Title
Subcutaneous and Intravenous Tissue Levels of Cefazolin During Abdominoplasty:        
A Pilot Study

Investigator
Barry N. Silberg, MD, F.A.C.S. Principal Investigator

Purpose
The purpose of this study is collection and analysis of tissue levels of cefazolin in a cohort of patients undergoing an abdominoplasty as a preliminary to a clinical trial.

Project Objectives
The objective of this proposal is to assess tissue levels of cefazolin following traditional intravenous administration with subcutaneous administration using a tissue dispersion technique in a small sample of patients undergoing elective abdominoplasty.

Specific Aims
Using a sample of adults undergoing elective abdominoplasty the study aim is to:

• Compare the dispersion of cefazolin using two different methods of administration

Hypothesis

• Tissue cefazolin concentrations are higher when cefazolin is administered subcutaneously using ultrasonic fluid dispersion directly into the surgical site compared to traditional intravenous administration.
  

Background and Significance
Nearly 30 million patients in the United States undergo surgical procedures annually ¹. Site infection following surgery negatively impacts patients, providers, and the health care system. Postoperative infections contribute to increased hospital stays, delay patients’ return to previous level of physical ability, cause increased pain, and increase the risk of death as a result of sepsis and multi-system organ failure ^1-3. It is estimated that over 600,000 surgical site infections (SSIs) occur annually ¹, with a health care cost of over one billion dollars ⁴. Open abdominal surgery has one of the highest rates of SSI. Recently, Kabon, et al ⁵ reported a prevalence of 9% to 27% incidence of SSI in colon surgery, and Sorenson et al ⁶, reported a rate of 6% to 16% in gastrointestinal surgery. The National Nosocomial Infection Surveillance System (NNIS) reported the incidence of infection for certain abdominal surgeries as between 1.7% and 11.6%¹⁴.

Subcutaneous delivery of antibiotics followed by external ultrasonic dispersion has been adapted from plastic surgery procedures used during liposuction and body contouring and is proposed as a new approach to an old problem. The antibiotic of interest is cefazolin (Ancef, Kefzol) mixed in a specific volume of saline which is introduced into the surgical area just prior to the incision being made, and after the patient has been anesthetized. The fluid is dispersed deeply into the subcutaneous tissue layer by application of external ultrasound for three minutes. The operation then proceeds in the usual fashion. Theoretical constructs underpinning the intervention are delivery of antibiotics directly to the wound site at the time of greatest need and prevention of tissue dehydration during exposure to air to decrease potential tissue necrosis. Dispersing the antibiotic directly into the tissue just prior to incision ensures high local tissue levels at the time when antibiotic protection is most needed.

Tissue and serum analysis compares the cefazolin levels between intravenous and subcutaneous administration. Prophylactic antibiotics are given ideally within 30 minutes of incision to ensure local tissue penetration and protection against infection from common skin bacteria (Fry, 2006). Assuring adequate tissue levels have been problematic, however, as tissue penetration is dependent upon the patient’s perfusion status, vascular state, timing of administration and appropriate dose.

Simultaneous serum and deep subcutaneous tissue samples collected at the completion of the incision and at one hour will yield levels of Cefazolin to compare between intervention and control groups. In general, plasma is spun off from serum and frozen at -40⁰ C until analyzed. Tissue samples are also frozen until analyzed. A buffer is added to weighed, minced samples, which are then centrifuged and decanted for assay ⁷.

Methods

A.	Design: A cross-sectional descriptive design with repeated measures.
B.	Sample Participants will be recruited from adults > 21 years scheduled for elective abdominoplasty procedures at Santa Rosa Memorial Hospital.
C.	Instruments The Silberg Tissue Preparation System TM Model ME 800 (9801427) (Mettler Surgical, Anaheim, CA) will be used for subcutaneous saline infusion and application of external ultrasound. The system consists of a 1 Mhz ultrasonic generator device, a 10 cm2 ultrasonic applicator, a peristaltic pump irrigation unit, a foot switch, a size 3 French hollow stainless steel cannula, an IV pole, irrigation tubing and a system cart.
D.	Procedure After approval by the Santa Rosa Memorial Hospital Institutional Review Board a convenience sample of patients scheduled for elective abdominoplasty will be screened in the usual manner to determine eligibility for the procedure. The investigator, at the initial consultation, will approach potential subjects preoperatively. Informed written consent will be obtained. Subjects in group A  will receive the following intervention: Participants will receive intravenous antibiotic (cefazolin) prophylaxis as ordered by the surgeon in accordance with hospital protocol. Fatty tissue samples will be obtained from fascial level of the wound at the time of incision and at 1 hour or prior to closing, whichever comes first. Simultaneous serum samples will be collected. Subjects in group B will receive the following intervention: Once in the operating suite, and under general anesthesia and sterile conditions, the operative area will be prepped in accordance with standard procedure. A small stab wound will be made with #15 scalpel blade at the end point of the intended incision. The irrigating cannula, previously connected to the peristaltic pump, will be introduced into the subcutaneous tissue through the stab wound. 250 mls of pre-warmed saline containing 1 gram of Cefazolin will be infused approximately 1 cm under the skin as the cannula is advanced along the intended path of the incision. Following infusion, ultrasound energy at 3 watts/cm2 will be continuously applied with the ultrasonic applicator for 3 minutes externally to disperse the saline into the surrounding tissue. Fatty tissue samples will be obtained from the level adjacent to deep fascia at the time of incision and at 1 hour or prior to closing, whichever comes first. Simultaneous serum samples will be collected.
E.	Protocols Tissue samples weighing approximately 15 grams each from all subjects will be obtained at the fascial level of the incision immediately after the incision is made and 1 hour later, or at closing, whichever occurs first. Blood samples of 10 mls each will be collected simultaneously. Samples will be frozen at -40o C and sent to David P. Nicolau, PharmD, FCCP, Center for Anti-Infective Research & Development, Hartford Hospital, Hartford, CT for analysis of antiobiotic levels. All data will be recorded on data specific collection sheets, filed in a locked cabinet kept in a locked room.  Data for all participants will be collected on gender, age, admission date, surgery date, discharge date, and readmission within 30 days. Data will include type and length of surgery, length, depth and placement of the incision, anesthetic class, hemoglobin, hematocrit, and antibiotic use beyond the expected prophylaxis.