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Polyurethane II catheter as long-indwelling intravenous catheter in patients with cancer
Polyurethane II catheter as long-indwelling intravenous catheter in patients with cancer Patricia Volkow, MD,a Carolina Va´zquez, RN,a Odilia Te´llez, RN,a Catalina Aguilar, RN,a Laura Barrera, RN,a Eneida Rodrı´guez, RN,a Diana Vilar-Compte, MD, MsC,a Juan Zinser, MD,a Ernesto Caldero´n, MD,a Jose´ Rogelio Pe´rez-Padilla, MD,b and Alejandro Mohar, MD, ScDa,c Mexico City, Mexico
Background: Silicone has been the standard material for indwelling devices to date. Polyurethane II exhibits properties that makes it suitable as a component of long-indwelling vascular access, with the added advantage of low cost. Objective: To describe the experience of an intravenous therapy team with 206 polyurethane II catheters used as long-indwelling vascular access in patients with cancer. Materials and Methods: All polyurethane II single- and double-lumen catheters implanted between January 1, 1994, and March 15, 1995, were analyzed, including time of stay and type and rate of infectious and noninfectious complications. Results: A total of 206 catheters were placed—164 single-lumen and 42 double-lumen catheters—in 190 patients; average stay was 101 days (range, 1-445 days). The infection incidence rate was 0.66 per 1000 catheter-days for single-lumen catheters and 1.6 per 1000 catheter-days for double-lumen catheters. Noninfectious complications included 1 thrombosis (incidence rate, 0.06 per 1000 catheter-days for single-lumen and none for double-lumen catheters), 5 catheter ruptures (2.4%), and 1 pneumothorax (0.48%). Twelve catheters (8.3%) were removed because of complications; only 1 was infectious. The remaining 17 infectious episodes (94.4%) were resolved without catheter removal. Our complication rate with single-lumen catheters in this series was similar to our previous experience with a nontunneled silicone catheter. Conclusions: Our findings indicate that polyurethane II catheters have proven useful and safe as long-indwelling vascular access in patients with cancer at our hospital at a considerably lower cost. (Am J Infect Control 2003;31:392-6.)
Silastic has been the standard material in the expanding technology for intravascular long-indwelling devices. This preference is due to its particular characteristics, which include its being biocompatible, soft, and nonthrombogenic.1,2 Although new materials for catheter manufacture have been developed, they have not proven to be safe for long duration.3,4 Polyurethane II (Arrow International, Inc, Reading, Penn) is a flexible, soft, low-thrombogenic material that is suitable for long-stay. It also offers the advantage of low cost. This is particularly important in developing countries where patients may not be able to afford
From the Instituto Nacional de Cancerologı´aa; Instituto Nacional de Enfermedades Respiratoriasb; and Instituto de Investigaciones Biome´dicas, Universidad Nacional Auto´noma de Me´xico, Me´xico.c Reprint requests: Patricia Volkow, MD, Infectious Diseases, Instituto Nacional de Cancerologı´a, San Fernando #22, Col. Tlalpan, 14000 Me´xico, DF, Me´xico. Copyright ª 2003 by the Association for Professionals in Infection Control and Epidemiology, Inc. 0196-6553/2003/$30.00 + 0 doi:10.1067/mic.2003.39
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the cost of a tunneled silastic catheter or a subcutaneous port. We previously published5 the experience our intravenous therapy team (IVTT) had in the care and control of a low-cost, nontunneled silastic catheter (Centrasil; Baxter-Travenol, Morton Grove, Ill) in patients with cancer receiving chemotherapy; the Centrasil catheter offered the same parameters of security compared with more costly catheters studied in other series. Unfortunately, Baxter-Travenol stopped producing this low-cost catheter in 1993. Thus, we needed to choose a new catheter that was both affordable and available in Mexico. In January 1994, we began to use polyurethane II (Arrow International, Inc) single- and double-lumen catheters for long-stay (weeks, months, or even years) in patients with cancer receiving chemotherapy, with use of the same protocol of care used with the Centrasil catheter.5 We report here the experience at the Instituto Nacional de Cancerologı´a (INCan) IVTT with insertion, care, and control of polyurethane II catheters in 190 patients with cancer between January 1994 and March 1995.
Volkow et al
MATERIALS AND METHODS Patients The National Institute of Cancer (INCan) in Mexico City is a national referral center for adult patients who have cancer. Fifty percent of the patient population did not complete elementary school; 14% are illiterate. Sixty-six percent of patients have a family income of less than $6 US dollars per day ($3 [US] is the daily minimum wage in Mexico City). The IVTT was established at INCan in 1988; this team controls care and follow-up of all patients with central venous catheters inserted at the hospital.
Catheters The devices used were single- and double-lumen polyurethane II, nontunneled, percutaneously implanted catheters (Arrow International, Inc). The cost of the single-lumen catheter in Mexico is $17 (US) and $20 (US) for the double-lumen catheter. All patients with cancer who needed a long term-indwelling catheter were selected for this study. In terms of intravenous (IV) line requirements, the treating oncologist chose to use either a single- or double-lumen catheter. Patients who received parenteral nutrition and/or bone marrow transplantation or peripheral blood stem cell transplantation were included. The catheter was also used to withdraw blood samples, always done exclusively by IVTT personnel, in all patients (whether hospitalized or outpatients). Local infection of the catheter insertion site was suspected if the patient had pain, erythema, or purulent secretion; in these cases, a Gram’s stain and culture were performed. In patients with fever, blood culture specimens were obtained from each lumen and at least 1 additional specimen was obtained through peripheral venipuncture.
Diagnostic criteria Local infection was diagnosed on the basis of purulent secretion or induration and culture-positive specimens of the central venous catheter insertion site (non-neutropenic patients) or local erythema and culture-positive specimens of the central venous catheter insertion site (neutropenic patients). Catheter-related bacteremia was diagnosed on the basis of at least 3 of the following 4 criteria: the patient had clinical signs of bacteremia or a temperature of more than 38.38C, blood cultures were positive for the same organism isolated from the catheter insertion site, cultures of the insertion-site specimen and catheter tip yielded the same organism, and remission of symptoms was noted after catheter removal. Neutropenia was defined as a total neutrophil count of less than 1000/mm3.
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In case of local infection, the insertion site was cleaned daily, and treatment with oral antibiotics was initiated. In patients with gram-positive bacteria, topical mupirocin was also used. Patients with catheterrelated bacteremia were treated as inpatients with parenteral antibiotics. The decision to keep the catheter in place was made 48 hours after diagnosis of infection if no signs of infection were present. In patients with persistent infections, the catheter was removed and the catheter tip was sent for culture. IVTTstructure, routine, and diagnostic and catheter removal criteria as well as microbiologic methods were detailed in our previous papers.5,6
Statistical analysis Incidence rates were determined and expressed per 1000 catheter-days. Survival distribution related to complication-free device life; length of catheterization was calculated by the Kaplan-Meier method.7 We estimated the odds ratio (OR), and statistical significance was assessed with the 95% confidence interval (95% CI). Rates of infectious and noninfectious complications in this study were compared with rates reported by Pessa,8 Larson,9 Simmons,10 Mueller,11 Pegues,12 and our previous experience with a nontunneled silicone catheter (Centrasil).5 Sample size was calculated according to Simon.13 A number of evaluable patients were entered into the study, and a frequency of infection was assumed to be 10%. For that number of events, we estimated a total number of 150 patients for statistical power of 80%.
RESULTS During the study period, 206 catheters were placed—164 single-lumen and 42 double-lumen—in 190 patients. One hundred forty four (79%) catheters were placed in 133 women and 62 (30%) in 57 men with mean age of 44 years (range, 13-80 years). Twenty percent of patients in this series had hematologic neoplasia, and 80% had a solid tumor; distribution of malignancies is shown in Table 1. Twelve percent of patients with a single-lumen catheter had hematologic neoplasia, whereas 54.7% of patients in this diagnostic group had a double-lumen catheter. The catheter was used for administration of chemotherapy (inpatient and ambulatory, short and long infusions), antibiotics, IV fluids, and parenteral nutrition; transfusion of blood products; and blood withdrawal for laboratory examinations. Catheters were placed in the following veins: subclavian, 199; internal jugular, 6; and supraclavicular, 1. Average catheter stay was 101 days (range, 1-445 days). The incidence rate of catheter-related infection was 0.66 per 1000 catheter-days for single-lumen
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Table 1. Distribution by neoplasm in patients with long-indwelling polyurethane II single-lumen and double-lumen catheters
Acute lymphoblastic leukemia Acute myeloblastic leukemia Non-Hodgkin’s lymphoma Hodgkin’s disease Multiple myeloma Lymphocytic leukemia Myeloproliferative symptoms Kaposi’s sarcoma (AIDS) Breast carcinoma Uterine cervix carcinoma Digestive tract Osteosarcoma Head and neck carcinoma Others* Total
Single-lumen
Double-lumen
6 (4.2%) 2 (1.2%) 4 (2.4%) 5 (3.0%) 1 (0.6%) 0 1 (0.6%) 6 (3.6%) 75 (45.7%) 15 (9.1%) 7 (4.3%) 12 (7.3%) 15 (9.1%) 15 (9.1%) 164
13 (30.9%) 6 (14.2%) 0 0 2 (4.8%) 1 (2.4%) 0 1 (2.4%) 11 (26.2%) 2 (4.8%) 0 2 (4.8%) 0 4 (9.5%) 42
*Others: ovary, kidney, lung, neuroblastoma, and endometrial.
catheters and 1.6 per 1000 catheter-days for doublelumen catheters. OR was 2.45 (95 %CI, 0.95-6.32) for double-lumen catheters compared with single-lumen catheters. Incidence rate of single-lumen catheterrelated infection during neutropenic periods was 2.05 per 1000 catheter-days and 0.57 per 1000 catheterdays for non-neutropenic periods (OR, 3.56; 95% CI, 0.77-16.45). The incidence rate for double-lumen catheter-related infection during neutropenic periods was 1.6 per 1000 catheter-days and 1.6 per 1000 catheter-days for non-neutropenic periods (OR, 1.01; 95% CI, 0.12-8.4). Eighteen catheter-related infections were recorded in 16 patients (8.4%); 11 were local infections of insertion site (5.3%) and 7 were bacteremia (3.9). Two patients had 2 infectious episodes with the same catheter. One catheter was removed because of infection, whereas the remaining 17 infectious episodes (94.4%) were resolved without catheter removal. Table 2 shows micro-organisms isolated in catheter-related infectious episodes. Overall, 80% were caused by grampositive bacteria and 20% by gram-negative bacteria. Coagulase-negative staphylococci were isolated in 66% cases of local infection and 37.5% cases of bacteremia. Noninfectious complications included 1 thrombosis (incidence rate, 0.06 per 1000 catheter-days for singlelumen catheters and none for double-lumen catheters), 5 catheter ruptures (2.4%), and 1 pneumothorax (0.48%). No cases of local hematoma, superior vena cava syndrome, or lymphatic fistula were detected. At the end of follow-up, 40 catheters (19.4%) were removed because of treatment completion, 38 (18.9%) patients died of cancer with no catheter complications, 75 (36.4%) patients had functioning catheters in place
Table 2. Microorganisms isolated from long-indwelling polyurethane II catheter-related infections Microorganism Coagulase-negative staphylococci Coagulase-positive staphylococci Streptococcus group D Klebsiella pneumoniae Proteus mirabilis Enterobacter species Escherichia coli
Local infection
Bacteremia
8 1 1 0 0 1 1
3 0 1 1 1 1 0
*No polymicrobial bacteremia identified.
at the time of this report, and 14 (6.8%) patients voluntarily discontinued treatment. In 10 (4.8%) patients, the catheter was changed for another type of catheter (eg, Permacath, Quinton Instrument, Seattle, Wash, or a single-lumen for a double-lumen catheter). In 6 cases, catheters were removed due to additional causes: 4 (1.9%) catheters were inadvertently removed by non-IVTT personnel, 1 patient attempted suicide, and another case was due to noncompliance to weekly catheter care. Twelve (5.8%) catheters were removed because of complications (4 catheter obstructions, 5 due to mechanical damage, 1 because of thrombosis, 1 catheter malposition, and 1 because of catheter-related infection). Eleven (5.3%) patients with catheters were lost to follow-up. Installation cost for single- and double-lumen catheters was $38 and $50 (US), respectively. Direct cost of weekly care for 12 months was $240 (US) for single-lumen catheters and $292 (US) for doublelumen catheters, respectively (including the device). Cost for a tunneled silicone catheter in Mexico is $100 (US) and for a nontunneled silicone catheter $80 (US), and the average cost for a subcutaneous port is 400 (US) (these prices are only for the device). Table 3 compares our results with those of 4 reported series, the first in which Hickman catheters (Bard, Crawley, West Sussex) were used; the second, Centrasil catheters; the third, either Hickman or Porta-cath devices (Pharmacia, Piscataway, NJ); and the fourth, our previous experience with the Centrasil catheter. These series and this study were analyzed in a similar method. Table 4 presents the incidence rate of catheter-related complications calculated per 1000 days in comparison with rates reported by Mueller,11 Pegues,12 and Groeger14 for the Hickman, Port-a-cath, Groshong, and our previous experience with the Centrasil catheters.5
DISCUSSION Although silastic has been used as the sole material for long-indwelling intravenous catheters, introduction
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Table 3. Comparison of percentage of noninfectious and infectious catheter-related complications with 3 other studies No.
Hickman 157*
Centrasil 195†
8 (5.1%) 3 (2.3%) 1 (0.6%) NI 2 (1.2%) 1 (0.6%) 4 (2.5%) 1 (0.6%) 20 (12.7%) 7 (4.5%) 13 (8.3%)
3 (1.5%) 3 (1.5%) NI 0% 1 (0.5%) 0 0 0 40 (8.1%) 15 (7.7%) 5 (2.6%)
Thrombosis Pneumothorax Embolism Hematoma Mechanical damage Rupture Superior caval vein syndrome Lymphatic fistula Total infections Local Local plus bacteremia Bacteremia
Centrasil 494‡ 3 3 1 35 9 2 0 0 40 28 8 4
Polyurethane II 206
(0.6%) (0.6%) (0.2%) (7.1%) (1.8%) (0.4%)
1 1 0 0 5 0 0 0 18 11 0 7
(10.3%) (5.6%) (1.61%) (0.8%)
(0.48%) (0.48%)
(2.4%)
(8.73%) (5.3%) (3.39%)
*Pessa M. Surg Gynecol Obstet 1985;161-257.5 ySimmons JR. Med Pediatr Oncol 1992;20:22.10 zVolkow P. CID 1994;18:719.5
Table 4. Rate of catheter-related complications calculated per 1000 catheter-days
Infection Mechanicalk Thrombosis
Hickman* (n = 46)
Port-a-cath* (n = 46)
Hickman† (n = 47)
Port-acath+ (n = 94)
1.6 0.7 0.5
1.2 0.3 0.2
1.8 NI NI
0.4 NI NI
Centrasil‡ (n = 496)
Port-acath§ (n = 680)
0.66 0.45 0.07
0.21 NI NI
Hickman*** (n = 788)
Polyurethane II single-lumen (n = 164)
Polyurethenane II double-lumen (n = 42)
2.76 NI NI
0.66 NI 0.06
1.62 0.45 0.0
NI, Not informed. *Adult and pediatric patients receiving chemotherapy and/or autologous bone marrow reconstitution.11 yAdult patients receiving chemotherapy and/or parenteral nutrition.12 zINCan series. Adult patients receiving chemotherapy.7 §Sloan-Kettering series. Adult patients receiving chemotherapy. No patients with ports had bone marrow transplantation.16 kMechanical: catheter rupture, obstruction, or dislodgment.
of new materials that share some characteristics of biocompatibility, flexibility, and low thrombogenicity such as polyurethane2-4 offers the possibility to use these new materials for long-indwelling IV lines. Polyurethane II has these characteristics in addition to a lower cost than silastic, an important advantage when health care budgets are restricted. The majority of authors postulate that risk of infection from these devices can be overcome by technologic advances such as the introduction of the Dacron cuff, vita cuff, or even additional sophisticated devices that release silver ions. This has led to an escalated design of sophisticated catheters.15-22 Extensive experiences5,23 question this position: not only does this enormously increase device prices, but also it can render the potential danger of allergic reaction. To date, no technologic implementation in an intravenous catheter can guarantee its safety if the catheter does not receive proper care. The experience we have presented leads us to postulate that strict protocol of catheter care can result in a safety index as high as indices for more sophisticated and expensive devices and highlights the importance of the IVTT in the care of
intravascular devices. Advantages achieved with use of polyurethane II catheters as long-indwelling IV lines are due both to the catheter itself and to the care provided by a professional team. Furthermore, we postulate that silastic should no longer be the sole material used for long-indwelling IV lines. Our complication rate with the single-lumen polyurethane II catheter is similar to our previous experience with a nontunneled, single-lumen silicone catheter. The infection incidence rate with doublelumen is 3 times higher; this difference could be related to patient type, as hematologic malignancies are overrepresented in this group, with longer periods of neutropenia, previously recognized as increasing risk of catheter-related infection.5 The fact that we found no find fungi could be because very few patients received parenteral nutrition, the main risk factor for catheter-related fungi infection at our hospital. Compared with the findings of Keung,23 thrombosis incidence rate is particularly low in our study, probably because of low thrombogenic potential of polyurethane II. These findings strongly suggest that polyurethane II catheters can be safe and useful for long-indwelling
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vascular access in cancer patients at our hospital. Our results are within the safety range of results published with more costly silicone catheters. References 1. Gravenstein N, Blackshear RH. In vitro evaluation of relative perforating potential of central venous catheters: comparison of materials, selected models, number of lumens, and angles of incidence to simulated membrane. L Clin Monitoring 1991;7:1-6. 2. Stenqvist O, Curelaru I, Linder LE, Gustavsson B. Stiffness of central venous catheters. Acta Anaesthesiol Scan 1983;27:153-7. 3. Linder LE, Curelaru I, Gustavsson B, Hansson HA, Stenqvist O, Wojciechowski J. Material thrombogenicity in central venous catheterization: a comparison between soft antebrachial catheters of silicone elastomer and polyurethane. J Parent Nutr 1984;8:400-6. 4. Zdrahala RJ, Solomon DD, Lentz DJ, McGary CW. Thermoplastic polyurethanes. Materials for vascular catheters. In: Planck H, et al, eds. Polyurethanes in biomedical engineering. II. Amsterdam: Elsevier Science; 1987. p. 1-18. 5. Volkow P, Sanchez-Mejorada P, Lazo S, Va´zquez C, Te´llez O, Baez RM, et al. Experience of an intravenous therapy team at the Instituto Nacional de Cancerologı´a (Mexico) with a long-lasting, low-cost silastic venous catheter. Can Infect Dis 1994;18:719-25. 6. Kaplan EL, Mieier P. Nonparametric estimation from incomplete observation. J Am Stat Assoc 1958;53:457-81. 7. Simo´n R. Clinical trials in cancer. In: De Vita V, Hellman S, Rosenberg SA, editors. Cancer principles and practices, 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 321-38. 8. Pessa ME, Howard RJ. Complications of Hickman-Broviac catheter. Surg Gynecol Obstet 1985;161:257-60. 9. Larson EB, Wooding M, Hickman RO. Infectious complications of right atrial catheters used for venous access in patients receiving intensive chemotherapy. Surg Gynecol Obstet 1981;153:369-73. 10. Simmons JR, Buzdar AU, Ota DM, Marts K, Hortobagyi GN. Complications associated with indwelling catheter. Med Pediatr Oncol 1992;20:22-5. 11. Mueller BU, Skelton J, Callender DP, et al. A prospective randomized trial comparing the infectious and noninfectious complications of an externalized catheter versus a subcutaneously implanted device in cancer patients. J Clin Oncol 1992;10:1943-8.
Volkow et al 12. Pegues D, Axelrod P, McClarren C, et al. Comparison of infections in Hickman and implanted port catheter in adult solid tumor patients. J Surg Oncol 1992;49:156-62. 13. Simon R. Optimal two-stage designs for phase II clinical trials. Cancer Clin Trials 1989;10:1-7. 14. Groeger JS, Lucas AB, Thaler HT, Friedlander-Klar H, Brown AE, Kiehan TE, Armstrong D. Infectious morbidity associated with longterm use of venous access devices in patients with cancer. Ann Intern Med 1993;119:1168-74. 15. Bach A, Bo¨hrer H, Motsch J, Martin E, Geiss HK, Sonntag HG. Prevention of bacterial colonization of intravenous catheters by antiseptic impregnation of polyurethane polymers. J Antimicrob Chemother 1994;33:969-78. 16. Maki DG, Garman JK, Shapiro JM, Ringer M, Helgerson RB. An attachable silver-impregnated cuff for prevention of infection with central venous catheters: prospective randomized multicenter trial. Am J Med 1988;85:307-14. 17. Flowers RH, Schwenzer KJ, Kopel RF, Fisch MJ, Tucker SI, Farr BM. Efficacy of an attachable subcutaneous cuff for the prevention of intravascular catheter-related infection. JAMA 1989;262:878-83. 18. Norwood S, Hajjar G, Jenkins L. The influence of an attachable subcutaneous cuff for preventing triple lumen catheter infections in critically ill surgical and trauma patients. Surg Gynecol Obstet 1992; 175:33-40. 19. Raad I, Darouchi R, Dupuis J, Abi-Said D, Gabrielli A, Hachem R, et al. Central venous catheters coated with minocycline and rifampin for the prevention of catheter-related colonization and bloodstream infections. A randomized, double-blind trial. Ann Intern Med 1997; 127:267-74. 20. Maki DG, Stolz SM, Wheeler S, Mermel LA. Prevention of central venous catheter-related bloodstream infection by use of an antisepticimpregnated catheter. A randomized controlled trial. Ann Intern Med 1997;127:257-66. 21. Daoruchi RO, Raad I, Head SO, Thornby JI, Wenker OC, Gabrielli A, et al. A comparison of two antimicrobial-impregnated central venous catheters. N Engl J Med 1999;340:1-8. 22. Raad I, Hachem R, Zermeno A, Stephens LC, Bodey GP. Silver iontophoretic catheter: a prototype of a long-term antiinfective vascular access device. J Infect Dis 1996;173(2):495-8. 23. Keung YK, Watkins K, Chen SC, Groshen S, Silberman H, Douer D. Comparative study of infectious complications of different types of chronic central venous access devices. Cancer 1994;73:2832-7.
Background: Silicone has been the standard material for indwelling devices to date. Polyurethane II exhibits properties that makes it suitable as a component of long-indwelling vascular access, with the added advantage of low cost. Objective: To describe the experience of an intravenous therapy team with 206 polyurethane II catheters used as long-indwelling vascular access in patients with cancer. Materials and Methods: All polyurethane II single- and double-lumen catheters implanted between January 1, 1994, and March 15, 1995, were analyzed, including time of stay and type and rate of infectious and noninfectious complications. Results: A total of 206 catheters were placed—164 single-lumen and 42 double-lumen catheters—in 190 patients; average stay was 101 days (range, 1-445 days). The infection incidence rate was 0.66 per 1000 catheter-days for single-lumen catheters and 1.6 per 1000 catheter-days for double-lumen catheters. Noninfectious complications included 1 thrombosis (incidence rate, 0.06 per 1000 catheter-days for single-lumen and none for double-lumen catheters), 5 catheter ruptures (2.4%), and 1 pneumothorax (0.48%). Twelve catheters (8.3%) were removed because of complications; only 1 was infectious. The remaining 17 infectious episodes (94.4%) were resolved without catheter removal. Our complication rate with single-lumen catheters in this series was similar to our previous experience with a nontunneled silicone catheter. Conclusions: Our findings indicate that polyurethane II catheters have proven useful and safe as long-indwelling vascular access in patients with cancer at our hospital at a considerably lower cost. (Am J Infect Control 2003;31:392-6.)
Silastic has been the standard material in the expanding technology for intravascular long-indwelling devices. This preference is due to its particular characteristics, which include its being biocompatible, soft, and nonthrombogenic.1,2 Although new materials for catheter manufacture have been developed, they have not proven to be safe for long duration.3,4 Polyurethane II (Arrow International, Inc, Reading, Penn) is a flexible, soft, low-thrombogenic material that is suitable for long-stay. It also offers the advantage of low cost. This is particularly important in developing countries where patients may not be able to afford
From the Instituto Nacional de Cancerologı´aa; Instituto Nacional de Enfermedades Respiratoriasb; and Instituto de Investigaciones Biome´dicas, Universidad Nacional Auto´noma de Me´xico, Me´xico.c Reprint requests: Patricia Volkow, MD, Infectious Diseases, Instituto Nacional de Cancerologı´a, San Fernando #22, Col. Tlalpan, 14000 Me´xico, DF, Me´xico. Copyright ª 2003 by the Association for Professionals in Infection Control and Epidemiology, Inc. 0196-6553/2003/$30.00 + 0 doi:10.1067/mic.2003.39
392
the cost of a tunneled silastic catheter or a subcutaneous port. We previously published5 the experience our intravenous therapy team (IVTT) had in the care and control of a low-cost, nontunneled silastic catheter (Centrasil; Baxter-Travenol, Morton Grove, Ill) in patients with cancer receiving chemotherapy; the Centrasil catheter offered the same parameters of security compared with more costly catheters studied in other series. Unfortunately, Baxter-Travenol stopped producing this low-cost catheter in 1993. Thus, we needed to choose a new catheter that was both affordable and available in Mexico. In January 1994, we began to use polyurethane II (Arrow International, Inc) single- and double-lumen catheters for long-stay (weeks, months, or even years) in patients with cancer receiving chemotherapy, with use of the same protocol of care used with the Centrasil catheter.5 We report here the experience at the Instituto Nacional de Cancerologı´a (INCan) IVTT with insertion, care, and control of polyurethane II catheters in 190 patients with cancer between January 1994 and March 1995.
Volkow et al
MATERIALS AND METHODS Patients The National Institute of Cancer (INCan) in Mexico City is a national referral center for adult patients who have cancer. Fifty percent of the patient population did not complete elementary school; 14% are illiterate. Sixty-six percent of patients have a family income of less than $6 US dollars per day ($3 [US] is the daily minimum wage in Mexico City). The IVTT was established at INCan in 1988; this team controls care and follow-up of all patients with central venous catheters inserted at the hospital.
Catheters The devices used were single- and double-lumen polyurethane II, nontunneled, percutaneously implanted catheters (Arrow International, Inc). The cost of the single-lumen catheter in Mexico is $17 (US) and $20 (US) for the double-lumen catheter. All patients with cancer who needed a long term-indwelling catheter were selected for this study. In terms of intravenous (IV) line requirements, the treating oncologist chose to use either a single- or double-lumen catheter. Patients who received parenteral nutrition and/or bone marrow transplantation or peripheral blood stem cell transplantation were included. The catheter was also used to withdraw blood samples, always done exclusively by IVTT personnel, in all patients (whether hospitalized or outpatients). Local infection of the catheter insertion site was suspected if the patient had pain, erythema, or purulent secretion; in these cases, a Gram’s stain and culture were performed. In patients with fever, blood culture specimens were obtained from each lumen and at least 1 additional specimen was obtained through peripheral venipuncture.
Diagnostic criteria Local infection was diagnosed on the basis of purulent secretion or induration and culture-positive specimens of the central venous catheter insertion site (non-neutropenic patients) or local erythema and culture-positive specimens of the central venous catheter insertion site (neutropenic patients). Catheter-related bacteremia was diagnosed on the basis of at least 3 of the following 4 criteria: the patient had clinical signs of bacteremia or a temperature of more than 38.38C, blood cultures were positive for the same organism isolated from the catheter insertion site, cultures of the insertion-site specimen and catheter tip yielded the same organism, and remission of symptoms was noted after catheter removal. Neutropenia was defined as a total neutrophil count of less than 1000/mm3.
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In case of local infection, the insertion site was cleaned daily, and treatment with oral antibiotics was initiated. In patients with gram-positive bacteria, topical mupirocin was also used. Patients with catheterrelated bacteremia were treated as inpatients with parenteral antibiotics. The decision to keep the catheter in place was made 48 hours after diagnosis of infection if no signs of infection were present. In patients with persistent infections, the catheter was removed and the catheter tip was sent for culture. IVTTstructure, routine, and diagnostic and catheter removal criteria as well as microbiologic methods were detailed in our previous papers.5,6
Statistical analysis Incidence rates were determined and expressed per 1000 catheter-days. Survival distribution related to complication-free device life; length of catheterization was calculated by the Kaplan-Meier method.7 We estimated the odds ratio (OR), and statistical significance was assessed with the 95% confidence interval (95% CI). Rates of infectious and noninfectious complications in this study were compared with rates reported by Pessa,8 Larson,9 Simmons,10 Mueller,11 Pegues,12 and our previous experience with a nontunneled silicone catheter (Centrasil).5 Sample size was calculated according to Simon.13 A number of evaluable patients were entered into the study, and a frequency of infection was assumed to be 10%. For that number of events, we estimated a total number of 150 patients for statistical power of 80%.
RESULTS During the study period, 206 catheters were placed—164 single-lumen and 42 double-lumen—in 190 patients. One hundred forty four (79%) catheters were placed in 133 women and 62 (30%) in 57 men with mean age of 44 years (range, 13-80 years). Twenty percent of patients in this series had hematologic neoplasia, and 80% had a solid tumor; distribution of malignancies is shown in Table 1. Twelve percent of patients with a single-lumen catheter had hematologic neoplasia, whereas 54.7% of patients in this diagnostic group had a double-lumen catheter. The catheter was used for administration of chemotherapy (inpatient and ambulatory, short and long infusions), antibiotics, IV fluids, and parenteral nutrition; transfusion of blood products; and blood withdrawal for laboratory examinations. Catheters were placed in the following veins: subclavian, 199; internal jugular, 6; and supraclavicular, 1. Average catheter stay was 101 days (range, 1-445 days). The incidence rate of catheter-related infection was 0.66 per 1000 catheter-days for single-lumen
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Table 1. Distribution by neoplasm in patients with long-indwelling polyurethane II single-lumen and double-lumen catheters
Acute lymphoblastic leukemia Acute myeloblastic leukemia Non-Hodgkin’s lymphoma Hodgkin’s disease Multiple myeloma Lymphocytic leukemia Myeloproliferative symptoms Kaposi’s sarcoma (AIDS) Breast carcinoma Uterine cervix carcinoma Digestive tract Osteosarcoma Head and neck carcinoma Others* Total
Single-lumen
Double-lumen
6 (4.2%) 2 (1.2%) 4 (2.4%) 5 (3.0%) 1 (0.6%) 0 1 (0.6%) 6 (3.6%) 75 (45.7%) 15 (9.1%) 7 (4.3%) 12 (7.3%) 15 (9.1%) 15 (9.1%) 164
13 (30.9%) 6 (14.2%) 0 0 2 (4.8%) 1 (2.4%) 0 1 (2.4%) 11 (26.2%) 2 (4.8%) 0 2 (4.8%) 0 4 (9.5%) 42
*Others: ovary, kidney, lung, neuroblastoma, and endometrial.
catheters and 1.6 per 1000 catheter-days for doublelumen catheters. OR was 2.45 (95 %CI, 0.95-6.32) for double-lumen catheters compared with single-lumen catheters. Incidence rate of single-lumen catheterrelated infection during neutropenic periods was 2.05 per 1000 catheter-days and 0.57 per 1000 catheterdays for non-neutropenic periods (OR, 3.56; 95% CI, 0.77-16.45). The incidence rate for double-lumen catheter-related infection during neutropenic periods was 1.6 per 1000 catheter-days and 1.6 per 1000 catheter-days for non-neutropenic periods (OR, 1.01; 95% CI, 0.12-8.4). Eighteen catheter-related infections were recorded in 16 patients (8.4%); 11 were local infections of insertion site (5.3%) and 7 were bacteremia (3.9). Two patients had 2 infectious episodes with the same catheter. One catheter was removed because of infection, whereas the remaining 17 infectious episodes (94.4%) were resolved without catheter removal. Table 2 shows micro-organisms isolated in catheter-related infectious episodes. Overall, 80% were caused by grampositive bacteria and 20% by gram-negative bacteria. Coagulase-negative staphylococci were isolated in 66% cases of local infection and 37.5% cases of bacteremia. Noninfectious complications included 1 thrombosis (incidence rate, 0.06 per 1000 catheter-days for singlelumen catheters and none for double-lumen catheters), 5 catheter ruptures (2.4%), and 1 pneumothorax (0.48%). No cases of local hematoma, superior vena cava syndrome, or lymphatic fistula were detected. At the end of follow-up, 40 catheters (19.4%) were removed because of treatment completion, 38 (18.9%) patients died of cancer with no catheter complications, 75 (36.4%) patients had functioning catheters in place
Table 2. Microorganisms isolated from long-indwelling polyurethane II catheter-related infections Microorganism Coagulase-negative staphylococci Coagulase-positive staphylococci Streptococcus group D Klebsiella pneumoniae Proteus mirabilis Enterobacter species Escherichia coli
Local infection
Bacteremia
8 1 1 0 0 1 1
3 0 1 1 1 1 0
*No polymicrobial bacteremia identified.
at the time of this report, and 14 (6.8%) patients voluntarily discontinued treatment. In 10 (4.8%) patients, the catheter was changed for another type of catheter (eg, Permacath, Quinton Instrument, Seattle, Wash, or a single-lumen for a double-lumen catheter). In 6 cases, catheters were removed due to additional causes: 4 (1.9%) catheters were inadvertently removed by non-IVTT personnel, 1 patient attempted suicide, and another case was due to noncompliance to weekly catheter care. Twelve (5.8%) catheters were removed because of complications (4 catheter obstructions, 5 due to mechanical damage, 1 because of thrombosis, 1 catheter malposition, and 1 because of catheter-related infection). Eleven (5.3%) patients with catheters were lost to follow-up. Installation cost for single- and double-lumen catheters was $38 and $50 (US), respectively. Direct cost of weekly care for 12 months was $240 (US) for single-lumen catheters and $292 (US) for doublelumen catheters, respectively (including the device). Cost for a tunneled silicone catheter in Mexico is $100 (US) and for a nontunneled silicone catheter $80 (US), and the average cost for a subcutaneous port is 400 (US) (these prices are only for the device). Table 3 compares our results with those of 4 reported series, the first in which Hickman catheters (Bard, Crawley, West Sussex) were used; the second, Centrasil catheters; the third, either Hickman or Porta-cath devices (Pharmacia, Piscataway, NJ); and the fourth, our previous experience with the Centrasil catheter. These series and this study were analyzed in a similar method. Table 4 presents the incidence rate of catheter-related complications calculated per 1000 days in comparison with rates reported by Mueller,11 Pegues,12 and Groeger14 for the Hickman, Port-a-cath, Groshong, and our previous experience with the Centrasil catheters.5
DISCUSSION Although silastic has been used as the sole material for long-indwelling intravenous catheters, introduction
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Table 3. Comparison of percentage of noninfectious and infectious catheter-related complications with 3 other studies No.
Hickman 157*
Centrasil 195†
8 (5.1%) 3 (2.3%) 1 (0.6%) NI 2 (1.2%) 1 (0.6%) 4 (2.5%) 1 (0.6%) 20 (12.7%) 7 (4.5%) 13 (8.3%)
3 (1.5%) 3 (1.5%) NI 0% 1 (0.5%) 0 0 0 40 (8.1%) 15 (7.7%) 5 (2.6%)
Thrombosis Pneumothorax Embolism Hematoma Mechanical damage Rupture Superior caval vein syndrome Lymphatic fistula Total infections Local Local plus bacteremia Bacteremia
Centrasil 494‡ 3 3 1 35 9 2 0 0 40 28 8 4
Polyurethane II 206
(0.6%) (0.6%) (0.2%) (7.1%) (1.8%) (0.4%)
1 1 0 0 5 0 0 0 18 11 0 7
(10.3%) (5.6%) (1.61%) (0.8%)
(0.48%) (0.48%)
(2.4%)
(8.73%) (5.3%) (3.39%)
*Pessa M. Surg Gynecol Obstet 1985;161-257.5 ySimmons JR. Med Pediatr Oncol 1992;20:22.10 zVolkow P. CID 1994;18:719.5
Table 4. Rate of catheter-related complications calculated per 1000 catheter-days
Infection Mechanicalk Thrombosis
Hickman* (n = 46)
Port-a-cath* (n = 46)
Hickman† (n = 47)
Port-acath+ (n = 94)
1.6 0.7 0.5
1.2 0.3 0.2
1.8 NI NI
0.4 NI NI
Centrasil‡ (n = 496)
Port-acath§ (n = 680)
0.66 0.45 0.07
0.21 NI NI
Hickman*** (n = 788)
Polyurethane II single-lumen (n = 164)
Polyurethenane II double-lumen (n = 42)
2.76 NI NI
0.66 NI 0.06
1.62 0.45 0.0
NI, Not informed. *Adult and pediatric patients receiving chemotherapy and/or autologous bone marrow reconstitution.11 yAdult patients receiving chemotherapy and/or parenteral nutrition.12 zINCan series. Adult patients receiving chemotherapy.7 §Sloan-Kettering series. Adult patients receiving chemotherapy. No patients with ports had bone marrow transplantation.16 kMechanical: catheter rupture, obstruction, or dislodgment.
of new materials that share some characteristics of biocompatibility, flexibility, and low thrombogenicity such as polyurethane2-4 offers the possibility to use these new materials for long-indwelling IV lines. Polyurethane II has these characteristics in addition to a lower cost than silastic, an important advantage when health care budgets are restricted. The majority of authors postulate that risk of infection from these devices can be overcome by technologic advances such as the introduction of the Dacron cuff, vita cuff, or even additional sophisticated devices that release silver ions. This has led to an escalated design of sophisticated catheters.15-22 Extensive experiences5,23 question this position: not only does this enormously increase device prices, but also it can render the potential danger of allergic reaction. To date, no technologic implementation in an intravenous catheter can guarantee its safety if the catheter does not receive proper care. The experience we have presented leads us to postulate that strict protocol of catheter care can result in a safety index as high as indices for more sophisticated and expensive devices and highlights the importance of the IVTT in the care of
intravascular devices. Advantages achieved with use of polyurethane II catheters as long-indwelling IV lines are due both to the catheter itself and to the care provided by a professional team. Furthermore, we postulate that silastic should no longer be the sole material used for long-indwelling IV lines. Our complication rate with the single-lumen polyurethane II catheter is similar to our previous experience with a nontunneled, single-lumen silicone catheter. The infection incidence rate with doublelumen is 3 times higher; this difference could be related to patient type, as hematologic malignancies are overrepresented in this group, with longer periods of neutropenia, previously recognized as increasing risk of catheter-related infection.5 The fact that we found no find fungi could be because very few patients received parenteral nutrition, the main risk factor for catheter-related fungi infection at our hospital. Compared with the findings of Keung,23 thrombosis incidence rate is particularly low in our study, probably because of low thrombogenic potential of polyurethane II. These findings strongly suggest that polyurethane II catheters can be safe and useful for long-indwelling
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vascular access in cancer patients at our hospital. Our results are within the safety range of results published with more costly silicone catheters. References 1. Gravenstein N, Blackshear RH. In vitro evaluation of relative perforating potential of central venous catheters: comparison of materials, selected models, number of lumens, and angles of incidence to simulated membrane. L Clin Monitoring 1991;7:1-6. 2. Stenqvist O, Curelaru I, Linder LE, Gustavsson B. Stiffness of central venous catheters. Acta Anaesthesiol Scan 1983;27:153-7. 3. Linder LE, Curelaru I, Gustavsson B, Hansson HA, Stenqvist O, Wojciechowski J. Material thrombogenicity in central venous catheterization: a comparison between soft antebrachial catheters of silicone elastomer and polyurethane. J Parent Nutr 1984;8:400-6. 4. Zdrahala RJ, Solomon DD, Lentz DJ, McGary CW. Thermoplastic polyurethanes. Materials for vascular catheters. In: Planck H, et al, eds. Polyurethanes in biomedical engineering. II. Amsterdam: Elsevier Science; 1987. p. 1-18. 5. Volkow P, Sanchez-Mejorada P, Lazo S, Va´zquez C, Te´llez O, Baez RM, et al. Experience of an intravenous therapy team at the Instituto Nacional de Cancerologı´a (Mexico) with a long-lasting, low-cost silastic venous catheter. Can Infect Dis 1994;18:719-25. 6. Kaplan EL, Mieier P. Nonparametric estimation from incomplete observation. J Am Stat Assoc 1958;53:457-81. 7. Simo´n R. Clinical trials in cancer. In: De Vita V, Hellman S, Rosenberg SA, editors. Cancer principles and practices, 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 321-38. 8. Pessa ME, Howard RJ. Complications of Hickman-Broviac catheter. Surg Gynecol Obstet 1985;161:257-60. 9. Larson EB, Wooding M, Hickman RO. Infectious complications of right atrial catheters used for venous access in patients receiving intensive chemotherapy. Surg Gynecol Obstet 1981;153:369-73. 10. Simmons JR, Buzdar AU, Ota DM, Marts K, Hortobagyi GN. Complications associated with indwelling catheter. Med Pediatr Oncol 1992;20:22-5. 11. Mueller BU, Skelton J, Callender DP, et al. A prospective randomized trial comparing the infectious and noninfectious complications of an externalized catheter versus a subcutaneously implanted device in cancer patients. J Clin Oncol 1992;10:1943-8.
Volkow et al 12. Pegues D, Axelrod P, McClarren C, et al. Comparison of infections in Hickman and implanted port catheter in adult solid tumor patients. J Surg Oncol 1992;49:156-62. 13. Simon R. Optimal two-stage designs for phase II clinical trials. Cancer Clin Trials 1989;10:1-7. 14. Groeger JS, Lucas AB, Thaler HT, Friedlander-Klar H, Brown AE, Kiehan TE, Armstrong D. Infectious morbidity associated with longterm use of venous access devices in patients with cancer. Ann Intern Med 1993;119:1168-74. 15. Bach A, Bo¨hrer H, Motsch J, Martin E, Geiss HK, Sonntag HG. Prevention of bacterial colonization of intravenous catheters by antiseptic impregnation of polyurethane polymers. J Antimicrob Chemother 1994;33:969-78. 16. Maki DG, Garman JK, Shapiro JM, Ringer M, Helgerson RB. An attachable silver-impregnated cuff for prevention of infection with central venous catheters: prospective randomized multicenter trial. Am J Med 1988;85:307-14. 17. Flowers RH, Schwenzer KJ, Kopel RF, Fisch MJ, Tucker SI, Farr BM. Efficacy of an attachable subcutaneous cuff for the prevention of intravascular catheter-related infection. JAMA 1989;262:878-83. 18. Norwood S, Hajjar G, Jenkins L. The influence of an attachable subcutaneous cuff for preventing triple lumen catheter infections in critically ill surgical and trauma patients. Surg Gynecol Obstet 1992; 175:33-40. 19. Raad I, Darouchi R, Dupuis J, Abi-Said D, Gabrielli A, Hachem R, et al. Central venous catheters coated with minocycline and rifampin for the prevention of catheter-related colonization and bloodstream infections. A randomized, double-blind trial. Ann Intern Med 1997; 127:267-74. 20. Maki DG, Stolz SM, Wheeler S, Mermel LA. Prevention of central venous catheter-related bloodstream infection by use of an antisepticimpregnated catheter. A randomized controlled trial. Ann Intern Med 1997;127:257-66. 21. Daoruchi RO, Raad I, Head SO, Thornby JI, Wenker OC, Gabrielli A, et al. A comparison of two antimicrobial-impregnated central venous catheters. N Engl J Med 1999;340:1-8. 22. Raad I, Hachem R, Zermeno A, Stephens LC, Bodey GP. Silver iontophoretic catheter: a prototype of a long-term antiinfective vascular access device. J Infect Dis 1996;173(2):495-8. 23. Keung YK, Watkins K, Chen SC, Groshen S, Silberman H, Douer D. Comparative study of infectious complications of different types of chronic central venous access devices. Cancer 1994;73:2832-7.