Preoperative prediction of prolonged mechanical ventilation following coronary artery bypass grafting

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1 Europen Journl of Crdio-thorcic Surgery 20 (2001) Preopertive prediction of prolonged mechnicl ventiltion following coronry rtery bypss grfting Abstrct J.F. Légré, G.M. Hirsch*, K.J. Buth, C. McDougll, J.A. Sullivn Dlhousie University, Hlifx, Nov Scoti, Cnd Received 27 December 2000; received in revised form 18 July 2001; ccepted 20 July 2001 Objective: Few studies hve ttempted to evlute who would require prolonged mechnicl ventiltion following hert surgery. The objectives of this study were to identify predictors of prolonged ventiltion in lrge group of coronry rtery bypss grfting (CABG) ptients from single institution. Methods: One thousnd, eight hundred nd twenty-nine consecutive ptients undergoing CABG were reviewed retrospectively nd evluted for preopertive predictors of prolonged ventiltion which included: ge, gender, ejection frction (EF), renl function, dibetes, ngin sttus, New York Hert Assocition Clss, number of disesed vessels, urgency of the procedure, reopertion, chronic lung disese (COPD) nd intropertive vribles such s IABP, inotropes, stroke nd myocrdil infrction. Prolonged ventiltion ws defined s $24 h. Stepwise logistic regression nlysis ws performed. Results: Ptients were on verge 65.4 ^ 10.6 yers of ge, 30% were dibetic, 80% hd triple vessel disese nd 93% were of functionl clss III/IV. The men ejection frction ws 60 ^ 16 percent. Overll peri-opertive mortlity ws 2.7%. There were 157 ptients tht required prolonged ventiltion with peri-opertive mortlity of 18.5% (P, 0:001). Preopertive independent predictors of prolonged ventiltion were found to be: unstble ngin (OR 5.6), EF, 50 (OR 2.3), COPD (OR 2.0), preop. renl filure (OR 1.9), femle gender (OR 1.8) nd ge. 70 (OR 1.7). Bsed on these predictors, model ws creted to estimte of the risk of prolonged ventiltion in individul ptients following CABG with results rnging from #3% in ptients without ny risk fctors to $32% in ptients with five or more independent risk fctors.certin intropertive vribles were strong predictors of prolonged ventiltion nd included: stroke (OR 12.3), re-opertion for bleeding (OR 6.9) nd periopertive MI (OR 5.8). Conclusion: We were ble to crete stble model where severl preopertive nd intr-opertive vribles were shown to be predictive of prolonged ventiltion fter CABG surgery. The bility to identify ptients t incresed risk for prolonged ventiltion my llow the development of pre-emptive strtegies nd more effective resource lloction. q 2001 Elsevier Science B.V. All rights reserved. Keywords: Coronry rtery bypss grfting; Ventiltion 1. Introduction Coronry rtery bypss grfting (CABG) surgery is n estblished tretment for ptients with ischemic hert disese. It is one of the most commonly performed surgicl interventions with over cses performed in Cnd nd in the United Sttes nnully [1]. Pre-opertive, opertive nd post-opertive cre of CABG ptients is ssocited with substntil utiliztion of helth cre resources. Current economic constrints in the helth cre system hs led to significnt efforts to shorten length of hospitliztion nd reduce helth cre cost [2,3]. To chieve this, mny progrms hve dopted policies to foster shorter * Corresponding uthor. New Hlifx Infirmry QEII HSC, 1796 Summer St Rm 2269, Division of Crdic Surgery, Hlifx, Nov-Scoti, Cnd B3H 3A7. Tel.: ; fx: E-mil ddress: ghirsch@is.dl.c (G.M. Hirsch). intensive cre unit sty in n effort to shorten hospitliztion nd reduce overll costs since these hve been shown to be sfe in ptients following CABG [4]. Survivl hs improved stedily over the pst decde despite incresing ppliction of CABG procedures to n older ptient popultion with more co-morbidities nd higher risk profile [5]. Adverse respirtory system events such s respirtory filure nd pneumoni hve been trditionlly the leding cuse of post-opertive complictions [6]. Prolonged mechnicl ventiltion is known to result in incresed intensive cre unit length of sty (ICU), decresed hospitl bed vilbility, incresed resource utiliztion nd helth cre cost. Prolonged mechnicl ventiltion hs lso been suggested to result in worse physiologicl outcomes for ptients post-extubtion s result of telectsis nd intr-pulmonry shunting [4]. In fct there re mny welldocumented benefits to erly extubtion especilly respirtory nd crdiovsculr [7,8]. However, few studies hve /01/$ - see front mtter q 2001 Elsevier Science B.V. All rights reserved. PII: S (01)00940-X

2 J.F. Légré et l. / Europen Journl of Crdio-thorcic Surgery 20 (2001) ttempted to evlute preopertive predictors of prolonged ventiltion in popultion of ptients undergoing CABG surgery [2,9]. Preopertive ptient demogrphics, lung function tests nd blood gs prmeters hve not lwys llowed relible predictions of who would require prolonged ventiltion [6,10]. The objectives of this study were to identify predictors of prolonged ventiltion in lrge group of CABG ptients from single institution. Such knowledge could llow better plnning of resource lloction nd guide some preventive strtegies. 2. Mterils nd methods 2.1. Ptients One thousnd, eight hundred nd twenty-nine consecutive ptients undergoing CABG surgery t single university ffilited institution between Jnury 1997 nd Mrch 1999 were reviewed retrospectively. Inclusion into the study ws bsed on the vilbility of ll the following preopertive vribles: ge, gender, ejection frction (EF), renl function, dibetes, ngin sttus, New York Hert Assocition Clss (NYHA), number of disesed vessels, urgency of the procedure, re-opertion, nd history of chronic lung disese (COPD). A totl of 1805 ptients were included in the multivrite nlysis with 24 ptients excluded becuse of missing preopertive dt, which mostly consisted of EF (98.7% inclusion). Indictions for CABG surgery ws bsed on weekly peer review process involving crdiologist, crdic surgeons nd crdic rdiologists such tht individul ptients were wit listed ccording to urgency of procedure. Crdiopulmonry bypss (CPB) for coronry bypss surgery t our institution ws performed in stndrdized fshion. Body temperture during the procedure ws llowed to drift to pproximtely 328C. Stndrd crdioplegi used ws intermittent cold blood delivered ntegrde unless otherwise indicted. Ptients who hd beting hert surgery (OPCAB) were not included in this nlysis in n ttempt to stndrdize our model (n ¼ 114) Dt collection Periopertive ptient vribles were collected on Society of Thorcic Surgeons (STS) forms, by three full time reserch ssistnts, nd mintined in computer dt bse formt (Summit Medicl Systems, Inc. MN, USA, 1997). This hs been stndrd prctice t this institution for ll crdic surgicl cses since 1995 with dt element vlidtion. EF were ssessed by left hert ctheteriztion preopertively. Durtion of mechnicl ventiltion ws from the time of rrivl to ICU to the time of extubtion. Prolonged ventiltion ws defined s ny mechnicl ventiltion of more thn 24 h s defined by the STS guidelines. Urgency sttus ws lso determined using the stndrd STS Crdic Surgery Dtbse definitions. An elective cse ws defined s ptient being stble for more thn 24 h prior to the procedure, urgent opertion required procedure to be performed within 24 h to prevent further clinicl deteriortion, nd emergent/emergent slvge in ptients who required n immedite opertion Clinicl decision mking The decision to extubte ws mde on n individul, ptient-by-ptient bsis by one of the seven ttending crdiovsculr surgeons, two crdic nesthetists, supporting resident housestff nd/or nurse tking cre of the ptient. To be considered for extubtion ptients hd to be wrm (.358C), wke, hemodynmiclly stble, nd hve the following gs exchnge findings on rteril blood gs: PO 2.60, PCO 2,55 nd ph of more thn Ptients were generlly not extubted erly fter surgery if they were considered t risk cliniclly for decresed oxygen delivery. This included ptients with signs of indequte tissue perfusion (lctte levels.2, mixed venous oxygen sturtion,60%, urine output,0.5 ml/kg/h, crdic index,2 l/m 2 min), significnt hemodynmic instbility, ptients requiring two or more inotropes, utiliztion of intr-ortic blloon pump (IABP) or ventriculr ssist device (VAD), nd ptients with multi-orgn dysfunction Dt nlysis Descriptive sttistics were obtined for ll vribles using the SAS softwre pckge (SAS, Cry, North Crolin). These included continuous nd discrete vribles which were nlyzed ccordingly with n unpired t-test, chisqure test, nd Fisher exct test. Logistic regression model ws developed to predict the occurrence of prolonged ventiltion bsed on pre-opertive vribles in ptients undergoing CABG. Pre-opertive vribles were chosen from previous studies predicting outcomes following CABG surgery [5,11,12]. Forwrd selection within the regression model ws stepwise where vribles were retined if their ssocited P vlue were #0.05. A c sttistic ws clculted s mesure of the explntory power of the logistic regression model. The c sttistic is equivlent to the re under the receiver-operting-chrcteristic (ROC) curve where c vlue of 0.5 indictes no discrimintory power, wheres c vlue of 1.0 indictes perfect discrimintion between ptients requiring prolonged mechnicl ventiltion. The model c-sttistic ws 0.81 nd the goodness of fit sttistic for the model ws P ¼ 0:92 indicting good, stble fit of the model. 3. Results 3.1. Ptient chrcteristics The ptients enrolled in this study represent typicl referrl prctice for most Cndin centers [13]. Ptients

3 932 J.F. Légré et l. / Europen Journl of Crdio-thorcic Surgery 20 (2001) Tble 1 Pre-opertive chrcteristics 1829 ptients undergoing CABG surgery t single institution between 1997 nd 1999 Chrcteristics n (%) Age $ (38) Gender Femle 487 (27) EF, (24) Renl filure Cretinine (6) Dibetes 546 (31) Angin Unstble 372 (20) NYHA I 5 (0.3) II 115 (6) III 973 (53) IV 736 (40) Disesed vessels Single 46 (3) Double 321 (18) Triple 1462 (80) Urgency Elective 1477 (81) Urgent 272 (15) Emergent 80 (4) Reopertion 142 (8) COPD 216 (12) COPD, chronic obstructive pulmonry disese; EF, ejection frction; NYHA, New York Hert ssocition clss. were predominntly mle with n verge ge of 65.4 ^ 10.6 yers with 38% being over 70 yers of ge. More thn 30% were dibetic with men EF of 60 ^ 16 percent. Twenty-four percent of ptients hd n EF of less thn 50 nd rnged from 9 to 92%. Ptients mostly hd triple vessel disese (80%) nd were of functionl clss III or IV (93%). Complete pre-opertive ptient demogrphics re illustrted in Tble 1. Both urgency sttus nd ngin clss definitions were bsed on STS guidelines outlined in the methods section of this mnuscript Ptient outcomes Out of 1829 CABG procedures performed there were 49 periopertive deths (2.7% mortlity rte). One hundred nd fifty seven ptients required ventiltion for more thn 24 h (8.6%) fter surgery with mortlity rte of 18.5% (P, 0:001). Ptients ventilted for more thn 24 h were ventilted for n verge of 7.9 ^ 8.5 dys (rnge dys) (Fig. 1). The overll medin length of hospitliztion ws 7 dys with rnge of dys. The use of intr-ortic blloon pump (IABP) ws defined s ny IABP use peri-opertively nd ws required in 8.4% of ptients. Inotropes were utilized in 14.7% of ptients nd were defined s ny inotrope used post-opertively, the most common of which ws dopmine (Abbot Lbortories, PQ, Cnd). Blood product use included: fresh frozen plsm, cryoprecipitte, pltelets or pcked red blood cells, nd ws limited to 22.1% of ptients with 15 (0.8%) ptients reoperted for bleeding. The incidence of peri-opertive MI ws 0.9% nd permnent stroke 1.7%. Detils of surgicl outcomes re illustrted in Tble Univrite predictors Pre-opertive ptient chrcteristics nd intr-opertive vribles were then evluted univritely s predictors of prolonged ventiltion defined s greter or equl to 24 h. These re listed in order of decresing odds rtio in Tble 3. Fig. 1. Grph illustrting the distribution over time of ptients ventilted for greter thn 24 h (n ¼ 157).

4 J.F. Légré et l. / Europen Journl of Crdio-thorcic Surgery 20 (2001) Tble 2 Opertive results following CABG (n ¼ 1829) Opertive results n (%) Mortlity 49 (2.7) Prolonged ventiltion 157 (8.6) LOS medin (rnge) 7 (3 177) IABP 153 (8.4) Inotropes 269 (14.7) Blood trnsfusion 404 (22.1) Pump time.120 min 485 (26.6) Reop.for bleeding 15 (0.8) Periop. MI 16 (0.9) Stroke 31 (1.7) IABP, intr-ortic blloon pump; LOS, length of sty; MI, myocrdil infrction. The strongest univrite predictor for prolonged mechnicl ventiltion ws the presence of n IABP with n odds rtio of 22.8, nd the lower significnt predictor ws re-opertion with n odds rtio of 1.7. The number of disesed vessels, dibetes nd NYHA were not significntly ssocited with prolonged ventiltion Multivrite predictors Tble 4 shows the logistic regression model for predicting the occurrence of prolonged ventiltion; this model ws developed s described in the mterils nd methods. The predictors re listed in descending order of the odds rtio mgnitude. The three most powerful predictors of prolonged mechnicl ventiltion were found to correspond to intropertive vribles or complictions: permnent stroke, reopertion for bleeding nd periopertive myocrdil infrction. On the other hnd independent pre-opertive predictors of prolonged mechnicl ventiltion were found to be: unstble ngin, ejection frction of less thn 50, history Tble 3 Univrite predictors of prolonged mechnicl ventiltion following CABG surgery Vrible P OR CI (95%) IABP, Emergent surgery, Stroke, Inotropes, Unstble ngin, Reop. For bleeding, Periop. MI, EF,50, Preop. Renl filure, Age greter thn 70, COPD, Pump time.120 min, Femle gender, Reopertion CI, confidence intervl; COPD, chronic obstructive pulmonry disese; EF, ejection frction; IABP, intr-ortic blloon pump; NYHA, New York Hert ssocition clss; OR, odds rtio. Tble 4 Multivrite predictors of prolonged mechnicl ventiltion obtined by logistic regression nlysis Vrible of chronic obstructive lung disese, preopertive renl filure (cretinine.177), femle gender nd ge greter thn 70. Coefficients obtined from the logistic regression were then utilized to crete cliniclly meningful predictive model using preopertive predictors only, not intropertive vribles. This predictive model llows one to estimte the preopertive risk of prolonged mechnicl ventiltion in individul ptients expressed s percent risk with 95% confidence intervl (Figs. 2 nd 3). In summry, ptients with no risk fctors hve less thn 3% risk of requiring prolonged mechnicl ventiltion fter CABG s compred to greter thn 32% risk in ptients with five or more risk fctors (Fig. 3). 4. Discussion Odds rtio Stroke 12.3 ( ) Reop. Bleeding 6.7 ( ) Periop. MI 5.8 ( ) Unstble ngin 5.6 ( ) EF, ( ) COPD 2.0 ( ) Preop. renl filure 1.9 ( ) Femle gender 1.7 ( ) Age ( ) COPD, chronic obstructive pulmonry disese; EF, ejection frction. Ptients undergoing isolted CABG surgery t our institution re usully mechniclly ventilted for less thn 24 h, re dischrged from ICU within 24 h nd often dischrged home within 1 week fter surgery [11]. Efforts to extubte ptients erly fter hert surgery hve been bsed on studies Fig. 2. Model predicting pre-opertively prolonged mechnicl ventiltion bsed on coefficients from the logistic regression model nd illustrted s percent risk of requiring prolonged mechnicl ventiltion. Risk fctors were evluted in isoltion. EF, ejection frction.

5 934 J.F. Légré et l. / Europen Journl of Crdio-thorcic Surgery 20 (2001) Fig. 3. Model predicting pre-opertively prolonged mechnicl ventiltion bsed on coefficients from the logistic regression model nd illustrted s percent risk of requiring prolonged mechnicl ventiltion. Risk of prolonged ventiltion ws evluted s combintion of one to five risk fctors. Ptients with six risk fctors resulted in 73% (rnge 4 100%) risk of prolonged ventiltion with wide confidence intervls presumbly becuse no ptients in this study were found to hve ll six pre-opertive risk fctors. tht demonstrte the sfety nd potentil to reduce length of hospitliztion of such pproches [2,4,14]. However, becuse CABG opertions continue to be commonly performed, nd represent significnt usge of helth cre resources, n bility to predict which ptients would require prolonged mechnicl ventiltion with ssocited prolonged ICU sty nd length of hospitliztion, could help llocte dequte resources nd my led to the developments of preventive strtegies [9]. Contrry to mny studies we hve defined prolonged ventiltion s greter thn 24 h becuse it pproximtes most closely current clinicl prctice [11,15]. Others hve utilized cutoff from 36 h to 6 dys for the definition of prolonged ventiltion but these cutoffs would hve resulted in lower event rtes we feel re less cliniclly relevnt [9,10,16 18]. The ptient popultion evluted in this study ws representtive of most lrge crdic surgicl centers in Cnd [13]. A significnt proportion of ptients were older thn 70 yers of ge (38%), 7.8% were re-opertions nd 92.8% were of functionl clss III or IV (NYHA). While the percentge of ptients undergoing elective procedures reched 83%, it should be noted tht this figure includes ptients witing surgery in n in-hospitl setting in ccordnce with the Society for Thorcic Surgeons dtbse definitions. Mny elective ptients require systemic heprin nd/or i.v. nitrtes nd were not considered unstble enough to require n opertion within 24 h. This indirectly reflects the sttus of witing lists in Cnd where hospitlized ptients my wit dys prior to their opertive procedure with unstble nginl syndromes. In this series of 1829 ptients undergoing CABG surgery there ws n 8.6% incidence of prolonged mechnicl ventiltion, which ws ssocited with significnt mortlity (18.5%) s compred to CABG ptients who did not require ventiltion for more thn 24 h (1.2%). This finding does not suggest tht prolonged ventiltion necessrily results in incresed mortlity but identifies group of ptient t incresed risk of morbidity nd mortlity following coronry bypss surgery. In n ttempt to predict pre-opertively who these ptients re, multiple logistic regression nlysis ws used to identify independent predictors of prolonged mechnicl ventiltion. Six independent predictors were identified nd include: unstble ngin, low ejection frction, COPD, pre-op renl filure, femle gender nd dvnced ge. Interestingly, severl vribles were not found to be independent risk fctors for prolonged ventiltion despite mny of them being often considered mrkers of disese severity. Non-predictive vribles included: reopertion, number of disesed vessels, dibetes, emergent surgery, NYHA III or IV, nd left ventriculr end distolic pressure of greter thn 20. The strongest predictor ws unstble ngin with 5.2- fold higher (9.3% risk) incidence of prolonged ventiltion compred with stble ngin. However, it is importnt to note tht unstble ngin ws defined s ptients with refrctory ngin tht required hospitliztion, ICU dmission nd prenterl nitrtes to control symptoms. This definition is very stringent nd differs from common prctice where ny chnge from previous ngin stte or new dignosis defines unstble ngin. In our study, unstble ngin ws n importnt mrker of disese severity, nd cuteness of disese. Preopertive unstble ngin hs lso been reported by others to predict prolonged intubtion following CABG surgery [2]. Ventriculr dysfunction ws lso found to be n independent predictor of prolonged ventiltion. Ptients with n EF of less thn 50% hd 2.3-fold incresed incidence (4.1% risk) of prolonged ventiltion. An EF of less thn 50% ws chosen rbitrrily becuse cliniclly it includes most ptients with left ventriculr dysfunction rnging from mild, moderte to severe. We demonstrte tht EF continues to be very strong predictor of mortlity nd morbidity in CABG ptients [10,19,20]. COPD represents brod spectrum of lung diseses often difficult to define. Ptients with COPD undergoing crdic opertions re influenced negtively by both sternotomy nd CPB with respect to post-opertive pulmonry complictions [21]. We Hve shown tht ptients with history of COPD hve 2-fold incresed incidence of prolonged ventiltion (3.5% risk). This is in keeping with other studies suggesting tht prolonged ventiltion (.48 h) is seen in 5.2% of ptients with COPD s compred to 2.8% of ptients without when undergoing CABG surgery [22]. These studies hve lso suggested tht ptients with COPD hve proportionlly higher mortlity rte [22]. Ptients with pre-opertive renl filure defined s cretinine of greter or equl to 177 were found to hve 1.9-

6 J.F. Légré et l. / Europen Journl of Crdio-thorcic Surgery 20 (2001) fold incresed incidence of prolonged ventiltion (3.3% risk). This group includes ptients which were both dilysis nd non-dilysis dependent. Renl filure defined s such hs been previously shown to be ssocited with worse outcome following crdic surgery with resulting prolonged length of hospitliztion often ssocited with prolonged mechnicl ventiltion nd ICU sty [11]. Femle gender is believed by mny to be predictor of incresed mortlity nd morbidity following CABG surgery for resons tht re not entirely cler nd tht re not simply relted to smll body surfce re [21]. In the current study femle ptients hd 1.8-fold incresed incidence of prolonged ventiltion (3.2% risk). Our findings re lso supported by recent evidence suggesting tht femle ptients hve longer intubtion times, intensive cre unit stys nd length of hospitliztion [23]. Seventy yers of ge ws chosen in this study s cutoff for dvnced ge since the men ge of CABG ptients ws 65 yers with 38% of ptients older thn 70 yers of ge. Ptients older thn 70 were shown to be 1.7-fold more likely (3% risk) to be ventilted for longer thn 24 h fter CABG just on the bsis of their ge. Age hs been suggested by others to be predictor for prolonged intubtion [2], result in prolong ventiltion [24] nd independently be ssocited with incresed long-term mortlity [24,25]. Tken together with stedy increse in the ge of CABG ptients over time [5], this finding will hve importnt implictions for future helth cre resource utiliztion [9]. If current trends in ptient demogrphics continue one could project in the ner future significnt increses in ICU bed utiliztion by n incresing proportion of elderly ptients resulting in further pressures on the current helth cre systems. Most outcome studies hve focused on mortlity or dverse outcomes in the broder sense following CABG [12,17]. Few hve ttempted to evlute pre-opertive prmeters to predict post-opertive respirtory outcome but hve identified in common ge s predictor of prolonged mechnicl ventiltion following CABG [2,10,15]. However, one must tke into considertion tht definitions for prolonged ventiltion, preopertive vribles evluted nd outcomes mesured hve differed between studies. A mjor limittion of our nlysis of pre-opertive predictors is tht intr-opertive complictions re known to hve significnt impct on post-opertive morbidity nd mortlity [9]. To ddress this we hve included in our nlysis the use of IABP, CPB for greter thn 120 min, postopertive MI, re-opertion for bleeding nd permnent stroke. The lter three vribles or complictions were shown to be very strong independent predictors of prolonged ventiltion regrdless of pre-opertive risk fctors. Therefore our bility to predict who will require prolonged mechnicl ventiltion will lwys be gretly influenced by intr-opertive outcomes. A potentil wekness is lso tht we did not sensor mortlity in our nlysis. It is likely tht ptients tht died within 24 h of surgery would hve required prolonged ventiltion, however, this represents only smll group of ptients (n ¼ 16). Given the reltively lrge cohort evluted (n ¼ 1829), the c sttistic of the multiple logistic regression model predicting good fit nd the representtiveness of the cohort, it is unlikely tht our findings re inccurte or bised. In summry, we hve demonstrted tht in lrge cohort of ptient undergoing coronry revsculriztion it is possible to predict using pre-opertive vribles the risk of ech individul ptient to require prolonged mechnicl ventiltion expressed s percent risk. Six independent predictors were identified nd represent the frmework of the predictive model. The bility to identify ptients with incresed risk for prolonged ventiltion my llow the development of pre-emptive strtegies nd pproprite resource lloction. References [1] Morris A, Almond D. 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