Novel Central Line Locking Fluid Reduces Certain Complications in ICU

As the locking fluid for central venous access device (CVAD) ports in the ICU, an investigational 4% solution of tetrasodium EDTA reduced complications compared with a standard fluid, a randomized trial showed.

Combined risk of CVAD-associated bloodstream infection, catheter occlusion requiring thrombolysis, or catheter removal due to occlusion came out 32% lower with the EDTA locking fluid versus a control of saline or 4% citrate (13.1 vs 19.9 events per 1,000 catheter days, rate ratio 0.68, 95% CI 0.47-0.96, P=0.03).

Driving the advantage of EDTA was a relative 34% lower risk of CVAD occlusion requiring administration of alteplase (Activase) compared with controls (11.67 vs 17.73 per 1,000 catheter-days, RR 0.66, 95% CI 0.46-0.96), reported Steven Reynolds, MD, of the Royal Columbian Hospital in New Westminster, British Columbia, Canada, at the American Thoracic Society annual meeting in Orlando.

The findings were published simultaneously in JAMA, and Reynolds’ group called the reduction in alteplase administration “clinically meaningful, as it represents decreased interruptions to clinical care during which nurses spend additional time managing occluded central lines. This is particularly relevant given the current worldwide nursing shortage.”

And, the “outcome is biologically plausible owing to potent chelation ability of t-EDTA to reduce intraluminal accumulation of debris caused by early stages of biofilm and thrombus formation, preceding development of [central line-associated bloodstream infection] or symptomatic thrombus,” they stated.

However, while technically positive, the clot prevention benefit alone was “a fairly unimpressive result that is hidden by the use of a more impressive-sounding composite outcome,” commented Rory J. Spiegel, MD, of MedStar Washington Hospital Center in Washington.

Moreover, the cost of switching from cheap saline to EDTA “doesn’t seem like it would be viable,” he added. “The commercial product, KiteLock, adds roughly $100 per patient in locking fluid costs over a typical ICU stay, and the only real savings on the other side of the ledger are from avoided alteplase doses, which works out to about $10,500 across the entire 700-patient intervention cohort. That doesn’t come close to covering the about $73,000 in additional drug costs.” The 4% tetrasodium EDTA solution is approved by Canadian and European regulators but has not yet been reviewed by the FDA for approval.

The pragmatic trial involved three community hospitals and three academic centers in Canada that were cluster-randomized to the locking fluid used for patients older than age 18 in the ICU with a CVAD in place and at least one lumen not in use. For 3.5 months, the ICUs in these centers were randomized to triple-blind use of prefilled syringes containing 2.5 mL of t-EDTA (KiteLock 4%) or control locking fluid (saline, or 4% citrate for hemodialysis lines) for all trial participants. Then after a 1-month follow-up period, the ICUs crossed over to the other treatment group for another 3.5 months, again with 1-month follow-up. The protocol called for aspirating the indwelling locking fluid whenever possible prior to line re-access or routine lock exchange.

The researchers highlighted a subgroup analysis that pointed to heightened EDTA effect in high-risk patients, including those with peripherally inserted central catheters (double lumen RR 0.16, 95% CI 0.03-0.55, and triple lumen RR 0.24, 95% CI 0.03-1.20) and femoral insertion sites (RR 0.80, 95% CI 0.40-1.56).

While suggestive, Spiegel said a prospective study looking exclusively at those subgroups would be needed to test the hypothesis.

Two “unexpected findings” that require further adequately powered study, according to Reynolds and colleagues, were the lack of benefit of EDTA in patients on hemodialysis, although only about 10% of catheters, and numerically more colonization events compared with controls (11 vs five cases).