Estimation of sample size
A software PASS 15.0 was used for estimating the sample size. We postulated Kappa coefficient between CR and US is about 0.843 with a standard deviation of 0.12. If class I error of the relevant parameters are set as 0.05 (α = 0.05) with an allowable error of 0.05 (δ = 0.05), the calculated sample size is 89 children. With the addition of 10% sample loss, at least 98 patients are required.
A consecutive series of 190 neonates who needed PICC in NICU of Children's Hospital of Chongqing Medical University were enrolled into the study. The period of recruitment was from April 2021 to August 2021. Inclusion criteria are newborns: (1) asking for PICC; (2) able to tolerate US and CR exams; (3) having the informed consent. Exclusion criteria are newborns: (1) with cardiovascular diseases; (2) with spinal deformity; (3) experiencing failed PICC attempts; (4) having contraindications of PICC including infection, skin allergy, skin injury and phlebitis, immune deficiency disease, abnormal bleeding and coagulation time and severe collapse of peripheral blood vessels, etc. The institutional review board has approved the study (Institutional Review Board of Children’s Hospital of Chongqing Medical University,Approval No., 2021-159; clinical trial registration No., ChiCTR2100045948).
Placement of PICC line
PICC placement was performed by two nurses with PICC operation qualification. Briefly, the child was placed in an incubator. Catheterization was performed with a puncturing kit containing 26 GA (1.9 F) single-lumen PICC catheter according to the neonatal PICC catheterization operation specifications8. After inserting the line, CR was taken to locate the catheter tip, then followed with US for relocating and guided adjustment.
According to the specifications, it should be avoided placing the catheter tip in the heart of neonates and infants9. The optimal tip position complied with the recommendation of the 2016 guidelines by the American Infusion Nurses Society (INS), i.e., the safest PICC tip be located within the lower third of SVC or just below the IVC-and-right-atrial junction10-12.
Locating catheter tips by CR
CR was conducted under a 0.7/1.3U163C-36 system (Shimadzu, Japan). An experienced radiologist and a PICC specialist nurse read the images together. According to the INS guidelines, a catheter tip at the level of 4th-6th thoracic vertebrae is regarded as the optimal placement for upper limb PICC and at the level of 8th-10th thoracic vertebrae for lower limb PICC13. Besides, our hospital also took the tracheal carina and the right cardiophrenic angle as the imaging marks of SVC-and-right-atrium junction and IVC-and-right-atrium junction, respectively.
Locating catheter tips by US
US is conducted under a LOGIQ e color Doppler ultrasonic diagnostic system (6S and 8C probes, GE company, USA) by two research members who have at least 3 years of experience in ultrasonic PICC positioning. The ultrasonic probe was set at the midline of the subxiphoid region or at the parasternal line of the right subclavicle region. A hyperechoic "equal sign" like or sandwich-like structure would be detected within the vena cava, which represents the inserted line. In detail, for clearly viewing the "equal sign" like echoes of the catheter tip in SVC, the probe was placed longitudinally at the 2nd-3rd intercostal spaces on the right of the sternum to delineate the long axis of aortic arch and the short axis of SVC, and then rotated clockwise for about 15° and tilted slightly to the right to show the long axis of SVC and the right atrial entrances of SVC and IVC (Fig. 1A)14. Under US guidance a small dose of 0.9% sodium chloride solution was injected into the catheter to confirm the position of the tip. Subsequently, distance between the tip and the right atrial inlet (thereafter referred to as "tip-to-atrium distance") was measured and improper tip position was US-guided readjusted. For clearly viewing the "equal sign" like echoes of the catheter tip in IVC, the probe should be placed longitudinally at the midsagittal position of the subxiphoid region and scan along the inferior rib to delineate the IVC and right atrial inlet (Fig. 1B). The tip-to-atrium distance was measured and improper tip position was readjusted.
Observation and analysis
Comparing US with CR in visualizing the key structures at PICC
Catheter tip, right-atrium inlets of SVC and IVC and tip-to-atrium distance that can be viewed on US and CR was recorded for each patient. US-visible right-atrium inlets of SUV or IVC is defined when it visually depicts the superior or inferior inlet of the right atrium. CR-visible right-atrium inlets of SUV or IVC is defined when it clearly images the tracheal carina or the right cardiophrenic angle. Measurement of tip-to-atrium distance is considered feasible when both of the tip and the right-atrium inlet are shown on a single image of US or CR.
Fluctuation of the measured data by US and CR
Tip-to-atrium distance of each patient was measured separately by US and CR. The quartile is calculated to represent fluctuation of the measured data; and fluctuation between the two data sets was compared. Narrower data fluctuation indicates the measurements made by the imaging tool more stable and reliable.
Consistency and correlation between US and CR
For further clarifying the validness of US, tip-to-atrium distances measured by US and CR were compared to investigate their consistency and correlation.
Comparison of operation time and babies’ body temperature drop between US and CR
Time period for each imaging checkup was recorded in minutes using a stopwatch. The time period recorded was defined as from the start of the imaging procedure to the time point the operators had confirmed the tip position. Data of the time periods were compared between US and CR. In addition, babies’ body temperature drop brought by US exam and CR exam was compared as well. For a bedside CR exam, babies must be taken out of incubators and sent to a dedicated room in NICU. The process may lead to babies’ body temperature drop.
Comparison of the direct expenses between US and CR
The direct cost of US and CR in locating the tips were recorded and compared.
A software SPSS 24.0 was used to statistically process the data. Data with normal distribution were expressed in mean ± standard deviation (x ± s); the count data were expressed in number of cases and percentage (%); and fluctuation of data was expressed in quartile. Intra-group correlation coefficient (ICC), Kappa coefficient analysis and Pearson correlation coefficient were used to investigate consistency and correlation between US and CR. Paired T-test was used to test the inter-group difference of operation time, body temperature change and direct cost. P < 0.05 means the difference is statistically significant.