Safety and Efficacy Study of Ethanol Locking to Prevent Central Line Infection in Premature Neonates

• Incidence of PICC-related sepsis in infants with ethanol-treated vs. Placebo treated lines [ Time Frame: Study Day #28 or sooner if PICC is discontinued before day #28 ] [ Designated as safety issue: No ]
  Primary endpoint of the study is to compare the incidence of PICC-related sepsis in infants with ethanol treated vs. Placebo treated lines by study day 28. PICC-related sepsis is defined by any 2 clinical signs or symptoms plus one positive peripheral blood culture for a recognized pathogen in this population other than coagulase-negative staphylococcus, or 2 positive peripheral blood cultures for coagulase-negative staphylococcus within 48 hours.
  
  

• Evaluation of PICC colonization following ethanol locking [ Time Frame: Duration of PICC use, average of 3 weeks ] [ Designated as safety issue: No ]
  PICC colonization is reflected by growth of >15 CFU from a 5-cm segement of the PICC tip by semiquantitative (roll-plate) culture, or growoth of >100 CFU by quantitative (sonication) broth culture in an otherwise asymptomatic patient.
  
  
• Whether the primary and secondary endpoints differ by birthweight strata [ Time Frame: Duration of PICC use, average of 3 weeks ] [ Designated as safety issue: No ]
  Birthweight stratification will use a 3-tiered subset (<1000g, 1000-1250g, and >1250g) consistent with existing neonatal literature.
  
  
• To determine whether ethanol lock treatment impacts incidence of clinical evaluations for suspected sepsis [ Time Frame: Duration of PICC use, average of 3 weeks ] [ Designated as safety issue: No ]
  Other evaluations for suspected sepsis are those not defined by the primary endpoint but meeting criteria for infection of some other sterile body fluid (urine or CSF).
  
  
• To determine whether antibiotic use for any indication (including non-bacteremia) alters the incidence of PICC-related infection or colonization as defined in the primary and secondary endpoints [ Time Frame: Duration of PICC use, average of 3 weeks ] [ Designated as safety issue: No ]
  See above
  
  
• Determine side effects of ethanol locking in premature babies [ Time Frame: Duration of PICC use, average of 3 weeks ] [ Designated as safety issue: Yes ]
  To determine the side effects of flushing ethanol locks into premature infants following lock therapy, if any
  
  
• To determine effect of ethanol locking on neonatal PICC lines [ Time Frame: Duration of PICC use, average of 3 weeks ] [ Designated as safety issue: Yes ]
  To determine how ethanol locking affects central line function and integrity in vivo, if at all.
  
  

PICC infection is of particular concern in the NICU because of the need for long term intravenous access in many very-low and the majority of extremely-low birthweight infants, the very populations at highest risk for infection in the first place. Central lines are a mainstay of treatment in these babies because of the need for extended parenteral nutrition, which itself has been associated with blood stream infection, not to mention the increased use of anti-infectives, added hospitalization costs, longer length of stay, and negative impact upon nutrition delivery when infectious complications occur.

Existing infection control practices differ by unit and region, and include hand washing, sterile precautions at insertion and dressing changes, elimination of mandatory scheduled dressing changes, minimizing port access to the extent permitted by clinical care, prophylactic antibiotics, and closed medication systems. Success is variable: there is no standard highly effective, safe approach to infection control, and central line infection remains a leading cause of morbidity and mortality in the NICU.

A standard practice to maintain central line patency when it is not in use is to lock it with a syringe containing a heparinized solution. Locks containing antibiotics have been used to prevent infection of central lines and to treat already-infected lines, but this approach confers risk of development of organisms resistant to treatment. External chlorhexidine-impregnated dressings have been used but can harm premature skin and do not achieve sterilization of the lumen or hub, where most infections originate.

Medical grade ethyl alcohol (ethanol) is a widely used compound with uses as a disinfectant, preservative, antidote to ingested ethylene glycol (anti-freeze), and anti-microbial. The FDA lists no specific approval or indication though it's use is widely recognized. Multiple studies have been conducted in sheep, children and adults, using 0.5-2 mL 70% ethanol locks to successfully prevent and/or treat catheter related infection without development of resistant organisms, adverse side effects to patients, or disruptions in catheter integrity. Though the ethanol lock approach has not yet been applied to premature neonates, safe and successful precedent in humans as young as 3 months is established; ours is the first trial of ethanol locking in a NICU setting.