Elsevier

The Lancet

Volume 397, Issue 10283, 17–23 April 2021, Pages 1447-1458
The Lancet

Articles
Effect of infusion set replacement intervals on catheter-related bloodstream infections (RSVP): a randomised, controlled, equivalence (central venous access device)–non-inferiority (peripheral arterial catheter) trial

https://doi.org/10.1016/S0140-6736(21)00351-2Get rights and content

Summary

Background

The optimal duration of infusion set use to prevent life-threatening catheter-related bloodstream infection (CRBSI) is unclear. We aimed to compare the effectiveness and costs of 7-day (intervention) versus 4-day (control) infusion set replacement to prevent CRBSI in patients with central venous access devices (tunnelled cuffed, non-tunnelled, peripherally inserted, and totally implanted) and peripheral arterial catheters.

Methods

We did a randomised, controlled, assessor-masked trial at ten Australian hospitals. Our hypothesis was CRBSI equivalence for central venous access devices and non-inferiority for peripheral arterial catheters (both 2% margin). Adults and children with expected greater than 24 h central venous access device–peripheral arterial catheter use were randomly assigned (1:1; stratified by hospital, catheter type, and intensive care unit or ward) by a centralised, web-based service (concealed before allocation) to infusion set replacement every 7 days, or 4 days. This included crystalloids, non-lipid parenteral nutrition, and medication infusions. Patients and clinicians were not masked, but the primary outcome (CRBSI) was adjudicated by masked infectious diseases physicians. The analysis was modified intention to treat (mITT). This study is registered with the Australian New Zealand Clinical Trials Registry ACTRN12610000505000 and is complete.

Findings

Between May 30, 2011, and Dec, 9, 2016, from 6007 patients assessed, we assigned 2944 patients to 7-day (n=1463) or 4-day (n=1481) infusion set replacement, with 2941 in the mITT analysis. For central venous access devices, 20 (1·78%) of 1124 patients (7-day group) and 16 (1·46%) of 1097 patients (4-day group) had CRBSI (absolute risk difference [ARD] 0·32%, 95% CI −0·73 to 1·37). For peripheral arterial catheters, one (0·28%) of 357 patients in the 7-day group and none of 363 patients in the 4-day group had CRBSI (ARD 0·28%, −0·27% to 0·83%). There were no treatment-related adverse events.

Interpretation

Infusion set use can be safely extended to 7 days with resultant cost and workload reductions.

Funding

Australian National Health and Medical Research Council.

Introduction

Many patient groups and therapies require a central venous access device or peripheral arterial catheter. These invasive devices can cause substantial patient harm from catheter-related bloodstream infection (CRBSI), requiring additional associated hospital days and costs.1, 2, 3 CRBSIs account for around 70% of all health-care associated bloodstream infections4 and are the most costly health-care associated infection, with an attributable cost of US$45 814 per case.3

Numerous CRBSI prevention guidelines exist, but the most effective known strategies are applied at the time of insertion.5, 6, 7 Conversely, the subsequent catheter dwell represents the majority of time at risk, but has less supporting evidence for infection prevention.5 One post-insertion intervention is the routine replacement of infusion sets. This requires the disconnection, discard, and replacement of all infusates, medications, tubing, and component parts at recurring intervals during catheter dwell.8 This strategy assumes that although infusion sets might become contaminated during use, CRBSI can be avoided by intermittent replacement with new, sterile sets. The procedure was instigated after endemic outbreaks in the USA half a century ago, amidst which the Centers for Disease Control (CDC) recommended 24 hourly infusion set replacement.9 Most contemporary guidelines recommend infusion set replacement every 4 days4, 5 with the CDC recommending replacement “no more frequently than 96 hours, but at least every 7 days”.6

Because infusion set replacement requires one or more skilled nurses and substantial amounts of disposable sterile equipment as well as pharmaceutical resources, the procedure affects workloads and costs. The optimal infusion set replacement frequency has not been established in randomised, controlled trials. Infusion sets might actually become contaminated during the handling required for the procedure, consistent with the source of most CRBSIs being direct contamination from health workers' hands.6 A 2013 Cochrane review identified no superior time interval for infusion set replacement, low to medium quality evidence, and only two small randomised, controlled trials investigating set use for longer than 4 days.8 We tested the efficacy and effect on costs of extending intervals for replacement of infusion sets from 4 to 7 days. Our aim was to provide high quality evidence to inform clinical practice guidelines that maintain patient safety and use resources wisely.

Research in context

Evidence before this study

We searched MEDLINE, CINAHL, Embase, Cochrane Central Register of Controlled Trials, and international clinical trials registries for randomised, controlled trials comparing durations of infusion set use. Search terms included “Catheterisation”, “Catheters, indwelling”, “Parenteral Nutrition”, “Infusions, intravenous”, “Line change”, “Administration/infusion set”, “Transducer”, “Tubing”, “Replacement”, “Timing”, and “Time-frame”. The search was not restricted by language or date. We also searched reference lists of articles identified by this strategy. We published a systematic review in 2013 with the last search being June, 2012; a repeat of this search in March, 2020, identified no additional trials.

Our review summarised 16 trials with a total of 5001 participants. The trials compared various timeframes of infusion set replacement, from 1 to 7 days. Many studies were of low to medium quality. No evidence was found for differences in catheter-related bloodstream infection (CRBSI) with more frequent infusion set replacement (risk ratio (RR) 1·06, 95% CI 0·67–1·69) although less frequent infusion set replacement reduced all-cause bloodstream infection (RR 0·72, 0·54–0·98). One study suggested that less frequent infusion set replacement increased mortality within the neonatal population (RR 1·84, 1·00–3·36). No evidence revealed interactions between the effects of frequency of set replacement and subgroups of infusion (parenteral nutrition or fat emulsions), participant (adults, children, or neonates), or catheter (arterial or venous) type.

Previous studies did not provide a conclusive answer as to the optimal timing for infusion set replacement. Only two small studies tested use beyond 4 days. Some studies were limited to particular groups of patients, and costs were not considered. We concluded that a large trial was needed.

Added value of this study

In this large, randomised, controlled, pragmatic trial in ten hospitals, adult and paediatric patients with central venous access devices or peripheral arterial catheters were randomised to infusion set replacement every 7 days, or 4 days (controls). The study showed that 7-day compared with 4-day infusion set replacement for the prevention of CRBSI was equivalent for central venous access devices and non-inferior for peripheral arterial catheters. Costs were lower in the 7-day infusion set replacement group.

Implications of all the available evidence

Our trial indicates that 7-day compared with 4-day replacement of infusion sets is safe. Our results confirm the findings of previous, smaller trials in patients in intensive care and in patients with cancer. Extension of use to 7 days can substantially reduce workload and health-care costs.

Section snippets

Study design and participants

We did a randomised, controlled, equivalence, assessor-masked trial at nine government-run and one private (eight adult and two paediatric), teaching hospitals in Australia. The trial was designed to separately test an equivalence hypothesis for central venous access devices and a non-inferiority hypothesis for peripheral arterial catheters (owing to low baseline CRBSI); otherwise the protocol was identical for both devices. Initially, the trial was designed to test the central venous access

Results

Between May 30, 2011, and Dec 9, 2016, we screened 6007 patients and enrolled 2944 (figure 1). We randomly assigned 1484 participants (1127 central venous access device; 357 peripheral arterial catheter) to 7-day infusion set replacements and 1460 (1097 central venous access device; 363 peripheral arterial catheter) to 4-day infusion set replacements. Patient accrual ended when the planned sample size was reached, with slight over recruitment owing to concurrent multi-site recruitment. Of 2944

Discussion

Vascular catheters are the source of one-third of health-care associated bloodstream infections20 and routine infusion set replacement has been an infection prevention strategy for half a century, despite scarce evidence. In our large, pragmatic, randomised, controlled trial of 7-day use versus 4-day use, the equivalence hypothesis for CRBSI was accepted for central venous access devices, as was the non-inferiority hypothesis for peripheral arterial catheters. These findings were consistent as

Data sharing

Data sharing procedures will be described once all publications have been completed.

Declaration of interests

CMR's employer has received on her behalf from manufacturers of vascular access products: investigator-initiated research grants and unrestricted educational grants from BD-Bard and Cardinal Health; and consultancy payments for educational lectures and expert advice from 3M, and BD-Bard. NMM's employer has received on her behalf from manufacturers of vascular access products investigator-initiated research grants and unrestricted educational grants from BD-Bard and Cardinal Health; and

References (31)

  • E Zimlichman et al.

    Health care-associated infections: a meta-analysis of costs and financial impact on the US health care system

    JAMA Intern Med

    (2013)
  • L Gorski et al.

    Infusion therapy standards of practice

    J Infus Nurs

    (2021)
  • NP O'Grady et al.

    Guidelines for the prevention of intravascular catheter-related infections

    Clin Infect Dis

    (2011)
  • AJ Ullman et al.

    Optimal timing for intravascular administration set replacement (review)

    Cochrane Database Syst Rev

    (2013)
  • Nosocomial bacteremia associated with intravenous fluid therapy

    MMWR Morb Mortal Wkly Rep

    (1971)
  • Cited by (0)

    View full text