The Journal of Arthroplasty Vol. 27 No. 5 2012

A Pilot Study of Computed Tomography–DetectedAsymptomatic Pulmonary Filling Defects After

Hip and Knee Arthroplasties

From thDepartmenToronto, ToHealth Scie§Division oToronto, To

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399 Bathu© 20120883-5doi:10.1

Rajiv Gandhi, MS, MD,* David Salonen, MD,y William H. Geerts, MD,zMonica Khanna, MRCS, FRCR,y Sean McSweeney, MB, BCH, BAO, FFRRCS,y

and Nizar N. Mahomed, MD, ScD§

Abstract: We asked what the incidence of asymptomatic filling defects is on routine multidetectorcomputed tomography (MDCT) in primary hip (total hip arthroplasty [THA]) and kneearthroplasties (TKA) patients. We prospectively performed MDCT scans on the first postoperativeday for THA (n = 21)/TKA (n = 27). Patients underwent routine postoperative care, and data werecollected for symptoms such as tachycardia or shortness of breath. More patients undergoing TKAhad positive computed tomography scans than those undergoing THA: 11 (41%) vs 1 (5%),respectively. All patients diagnosed with a filling defect were discharged from the hospital withouttreatment of symptomatic pulmonary embolism. Our study demonstrates a high rate of abnormalMDCT early after lower extremity arthroplasty, the clinical importance of which may be benign.Keywords: pulmonary embolism, hip arthroplasty, knee arthroplasty.© 2012 Elsevier Inc. All rights reserved.

Despite the routine use of thromboprophylaxis, theincidence of symptomatic and fatal pulmonary embo-lism (PE) after arthroplasty are approximately 1.0% and0.1%, respectively [1,2]. The diagnosis of PE hassubstantial implications for the patient, including pro-longed anticoagulation, possible insertion of an inferiorvena cava filter, and the long-term impact on future carerelated to having this diagnosis [3,4].Some centers have reported an increasing incidence of

PE, perhaps attributable to a greater number of imagingtests being ordered combined with the greater sensitivityof the newer diagnostic tools [2,3,5]. For decades, theventilation/perfusion (V/Q) scan was the imagingmodality of choice for patients with suspected PE. Ahigh-probability V/Q scan has a positive predictive valueof at least 85% for a diagnosis of acute PE [6]. However,in most patients, the V/Q scans are nondiagnostic and

e *Toronto Western Hospital, Toronto, Ontario, Canada; yJointt of Medical Imaging, University Health Network, University ofronto, Ontario, Canada; zDepartment of Medicine, Sunnybrooknces Centre, University of Toronto, Toronto, Ontario, Canada; andf Orthopedic Surgery, University Health Network, University ofronto, Ontario, Canada.ted July 11, 2011; accepted October 17, 2011.nflict of Interest statement associated with this article can beoi:10.1016/j.arth.2011.10.019.requests: Rajiv Gandhi, MS, MD, Toronto Western Hospital,rst St, EW 1-439, Toronto, Ontario M5T 2S8, Canada.Elsevier Inc. All rights reserved.

403/2705-0012$36.00/0016/j.arth.2011.10.019

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lack the ability to evaluate for other etiologies to accountfor a patient's clinical symptoms (such as pulmonaryedema or pneumonia) [7].More recently, computed tomography (CT) pulmonary

angiography (CTPA) has replaced V/Q scanning toinvestigate suspected PE because of substantially in-creased specificity (∼73%-86% in the larger arteries [8]),much shorter testing time, and the potential to diagnosealternate causes for the patients' symptoms [7,9,10].Multidetector CT (MDCT) has the capability of rapidscanning with improved spatial resolution to thesubsegmental pulmonary artery level [11-13]. Afterarthroplasty in more than 13 000 patients, 1 group hasreported an increasing incidence of symptomatic PE,from 0.21% when V/Q scans were used to 0.98% withearly generation CT imaging and to 1.72% with the useof MDCT despite a stable mortality rate [2]. Theimportant clinical dilemma is to understand whichCTPA findings require therapeutic anticoagulation andwhich patients can be managed with continuation oftheir usual thromboprophylaxis only.The diagnosis of acute PE in the arthroplasty popula-

tion is particularly challenging. Although the pretestprobability of PE substantially affects the interpretationof PE imaging [8], the relevance of transient tachycardiaand dyspnea in these patients is unclear because theirpredictive values have not been specifically assessed afterarthroplasty [5,14]. The incidence of hypoxemia aftersurgery reportedly ranges from 4% to 42% [15,16]. A

Asymptomatic Filling Defects and Arthroplasty � Gandhi et al 731

model useful for predicting clinical PE in the generalmedical population is apparently not useful in thearthroplasty population [17,18].Our primary objective was to determine the incidence

of asymptomatic filling defects in the early postopera-tive period for patients undergoing knee and hiparthroplasties. Our secondary objectives were to iden-tify any demographic or surgical technique predictors ofthose patients diagnosed with a filling defect and also toreport on the incidence of symptomatic PE in ourcohort. We hypothesized that a high proportion ofpatients undergoing arthroplasty would be diagnosedwith an asymptomatic filling defect, equal across both hipand knee patients.

Patients and MethodsFrom a single, high-volume arthroplasty center, we

recruited 50 patients on a waiting list for primaryunilateral total hip (THA) or knee (TKA) arthroplastyto participate between February and July 2009. Allpatients had a diagnosis of primary hip or kneeosteoarthritis as defined by the American College ofRheumatology criteria [19].We excluded patients with ahistory of thromboembolic disease, hematologic orknown coagulation abnormality, contrast allergy, creat-inine clearance less than 30 mL/min, or a history ofsevere respiratory disease. Of the 50 selected patients, 2did not have an early MDCT: 1 developed angioedemaduring contrast injection, was treated with antihista-mines and supportive oxygen, and remained stable froma cardiorespiratory perspective and another had a smallvolume of contrast accidentally injected into the inter-stitial space of her forearm, which resolved with ice andcompression bandaging. This left 48 patients: 27 havingTKA and 21 having THA.This study was designed to provide preliminary data to

generate further hypotheses. Therefore, an a prioripower analysis was not performed.Demographic data of age, sex, and body mass index

(BMI) were collected. Medical comorbidity was col-lected using the self-administered comorbidity measure[20]. Patients undergoing TKA were older, heavier,and more likely to be women than patients undergoingTHA (Table 1).All patients had a chest radiograph before surgery as

part of the medical workup, and those with confirmedlung tumors were excluded. The consent process wasperformed by an independent study coordinator (PT)

Table 1. Demographic Data in the Study Patients

Knee Patients(n = 27)

Hip Patients(n = 21) P

Mean age, y (SD) 61.8 (8.4) 55.1 (15.2) .03Males, % 41 67 .06Mean BMI, kg/m2 (SD) 34.9 (9.3) 28.9 (5.8) .006Comorbidity (SD) 6.9 (2.7) 6.4 (3.2) .44

not involved in the medical care or outcome assessmentof the patients. In particular, patients were told of theincreased radiation and contrast exposure associatedwith CTPA. The radiation dose of the scan was estimatedat 6.0 to 8.0 mSv [21], and the slightly elevated long-term cancer risks were explained to the patients. Giventhat the risk of cancer induction to breast tissue isgreatest in those aged 40 years and younger, we did notrecruit any women younger than this age threshold. Thestudy protocol was approved by the human subjectsreview committee of the hospital.All patients had their surgery performed during 2009

by 1 of 3 fellowship-trained arthroplasty surgeons (KS,NM, and JRD). All patients had a hypotensive spinalanesthetic for THA and hypotensive spinal anestheticcombined with continuous femoral nerve block analge-sia for TKA. All hip surgeries were performed withuncemented implants. Knee surgery was performedwith use of a tourniquet and fully cemented implants.Intramedullary guides for femoral alignment were usedin 100% of patients, whereas intramedullary guides fortibial alignment were used in 74% of patients.All patients received low-molecular-weight heparin

for thromboprophylaxis starting on the morning of thefirst postoperative day (POD) for a total duration of 10days after knee surgery and 21 days after hip surgery,per the American College of Chest Physicians recom-mendations [22]. No patient received additional me-chanical prophylaxis with intermittent pneumaticcompression devices, foot pumps, or stockings. Allpatients were placed on nasal oxygen postoperativelyand weaned over a 24-hour period, and all patients wereprovided with and encouraged to use incentive spirom-etry devices. All patients were encouraged to mobilizewith physiotherapy assistance starting on POD 1.Postoperative data collection included chest pain,

shortness of breath, tachyarrhythmia, hypoxemia (de-fined as a pulse oximetry reading b90%), or fever at anytime until discharge from acute care (ranging from 3 to 6days). The results of electrocardiogram or arterial bloodgases were recorded if they were obtained.All CTPA examinations were performed between 24

and 36 hours after surgery using a threshold-triggeredregion of interest in the main pulmonary artery using astandard technique. The examinations were performedon a 64-row MDCT unit (Aquilion; Toshiba MedicalSystems, Markham, Ontario, Canada). For all studies,volumetric acquisition was performed during arrestedinspiration, from the lung apices to the costophrenicangles, using 120-kVp 350-mA 0.5-second rotation time.All studies were reconstructed with a 1-mm slicethickness. Coronal reformats (1 mm) were provided forall cases. Nonionic iodinated contrast agent (270 mg/L)was injected at a rate of 5 mL/s using 60 to 100 mLdepending on patient size. Computed tomographyvenography was not performed in conjunction with the

Table 2. Distribution of Asymptomatic Filling Defects

Knee Patients11 Asymptomatic PE

Location of LargestFilling Defect

Total ClotBurden

Main pulmonary artery 1 1Lobar artery 5 6Segmental artery 5 11Subsegmental artery 0 7

Table 3. Demographic Covariates Compared Between ThoseDiagnosed With an Asymptomatic Filling Defect on Imagingand Those Without

Asymptomatic FillingDefects (n = 12)

Negative Scans(n = 36) P

Mean age, y (SD) 62.2 (8.0) 56.6 (12.6) .14Males, % (n) 58 (7) 56 (20) .85Mean BMI (SD) 30.3 (4.3) 32.4 (9.1) .42Comorbidity (SD) 7.0 (2.3) 6.6 (3.1) .65TKA/THA 11/1 16/20 .004

732 The Journal of Arthroplasty Vol. 27 No. 5 May 2012

chest CTs. The scans were all performed under anony-mous study identification numbers, were not available tothe clinical team, and were not interpreted until the lastpatient had enrolled. If patients developed a clinicalsuspicion of PE during their postoperative hospital stay,they underwent standard investigations, which mayhave included further CT scans; however, the asymp-tomatic scan remained blinded until study completion.Scan quality was assessed because motion artifact andflow-related phenomena can mimic acute PE. Multi-planar reconstructions were used to help discern truefindings from flow-related phenomena.All MDCT scans were read at completion of study

enrollment and were independently evaluated by 2fellowship-trained chest radiologists (SM and MK) usinga standard reporting form. Any discrepancies betweenreadings were resolved through consensus with a thirdchest radiologist (DS). All scans were read for thepresence of intraluminal filling defects consistent withacute PE and for the arterial distribution of these defects.Acute PE was defined as an intraluminal filling defectwith or without an expanded vessel. Other findings suchas a dilated right ventricle, parenchymal infarcts,atelectasis, pulmonary edema, and pneumonia werealso recorded. Interobserver κ correlations with 95%confidence intervals were calculated for the outcome ofacute PE between the 2 scan readers. The coefficient ofagreement was excellent at 0.89 (95% confidenceinterval, 0.74-1.0).We compared the incidence of filling defects between

TKA and THA with the Fisher exact test. We evaluatedfor possible predictors of asymptomatic filling defectson MDCT, including age, sex, BMI, comorbidity,procedure (hip vs knee), and number of long bonescannulated (knees). Categorical data for this compar-ison (age and procedure) were analyzed with theFisher exact test, whereas continuous data (age, BMI,and comorbidity) were compared with the nonpara-metric Mann-Whitney U test. It should be noted thatthe study was not powered based on these comparisonsand that the reader should evaluate data for clinicaldifferences rather than relying on P values alone. Thestatistical analyses were performed with SPSS version13.0 (SPSS Inc, Chicago, Ill).

ResultsAll of the early scanswere of adequate technical quality

for interpretation. Among the 27 patients undergoing

TKA, 11 (41%) had chest scans that were read as positivefor 1 or more filling defects. None of these patients hadsymptoms suggestive of PE before the scans. During theremainder of the acute care stay for these 11 patients, 2had a low-grade fever on POD 1, 2 developed unsus-tained supraventricular tachycardia on POD 2, 1 devel-oped mild hypoxemia on POD 2, and 1 had chest painthat led to an electrocardiogram and cardiac enzymedetermination. Three patients had excessive leg swellingand underwent whole-leg Doppler scans that were readas negative for deep vein thrombosis. None of these 11patients required subsequent chest scans, and none werediagnosedwith symptomatic deep vein thrombosis or PE.Among the 11 patients undergoing TKA diagnosed withearly PE, the prevalence of fever, chest pain, andhypoxemia was similar to the 16 patients with negativeearly scans. The largest filling defect was in the mainpulmonary artery in 1 patient, a lobar artery in 5 patients,and a segmental artery in 5 patients (Table 2).Within theknee cohort, the incidence of filling defects was 9 (45%)of 20 for those patients whose surgery was performedwith cannulation of both the femoral and tibial canals.For those patients having just the femoral canalcannulated, the incidence of filling defects on imagingwas 2 (29%) of 7.Among the 21 patients undergoing THA, 1 (5%) had a

chest scan that was read as positive for a filling defect.This patient remained asymptomatic from a cardiore-spiratory perspective during the acute hospital stay. Inthe remaining 20 patients, no patient had chest pain, 1had shortness of breath on POD 2, 5 had unsustainedsupraventricular tachycardia, 2 had transient hypoxemicevents, and 9 had a fever. The single patient with earlyasymptomatic PE demonstrated filling defects in thelobar, segmental, and subsegmental arteries.Symptomatic PE was diagnosed in 1 patient (4%)

undergoing TKA and in none of the patients undergo-ing THA. Overall, this represents a 1.7% (1/48)symptomatic PE rate. The single patient with symp-tomatic PE on POD 2 after TKA had a negative study-related scan 12 hours earlier. This patient had pleuriticchest pain with tachycardia prompting CT investigation.He was then treated with therapeutic anticoagulationand had an uneventful recovery. At the 3-monthfollow-up, all patients were alive, and no additional

Table 4. Summary of Studies Reporting Asymptomatic PE After THA and TKA

Authors Year of Publication Study Population Diagnostic Tool Asymptomatic PE (%)

Dorr et al [24] 1979 25 THA V/Q and PA 4Guyer et al [25] 1982 184 THA PLS 6.4Harris et al [26] 1984 73 THA Radiolabeled V/Q 19Westrich et al [27] 1984 475 TKA V/Q 6.1Foley et al [28] 1989 228 THA V/Q 2.0

175 TKA 4.6Balderston et al [29] 1989 1392 THA V/Q 2.1Parmet et al [30] 1990 159 THA V/Q 10.7Wolf et al [31] 1992 736 THA V/Q 4.0Haas et al [32] 1992 1257 TKA V/Q 3.6Miniati et al [14] 1992 1344 THA V/Q 3.1 combined

1004 TKAMoriyama et al [33] 1996 133 THA V/Q 18.3 combined

179 TKADahl et al [23] 1997 308 THA V/Q 12.1Kim and Kim [34] 2002 227 TKA PLS 0Kim et al [35] 2003 300 THA PLS 0Gandhi et al 27 TKA MDCT 25 combined

21 THA

PLS indicates perfusion lung scan; PA = pulmonary angiography.

Asymptomatic Filling Defects and Arthroplasty � Gandhi et al 733

patients were diagnosed with deep vein thrombosis orPE. Patients who had abnormal MDCT results werefollowed up with consultation from an internist as aprecautionary measure.There were no demographic differences, other than

the surgical procedure itself between those with andwithout asymptomatic filling defects onMDCT (Table 3).

DiscussionCoupled with the high sensitivity of MDCT and the

greater volume of tests being ordered, the reportedprevalence of PE is increasing in this population [2]. Ourstudy demonstrated that 41% of asymptomatic patientsundergoing TKA and 5% of patients undergoing THAhad an abnormal MDCT 24 to 36 hours after surgery.Our study has several limitations. First, the radiologists

reading the scans were aware that patients wereasymptomatic at the time of the scan. However, this islikely to bias the interpretation away from a diagnosis ofPE and could underestimate the filling defect rate.Second, the sample size is small, particularly withrespect to clinical outcomes in patients who hadasymptomatic filling defects and were not treated.Regardless, the strength of the findings highlights asignificant clinical problem of early asymptomatic fillingdefects. Third, the actual histologic cause of the fillingdefects could not be determined; however, the findingsremain relevant as the radiologist would have called a PEhad the patients been symptomatic. Fourth, the asymp-tomatic scans were done 24-36 hours after surgery,which is possibly earlier than when patients becomesymptomatic with a true PE. However, our study addsvaluable knowledge as to what a chest scan would revealshortly after surgery.

One study [23] performed routine imaging forasymptomatic PE after joint arthroplasty using low-molecular-weight heparin for thromboprophylaxis butnone using MDCT. As compared with the other articlesreviewed, our 41% incidence of abnormal scans inpatients undergoing TKA is substantially higher. Our 5%rate in those undergoing THA is consistent with whatothers have shown (Table 4).The difference in abnormal MDCT findings between

hip and knee surgeries is substantial (P = .004). Thereported symptomatic PE rates after these surgeries havegenerally been similar [27,36-39], although somestudies suggest greater rates of PE in patients undergoingTKA [5,40]. Recently, among 683 patients undergoingarthroplasty, the rates of symptomatic PE were 4.6%after TKA compared with 0.4% after THA, whereas deepvein thrombosis (DVT) rates were similar [5]. In 67% ofthe patients diagnosed with PE, the most proximalembolus was at the segmental level in 67%. Onepotential explanation for the greater rate of abnormalMDCT findings in our knee cohort as compared with thehip cohort relates to the use of a tourniquet [30,41].Some authors have suggested a thrombogenic process iscreated from the venous stasis and intimal wall damagecreated with tourniquet use [41]. A second explanationis based on findings of transesophageal echocardiogra-phy (TEE) studies that have shown fat embolic loads aregreater after cemented TKA as compared with unce-mented THA [21,33,42], and it is possible that thisadditional embolic load contributes to pulmonaryperfusion defects that are similar to thromboembolic PE.Within TKA surgery, we found that the incidence of

filling defects was greater when both the femoral andtibial canals were cannulated as compared with just one.

734 The Journal of Arthroplasty Vol. 27 No. 5 May 2012

This is consistent with the findings of less cardiac embolicload with computer-assisted surgery and avoidance ofbone cannulation [43]. Our findings, however, do notresolve the controversy of whether the imaging findingsrepresent thrombus, marrow contents, or both. Onegroup performed pulmonary artery and femoral veinaspirations immediately after tourniquet release forpatients undergoing TKA. Of the 10 blood samples fromthe pulmonary artery, only 1 demonstrated freshthrombus as compared with 5 of 10 femoral vein samples[44]. This finding suggests that the embolic load seen inthe early postoperative period on TEEmay not all be clots.We believe that our findings emphasize the impor-

tance of having appropriate thresholds for the investi-gation of possible PE in patients undergoing arthroplastyand having a diagnostic algorithm to assist the clinicianin the diagnostic workup and management of thesepatients [2]. The Prospective Investigation of PulmonaryEmbolism Diagnosis II study demonstrated that thediagnostic accuracy of MDCT was strongly dependent onthe pretest probability and on the extent of theabnormalities found [8]. For example, only 38% ofMDCT scans that read positive for PE actually had PE.Similarly, 39% of patients with a high clinical probabilityof PE but a CTPA reported as “negative” actually had PE.With newer generation CT scans, the frequency of

finding smaller abnormalities that are labeled as PE isincreasing [13]. Therefore, it appears that technology isdefining a new subset of patients without evidence thattreatment provides benefit to the patients so identified.Most filling defects found in our study were in thesegmental and subsegmental arteries of the lung. Howev-er, 6 patients had filling defects in the main or lobarpulmonary artery. A recent review of patients withisolated subsegmental PE concluded that they have lessdyspnea and are less likely to have a proximal DVT ascompared with those with a segmental or more proximalperfusion defect (3.3% vs 43.8%, respectively) [45]. Eyerand Goodman [46] followed up a cohort of 131 patientswith either an isolated subsegmental filling defect orindeterminate finding on MDCT who were not antic-oagulated but were followed up clinically and comparedtheir outcomes with 61 patients treated with anticoagula-tion for the same diagnosis. There were no recurrentvenous thromboembolism (VTE) events in either group.In conclusion, a substantial proportion of asymptom-

atic patients undergoing arthroplasty had pulmonaryartery filling defects on early MDCT. These abnormalitieswere seen 8 times more commonly in patients under-going TKA than in patients undergoing THA. In majororthopedic surgery, imaging for PE is being done withincreasing frequency because of a combination ofincreased awareness of VTE as a complication of theseprocedures and the ease of obtaining CT scans. Ourfindings emphasize that the importance of a need for avalidated, diagnostic algorithm to assist clinicians deter-

mine the need for ordering imaging [2]. Furthermore,there is a need for studies in which postoperativepatients with small filling defects are randomized totreatment or not and then followed up to determine ifthere is any clinical benefit (or harm) associated withtreating these findings.

AcknowledgmentsThe authors thank Ms Peggy Tso, the project coordi-

nator, for her role in study organization and consentingof patients. The authors also thank Dr Khalid Syed andDr J Rod Davey, arthroplasty surgeons, who contributedpatients to this study, participated in study design, andalso reviewed the final manuscript.

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