Pediatric Ethanol Lock Therapy Study.

Central venous catheters (CVCs) are crucial for patients who require long term vascular
access due to a variety of underlying diseases. Children with intestinal insufficiency and
other diseases require vascular access to receive total parenteral nutrition, chemotherapy,
fluid support and for the convenience of avoiding peripheral sticks when multiple blood
draws are required. While these catheters have many benefits, they are also associated with
complications such as catheter-related bloodstream infections (CRBSI). These infections can
be a major cause of morbidity, mortality, and increased health care costs.
Coagulase-negative staphylococci, Staphylococcus aureus, aerobic gram-negative bacilli, and
Candida species (especially albicans) are the most common organisms responsible for these
infections. These infections are traditionally treated with systemic antimicrobial therapy.
There are times when the catheter must be removed to adequately treat the infection,
however, indications for catheter removal in children are controversial. For some children
with a history of multiple line infections, there are limited sites available to place new
vascular access when the CVC needs to be replaced. Reducing the number of infections in this
group of children is highly desirable. The goal of this study is to improve patient outcomes
by reducing the risk of infection, thereby decreasing waitlist morbidity and mortality and
improving post transplant care.

Lock therapy is the procedure of allowing medications to dwell in the line for extended
periods of time without interruption. Many different agents such as ethanol, vancomycin and
gentamicin have been used successfully as a means to salvage a CVC that has become infected.
There is limited information regarding the use of lock therapy to prevent CRBSI in patients
with CVCs. However, in patients with a history of multiple CRBSI, who have a critical need
to maintain vascular access, lock therapy with a solution of 25% ethanol has been suggested
to prevent future CRBSI. There is sufficient data to suggest that this combination is likely
to be effective, is unlikely to lead to the development of multidrug resistant organisms and
is well tolerated. Our hypothesis is that the use of ethanol as a lock therapy can reduce
the number of CRBSI in both pre and post transplant patients with intestinal insufficiency.

Specific Aim: To compare the number of CRBSI in patients who receive ethanol lock therapy
with the number of infections while on placebo lock therapy with heparin. This will be
accomplished by conducting a prospective cross-over, double blind, placebo controlled study
in children who have intestinal insufficiency and a history of multiple CRBSIs. Each child
will receive 3 months of study lock therapy (25% ethanol) and 3 months of placebo lock
therapy (heparin). The investigators, the patient and their family will be blinded to the
treatment. The primary outcome measure will be the number of CRBSIs. Patients will also be
observed for possible side effects from the therapy, and the need for line removal. This
pilot study should provide preliminary data and information regarding the feasibility for a
larger, multi-center study of ethanol lock therapy for the prevention of CRBSI.

Inclusion criteria:

- patients with central venous access and a history of three or more CRBSI in the prior
6 months

- age greater than 6 months

- anticipation for the need for continued central venous access over the next 7 months

- availability to come for a monthly study visit

- anticipation that the patient will receive medical care at Children's Hospital of
Pittsburgh for the majority of the CRBSI which occur during the next 7 months and the
ability to lock the central venous catheter for a minimum of 4 hours per day

Exclusion criteria:

- age less than 6 months and greater than or equal to 21 years

- known immunodeficiency (with the exception of immunosuppression in a patient after
organ transplantation)

- known allergy or intolerance to ethanol or heparin lock therapy