Study patients and inclusion criteria
We conducted a retrospective cohort study to investigate the incidence of CRBSI following CVC placement with or without ultrasound guidance. We observed 395 consecutive CVC insertions performed between April 2009 and January 2013 (3 years and 10 months). The study population included patients with hematological or immunological diseases who required CVC replacement for nutritional support and/or intravenous drug treatment.
The research period was divided into two terms based on substantial differences in the use of ultrasound-guided CVC insertion in the hematological oncology unit: before December 2011 (early term) and after January 2012 (late term). Between the early and the late terms, the insertion maneuvers changed from a blind approach to an ultrasound-guided approach after 2012.
The following devices were used in this study: SMAC Plus MicroNeedle (15G, 13 cm or 12G, 20 cm; Covidien Tokyo Inc., Tokyo, Japan), Argyle peripherally inserted central catheter (PICC) kit (4.5Fr, 60 cm; Covidien Tokyo, Japan), Arrow triple lumen (7Fr; Arrow, Tokyo, Japan), and Blood Access UK catheter kit, double (11Fr; UNITIKA, Tokyo, Japan).
All of the practitioners involved in this study had attended a hospital training program providing information on the standard insertion technique. The need for a CVC was determined by each practitioner; the practitioners also determined the preferred CVC device and the insertion site for each patient. Maximal sterile barrier precautions were routinely adopted. A 10% tincture of povidone iodine was used for skin preparation, and Tegaderm Transparent Film Dressing (3 M Japan, Tokyo, Japan) was used as the routine catheter site dressing unless otherwise specified. Study competency in CVC insertion was guaranteed by the training of the CVC providers. Our institute demands institutional certification to perform CVC/PICC insertion, which is only granted after the regulated orientation and training program and three instances of practical performance under a qualified instructor. All the CVC/PICC providers, who were a combination of staff and residents, were certified according to Kagawa University Hospital institutional regulation. The staff practitioners (N = 24) all had > 4 years of experience (median 5, range 4–15 years) in CVC/PICC intervention performance. The residents (N = 32) had < 4 years of experience (median 2, range 1–3 years). We used 10% povidone iodine solution for skin decontamination for the preparation of CVC/PICC insertion. Chlorhexidine gluconate dressing (CHGD) was applied as a form of infection prevention for stem cell transplantation. Levofloxacin and azoles were used as prophylactic antimicrobials during chemotherapy. Other interventions were not applied.
A bloodstream infection (BSI)  was defined by the first set of positive blood cultures in a series . To distinguish between a true BSI and contamination, more than two investigators critically analyzed the blood culture results. In addition, a CRBSI [5, 7] was defined as a positive culture result from at least one peripheral blood sample, a catheter tip culture positive for the same microorganism as the peripheral blood sample, and clinical signs of bacteremia. The concomitance of any other source of bacteremia was clinically assessed. The diagnosis of catheter-related infection was made in accordance with the HICPAC guidelines definition . Mechanical complications included arterial puncture, hematoma, and pneumothorax. The grading scales used in assessing complications were from the Common Terminology Criteria for Adverse Events Version 4.0 https://ctep.cancer.gov/protocolDevelopment/electronic_applications/CTC.htm. The grade 1 to 4 pneumothoraxes are asymptomatic, symptomatic, sclerosis and/or operative intervention indicated, and life-threatening, respectively. The grade 1 hematoma has mild symptoms, grade 2 has minimally invasive evacuation or aspiration indication, grade 3 has transfusion or radiologic, endoscopic, or elective operative intervention indicated, and grade 4 has life-threatening consequences. The grade 1 bleeding has mild symptoms, grade 2 has medical intervention indicated, grade 3 has transfusion or radiologic, endoscopic, or operative intervention indicated, and grade 4 has life-threatening respiratory or hemodynamic compromise. We evaluated comorbidities using the Charlson comorbidity index, which is a common and useful tool for evaluating general complications, and organ dysfunction . The primary endpoint of the study was to determine the effect of ultrasound guidance in CVC insertion on the incidence of CRBSI.
We used basic statistics and described representative values for the patients’ backgrounds. To compare values between the two groups, a two-tailed paired Student’s t-test was used for the parametric analyzes, and the Wilcoxon signed-rank test was used for the non-parametric analyzes. The contributing risk factors for catheter-related infection were analyzed using the multivariate analysis method. For the multivariate analysis, we evaluated patient background (age, sex, and clinical characteristics) and catheter conditions (insertion site, catheter indwelling duration, catheter insertion situation, and catheter device) as independent variables, and the onset of CRBSI as a dependent variable using the regression model. All potential confounders were included as independent variables. A stepwise selection procedure was used to build the multivariable logistic regression model using the above background risk variables. The entry criterion was set at P < 0.15. Statistical significance was defined as P < 0.05. An interrupted time-series analysis (TSA) was performed to analyze the trends and test the significance over the study period . The t-test or Chi-squared test was used to compare values between the two groups. For the comparison tests, P-values < 0.05 were considered significant. Statistical analyzes were performed using SPSS version 19.0 J software (SPSS Japan, Tokyo, Japan).
This study was conducted in accordance with the ethical standards of the responsible committee on human experimentation (Kagawa University Hospital Institutional Review Board, IRB) and with the Declaration of Helsinki (1964, amended most recently in 2008) of the World Medical Association.