In-line Filtration to Reduce Systemic Inflammatory Response Syndrome in Babies Born Very prEtErm
Condition: Babies Born Very Preterm
MeSH terms: Premature Birth; Systemic Inflammatory Response Syndrome
Study type: Interventional

Summary: 
      While venous access is an essential part of caring for the preterm neonate potential severe
      adverse events, including contamination of fluids with bacteria, endotoxins and particulates
      could occur (Bethune 2001).

      Infusion therapy carries a risk for catheter-associated septicaemia (Geiss 1992) originated
      from the catheter tubing, the ports, at the cannula site or from contaminated infusion fluid.
      While not all infections lead to septicaemia, immuno-compromised patients such as neonates
      are at greater risk, and infection becomes a major problem (Ng 1989) and a major risk factor
      for neurodevelopmental disabilities (Volpe 2008). Indeed, it has been postulated that
      endotoxins may be involved in the pathogenesis of a proportion of cases of periventricular
      leukomalacia, the most frequent brain damage associated with neurocognitive handicaps in the
      human neonate (Volpe 2001).

      The presence of calcium in parenteral nutrition mixture leads to precipitation due to its
      incompatibility with the other components of the admixtures and leads to high concentration
      of particles (Athanasiou 2014). Adverse systemic effects of particulate matter including
      phlebitis, granulomata formation in the lung (Marshall 1987) and ischaemic necrosis, are a
      common finding in necrotizing enterocolitis another serious complication flowing preterm
      birth (Ballance 1990). Particle contamination of infusion solutions exists despite a
      stringent infusion regiment. The number and composition of particles depends on the
      complexity of the applied admixtures (Jack 2010).

      Particulate contamination is due to drug incompatibility reactions or their incomplete
      reconstitution during the preparation process (Schroder 1994). Various studies have
      demonstrated the contamination of infusion solutions with glass particles from opening glass
      ampoules, particles from rubber stoppers or conglomerates of the parenteral nutrition
      components (Ball 2003). Particles have also been shown to be inherent to generic drug
      formulation (Oie 2005). In an intensive care setting the particle burden may rise up to one
      million infused particles per day, increasing with the complexity and quantity of the
      administered infusions (Walpot 1989).

      There are two main IV filter pore sizes; the 0.2 micron filter is used for aqueous solutions,
      and the 1.2 micron filter is recommended for larger molecule solutions such as lipids. The
      0.2 micron filter has also been reported to remove air, microorganisms and particulate
      matter. In addition, endotoxin retention is reportedly achieved by using a positively charged
      filter membrane; toxic macro-molecules are released by gram-negative bacteria and are claimed
      to be effective for up to ninety six hours (Bethune 2001).

      In-line IV filters are currently claimed to be an effective strategy for the removal of
      bacteria, endotoxins and particulates associated with intravenous therapy in adults (Ball
      2003) and particularly effective in the removal of particles caused from drug precipitate
      such as antibiotics (Chee 2002; Ball 2003).

      However, evidence of the beneficial effect of in-line IV filters in children and neonates is
      much weaker, despite some positive studies (Jack 2012; Boehne 2013; Sasse 2015). In the
      population of preterm infants, no study is currently available while particulate
      contamination due to infusion therapy carries a higher health risk in this subpopulation.

      The benefits of using IV in-line filters in critically-ill preterm neonates remains to be
      demonstrated. This intervention in adults has also been challenged by several authors
      (Pearson 1996; Newell 1998). Friedland reported that certain drugs such as antibiotics may be
      retained in the filters causing a reduction in potency (Friedland 1985). On the other hand,
      there are no known adverse effects from the use of IV in-line filters.
    

Detailed description: 
      While venous access is an essential part of caring for the preterm neonate potential severe
      adverse events, including contamination of fluids with bacteria, endotoxins and particulates
      could occur (Bethune 2001).

      Infusion therapy carries a risk for catheter-associated septicaemia (Geiss 1992) originated
      from the catheter tubing, the ports, at the cannula site or from contaminated infusion fluid.
      While not all infections lead to septicaemia, immuno-compromised patients such as neonates
      are at greater risk, and infection becomes a major problem (Ng 1989) and a major risk factor
      for neurodevelopmental disabilities (Volpe 2008). Indeed, it has been postulated that
      endotoxins may be involved in the pathogenesis of a proportion of cases of periventricular
      leukomalacia, the most frequent brain damage associated with neurocognitive handicaps in the
      human neonate (Volpe 2001).

      The presence of calcium in parenteral nutrition mixture leads to precipitation due to its
      incompatibility with the other components of the admixtures and leads to high concentration
      of particles (Athanasiou 2014). Adverse systemic effects of particulate matter including
      phlebitis, granulomata formation in the lung (Marshall 1987) and ischaemic necrosis, are a
      common finding in necrotizing enterocolitis another serious complication flowing preterm
      birth (Ballance 1990). Particle contamination of infusion solutions exists despite a
      stringent infusion regiment. The number and composition of particles depends on the
      complexity of the applied admixtures (Jack 2010).

      Particulate contamination is due to drug incompatibility reactions or their incomplete
      reconstitution during the preparation process (Schroder 1994). Various studies have
      demonstrated the contamination of infusion solutions with glass particles from opening glass
      ampoules, particles from rubber stoppers or conglomerates of the parenteral nutrition
      components (Ball 2003). Particles have also been shown to be inherent to generic drug
      formulation (Oie 2005). In an intensive care setting the particle burden may rise up to one
      million infused particles per day, increasing with the complexity and quantity of the
      administered infusions (Walpot 1989).

      There are two main IV filter pore sizes; the 0.2 micron filter is used for aqueous solutions,
      and the 1.2 micron filter is recommended for larger molecule solutions such as lipids. The
      0.2 micron filter has also been reported to remove air, microorganisms and particulate
      matter. In addition, endotoxin retention is reportedly achieved by using a positively charged
      filter membrane; toxic macro-molecules are released by gram-negative bacteria and are claimed
      to be effective for up to ninety six hours (Bethune 2001).

      In-line IV filters are currently claimed to be an effective strategy for the removal of
      bacteria, endotoxins and particulates associated with intravenous therapy in adults (Ball
      2003) and particularly effective in the removal of particles caused from drug precipitate
      such as antibiotics (Chee 2002; Ball 2003).

      However, evidence of the beneficial effect of in-line IV filters in children and neonates is
      much weaker, despite some positive studies (Jack 2012; Boehne 2013; Sasse 2015). In the
      population of preterm infants, no study is currently available while particulate
      contamination due to infusion therapy carries a higher health risk in this subpopulation.

      The benefits of using IV in-line filters in critically-ill preterm neonates remains to be
      demonstrated. This intervention in adults has also been challenged by several authors
      (Pearson 1996; Newell 1998). Friedland reported that certain drugs such as antibiotics may be
      retained in the filters causing a reduction in potency (Friedland 1985). On the other hand,
      there are no known adverse effects from the use of IV in-line filters.
    

Intervention name(s): 0.2 micron positively charged PALL Corporation filters and 1.2 micro IV in-line filters used for lipid administration
Intervention type(s): Device
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention