Coagulation Disorders in Patients with Cancer

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From the Division of Radiology, Interventional Radiology Unit (P.D.V., L.M., G.B., F.O.), Department of Medicine, Division of Medical Oncology (G.C.), Department of Medicine, Division of Onco-Haematology (A.A.), and Division of Radiology (M.B.), European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy; and School of Medicine, University of Milan, Italy (M.B.). Received November 5, 2008; revision requested December 15; revision received December 31; accepted March 27, 2009; final version accepted April 14. Address correspondence to P.D.V. (e-mail: [email protected] ).

Purpose:

To assess the feasibility and safety of ultrasonographic (US) guidance in the placement of nontunneled central venous catheters (CVCs) in patients with cancer who had altered coagulation profiles.

Materials and Methods:

The study was approved by the institutional review board; informed consent was obtained. Medical charts of all patients with cancer who underwent nontunneled CVC placement at the European Institute of Oncology, Milan, from September 2001 to August 2008 were retrospectively reviewed. Patients were considered to have coagulation disorders or risk of bleeding when they had the following: prothrombin time more than 1.2 times normal or activated partial thromboplastin time more than 1.2 times normal and/or platelet count less than 150 ⫻ 109/L. Patients with a prothrombin time and partial thromboplastin time more than 2.2 times normal and/or a platelet count less than 50 000/mm3 were considered to be at high risk for bleeding. Two hundred thirty-nine nontunneled CVCs were placed with US guidance in 157 patients.

Results:

One hundred twenty-two (51%) of 239 nontunneled CVCs were inserted in patients with cancer who had hemostasic disorders. Forty-five (37%) of 122 nontunneled CVCs were implanted in patients considered to be at high risk for bleeding. All catheters were successfully placed at the first needle pass with no major complications such as bleeding or pneumothorax. Two hundred thirty-three (97%) nontunneled CVCs were placed in the subclavian vein, and six (3%) were placed in the internal jugular vein. No patient underwent any correction for an abnormal coagulation profile.

Conclusion:

In patients with cancer who had coagulation disorders, nontunneled CVC placement with US guidance was feasible and safe and did not require correction of coagulation parameters. 娀 RSNA, 2009

姝 RSNA, 2009 Radiology: Volume 253: Number 1—October 2009 ▪ radiology.rsna.org

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䡲 VASCULAR AND INTERVENTIONAL RADIOLOGY

Paolo Della Vigna, MD Lorenzo Monfardini, MD Guido Bonomo, MD Giuseppe Curigliano, MD Alberto Agazzi, MD Massimo Bellomi, MD Franco Orsi, MD

ORIGINAL RESEARCH

Coagulation Disorders in Patients with Cancer: Nontunneled Central Venous Catheter Placement with US Guidance—A SingleInstitution Retrospective Analysis1

VASCULAR AND INTERVENTIONAL RADIOLOGY: US Guidance for Catheter Placement

A

dequate vascular access is of paramount importance in patients with cancer. It is essential in the initial phase of treatment, as well as in the chronic management of advanced cancer and in the palliative care setting. Complications such as pneumothorax, mediastinal hematoma, hemothorax, tracheal injury, or local bleeding related to percutaneous puncture have been described (1). In patients with cancer, central venous catheter (CVC) placement may frequently involve additional risks due to disease or treatment-related hemostatic disorders (2). It is standard practice to correct coagulation profiles for simple, nontunneled lines in any patient, but at present, to our knowledge, there are no data to support this. The advantages of image-guided catheter placement over blind placement based on known anatomic landmarks have been confirmed in nonrandomized and randomized studies in a large series of investigations, which show a lower complication rate when ultrasonographic (US)-guided techniques are used (3,4). The purpose of this study was to assess the safety of US guidance for nontunneled CVC insertion in patients with cancer who had altered but uncorrected coagulation parameters.

Materials and Methods No financial support has been provided for the present study. Informed consent was obtained from each patient before the procedure. Retrospective review of medical charts was approved by our institutional review board.

Patient Population We retrospectively reviewed the medical charts of all patients who underwent nontunneled CVC placement in our Interventional Radiology Unit from September 2001 to August 2008. During the study period, we placed a total of

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239 nontunneled CVCs in 157 patients with malignancy; 130 (82.8%) had hematologic malignancy, and 27 (17.2%) were affected by solid tumors (Table 1). For all patients, we analyzed the platelet count, the activated partial thromboplastin time, and the prothrombin time. Patients with a prothrombin time or partial thromboplastin time of more than 1.2 times normal and/or a platelet count less than 150 ⫻ 109/L were considered to have a hemostatic profile disorder. Profiles of patients are reported in Table 2. Coagulation disorders were not corrected in any patient before nontunneled CVC insertion. The number of passes required to achieve venous access was registered. The number and extent of complications were recorded. Complications were defined as hemorrhagic (when any treatment for bleeding was undertaken) or nonhemorrhagic (pneumothorax, inadvertent arterial puncture, tracheal injury, or vascular injury).

Technique All interventional procedures were performed with US guidance, with a 7.5-MHz linear probe (Esaote Biomedical, Genoa, Italy). Four operators (P.D.V., L.M., G.B., F.O.) performed all procedures; operators had performed a mean of 682 central venous procedures with US guidance (range, 338 –1089 procedures). Central venous access was obtained through the subclavian or the internal jugular vein. Longitudinal scanning was used for an initial check of the vein to assess the safest and easiest access site and to confirm vein patency. Five milliliters of local anesthetic (100 mg of mepivacaine [Mepivacaina; Angelini, Rome, Italy]) was injected immediately adjacent to the anterior vein wall and in the subcutaneous tissue by using a 22-gauge needle with US guidance. An 18-gauge needle (Logicath AgTive; Smiths Medical Deutschland, Grasbrunn, Germany) was then inserted

Advance in Knowledge

Implication for Patient Care

䡲 The standard but unsubstantiated practice to correct coagulation profiles for placement of simple, nontunneled lines was not supported by the results of our study.

䡲 In patients with coagulation disorders, central venous cannulation with US guidance was safe and did not require correction of coagulation parameters.

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with US guidance until the anterior vein wall was reached and crossed (Figure). A J-shaped metallic 0.035-inch guidewire (Logicath AgTive; Smiths Medical Deutschland) was then introduced into the vein by using fluoroscopic guidance, and, after subcutaneous tract dilation was performed, a 7-F catheter (Smiths Medical Deutschland) was inserted by using the Seldinger technique. Position of the catheter tip was immediately checked by using fluoroscopy. The catheter was then fixed to the skin by using glue (StatLock; Bard, Murray Hill, NJ) or surgical suture. The subclavian vein was chosen most often because of a lower reported CVC infection rate than for the internal jugular and femoral veins (5). However, the choice of left versus right side or internal jugular versus subclavian access was made on the basis of the presence of local disease (malignancyrelated disease such as lymph nodes or softtissue mass) or vein occlusion. A postprocedural chest radiograph was obtained in each case to confirm catheter position and to assess for any immediate complication, such as pneumothorax, hemothorax, or mediastinal hematoma.

Results From September 2001 to August 2008, of the 239 CVCs placed in 157 patients with cancer, 93 (59%) were in men and 64 (41%) were in women. Mean patient age was 49.2 years (age range, 19 –79 years). Coagulation disorders and/or al-

Published online before print 10.1148/radiol.2531081963 Radiology 2009; 253:249 –252 Abbreviation: CVC ⫽ central venous catheter Author contributions: Guarantors of integrity of entire study, P.D.V., L.M., A.A., F.O.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, P.D.V., L.M., G.C., A.A., F.O.; clinical studies, all authors; statistical analysis, P.D.V., L.M., A.A., F.O.; and manuscript editing, P.D.V., L.M., G.C., A.A., F.O. Authors stated no financial relationship to disclose.

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teration of platelet count were observed in 122 procedures, including 67 defined as intermediate and high risk for potential bleeding during the procedure (Table 2). All procedures required only a single attempt to access the vein. No Table 1 Patient Tumor Characteristics Parameter Hematologic disease Non-Hodgkin lymphoma Acute myeloid leukemia Hodgkin lymphoma Acute lymphocytic leukemia Chronic lymphoid leukemia Chronic myeloid leukemia Multiple myeloma Hair cell leukemia Solid tumor Breast cancer Head and neck cancer Gynecologic cancer Lung cancer Pancreatic cancer Gastric cancer Bladder cancer Sarcoma Colon cancer Total

No. of Patients

55 (35) 29 (18) 27 (17) 5 (3) 6 (4) 4 (2) 3 (2) 1 (0.6) 5 (3) 4 (2) 4 (2) 3 (2) 2 (1) 3 (2) 3 (2) 2 (1) 1 (0.6) 157

early or late complications were reported after any procedure. Arterial puncture did not occur in any case. Of 239 implanted catheters, 233 (97%) were placed in the subclavian vein, and six (3%) were placed in the internal jugular vein. In one patient, we observed blood oozing around the point of insertion. Compression was required, and no late complication was observed. Patients who had a catheter inserted underwent a clinical or, if needed, a US follow-up to exclude late complications.

Discussion Central venous access is frequently required in the treatment of a hospitalized patient with cancer. In patients with a low platelet count and/or prolonged

Della Vigna et al

prothrombin time, partial thromboplastin time, or international normalized ratio, there is a concern for bleeding during placement of a CVC, be it tunneled or nontunneled. It is common practice to attempt to optimize coagulation profiles in this scenario. Because blind catheterization is associated with adverse events in 5%–19% of cases (6–8), US guidance has become more prevalent because of its reduced risk of complications (9–13). In our institution (a comprehensive cancer center), central venous access is referred to the Interventional Radiology Unit for catheter placement with US guidance when an alteration in hemostatic parameters is present. All disorders of hemostasis were not corrected in any case, and this has become our standard practice.

Table 2 Distribution of Procedures according to Hemostatic Disorders Risk Grade Low risk Intermediate risk High risk

Hemostatic Profile*

No. of Procedures†

PT or PTT ⬎ 1.2 and ⬍ 1.7 times normal and/or platelet count ⬎ 80 000 and ⬍ 150 000/mm3 PT or PTT ⬎ 1.7 and ⬍ 2.2 times normal and/or platelet count ⬎ 50 000 and ⬍ 80 000/mm3 PT or PTT ⬎ 2.2 times normal and/or platelet count ⬍ 50 000/mm3

55 (45) 22 (18) 45 (37)

* PT ⫽ prothrombin time, PTT ⫽ partial thromboplastin time. Note.—Data in parentheses are percentages.

†

Data in parentheses are percentages.

US images show that the US-guided percutaneous approach of subclavian vein allows for detection of (a) hyperechoic line (arrows) caused by ultrasound reflections of the needle approaching the anterior wall of subclavian vein (S), (b) anterior wall of subclavian vein, invaginated by the approaching needle (arrow), used for percutaneous access, and (c) hyperechoic spot (arrow) that represents the needle tip within the subclavian lumen. Radiology: Volume 253: Number 1—October 2009 ▪ radiology.rsna.org

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In the literature concerning non–image-guided CVC placement, no significant difference was reported in the outcome of bleeding complications for patients with abnormal hemostasis versus those who had correction of hemostasis before catheter insertion; in the case series of DeLoughery et al (15), percentage of transfusion was the same (18%) for the bleeding (three of 16) and nonbleeding (141 of 761) groups (14,15). The skill level of the physician performing the blind procedure also affects bleeding complications. For example, DeLoughery et al (15) found a higher rate of complication of line placement for patients receiving medical service rather than surgical service; this result has been interpreted as related to the greatly reduced number of procedures performed by medical house staff. Additionally, Bernard and Stahl (16) found a higher rate of complication (specifically for subclavian vein catheterization) for a group of physicians who had performed fewer non– image-guided catheterizations (⬍50 placements). Finally, Fisher and Mutimer (17) found that the most significant predictor of hematoma formation following non–image-guided placement of a central line was failure to successfully place the guidewire. Hence, we believe that a major reason for the lack of complications in our study population was the level of experience of the radiologists performing CVC placement. Our retrospective study allowed us to indirectly assess for the additional safety offered by US-guided access for nontunneled CVC placement in patients with cancer who had coagulation disorders. Although we did not formally compare it with non–image-guided placement in our patient population, the complete absence of complications makes us confident in stating that US-guided placement of nontunneled catheters in patients at risk for bleeding appears to be safe, and correction of coagulation parameters probably is not needed. In fact, 45 patients with high risk of bleeding (plate-

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lets count ⬍ 50 000/mm3 and/or prothrombin time or partial thromboplastin time ⬎ 2.2 times normal) did not experience any bleeding complication. Several limitations can be highlighted in our study, in addition to the retrospective nature of our analysis. We did not study patients receiving tunneled central venous lines. Because of the absence of assessment of noncorrected bleeding parameters in this scenario, we cannot make recommendations concerning correction of coagulation parameters prior to central venous line placement for this group of patients. Another potential limitation was the absence of a matched population of patients without cancer. We would assume, however, that our results can be translated to this population. In conclusion, in patients with cancer who had coagulation disorders, nontunneled CVC placement with US guidance was feasible and safe and did not require correction of coagulation parameters. Our results should also translate into the avoidance of the transfusion of blood products and their potential related complications and cost, as well as the cost of repetition of coagulation tests in this patient population.

References 1. McGee DC, Gould MK. Preventing complications of central venous catheterization. N Engl J Med 2003;348:1123–1133. 2. Mumtaz H, Williams V, Hauer-Jensen M, et al. Central venous catheter placement in patients with disorders of hemostasis. Am J Surg 2000;180:503–506. 3. Oguzkurt L, Tercan F, Kara G, Torun D, Kizilkilic O, Yildirim T. US-guided placement of temporary internal jugular vein catheters: immediate technical success and complications in normal and high-risk patients. Eur J Radiol 2005;55:125–129. 4. Mey U, Glasmacher A, Hahn C, et al. Evaluation of an ultrasound-guided technique for central venous access via the internal jugular vein in 493 patients. Support Care Cancer 2003;11:148 –155.

5. Lorente L, Henry C, Martıń MM, Jimeńez A, Mora ML. Central venous catheter-related infection in a prospective and observational study of 2,595 catheters. Crit Care 2005;9:R631–R635. 6. Sznajder JI, Zveibil FR, Bitterman H, Weiner P, Bursztein S. Central vein catheterization: failure and complication rate by three percutaneous approaches. Arch Intern Med 1986; 146:259 –261. 7. Mansfield PF, Hohn DC, Fornage BD, Gregurich MA, Ota DM. Complications and failures of subclavian-vein catheterization. N Engl J Med 1994;331:1735–1738. 8. Merrer J, De Jonghe B, Golliot F, et al. Complications of femoral and subclavian venous catheterization in critically ill patients: a randomized controlled trial. JAMA 2001;286:700–707. 9. Randolph AG, Cook DJ, Gonzales CA, Pribble CG. Ultrasound guidance for placement of central venous catheters: a metaanalysis of the literature. Crit Care Med 1996;24:2053–2058. 10. Hind D, Calvert N, McWilliams R, et al. Ultrasonic locating devices for central venous cannulation: meta-analysis [paper]. BMJ 2003;327:361. 11. Calvert N, Hind D, McWilliams R, et al. Ultrasound for central venous cannulation: economic evaluation of cost-effectiveness. Anaesthesia 2004;59:1116 –1120. 12. Lefrant JY, Cuvillon P, Beńe´zet JF, et al. Pulsed Doppler ultrasonography guidance for catheterization of the subclavian vein: a randomized study. Anesthesiology 1998;88:1195–1201. 13. Bold RJ, Winchester DJ, Madary AR, et al. Prospective, randomized trial of Doppler-assisted subclavian vein catheterization. Arch Surg 1998;133:1089 –1093. 14. Doerfler ME, Kaufman B, Goldenberg AS. Central venous catheter placement in patients with disorders of hemostasis. Chest 1996;110:185–188. 15. DeLoughery TG, Liebler JM, Simonds V, Goodnight SH. Invasive line placement in critically ill patients: do hemostatic defects matter? Transfusion 1996;36:827– 831. 16. Bernard RW, Stahl WM. Subclavian vein catheterizations: a prospective study. I. Noninfectious complications. Ann Surg 1971; 173:184 –190. 17. Fisher NC, Mutimer DJ. Central venous cannulation in patients with liver disease and coagulopathy: a prospective audit. Intensive Care Med 1999;25:481– 485.

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