Flushing & Locking Practices

What are the optimal flushing and locking solutions, dose, volume, technique and frequency for the prevention of occlusions in peripheral intravenous cannulas (PIVC) and central venous access devices (CVAD) in paediatric and adult patients with cancer?

TERMINOLOGY

Common language facilitates communication between professional and organisations, the translation of evidence into clinical practice, data sharing, and research. CNSA, eviQ and eviQ Education are leading vascular access management and education in cancer care in Australia utilizing common, contemporary terminology (Table 1).

Table 1: CVAD terminology

INTRODUCTION

The aim of flushing and locking practices is to prevent intraluminal CVAD occlusion and infection (1). However, occlusions remain one of the most frequent CVAD complications, ranging between 14-36% (2-15). This question will discuss six practice components which influence locking and flushing practices:

Locking solution
Frequency
Technique
Administrator
Syringe size
Type of syringe

Factors which impact flushing and locking practices include:

Patient factors
1. Age – paediatric or adult
2. Type of disease
3. Disease stage
4. Type of infusate
5. Diseases that impact coagulability
6. Body mass index (BMI)
7. Comorbidities
Device factors
1. Type of CVAD
2. Number of lumens or external diameter of catheter
3. Side
4. Valved or non-valved catheters
5. Catheter tip position – ideal position or malposition

The complexity of managing PIVCs and CVADs in people with cancer, with varied locking practices makes the prevention of occlusion challenging for the clinician and the researcher to analyse. There are numerous recommendations regarding PIVC maintenance such as flushing and locking practices (16), however Australian and international data suggests a large proportion of patients do not receive evidence based care to optimize the outcomes of PIVCs (17). This is evident with unacceptably high Peripheral Intravenous Cannula premature removal rates of up to 90% (18-23). Currently available evidence to support recommendations for the optimal solution, dose and frequency to lock CVADs is lacking, inconclusive and of very low to low level quality (24,25). The published literature is comprised of low quality, retrospective chart reviews and non-interventional observational studies with a definite lack of randomized controlled studies (26). This gap in high quality evidence has resulted in wide variations in local policy recommendations and to a diverse range of locking practices and products evident in clinical practice (16).

SUMMARY OF RECOMMENDATIONS

1. FOUR FUNDAMENTAL PRINCIPLES FOR CLINICAL PRACTICE

Despite the lack of definitive evidence to support recommendations for locking practices to prevent CVAD occlusion, the following four clinical practices are evident in the literature are:

1. Education and competency:

CNSA recommends training and competency is essential for the management of Peripheral Intravenous Cannulas (PIVC) and Central Venous Access Devices (CVAD) (27-36) and should include -

All maintenance procedures including flushing and locking practices, catheter tip position management, reduced patency assessment and management (12,30,34)
Dressing and PIVC/CVAD securement practices that prevent catheter migration cannula dislodgement and maintain the tip position (30,37,38).
Needleless connector – completing the flushing and locking practice with the appropriate clamping-disconnection technique according to the type of needleless connector: negative, positive, neutral or anti-reflux (9,12,24,27,28,30,39-42)

2. Regular flushing practices:

CNSA recommends Peripheral Intravenous Cannulas and Central Venous Access Devices should be flushed at regular intervals because flushing facilitates the removal of intraluminal blood components which potentially lead to thrombotic occlusions and drug residues to reduce the risk of contact between incompatible solutions (43)

3. Pulsatile or start-stop technique:

CNSA recommends to instil flushing and locking solutions using the appropriate technique for Peripheral Intravenous Catheters and Central Venous Access Devices to clear the device of medications and solutions and complete with the appropriate technique to maintain positive pressure to prevent blood reflux into the catheter/cannula tip (9,12,24,27,28,30,31,34,39-42,44-47).

4. Consistent flushing and locking practices:

CNSA recommends consistent flushing and locking practices including:

Completion for every patient, every time, for every PIVC and CVAD by all clinical staff accessing CVADs (48)
Prompt and consistent assessment, appropriate management and documentation of any signs and symptoms of reduced patency is essential for prevention of PIVC and CVAD occlusion (49)

Central Venous Access Devices

2. FLUSHING PRACTICES

CNSA recommends to flush Central Venous Access Devices:

SOLUTION:

With 0.9% sodium chloride for paediatric and adult patients with cancer (6,12,15,24,27,28,30,34,39,42,50-62).

Refer to section below for more information and discussion of current evidence.

TECHNIQUE:

Using a pulsatile/start-stop flush technique (9,12,24,27,28,33,34,39,41,42,44,53,54,57,63,64)
And complete the flush with the appropriate clamping-disconnection sequence to maintain positive pressure at the catheter tip (9,12,24,27,28,34,41,42,44,53,54,63,64) according to the type of needleless connector.
Leaving 0.5-1 mL of fluid to prevent blood reflux into the catheter tip by ‘bottoming out’ or emptying the syringe fully (65) or using a manufactured prefilled syringe with anti-reflux features (30).

Refer to section below for more information and discussion of current evidence.

LUMENS:

For each lumen of a CVAD (41)

FREQUENCY:

Routinely including
- Intermittent use: after each use for example, post medication administration, blood sampling, blood product administration, parenteral nutrition administration and contrast (6,12,33,39,42-44,51,53,57) or at least once per shift (8-12 hourly) to align with patency assessment and documentation (1,31)
- In between incompatible solutions or medications (62)
- Before lock solution administration (12,15,33,42,44,52,58,63,66)
- Paediatric catheters: open catheters - every 8-12 hours during intermittent use (6)

Refer to section below for more information and discussion of current evidence.

VOLUME:

Adult:
- Flush with 10 mLs (15,39,59).
- Increase to 20 mLs (6,27,42,51,53) in a 20 mL syringe or two 10 mL syringes after medication administration, blood sampling or blood product administration, viscous fluids for example parenteral nutrition, computerised tomography (CT) contrast (6,27,42,51,53) or in between incompatible solutions if clinically appropriate (for example, not for renal, cardiac, critical care or fluid intake restricted patients).
Paediatric:
- At least double the volume of the CVAD and attachments for paediatric patients (1,65). Consider 10-20mL when clinically appropriate (6).

Complete flushing practices for every patient, every time, for every CVAD (48).

Refer to section below for more information and discussion of current evidence.

3. LOCKING PRACTICES

CNSA recommends to lock Central Venous Access Devices:

SOLUTION, DOSE AND VOLUME:

With 0.9% sodium chloride for patients with cancer (24,25,28,34,46,50,51,67,68) and:
- Adult: Lock with 20mL (34,51), and if clinically indicated, for example for renal, cardiac, critical care or fluid intake restricted patients (53) - lock with 10 mL (28).
- Paediatric: Lock with at least double the volume of the CVAD for paediatric patients (65). Consider 10-20mL when clinically appropriate (6).

Refer to section below for more information and discussion of current evidence.

FREQUENCY

According to the type of CVAD.

Refer to section below for more information and discussion of current evidence.

TECHNIQUE

Using a pulsatile / start-stop flush technique (9,28,30,31,34,39,40,44-46) and completed with the appropriate clamping-disconnection sequence to maintain positive pressure at the catheter tip according to the type of needleless connector (9,12,24,27,28,30,39-42).

Refer to section below for more information and discussion of current evidence.

Complete locking practices for every patient, every time, for every CVAD (48).

4. ADMINISTRATOR - Locking/Flushing

CNSA recommends clinicians, patients and carers with appropriate, comprehensive education and deemed competent, can attend to flushing and locking practices which aim to prevent occlusions of Centrally Venous Access Devices for paediatric and adult patients with cancer (7,9,10,12,29,32,39,42,49,51,55,69-71).

CNSA recommends competency assessment post education is required (1,53,72,73).

Refer to section below for more information and discussion of current evidence.

5. SYRINGE FEATURES

CNSA recommends:

Using 10 mL or larger volume syringes for flushing and locking.
To consider the use of manufactured, single use, prefilled 0.9% sodium chloride syringes with anti-reflux and pressure limiting features which may assist to prevent occlusions (30,39).

Refer to section below for more information and discussion of current evidence.

6. BASELINE INTRAVENOUS FLOW RATE – To Keep Vein Open (TKVO)

CNSA recommends to consider a baseline intravenous flow rate (To Keep Vein Open TKVO) for Peripheral Intravenous Cannula (PIVC) and Central Venous Access Devices (CVADs) (74) in patients with cancer:

Using a volumetric pump at 10 mL/hr for
- Patients without contraindications for example without renal, cardiac, critical care or fluid intake restrictions
- Patients that require regular access for intravenous medications
- Paediatric patients as clinically appropriate
Consider locking and not using continuous TKVO rate for
- Renal, cardiac, critical care or fluid impaired patients
- Paediatric patients as clinically appropriate
And monitor occlusion rates and thrombolytic use.

Every time a closed intravenous system is accessed it increases the risk of infection, for example for connection and disconnection of intravenous lines or syringes.

Routine surveillance of occlusion rates and/or thrombolytic usage for treating intraluminal occlusions should be completed. This may include partial occlusions (flushes easily but no blood return, resistance when flushing, blood flash back with no full blood return) or complete occlusions (no blood return or no ability to instill fluids). An increase in occlusion rates or thrombolytic medication usage should be evaluated by assessing compliance rates of clinical practice with the four practice principles: 1. Education and Competency; 2. Regular flushing practices; 3. Pulsatile or start - stop technique and 4. Consistent flushing and locking practices, including documentation of all assessments, findings and interventions.

PERIPHERAL INTRAVENOUS CANNULA (PIVCs)

7. FLUSHING PRACTICES

CNSA recommends to flush Peripheral Intravenous Catheters:

SOLUTION and VOLUME

To flush with 3 mL 0.9% sodium chloride (1,75-77). Increase the volume, for example to 5 mL post administration of blood products or viscous fluids (1), for example parenteral nutrition, contrast media.

Refer to section below for more information and discussion of current evidence.

TECHNIQUE

To consider flushing using a slow and steady technique, for example less than 1 mL per second to limit the damage to the vein wall potentially caused by fast flow rates (47) and completing the flush by maintaining positive pressure (38).

Refer to section below for more information and discussion of current evidence.

FREQUENCY

Intermittent use: to flush Peripheral Intravenous Cannulas before and after medication administration and at least once per shift (8-12 hourly) (1,78). Remove cannula as soon as possible, as clinically indicated in collaboration with the health team (1).

Refer to section below for more information and discussion of current evidence.

8. LOCKING PRACTICES

SOLUTION

To lock with 0.9% sodium chloride for paediatric and adult patients with cancer (1,17,75-77).

Refer to section below for more information and discussion of current evidence.

TECHNIQUE

To consider flushing using a slow and steady technique, for example less than 1 mL per second to limit the damage to the vein wall potentially caused by fast flow rates (47) and completing the flush by maintaining positive pressure (38).

Refer to section below for more information and discussion of current evidence.

FREQUENCY

To lock Peripheral Intravenous Cannulas not in continuous use with 0.9% sodium chloride for paediatric and adult patients with cancer at least once per shift (8-12 hourly) to align with patency assessment and documentation of once per shift (1,31,78,79). Remove as soon as possible, as clinically indicated in collaboration with the health team (1).

Refer to section below for more information and discussion of current evidence.

SECTION A: CENTRAL VENOUS DEVICES

FLUSHING PRACTICES

The flushing sections below will amalgamate paediatric and adult studies (unless otherwise stated) as all CVADs require flushing to clear a lumen of blood components and flush in between incompatible solutions.

1. FLUSH SOLUTION

1.1 Summary of Evidence

0.9% sodium chloride is supported in numerous studies to flush CVADs (6,12,15,24,27,28,30,34,39,42,50-62).

1.2 Practice Recommendation

CNSA recommends to flush Central Venous Access Devices for paediatric and adult patients with cancer with 0.9% sodium chloride (6,12,15,24,27,28,30,34,39,42,50-62).

GRADE: V

Rationale: flushing was part of the study protocol i.e. flushing practice, and not a study outcome.

2. FLUSH TECHNIQUE

2.1 Summary of Evidence

There are two key components of flushing techniques identified in the studies including:

Pulsatile / start - stop technique: supported and recommended in the majority of studies, in both paediatric and adult populations and all types of CVADs (9,12,24,27,28,33,34,39,41,42,44,53,54,57,63,64)
Maintenance of positive pressure at the end to ensure the outward movement of the locking solution during disconnection of the syringe, prevents blood reflux into the catheter tip and subsequent occlusion (9,12,24,27,28,34,41,42,44,53,54,63,64). The technique varies according to the type of needleless connector (negative, positive, neutral and anti-reflux) technique.

Needleless connector clamping-disconnection technique varies, therefore refer to manufacturer’s recommendations. These techniques may include (1,65):

Negative: clamp whilst instilling the last 0.5mL and before disconnection of the syringe to prevent the back flow of blood in the catheter tip when the syringe is disconnected.
Positive: clamp after the syringe is disconnected
Neutral: no specific clamping procedure is required for neutral needleless connectors
Anti-reflux: no specific clamping procedure is required for anti-reflux needleless connectors

Education improves the clinician’s compliancy to flushing practices including the flushing technique which results in reduced occlusion rates (12).

This should be completed for each lumen of multi-lumen CVAD according to expert opinion (41)

2.2 Practice Recommendation

CNSA recommends to flush Central Venous Access Devices:

Using a start-stop flush technique (9,12,24,27,28,33,34,39,41,42,44,53,54,57,63,64).
And complete the flush with the appropriate clamping-disconnection sequence to maintain positive pressure at the catheter tip (9,12,24,27,28,34,41,42,44,53,54,63,64) according to the type of needleless connector.
Leaving 0.5 mL of fluid to prevent blood reflux into the catheter tip by ‘bottoming out’ or emptying the syringe fully (65).
For each lumen of a CVAD (41).

GRADE: V

3. FLUSH FREQUENCY

3.1 Summary of Evidence

Adult:

Flushing frequency noted in studies is highly variable (24), however key times for flushing include:

After each use, for example post medication administration, blood sampling, blood product administration, parenteral nutrition administration, contrast (6,12,33,39,42-44,51,53,57) or after accessing a Totally Implanted Venous Access Devices / Portacaths (42)
Between incompatible solutions (62)
Periodically (43) or routinely (60) when not in use, for example once a day (30) or alternate days (52).
And before the administration of the lock solution (12,15,33,42,44,52,58,63,66).

Refer to Locking Practices - Solutions, Dose and Volume section below.

Paediatric:

A sequential, observational study stated routine flushing practice included (6)

Valved catheters – after each use and weekly when not in use
Open catheters: every 12 hours during intermittent use or when not in use

3.2 Practice Recommendation

CNSA recommends to flush Central Venous Access Devices routinely including:

Intermittent use: after each use, for example post medication administration, blood sampling, blood product administration, parenteral nutrition administration, contrast (6,12,33,39,42-44,51,53,57) or at least once per shift (8-12 hourly) to align with patency assessment and documentation of once per shift (1,31)
In between incompatible solutions or medications (62).
Before lock solution administration (12,15,33,42,44,52,58,63,66).
After accessing a Totally Implanted Venous Access Device (42,78)
Paediatric catheters: regularly during intermittent use, for example every 12 hours – catheters > 3FR; (6).

GRADE: V

4. FLUSH VOLUME

4.1 Summary of Evidence

Adults:

There are two volumes discussed in the literature including:

10 mLs (15,39,59)
Increasing volume to 20mls after blood sampling or blood product administration, viscous fluids for example parenteral nutrition computerised tomography (CT) contrast (6,27,42,51,53)
20 mLs (34,44,50)

Paediatrics:

Two studies included:

A prospective observational study of paediatric and adolescent participants (age 4.9-18 years) stated flushing practice was to use 20 mLs (52)
A sequential, observational study stated routine flushing practices included:
- Valved catheters – 5-10 mLs
- Open catheters ≥2.6 Fr – 2-3 mL and 10-20 mLs after blood sampling

4.2 Practice Recommendation

CNSA recommends to flush Central Venous Access Devices with 0.9% sodium chloride for patients with cancer and:

Adult:
- Flush with 10 mLs (15,39,59).
- Increase to 20 mLs in a 20 mL syringe or two 10 mL syringes (6,27,42,51,53) after medication administration, blood sampling or blood product administration, viscous fluids for example parenteral nutrition computerised tomography (CT) contrast (6,27,42,51,53) or in between incompatible solutions if clinically appropriate (for example, not for renal, cardiac, critical care or fluid intake restricted patients).
Paediatric:
- At least double the volume of the CVAD and attachments for paediatric patients (1,65). For >3Fr catheters, consider 10-20 mLs when clinically appropriate (6).
- Complete lock for every patient, every time, for every CVAD (48).

GRADE: V

LOCKING PRACTICES

5. LOCK SOLUTIONS

5.1 Summary of Evidence

There is no compelling, conclusive evidence to support the use of one specific locking solution over another. Historically, heparin was recommended by manufacturers as a locking solution (68). However, the debate continues about the most efficacious locking solution with the maximum safety profile (40,43) including:

Adult:

Heparin versus 0.9% sodium chloride.

A systematic review concluded current studies supported both 0.9% sodium chloride and heparin, but the quality of evidence is poor. “Low-quality evidence suggests that heparin may have little or no effect on catheter patency” (25). Furthermore, the review found “no evidence of an increased effect with increasing concentrations of heparin” (25). Therefore, no definitive recommendation for practice could be made based on current evidence.

An evidence-based guideline based on a systematic review of randomised controlled trials stated numerous flushing protocols existed including heparin, 0.9% sodium chloride and tissue plasminogen activator (t-PA) with varying volumes and concentrations therefore considering no conclusive recommendations can be made (60).

A prospective observational study of 116 participants with a weekly lock of heparin and daily flushing of 0.9% sodium chloride resulted in occlusions in two CVADs, both resolved with urokinase or heparin flushing (80).

Novel lock solutions.

Surveys in adults (81), and adults and paediatric cancer health care services (63) identified variance in locking solutions, doses and volumes used in clinical practice including citrate, taurolidine +/- other solutions, urokinase, 0.9% sodium chloride and heparin.

The efficacy of other types of locking solutions being investigated include:

Citrate: a prospective observational study of 135 PICCs in 124 patients noted one device (0.7%) removed due to complete occlusion and occlusion rate of 0.68 per 1000 catheter days (33). A small, retrospective observational study of haematology patients receiving stem cell transplants with mainly TC-CICC locked with heparin for the inpatient period and hypertonic citrate for the outpatient period found 3 out of 23 patients had catheter thrombosis (59).
Alteplase: a retrospective chart review of 10 participants with large bore, tunnelled cuffed centrally inserted central catheters (TC-CICC) for apheresis procedures compared alteplase with practice of heparin (standard practice) and found “heparin may increase a patient’s odds of having CVC flow rate problems compared to rt-PA” (recombinant tissue plasminogen activator) but further larger studies were required to make definite conclusions (58).

Paediatric:

Heparin versus 0.9% sodium chloride.

A systematic review in the paediatric patient population concluded “there was not enough evidence to determine which solution, heparin or saline, is more effective for reducing complications” and the current evidence was low to very low (24).

A prospective data registry of 262 patients with 423 devices when the CVADs were locked with heparin, occlusions were noted in 102 CVAD and 21 removals were due to occlusion (82)

Novel lock solutions.

The efficacy of other types of locking solutions being investigated include:

Taurolidine and citrate versus heparin: a prospective randomized controlled clinical trial of 51 participants with TC-CICC found 11 patients developed catheter occlusion of which 10 responded to urokinase treatment (69)
Alteplase: results of an effectiveness, pilot study of 8 participants having long-term parenteral nutrition (PN) for short bowel syndrome using alteplase in between PN infusions and heparin on the days alteplase was not used included 2 patients who required reinsertion due to occlusion (83)
Ethanol versus heparin: Expert review of the literature (84). A randomised controlled superiority trial followed in 2018 with 94 participants comparing ethanol locking solution to heparin found statistically significant more devices with occlusion required thrombolytic treatment with ethanol compared to heparin (61).

LOCK DOSES/VOLUME:

Adult:

In adult studies, heparin doses greatly vary between 10 units to 5000 units (8,25,32,49,70,81,85-88) and can be influenced by whether the CVADs were valved or non-valved (63). Locking solutions can also vary from the filling volume of the device to 20mLs (63).

0.9% sodium chloride 10 mLs 28 and 20 mLs (34,51) were both considered effective (46).

Paediatrics:

Paediatric studies also vary greatly in heparin doses 10 to 500 units to infusional heparin with a median of 1 unit / mL (24,89). Volume of the locking agents vary from the filling volume of the device to 5 mLs (7,24,69).

5.2 Practice Recommendation

CNSA recommends to lock Central Venous Access Devices with 0.9% sodium chloride for patients with cancer (24,25,28,34,46,50,51,67,68) and:

Adult:

Lock with 20mLs (34,51), and if clinically appropriate for example, for renal, cardiac, critical care or fluid intake restricted patients (53) - lock with 10 mLs (28).

Paediatric:

Lock with least double the volume of the CVAD for paediatric patients (65). For >3FR catheters, consider 10-20mls when clinically appropriate (6).

Complete lock for every patient, every time, for every CVAD (48).

Routine surveillance of occlusion rates and/or thrombolytic usage for treating intraluminal occlusions should be completed. An increase in occlusion rates or thrombolytic medication usage should be evaluated by compliance with the four practice principles:

Education and Competency
Regular flushing practices
Pulsatile or start - stop technique and
Consistent flushing and locking practices, including documentation of all assessments, findings and interventions.

GRADE: V

NOTE: caution with patients with CVADs with infective complications where other locking solutions (anti-infective) may be used.

LOCKING PRACTICES ACCORDING TO TYPE OF CVAD

The following sections will discuss locking solutions according to the type of CVAD in the paediatric and adult patient populations.

6. TOTALLY IMPLANTED VASCULAR ACCESS DEVICES (TIVAD)

6.1 Summary of Evidence

Adult:

In the adult patient population, the use of heparin and 0.9% sodium chloride as locking solutions to prevent TIVAD occlusion remains unresolved (44).

Studies that compare 0.9% sodium chloride and heparin -

Studies that compared 0.9% sodium chloride and heparin demonstrated both solutions were effective. Two large retrospective studies concluded that 0.9% sodium chloride was effective as heparin (40) and there was no statistical significance for occlusion, reflux dysfunction and flow dysfunction between both solutions (67).

Furthermore, a Cochrane Review identified that ‘despite results suggesting no differences in safety, it is probable that a high proportion of patients could be at increased risk with heparin use (25). It was also concluded that there was no beneficial effect from increasing the heparin dose (25).

Heparin -

Studies that discuss the use of heparin to prevent occlusion include one prospective study with an occlusion rate of less than 1.5% which were treated successfully with thrombolytic administration (70) and seven retrospective studies with less than 2% occlusion rates (8,49,86-88,90,91).

0.9% sodium chloride -

Comparatively, other studies support the use of 0.9% sodium chloride to prevent TIVAD occlusion including two prospective studies (34,36) with occlusion rates less than 1.1% and two retrospective studies with less than 1% (46) or no devices (28) removed due to occlusion. These studies were supported by Milani (2016) (50) who stated the results from three large studies that supported 0.9% sodium chloride as an effective locking solution should be taken into account before any future large prospective studies are undertaken.

Paediatric:

Heparin -

There is a lack of definitive evidence for the paediatric population. Two retrospective observational studies supported heparin as an effective locking solution with occlusion rates of 1.38% (92) and 1.8% (71) whilst a small retrospective chart audit identified an occlusion rate of 7.7% (45). Furthermore, a Quality Improvement project concluded standardizing heparin doses increased safety and efficacy (85).

Adult and Paediatric:

Comparatively, an adult and paediatric randomised, parallel-group, open labelled study concluded heparin was not sufficiently effective and 0.9% sodium chloride was safe and effective (27).

Expert opinion of current evidence of TIVAD for adult and paediatric patients was heparin locking can prevent thrombotic occlusions and prophylactic administration of fortnightly urokinase can improve occlusive events in TIVAD and tunnelled catheters in paediatric patients (62).

Cost:

A quantitative, exploratory-descriptive study investigating the cost of replacing heparin with 0.9% sodium chloride for locking TIVADs in a day hospital identified a cost reduction per procedure when locking with 0.9% sodium chloride compared to heparin (93).

6.2 Practice Recommendation

CNSA recommends to lock Totally Implanted Vascular Access Devices with 0.9% sodium chloride for paediatric and adult patients with cancer (28,34,36,40,46,50,67).

GRADE: V

NOTE: Caution with patients with TIVADs with infective complications where other locking solutions (anti-infective) may be used

7. PERIPHERALLY INSERTED CENTRAL CATHETER (PICC)

7.1 Summary of Evidence

Adult:

There is no definitive evidence supporting the use of one locking solution over another to prevent occlusion for adult patients diagnosed with cancer with a PICC insitu.

Heparin -

The use of heparin is supported by two large prospective observational studies: (1) with an occlusion rate of 3.4% and removal rate of 1.7% (15) and (2) despite the most frequent complication being partial occlusion, the removal rate due to occlusion was under 1% (33). Also, two retrospective studies using heparin locks had minimal or no removals due to occlusion (90,94).

Sodium Chloride -

In contrast, a literature review and international expert consensus recommended 0.9% sodium chloride for PICC patency maintenance (95). This was supported by (1) large prospective study which resulted in an occlusion rate of 2.4% (39) and (2) small study of haematology patients requiring autologous stem cell transplantation with 1.6% occlusion rate using 0.9% sodium chloride as a locking solution (51). This contrasted with a large study (56) with an occlusion rate of 14.68%, however the majority of participants (53%) were admitted for hospice care.

Citrate –

A prospective observational study of 135 PICCs in 124 participants noted one device (0.7%) removed due to complete occlusion, 22 episodes of partial occlusion over the 2 year study and occlusion rate of 0.68 per 1000 catheter days (33)

Paediatric:

One retrospective, population-based cohort study over 15 years in Canada concluded that PICCs are associated with high rates of complications; occlusion and infection were the most frequent complications. Heparin was used as the locking agent (7).

7.2 Practice Recommendation

CNSA recommends to lock Peripherally Inserted Central Catheters with 0.9% sodium chloride for paediatric and adult patients with cancer (39,51,95).

GRADE: V

Note: Caution with patients with infective CVAD complications where other locking solutions (anti-infective) may be used.

8.TUNNELLED-CUFFED CENTRALLY INSERTED CENTRAL CATHETERS (TC-CICCs)

8.1 Summary of Evidence

A survey in both adults and paediatric cancer health care services across Canada identified variance in locking solutions, doses, and volumes of heparin and 0.9% sodium chloride used in clinical practice (55).

Adults:

There are currently no definitive evidence-based recommendations for patients with cancer and a TC-CICC insitu. Occlusions remain one of the most frequent complications for TC-CICCs. Currently, a variety of solutions are used including 0.9% sodium chloride and heparin (25,90).

Paediatrics:

Locking solutions used in paediatric studies varied.

Heparin –

A prospective database from a conference abstract including 563 Tunnelled-Cuffed Centrally Inserted Central Catheters locked with heparin found occlusions in 20%, and when urokinase was used, 30% of the catheters remained occluded and were removed (96).

A large prospective surveillance study identified occlusion was the most frequent complication, 42% when locking with heparin (29). A large prospective observational study, over 8 years, which locked the TC-CICCs with heparin noted occlusions were the most frequent complication at a 3.9% occlusion rate (52). An observational study concluded heparin was not sufficient to prevent occlusions with at least one thrombotic complication in 45% of participants requiring 23.2% to be removed (97).

Sodium Chloride -

Comparatively, a small retrospective study of mainly haematology participants using a 0.9% sodium chloride locking solution resulted in occlusions in 27%, however the majority were chemical occlusions (9).

Novel Locking Solutions –

Three studies investigated novel locking agents. A small prospective, randomized controlled clinical trial compared heparin and a taurolidine and sodium citrate solution which found similar occlusion rates in both groups and more reported side-effects with taurolidine solution group (69). A small pilot study with short bowel syndrome patients using alteplase as a locking solution which resulted in improved rates of infective complications and indications for potential improvement in occlusion rates. However future studies with larger patient cohorts were required (83). The third study was a small retrospective chart review which compared the vascular access outcomes of paediatric patients with intestinal failure on long-term parenteral nutrition during the times their devices were locked with heparin compared to ethanol (98). The results showed ethanol was an effective locking solution for decreasing CVAD related infections however, it was associated with an increase in occlusions and line fractures compared to heparin (98).

A large chart review study of 358 paediatric patients with Acute Myeloid Leukaemia, Acute Lymphocytic Leukaemia, Lymphoma and other non-central nervous system cancers with Tunnelled Cuffed-Centrally Inserted Central Catheters and Totally Implanted Venous Access Devices concluded persistent or recurrent issues with occlusions were an “an independent predictor of poor OS [overall survival] and EFS [event-free survival] in children with cancer” (99).

8.2 Practice Recommendation

CNSA recommends to lock Tunnelled-cuffed Centrally Inserted Central Catheters with 0.9% sodium chloride for paediatric and adult patients with cancer.

GRADE: Committee Consensus

NOTE: caution with patients with infective CVAD complications where other locking solutions (anti-infective) may be used.

9. CENTRALLY INSERTED CENTRAL CATHETERS (CICCS) – TUNNELLED, NON-TUNNELLED AND APHERESIS CICCS

9.1 Summary of Evidence

Adults:

Studies investigating CICCs are inconclusive.

Heparin and sodium chloride –

A small, randomised controlled pilot study of tunnelled, non-tunnelled and apheresis CICCs which compared heparin and 0.9% sodium chloride identified similar occlusion rates and use of thrombolytic administration rates in each group (31).

A Cochrane Clinical Question/Answer stated it was not possible to make conclusions about heparin and 0.9% sodium chloride based on low quality of evidence and variance in duration of follow up (100).

Heparin:

A small observational study identified no occlusions when locking TC-CICCs with heparin (90).

Heparin and alteplase – with Large Bore TC-CICC / Apheresis Catheters –

A small retrospective study investigating large bore TC- CICC used with photopheresis procedures, compared alteplase and heparin locking solutions. The authors concluded heparin may have increased the risk of flow rate issues but this would need to be confirmed in future larger patient sample sizes to be conclusive (58).

Paediatrics:

One prospective, randomized controlled study concluded 0.9% sodium chloride resulted in higher rates of occlusion compared to heparin (10). However, the frequency of flushing and type of needleless connector were concurrently changed which potentially impacted the results.

9.2 Practice Recommendation

CNSA recommends to lock Centrally Inserted Central Catheters with 0.9% sodium chloride for paediatric and adult patients with cancer (31).

GRADE: IV

Rationale: randomized control trial with an unclear risk of bias

NOTE: caution with patients with CVAD with infective complications where other locking solutions (anti-infective) may be used.

LOCKING PRACTICES - FREQUENCY

10. CENTRAL VENOUS ACCESS DEVICE

10. CENTRAL VENOUS ACCESS DEVICE

10.1 Summary of Evidence

Evidence for the frequency of locking practices for CVADs varies primarily according to type of CVAD.

A survey of 23 haematology centres identified practice varied from once per day to once per week for PICCs and CICCs (81). A questionnaire of 44 paediatric and adult centres identified TIVADs were locked every 35 days (range 21-90 days) (63). This was supported by a narrative literature review which identified TIVADs were commonly locked once every four weeks (68). Expert opinion is to “flush the catheter regularly after use and periodically if the catheter is not in use” (43). Refer to sections below for specific recommendations according to type of CVAD.

There are no studies that investigated the frequency of flushing and locking unused lumen/s when one or more of the other lumens of a multi-lumen CVAD are in use.

10.2 Practice Recommendation

CNSA recommends to lock CVADs for paediatric and adult patients with cancer according to the evidence for the type of CVAD. Refer to the sections below.

11. TOTALLY IMPLANTED VASCULAR ACCESS DEVICES (TIVAD)

11.1 Summary of Evidence

A survey of 41 paediatric and adult cancer services identified locking frequency of TIVADs ranged between 3 weeks to 3 months (63). However, consensus for the most common frequency in practice is after use and prior to huber needle removal and once per month for both adults and paediatric patients (41,42,68). However, a number of studies have investigated extending current practice of every month to varying intervals from 3 monthly (28,66,86) to indefinitely i.e. no locking until next use (36,46,87) (see below for results).

Adults:

Inpatients:

Flushing practices including after infusions/chemotherapy/blood products/antibiotic administration and at least once per day was considered effective in a large prospective study (70).

Ambulatory patients having regular treatments:

Consensus is to lock after each chemotherapy administration or infusion (for example antibiotics, parenteral nutrition) (28,40,49,66,67,70,86,90,91).

Routine flushing when device not in regular use:

Studies supporting the frequency of locking TIVADs every 4 weeks include a large prospective study with 1% partial occlusion rates and no complete occlusions (34) and four retrospective studies with complete occlusions in 0% (90), 0.39% (91), under 3% (67) and 6.2% (40) of patients.

Studies also investigated and demonstrated the effectiveness of locking practices with extended periods between procedures including:

Six weekly: a prospective study with less than 1% occlusions (70) and a retrospective study with no devices removed due to occlusion (49)
Six to eight weekly: a large retrospective study of 7118 TIVADs identified the majority (72.2%) of requests to the vascular access nursing team were malfunction related, 4.4% required removal and 80.6% of these cases had compounding factors e.g. catheter tip malposition (42). An explorative, pragmatic, prospective study of 37 participants and 961 flushing episodes showed no statistical significance between flushing once every 4 weeks compared to 8 weeks (101).
Twelve weekly: a prospective study resulted in one removal due to occlusion (66) and two large retrospective studies resulted in zero (28) or one removal due to occlusion (86)
Indefinite time in between locking procedures, that is no locking procedure until the next use: a large prospective observational study identified one device was non-functional (36) and two large retrospective studies found no difference between frequent and infrequent locking practices (46,87)

Paediatric:

The frequency documented in the literature for paediatric patients varies markedly from monthly with occlusion rates in a large retrospective study of 1.8% (71) and a small retrospective study of 1.38% (92) compared to indefinitely (ranging from 64-596 days) with a small retrospective chart audit with two episodes of occlusion (45).

11.2 Practice Recommendation

CNSA recommends the locking frequency for Totally Implanted Vascular Access Devices paediatric and adult patients with cancer to include:

Inpatients - accessed but not in regular use:
- Lock with 0.9% sodium chloride and de-access the TIVAD, if clinically appropriate.
- Lock with 0.9% sodium chloride after each use (70) for example post drug administration, blood sampling and at least once or at least once per shift (8-12 hourly) to align with patency assessment and documentation of once per shift (1,31)
Ambulatory patients:
- Lock with 0.9% sodium chloride after use at each visit (28,40,49,66,67,70,86,90,91).
TIVADs not in use:
- Lock every 4 to 6 weeks (41,42,49,68,86).
- Locking frequency can be extended (28,36,45,46,66,86,87,92) but must be accompanied by routine monitoring of occlusion rates and thrombolytic medication administration rates.

GRADE: V

12. PERIPHERALLY INSERTED CENTRAL CATHETERS (PICC)

12.1 Summary of Evidence

Adults:

Frequency of locking practices for PICCs varied from after each intermittent use for inpatients to once a week if not in use. A large prospective study identified a removal rate of 2.4% (39) and 11% in a small observational study (90) when locked once a week when the PICC was not in use. A small observational studying involving patients undergoing autologous peripheral blood stem cell transplantation resulted in removal of 1.6% devices when locked after use (51).

Paediatric:

A large, retrospective, population-based study over 14 years, PICCs not in use were locked at a minimum of once every 24 hours for inpatients, which parents continued once daily after discharge. Results indicated 33% of the first inserted PICCs were removed due to complications, occlusion was the most frequent complication (28%) (7).

12.2 Practice Recommendation

CNSA recommends the locking frequency of Peripherally Inserted Central Catheters for paediatric and adult patients with cancer to include:

Adult inpatient:
- Intermittent use: lock with 0.9% sodium chloride after each use (51) or at least once per shift (8-12 hourly) to align with patency assessment and documentation of once per shift (1,31).
- Not in use: lock with 0.9% sodium chloride weekly (39,90).
- Single lumen: lock with 0.9% sodium chloride after each use and at least weekly (51).
- Unused lumens of multi-lumen PICC: Lumens in continuous use do not require flushing. However, unused lumens should be flushed with 0.9% sodium chloride at least once per day. This aligns with regular assessment and documentation of patency to prevent luminal occlusion (1). Potential pressure changes created by variance in pressure in an adjacent lumen may cause blood reflux into the opening of the unused lumen, for example by disconnection and connection of syringes and intravenous lines, pulsatile flushing, pulsatile intravenous pumps.
Adult ambulatory setting:
- Lock with 0.9% sodium chloride after use or at least weekly at the time of dressing replacement (39,90).
Paediatrics:
- Routinely – for example as per recommendations for adult (above) if clinically appropriate.

GRADE: V

13. TUNNELED CUFFED CENTRALLY INSERTED CENTRAL CATHETERS (TC-CICC)

13.1 Summary of Evidence

Adult:

An observational study with 17 patients with TC-CICCs locked every 7 days when not in use - 10 out of 19 patients with complications (the type of complication was not specified and may not have been occlusion related (90).

Paediatric:

Paediatric studies included two prospective studies: (1) a small randomized controlled trial that compared prefilled and manually filled 0.9% sodium chloride locked once a day with zero occlusions in both groups in TC-CICCs (all occlusions were in TIVADs – more in the manually prepared vs prefilled syringes) (30) and (2) a large prospective study locked TC-CICCs twice a week which resulted in malfunction/occlusions being 42% of the complications (29). Also a small retrospective cohort study locked the device every 7 days when not in use with (9).

13.2 Practice Recommendation

CNSA recommends the locking frequency of Tunneled Cuffed Centrally Inserted Central Catheters for paediatric and adult patients with cancer to include:

Inpatient:
- Intermittent use: lock with 0.9% sodium chloride after each use or at least once per shift (8-12 hourly) to align with patency assessment and documentation of once per shift (1,31).
- Not in use: lock at least weekly (90).
- Single lumen: lock with 0.9% sodium chloride after each use and at least weekly (90).
- Unused lumens, of a multi-lumen TC-CICC in use: Lumens in continuous use do not require flushing. However, unused lumens should be flushed with 0.9% sodium chloride after each use and at least once per day. This aligns with regular assessment and documentation of patency to prevent luminal occlusion (1). Potential pressure changes created by variance in pressure in an adjacent lumen may cause blood reflux into the opening of the unused lumen, for example by disconnection and connection of syringes and intravenous lines, pulsatile flushing, pulsatile intravenous pumps.
Ambulatory setting:
- Lock with 0.9% sodium chloride after use or at least weekly at the time of dressing replacement (1).

GRADE: V

14. CENTRALLY INSERTED CENTRAL CATHETERS (CICC) AND TUNNELED CENTRALLY INSERTED CENTRAL CATHETERS (T-CICC)

14.1 Summary of Evidence

One study, a survey of 23 adult centres demonstrated variance in practice from once a day to once a week (81).

14.2 Practice Recommendation

CNSA recommends to lock Centrally Inserted Central Catheters for paediatric and adult patients with cancer:

Inpatient:
- CICC not in use and no longer clinically required: prompt removal in consultation with the medical team (1,65,75).
- Unused lumens, of multi-lumen CICC in use: Lumens in continuous use do not require flushing. However, unused lumens should be flushed with 0.9% sodium chloride after each use and at least once per day. This aligns with regular assessment and documentation of patency to prevent luminal occlusion (1). Potential pressure changes created by variance in pressure in an adjacent lumen may cause blood reflux into the opening of the unused lumen, for example by disconnection and connection of syringes and intravenous lines, pulsatile flushing, pulsatile intravenous pumps.

GRADE: V

Rationale: not all references from literature search

TECHNIQUE OF LOCKING PRACTICES

15. LOCKING TECHNIQUE FOR CVADS

15.1 Summary of Evidence

There are two key components of locking techniques identified in the studies including:

Pulsatile / start - stop technique: supported and recommended in the majority of studies, in both paediatric and adult populations and all types of CVADs (9,28,30,31,34,39,40,44-46,101)
Maintenance of positive pressure at the end to ensure the outward movement of the locking solution during disconnection of the syringe, prevents blood reflux into the catheter tip and subsequent occlusion (40,44). The technique varies according to the type of needleless connector (negative, positive, neutral and anti-reflux) technique.

Needleless connector clamping-disconnection technique varies, therefore refer to manufacturer’s recommendations. These techniques may include:

Negative: clamp whilst instilling the last 0.5mL and before the syringe is disconnected to prevent the ingress of blood in the catheter tip when the syringe is disconnected.
Positive: clamp after the syringe is disconnected
Neutral: no specific clamping procedure is required for neutral needleless connectors
Anti-reflux: no specific clamping procedure is required for anti-reflux needleless connectors

Education improves nurse’s compliancy to flushing practices including the flushing technique which results in reduced occlusion rates (12).

15.2 Practice Recommendation

CNSA recommends the locking technique of Central Venous Access Devices for paediatric and adult patients with cancer to include:

A pulsatile / start - stop technique (9,28,30,31,34,39,40,44-46,101) and
Complete the procedure with the appropriate clamping-disconnection sequence technique to maintain positive pressure during disconnection of the syringe according to the type of needleless connector to prevent occlusions (40,44).
Leaving 0.5-1 mL of fluid to prevent blood reflux into the catheter tip by ‘bottoming out’ or emptying the syringe fully (65)
For each lumen of a CVAD (41)

GRADE: V

FLUSH / LOCK ADMINISTRATOR

16. ADMINISTRATOR OF CVAD FLUSHING/LOCKING PRACTICES

16.1 Summary of Evidence

Different professions are involved with administering locking solutions including:

Nurses
- PICC Nurse Teams (55)
- Specialised PICC team of oncology nurses (39)
- Specially trained nurses in haematology or oncology units in (a) adults (49,51) or (b) paediatric patients (9,10,29,42)
Doctors
- experienced medical staff (69,70)
Patients and/or parent, carers, family with prime responsibility
- During inpatient stage (32)
- After discharge (7,71)

Education is an essential principle for any administrator of locking solutions in order to reduce occlusion rates (12).

16.2 Practice Recommendation

Competency assessment post education is required (1,53,72,102).

GRADE: V

SYRINGE FEATURES

17. CVAD SYRINGE FEATURES – SIZE, MANUAL VS PREFILLED

17.1 Summary of Evidence

Syringe Size:

Consensus supports the use of 10mL syringes or larger e.g. 20mL. Evidence includes a pilot random controlled trial (30), three observational studies (39,40,90), a questionnaire (63) and expert consensus statement (53) for 10ml syringes; and literature review (54) and letter to the editor (50) for 20mL syringes.

Syringe – prefilled versus manually filled

0.9% sodium chloride flushing and locking solutions are either drawn up by the clinician or provided as a manufactured prefilled, single-use syringe. Two studies used manufactured prefilled 0.9% sodium chloride syringes: (1) a large adult study investigating PICC failure and complications identified 2% of patients required CVAD removal due to occlusion (39) and (2) a prospective, paediatric randomised controlled study of TIVAD and TC-CICC concluded there were less occlusions in the patient group locked with manufactured prefilled versus manually prepared syringes (both 0.9% sodium chloride) (30). Gerceker (2018) (30) also identified previous studies where cost effectiveness and significant lower infection rate was attributed to the use of prefilled syringes and studied their use in the paediatric cohort.

17.2 Practice Recommendation

CNSA recommends the use of 10mL or larger volume luer lock syringes for flushing and locking Centrally Venous Access Devices (CVADs) for paediatric and adult patients with cancer (30,39,40,50,53,54,63,90).

GRADE: V

CNSA recommends clinicians consider the use of manufactured, single use, prefilled locking solutions with anti-reflux and pressure limiting features which may assist to prevent occlusions of Centrally Venous Access Devices (CVADs) for paediatric and adult patients with cancer (30,39).

GRADE: III

BASELINE INTRAVENOUS FLOW RATE - To Keep Vein Open (TKVO)

18. BASELINE INTRAVENOUS FLOW RATE - To Keep Vein Open (TKVO)

18.1 Summary of Evidence

‘To Keep Vein Open’ is the minimum rate of continuous intravenous fluids that aims to keep a cannula or catheter patent and prevent occlusion. It is a widespread practice for which there is no evidence or practice recommendations (103).

A survey in Canada found rates varied between 1 mL to 75 mLs per hour; 21-30 mLs per hour was the most common (nearly 50% respondents) (74). Disadvantages of administering intravenous fluids at a TKVO rate compared to intermittent flushing is (1) an increased volume of fluids administered over a 24 hour period which may be clinically relevant to cardiac or renal patients and (2) the potential to reduce the incentive to mobilize if the patient is attached to an intravenous pole and fluids. Theoretical advantages include a reduction in the number of times the catheter/cannula hub is manipulated potentially reducing the risk of infection, especially if needleless connection disinfection practices are suboptimal and reduction in the number of changes in intravenous administration lines (74). The authors acknowledge there is currently no evidence but suggested:

Peripheral Intravenous Cannulas – lock and not use continuous fluids
Renal, cardiac, critical care or fluid impaired patients – lock or use a volumetric pump at 10mls/hr as clinically appropriate
Adults – who require > 4 hourly access of cannula/catheter to use a volumetric pump at 10mls/hr
Patients without contraindications to use a volumetric pump at 10mls/hr or via a gravity set (rate will vary according to the set)

It is evident more research is required.

18.2 Practice Recommendation

CNSA recommends to consider a baseline intravenous flow rate (To Keep Vein Open TKVO) for Peripheral Intravenous Cannula (PIVC) and Central Venous Access Devices (CVADs) in patients with cancer (74):

Using a volumetric pump at 10mls/hr for
- Patients without contraindications for example without renal, cardiac, critical care or fluid intake restrictions
- Patients that require regular access more frequently than 8 hourly or more for all intravenous medications
- Paediatric patients as clinically appropriate
Consider locking and not using continuous TKVO rate for
- Patients that require regular access less frequently than 8 hourly for all intravenous medications
- Renal, cardiac, critical care or fluid impaired patients
- Paediatric patients as clinically appropriate

GRADE: Committee Consensus

Rationale: Paquet not part of literature review

Education and Competency
Regular flushing practices
Pulsatile or start - stop technique and
Consistent flushing and locking practices, including documentation of all assessments, findings and interventions.

SECTION B: PERIPHERAL INTRAVENOUS CANNULAS (PIVC)

FLUSHING PRACTICES

There is one expert opinion article that briefly discuss Peripheral Intravenous Cannulas in relation to patients with cancer. Practice recommendations in the following sections are supported by evidence not specific to patients with cancer but from general patient populations.

19. FLUSHING SOLUTION AND VOLUME

19.1 Summary of Evidence

Solution

It is frequently identified in the literature to flush Peripheral Intravenous Cannulas with 0.9% sodium chloride (1,38,75-77).

Volume

A pilot randomised controlled study in 160 adult participants in Australia found the failure rates of Peripheral Intravenous Cannulas increased in the 10 mL group (44%) compared to the 3 mL group (29%) (78). A review article by a vascular access expert stated the volume of a cannula is approximately 0.3 mL and small volumes of flushing or locking solutions were required, for example 5mls (104).

Also current recommendations state that flush volume can be increased for example to 5mls, post blood product and viscous fluid administration such as parenteral nutrition and contrast media (1).

19.2 Practice Recommendation

CNSA recommends to flush Peripheral Intravenous Cannulas with 3mls 0.9% sodium chloride for paediatric and adult patients with cancer (1,75-77).

Increased volume, for example 5mls can be used post administration of blood products or viscous fluids (1), for example parenteral nutrition, contrast media.

GRADE: Committee Consensus

Rationale: literature not from literature search

20. FLUSHING TECHNIQUE

20.1 Summary of Evidence

A computational study of Peripheral Intravenous Cannulas investigating the ‘hemodynamic environment likely to contribute to device failure’ showed the most influential factor for potential damage to a vein wall was the rate of instillation of fluids through the cannula (47).

Completing the flushing procedure of a Peripheral Intravenous Cannula by maintaining a positive pressure aims to prevent the reflux of blood and blockage of the cannula tip by continuing the outward movement of the flush solution at the end. This can be completed by:

Using the appropriate clamping-disconnection technique according to the type of needleless connector being used and if a clamp is present on the extension tubing attached to the cannula – refer to 2. Flush Technique (41).
Continuing to push on the flush syringe plunger during the last 0.5mls of whilst withdrawing the syringe from the needleless connector (38).

20.2 Practice Recommendation

CNSA recommends to consider flushing Peripheral Intravenous Cannulas using a slow and steady technique, for example less than 1 mL per second to limit the damage to the vein wall potentially caused by fast flow rates and completing the flush by maintaining positive pressure.

GRADE: Committee Consensus

21. FLUSHING FREQUENCY

21.1 Summary of Evidence

Adults:

Current recommendations are to flush PIVC before and after the administration of medications and regularly when not in use (1).

Frequency of flushing in the literature varies from PRN (Pro Re Nata, as needed), to every 6, 8 to 24 hours (17). 1A pilot randomised controlled study in 160 adult participants in Australia found there was no difference in failure rates between frequent flushing (6 or 12 hourly) and less frequent (24 hourly). By minimising the number of accesses into a closed intravenous system (from 4 times to once in 24 hours) would reduce the risk of infection by reducing the number of opportunities for potential pathogens to enter the blood stream.

Paediatric:

Studies support once per day flushing for paediatric patients without compromising patency (105,106)

21.2 Practice Recommendation

CNSA recommends to flush Peripheral Intravenous Cannulas not in continuous use for paediatric and adult patients with cancer, before and after medication administration and or at least once per shift (8-12 hourly) to align with patency assessment and documentation of once per shift (1,31,78,79).

Remove as soon as possible, as clinically indicated in collaboration with the health team (1).

GRADE: Committee Consensus

LOCKING PRACTICES

22. LOCKING SOLUTION AND VOLUME

22.1 Summary of Evidence

Adult:

Studies have not demonstrated the benefit of heparin compared to saline as lock solution for Peripheral Intravenous Cannulas (17,76,77). Current recommendations state to lock with 0.9% sodium chloride for adults (1,65,75)

Paediatric:

A large randomised control study of 400 participants found locking with 0.9% sodium chloride effective (106). Current recommendations state to (1,65,75) lock with heparin or 0.9% sodium chloride for paediatrics (1).

22.2 Practice Recommendation

CNSA recommends to lock Peripheral Intravenous Cannulas with 0.9% sodium chloride for paediatric and adult patients with cancer (1,17,75-77).

GRADE: Committee Consensus

23. LOCKING TECHNIQUE

23.1 Summary of Evidence

The same principles for the flushing technique apply to flushing with locking solutions. Refer to 19.1.

23.2 Practice Recommendation

CNSA recommends to consider to lock Peripheral Intravenous Cannulas in paediatric and adult patients with cancer by a slow and steady technique, for example less than 1 mL per second to limit the damage to the vein wall potentially caused by fast flow rates (47).

GRADE: Committee Consensus

24. LOCKING FREQUENCY

24.1 Summary of Evidence

Adult:

Current recommendations are to consider locking Peripheral Intravenous Cannulas not in use, once every 24 hours and should be removed as soon as it is no longer clinically required in consultation with the health care team (1).

Paediatric:

Current evidence indicates to lock PIVCs without continuous infusions once every 24 hours (105,106).

24.2 Practice Recommendation

CNSA recommends to lock Peripheral Intravenous Cannulas not in continuous use with 0.9% sodium chloride for paediatric and adult patients with cancer at least once per shift (8-12 hourly) to align with patency assessment and documentation of once per shift (1,31,78,79). Remove as soon as possible, as clinically indicated in collaboration with the health team (1).

GRADE: Committee Consensus

25. SYRINGE

25.1 Summary of Evidence

The pressure exerted by a 10ml syringe is less than a 5 mL or 2 mL syringe, so using a 10 mL syringe for the flushing or locking procedure will reduce the risk of damaging the internal wall of a vein (38,78).

A randomised control trial discussed that manufactured, prefilled flush solution syringes with “pressure limiting syringe technology” align with this principle as the 3 mL and 5mL syringes also have the barrel size of the 10 mL syringe (with a reduced volume) (78). Furthermore, this technology prevents the backflow of blood at the cannula tip caused by ‘bottoming out’ the syringe (emptying the syringe fully leading to blood reflux).

25.2 Practice Recommendation

CNSA recommends to use a 10ml syringe to flush and lock Peripheral Intravenous Cannulas in paediatric and adult patients with cancer (38,78).

GRADE: Committee Consensus

CNSA recommends to use syringes with pressure limiting technology to minimise the risk of blood reflux (78).

GRADE: Committee Consensus

FLUSHING and LOCKING REFERENCES

1. Gorski L, Hadaway L, Hagle ME, McGoldrick M, Orr M, Doellman D. Infusion therapy: standards of practice. J Infus Nurs. 2016;39(1S):S1-S159.

2. Tsao K, Fuller CL, Green HL, Jacquez RA, Jackson AA, Andrassy RJ, et al. Risk factors and treatment of port thrombosis in pediatric oncology patients. J Surg Res. 2010;158(2):367-8.

3. Stammers D, Connolly B, Brandao LR, Zupanec S, Gupta S. Evaluation of the need for chest X-rays in the management of asymptomatic, intraluminal vascular access device occlusion in childhood cancer. Pediatr Blood Cancer. 2017;64(7).

4. Mason TM, Ferrall SM, Boyington AR, Reich RR. Central Venous Access Devices: An Investigation of Oncology Nurses' Troubleshooting Techniques. Clin J Oncol Nurs. 2014;18(4):421-5.

5. MacLean J, MacDonald T, Digout C, Smith N, Rigby K, Kulkarni K. Need for tissue plasminogen activator for central venous catheter dysfunction is significantly associated with thrombosis in pediatric cancer patients. Pediatr Blood Cancer. 2018;65(6):1-.

6. Holt D, Lawrence S. The Influence of a Novel Needleless Valve on Central Venous Catheter Occlusions in Pediatric Patients. JAVA - Journal of the Association for Vascular Access. 2015;20(4):214-20.e2.

7. Borretta L, MacDonald T, Digout C, Smith N, Fernandez CV, Kulkarni K. Peripherally Inserted Central Catheters in Pediatric Oncology Patients: A 15-Year Population-based Review From Maritimes, Canada. J Pediatr Hematol Oncol. 2018;40(1):e55-e60.

8. Granic M, Zdravkovic D, Krstajic S, Kostic S, Simic A, Sarac M, et al. Totally implantable central venous catheters of the port-acath type: complications due to its use in the treatment of cancer patients. J. 2014;19(3):842-6.

9. Buchini S, Scarsini S, Montico M, Buzzetti R, Ronfani L, Decorti C. Management of central venous catheters in pediatric onco-hematology using 0.9% sodium chloride and positive-pressure-valve needleless connector. Eur J Oncol Nurs. 2014;18(4):393-6.

10. Cesaro S, Tridello G, Cavaliere M, Magagna L, Gavin P, Cusinato R, et al. Prospective, randomized trial of two different modalities of flushing central venous catheters in pediatric patients with cancer. J Clin Oncol. 2009;27(12):2059-65.

11. Hung CY, Chiu SY, Shum SK, Chan HY, Cheuk DKL, Chiang AKS, et al. Surveillance on central venous catheter complications in paediatric haematology-oncology unit. Pediatric Blood and Cancer. 2013;60(S3):184.

12. Chong LM, Chow YL, Kong SS, Ang E. Maintenance of patency of central venous access devices by registered nurses in an acute ambulatory setting: an evidence utilisation project. Int. 2013;11(1):20-5.

13. Giordano P, Saracco P, Grassi M, Luciani M, Banov L, Carraro F, et al. Recommendations for the use of long-term central venous catheter (CVC) in children with hemato-oncological disorders: management of CVC-related occlusion and CVC-related thrombosis. On behalf of the coagulation defects working group and the supportive therapy working group of the Italian Association of Pediatric Hematology and Oncology (AIEOP). Ann Hematol. 2015;94(11):1765-76.

14. Jain SA, Shukla SN, Talati SS, Parikh SK, Bhatt SJ, Maka V. A retrospective study of central venous catheters GCRI experience. Indian J Med Paediatr Oncol. 2013;34(4):238-41.

15. Kang J, Chen W, Sun W, Ge R, Li H, Ma E, et al. Peripherally inserted central catheter-related complications in cancer patients: a prospective study of over 50,000 catheter days. The Journal of Vascular Access. 2017;18(2):153-7.

16. Keogh S, Flynn J, Marsh N, Higgins N, Davies K, Rickard CM. Nursing and midwifery practice for maintenance of vascular access device patency. A cross-sectional survey. Int J Nurs Stud. 2015;52(11):1678-85.

17. Keogh S, Mathew S. Peripheral intravenous catheters: A review of guidelines and research. Sydney: Australian Commission on Safety and Quality in Health Care; 2019.

18. Rickard CM, Marsh N, Webster J, Runnegar N, Larsen E, McGrail MR, et al. Dressings and securements for the prevention of peripheral intravenous catheter failure in adults (SAVE): a pragmatic, randomised controlled, superiority trial. Lancet Infect Dis. 2018;392:419-30.

19. Australian Commission on Safety and Quality in Health Care. Consultation Draft Peripheral Venous Accerss Clincial Care Standard. Sydney: Australian Commission on Safety and Quality in Health Care; 2019.

20. Helm RE, Klausner JD, Klemperer JD, Flint LM, Huang E. Accepted but unacceptable: peripheral IV catheter failure. J Infus Nurs. 2015;38(3):189–203.

21. Marsh N, Webster J, Larson E, Cooke M, Mihala G, Rickard CM. Observational Study of Peripheral Intravenous Catheter Outcomes in Adult Hospitalized Patients: A Multivariable Analysis of Peripheral Intravenous Catheter Failure. J Hosp Med. 2018;13:83-9.

22. Wallis MC, McGrail M, Webster J, Marsh N, Gowardman J, Playford EG, et al. Risk Factors for Peripheral Intravenous Catheter Failure: A Multivariate Analysis of Data from a Randomized Controlled Trial. Infect Control Hosp Epidemiol. 2014;35(1):63-8.

23. Alexandrou E, Ray-Barruel G, Carr PJ, Frost SA, Inwood S, Higgins N, et al. Use of Short Peripheral Intravenous Catheters: Characteristics, Management, and Outcomes Worldwide. J Hosp Med. 2018;13(5).

24. Bradford NK, Edwards RM, Chan RJ. Heparin versus 0.9% sodium chloride intermittent flushing for the prevention of occlusion in long term central venous catheters in infants and children. Cochrane Database Syst Rev. 2015(11).

25. López‐Briz E, Ruiz Garcia V, Cabello JB, Bort‐Martí S, Carbonell Sanchis R, Burls A. Heparin versus 0.9% sodium chloride locking for prevention of occlusion in central venous catheters in adults. Cochrane Database Syst Rev. 2018(7).

26. Takashima M, Ray-Barruel G, Ullman A, Keogh S, Rickard CM. Randomized controlled trials in central vascular access devices: A scoping review. PLoS ONE. 2017;12(3):e0174164.

27. Goossens GA, Jerome M, Janssens C, Peetermans WE, Fieuws S, Moons P, et al. Comparing normal saline versus diluted heparin to lock non-valved totally implantable venous access devices in cancer patients: a randomised, non-inferiority, open trial. Ann Oncol. 2013;24(7):1892-9.

28. Solinas G, Platini F, Trivellato M, Rigo C, Alabiso O, Galetto AS. Port in oncology practice: 3-monthly locking with normal saline for catheter maintenance, a preliminary report. J. 2017;18(4):325-7.

29. Cesaro S, Cavaliere M, Pegoraro A, Gamba P, Zadra N, Tridello G. A comprehensive approach to the prevention of central venous catheter complications: results of 10-year prospective surveillance in pediatric hematology-oncology patients. Ann Hematol. 2016;95(5):817-25.

30. Gerceker GO, Sevgili SA, Yardimci F. Impact of flushing with aseptic non-touch technique using pre-filled flush or manually prepared syringes on central venous catheter occlusion and bloodstream infections in pediatric hemato-oncology patients: A randomized controlled study. Eur J Oncol Nurs. 2018;33:78-84.

31. Klein J, Jepsen A, Patterson A, Reich RR, Mason TM. Heparin Versus Normal Saline: Flushing Effectiveness in Managing Central Venous Catheters in Patients Undergoing Blood and Marrow Transplantation. Clin J Oncol Nurs. 2018;22(2):199-202.

32. Leung TK, Lee CM, Tai CJ, Liang YL, Lin CC. A retrospective study on the long-term placement of peripherally inserted central catheters and the importance of nursing care and education. Cancer Nursing. 2011;34(1):E25-30.

33. Lo Priore E, Fliedner M, Heverhagen JT, Novak U, Marschall J. The role of a surveillance programme for intro-ducing peripherally inserted central catheters: a 2-year observational study in an academic hospital. Swiss Med Wkly. 2017;147:w14441.

34. Milani A, Mazzocco K, Gandini S, Pravettoni G, Libutti L, Zencovich C, et al. Incidence and determinants of port occlusions in cancer outpatients. Cancer Nurs. 2017;40(2):102-7.

35. Petroulias PL. Use of Electronic Tablets for Patient Education on Flushing Peripherally Inserted Central Catheters. J Infus Nurs. 2017;40(5):298-304.

36. Voog E, Campion L, du Rusquec P, Bourgeois H, Domont J, Denis F, et al. Totally implantable venous access ports: a prospective long-term study of early and late complications in adult patients with cancer. Support Care Cancer. 2018;26(1):81-9.

37. Corley A, Ullman AJ, Mihala G, Ray-Barruel G, Alexandrou E, Rickard CM. Peripheral intravenous catheter dressing and securement practice is associated with site complications and suboptimal dressing integrity: A secondary analysis of 40,637 catheters. Int J Nurs Stud. 2019;100:103409.

38. Alexander M. Infusion nursing: an evidence-based approach. Third edition. ed. Corrigan A, Gorski L, Hankins J, Perucca R, editors. St. Louis, Missouri: Elsevier Health Sciences; 2011.

39. Bertoglio S, Faccini B, Lalli L, Cafiero F, Bruzzi P. Peripherally inserted central catheters (PICCs) in cancer patients under chemotherapy: A prospective study on the incidence of complications and overall failures. J Surg Oncol. 2016.

40. Bertoglio S, Solari N, Meszaros P, Vassallo F, Bonvento M, Pastorino S, et al. Efficacy of normal saline versus heparinized saline solution for locking catheters of totally implantable long-term central vascular access devices in adult cancer patients. Cancer Nurs. 2012;35(4):E35-42.

41. Gabriel J. Vascular device occlusion: causes, prevention and management. Nursing standard (Royal College of Nursing (Great Britain) : 1987). 2011;25(44):49-55.

42. Goossens GA, Stas M, Moons P. Management of functional complications of totally implantable venous access devices by an advanced practice nursing team: 5 years of clinical experience. Eur J Oncol Nurs. 2012;16(5):465-71.

43. Linnemann B. Management of complications related to central venous catheters in cancer patients: an update. Semin Thromb Hemost. 2014;40(3):382-94.

44. Dal Molin A, Clerico M, Baccini M, Guerretta L, Sartorello B, Rasero L. Normal saline versus heparin solution to lock totally implanted venous access devices: Results from a multicenter randomized trial. Eur J Oncol Nurs. 2015;19(6):638-43.

45. Lee AC, Ong ND. Can implanted venous access ports remain patent without maintenance flush-lock? Pediatr Blood Cancer. 2014;61(12):2326.

46. Rasero L, Golin L, Ditta S, Di Massimo DS, Dal Molin A, Piemonte G. Effects of prolonged flushing interval in totally implantable venous access devices (TIVADs). Br J Nurs. 2018;27(8):S4-s10.

47. Piper R, Carr PJ, Kelsey LJ, Bulmer AC, Keogh S, Doyle BJ. The mechanistic causes of peripheral intravenous catheter failure based on a parametric computational study. Scientific reports. 2018;8(1):1-12.

48. Institute for Healthcare Improvement. What is a bundle? 2011 [Available from: http://www.ihi.org/knowledge/Pages/ImprovementStories/WhatIsaBundle.aspx.

49. Kefeli U, Dane F, Yumuk PF, Karamanoglu A, Iyikesici S, Basaran G, et al. Prolonged interval in prophylactic heparin flushing for maintenance of subcutaneous implanted port care in patients with cancer. Eur J Cancer Care (Engl). 2009;18(2):191-4.

50. Milani A. The maintenance of totally implanted venous access devices: When the difference is made by the nursing practice: Correspondence about the paper "Normal saline versus heparin solution to lock totally implanted venous access devices: Results from a multicenter randomized trial" by Dal Molin et al. (EJON 19;2015:638-643). Eur J Oncol Nurs. 2016;21:272-3.

51. Bellesi S, Chiusolo P, De Pascale G, Pittiruti M, Scoppettuolo G, Metafuni E, et al. Peripherally inserted central catheters (PICCs) in the management of oncohematological patients submitted to autologous stem cell transplantation. Support Care Cancer. 2013;21(2):531-5.

52. Abate ME, Sanchez OE, Boschi R, Raspanti C, Loro L, Affinito D, et al. Analysis of risk factors for central venous catheter-related complications: a prospective observational study in pediatric patients with bone sarcomas. Cancer Nurs. 2014;37(4):292-8.

53. Bonciarelli G, Batacchi S, Biffi R, Buononato M, Damascelli B, Ghibaudo F, et al. GAVeCeLT consensus statement on the correct use of totally implantable venous access devices for diagnostic radiology procedures. J. 2011;12(4):292-305.

54. Fleury M, Guignard B, Fonzo-Christe C, Bonnabry P. Subcutaneously implanted port-chamber central venous catheters: Prevention and care of occlusion. European Journal of Hospital Pharmacy. 2014;21 (Supplement 1):A25.

55. Keeler M. Central line practice in Canadian blood and marrow transplant. Can Oncol Nurs J. 2014;24(2):67-77.

56. Lin S, Wen K, Liu C, Wei C. The Use of Peripherally Inserted Central Catheters in Cancer Patients. Journal of the Association for Vascular Access. 2010;15(1):16-9.

57. Matey L, Camp-Sorrell D. Venous Access Devices: Clinical Rounds. Asia-Pac. 2016;3(4):357-64.

58. Mathur G, Mott SL, Collins L, Schlueter AJ. Tissue plasminogen activator vs heparin for locking central venous catheters between apheresis procedures. J Clin Apher. 2019.

59. Sahin Balcik O, Akkaya C, Uz B, Aksoy C, Guvenc B, Dincer S. The efficacy and safety of hypertonic citrate as catheter-locking solution in hematopoietic stem cell transplant recipients. Turkiye Klinikleri Cardiovascular Sciences. 2011;23(1):48-53.

60. Schiffer CA, Mangu PB, Wade JC, Camp-Sorrell D, Cope DG, El-Rayes BF, et al. Central venous catheter care for the patient with cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2013;31(10):1357-70.

61. Wolf J, Connell TG, Allison KJ, Tang L, Richardson J, Branum K, et al. Treatment and secondary prophylaxis with ethanol lock therapy for central line-associated bloodstream infection in paediatric cancer: a randomised, double-blind, controlled trial. The Lancet Infectious diseases. 2018;18(8):854-63.

62. Zaghal A, Khalife M, Mukherji D, El Majzoub N, Shamseddine A, Hoballah J, et al. Update on totally implantable venous access devices. Surg Oncol. 2012;21(3):207-15.

63. Dal Molin A, Guerretta L, Mazzufero F, Rasero L. The management of totally implanted venous ports in the ambulatory oncologic patient. J. 2009;10(1):22-6.

64. Dal Molin A, Rasero L, Guerretta L, Perfetti E, Clerico M. The late complications of totally implantable central venous access ports: the results from an Italian multicenter prospective observation study. Eur J Oncol Nurs. 2011;15(5):377-81.

65. Canadian Vascular Access Association. Canadian Vascular Access and Infusion Therapy Guidelines. Pembroke, ON: Pappin Communications.; 2019.

66. Diaz JA, Rai SN, Wu X, Chao JH, Dias AL, Kloecker GH. Phase II Trial on Extending the Maintenance Flushing Interval of Implanted Ports. J Oncol Pract. 2017;13(1):e22-e8.

67. Brito ARO, Nishinari K, Saad PF, Saad KR, Pereira MAT, Emidio SCD, et al. Comparison between Saline Solution Containing Heparin versus Saline Solution in the Lock of Totally Implantable Catheters. Ann Vasc Surg. 2018;47:85-9.

68. Tabatabaie O, Kasumova GG, Eskander MF, Critchlow JF, Tawa NE, Tseng JF. Totally Implantable Venous Access Devices: A Review of Complications and Management Strategies. Am J Clin Oncol. 2017;40(1):94-105.

69. Dumichen MJ, Seeger K, Lode HN, Kuhl JS, Ebell W, Degenhardt P, et al. Randomized controlled trial of taurolidine citrate versus heparin as catheter lock solution in paediatric patients with haematological malignancies. J Hosp Infect. 2012;80(4):304-9.

70. Heibl C, Trommet V, Burgstaller S, Mayrbaeurl B, Baldinger C, Koplmuller R, et al. Complications associated with the use of Port-a-Caths in patients with malignant or haematological disease: a single-centre prospective analysis. Eur J Cancer Care (Engl). 2010;19(5):676-81.

71. Nam SH, Kim DY, Kim SC, Kim IK. Complications and risk factors of infection in pediatric hemato-oncology patients with totally implantable access ports (TIAPs). Pediatr Blood Cancer. 2010;54(4):546-51.

72. Hitchcock J. Preventing intraluminal occlusion in peripherally inserted central catheters. Br J Nurs. 2016;25(19):S12-S8.

73. Hill J, Broadhurst D, Miller K, Cook C, Dumanski J, Friesen N, et al. Occlusion Management Guideline for Central Venous Access Devices (CVADs). Vascular Access. 2013;7(supp 1).

74. Paquet F, Marchionni C. What Is Your KVO? Historical Perspectives, Review of Evidence, and a Survey About an Often Overlooked Nursing Practice. J Infus Nurs. 2016;39(1):32-7.

75. Loveday HP, Wilson JA, Pratt RJ, Golsorkhi M, Tingle A, Bak A, et al. epic3: National Evidence-Based Guidelines for Preventing Healthcare-Associated Infections in NHS Hospitals in England. J Hosp Infect. 2014;86:S1-S70.

76. Wang R, Zhang M-G, Luo O, He L, Li J-X, Tang Y-J, et al. Heparin Saline Versus Normal Saline for Flushing and Locking Peripheral Venous Catheters in Decompensated Liver Cirrhosis Patients: A Randomized Controlled Trial. Medicine (Baltimore). 2015;94(31):e1292-e.

77. Xu L, Hu Y, Huang X, Fu J, Zhang J. Heparinized saline versus normal saline for maintaining peripheral venous catheter patency in China: An open-label, randomized controlled study. Journal of International Medical Research. 2017;45(2):471-80.

78. Keogh S, Flynn J, Marsh N, Mihala G, Davies K, Rickard C. Varied flushing frequency and volume to prevent peripheral intravenous catheter failure: a pilot, factorial randomised controlled trial in adult medical-surgical hospital patients. Trials. 2016;17(1):348.

79. Cope DG, Elledge CM, Thompson Mackey H, Moran AB, Rogers MA, Schulmeister L, et al. Access Device Standards of Practice for Oncology Nursing. Society ON, editor. Pittsburgh, Pennsylvania: Oncology Nurses Society.; 2017.

80. Kim HJ, Yun J, Kim HJ, Kim KH, Kim SH, Lee SC, et al. Safety and effectiveness of central venous catheterization in patients with cancer: prospective observational study. J Korean Med Sci. 2010;25(12):1748-53.

81. Boersma RS, Schouten HC. Clinical practices concerning central venous catheters in haematological patients. Eur J Oncol Nurs. 2010;14(3):200-4.

82. Revel-Vilk S, Yacobovich J, Tamary H, Goldstein G, Nemet S, Weintraub M, et al. Risk factors for central venous catheter thrombotic complications in children and adolescents with cancer. Cancer. 2010(Jun 8).

83. Malec LM, Cooper J, Rudolph J, Michaels MG, Ragni MV. Prophylactic rtPA in the Prevention of Line-associated Thrombosis and Infection in Short Bowel Syndrome. J Pediatr Gastroenterol Nutr. 2018;66(6):972-5.

84. Wolf J, Shenep JL, Clifford V, Curtis N, Flynn PM. Ethanol lock therapy in pediatric hematology and oncology. Pediatr Blood Cancer. 2013;60(1):18-25.

85. Rosenbluth G, Tsang L, Vittinghoff E, Wilson S, Wilson-Ganz J, Auerbach A. Impact of decreased heparin dose for flush-lock of implanted venous access ports in pediatric oncology patients. Pediatr Blood Cancer. 2014;61(5):855-8.

86. Jan HC, Chou SJ, Chen TH, Lee CI, Chen TK, Lou MA. Management and prevention of complications of subcutaneous intravenous infusion port. Surg Oncol. 2012;21(1):7-13.

87. Odabas H, Ozdemir NY, Ziraman I, Aksoy S, Abali H, Oksuzoglu B, et al. Effect of port-care frequency on venous port catheter-related complications in cancer patients. Int J Clin Oncol. 2014;19(4):761-6.

88. Wu CY, Hu HC, Ko PJ, Fu JY, Wu CF, Liu YH, et al. Risk factors and possible mechanisms of superior vena cava intravenous port malfunction. Ann Surg. 2012;255(5):971-5.

89. Onyeama SJN, Hanson SJ, Dasgupta M, Hoffmann RG, Faustino EVS. Factors associated with continuous low-dose heparin infusion for central venous catheter patency in critically ill children worldwide. Pediatr Crit Care Med. 2016;17(8):e352-e61.

90. Coady K, Ali M, Sidloff D, Kenningham RR, Ahmed S. A comparison of infections and complications in central venous catheters in adults with solid tumours. J. 2015;16(1):38-41.

91. Garajova I, Nepoti G, Paragona M, Brandi G, Biasco G. Port-a-Cath-related complications in 252 patients with solid tissue tumours and the first report of heparin-induced delayed hypersensitivity after Port-a-Cath heparinisation. Eur J Cancer Care (Engl). 2013;22(1):125-32.

92. Redkar R, Bangar A, Krishnan J, Raj V, Swathi C, Joshi S. Role of Chemoports in Children with Hematological/Solid Tumor Malignancies - Technical Implications and Complications: An Institutional Experience. J Indian Assoc Pediatr Surg. 2019;24(1):27-30.

93. Homo RFB, Lima AFC. Direct cost of maintenance of totally implanted central venous catheter patency. Rev Lat Am Enfermagem. 2018;26:e3004.

94. Szeinbach SL, Pauline J, Villa KF, Commerford SR, Collins A, Seoane-Vazquez E. Evaluating catheter complications and outcomes in patients receiving home parenteral nutrition. J Eval Clin Pract. 2015;21(1):153-9.

95. Chopra V, Flanders SA, Saint S, Woller SC, O'Grady NP, Safdar N, et al. The Michigan Appropriateness Guide for Intravenous Catheters (MAGIC): Results From a Multispecialty Panel Using the RAND/UCLA Appropriateness Method. Ann Intern Med. 2015;163(6 Suppl):S1-40.

96. Wells J, Sharif B, Najran P, Hughes A, Hawkins J, Bromley P, et al. How effective are urokinase and lineograms in the management of hickman line occlusions? Pediatric Blood and Cancer. 2011;57 (5):752.

97. Ociepa T, Maloney E, Urasinski T, Sawicki M. Thrombotic complications of tunneled central lines in children with malignancy. J Pediatr Hematol Oncol. 2010;32(2):88-92.

98. Abu-El-Haija M, Schultz J, Rahhal RM. Effects of 70% ethanol locks on rates of central line infection, thrombosis, breakage, and replacement in pediatric intestinal failure. Journal of Pediatric Gastroenterology and Nutrition. 2014;58(6):703-8.

99. Athale UH, Siciliano S, Cheng J, Thabane L, Chan AK. Central venous line dysfunction is an independent predictor of poor survival in children with cancer. J Pediatr Hematol Oncol. 2012;34(3):188-93.

100. KoKo A. How does heparin compare with normal saline for locking central venous catheters? Cochrane Clinical Answers. 2018.

101. Palese A, Baldassar D, Rupil A, Bonanni G, Capellari Maria T, Contessi D, et al. Maintaining patency in totally implantable venous access devices (TIVAD): a time-to-event analysis of different lock irrigation intervals. Eur J Oncol Nurs. 2014;18(1):66-71.

102. Hill J, Broadhurst D, Miller K, Cook C, Dumanski J, Friesen N, et al. Occlusion Management Guideline for Central Venous Access Devices (CVADs). Vascular Access. 2013;7(1):1-35.

103. Alliance for Vascular Access Teaching and Research. What rate is best to 'keep vein open'? 2020 [Available from: https://www.avatargroup.org.au/faq---pivc-patency.html.

104. Goossens GA. Flushing and Locking of Venous Catheters: Available Evidence and Evidence Deficit. Nursing research and practice. 2015;2015:985686-.

105. Kleidon TM, Keogh S, Flynn J, Schults J, Mihala G, Rickard CM. Flushing of peripheral intravenous catheters: A pilot, factorial, randomised controlled trial of high versus low frequency and volume in paediatrics. J Paediatr Child Health. 2020;56(1):22-9.

106. Schreiber S, Zanchi C, ., Ronfani L, Delise A, Corbelli A, Bortoluzzi R, et al. Normal saline flushes performed once daily maintain peripheral intravenous catheter patency: a randomised controlled trial. Arch Dis Child. 2015;100(7):700.