癌患者外周静脉置入中心静脉导管上肢静脉血栓形成的危险因素分析

Original Contribution

Upper Extremity Venous Thrombosis in Patients With Cancer With Peripherally Inserted Central Venous Catheters:

A Retrospective Analysis of Risk Factors

By Daniel H.Ahn,DO,Henrik Bo Illum,MD,David H.Wang,MD,Anant Sharma,MD,

and Jonathan E.Dowell,MD

University of Texas Southwestern Medical Center;and Dallas Veterans Affairs Medical Center,Dallas,TX

Abstract

Purpose:Peripherally inserted central catheters(PICCs)are often used in place of mediport catheters because of cost and lack of operating room time and to prevent delays in therapy.One common complication associated with their use is upper extrem-ity venous thrombosis(UEVT).The purpose of this study was to ascertain risk factors associated with an increased risk of PICC-associated UEVT in patients with cancer.

Methods:Retrospective analysis identi?ed237patients with cancer who received PICCs at the Dallas Veterans Affairs Medi-cal Center from2006to2009.We analyzed many risk factors, including PICC infection(PI),use of erythropoiesis-stimulating agents(ESAs),antiplatelet agents(APAs),treatment dose anti-coagulation(TDA),and bevacizumab.Results:Of237patients,36(15%)were found to have UEVT. Stepwise logistic regression analysis showed risk factors posi-tively associated with UEVT were use of ESAs(odds ratio[OR], 10.66;95%CI,2.25to50.49),hospitalization(OR,2.38;95%CI, 1.05to5.39),PI(OR,2.46;95%CI,1.03to5.86),and TDA(OR, 8.34;95%CI,2.98to23.33),whereas patients receiving APAs had a lower risk of UEVT(OR,0.25;95%CI,0.07to0.92). Conclusion:Speci?c factors signi?cantly increase the risk of UEVT in patients with cancer with PICCs,whereas use of APAs seems to have a protective effect against UEVT.These results may aid in the development of a predictive model for identifying patients at high risk of UEVT who may bene?t from APAs,as well as in determining preventive strategies for reducing the risk of PICC-associated UEVT.

Introduction

The advent of central venous catheters(CVCs)has had a sig-ni?cant impact in medicine,as increased numbers of patients require long-term venous access for intravenous antibiotics, ease of blood draws,chemotherapy,nutrition,and analgesia.1It is estimated that in the United States,more than5million CVCs are inserted annually,with approximately15%of them being in patients with cancer.2Frequently,central access is pro-vided through peripherally inserted central catheters(PICCs). PICCs offer several advantages over other CVCs because they can be inserted at the bedside without the need for a surgical procedure or operating room.In addition,they are more cost effective,and their relative ease of placement prevents delays in therapy.3-5Unfortunately,one common complication with the use of long-term venous catheters is upper extremity venous thrombosis(UEVT).The incidence of catheter-associated asymptomatic UEVT has been reported to be as high as66%.1,6 Although most cases are asymptomatic and of uncertain clinical signi?cance,UEVT can have a signi?cant impact on a patient’s health care.Catheters that have lost functioning often need to be replaced at an average cost of approximately$5,000 and can lead to serious morbidity,including recurrent UEVT,postphlebitic syndrome,and pulmonary embo-lism.7-9The incidence of UEVT in patients with cancer has been reported to be from0.3%to28.3%,but the data on PICC-related UEVT in patients with cancer are limited.10 The purpose of this study was to ascertain and identify which factors are associated with PICC-associated symptomatic UEVT in patients with cancer.

Methods

The Dallas Veteran Affairs(VA)Medical Center(DVAMC)is a544-bed referral center for the VA North Texas Health Care System.We conducted a retrospective study identifying all pa-tients with cancer in both the ambulatory and inpatient settings who received PICCs at the DVAMC during a4-year span from January1,2006,to December31,2009.This study was ap-proved by the institutional review board of the DVAMC.We acquired data by identifying patients using the VA electronic medical record database in addition to the PICC service ar-chive.A member of the PICC nursing team inserted all PICC lines.A speci?c protocol was implemented by the VA for PICC insertion to minimize complications,entailing the use of ultra-sound for placement and sterile barrier precaution to minimize infections,which was documented in the VA electronic medical record system.The position of the tip of the PICC in the superior vena cava was con?rmed by chest x-ray by a physician in the radiology department.In the4-year period,237patients with cancer received PICCs.Risk factors investigated include: age,WBC,platelet count,ethnicity,catheter size(diameter), number of lumens,use of capecitabine/?uorouracil(FU),loca-tion of the tip of the catheter,PICC-associated infection,prior CVC,use of erythropoiesis-stimulating agents(ESAs),use of antiplatelet agents(APAs),solid versus hematologic malig-

Health Care Delivery

nancy,stage of cancer,chemotherapy,radiotherapy treatment, hospitalization,use of prophylactic dose versus treatment dose anticoagulation,and if the patient was receiving bevacizumab. Patients were categorized as receiving capecitabine/FU if these drugs were administered after PICC placement.Chemotherapy was de?ned as patients who received chemotherapy after PICC insertion,and radiotherapy as patients receiving concurrent ra-diation treatment.All laboratory results were obtained on the day before or the day of PICC insertion.We de?ned a PICC-related infection as a positive blood culture either from the catheter segment or peripheral blood in patients with clinical symptoms of bacteremia and no other apparent source of infec-tion.Hospitalization was de?ned as any23-hour stay for obser-vation or inpatient admission for more than23hours. Prophylactic dose anticoagulation was de?ned as unfraction-ated heparin5,000units subcutaneously three times per day, dalteparin5,000units subcutaneously daily,or enoxaparin40 mg subcutanously daily.Patients with symptoms concerning for UEVT underwent Doppler ultrasound of the affected ex-tremity for evaluation.?2or Fisher’s exact tests were conducted

to examine association between UEVT and categorical risk fac-tors.Also,t-tests were performed to examine association be-tween UEVT and continuous risk factors.Stepwise logistic regression analysis was conducted to identify signi?cant inde-pendent risk factors associated with UEVT,using risk factors with P values?0.2from univariate analyses.

Results

During the4-year investigative period,a total of237patients with cancer received PICCs.The demographic pro?le of the 237patients is listed in Table1,with baseline characteristics listed in Table2.Overall,the patient population included229 men and eight women,with a mean age of64.09years(range, 39to86years).Within a month of PICC insertion,180pa-tients received chemotherapy,and64received radiation ther-apy.At the time of PICC insertion,21patients were already receiving therapeutic dose anticoagulation(TDA)for throm-botic indications(eg,atrial?brillation,mechanical heart valve), and all continued to receive anticoagulation after insertion.Five of these patients were receiving low–molecular weight heparin, and16patients were receiving warfarin.Also,70patients were receiving prophylactic anticoagulation at the time of PICC placement.In these cases,prophylactic anticoagulation contin-ued until hospital discharge.The results also showed PICC-associated infection in33(13.9%)of237patients.In these individuals,the median time from PICC insertion to infection was50days.

The incidence of symptomatic UEVT was15%(36of237 patients).Stepwise logistic regression analysis revealed four sta-tistically signi?cant risk factors for UEVT(Table3):use of ESAs(odds ratio[OR],10.66;95%CI,2.25to50.49;P?.003),hospitalization(OR,2.38;95%CI,1.05to5.39;P?.04),infection(OR,2.46;95%CI,1.03to5.85;P?.04),and TDA(OR,8.34;95%CI,2.98to23.33;P?.001).The analysis also revealed that patients receiving APAs(OR,0.25;95%CI,0.07to0.92;P?.037)had a75%lower likelihood of UEVT.

Discussion

UEVT is a well-recognized complication of PICCs,and in pa-tients without cancer,asymptomatic UEVT has been detected in37%to66%.1,6,10This retrospective study is the?rst to our knowledge to determine the incidence of symptomatic UEVT in patients with cancer and identify the risk factors speci?cally associated with PICC-related UEVT in this population.Al-though previous studies have identi?ed PICC-speci?c qualities that increase UEVT risk,this study also evaluated patient-spe-ci?c risk factors.In the present study,36(15%)of237patients with cancer developed symptomatic UEVT.The incidence of 15%is somewhat higher than that in previous studies,which have reported rates of2%to7.8%.8,11-15In addition,the infec-tion rate in this study(13.9%)is higher than the2.46%to 13.04%reported in previous studies.3,5,11,14This was seen de-spite the fact that evidence-based infection-prevention strate-gies were performed with every PICC insertion,which entailed using appropriate sterile conditions and follow-up care.3,16-18 The higher observed rate of both UEVT and infection may be related to the number of days spent with a PICC inserted, because there was no institutional standard for the duration of PICC placement.Our results showed a median time of50days from the day of line insertion to infection.However,we did not examine the duration of PICC placement in those without symptomatic UEVT.Further investigation would be needed to determine the association between PICC placement duration and time to infection.Additionally,we did not examine length of hospitalization or admission diagnosis to determine if either of these variables had a signi?cant impact on the rate of UEVT.

This analysis identi?ed three baseline risk factors(hospital-ization at time of PICC placement,infection,and use of ESAs) that predicted for development of symptomatic UEVT as well Table1.Patient Demographic

Characteristics

Thrombosis in Patients With Cancer With Peripherally Inserted CVCs

Ahn et al

Characteristics

Table2.Baseline Patient Array NOTE.All P values based on?2test unless otherwise noted.

Abbreviations:APA,antiplatelet agent;CVC,central venous catheter;ESA,erythropoiesis-stimulating agent;FU,?uorouracil;PICC,peripherally inserted central catheter; SD,standard deviation;SVC,superior vena cava;TDA,therapeutic dose anticoagulation.

*t-test.

?Fisher’s exact test.

?All other malignancies not included in hematologic malignancy(eg,colon,breast,lung,and so on).

§Leukemia,lymphoma,myeloma,and myelodysplastic syndrome.

?Warfarin and enoxaparin/dalteparin were combined and categorized as yes.

?Lovonex;sano?-aventis,Bridgewater,NJ.

as one that showed a protective effect.Hospitalization and in-fection are well-established risk factors for thrombosis.19,20The present results,showing an OR of2.38for hospitalization and UEVT,con?rm the rate of PICC-associated thrombosis from previous studies.21-23Of note,this study is the?rst to our knowledge to identify that concurrent use of ESAs signi?cantly increased the risk for PICC-associated UEVT.This further adds to the body of literature suggesting a link between ESA use in patients with cancer and negative outcomes including thrombosis,which ultimately led the US Food and Drug Ad-ministration to restrict the use of these agents in those with cancer.Somewhat paradoxically,this analysis also demon-strated a statistically signi?cant association between the use therapeutic anticoagulation at the time of PICC placement and UEVT.Although the precise explanation for this observation is not clear,it is possible that this group of patients is at higher risk of additional thrombotic events despite attempted therapeutic anticoagulation.A majority of these patients were receiving warfarin,and we did not attempt to ascertain whether these patients were at therapeutic dosing of anticoagulation at the time of PICC insertion or throughout the duration of place-ment.Results from our analysis also identi?ed that patients receiving APAs had a lower rate of PICC-associated UEVT (OR,0.25;95%CI,0.07to0.92;P?.04).APAs have been well documented to protect against arterial and venous throm-bosis in speci?c settings,but their role as antithrombotic agents in CVCs has not.

There are several limitations with our study.This was a retrospective single-center study,so the results may not be ap-plicable to other institutions,especially if the type of catheter used and protocol for catheter maintenance and care differ from those in our institution.The present cohort consisted of pre-dominately white male patients who received care in the VA system.As a result,the application of these results to the general population is uncertain.Furthermore,the true incidence of UEVT is likely higher,because the diagnosis of UEVT via ultrasound is less sensitive in the upper than in the lower ex-tremity.24Additionally,UEVT was only recorded in those pa-tients who were symptomatic;early UEVT may not have https://www.wendangku.net/doc/cc14907614.html,st,the relationship between speci?c cancer type and primary site was not examined;because of our sample size,it would not have been signi?cant.In addition,with the excep-tions of capecitabine/FU and bevacizumab,we did not consider other potentially prothrombotic chemotherapy agents such as lenalidomide and thalidomide because their use was limited in our cohort of patients with PICCs.

In conclusion,our study identi?ed several patient character-istics that may predispose those with cancer to PICC-associated UEVT.Speci?cally,at the time of PICC insertion,patients with active infections,hospitalized patients,patients receiving ESAs,and patients receiving TDA had a signi?cantly increased risk of UEVT,whereas the use of APAs had a protective effect against UEVT.Future prospective studies are required to better de?ne the signi?cant risk factors for PICC-associated UEVT in this population and may then allow the development of risk strati?cation models for development of UEVT.Currently, there is a lack of consistent evidence on the ef?cacy of throm-bosis prophylaxis in patients with cancer.25Our results suggest that the use of APAs is one prophylactic strategy that could be further evaluated in those patients with cancer felt to be at high risk for the development of PICC-associated UEVT. Authors’Disclosures of Potential Con?icts of Interest

The author(s)indicated no potential con?icts of

interest.

Author Contributions

Conception and design:Daniel H.Ahn,Jonathan E.Dowell Administrative support:Jonathan E.Dowell

Provision of study materials or patients:Henrik Bo Illum,David H. Wang,Anant Sharma,Jonathan E.Dowell

Collection and assembly of data:Daniel H.Ahn

Data analysis and interpretation:All authors

Manuscript writing:All authors

Final approval of manuscript:All authors

Corresponding author:Daniel H.Ahn,DO,University of Texas South-western Medical Center,Department of Palliative Care,5323Harry Hines Blvd,Dallas,TX,75390-8889;e-mail:danielahn@https://www.wendangku.net/doc/cc14907614.html,. DOI:10.1200/JOP.2012.000595;published online ahead of print

at https://www.wendangku.net/doc/cc14907614.html, October23,2012.

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Table3.Clinical Variables and Risk of PICC-Associated

UEVT

Abbreviations:APA,antiplatelet agent;ESA,erythropoiesis-stimulating agent;

OR,odds ratio;PICC,peripherally inserted central catheter;TDA,therapeutic

dose anticoagulation;UEVT,upper extremity venous thrombosis.

Thrombosis in Patients With Cancer With Peripherally Inserted CVCs

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