The Art and Science of Infusion Nursing Margaret G. Lyons, DNP, RN, CRNI® Ann G. Phalen, PhD, CRNP, NNP-BC

A Randomized Controlled Comparison of Flushing Protocols in Home Care Patients With Peripherally Inserted Central Catheters ABSTRACT Introduction/Significance/Population: Research has failed to demonstrate an optimal flushing solution or frequency for central catheters. In a 2002 study of 50 000 home care patients, catheter dysfunction with loss of patency was the most common complication and occurred in 29% of the peripherally inserted central catheters (PICCs) tracked. With the advent of the Affordable Care Act and the promise of expanded home care services, this study offers evidence as to a preferred flushing protocol to prevent catheter patency complications for home infusion patients with PICCs. Methods: This prospective, randomized, 1-way, singleblinded posttest with control group study was performed to compare 3 commonly used flushing protocols in home infusion patients with PICCs. The independent variable was the flushing protocol, and dependent variables included the development of patency-related complications and other significant issues such as sluggishness, occlusion, missed medi-

cation doses, catheter replacement, additional nursing visits, and the use of alteplase (Cathflo Activase). Data Analysis/Results: Each of the study groups had patients who experienced 1 or more patencyrelated complications. Additional factors that may affect catheter function, including patient age, gender, diagnosis, therapy type, frequency of catheter use, catheter brand/size/number of lumens, concomitant use of anticoagulant medications, and whether PICCs were used for routine lab testing, were analyzed, and no statistical significance was determined. Catheter dwell time (catheter days) was statistically significant (p = .003, confidence interval = 95%; assuming equal variance) and confirmed the assumption that the longer a home care patient’s catheter was in place, the more complications occurred. There were no cases of heparin allergy, heparin-induced thrombocytopenia, or line infection. Discussion/Conclusion/Recommendations for Practice: The data provide some evidence to support the elimination of heparin flushing in home care

Author Affiliations: Villanova University College of Nursing, Villanova, Pennsylvania (Dr Lyons), Thomas Jefferson Home Infusion Service, Philadelphia, Pennsylvania (Dr Lyons), and Thomas Jefferson University School of Nursing, Philadelphia, Pennsylvania (Dr Phalen). Margaret G. Lyons, DNP, RN, CRNI®, is the Nurse Faculty Coordinator for the RN-BSN Online Program at Villanova University College of Nursing, Villanova, PA, and is a per-diem staff nurse for Jefferson Home Infusion Service in Philadelphia, PA. She maintains her infusion nursing certification and is active in the Pennsylvania State Nurses Association and the Infusion Nurses Society. She has published and presented on a variety of nursing topics. Ann G. Phalen, PhD, CRNP, NNP-BC, is the Associate Dean for Undergraduate Programs at Thomas Jefferson University, School of Nursing. She teaches in the Doctor of Nursing Practice (DNP)

program and coordinates clinical courses for the Neonatal Nurse Practitioner program track. She remains active in the clinical practice arena as well as in her specialty organizations and has published numerous articles and presented on various topics. Corresponding Author: Margaret G. Lyons, DNP, RN, CRNI®, Driscoll Hall Room 222, 800 Lancaster Avenue, Villanova, PA 19085 (e-mail: [email protected]). Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (http://journals.lww.com/journalofinfusionnursing). The authors of this article have no conflicts of interest to disclose.

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DOI: 10.1097/NAN.0000000000000050

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patients with PICCs, although data in the saline-only group that related to additional registered nurse visits to assess PICC patency and the use of alteplase (Cathflo Activase) were trending toward significance because this group experienced a higher incidence of these complications than both the heparin groups. These findings should not be translated to home care patients with cancer or pregnancy diagnoses because these populations were excluded from this study. More studies of this topic area should be initiated. Please see video abstract, Supplemental Digital Content 1, for more information (http://links. lww.com/JIN/A3).

W

ith the passage of the Affordable Care Act (ACA) of 2010 and its call for the formation of accountable care organizations and patient-centered medical homes, health care is moving toward preventive and community care options.1 Government incentives will allow for expanded home care services.2 Medical therapies in the home have become more complex and include the delivery of intravenous fluids, antibiotics, nutrition, chemotherapy, and blood products, which can necessitate the use of peripherally inserted central catheters (PICCs) for administration. PICCs are less invasive and have a lower incidence of infection when compared with implanted ports and tunneled catheters.3 The advantages of PICCs include a decrease in insertion-related complications, lower costs when compared with surgically inserted vascular devices, and the avoidance of frequent reinsertions of short peripheral intravenous catheters (PIVs).3 This makes them an ideal choice for home infusion patients who require relatively shortterm treatments. In the inpatient setting, the health care staff cares for PICCs on a continual basis. In the home, however, they may not be used with the same frequency as in the inpatient setting or by personnel with the same level of experience. Medication and intravenous fluids are often administered intermittently. The intermittent nature of PICC use in the home may contribute to patency issues.

BACKGROUND PICCs require careful maintenance to avoid complications and ensure best outcomes. In the 2002 PICC Occlusion Line Opening study, more than 50 000 home care patients with central venous and midline catheters were followed for complications.4 Catheter dysfunction with loss of patency was the most common complication;

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it occurred in 29% of the PICCs tracked.4 Historically, intravenous catheters were flushed with saline and locked with heparinized saline solutions to prevent drug interactions and to maintain patency.5,6 More recently, strong evidence has shown that heparin isn’t necessary to maintain patency in PIVs.7-10 Is the same evidence for PIVs applicable to PICCs? In March 2008, a nationwide heparin shortage affected policies for PICC flushing.11 Some organizations stopped using heparin sodium solutions, citing additional reasons such as cost containment, heparin dose-related medication errors, and the potential for heparin-induced thrombocytopenia (HIT).12 Increases in the use of alteplase (Cathflo Activase) to declot PICCs have been reported.13 Alteplase is the only Food and Drug Administration-approved lytic medication marketed for restoring function of occluded venous catheters.14 Best practices related to PICC flushing have yet to be clearly established.15,16 As a direct result of the heparin shortage, the home infusion service arm of a large northeastern university medical center changed its PICC flush policy from one that included heparin, SASH, to one that did not, SAS. The SASH method is the acronym for the flushing sequence of (S) saline solution (0.9%, 10 mL), followed by the (A) administration of prescribed intravenous medication or solution, followed by another (S) saline solution (0.9%, 10 mL), and finally the “locking” of the PICC with a (H) heparin flush solution (100 units/ mL; 3 mL or 300 units). The SAS method is similar to the SASH method, with the exception of the elimination of the heparin flush. SAS is currently the standard practice for the medical center’s home infusion service. Other organizations use the SASH method, but with lower concentrations of heparin (10 units/mL; 5 mL or 50 units). The lower-dose heparin flush is recommended by the Infusion Nurses Society (INS).17 The higherdose heparin flush is preferred by the Cancer Care Ontario (CCO) group and the Oncology Nursing Society (ONS).18,19 Since this policy revision, reports of increased PICC complications have occurred. The medical center’s infusion service admits approximately 330 patients with PICCs each quarter. In April 2009, its policies were amended to include the administration of alteplase in the home, if a catheter occlusion was noted. Since then, the medical center’s infusion service has cared for more than 3300 patients with PICCs. During a 28-month time span (April 2009 to October 2011), 584, or 17.69%, of catheters experienced an occlusion that required a prescription of alteplase; 1009 doses of alteplase were dispensed. Of the 584 catheters, approximately 35 required multiple doses of alteplase for catheter clearance. Complications related to catheter patency include catheter sluggishness and occlusion. These conditions

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can lead to missed medication doses, which lengthen therapy duration. Occlusion can also necessitate the use of alteplase to clear and restore patency.14 The drug has a potential for serious side effects if administered intravenously instead of instilled into the catheter and withdrawn. Side effects include allergic reactions and unnecessary systemic anticoagulation resulting in bleeding.14 Its use necessitates additional unscheduled nursing visits and additional costs. Alteplase costs approximately $70.88 a dose and may require 2 doses to clear a catheter, not including the costs of pharmacy delivery and additional nursing visits.20 If the catheter cannot be cleared, a new catheter must be inserted at a cost of approximately $1900, plus the costs of peripheral IV insertion to allow for continuation of therapy, provided the therapy ordered can be given peripherally.15 PICCs are replaced as scheduled outpatient cardiovascular interventional radiology visits, which generally are not available on weekends. Monetary costs are calculable, but missed medication doses, pain of repeat PIV and/or PICC insertions, and patient anxiety do not have a price tag. In an effort to decrease these complications, the medical center’s infusion service is considering a return to the SASH policy but would like to make an evidencebased decision.

METHODS Statement of Purpose The purpose of the study was to evaluate the most effective flushing solution for the maintenance of PICCs in the home care patient. Study Objectives The objectives of the inquiry were (1) to compare 3 flushing solutions (saline alone, saline with heparin 100 units/mL, and saline with heparin 10 units/mL) and their relationship with PICC patency-related complications, such as sluggishness and occlusion, missed medication doses, catheter replacement, additional nursing visits, and the use of alteplase; and (2) to identify any risks associated with the use of a particular flushing solution.

2. PICCs maintained with saline solutions alone are at greater risk for sluggishness and occlusion. 3. There is a positive relationship between the use of heparin and decreased incidence of PICC complications in home care patients. 4. Continuous PICC infusions decrease the risk of patency-related catheter complications. 5. Smaller-gauge PICCs have an increased risk of developing a patency-related complication. 6. There may be variations in flushing by patients and their caregivers in the home that cannot be controlled even after standardized instructions are given. Benefits and Risks Establishing evidence-based, standardized PICCflushing protocols for home care patients has many benefits. Using the best method for PICC flushing will lead to decreases in PICC occlusions, allow for the judicious use of alteplase, and lessen therapy interruptions and PICC reinsertions for patients. The identified benefits can lead to cost savings by (1) decreasing the number of additional nursing visits to evaluate sluggish or occluded catheters or to administer alteplase, (2) having patient therapies completed on time, and (3) reducing the number of PICC replacements. Standard flushing protocols will support consistency in care and foster universal adoption of best practices. There is limited supporting research on the use of the best flushing solution in home care patients with a PICC. This study adds to the literature by providing evidence on the appropriate flushing solutions to be used for home care patients with a PICC. Risks involved in the study included the development of heparin allergy and HIT. The incidences of these conditions are very low (< 0.6%), and subjects were screened before participating in the study to further minimize risks.21 Risks related to potential bleeding are negligible because both doses of heparin proposed are considered to be diluted forms of the drug and are currently used in many health care settings. Patients were administered doses of heparin that did not induce therapeutic anticoagulation levels.22 Review of the Literature

Assumptions and Limitations The underlying hypothesis postulated an association between PICC-flushing solutions and patency-related PICC complications in home care patients. The following assumptions and limitations were made: 1. The longer a PICC is in place, the greater the risk of sluggishness and occlusion.

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An extensive search of the literature was performed to retrieve articles describing definitive flush protocols for PICCs/central venous catheters (CVCs), as well as articles comparing the use of heparinized sodium solutions to saline solutions in the maintenance of PICCs. The literature review was divided according to the topics of controversy, risks and benefits, financial costs, and other issues having an impact on occlusion rates.

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A lot of confusion and controversy surrounds flushing protocols used to maintain the patency of central catheters. Standardization of care differs between individual health care settings and the various practice areas.5 Higher-level evidence to support specific CVCs—PICCs are a type of CVC—was sparse. The few randomized controlled trials that were identified revealed methodological concerns related to randomization processes, variable control, blinding of the investigators, and the fidelity of the interventions. Pertinent Web sites, such as the Agency for Healthcare Research and Quality, the Association for Professionals in Infection Control and Epidemiology, the Centers for Disease Control and Prevention, the Infectious Diseases Society of America, the Institute for Healthcare Improvement, and the Society for Healthcare Epidemiology of America, make specific recommendations for the bundling of care measures for CVCs.23-32 All refer to practices related to the prevention of central lineassociated bloodstream infections, but none recommends or specifies evidence-based flush solutions, or amounts, or frequency of flushing for central catheters.23-32 Given the controversy regarding the preferred flushing solution from the evidence evaluated, the proposed recommendations for PICC-flushing protocols to be used in the study were based on the expert opinions of INS, CCO, and ONS, as well as position statements of the Pediatric Pharmacy Advocacy Group (PPAG) for the use of heparin in the home care population of patients with PICCs.17-19,33 The guidelines were the only guidelines to attempt to specify solution, frequency, and amount of solution for maintaining specific CVCs, including PICCs. INS states in the Infusion Nursing Standards of Practice (2011), section O17(pS60): While many studies report equivalent outcomes in central vascular access catheters when locked with heparin lock solution or preservative-free 0.9% sodium chloride (USP), others have reported greater complications with saline locking. Due to the risk and costs associated with central vascular access device (CVAD) insertion, heparin lock solution 10 units/mL is the preferred lock solution after each intermittent use. The CCO indicates18 … heparin flush (3mL, 300 U/mL) should be used for open-ended CVC or PICC.(p21) The Central Venous Access Device Guideline Panel recommends, based on the absence of randomized trials or well-designed epidemiologic studies on any of the questions addressed by this report, that research institutions develop trials that can supply evidence to inform decision making on these issues. This is especially the case in the pediatric setting.(p20)

ONS echoes CCO,8,19 and PPAG has stated “it is the position of PPAG that the benefit of heparin use exceeds

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the safety concerns in neonates and children when institutions serving these patients take the safety measures to minimize these risks.”33 Project Design and Methodology A 1-way, single-blinded posttest with control group design was chosen for the study; the independent variable was the flushing protocol. Study Group I was the control group. Patients used the SAS method (saline only) for PICC flushing: a flushing sequence of saline 10 mL, followed by administration of prescribed intravenous medication or solution, followed by another saline 10 mL. Study Group II used both saline and heparin in a flushing method called SASH High: saline 10 mL before administration of medication or solution, followed by saline 10 mL, and then locked with heparinized saline solution with a concentration of 100 units/mL (3 mL or 300 units). Study Group III used the SASH Low method, in which the concentration of heparinized saline used was 10 units/mL (5 mL or 50 units). Frequency of flushing coincided with the patient’s medication dosing schedule—before and after each medication—or every 12 hours, if the PICC was being maintained according to the medical center’s infusion service policies. Project Timeline Data were collected between February 1, 2012, and April 28, 2013. Subjects’ length of time in the study was determined by their prescribed therapy length and/or the study’s end date. Time in study was calculated in terms of catheter days. Early termination from the study occurred if the patient was discharged from the medical center’s infusion service, developed HIT or heparin allergy, or needed additional treatments requiring inpatient services or another organization to participate in PICC care. Subjects Patients were recruited from the home infusion service’s affiliated university medical center at the time of their discharge to home. A small number of patients were recruited from outpatient sources affiliated with the infusion service. The study included adults age 18 or older, with PICCs placed at the university medical center, whose anticipated duration of therapy was longer than 1 week. Children were not included because the infusion service does not routinely care for pediatric populations. Other exclusion criteria included patients with a history of heparin allergy; cancer and pregnancy diagnoses, because these conditions predispose patients to hypercoagulable states34 and can affect catheter outcomes; and a history of HIT. Patients who were not

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being served exclusively by the medical center’s infusion service were also excluded. Eligible patients’ catheters were assessed by the hospital staff and deemed patent and free of complications before discharge. A home visit occurred within 24 hours of each patient’s enrollment in the study, and the catheter was reassessed for patency and for complications. Sample Size A power analysis was performed before the study to determine an appropriate sample size. Thirty subjects in each study group should have achieved a medium or greater effect. An oversample of 99 (10%) was planned to compensate for potential attrition. Because recruitment of subjects extended beyond the expected 3 months, enrollment was ended when 90 patients were enrolled. The significance level was set at .05 and the power level at .80 to achieve the specific outcomes. Institutional Review Board and Informed Consent Protection of human rights was ensured by informed consent, with written assurance of confidentiality, and institutional review board approval by the medical center’s affiliated university. Randomization Method Subjects were randomly assigned to one of the study groups using the sequentially numbered, opaque sealedenvelope method.35 The principal investigator was blind to which study group a patient was assigned. Intake coordinators maintained a spreadsheet indicating a subject’s study group assignment and a de-identifying code that was used during statistical analysis.

IMPLEMENTATION AND PROCEDURES Before beginning the study, standardized training was provided to nurses who would enroll patients and to field nurses who would implement the procedures. Training included operationally defining and understanding the variables studied (Appendix), study procedures, and documentation. Pre-study training and standardization helped ensure reliability among nurses participating in the study. Field nurses instructed patients to use the flushing solutions that were sent to their home after study/treatment consents had been obtained and randomization occurred. Oral instructions provided by the field nurse were standardized and repeated the written instructions that were left for patients to refer to at home.

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The university medical center primarily uses open-ended Cook 4Fr, single-lumen/5Fr, double-lumen catheters and Meditech 6Fr, triple-lumen catheters. Patients who had undergone recent orthopedic surgery (< 6 months) had routine platelet testing as required by the infusion service’s established protocols. Injection end cap connectors for all subjects were standardized, using the MicroCLAVE by ICU Medical, a reversed split-septum, neutral-displacement connector.36 The connector can be used with or without heparin.36 Patients were instructed to clean the PICC end connector for 30 seconds with an alcohol swab and attach a flush syringe using aseptic technique. Hand washing for patients and health care providers was reinforced and required before and after all PICC uses. The infusion service patients were taught to flush the PICC according to their internal policies, which included using a pulsatile or “push-pause” motion for both saline and heparin flushes. This is thought to increase intraluminal friction. Flushing was completed by clamping the line while injecting the last 0.5 mL of flush solution, and then disconnecting the syringe from the PICC. Data Collection The principal investigator called patients weekly to collect data, which included any incidence of PICC sluggishness or occlusion, additional registered nurse (RN) visits to the patient to evaluate PICC sluggishness or occlusion, incidence of PICC occlusion requiring alteplase administration, missed medication doses resulting from occlusion, and the need for catheter replacement. The infusion service’s patient charts and patient-event tracking reports (which included incidences of alteplase administration, missed medication doses, PICC replacements, and unscheduled nursing visits) were reviewed to verify patients’ reports. In accordance with federal guidelines, data were stored in a secure location accessible only by the investigators. All data will be stored for at least 3 years after dissemination of the findings and then destroyed.

RESULTS Demographics, Baseline Characteristics, and Subject Disposition (n = 90) Demographic composition of study participants is noted in Table 1. There were 56 males and 36 females; the average age of participants was 52 years. Data showed that the study arms were approximately equal in the number of subjects. The majority of subjects received antibiotic therapy (Table 2 and Table 3). The

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TABLE 1

TABLE 2

Demographic Composition

Breakdown of Subjects by Therapy Type

Gender

Therapy Type

Frequency

Percentage

72

80.0%

Male

54

Antibiotic therapy

Female

36

Parenteral nutrition

7

7.8%

Inotropic therapy

4

4.4%

Multiple therapies

4

4.4%

Catheter maintenance therapy

3

3.3%

Age (years) Average

52

Range

19-77

PICC flushing group SAS

28

SASH High

32

SASH Low

30

Catheter days Average

23

Range

2-143

Frequency of PICC use for medication administration Q24

29

Q12

20

Q8

19

Continuous

11

Other

11

PICC brand Cook

67

Cook Power

17

Other

6

most common diagnoses of study patients included postoperative infections and osteomyelitis. Table 4 provides a description of subjects’ diagnoses. PICC use was divided into 3 groups: patients intermittently using their catheters (68 subjects, 75.5%); those who used their PICCs in a continuous manner (11 subjects, 12.25%); and a combination of intermittent and continuous therapies—that is, continuous parenteral nutrition and intermittent antibiotics via dual lumens (11 subjects, 12.25%). Sixty subjects (54%) had double-lumen, 5Fr Cook PICCs, 17 of which were the “power” type. The majority of PICCs were inserted by nurses (68 catheters, 75.5%). Catheter days ranged between 2 and 143 days, with a mean of 23 days per patient. About half of the subjects (44) were taking an additional medication that affected clotting; for example, low-molecular-weight TABLE 3

PICC gauge 4Fr

26

5Fr

60

6Fr

4

Type of Antibiotics Infused Antibiotics

Number of lumens Single

26

Double

60

Triple

4

Provider who inserted PICC (all PICCs were placed using ultrasound guidance)

Frequency

Percentage

Cefazolin (Ancef)

17

18.9%

Vancomycin (Vancocin)

13

14.4%

Daptomycin (Cubicin)

13

14.4%

Multiple antibiotics

8

9.0%

Ceftriaxone (Rocephi)

5

5.6%

RN

68

Ertapenem (Invanz)

5

5.6%

MD

19

Ampicillin (Omnipen)

4

4.4%

Nafcillin (Unipen)

4

4.4%

Piperacillin/tazobactam (Zosyn)

2

2.2%

Ceftazidime (Fortaz)

2

2.2%

Participants on anticoagulant medications Yes

44

No

46

Labs drawn via PICC Yes

22

Gentamicin (Garamycin)

1

1.1%

No

68

Penicillin G

2

2.2%

None

14

15.6%

Total

90

100%

Abbreviations: PICC, peripherally inserted central catheter; SAS, saline-only flushing protocol; SASH High, saline and higher-dose heparin flushing protocol; SASH Low, saline and lower-dose heparin flushing protocol.

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TABLE 4

Participants’ Diagnoses for Peripherally Inserted Central Catheter Diagnosis Infection diagnosis

Frequency

Percentage

73

86.7%

Postoperative infection

27

30%

Osteomyelitis

13

14.4%

Cellulitis

7

7.8%

Urinary tract infection

5

5.6%

Bacteremia

4

4.4%

Pneumonia

3

3.3%

Septic arthritis

2

2.2%

Syphilis

2

2.2%

Septic bursitis

1

1.1%

Intestinal abscess

1

1.1%

Endocarditis

1

1.1%

Rectal abscess

1

1.1%

Pyelonephritis

1

1.1%

Lyme disease

1

1.1%

Intercranial abscess

1

1.1%

Cholangitis

1

1.1%

Meningitis

1

1.1%

Sinusitis

1

1.1%

Malnutrition

5

5.6%

Intestinal obstruction

1

1.1%

Congestive heart failure

4

4.4%

Sickle cell anemia

2

2.2%

Total

28

100.0%

heparin (Lovenox) or warfarin (Coumadin). Routine labs drawn through the PICC were documented in 22 patients. Statistical Analyses Descriptive statistics of cross tabulation and frequencies were computed using SPSS version 19. Comparisons using Pearson χ2 test and linear by linear association were also applied. Statistical significance was not achieved. In some cells tested, the sample size did not reach the expected counts, and if the sample size had been larger, the results were trending toward significance (Table 5).

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In evaluating the effects of 3 PICC-flushing protocols and analyzing data, the following are the results according to the clinical questions: 1. In home care patients with PICCs who used the saline-only, or the SAS, protocol, what were the risks of catheter complications? Data revealed that this group had the highest percentage of additional RN visits to assess PICC sluggishness/occlusion (32.1%), as well as PICC occlusions requiring alteplase administration (25.0%), and the highest percentage of subjects who experienced missed or delayed medication doses related to PICC occlusion (14.3%). Equal incidences of episodes of PICC sluggishness and PICC replacement or exchanges occurred in all study groups. 2. In home care patients with PICCs who used the saline and higher-dose heparin protocol, or SASH High method, what were the risks of catheter complications? This group had the lowest percentage of alteplase use (9.4%), which was comparable with the SASH Low group (10.0%). 3. In home care patients with PICCs who used the saline and lower-dose heparin protocol, or SASH Low method, what were the risks of catheter complications? The SASH Low group had the lowest occurrences of episodes of PICC sluggishness (26.7%), additional RN visits (13.3%), and the lowest overall percentage for the number of subjects who experienced missed or delayed medication doses related to PICC occlusions (3.3%). When comparing the SASH High group with the SASH Low group, participants in the SASH High group had more incidences of PICC sluggish episodes (32.2% versus 26.7%) and experienced more missed or delayed medications related to PICC occlusion (6.2% versus 3.3%). 4. Of the 3 protocols tested, which was most effective for use in the prevention of PICC patencyrelated complications in home care patients with PICCs? According to the data, each group experienced PICC complications, and no statistical significance was achieved. However, the study reveals clinical importance. In the SAS group, additional RN visits were necessary to assess PICC sluggishness/occlusion, and compared with the other study groups, there was an increased number of PICC occlusions requiring alteplase administration. The SASH Low group had the lowest incidences of PICC sluggishness, alteplase use, and missed or delayed medication doses. Frequency of incidences of catheter complications is summarized in Table 5 and Table 6. The overall percentage of sluggishness was 28.8% of the 90 participants. For additional RN visits required to assess sluggish or occluded lines, the overall incidence

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TABLE 5

Frequency of Incidences of Catheter Complications per Study Group Catheter Complications

SAS (1) (% Within Group)

SASH High (2) (% Within Group)

SASH Low (3) (% Within Group)

Overall Incidence (%)

Pearson ␹2 P Value

Occurrences of PICC sluggishness/ occlusion

9 (32.1%)

9 (32.2%)

8 (26.7%)

26 (28.9%)

.893

Occurrences of additional RN visits to assess PICC sluggishness/occlusion

9 (32.1%)

5 (15.6%)

4 (13.3%)

18 (20.0%)

.150

Number of PICC occlusions requiring alteplase (Cathflo Activase) administration

7 (25.0%)

3 (9.4%)

3 (10.0%)

13 (14.4%)

.160

Number of subjects missed or delayed medication doses related to PICC occlusion

4 (14.3%)

2 (6.2%)

1 (3.3%)

7 (7.8%)

.275

Number of catheter replacements or exchange over guidewire

1 (3.6%)

1 (3.1%)

1 (3.3%)

3 (3.3%)

.995

Note: Several cells had counts lower than expected. Had the sample size been increased, statistical significance may have been achieved. Bold values were trending toward significance. Abbreviations: PICC, peripherally inserted central catheter; SAS, saline-only flushing protocol; SASH, saline and higher-dose heparin flushing protocol.

for all groups was 20.0%, but within the study groups, SAS had the highest percentage (32.1%). When tracking the number of occlusions that required the administration of alteplase, the overall percentage for all participants during the data collection time frame was 14.4%. Per study group, SAS had the highest percentage of

patients requiring alteplase (25.0%). The overall incidence of subjects who had missed or delayed medication doses related to a PICC occlusion was 7.8%. The SAS group was highest in this category at 14.3%. Lastly, the overall rate of catheter replacement or exchanges over guidewire that were related to occlusion

TABLE 6

Total Number of Incidences of Each Catheter Complication—Frequency and Percentage Catheter Complications

None

1

2 or More

Total Complications

Occurrences of PICC sluggishness/occlusion

64 (71%)

10 (11.1%)

16 (17.7%)

26 (28.8%)

Occurrences of additional RN visits to assess PICC sluggishness/occlusion

72 (80%)

14 (15.6%)

4 (4.4%)

18 (20%)

Number of PICC occlusions requiring alteplase (Cathflo Activase) administration

77 (85.6%)

12 (13.3%)

1 (1.1%)

13 (14.4%)

Number of subjects missed or delayed medication doses related to PICC occlusion

83 (92%)

7 (7.8%)

0 (0%)

7 (7.8%)

Number of catheter replacements or exchange over guidewire

87 (96.7%)

3 (3.3%)

0 (0%)

3 (3.3%)

Abbreviation: PICC, peripherally inserted central catheter.

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was 3.3%. All groups had a participant who needed a catheter replaced or exchanged. A secondary analysis of the study data was performed. The goal of the secondary analysis was to determine what contributing or predictive factors influenced PICC catheter patency among subjects who experienced 1 or more PICC complications. Additional factors considered to affect patency included patient age; gender; diagnosis; therapy type; frequency of catheter use; catheter brand, size, and number of lumens; RN versus physician PICC insertion; concomitant use of anticoagulant medications; and if PICCs used for routine lab testing were analyzed and no statistical significance was found. Catheter dwell time (catheter days) was the only factor determined to be statistically significant (p = .003, confidence interval = 95%). As a result, the original assumption was substantiated that the longer a home care patient’s catheter remained in place, the more complications would occur.

DISCUSSION Data are inconclusive, and the underlying hypothesis was not validated. The SAS group had the highest incidence of PICC occlusions requiring alteplase use and additional RN visits to address occlusion, as well as the highest number of patients who missed medication doses. The SASH High group and the SAS group were the same with regard to episodes of PICC sluggishness. SASH Low was the lowest group in occlusion episodes and the use of alteplase, and in missed medication doses. All groups were similar in incidences of catheter replacement or exchange. No incidences of the development of HIT, heparin allergy, or PICC infections were reported. The patients included in the study reflected patient populations treated at an urban/suburban home infusion program. Most were admitted for postoperative and bone infections. Therefore, the results of the study may not be directly applicable to acute care patients or to those with noninfectious disease states because there were a limited number of such patients included in the study. There were other potentially confounding issues. The SASH High group used 300 units of heparin in 3 mL. The SASH Low group used 50 units of heparin in 5 mL. The SASH Low group showed some advantage over the SASH High group in the final analysis, as it had the lowest occurrences of PICC sluggishness episodes and additional RN visits, and the lowest overall percentage of subjects who experienced missed or delayed medication doses, but not alteplase use. Was it the concentration of heparin that was the cause, or could the additional 2 mL of fluid be a factor in SASH Low’s effectiveness in preventing these complications?

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Could the flushing protocol used from the time the PICC catheter was inserted and the subject’s length of hospital stay before joining the study have had an impact on the results? There is evidence to indicate that within 24 hours of central line insertion, a fibrin coating develops around catheter material.37 Over time, intraluminal blood reflux leads to continued fibrin buildup, which is a precursor to thrombus formation.38 Fibrin is also involved in the development of biofilm, which can be a precursor to infection.39,40 Heparin has been shown to prevent adhesion between fibrin-coated surfaces.41 The university medical center where most subjects were recruited does not use heparin for routine PICC flushing. A patient’s length of stay before coming on the home infusion service, coupled with the postinsertion choice of flushing agent, may have had an impact on the infusion service’s PICC complication rates, including infection. The idea of heparin use leading to less biofilm development—and therefore less potential for infection—was seen in Schilling and colleagues’ study,42 which concluded “heparinized saline affords no advantages over saline in reducing occlusion rate, however there was a trend toward lower infection rate with the use of heparinized saline.”(p85)

LIMITATIONS A limitation of the study included not obtaining expected subject numbers within the proposed time frame. Were there characteristics of subjects who did not participate that may have affected study results? There was the potential for the Hawthorne effect because subjects were aware that their behavior (PICC flushing) was being evaluated. They may have performed required tasks in a manner they may not have if they were not being studied.

IMPLICATIONS The study should be replicated with similar populations, as well as with clients who have diagnoses that can affect blood coagulation (ie, cancer and pregnancy), because the results could have an impact on home infusion service policies and the care of home care patients with PICCs.

RECOMMENDATIONS The data suggest that the SAS protocol could be maintained in nonhypercoaguable clients, but efforts to monitor complication incidences should continue. There is some evidence to support the use of the lower-dose

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heparin in this population, because that group had the lowest incidences of occlusions, additional RN visits, and missed medication doses. Given that heparin prevents fibrin adherence and that fibrin is a component of biofilm, which has been implicated in catheter occlusion and infection, it is reasonable to recommend the use of heparin in catheter maintenance.37-41

CONCLUSIONS Safe, evidence-based maintenance of PICC patency in home care patients is essential to efficiently and effectively provide necessary infusions required in this population. This is especially salient today given the passage of the ACA in 2010 and the government incentives that will allow for expanded home care services.2 Institutional flushing protocols are not standardized and are not based on high levels of evidence.17 It is the intention of the authors that findings from this study will provide some evidence that can be used by providers of home infusion services to reevaluate their PICC flushing-related practices. Analysis of the data concludes that among home care patients without a diagnosis that could have an impact on coagulation, the 3 flushing protocols tested in this study were equally effective. There was some evidence that the SAS group had more issues of additional RN visits and alteplase use, which would justify using one of the heparin solution groups, but statistical significance to support this was not achieved. As a note, the infusion service that assisted in the study has recently made a practice change based on the results of the study. It decided to institute a flush policy that includes the use of heparin flushes (10 units/mL, 5-mL fill volume) for central catheters—such as PICCs or Hickman and Broviac catheters—and will maintain its policy of heparin flushes (100 units/mL 3 mL) for implanted ports as part of its catheter maintenance procedures. ACKNOWLEDGMENTS The authors would like to thank the following persons for their efforts in assisting with this study; Nancy Dubois, DNP, RN, CRNI®; Lawrence Carey, PharmD; Martha Michael, BSN, RN, CRNI®; Thomas Brown, MBA, PharmD; and statistician Mary Ann Heverly, PhD. Additional thanks go to all the personnel of Jefferson Home Infusion Services, especially the subject recruiters: Diana Acker, RN; Sally Kakas, RN, CRNI®; Mary Kampf; and Lisa Patrick, RN; the pharmacists, the field nurses, and the pharmacy/delivery staff for all of their efforts in bringing this project to its completion. This project was supported by generous grants from the Gardner Foundation of the INS as well as the Alpha Nu Chapter of Sigma Theta Tau International.

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REFERENCES 1. Patient Protection and Affordable Care Act. 42 USC §2702 (2010). 2. National Prevention, Health Promotion and Public Health Council. National prevention strategy: America’s plan for better health and wellness. http://www.healthcare.gov/prevention/ nphpphc/index.html. Published June 2011. Accessed October 23, 2011. 3. Chopra V, O’Horo JC, Rogers MA, Maki DG, Safdar N. The risk of bloodstream infection associated with peripherally inserted central catheters compared with central venous catheters in adults: a systematic review and meta-analysis. Infect Control and Hosp Epidemiol. 2013;34(9):908-918. 4. Moureau N, Poole S, Murdoch MA, Gray S, Semba CP. Central venous catheters in home infusion care: outcomes analysis in 50,470 patients. J Vasc Intervent Radiol. 2002;13:1009-1016. 5. Gorski L, Czaplewski LM. Peripherally inserted central catheters and midline catheters for the home care nurse. J Infus Nurs. 2004;27(6):399-409. 6. Hadaway L. Technology of flushing vascular access devices. J Infus Nurs. 2006;29(3):137-145. 7. Goode C, Titler M, Rakel B, et al. A meta-analysis of effects of heparin flush and saline flush: quality and cost implications. Nurs Res. 1991;40(8):324-330. 8. LeDuc K. Efficacy of normal saline solution versus heparin solution for maintaining patency of intravenous catheters in children. J Emerg Nurs. 1997;23:306-309. 9. Peterson FY, Kirchoff KT. Analysis of the research about heparinized verses nonheparinized intravascular lines. Heart Lung. 1991;20:631-642. 10. Randolph A, Cook D, Gonzales C, Andrew M. Benefit of heparin in peripheral venous and arterial catheters: systematic review and meta-analysis of randomised controlled trials. Br Med J. 1998;316:969-975. 11. US Food and Drug Administration. Public health update: recall of heparin sodium for injection. http://www.fda.gov/drugs/drugsafety/ postmarketdrugsafetyinformationforpatientsandproviders/ ucm112665.htm. Published February 28, 2008. Accessed September 30, 2011. 12. Cooney MF. Heparin-induced thrombocytopenia: advances in diagnosis and treatment. Crit Care Nurs. 2006;26:30-36. 13. Jonker M, Osterby K, Vermeulen LC, Kleppin S, Kudsk K. Does low-dose heparin maintain central venous access device patency? A comparison of heparin versus saline during a period of heparin shortage. J Parenter Enteral Nutr. 2010;34(4): 444-449. 14. Cathflo Activase (alteplase) [package insert]. South San Francisco, CA: Genentech, Inc; 2001. http://www.fda.gov/downloads/ Drugs/…/ucm088609.pdf. Accessed September 30, 2011. 15. Bowers L, Speroni K, Jones L, Atherton M. Comparison of occlusion rates by flushing solutions for peripherally inserted central catheters with positive pressure luer-activated devices. J Infus Nurs. 2008;31(1):22-27. 16. Alexander M, Corrigan A, Gorski L, Hankins J, Perucca R, eds. Infusion Nursing: An Evidence-Based Approach. 3rd ed. St Louis, MO: Saunders/Elsevier; 2010:499-500. 17. Infusion Nurses Society. Infusion nursing standards of practice. J Infus Nurs. 2011;34(1 suppl):S1-110. 18. Cancer Care Ontario. Central Venous Access Device Guideline Panel. Managing central venous access devices in cancer patients: a clinical practice guideline. http://www.cancercare.on.ca/

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APPENDIX Selected Operational Definitions Flushing protocol: A method of keeping catheters patent using saline alone or saline and dilute heparin sodium solutions before and after medication, or solution administration, and/or blood withdrawal. Flushing protocols are also used to keep the line open when no solutions are used (catheter maintenance). For the purposes of this study, there will be 3 protocols: 1. SAS: Saline 10 mL (S) prior to administration (A) and saline 10 mL (S) after administration. 2. SASH High: Saline 10 mL (S) prior to administration (A), then saline 10 mL (S), and locked with heparin sodium solution (H) 100 U/mL = 300 U in 3 mL. 3. SASH Low: Saline 10 mL (S) prior to administration (A), then saline 10 mL (S), and locked with heparin sodium solution (H) 10 U/mL = 50 U in 5 mL. Saline flush: Solution of 0.9% physiologic saline in sterile prefilled syringes used to keep IV catheters patent. Heparin flush (higher dose): Heparin sodium solution of 300 U/3 mL (concentration 100 U/mL) in sterile prefilled 10-mL syringes. Heparin flush (lower dose): Heparin sodium solution of 50 U/5 mL (concentration 10 U/mL) in sterile prefilled 10-mL syringes. Occluded catheter: A catheter that cannot be flushed using normal flushing pressures or by aspiration of blood.

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Partially occluded catheter: A catheter that is able to infuse medications, but when aspirated, blood return is not obtained. Sluggish catheter: A catheter that requires additional pressure to flush solutions through. This condition is usually reported by the patient to the on-call nurse by the patient saying that the “PICC” is hard to flush or that infusion is taking longer than the prescribed time to infuse. It can also be assessed by the nurse during routine patient visits. Blood return may or may not be obtained. Alteplase (Cathflo Activase): The only FDAapproved and marketed lytic medication for restoration of central vascular access device function. It is available in a single-use, 2-mg vial. Drug is instilled into occluded catheters for approximately 30 minutes and withdrawn. If blood return is obtained, the catheter is then flushed with saline. Risks include allergic reaction and bleeding. In clinical trials, the most serious adverse events reported after treatment were sepsis, gastrointestinal bleeding, and venous thrombosis. Alteplase (Cathflo Activase) should be used with caution in the presence of known or suspected infections in the catheter.14 Catheter replacement: Having an original PICC replaced over a guidewire or an additional PICC placed in another location to complete therapy because of original device failure related to lack of patency. This is performed at the university medical center’s Interventional Radiology Department.

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