In-line filtration in very preterm neonates: a randomized controlled trial

Abstract

In-line filtration is increasingly used in critically-ill infants but its benefits, by preventing micro-particle infusion in very preterm neonates, remain to be demonstrated. We conducted a randomized controlled trial among very preterm infants allocated to receive either in-line filtration of all the intra-venous lines or standard care without filters. The primary outcome was differences greater than 20% in the median changes in pro-inflammatory cytokine serum concentrations measured at day 3 and day 8 (+/−1) using a Luminex multianalytic profiling technique. Major neonatal complications were analyzed as secondary predefined outcomes. We randomized 146 infants, assigned to filter (n = 73) or control (n = 73) group. Difference over 20% in pro-inflammatory cytokine concentration between day 3 and day 8 was not found statistically different between the two groups, both in intent-to-treat (with imputation) and per protocol (without imputation) analyses. The incidences of most of neonatal complications were found to be similar. Hence, this trial did not evidence a beneficial effect of in-line filtration in very preterm infants on the inflammatory response syndrome and neonatal morbidities. These data should be interpreted according to local standards in infusion preparation and central line management.Despite improvements in perinatal care during the past three decades, prematurity is still associated with substantial mortality and morbidities for which inflammation plays a causal role 1,2 , including brain damage 3-6 , bronchopulmonary dysplasia (BPD) 7-9 and retinopathy of prematurity (ROP) 10-14 . Perinatal inflammation is not only a major risk factor for prematurity but also the best predictor of poor neurological outcome, leading to permanent sequelae in 9 million infants every year 2,4,15-17 . Therefore, reducing factors involved in systemic inflammation appears to be a relevant strategy to improve outcomes of infants delivered very preterm.Intra-venous (IV) drugs and parenteral nutrition infusion through central lines are among the most essential interventions in preterm neonates but they are associated with potential risks including bloodstream infections, thrombi and infusion of macro/micro particulates 18 . Particles in the infusion, containing metals, drug crystals 19 , glass fragments or cotton fibres 20 , can be generated by drug preparation process from packaging, incomplete reconstitution and chemical incompatibilities 21 . Parenteral infusion of micro-macro particles was reported to be associated with an increased risk of microvessels obstruction and inflammation, as reported in the lung and increased circulating cytokines release by the endothelium 22 . In-line filtration has therefore been proposed to limit the load of particles infused through central lines 23,24 , and to prevent bacterial and endotoxin infusion 25 . In-line filtration was found associated with a reduction of systemic inflammation and severe complications in critically-ill pediatric patients 26 . In neonates, a significant decrease...

Management of Y-Site Incompatibility of Intravenous Medication: A Systematic Review

“…Of those should be applied as a complimentary with the above main approaches were as follows: 1) standardisation of the concentration (Nemec, 2008), 2) optimisation of administration schedule (Maison et al, 2019) and 3) accurate pharmacist intervention. The standardisation of concentrations ensuring the preparation and administration of intravenous admixture was compatible (8). However, this finding should be further explored to confirm the compatibility of various combinations.…”

“…Some studies showed a benefit, and others could not prove the significance of filter use. Two systematic reviews, one observational study, and one clinical trial have failed to prove the effectiveness of filters significantly in reducing complications, and also doubt the value of the filter (Foster et al, 2015;Niël-Weise et al, 2010;Tanaka et al, 2016;Virlouvet et al, 2020). However, some studies have been performed under ideal conditions, considered well-controlled and compliant to protocols so the incompatibilities were not identified.…”

Effect of in-line filtration in newborns. Study protocol of the Intravenous Neonatal Central Access Safety (INCAS) randomized controlled trial.

“…Two German studies examined the use of lters in patients admitted to a pediatric intensive care unit (PICU), demonstrating the association between in-line ltration and a reduction in the incidence of SIRS (systemic in ammatory response syndrome) and serious complications (5,18). These results thought were not con rmed by a recent French study (19): they compared the pro le of pro-in ammatory cytokine levels when using lters or not in 146 very preterm infants and didn't found any signi cant change. The authors conclude that, despite this negative result, several bene ts provided by lters should be considered.…”

WoCoVA consensus on the clinical use of in-line filtration during intravenous infusions: Current evidence and recommendations for future research

“…A French study addressing the blood concentration of cytokine in preterm infants with or without filter is currently in progress. 54…”