A triple-blinded, multi-center, cluster-randomized, crossover trial of central venous access device locking with 4% tetrasodium EDTA in the adult critical care population

This thesis investigated the rationale, feasibility, and efficacy of utilizing a 4% tetrasodium ethylenediaminetetraacetic acid (t-EDTA) locking fluid to prevent infective and thrombotic complications associated with central venous access device (CVAD) use in adult critical care patients.

To evaluate the rationale behind use of locking fluid interventions in the context of this patient population, I conducted a systematic review to appraise the quality of available evidence from previously-conducted locking fluid trials. Findings from this review suggest only one fluid type investigated over the last 15 years (citrate 46.7%) shows any evidence of reducing rates of CVAD complications. There is no evidence to support infection, thrombosis, and occlusion prevention with utilization of saline, citrate 4%, and heparin currently incorporated into the standard of care. 

The second investigation included completion of a one-month observational study to assess feasibility of a formal assessment of t-EDTA efficacy. Results showed a single CVAD lumen to be locked for up to one-third of its lifespan, establishing adequate timeline for the mechanism of action of the t-EDTA intervention to be effective. 

Evidence from the first two studies cumulated in the planning and execution of a triple-blinded, multi-center, cluster-randomized, crossover trial in adult critical care units at six Canadian hospitals. T-EDTA was trialed against a control condition comprising of saline and citrate 4% locking fluids. The trial enrolled over 1400 participants, and revealed 33% lower incidence rate of clinically important complications in participants randomized to the t-EDTA group (RR 0.67, 95% CI 0.48-0.93). Our study is the first and only of this magnitude to investigate t-EDTA locking overall, in addition to being one of the largest locking fluid trials ever performed in the adult ICU population. Study results provide evidence for the incorporation of t-EDTA locking fluid into standard ICU practice.