Pharmacokinetics of Preoperative Vancomycin

Phase 4

Completed

Conditions: Vancomycin
Surgical Site Infection

Interventions: Drug: Administration of Vancomycin

Registration Number: NCT03453684

Lead Sponsor: University of Colorado, Denver

Brief Summary: A study of plasma and tissue vancomycin pharmacokinetics in pediatric surgical patients.

Detailed Description: Background: Vancomycin is used for antibiotic prophylaxis in pediatric surgical patients without a complete understanding of plasma and soft tissue pharmacokinetics. Guidelines recommend incision within 60 minutes after administration; however, tissue concentrations of vancomycin at that early time may not be therapeutic. The Investigators conducted a study of plasma and tissue concentrations in pediatric neurosurgical and orthopedic patients to characterize intraoperative vancomycin pharmacokinetics.

Patients, ages (0.1-18.8 years), undergoing posterior spinal fusion (n=30) or ventriculoperitoneal shunt placement (n=30), received intravenous vancomycin 15 mg/kg over one hour. Skin biopsies were taken at incision and skin closure. Blood samples were also collected at incision and closure; additional samples were drawn at 2- and 4-hours if patient was still in surgery. Population pharmacokinetic (PK) analysis was performed to characterize PK parameter estimates and to develop a model of intraoperative plasma and tissue vancomycin concentrations vs. time.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

Inclusion Criteria

Neurosurgery patients between the ages of 31 days up to 18 years
Receiving a single dose of vancomycin administered prior to surgery for cerebrospinal fluid (CSF) shunt placement or revision.
Orthopedic surgical patients between the ages of 31 days up to 18 years
Receiving a single dose of vancomycin administered prior to surgery for definitive spinal fusion.

Exclusion Criteria

Patients already receiving vancomycin for treatment of an active infection,
Patients who have a Creatinine ≥1.2,
Patients who's creatinine clearance less than 50,
Known chronic renal failure and are on dialysis,
Patients with a known allergy to vancomycin, not including Red Man Syndrome.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Administration of Vancomycin	Administration of Vancomycin	Administration of Vancomycin 15 mg/kg over 1 hour prior to surgical incision

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics Analysis: V˅c	1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed).	Volume of the central compartment. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.
Pharmacokinetics Analysis: V˅2	1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed).	Volume of the peripheral compartment Typical value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.
Pharmacokinetics Analysis: Q	1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed).	Intercompartmental clearance between central compartment (Vc) and peripheral compartment (V2) Typical Value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.
Pharmacokinetics Analysis: Cle	1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed).	Elimination clearance. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.
Pharmacokinetics Analysis: sf˅V2	1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed).	Scaling Factor for Body weight covariate for V2 (Volume of the peripheral compartment) Typical Value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.
Pharmacokinetics Analysis: sf˅Cle	1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed).	Scaling Factor for Body weight covariate for Cle (elimination clearance) Typical Value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.
Pharmacokinetics Analysis: K˅skin0	1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed)	Accounts for the equilibration rate between plasma and skin. Typical Value should be read as 3.6E-05. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.
Pharmacokinetics Analysis: PC	1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed)	Partition coefficient, models skin drug concentration between plasma and skin. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.
Pharmacokinetics Analysis: δ ˅R-plasma	1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed)	Proportional or relative intrasubject variability for plasma data Typical Value. There is no unit of measure for this measurement. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.
Pharmacokinetics Analysis: δ ˅A-skin	1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed)	Additive intrasubject variability for skin data Typical Value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.