Pediatr Blood Cancer 2014;61:855–858
Impact of Decreased Heparin Dose for Flush-Lock of Implanted Venous Access Ports in Pediatric Oncology Patients Glenn Rosenbluth, MD,* Lisa Tsang, RN, MN, Eric Vittinghoff, PhD, Stephen Wilson, Julie Wilson-Ganz, PharmD, and Andrew Auerbach, MD, MPH Background. Faced with a lack of evidence, institutions often develop local protocols for use of heparin to flush-lock venous access ports. Our objective was to evaluate catheter-related complications in patients after introduction of a lower-concentration heparin flush protocol. Procedure. Patients with implanted vascular access devices followed by a Pediatric Oncology service were exposed to a practice change in which heparin dose for flush-lock was decreased from 5 ml of 100 units/ml to 5 ml of 10 units/ml. Outcome measures included port malfunctions leading to use of intra-port tissue plasminogen activator (tPA), and positive blood cultures. Results. Rates of tPA
MD, PhD,
usage were statistically similar before and after the practice change (0.82 compared to 0.59 per 100 line days absolute change 0.23, 95% CI 0.66, 0.20). Positive blood culture rates were also statistically similar before and after the practice change. Conclusions. Children with implanted ports had similar complication rates and care safety measures whether their ports were flushed with 10 units/ ml of heparin or 100 units/ml. Standardizing flush-locks to lower doses of heparin may be a promising approach to maintaining port patency without compromising patient safety. Pediatr Blood Cancer 2014;61:855–858. # 2014 Wiley Periodicals, Inc.
Key words: heparin; implanted ports; patient safety
INTRODUCTION The Institute for Safe Medication Practices (ISMP) categorizes heparin as a “high-alert” medication because of the potential for catastrophic complications. In 2007, The Joint Commission first charged hospitals to “reduce the likelihood of patient harm associated with the use of anticoagulant therapy,” by inclusion as a National Patient Safety Goal (NSPG) [1]. A review of reporting systems covering over 1,000 institutions identified the prescribing and administration phases as the most error-prone and highest risk [2]. Another recent study found that as many as one in seven patients receiving heparin may experience an adverse drug event [3], , though presumably this refers to systemic usage. Perhaps the most common use of heparin in children is to maintain patency of central venous catheters (tunneled and nontunneled), peripherally inserted central catheters (PICC), and implanted vascular access devices. Guidelines are available which provide recommendations for reducing risk of thrombus [4–6] and infection [7] associated with central venous access devices in general. However, the guidelines do not provide specific recommendations for implanted ports. Implanted venous access ports present a particular challenge because they cannot be easily repaired or removed. Concern for medical errors combined with lack of robust data to support any single flushing strategy as superior, has led to wide variation in practices. A 2010 national survey identified a lack of consistency in practice among 75 different children’s hospitals [8]. Specifically, significant variation in use of heparin for flush-lock (vs. nonheparinized solutions), concentration of flush-lock medication used, and frequency of flush-lock were all noted. Lack of consistency affected all catheter types and no single variable consistently predicted misuse in any type of catheter. In order to standardize local practice and reduce risk for complications, UCSF Benioff Children’s Hospital implemented a quality improvement project to decrease the potential for heparinrelated errors by standardizing heparin concentrations to 10 units/ ml for all central venous access devices except Groshong catheters, which are saline-locked, and dialysis catheters, which are sodium citrate-locked. As a balancing measure, we tracked both tPA usage C
2014 Wiley Periodicals, Inc. DOI 10.1002/pbc.24949 Published online 24 January 2014 in Wiley Online Library (wileyonlinelibrary.com).
(as a proxy for clot formation) and rates of positive blood cultures [9].
METHODS Site and Subjects We identified children with implanted vascular access ports who were cared for by our Division of Pediatric Oncology at any time between October 1, 2007 and September 30, 2011. Patients may have been seen on our inpatient medical unit or in our outpatient Pediatric Treatment Center. Outpatient visits included physician appointments as well as ambulatory procedures including chemotherapy and other medication administration, transfusions, lumbar punctures, phlebotomy, etc. We did not set age limitations as long as the patients were followed by the Pediatric Oncology service. We excluded patients who did not have a cancer diagnosis (e.g., patients with bleeding diathesis). The study was approved by the University of California San Francisco, Institutional Review Board.
Intervention UCSF Benioff Children’s Hospital standardized heparin concentrations for use in flush-locking central venous catheters in the inpatient and outpatient settings in October 2009. Prior to this date, ports were flush-locked monthly with 5 ml of heparin 100 units/ml, and after this date they were flush-locked monthly with 5 ml of heparin 10 units/ml. This practice was in place within our Department of Pediatrics, UCSF Benioff Children’s Hospital, San Francisco, California Grant sponsor: NHLBI; Grant number: K24HL098372; Grant sponsor: Young Investigators Award from the Academic Pediatrics Association Conflict of Interest: Nothing to report. Correspondence to: Glenn Rosenbluth, 505 Parnassus Ave., M-691, San Francsico, CA. E-mail: [email protected]
Received 8 October 2013; Accepted 20 November 2013
856
Rosenbluth et al.
institution, and in our outpatient orders for patients who get their ports flushed via a home-health company. During inpatient stays, ports are rarely flush-locked as they need to be accessed frequently and often IV fluids are being administered.
Outcomes Primary outcomes were use of tissue plasminogen activator (tPA) and positive blood cultures. There are no standards for confirming port thrombosis without either radiologic studies or port removal, but use of tPA is a clinically reasonable indicator of thrombotic complications related to inadequate flushing (particularly if tPA resolves the malfunction), while also representing an event prior to premature port removal. Any IV tPA administered in our treatment center at outpatient visits was presumed to be in response to presumed occlusion. Home-health companies routinely contact primary physicians when there are problems with ports, and orders for tPA are never given via these services. Therefore, tPA in the outpatient setting would only be administered in our treatment center. Intravenous tPA administered on the inpatient unit was counted if it was within the first 24 hours of admission, as that would be most likely to be related to pre-hospitalization flush-lock. Total tPA events, including any point during hospitalization, are also presented. Blood cultures were considered positive if they were drawn from the port and grew any bacterial organism within 48 hours.
data capture for research studies, providing: (1) an intuitive interface for validated data entry; (2) audit trails for tracking data manipulation and export procedures; (3) automated export procedures for seamless data downloads to common statistical packages; and (4) procedures for importing data from external sources.
Statistical Analysis We used exact methods in Stata [11] to compare overall rates of malfunction, rates of tPA administration, and rates of positive blood cultures, both pre- and post-intervention.
RESULTS Patient Characteristics There were no significant differences in gender makeup, age, BMI, or cancer diagnoses in the pre- versus post-intervention periods (Table I). Our intervention was at a defined time point universal to all patients, without regard for when their ports were placed and/or removed. Therefore, some patients had port-days only in the pre-intervention period, some had port-days only in the post-intervention period, and some had both. There were 86 patients with line-days in the pre-intervention period and, 89 in the postintervention, resulting in 28,857 port-days pre-intervention and 29,348 port-days post-intervention.
Port Malfunctions and tPA Usage Data Collection and Analysis Our study was conducted during a time period when we used paper charts in the outpatient setting and an electronic health record in the inpatient setting. We collected pre- and post-intervention data in the outpatient setting retrospectively using a standardized tool. At each outpatient visit during the study-period we identified whether any port related problems were noted, including referral for additional evaluation. Within this group, we identified those patients in whom the port was noted to not flush briskly and if tPA was administered. If tPA administration resolved the problem, it was assumed that there was an occlusive thrombus. For inpatients, we were able to collect tPA usage data via our inpatient pharmacy database; doses were verified to ensure that they were consistent with line-occlusion, rather than other indications such as thrombotic stroke. If tPA was administered and the port was used afterwards it was assumed there was an occlusion resolved by the tPA. Our primary endpoint for inpatient data were occlusions noted in the first 24 hours of admission, as those were thought to be more related to the outpatient heparin flush-locks. Of note, inpatient tPA usage was also reviewed on a monthly basis post-intervention to monitor in real-time for unexpected adverse events. However for final analysis we collected pre- and post-intervention data retrospectively using similar methodology. Microbiologic data were collected by direct chart reviews of both clinic notes, History and Physical notes, and Progress notes for the first 2 days of any hospitalization during the study period to determine if any blood cultures were sent at UCSF or a referring institution. Any positive blood cultures were logged. Study data were collected and managed using the Research Electronic Data Capture (REDCap) tools hosted at UCSF [10]. REDCap is a secure, web-based application designed to support Pediatr Blood Cancer DOI 10.1002/pbc
We identified a total of 41 instances of tPA usage in 33 unique patients during our study period, including inpatient and outpatient settings. There were 24 instances pre-intervention (0.82 per 1,000 port-days) and 17 post-intervention (0.59 per 1,000 port-days), with an absolute rate reduction of 0.23 per 1,000 (95% CI 0.66, 0.20). We also analyzed inpatient usage in the first 24 hours of hospitalization (Table II). In all cases where tPA was administered, obstruction was resolved. Cancer diagnoses for patients with tPA events are shown in Table III.
Positive Blood Cultures Positive blood cultures were less common than port malfunctions. We identified 15 positive blood cultures in the preintervention period (0.51 per 1,000 port-days) and 15 in the postintervention period (0.52 per 1,000 port-days), with an absolute rate increase of 0.01 per 1,000, 95% CI 0.36, 0.38. There were no positive blood cultures in patients who had tPA-related port malfunctions.
DISCUSSION In our single site study, a protocol to flush-lock implanted vascular access ports with 5 ml of heparin 10 units/ml appeared to TABLE I. Subject Demographics
Total line days Age (y), range Gender (% male)
Pre-intervention
Post-intervention
29,660 9.2 (1–22) 63%
27,804 9.8 (0–28) 56%
Decreasing Heparin Dose in Implanted Ports
857
TABLE II. Breakdown of tPA Usage Based on Setting Pre-intervention (heparin 100 units/ml)
Post-intervention (heparin 10 units/ml)
Absolute change (95% CI)
0.48 0.82 0.51
0.28 0.59 0.52
0.20 (0.51, 0.12) 0.23 (0.66, 0.20) 0.01 (0.36, 0.38)
tPA in outpatient or inpatient in first 24 hours of admission tPA in outpatient or inpatient, any time Positive blood cultures in any setting All data are in events-per-1,000 port-days.
have similar complication and infection rates as a higher-dose flush strategy. While these findings could be related to our small sample size, our results are a promising potential indication of a strategy which could reduce risks related to heparin flushing or medication errors in the administration of heparin. Medication errors are common, and heparin is one of the most common medications implicated in errors and adverse events [3]. Used appropriately, standardization can improve patient safety [12]. Our institution took the pro-active step of trying to reduce the likelihood of a heparin error by standardizing its usage to the 10 units/ml concentration when needed for flush-locking central venous access devices, thus enabling us to routinely stock only one concentration on acute care inpatient units. Clinicians should be aware of the potential negative complications of lower doses of heparin, which have been reported in other studies. A single randomized trial found increased complication rates in patients with Broviac–Hickman CVCs flush-locked with normal saline and positive-pressure locked once-weekly, compared to those flushed with heparin 200 units/ml twice-weekly [13]. The occlusion rate with heparin in this study (1.11 per 1,000 line days) is lower than has been published [14] using 50 units/ml concentration, though both studies are reporting rates in tunneled catheters, not implanted ports. Catheter-associated deep-vein thrombosis (DVT) is a known complication of implanted venous access devices [15,16] and a decreased dose of heparin has the potential to increase the risk of DVT. We did not routinely perform ultrasounds on our patients with implanted devices. However, it is unlikely that the variation in heparin dose in our study would have any effect on deep-vein thrombi since the dose used for flush locking is significantly lower than that used for thromboprophylaxis (5,000 units q8– 12 hours) [17]. Malfunctioning catheters are associated with higher likelihood of bacteremia [9] and a variety of strategies have been shown to decrease this risk, including continuous infusion of heparin [18] TABLE III. Patients and Diagnoses With tPA Usage Cancer type ALL Ewing sarcoma Rhabdomyosarcoma Osteosarcoma Brain tumor Histiocytosis Hepatoblastoma Retinoblastoma Spindle cell sarcoma Wilms tumor Neuroblastoma
Total events
Discrete patients with events
13 5 5 4 4 2 3 2 1 1 1
11 4 4 4 2 2 1 2 1 1 1
Pediatr Blood Cancer DOI 10.1002/pbc
(not practical for outpatients) and heparin-coated catheters [19,20]. However, other studies have questioned the antibacterial benefits of heparin over other flush-lock solutions, particularly at the higher doses used in dialysis catheters [21,22]. Our study has several important limitations. We did not collect all data prospectively nor did we randomize patients, and we relied on surrogate measures of thrombi rather than documented thrombi. Our data suggest that we can safely flush-lock implanted vascular access ports with a heparin concentration of 10 units/ml without compromising the patency of the port. We saw no significant difference in complication rates for patients with ports flush-locked at this lower dose. Ongoing prospective evaluation is needed to confirm these results. Standardization of dosage across line-types is simply one approach to reduce the risk associated with heparin in central venous catheters. A possibly more clinically critical endpoint would be to eliminate heparin usage in settings where it is not clinically indicated. This preliminary study should support additional studies in the pediatric and adult populations, and eventually evidencebased guidelines for standardization across institutions.
ACKNOWLEDGMENTS Lori Fineman, RN, MS was essential to the early development of the quality improvement project. Emily Asher, MS, MPH, MPA, Lauren Dickey, MPH, and Ashley Diaz, BS provided support for data entry. This project was supported by a Young Investigators Award from the Academic Pediatrics Association, awarded to Dr. Rosenbluth. Dr. Auerbach was supported by NHLBI grant K24HL098372 during the course of this study.
REFERENCES 1. The Joint Commission. 2010. National Patient Safety Goals (NPSGs), 2010. http://www.jointcommission.org/GeneralPublic/NPSG/10_npsgs.htm Accessed October 12, 2010. 2. Grissinger MC, Hicks RW, Keroack MA, et al. Harmful medication errors involving unfractionated and low-molecular-weight heparin in three patient safety reporting programs. Jt Comm J Qual Patient Saf 36:195–202. 3. Classen DC, Jaser L, Budnitz DS. Adverse drug events among hospitalized Medicare patients: Epidemiology and national estimates from a new approach to surveillance. Jt Comm J Qual Patient Saf 2010;36:12–21. 4. Monagle P, Chan AK, Goldenberg NA, et al. Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e737S–e801S. 5. ASHP Commission on Therapeutics. ASHP therapeutic position statement on the institutional use of 0.9% sodium chloride injection to maintain patency of peripheral indwelling intermittent infusion devices. Am J Health Syst Pharm 2006;63:1273–1275. 6. Program in Evidence-based Care (PEBC) CCOC. Managing Central Venous Access Devices in Cancer Patients. Nursing Evidence-based Series 2006. http://www.cancercare.on.ca/cms/One.aspx? portalId¼1377&pageId¼10369. Accessed October 12, 2010, 2010. 7. O’Grady NP, Alexander M, Burns LA, et al. Guidelines for the prevention of intravascular catheterrelated infections. Am J Infect Control 2011;39:S1–S34. 8. Harris JM, Wilson Ganz J, Scarpace Lucas S, et al. Heparin flush lock practices in children’s hospitals. National Association of Children’s Hospitals and Related Institutions 2010 Leadership Conference, 2010. http://www.childrenshospitals.net/Content/ContentFolders34/EducationMeetings2/AnnualMeeting/ 2010/posters/HeparinFlushLock_poster.pdf. Accessed October 4, 2013. 9. Rowan CM, Miller KE, Beardsley AL, et al. Alteplase use for malfunctioning central venous catheters correlates with catheter-associated bloodstream infections. Pediatr Crit Care Med 2013;14:306–309.
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10. Harris PA, Taylor R, Thielke R, et al. Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42:377–381. 11. Stata Statistical Software: Release 12 [computer program]. College Station, TX: StataCorp LP; 2011. 12. Institute of Medicine (U.S.). Committee on Quality of Health Care in America. Crossing the quality chasm: A new health system for the 21st century. Washington, DC: National Academy Press; 2001. 13. Cesaro S, Tridello G, Cavaliere M, et al. Prospective, randomized trial of two different modalities of flushing central venous catheters in pediatric patients with cancer. J Clin Oncol 2009;27:2059–2065. 14. Ociepa T, Maloney E, Urasinski T, et al. Thrombotic complications of tunneled central lines in children with malignancy. J Pediatr Hematol Oncol 2010;32:88–92. 15. Revel-Vilk S, Yacobovich J, Tamary H, et al. Risk factors for central venous catheter thrombotic complications in children and adolescents with cancer. Cancer 2010;116:4197–4205. 16. Journeycake JM, Buchanan GR. Catheter-related deep venous thrombosis and other catheter complications in children with cancer. J Clin Oncol 2006;24:4575–4580.
Pediatr Blood Cancer DOI 10.1002/pbc
17. Lexi-Drugs. 2013. http://www.crlonline.com/lco/action/home. Accessed June 28, 2013. 18. Birch P, Ogden S, Hewson M. A randomised, controlled trial of heparin in total parenteral nutrition to prevent sepsis associated with neonatal long lines: The Heparin in Long Line Total Parenteral Nutrition (HILLTOP) trial. Arch Dis Child Fetal Neonatal Ed 2010;95:F252–F257. 19. Pierce CM, Wade A, Mok Q. Heparin-bonded central venous lines reduce thrombotic and infective complications in critically ill children. Intensive Care Med 2000;26:967–972. 20. Gilbert RE, Harden M. Effectiveness of impregnated central venous catheters for catheter related blood stream infection: A systematic review. Curr Opin Infect Dis 2008;21:235–245. 21. Power A, Duncan N, Singh SK, et al. Sodium citrate versus heparin catheter locks for cuffed central venous catheters: A single-center randomized controlled trial. Am J Kidney Dis 2009;53:1034– 1041. 22. Solomon LR, Cheesbrough JS, Ebah L, et al. A randomized double-blind controlled trial of taurolidinecitrate catheter locks for the prevention of bacteremia in patients treated with hemodialysis. Am J Kidney Dis 2010;55:1060–1068.
Impact of Decreased Heparin Dose for Flush-Lock of Implanted Venous Access Ports in Pediatric Oncology Patients Glenn Rosenbluth, MD,* Lisa Tsang, RN, MN, Eric Vittinghoff, PhD, Stephen Wilson, Julie Wilson-Ganz, PharmD, and Andrew Auerbach, MD, MPH Background. Faced with a lack of evidence, institutions often develop local protocols for use of heparin to flush-lock venous access ports. Our objective was to evaluate catheter-related complications in patients after introduction of a lower-concentration heparin flush protocol. Procedure. Patients with implanted vascular access devices followed by a Pediatric Oncology service were exposed to a practice change in which heparin dose for flush-lock was decreased from 5 ml of 100 units/ml to 5 ml of 10 units/ml. Outcome measures included port malfunctions leading to use of intra-port tissue plasminogen activator (tPA), and positive blood cultures. Results. Rates of tPA
MD, PhD,
usage were statistically similar before and after the practice change (0.82 compared to 0.59 per 100 line days absolute change 0.23, 95% CI 0.66, 0.20). Positive blood culture rates were also statistically similar before and after the practice change. Conclusions. Children with implanted ports had similar complication rates and care safety measures whether their ports were flushed with 10 units/ ml of heparin or 100 units/ml. Standardizing flush-locks to lower doses of heparin may be a promising approach to maintaining port patency without compromising patient safety. Pediatr Blood Cancer 2014;61:855–858. # 2014 Wiley Periodicals, Inc.
Key words: heparin; implanted ports; patient safety
INTRODUCTION The Institute for Safe Medication Practices (ISMP) categorizes heparin as a “high-alert” medication because of the potential for catastrophic complications. In 2007, The Joint Commission first charged hospitals to “reduce the likelihood of patient harm associated with the use of anticoagulant therapy,” by inclusion as a National Patient Safety Goal (NSPG) [1]. A review of reporting systems covering over 1,000 institutions identified the prescribing and administration phases as the most error-prone and highest risk [2]. Another recent study found that as many as one in seven patients receiving heparin may experience an adverse drug event [3], , though presumably this refers to systemic usage. Perhaps the most common use of heparin in children is to maintain patency of central venous catheters (tunneled and nontunneled), peripherally inserted central catheters (PICC), and implanted vascular access devices. Guidelines are available which provide recommendations for reducing risk of thrombus [4–6] and infection [7] associated with central venous access devices in general. However, the guidelines do not provide specific recommendations for implanted ports. Implanted venous access ports present a particular challenge because they cannot be easily repaired or removed. Concern for medical errors combined with lack of robust data to support any single flushing strategy as superior, has led to wide variation in practices. A 2010 national survey identified a lack of consistency in practice among 75 different children’s hospitals [8]. Specifically, significant variation in use of heparin for flush-lock (vs. nonheparinized solutions), concentration of flush-lock medication used, and frequency of flush-lock were all noted. Lack of consistency affected all catheter types and no single variable consistently predicted misuse in any type of catheter. In order to standardize local practice and reduce risk for complications, UCSF Benioff Children’s Hospital implemented a quality improvement project to decrease the potential for heparinrelated errors by standardizing heparin concentrations to 10 units/ ml for all central venous access devices except Groshong catheters, which are saline-locked, and dialysis catheters, which are sodium citrate-locked. As a balancing measure, we tracked both tPA usage C
2014 Wiley Periodicals, Inc. DOI 10.1002/pbc.24949 Published online 24 January 2014 in Wiley Online Library (wileyonlinelibrary.com).
(as a proxy for clot formation) and rates of positive blood cultures [9].
METHODS Site and Subjects We identified children with implanted vascular access ports who were cared for by our Division of Pediatric Oncology at any time between October 1, 2007 and September 30, 2011. Patients may have been seen on our inpatient medical unit or in our outpatient Pediatric Treatment Center. Outpatient visits included physician appointments as well as ambulatory procedures including chemotherapy and other medication administration, transfusions, lumbar punctures, phlebotomy, etc. We did not set age limitations as long as the patients were followed by the Pediatric Oncology service. We excluded patients who did not have a cancer diagnosis (e.g., patients with bleeding diathesis). The study was approved by the University of California San Francisco, Institutional Review Board.
Intervention UCSF Benioff Children’s Hospital standardized heparin concentrations for use in flush-locking central venous catheters in the inpatient and outpatient settings in October 2009. Prior to this date, ports were flush-locked monthly with 5 ml of heparin 100 units/ml, and after this date they were flush-locked monthly with 5 ml of heparin 10 units/ml. This practice was in place within our Department of Pediatrics, UCSF Benioff Children’s Hospital, San Francisco, California Grant sponsor: NHLBI; Grant number: K24HL098372; Grant sponsor: Young Investigators Award from the Academic Pediatrics Association Conflict of Interest: Nothing to report. Correspondence to: Glenn Rosenbluth, 505 Parnassus Ave., M-691, San Francsico, CA. E-mail: [email protected]
Received 8 October 2013; Accepted 20 November 2013
856
Rosenbluth et al.
institution, and in our outpatient orders for patients who get their ports flushed via a home-health company. During inpatient stays, ports are rarely flush-locked as they need to be accessed frequently and often IV fluids are being administered.
Outcomes Primary outcomes were use of tissue plasminogen activator (tPA) and positive blood cultures. There are no standards for confirming port thrombosis without either radiologic studies or port removal, but use of tPA is a clinically reasonable indicator of thrombotic complications related to inadequate flushing (particularly if tPA resolves the malfunction), while also representing an event prior to premature port removal. Any IV tPA administered in our treatment center at outpatient visits was presumed to be in response to presumed occlusion. Home-health companies routinely contact primary physicians when there are problems with ports, and orders for tPA are never given via these services. Therefore, tPA in the outpatient setting would only be administered in our treatment center. Intravenous tPA administered on the inpatient unit was counted if it was within the first 24 hours of admission, as that would be most likely to be related to pre-hospitalization flush-lock. Total tPA events, including any point during hospitalization, are also presented. Blood cultures were considered positive if they were drawn from the port and grew any bacterial organism within 48 hours.
data capture for research studies, providing: (1) an intuitive interface for validated data entry; (2) audit trails for tracking data manipulation and export procedures; (3) automated export procedures for seamless data downloads to common statistical packages; and (4) procedures for importing data from external sources.
Statistical Analysis We used exact methods in Stata [11] to compare overall rates of malfunction, rates of tPA administration, and rates of positive blood cultures, both pre- and post-intervention.
RESULTS Patient Characteristics There were no significant differences in gender makeup, age, BMI, or cancer diagnoses in the pre- versus post-intervention periods (Table I). Our intervention was at a defined time point universal to all patients, without regard for when their ports were placed and/or removed. Therefore, some patients had port-days only in the pre-intervention period, some had port-days only in the post-intervention period, and some had both. There were 86 patients with line-days in the pre-intervention period and, 89 in the postintervention, resulting in 28,857 port-days pre-intervention and 29,348 port-days post-intervention.
Port Malfunctions and tPA Usage Data Collection and Analysis Our study was conducted during a time period when we used paper charts in the outpatient setting and an electronic health record in the inpatient setting. We collected pre- and post-intervention data in the outpatient setting retrospectively using a standardized tool. At each outpatient visit during the study-period we identified whether any port related problems were noted, including referral for additional evaluation. Within this group, we identified those patients in whom the port was noted to not flush briskly and if tPA was administered. If tPA administration resolved the problem, it was assumed that there was an occlusive thrombus. For inpatients, we were able to collect tPA usage data via our inpatient pharmacy database; doses were verified to ensure that they were consistent with line-occlusion, rather than other indications such as thrombotic stroke. If tPA was administered and the port was used afterwards it was assumed there was an occlusion resolved by the tPA. Our primary endpoint for inpatient data were occlusions noted in the first 24 hours of admission, as those were thought to be more related to the outpatient heparin flush-locks. Of note, inpatient tPA usage was also reviewed on a monthly basis post-intervention to monitor in real-time for unexpected adverse events. However for final analysis we collected pre- and post-intervention data retrospectively using similar methodology. Microbiologic data were collected by direct chart reviews of both clinic notes, History and Physical notes, and Progress notes for the first 2 days of any hospitalization during the study period to determine if any blood cultures were sent at UCSF or a referring institution. Any positive blood cultures were logged. Study data were collected and managed using the Research Electronic Data Capture (REDCap) tools hosted at UCSF [10]. REDCap is a secure, web-based application designed to support Pediatr Blood Cancer DOI 10.1002/pbc
We identified a total of 41 instances of tPA usage in 33 unique patients during our study period, including inpatient and outpatient settings. There were 24 instances pre-intervention (0.82 per 1,000 port-days) and 17 post-intervention (0.59 per 1,000 port-days), with an absolute rate reduction of 0.23 per 1,000 (95% CI 0.66, 0.20). We also analyzed inpatient usage in the first 24 hours of hospitalization (Table II). In all cases where tPA was administered, obstruction was resolved. Cancer diagnoses for patients with tPA events are shown in Table III.
Positive Blood Cultures Positive blood cultures were less common than port malfunctions. We identified 15 positive blood cultures in the preintervention period (0.51 per 1,000 port-days) and 15 in the postintervention period (0.52 per 1,000 port-days), with an absolute rate increase of 0.01 per 1,000, 95% CI 0.36, 0.38. There were no positive blood cultures in patients who had tPA-related port malfunctions.
DISCUSSION In our single site study, a protocol to flush-lock implanted vascular access ports with 5 ml of heparin 10 units/ml appeared to TABLE I. Subject Demographics
Total line days Age (y), range Gender (% male)
Pre-intervention
Post-intervention
29,660 9.2 (1–22) 63%
27,804 9.8 (0–28) 56%
Decreasing Heparin Dose in Implanted Ports
857
TABLE II. Breakdown of tPA Usage Based on Setting Pre-intervention (heparin 100 units/ml)
Post-intervention (heparin 10 units/ml)
Absolute change (95% CI)
0.48 0.82 0.51
0.28 0.59 0.52
0.20 (0.51, 0.12) 0.23 (0.66, 0.20) 0.01 (0.36, 0.38)
tPA in outpatient or inpatient in first 24 hours of admission tPA in outpatient or inpatient, any time Positive blood cultures in any setting All data are in events-per-1,000 port-days.
have similar complication and infection rates as a higher-dose flush strategy. While these findings could be related to our small sample size, our results are a promising potential indication of a strategy which could reduce risks related to heparin flushing or medication errors in the administration of heparin. Medication errors are common, and heparin is one of the most common medications implicated in errors and adverse events [3]. Used appropriately, standardization can improve patient safety [12]. Our institution took the pro-active step of trying to reduce the likelihood of a heparin error by standardizing its usage to the 10 units/ml concentration when needed for flush-locking central venous access devices, thus enabling us to routinely stock only one concentration on acute care inpatient units. Clinicians should be aware of the potential negative complications of lower doses of heparin, which have been reported in other studies. A single randomized trial found increased complication rates in patients with Broviac–Hickman CVCs flush-locked with normal saline and positive-pressure locked once-weekly, compared to those flushed with heparin 200 units/ml twice-weekly [13]. The occlusion rate with heparin in this study (1.11 per 1,000 line days) is lower than has been published [14] using 50 units/ml concentration, though both studies are reporting rates in tunneled catheters, not implanted ports. Catheter-associated deep-vein thrombosis (DVT) is a known complication of implanted venous access devices [15,16] and a decreased dose of heparin has the potential to increase the risk of DVT. We did not routinely perform ultrasounds on our patients with implanted devices. However, it is unlikely that the variation in heparin dose in our study would have any effect on deep-vein thrombi since the dose used for flush locking is significantly lower than that used for thromboprophylaxis (5,000 units q8– 12 hours) [17]. Malfunctioning catheters are associated with higher likelihood of bacteremia [9] and a variety of strategies have been shown to decrease this risk, including continuous infusion of heparin [18] TABLE III. Patients and Diagnoses With tPA Usage Cancer type ALL Ewing sarcoma Rhabdomyosarcoma Osteosarcoma Brain tumor Histiocytosis Hepatoblastoma Retinoblastoma Spindle cell sarcoma Wilms tumor Neuroblastoma
Total events
Discrete patients with events
13 5 5 4 4 2 3 2 1 1 1
11 4 4 4 2 2 1 2 1 1 1
Pediatr Blood Cancer DOI 10.1002/pbc
(not practical for outpatients) and heparin-coated catheters [19,20]. However, other studies have questioned the antibacterial benefits of heparin over other flush-lock solutions, particularly at the higher doses used in dialysis catheters [21,22]. Our study has several important limitations. We did not collect all data prospectively nor did we randomize patients, and we relied on surrogate measures of thrombi rather than documented thrombi. Our data suggest that we can safely flush-lock implanted vascular access ports with a heparin concentration of 10 units/ml without compromising the patency of the port. We saw no significant difference in complication rates for patients with ports flush-locked at this lower dose. Ongoing prospective evaluation is needed to confirm these results. Standardization of dosage across line-types is simply one approach to reduce the risk associated with heparin in central venous catheters. A possibly more clinically critical endpoint would be to eliminate heparin usage in settings where it is not clinically indicated. This preliminary study should support additional studies in the pediatric and adult populations, and eventually evidencebased guidelines for standardization across institutions.
ACKNOWLEDGMENTS Lori Fineman, RN, MS was essential to the early development of the quality improvement project. Emily Asher, MS, MPH, MPA, Lauren Dickey, MPH, and Ashley Diaz, BS provided support for data entry. This project was supported by a Young Investigators Award from the Academic Pediatrics Association, awarded to Dr. Rosenbluth. Dr. Auerbach was supported by NHLBI grant K24HL098372 during the course of this study.
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