A Propensity-Matched Cohort Study

Transcription

1 380 COPYRIGHT Ó 2014 BY THE JOURNAL OF BONE AND JOINT SURGERY, INCORPORATED Delaye Woun Closure Increases Deep-Infection Rate Associate with Lower-Grae Open Fractures A Propensity-Matche Cohort Stuy Richar J. Jenkinson, MD, MSc, FRCS(C), Alexaner Kiss, PhD, Samuel Johnson, MD, Davi J.G. Stephen, MD, FRCS(C), an Hans J. Kreer, MD, MPH, FRCS(C) Investigation performe at the Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canaa Backgroun: Primary closure of skin wouns after ebriement of open fractures is controversial. The purpose of the present stuy was to etermine whether primary skin closure for grae-iiia or lower-grae open extremity fractures is associate with a lower eep-infection rate. Methos: We ientifie 349 Gustilo-Anerson grae-i, II, or IIIA fractures treate at our level-i acaemic trauma center from 2003 to Eighty-seven injuries were treate with elaye primary closure, an 262 were treate with immeiate closure after surgical ebriement. After application of a propensity score-matching algorithm to balance prognostic factors, 146 open fractures (seventy-three matche pairs) were analyze. Results: After application of a propensity score-matching algorithm with ajustment for age, sex, time to ebriement, American Society of Anesthesiologists (ASA) class, fracture grae, evience of gross contamination, an a tibial fracture rather than a fracture at another anatomic site, the two treatment groups were compare with respect to the prevalence of infection. Deep infection evelope at the sites of three of the seventy-three fractures treate with immeiate closure (infection rate, 4.1%; 95% confience interval [CI], 0.86 to 11.5) compare with thirteen in the matche group of seventythree fractures treate with elaye primary closure (infection rate, 17.8%; 95% CI, 9.8 to 28.5) (McNemar test, p = ). Conclusions: Immeiate closure of carefully selecte wouns by experience surgeons treating grae-i, II, an IIIA open fractures is safe an is associate with a lower infection rate compare with elaye primary closure. Level of Evience: Therapeutic Level III. See Instructions for Authors for a complete escription of levels of evience. Peer Review: This article was reviewe by the Eitor-in-Chief an one Deputy Eitor, an it unerwent bline review by two or more outsie experts. It was also reviewe byan expert in methoologyan statistics. The Deputy Eitor reviewe each revision of the article, an it unerwent a final reviewbythe Eitor-in-Chief prior to publication. Final corrections an clarifications occurre uring one or more exchanges between the author(s) an copyeitors. Treatment stanars for open fractures require timely irrigation an aequate ebriement 1. Traumatic openfracture wouns traitionally have been left open after the initial ebriement in orer to minimize the risk of later eep infection, especially with Clostriium 2.Thistreatment strategy is trace to the experience of trauma surgeons from the pre-antibiotic era, especially uring Worl War I an Worl War II 3,4. Delaye woun closure until a few ays post-injury is currently avocate by many surgeons to allow rainage of any collecting infectious material an to allow for a universal seconlook ebriement 2,5. However, with avances in stabilization methos, antibiotics, an woun management, the strict avoiance of immeiate woun closure has been challenge, with several investigators reporting low infection rates 6-8. Immeiate woun closure after initial ebriement has the avantage of proviing immeiate soft-tissue cover to the traumatize limb as well as some protection against nosocomial pathogens 9. Also, subsequent visits to the operating room for secon-look ebriements may be avoie if immeiate closure is chosen, thereby simplifying an streamlining management of the traumatize patient. There are no clear guielines for etermining the time frame for safe closure of traumatic open fracture wouns, an Disclosure: None of the authors receive payments or services, either irectly or inirectly (i.e., via his or her institution), from a thir party in support of any aspect of this work. One or more of the authors, or his or her institution, has ha a financial relationship, in the thirty-six months prior to submission of this work, with an entity in the biomeical arena that coul be perceive to influence or have the potential to influence what is written in this work. No author has ha any other relationships, or has engage in any other activities, that coul be perceive to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitte by authors are always provie with the online version of the article. J Bone Joint Surg Am. 2014;96:

2 381 TABLE I Baseline Characteristics Variable Average age (yr) 40.7 Male sex* 240 (68.8%) ASA class >2* 66 (18.9%) ISS >25 points* 155 (44.4%) Gunshot mechanism* 28 (8.0%) Average injury to ebriement time (hr) Average injury to first antibiotic time (hr) 2.53 Tibial fracture* 148 (42.4%) Gross contamination* 140 (40.1%) Fracture grae* Grae I 53 (15.2%) Grae II 141 (40.4%) Grae IIIA 155 (44.4%) Primary closure* 262 (75.0%) Deep infection* 25 (7.2%) *Values are given as the number of patients, with the percentage in parentheses. this etermination is left to the jugment an experience of the treating orthopaeic surgeon. Higher-risk open fractures woul be expecte to have higher rates of more conservative woun management. We compare the rate of subsequent eep infection between patients in whom an open fracture ha been treate with immeiate primary closure after ebriement an those in whom the fracture ha been treate with elaye primary closure. Bias was reuce with use of a matche-pairs esign. We hypothesize that early woun closure woul reuce the rate of subsequent eep infection. Materials an Methos Consecutive patients treate for an open extremity fracture from January 1, 2003, to January 1, 2007, at our level-i trauma center were ientifie with use of our trauma atabase. Open han an pelvic fractures were exclue. We supplemente case ientification with the billing atabase of the central orthopaeic epartment with use of specific coing ientifiers for open fractures (E556 moifier). Meical recors were abstracte by two orthopaeic surgeons (R.J.J. an S.J.). We ientifie 417 patients who ha a total of 459 fractures. The inclusion an exclusion criteria are shown in Figure 1. Gustilo-Anerson grae- IIIB fractures usually are not amenable to primary closure an were exclue. Gustilo-Anerson grae-iiic fractures also were exclue because these injuries often are treate simultaneously with fasciotomies, for which skin closure is contrainicate. This left 345 patients with a total of 415 fractures. Thirteen patients ie from their traumatic injuries uring the inex hospital stay an were exclue, which left 332 patients available for follow-up. Complete follow-up was efine as twelve months, which was not achieve for thirtyeight patients (rate of complete follow-up = 89%). Our final cohort consiste of 294 patients with a total of 349 Gustilo-Anerson grae-i, II, or IIIA fractures. The collecte patient emographic characteristics inclue age, sex, an American Society of Anesthesiologists (ASA) class. The collecte injury variables inclue the injury severity score (ISS), evience of gross contamination of the fracture, the anatomic fracture location, an the time elay to surgery (efine as from ambulance call time to surgical start time). A Gustilo-Anerson grae 1,10 was assigne to the fracture on the basis of the surgical escription of the injury after ebriement. Gross contamination was ocumente if irt or foreign material was present. None of the wouns ha fecal or farmyar contamination or contamination with grass. The primary outcome measure for the present stuy was eep infection, efine as infection of the injure bone an eep tissue necessitating an unplanne operative irrigation an ebriement at more than two weeks after the injury. We chose a two-week cutoff in orer to aress the concern of whether an early ebriement was planne or unplanne. Planne repeat ebriements an superficial infections not requiring surgery were not consiere to be eep infections. All eep infections were treate with one or more surgical ebriements, possible implant removal, an/or skeletal stabilization. Initial characteristics of the injuries are shown in Table I. The stanar treatment protocol at our institution inclue intravenous antibiotics immeiately aministere on arrival in the emergency epartment an continue uring hospitalization until at least twenty-four hours after efinitive woun closure. Intravenous cefazolin was aministere, although clinamycin was use when a severe penicillin allergy was known. Gentamicin was ae for grae-iii open fractures. Debriements were performe urgently, Fig. 1 Patients inclue an exclue from the stuy.

3 382 TABLE II Characteristics of Woun Closure Treatment Groups Prior to Matching Variable Primary Closure (N = 262) Delaye Closure (N = 87) P Value Average age (yr) Male sex 66.7% 74.7% 0.17 ASA class >2* 58 (22.1%) 8 (9.2%) Average injury to ebriement time (hr) Average injury to first antibiotic time (hr) Tibial fracture* 104 (39.7%) 44 (50.6%) Gross contamination* 84 (32.1%) 56 (64.4%) Fracture grae* Grae I 49 (18.7%) 4 (4.6%) Grae II 112 (42.7%) 29 (33.3%) Grae IIIA 101 (38.5%) 54 (62.1%) Deep infection* 9 (3.4%) 16 (18.4%) *Values are given as the number of patients, with the percentage in parentheses. on the basis of availability of the operating room. Normal saline solution was use for irrigation, with gravity or pulse lavage use at the iscretion of the treating surgeon. Woun culture specimens were not routinely taken at the time of initial ebriement. Antibiotic choice, fixation metho, an woun closure were also at the iscretion of the treating physicians. Vacuum-assiste closure ressings were not use for any of these fractures. Secon-look ebriement after approximately forty-eight hours was performe routinely when elaye closure was chosen an was performe in patients who ha unergone primary closure when chosen by the treating surgeon on the basis of the impression of the aequacy of the ebriement. All statistical analyses were performe with use of SAS version 9.2 (SAS Institute, Cary, North Carolina) with input from a statistician (A.K.). To ajust for confouning by inication 11, a propensity-score 12,13 matche-cohort stuy was evelope from the original ata set (Table I). Injury characteristics were use in a logistic regression moel to preict the likelihoo of the nee for treatment with elaye woun closure. As eighty-seven patients were manage with elaye woun closure, up to eight egrees of freeom coul be specifie in the propensity score 14. Dichotomous an continuous variables use one egree of freeom each, whereas the three-level variable use two egrees of freeom. The factors consiere to be the most important confouners also contributing to eep-infection risk were chosen for the propensity-score algorithm. These factors inclue patient age, sex, time elay to ebriement, fracture grae (Gustilo-Anerson grae I, II, or IIIA), evience of gross contamination, tibial compare with nontibial site, an ASA class (1 or 2 compare with 3 or higher). These factors were chosen, base on consensus among the investigators, as the factors most important for preicting later infection but also as those most ivergent between the immeiate an elaye-closure groups (Table II). A one-to-one matching algorithm 15 wasusetopairinjurieswitha similar propensity for elaye woun closure. This algorithm searches for the most exact match available to eight ecimal places an then works back to one TABLE III Characteristics of Woun Closure Treatment Groups After Matching Variable Primary Closure (N = 73) Delaye Closure (N = 73) P Value Average age (yr) Male sex 76.7% 73.9% 0.70 ASA class >2* 7 (9.6%) 8 (11.0%) 0.78 Average injury to ebriement time (hr) Average injury to first antibiotic time (hr) Tibial fracture* 30 (41.1%) 33 (45.2%) Gross contamination* 44 (60.3%) 43 (58.9%) Fracture grae* Grae I 4 (5.5%) 4 (5.5%) 1.0 Grae II 22 (30.1%) 27 (37.0%) 0.38 Grae IIIA 47 (64.4%) 42 (57.5%) 0.40 Deep infection* 3 (4.1%) 13 (17.8%) *Values are given as the number of patients, with the percentage in parentheses.

4 383 Fig. 2 Comparison of major fracture characteristics between ifferent closure treatment groups prior to matching. ecimal place. The maximum ifference between propensity probabilities for matching was set at 0.1. Seventy-three matche pairs of patients were ientifie. Fourteen open fractures from the elaye-closure group were not paire because of a lack of a suitable similar injury from the immeiate primary-closure group with which to match them. These unpaire injuries were more severe, with higher open-fracture graes an more contamination. This process generate matche pairs with similar injury characteristics for analysis of the infection outcome. The results were analyze with stanar escriptive statistics for the baseline unpaire ata. Infection rates were compare between the paire cohorts with use of the McNemar test an conitional logistic regression. Source of Funing No external funing was receive for this stuy. Results Table II shows the fracture characteristics of the cohort of patients prior to matching. As expecte, patients manage with elaye woun closure ha fractures with more negative prognostic factors, incluing a higher proportion of grae-iiia fractures (p = ), tibial fractures (p = ), an gross contamination (p = ) (Fig. 2). The patients manage with elaye woun closure also ha a higher proportion of eep infection before matching (18.4% compare with 3.4%, p = ), but this is an invali comparison because of the selection bias that results in more severe injuries being preferentially treate with elaye woun closure. Fig. 3 Comparison of major fracture characteristics between ifferent closure groups after matching.

5 384 TABLE IV Infecting Organisms by Closure Group* Primary Closure Enterococcus faecalis Delaye Closure Staphylococcus aureus Staphylococcus aureus Staphylococcus aureus Coagulase-negative Staphylococcus Pseuomonas aeruginosa Pseuomonas aeruginosa Enterococcus faecalis Enterococcus faecalis Escherichia coli Gram-negative bacilli Mixe aerobic organisms Hafnia alvei Cania Negative culture in one patient * = methicillin-resistant Staphylococcus aureus. After the propensity score-matching algorithm was applie, there were seventy-three matche pairs of patients an fractures available for comparison (Table III). The two matche treatment groups showe similar characteristics among all of the elements of the propensity score, incluing fracture grae (p = 0.4), gross contamination (p = 0.87), an tibial fractures (p = 0.62) (Fig. 3). Patients with elaye closure ha routine secon-look ebriements, whereas planne secon-look ebriements were carrie out in fourteen (19%) of the seventy-three patients who ha unergone a primary closure. Deep infection evelope at the sites of three of the seventythree open fractures treate with primary closure (infection rate, 4.1%; 95% confience interval [CI], 0.86 to 11.5) compare with thirteen of the seventy-three fractures treate with elaye closure (infection rate, 17.8%; 95% CI, 9.8 to 28.5) (McNemar test, p = ) (see Appenix). This fining suggests an absolute risk reuction of 13.7% for evelopment of eep infection for the primary-closure group. This value correspons to a number neee to treat of 7.3 patients. Conitional logistic regression was also use to confirm the significance of this fining while accounting for paire ata. This yiele an os ratio of 11.0 (95% CI, 1.42 to 85.2) times more likely to evelop eep infection if elaye rather than primary closure was performe. No patient ha a Clostriium infection. The infecting organisms in each patient group are shown in Table IV. Discussion Current orthopaeic literature oes not provie clear irection to guie the choice between immeiate woun closure an the more traitional elaye techniques. A small ranomize trial 6 showe no increase in the rate of infection with primary closure. Primary closure has also been avocate by DeLong et al. 8, who reviewe 119 open fractures treate with either primary closure or elaye methos. They foun infection rates to be inepenent of closure technique an suggeste that primary closure after thorough ebriement is a viable option when carrie out by an experience surgeon. The eferral to surgical jugment is a common theme in the literature regaring this subject. Most orthopaeic surgeons woul not suggest that primary closure be performe for patients with persistent woun contamination with irt, feces, an nonviable tissue. Definitive closure of a woun without an aequate ebriement increases reoperation an infection rates. However, objective characterization of what makes a woun clean enough for primary closure is not available. Because more severe open fractures will be consiere not clean enough for primary closure, a selection bias will occur in retrospective stuies on this topic, incluing the current stuy prior to matching. There is confouning by inication when the treatment metho is chosen at least partially on the basis of the external prognostic factors that are associate with the injury 11.Inour stuy, higher-grae tibial fractures with a egree of gross contamination were more likely to be selecte for elaye-closure treatment. Because these more severe injuries carry a higher risk for eep infection, we cannot conclue that treatment with elaye closure leas to a higher likelihoo of infection without accounting for this confouning. Traitional matching for each iniviual variable is often too restrictive an oes not allow enough pairs to be create because of the constraints of fining an exact match for each variable. The benefit of a propensity score is that it allows matching for many ifferent factors by creating a composite probability of receiving a particular treatment in the present stuy, either primary or elaye closure. Propensity-score matching is a metho of balancing treatment groups base on known confouning variables an is particularly suite to account for confouning by inication 12. In the current stuy, the patients manage with elaye closure were matche with patients who ha a similar severity of injury. After matching, similar groups of patients an injuries were available for comparison. This creates a pseuo-ranomize or quasi-ranomize stuy 12 in which the two treatment groups can be effectively matche accoring to the known prognostic factors that inform the propensity score. However, this metho can control only for known factors that are inclue in the algorithm. Propensity score-matching techniques are referre to as pseuo-ranomize because matching of treatment groups for all nontreatment variables is possible in only a prospective, truly ranomize stuy. A higher infection rate was foun among the fractures treate with elaye closure, even after we accounte for important prognostic factors, incluing contamination, fracture grae, an anatomic location. This fining suggests that primary closure is safe an actually may be preferable to elaye closure for selecte lower-grae open fractures. Infection rates may be ecrease when primary closure is employe for these carefully chosen injuries. The elimination of

6 385 an automatic secon-look ebriement for all open fractures has the potential for streamlining patient care an for large cost-savings. The present stuy shoul be interprete with its limitations in min. A propensity score is a valuable tool to use to balance groups on the basis of known confouning variables. A limitation of this technique is that unknown or nonmeasurable variables cannot be accounte for. An experience trauma surgeon will use many ifferent injury an patient characteristics often unconsciously an intuitively to make an informe ecision about woun management. A ranomize trial remains the gol stanar, as it allows balance treatment groups that are base on both known an unknown confouning variables. Aitionally, the ata use in the present stuy were collecte retrospectively. Complete initial an follow-up ata were available for 89% of the possible patients who coul have been examine. Efforts were mae to efine the injury an outcome variables as objectively as possible in orer to minimize classification errors; however, some inaccuracy is inevitable in a retrospective stuy. Not all meical ata were easily obtaine via chart review; for example, smoking status was inconsistently recore an thus was not a useful variable for ata analysis. The ASA grae was use as an inicator of meical frailty but oes not provie a complete picture of the patient s meical status. Time to first antibiotic ose was similar between treatment groups (Table II). We i not inclue this variable in the propensity-score algorithm because we ha to select the most important variables that inicate a ifference between treatment groups. Time to ebriement was inclue in the propensity-score algorithm because it was a major factor that iffere between treatment groups. This suggests that, for the surgeons at this institution, elay to surgery likely was a consieration for choosing elaye rather than primary closure. However, the ata presente in this paper o not irectly support or refute elay to surgery as an important factor in the evelopment of infection after open fracture. Defining a superficial infection is ifficult with these retrospective ata, especially because many patients are given oral antibiotics for various inications. Early antibiotic treatment alone may suppress an elay but will not usually eliminate a eep infection. This is why eep infection was chosen as our primary outcome of interest. All eep infections were treate with surgical ebriement(s), possible implant removal, an/ or skeletal stabilization. Some infections that were exclue as being superficial actually may have been eeper infections that resolve without surgical ebriement. The Gustilo-Anerson classification scheme has limitations in terms of interobserver variability 16 ;however,itisthemost frequently use classification scheme in current practice. Although newer schemes are in evelopment 17,theGustilo- Anerson classification remains the most useful tool currently available to characterize open-fracture severity. The chart abstractors in our stuy both were experience orthopaeic surgeons (an orthopaeic trauma fellowship-traine surgeon [R.J.J.] an a trauma fellow with more than five years of community experience [S.J.]), which helpe to improve the interpretation of the clinical variables. Treatment was not stanarize, an iniviual surgeons mae choices regaring primary closure an many other treatment variables. Also, the follow-up time to etermine whether an infection was present was one year. Posttraumatic infections can be relatively quiescent an may not present for longer times. We acknowlege that a longer uration of follow-up may result in more infections presenting at a later follow-up interval. The patients were all treate at a level-i acaemic trauma center. All participating clinicians ha an interest in orthopaeic trauma an woul be expecte to have ha sufficient clinical experience to perform aequate initial ebriements. This may help to explain why few eep infections were foun among patients manage with primary closure without secon-look ebriement. Surgeons with less experience in open fracture management may be more likely to perform insufficient ebriements, possibly leaing to complications from immeiate closure. Also, the more severe (grae-iiib an grae-iiic) injuries were exclue from the current stuy. Generalization of the stuy finings to more severe injuries an those not treate with aequate initial ebriement is not warrante. It shoul also be state that patients with fasciotomies or those who are at high risk for eveloping compartment synrome shoul not unergo primary woun closure. Primary closure was chosen for several patients even when a secon-look ebriement was planne, which may have restore some egree of skin barrier to nosocomial contamination (Table IV). Negative-pressure woun therapy an bea pouch techniques were not employe in this cohort. Future work in this area shoul consist of prospective stuies preferably large, ranomize trials. Sample-size calculations for potential ranomize trials must be base on previous finings so that potential effects can be estimate, an the present stuy provies some such finings. Aitional work is require in orer to ientify the particular injury factors that allow for safe primary closure. Surgeon jugment regaring the aequacy of ebriement an woun closure is still paramount in the treatment of open fractures; however, primary closure may be preferable for carefully selecte low-grae injuries. Patients must be monitore closely, regarless of closure type, in orer to assess for a surgicalsite infection an to institute timely treatment. Appenix A figure comparing the infection rates between the matche treatment groups is available with the online version of this article as a ata supplement at jbjs.org. n Richar J. Jenkinson, MD, MSc, FRCS(C) Alexaner Kiss, PhD Samuel Johnson, MD Davi J.G. Stephen, MD, FRCS(C) Hans J. Kreer, MD, MPH, FRCS(C) Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Suite MG-321, Toronto, ON M4N 3M5, Canaa. aress for R.J. Jenkinson: richar.jenkinson@sunnybrook.ca

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