Perioperative Hyperglycemia and Postoperative Infection after Lower Limb Arthroplasty

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1 Journl of Dibetes Science nd Technology Volume 5, Issue 2, Mrch 2011 Dibetes Technology Society ORIGINAL ARTICLES Periopertive Hyperglycemi nd Postopertive Infection fter Lower Limb Arthroplsty Boris, M.D., 1 Donghun Suh, M.D., 2 Christin Jcovides, B.S., 2 nd Jvd Prvizi, M.D. 2 Abstrct Bckground: One of the most serious complictions fter mjor orthopedic surgery is deep wound or periprosthetic joint infection. Vrious risk fctors for infection fter hip nd knee replcement surgery hve been reported, including ptients comorbidities nd surgicl technique fctors. We investigted whether hyperglycemi nd dibetes mellitus (DM) re ssocited with infection tht requires surgicl intervention fter totl hip nd knee rthroplsty. Methods: We reviewed our computerized dtbse for elective primry totl hip nd knee rthroplsty from 2000 to Demogrphic informtion, pst medicl history of ptients, periopertive biochemistry, nd postopertive complictions were reviewed. Ptients were divided into two groups: infected group (101 ptients who hd surgicl intervention for infection t our institution within 2 yers fter primry surgery) nd noninfected group (1847 ptients with no intervention with minimum of one yer follow-up. The dt were nlyzed using t, chi-squred, nd Fisher s exct tests. Results: There were significntly more dibetes ptients in the infected group compred with the noninfected group (22% versus 9%, p <.001). Infected ptients hd significntly higher periopertive blood glucose (BG) vlues: preopertive BG (112 ± 36 versus 105 ± 31 mg/dl, p =.043) nd postopertive dy (POD) 1 BG (154 ± 37 versus 138 ± 31 mg/dl, p <.001). Postopertive morning hyperglycemi (BG >200 mg/dl) incresed the risk for the infection more thn two-fold. Non-DM ptients were three times more likely to develop the infection if their morning BG ws >140 mg/dl on POD 1, p =.001. Mle gender, higher body mss index, knee rthroplsty, longer opertive time nd hospitl sty, higher comorbidity index, history of myocrdil infrction, congestive hert filure, nd renl insufficiency were lso ssocited with the infection. continued Author Affilitions: 1 Deprtment of Anesthesiology, Thoms Jefferson University Hospitl, Phildelphi, Pennsylvni; nd 2 Rothmn Institute of Orthopedics, Thoms Jefferson University Hospitl, Phildelphi, Pennsylvni Abbrevitions: (ASAPS) Americn Society of Anesthesiologists physicl sttus, (BG) blood glucose, (BMI) body mss index, (BUN) blood ure nitrogen, (DM) dibetes mellitus, (I&D) irrigtion nd debridement, (INR) interntionl stndrdized rtio, (MI) myocrdil infrction, (PJI) periprosthetic joint infection, (POD) postopertive dy Keywords: blood glucose, dibetes mellitus, hip nd knee rthroplsty, infection, orthopedic surgery Corresponding Author: Boris, M.D., Artificil Pncres Center, Thoms Jefferson University, Jefferson Alumni Hll Suite #565, 1020 Locust Street, Phildelphi, PA 19107; emil ddress: Boris.@jefferson.edu 412

2 Abstrct cont. Conclusions: Dibetes mellitus nd morning postopertive hyperglycemi were predictors for postopertive infection following totl joint rthroplsty. Even ptients without dignosis of DM who developed postopertive hyperglycemi hd significntly incresed risk for the infection. J Dibetes Sci Technol 2011;5(2): Introduction Totl hip or knee replcement surgery re mjor opertions frequently performed in the United Sttes. Over 500,000 hip nd knee rthroplsties re performed ech yer, nd by yer 2030, the number is projected to increse to over 4 million. 1 One of the most serious complictions fter totl hip nd knee replcement surgery is deep wound or periprosthetic joint infection (PJI), which increses morbidity nd mortlity, doubling rehospitliztion rtes nd incresing helth cre costs more thn three times. 2 It hs been estimted tht more thn 8% of ptients with dibetes mellitus (DM) undergo primry or revision totl hip or knee rthroplsty in the United Sttes. 3 The Americn Dibetes Assocition reported on their Web site ( tht, in 2007, the prevlence of DM in the United Sttes ws 23.6 million (7.8% of the popultion), with 1.6 million new cses of DM ech yer. Ptients with DM hve incresed risk for postopertive complictions. Dibetes mellitus my increse risk for postopertive infection fter lminectomy, 4 crdic surgery, 5 nd noncrdic surgery. 6 Although DM ws ssocited with infection fter totl joint rthroplsty, 7 10 some studies did not find this correltion Actul periopertive blood glucose (BG) levels were not mesured in these studies. One study found tht mjority of non-dm ptients develop hyperglycemi during the first 2 dys fter mjor limb surgery, but high glucose could not be correlted with infection following rthroplsty becuse there ws no postopertive infections in their cohort up to yer following the surgery. 14 In contrst, periopertive hyperglycemi incresed the rte of infection fter crdic surgery, 15 generl surgery, 16 colorectl surgery, 17 spinl surgery, 18 nd mstectomy 19 but did not increse the risk for infections fter esophgectomy. 20 Whether postopertive hyperglycemi increses the risk for PJI fter hip nd knee rthroplsty is not estblished. Hyperglycemi my result from medictions, stress, impired glucose tolernce, or uncontrolled DM. Stress hyperglycemi is common in surgicl ptients. It is usully mnifesttion of counter-regultory hormonl responses nd proinflmmtory meditors. Acute hyperglycemi my impir the bility of the host to combt infection. 21 Thus hyperglycemi my hve n impct on infection fter totl joint rthroplsty independent of DM sttus. In this retrospective study, we investigted the effects of periopertive hyperglycemi nd DM on the incidence of infection tht requires surgicl intervention fter totl hip nd knee rthroplsty. Methods After obtining the institutionl review bord pprovl, we queried our institutionl computerized dtbse from Jnury 2000 to Februry The dtbse prospectively records ll hip nd knee surgeries performed t our institution. In this study, we included ptients who underwent primry totl hip or knee rthroplsty, developed PJI, nd subsequently hd surgicl intervention for the infection within 2 yers of the primry procedure t our institution (infected group). Periprosthetic joint infection ws defined s deep infection below fsci with involvement of muscle nd/or bone. Becuse dignosis of PJI fter hip nd knee rthroplsty still presents significnt clinicl chllenge, we included in the study ptients who hd surgicl interventions tht confirmed the clinicl dignosis of PJI. 413

3 As control group, we identified ptients who underwent primry hip or knee rthroplsty during the sme time period, did not undergo surgicl tretment for infection t our institution postopertively, nd hd follow-up dt for minimum of 1 yer postopertively (noninfected group). Demogrphic informtion, pst medicl history of ptients, periopertive biochemistry, nd postopertive complictions were reviewed. All periopertive BG levels were recorded. Preopertive BG vlues were rndom BG vlues (ptients were not instructed to fst) tken t the preopertive visit. For postopertive BG vlues, we used morning fsting BG. Since our hospitl dtbse records the time of mesurement of BG but does not record whether glucose vlues were fsting or not, we used only BG vlues tken before 1:00 pm on the dy of surgery (ptients were fsting overnight prior to surgery nd did not et before dinnertime fter the surgery). For subsequent postopertive dys (PODs), we used BG vlues closest to 6:00 m but not lter thn 8:00 m (when brekfst is served in the hospitl). During the period of the study, preopertive glycemic control ws left to the ptients primry cre physicin nd endocrinologist. If preopertive rndom glucose ws 200 mg/dl, letter ws sent to the physicin to ddress glycemic control. There ws no hospitl policy regrding BG preopertive glycemic control in ptients with BG 200 mg/dl on the morning of surgery. Postopertively, ptients were treted if BG ws 180 mg/dl. Persistent hyperglycemi clled for n endocrinology consult nd insulin infusion. The severity of ptients comorbidities ws clculted using Chrlson comorbidity index modified by Deyo et l. 22 nd the Americn Society of Anesthesiologists physicl sttus (ASAPS). All ptients received stndrdized periopertive mngement for infection prophylxis throughout the study period. Intrvenous ntibiotic (cefzolin or vncomycin in llergic ptients) ws given within 1 h of the incision nd for 24 h postopertively. The surgery ws performed in operting rooms with verticl lminr flow nd use of helmet spirtor suits nd double gloves. Skin ws prepred with lcohol nd iodine lvge. Uncemented nd cemented prostheses were used, respectively, for hip nd knee rthroplsties, without postopertive drins. Regionl nesthesi, spinl, nd/or epidurl, trgeting men rteril pressure of 60 mm Hg, ws used unless contrindicted. Over 90% of hip nd knee surgeries were performed under spinl/epidurl nesthesi t our institution. Thromboembolic prophylxis ws with intropertive intrvenous heprin 1000 IU nd postopertive wrfrin titrted to interntionl normlized rtio (INR) 1.5 to 2.0. Sttisticl Anlysis Dt nlysis ws performed using t-tests for ll continuous vribles nd chi-squred or Fisher s exct tests for ll ctegoricl vribles. Blood glucose vlues were nlyzed s continuous nd ctegoricl vribles. Ctegories were (1) BG 100 mg/dl, (2) BG >100 mg/dl to BG 200 mg/dl, nd (3) BG >200 mg/dl. A one-wy nlysis of vrince ws used to ssess the ssocition between periopertive BG levels nd time to infection in the infected cohort. Further cross-sectionl nlysis ws performed to ssess the combintoril effects of DM nd hyperglycemi on likelihood for infection. For this nlysis, hyperglycemi ws defined s BG >140 mg/dl on POD 1; p <.05 ws considered sttisticlly significnt. Results A totl of 101 ptients were included in the infected group nd 1847 ptients in the noninfected group. Surgicl interventions included resection of rthroplsty components nd insertion of n ntibiotic spcer (40 ptients), deep (i.e., with rthrotomy) irrigtion nd debridement (I&D) with or without polyethylene exchnge (56 ptients), superficil I&D (2 ptients), or one-stge revision rthroplsty for infection (3 ptients). Opertive notes were reviewed to confirm tht the infection ws the cuse for the reopertion. In 5 cses in which this dignosis ws not cler, medicl records were reviewed further to confirm infection. Four of these 5 ptients hd positive intropertive cultures, nd the finl ptient hd superficil I&D for wound dehiscence with subsequent resection nd ntibiotic spcer plcement less thn 1 yer following the I&D. Only one ptient developed infection in both hips performed 3 yers prt, ech infection developed within 2 yers of surgery. We counted this ptient s two seprte episodes of infection. The interventions for the infected joint were performed on verge of 0.4 ± 0.5 yers fter the primry surgery (rnge yers). There ws no difference between infected nd noninfected ptients in ge nd ethnicity s well s preopertive hemoglobin nd white blood cell count (Tbles 1 nd 2). Infected ptients tended to be mle nd hd significntly higher body mss index (BMI), longer opertive time, longer hospitl sty, were undergoing knee (versus hip) rthroplsty, nd hd bilterl (versus unilterl) surgery (Tbles 1 nd 2). Both comorbidity indices, the ASAPS score, nd the Chrlson comorbidity 414

4 Tble 1. Ptients Dt, Continuous Vribles Vrible Infected (n = 101) Noninfected (n = 1847) p Age (yers) 64.7 ± ± BMI (kg/m 2 ) 32 ± 9 30 ± b Hospitl sty (dys) 6.5 ± ± 1.4 <0.001 b Opertive time (minutes) ± ± 35.5 <0.001 b Preopertive lbs Cretinine (mg/dl) 1.0 ± ± 0.3 <0.001 b Hemoglobin (g/dl) 13.4 ± ± INR 1.10 ± ± b Pltelet count (1000 cells/µl) ± ± b BUN (mg/dl) 20.3 ± ± 6.1 <0.001 b Serum WBC (1000 cells/µl) 7.5 ± ± Postopertive Lbs Cretinine (mg/dl) 1.1 ± ± 0.3 <0.001 b Hemoglobin (g/dl) 10.2 ± ± INR 1.42 ± ± b Pltelet count (1000 cells/µl) ± ± BUN (mg/dl) 16.8 ± ± 5.2 <0.001 b Serum WBC (1000 cells/µl) 9.8 ± ± b Dt re men ± stndrd devition. WBC, white blood cell count. b Tble 2. Ptients Dt, Ctegoricl Vribles Vrible Infected (n = 101) Noninfected (n = 1847) (N) Percentges (%) (N) Percentges (%) Gender (mle/femle) 56/45 55/45 682/ /63 <0.001 Ethnicity (white/blck/other) 83/14/3 b 83/14/3 1288/164/15 b 88/11/ Joint (hip/knee) 31/70 31/ /763 59/41 <0.001 Lterlity (unilterl/bilterl) 75/24 b 76/ /256 86/ ASAPS score (1 2/3 4) 28/53 b 35/65 734/470 b 61/39 <0.001 Chrlson index ( 3/>3) 74/27 73/ /229 88/12 <0.001 Prior MI / Congestive hert filure / <0.001 Lung disese / Connective tissue disese / Renl disese / <0.001 Homologous trnsfusions 44 b /1526 b 17 <0.001 Autologous trnsfusions 54 b /497 b 73 <0.001 DM / <0.001 b Vlues do not dd up to the totl number of ptients (some dt were missing). p 415

5 index were significntly ssocited with infection s well s history of myocrdil infrction (MI), congestive hert filure, nd renl disese (Tbles 1 nd 2). Ptients who becme infected were more likely to hve hd homologous blood trnsfusions nd were less likely to hve hd utologous blood trnsfusions (Tble 2). Preopertive lbortory vlues ssocited with infection included higher cretinine nd blood ure nitrogen (BUN), higher INR, nd lower pltelet count. Significnt postopertive lbs included higher cretinine nd BUN, higher INR, nd higher white blood cell count (Tbles 1 nd 2). Anlysis of BG s continuous vlues showed tht ptients in the infected group were more likely to hve hd higher periopertive BG vlues. Ptients with PJI hd significntly higher preopertive BG (112 ± 36 versus 105 ± 31 mg/dl, p =.043) nd POD 1 BG (154 ± 37 versus 138 ± 31 mg/dl, p <.001). Ctegoricl nlysis of periopertive glucose vlues showed only significnt differences between groups on POD 1, but tken ll together, ptients with BG >200 mg/dl hve hd greter thn two-fold incresed rte of the infection (Tble 3). The infection rte of PJI nd fsting BG levels during totl hospitliztion ws lso sttisticlly significnt, p <.001 (Figure 1). Ptients in the infected group were lso more likely to hve prior dignosis of DM, p <.001 (Tble 2). In cross-sectionl nlysis, we compred the likelihood of developing PJI in ptients with low nd high BG vlues on POD 1 nd with or without DM. In non-dm ptients, high BG on POD 1 ws significntly ssocited with n incresed risk for the postopertive infection, p <.001 (Tble 4). There ws no ssocition between n incresed risk for infection nd high BG on POD 1 mong DM ptients. When we compred infection rtes for DM ptients with cutoff of 180 mg/dl, ptients with high BG hd 22% (8/37) infection rte compred to 9% (5/54) in ptients with low BG but did not rech sttisticl significnce (p =.23), possibly due to low number of ptients. Discussion Our retrospective study showed tht periopertive fsting BG incresed, by more thn two-fold, the risk of infection requiring surgicl intervention fter totl hip nd knee rthroplsty. Even ptients without dignosis of DM were three times more likely to develop the infection if their fsting BG on POD 1 ws >140 mg/dl. The study lso confirmed known risk fctors for the infection: incresed BMI, higher ASAPS score nd Chrlson index, history of MI, congestive hert filure or renl disese, longer durtion of the surgery nd longer hospitl sty, higher INR, nd homologous trnsfusions. Figure 1. The infection rte of PJIs nd fsting BG levels during totl hospitliztion. The sterisk represents p <.001 for >200 versus 100 mg/dl nd >200 versus mg/dl. p <.001 for trend. Tble 3. Ctegoricl Periopertive Fsting Glucose Vlues Glucose vlue Infected Noninfected 100 mg/dl mg/dl >200 mg/dl 100 mg/dl mg/dl >200 mg/dl Dy of surgery POD POD POD POD All (%) b 22 (15) 111 (78) 10 (7) 373 (18) 1668 (79) 58 (3) <0.001 b Vlue in prentheses is the percentge of ptients in ech BG ctegory in infected nd noninfected groups. p 416

6 Severl studies hve evluted risk fctors for infection fter hip nd knee replcement surgery. Dibetes mellitus s risk fctor for infection is controversil. Some studies hve found n ssocition between DM nd infection, 7 10 but some studies hve not The controversy might exist becuse the dignosis of DM ws used from the dischrge summries or becuse the studies were not powered enough to show the difference. More importntly, periopertive BG levels were not mesured in these studies. As our study showed, postopertive hyperglycemi my hve more influence on the prediction on the infection in non-dm ptients thn in ptients dignosed with DM (Tble 4). Hence periopertive BG levels my be more importnt thn dignosis of DM in prediction of the PJI fter hip nd knee rthroplsty. Indeed, in generl nd vsculr surgery ptients, postopertive hyperglycemi incresed the risk for postopertive infection independent of preopertive BG levels nd DM sttus. 6 Although our cohort of infected cses is mong the lrgest in which the risks for the postopertive infection fter totl hip nd knee rthroplsty were evluted, it might yet be underpowered to show the difference in BG level on every POD. But when ll fsting BG levels were tken together, hyperglycemi ws significntly ssocited with the infection, p <.001 (Tble 4). We used BG levels on POD 1 for cross sectionl nlysis since these vlues were the most complete in our dt set. Due to the smll number of DM ptients with the infection, we divided BG into only two ctegories. Although there ws trend for higher rte of infection in DM ptients if BG ws >180 mg/dl, it did not rech sttisticl significnce, probbly becuse of the smll number of ptients. Conversely, in non-dm ptients, the infection rte ws sttisticlly significnt if BG ws >140 mg/dl, p <.001 (Tble 4). Similr to our study, fsting BG vlues t 6:00 m on POD 1 nd POD 2 Tble 4. Cross-sectionl Anlysis Results with Postopertive Dy 1 Glucose Vlues DM No DM BG Infected/noninfected N (%) 140 mg/dl 3/22 (14%) >140 mg/dl 10/69 (14%) 140 mg/dl 20/582 (3%) >140 mg/dl 27/285 (9%) p 1 <0.001 <200 mg/dl re used for mesuring qulity control for surgicl site infection prevention fter crdic surgery in the Surgicl Cre Improvement Project, the Joint Commission on Accredittion of Helthcre Orgniztions performnce mesure set, nd the Ntionl Qulity Forum stndrds. A limittion of our study is its retrospective nture. All retrospective studies depend on the qulity nd vilbility of the dt nd the ccurcy nd completeness of the medicl records. Some ptients my be lost in follow-up, nd BG vlues might be missing from the dtbse. We used 2-yer follow-up period to increse the power of the study, but we did not hve dt on glycemic control during this period nor preopertive hemoglobin A1c vlues. Non-DM ptients who developed hyperglycemi during the periopertive period my not hve incresed BG lter in the recovery period. How mny ptients eventully develop DM if they hd periopertive hyperglycemi is unknown. We did not perform multivrite nlysis becuse of the low number of ptients with PJI nd BG vlues. Also, the number of BG vlues ws too smll to clculte BG vribility, which might be importnt since the vribility increses oxidtive stress nd triggers cogultion nd inflmmtion cscdes. 23 Finlly, lthough we limited our uninfected cohort to ptients with t lest one yer of known follow-up t our institution, it is possible tht we my hve missed some ptients who were operted on t nother institution. The strength of our study is tht it ws performed t high-volume orthopedic center tht hs strict periopertive protocols; s result, ptients received uniform infection precutions, ntibiotic prophylxis, nd thromboprophylxis. Additionlly, by including only ptients who developed PJI tht required opertive interventions, we defined our cohort to the group of cliniclly importnt infections tht re known to increse morbidity, mortlity, nd helth cre costs. Ptients with severe orthopedic postopertive infections hve substntilly greter physicl limittions nd significnt reductions in their helth-relted qulity of life. 2 Finlly, ll BG vlues used in the study were tested in the centrl lbortory. Point of cre mesurements were not used for the nlysis. The mechnism of how hyperglycemi might cuse postopertive infections hs been described elsewhere. 21 A review rticle reported tht the most obvious findings relted to hyperglycemi included reduced neutrophil ctivity (e.g., chemotxis, formtion of rective oxygen species, phgocytosis of bcteri) nd concluded tht 417

7 cute, short-term hyperglycemi ffects ll mjor components of innte immunity nd impirs the bility of the host to combt infection. 21 Our study suggests tht the gol of periopertive glycemic control fter orthopedic surgery should be <200 mg/dl on morning BG vlues to reduce incidence of PJI tht requires surgicl intervention. Controlling BG postopertively might be simple wy to reduce the rte of infection fter mjor orthopedic surgery. A prospective rndomized controlled study is needed to determine whether tight control of preopertive BG levels leds to decresed incidence of PJI in this clinicl setting. Conclusion Our study showed tht periopertive morning hyperglycemi >200 mg/dl incresed by more thn two times the risk of infection tht requires surgicl intervention fter elective totl hip nd knee rthroplsty. Even ptients without dignosis of DM hd three-fold incresed risk for the infection if fsting BG on POD 1 ws >140 mg/dl. References: 1. Kurtz S, Ong K, Lu E, Mowt F, Hlpern M. 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