,369 €4,321,505 €25,015,106 -€20,877,969 Deep Rocu onium + No e e sal €53,225 €3,083,001 €9,077,049 -€6,047,274 To al Budge Impac €450,498 €13,676,960 €70,400,354 -€57,173,892 Ma inez-Ubie o e al. BMC Anes hesiology (2021) 21:55 Page 6 o 10 min, which esul ed in an economic alue o £2.87 pe minu e. Ozdemi e al. (2010) [42] p esen ed a s udy compa - ing he cos s o he pulmona y complica ions associa ed wi h he esidual NMB using sugammadex and neos ig- mine. Cos s in he spon aneous eco e y g oup we e CZK 126.45, CZK 114.56 in he neos igmine g oup and CZK 34.93 in he sugammadex g oup. All hese pha macoeconomic s udies ha e s udied di - ec cos s [38–43], howe e , o he indi ec aspec s ha e no been e alua ed o aken in o accoun , such as he in- angible alue o he ime sa ed by s a membe s, he loss o pe sonal and wo k ime o pa ien s and amily membe s, he impac o cancella ion o subsequen su - gical p ocedu es, ep og amming o he su gical pa s o a possible inc ease in su gical wai ing imes. Al hough mo e p ospec i e s udies a e needed, he e- sul s o ou analysis a e aligned wi h he p e ious s udies conclusions, showing ha sugammadex is cos sa ing compa ed o neos igmine. Limi a ions Ou s udy has se e al limi a ions, mainly due o he numbe o assump ions included in he budge impac model. The i s limi a ion is ha he spli o mode a e/ deep muscula blockage o 80/20 was based on an in- e nal ma ke esea ch and no in published da a. Un o - una ely, we did no ind published s udies suppo ing, in clinical p ac ice, his dis ibu ion. To educe bias de- i ed om his assump ion, we alida ed his 80/20 spli wi h he in es iga o s acco ding o clinical p ac ice in hei hospi als be o e aken i o de elop he economic model. Ne e heless, we ha e o ake in o accoun ha his spli is an o e all es ima ion and can di e in hospi- als whe e ce ain speci ic p ocedu es a e mo e equen han o he s ( equi ing, o example, a highe pe cen age Table 6 Numbe o pos -ope a i e e en s and cos s a oided (na ional-le el esul s) Block Dep h A Re e sal P io NMBA & Re e sal Agen Numbe o Pos -ope a i e e en s (P io Scena io) Numbe o Pos -ope a i e e en s (Al e na i e Scena io) Cos s o pos -ope a i e e en s (P io scena io) Cos s o pos -ope a i e e en s (Al e na i e scena io) Mode a e Rocu onium + No e e sal 13,296 3599 €54,335,758 €18,027,560 Mode a e Rocu onium + Neos igmine 9161 2480 €37,435,478 €12,420,372 Deep Rocu onium + No e e sal 3324 900 €13,583,939 €4,506,890 To al 25,781 6979 €105,355,176 €34,954,822 4806 pneumonia cases a oided 13,996 a elec asis cases a oided €70,400,354 cos s a oided wi h sugammadex use Fig. 3 To nado Diag am. Resul s om he De e minis ic Sensi i i y Analysis) Ma inez-Ubie o e al. BMC Anes hesiology (2021) 21:55 Page 7 o 10 o pa ien s wi h deep NMB) o depending on he clinical p ac ice in each hospi al o he cha ac e is ics o su gical pa ien s. As his could be a c i ical pa ame e , one o he scena ios included in he DSA educed he p opo ion o mode a e block in he dis ibu ion and did no esul in signi ican change in he model. Second, he assump ion o he dose o sugammadex used o NMB e e sal was o 4 mg/kg o deep NMB and 2 mg/kg o mode a e NMB. This assump ion was based on he phase III clinical ials desc ibed in he sugammadex label, in which he abo e-men ioned doses we e used. Again, his was alida ed by he in es iga o s based on hei clinical p ac ice, bu clinical p ac ice can di e om hospi al o hospi al and he model could no be alid should doses di e en o hose desc ibed in he sugammadex label we e used. Ano he limi a ion could be he es ima ion o he cos o pos -ope a i e pneumonias and a elec asis. The da a was e ie ed om he o icial bulle in o Conseje ía de Salud de la Jun a de Andalucía del 2016 and upda ed o €2019 conside ing in la ion. Howe e , hese cos s, specially he a i o pneumo- nia, could ha e been unde es ima ed because add- i ional complica ions associa ed wi h pneumonia o a elec asis we e no aken in o accoun . Depending on he Spanish egion and he se e i y, he cos o a case o pneumonia wi h de i ed complica ions can ap- p oach €8300 [34]. Howe e , he sensi i i y analysis sugges s ha ou con- clusions a e obus and s able ac oss a ange o pa am- e e es ima es. Addi ionally, he model did no conside di e en isk le els o each pos -ope a i e e en depending on he ype o su gical p ocedu e. Finally, se e al po en ial a eas o sugammadex bene i we e no explici ly modeled due o lack o e idence o guide modeling, o because ela ed cos o se s would be small ela i e o hose o pos -ope a i e a elec asis, o pneumonias. These a eas include: 1) a oidance o e- sidual neu omuscula blockade and common sequelae managed ou inely and inexpensi ely in he ope a ing oom o pos anes hesia ca e uni s [44–46]. Examples o his sequelae could be uncomplica ed aspi a ion, hypox- emia, muscle weakness and uppe ai way obs uc ion. 2) Ope a ing oom ime sa ings unde usual s anda ds o ca e o neu omuscula moni o ing and ex uba ion. 3) A oidance o ad e se e en s associa ed wi h neos igmine ha could po en ially be p e en ed wi h sugammadex usage. 4) Imp o ed pa ien , su geon and anes he is sa is ac ion. Conclusion This economic analysis shows ha sugammadex can po- en ially lead o cos sa ings o he e e sal o ocu onium-induced mode a e o deep NMB compa ed o e e sal wi h neos igmine o no pha macological e- e sal in he Spanish heal h ca e se ing. The economic model was based on da a ob ained om Spain and om assump ions om clinical p ac ice and may no be alid o o he coun ies. Abb e ia ions DRG: Diagnosis- ela ed g oup; DSA: De e minis ic sensi i i y analysis; NMB: Neu omuscula blockade/blocking; PACU: Pos anes hesia ca e uni s; esidual NMB: Residual neu omuscula blockade; T2: Second wi ch; ToF: T ain-o - ou ; ISPOR: In e na ional Socie y o Pha macoeconomics and Ou comes Resea ch Acknowledgmen s No applicable. Au ho s’con ibu ions JY, CS, RBP, PJ, CCL designed he budge impac model, acqui ed he da a, analyzed and in e p e ed he da a, d a ed and e ised he manusc ip . MUJ, ABC, PBAM and MA acqui ed he clinical da a, ad ised he in e p e a ion o he da a, w i e and c i ically e ised he manusc ip . All au ho s ead and app o ed he inal manusc ip . Funding The s udy was unded by MSD, Spain, a subsidia y o Me ck & Co., Inc., Kenilwo h, NJ, USA. A ailabili y o da a and ma e ials All s udy da a a e p esen ed ei he in he a icle o in he addi ional iles. Access o non-publicly a ailable da abases used in he analysis (eSalud and Bo Plus) we e ob ained by subsc ip ion. Numbe o annual su gical p ocedu es was ex ac ed om Conjun o Minimo Básico de Da os (CMBD), a public da abase which can be accessed om he Spanish Minis y o Heal h websi e (h ps://pes adis ico.in eligenciadeges ion. mscbs.es/publicoSNS/S/ ae-cmbd). The cos pe clinical e en was e ie ed om he eSalud. This pla o m is he access po al o he Spanish heal hca e cos s da abase se up by Oblikue Consul ing. eSalud access pla o m is a ailable on subsc ip ion a www. oblikue.com/bddcos es. Lis p ices o NMB agen s and e e sal agen s we e ob ained om Bo plus (h ps://bo plusweb.po al a ma.com/). Bo plus is he o icial da abase o he Consejo Gene al de Colegios O iciales de Fa macéu icos and, al hough some o he p oduc in o ma ion is public, lis p ices a e only a ailable by subsc ip ion. Addi ional da a suppo ing he indings o his s udy a e a ailable om he co esponding au ho upon easonable eques . E hics app o al and consen o pa icipa e Access o non-publicly a ailable da abases used in he analysis (eSalud and Bo Plus) we e ob ained by subsc ip ion. This was a non-clinical s udy ha did no collec in o ma ion om indi iduals, and e hic commi ee app o al o in o med consen was no necessa y. Consen o publica ion No applicable. Compe ing in e es s MSD Spain and Me ck & Co. employees pa icipa ed in he model design, analysis, in e p e a ion o da a and w i ing o he manusc ip . JY is employee o MSD L d., UK, and may own s ock and/o hold s ock op ions in Me ck & Co., Inc., Kenilwo h, NJ, USA. PJ, RBP and CCL a e employees o MSD, Spain. CS is an employee o Co ance Clinical De elopmen , a con ac esea ch o ganiza ion p o iding suppo o MSD, Spain. MUJ, ABC, PBAM and MA decla e NO compe ing in e es s. Au ho de ails 1 Hospi al Uni e si a io Miguel Se e , Za agoza, Spain. 2 Hospi al Uni e si a io de Mós oles, Mad id, Spain. 3 MSD, Mad id, Spain. 4 Hospi al Uni e si a io de la Ma inez-Ubie o e al. 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