Comparative Effect of Multi-Dose Contrast Median on Contrast-Enhanced Computed Tomography Workflow of Nurses and Hospital Efficiency: A Multi-CenterReal-World Prospective Observational Study in China

Objective This study aims to evaluate and compare computed tomography (CT)-contrast operational workflow and hospital imaging efficiency when using a multi-dose bulk IV contrast delivery system and when using a single-dose packaging contrast. Materials and Methods A multi-center prospective observational study was conducted in six regions in China. The operating time and workflow of radiology nursing staff were evaluated and observed using an investigational tool and recorded by the investigators using a stopwatch. Nursing staff's knowledge and the imaging capabilities of hospitals were collected using a questionnaire. Rate, t-test, χ2 test, and partial correlation analysis were used to describe the knowledge of nursing staff. The operation time and frequency of the two contrast agent packages were further compared using the Stata 15.0 software. Results A total of 42 radiology nurses and 1,167 CT contrast-operating procedures in six provinces in China were evaluated. The total operating times for the 100 ml contrast agent versus the 200 ml contrast agent were 80.67 s and 63.81 s, respectively (P < 0.01). According to the average annual hospital CT scans (49,807 scans) and the power injector (PI) market share, approximately 233 h yearly could be saved in a hospital. Regarding CT contrast knowledge, approximately 57.14% nurses expressed their willingness to use multi-dose packaging contrast agents. Conclusion Through difference and correlation analysis on real-world data, this study suggests that, considering safety, the use of a multi-dose bulk IV contrast agent is more time-saving and efficient for Chinese nurses and medical institutions compared with that of a single-dose package.


Introduction
Several health technologies including computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography and CT (PET/CT), and PET/MRI can be used for medical diagnostic imaging. Among these technologies, CTplays an essential role in diagnostic imaging, especially in the assessment of bones and calcifcations [1]. Despite the increasing rate of CT supply in China, there are still huge gaps between the number of CT and MRI scanners per million population in China compared with the Organisation for Economic Cooperation and Development (OECD) countries [2]. Meanwhile, the demand for CT diagnosis is high. Moreover, the number of annual CT examinations has increased gradually and yearly over the last decades [3]. Unlike unenhanced CT, intravenous (IV) contrast-enhanced CT (CECT) features a contrast agent, a pharmaceutical agent that can improve diagnostic image quality, consequently increasing accuracy for disease diagnosis.
Nurses in Chinese hospitals constantly work in a highintensity work environment, typically with long working hours weekly during both day and night shifts [4]. Highintensity workloads and burnout afect nurses on a daily basis, jeopardizing their job performance, sleep quality, and-indirectly-patient safety [5,6]. Nursing in the radiology department is particularly complex and stressful: radiology nursing duties often include mandatory overtime, which are attributable to the cumbersome operations involved in handling contrast agents [7]. Generally, contrast agents are diverse in contrast dose standards and packages. Currently, single-dose packaging of the 50 and 100 ml vials makes up the majority of contrasts used in IV contrastenhanced CT in China, while multi-dose IV contrast media (in 200 and 500 ml bulk packages) remain more seldomly used. Multi-dose packaging contrast, however, has many known benefts. It not only simplifes the operations process for the nursing staf but also reduces the medical cost for patients through medical reimbursement and improves the CT scanning efciency in hospitals. Previous studies on IV contrast-enhanced computed tomography (CECT) mainly examine three relevant topics: (1) the microbiologic contamination and time efciency of using diferent power injectors (PIs) [8][9][10][11]; (2) contrast cost savings and waste evaluation using a multi-dose bulk IV contrast system [12,13]; and (3) cost savings of using multi-dose packaging contrast media together with reimbursement units for patients undergoing IV contrast-enhanced CT [14].
Tis study aims to evaluate CT-contrast operational workfow and hospital imaging efciency when using a multi-dose bulk IV contrast delivery system (under two types of PIs) compared with a single-dose packaging contrast. Specifcally, this analysis is aimed at evaluating the nursing staf's knowledge, operating time saved, and scanning efciency improvements resulting from the replacement of 100 ml single-use IV contrast vials (350 mg/ml iodine concentration) with a multi-dose bulk IV contrast delivery system (350 mg/ml iodine concentration). Tis study was conducted from the Chinese nurses' and medical institutions' perspectives, accordingly providing evidence, countermeasures, and references for decision making in hospitals in China.  ), and Northwest China (Shaanxi Province). One tertiary hospital was selected per province, and a total of eight tertiary hospitals were surveyed for real-world data collection. Nurses were assigned to diferent CT scanner rooms in each observation and followed up for one to three days (mostly from 7:30 AM to 7:30 PM). Te investigators further recorded the operating time and workfow of the nurses. Te investigators also collected information on the nurses' basic characteristics as well as their understanding, attitude, willingness to use, and knowledge about the multi-dose packaging contrast.

. Materials and Methods
In the study, nursing staf used either 100 ml single-use IV contrast vials (350 mg/ml iodine concentration) or a multi-dose bulk IV contrast delivery system (350 mg/ml iodine concentration, 200 ml). Two PIs, i.e., syringeless and dual-syringe PIs, were considered in this study. Accordingly, four strategies were generated: (1) 100 ml and syringeless PI, (2) 100 ml and dual-syringe PI, (3) 200 ml and syringeless PI, and (4) 200 ml and dual-syringe PI. Moreover, based on the analysis of the 200 ml sample, this study simulated the scenario of using a 500 ml product contrast agent.

Evaluation of Nursing Staf's Knowledge. A 5-point
Likert scale was used to evaluate the nursing staf's degree of understanding, attitude, and intention of use toward the multi-dose packaging contrast (i.e., 1 for "very poorly understood/unsupportive/unwilling," 3 for "general/unknown," and 5 for "strongly understood/supportive/ willing"). We further collected data on the nursing staf's knowledge of the advantages and disadvantages of the multidose packaging contrast compared with those of the singledose packaging contrast.

Evaluation of Operating Time, Number of Operating
Times, and Hospital Imaging Capabilities. Te operating time and amount of time needed to change the contrast bottle were mainly recorded using a stopwatch. Evaluations were conducted across six steps of the operating procedure: (1) changing injectors (when using dual-syringe PIs), (2) changing catheters, (3) changing the bottle of normal saline, (4) changing the bottle of contrast, (5) exhausting the air out of the bottle and the catheter, and (6) connecting a catheter to the indwelling needle of the patient. To ensure accurate recording, each time point was defned after the pilot survey, and the time period of each process was obtained by subtracting the previous time point from the next time point. Table 1 presents defnitions for each time point. Moreover, the evaluation of hospital imaging capabilities, such as counting the number of CTmachines and the annual number of CTs and enhanced scans, was conducted using a questionnaire.

Statistical Analysis.
Te sample size was calculated using the PASS software, with a power of 80%, signifcance of 0.05, and level of confdence of 95%. Real-world data, such as the catheter's operating time, were recorded and sorted by the investigators using Excel Spreadsheet 2018. Qualitative data (nursing staf's knowledge and attitude toward diferent contrast agent specifcation) were summarised with descriptive statistics using frequency and percentages; quantitative data (nursing staf workfow under diferent packages of contrast) were summarised using mean and standard deviation. Te statistical signifcance of any diference in the frequency distributions was tested using the two-samplettest and the χ 2 test. Correlation and partial correlation analyses were further performed to assess potential infuence of the nursing staf's operating time, knowledge, and attitude toward diferent dose-response contrast methods. A value of P < 0.05 was considered statistically signifcant. All data were analysed using Stata 15.0 software. Our study results show that contrast agent replacement procedures are less cumbersome with multi-dose packaging contrast compared with single-dose packaging contrast. When a single-dose packaging contrast was used with the dual-syringe PI, the nursing staf conducted 227 contrastagent bottle replacements in 7.0 days, with an average of 32.43 bottle replacements in a day and 41.97 ± 24.72 s per capita daily time. However, when multi-dose packaging contrast was used, the nursing staf conducted only 135 bottle replacement operations within 7.5 days, with an average of 18.00 bottle changes per day and 19.71 ± 14.79 s per capita daily time, which is signifcantly shorter than the replacement time reported for using a single-dose packaging contrast (t � 12.88, P < 0.001). Additionally, contrary to single-dose packaging contrast (which requires replacing a new agent bottle each time, i.e., frequency of change-� 1 time/person), the frequency of changing contrast agent was signifcantly reduced using multi-dose packaging contrast, i.e., 0.45 times/person (χ 2 � 183.44, P < 0.001) when delivered by dual-syringe PI and 0.30 times/person (χ 2 � 429.59, P < 0.001) when delivered by syringeless PI.
Similarly, overall operating times were more favorable with multi-dose packaging contrasts. When a single-dose packaging contrast was used with a dual-syringe PI, the nursing staf's average overall operating time was 84.64 ± 11.67 s; when the multi-dose packaging contrast was used with a dual-syringe PI, the nursing staf's average overall operating time was 68.47 ± 8.11 s, signifcantly shorter than the time required for a single-dose packaging contrast (t � 18.79, P < 0.01). Similar conclusions were made regarding contrast delivery using a syringeless PI. Te average operating time of the nurses when a single-dose packaging contrast was used with a syringeless PI was 64.81 ± 19.72 s; the average overall operating time of the nurses when a multi-dose packaging contrast was used together with a syringeless PI was 45.18 ± 0.06 s, signifcantly shorter than the time required for a single-dose packaging contrast (t � 8.90, P < 0.01) ( Table 2).
Given that diferent types of PI could infuence the overall operating time of nurses, the nurses' operating time for diferent packaging contrast agents was standardized according to the market ratio of diferent PIs. According to interviews with key informants, the market ratio of dualsyringe and syringeless power injectors was close to 4 : 1. Terefore, the operating time per capita was inferred to be 80.67 s with a single-dose packaging contrast (100 ml) and 63.81 s with a multi-dose packaging contrast (200 ml), indicating a diference of 16.86 s.
Additionally, based on the 200 ml product contrast agent scenario, our study simulates a 500 ml product contrast agent scenario. Given that the operating time saved was mainly from the replacement of the contrast agent bottle, compared with the 200 ml specifcation, the 500 ml contrast agent bottle was replaced once for every three patients, and the operating time was reduced to once per cycle. In other words, the decanting time of the 500 ml bottle was half of the time required for a 200 ml bottle. Terefore, the simulation results suggest that, when a multi-dose packaging contrast (500 ml) is used with a syringeless PI, the daily operating time per capita would be 43.83 s. When used with a dualsyringe PI, the daily per capita operating time would be 51.89 s. After standardizing to the market share of diferent PIs, the daily per capita operating time of the multi-dose packaging contrast (500 ml) would be 50.22 s (Table 3).

Efect of Diferent Packaging Contrast Agents on
Scanning Efciency. From the hospital's perspective, considering that the time saved by the nursing staf could be used to scan more patients, this study calculates the time saved by using contrast agents of diferent specifcations and the average total scanning time of patients. Te daily per capita operating times of the patients using the 200 and 500 ml specifcations were 63.81 s and 50.22 s, respectively, and the time savings were 16.86 s and 30.45 s, respectively. Scanning efciency was also assessed based on the average total scanning time of patients and the annual number of enhanced scans in the hospital. When the annual number of enhanced scans in the hospital was 49,807 (the mean value of this study), the annual increase in enhanced scanning with 200 and 500 ml contrast agents was 2,143 and 4,010 cases, respectively. Daily scans further increased by 7 and 13, respectively (Table 4).

Partial Correlation Analysis of Nursing Staf Operating Time and Related Factors.
To further explore the infuence of contrast agent specifcation, the type of PIs, and the daily scanning times on the replacement and overall operating time of contrast agents, this study performs partial correlation analysis under the premise of controlling all other   Table 3. Partial correlation analysis shows that after controlling the type of PI and the number of daily scans, the contrast agent specifcation (0 � 100 ml, 1 � 200 ml) and the replacement time of the contrast agent were signifcantly correlated. In other words, the larger the contrast agent specifcation, the shorter the corresponding replacement time (Table 5).

Knowledge, Attitude, Willingness to Use, and Experience of
Nurses. Among the 42 nurses enrolled, a higher proportion (83.33%) of the nursing staf thought that they were very or quite familiar with the multi-dose packaging contrast, 59.53% supported the use of the multi-dose packaging contrast, 57.14% expressed willingness to use the multi-dose packaging contrast to carry out relevant work, and 11.9% expressed strong willingness to use the multi-dose packaging contrast.
Te nursing staf's knowledge of the advantages and disadvantages of the multi-dose packaging contrast compared with that of those of the single-dose packaging contrast was also examined. Among the 29 nurses (69.05%) who responded about the comparative advantage of the multi-dose packaging contrast, the frst three answers were "saves operating time" (n � 9, 31.03%), "reduces operating times" (n � 9, 31.03%), and "allows more convenient operations" (n � 6, 20.69%). Among the 28 nurses (66.67%) who responded about the relevant disadvantages, the top two answers were "inconvenient for patients to prescribe drugs and charge fees" (n � 5, 17.86%) and "if the contrast agent is contaminated, many patients will be afected" (n � 3, 10.71%).

Discussion
Medical diagnostic imaging, especially enhanced CT scanning, is an important health technology for disease diagnosis. Many physicians and patients prefer enhanced CT scanning to better detect diseases and improve imaging quality, resulting in the extensive use of contrast agents. Over the last few decades, IV CECT has only been available in single-dose packages. When using single-dose packages, nursing staf are required to conduct an entire operating process which includes changing the contrast agent bottle for each enhanced CT scan. Not only were the workfow and workload of the nursing staf complicated and heavy but also hospital efciency was often afected, resulting in long waiting times for enhanced CT scanning. Tis is the frst study to evaluate the efect of diferent contrast agent specifcations on the nursing staf's workfow, operating time, knowledge, and hospital efciency based on the different types of PIs and therefore can serve as a reference for clinical and hospital-based decisions.
We divided the contrast agent injection workfow of the nursing staf into six main steps: changing injectors, changing catheters, changing the bottle of normal saline, changing the bottle of contrast, exhausting the air out of the bottle and catheter, and connecting the catheter to the indwelling needle on patients. According to the quantitative results, the number of contrast bottle changes and the time consumed can be reduced, and the steps for injecting the contrast agent can be simplifed. Assuming that nursing staf adopt the multi-dose packaging contrast and the work pace remains unchanged, hospital income may increase, thereby improving the nursing staf's performance evaluation index  Tis study demonstrates that a 200 or 500 ml contrast agent could reduce CT wait times and overall hospital workfow burden. Typically, registering for a CT examination on the same day is usually impossible owing to the large number of outpatients and inpatients undergoing enhanced scanning; in fact, patients must book an appointment one to two days in advance or even earlier. Following the use of a multi-dose packaging contrast agent, however, the nursing staf's operating time can be reduced, thereby reducing the total time for enhanced scanning. On the one hand, the CT wait times for patients can be reduced. On the other hand, hospitals can use the time saved to perform enhanced CT scans on more patients, thereby improving hospital workfow under the same work intensity and further increasing hospital economic benefts.
Te type of PI could also afect the nursing staf's operating time. Unlike the dual-syringe PI, the syringeless PI can automatically extract the contrast agent from the bottle without manual suction [11,15], thereby signifcantly reducing the operating time with a 200 ml contrast agent. However, considering the high cost of syringeless PIs, this study only suggests popularizing the multi-dose packaging contrast and the syringeless PI in appropriate medical institutions, namely, hospitals with more rather than fewer outpatients.
Responses from the nursing staf at the eight tertiary hospitals analysed in this study showed that more than half of the nursing staf exhibit positive sentiments toward the degree of understanding, attitude, and intention of use for multi-dose packaging contrasts. Te correlation analysis results showed a signifcant correlation between degree of understanding, attitude tendency, and intention of use, further confrming the consistency of the nursing staf's positive sentiment toward multi-dose packaging contrasts. Regarding understanding the advantages and disadvantages of the multi-dose packaging contrast (compared with the single-dose packaging contrast), 19 of the 28 respondents mentioned the word "waste," with part of the answer being based on the "one person one bottle case," i.e., using one bottle of the multi-dose packaging contrast for only one patient results in wastage. Although 83.33% of the nursing staf had knowledge of the contrast agent according to the self-rating scale, the realistic clinical setting may be diferent.
By popularizing the use of multi-dose packaging contrasts, we can help reduce gaps in the nursing staf's knowledge and relatively improve their attitude and acceptance degree.
However, this study has some limitations. First, currently, formal standardized operating procedures on contrast agents do not exist, resulting in diferent sequences of operating steps for nursing staf. Although evaluating operating procedures became more difcult, we divided the entire operating process into specifc steps and timed each step. Second, compared with the scanning volume of the 100 ml contrast agent specifcation using a syringeless PI, the scanning volume of the 200 ml contrast agent was 80 patients. Accordingly, the sample size of 100 ml contrast agent specifcation scans may need further research to verify the results of this study. Lastly, considering the relatively small total sample size (i.e., only eight sampled hospitals), the extrapolation of this study may have certain limitations; if the study results are to be extrapolated, there may be a need to evaluate a larger sample in future research.

Conclusion
Trough diference and correlation analysis on real-world data, this study suggests that, considering safety, the use of a multi-dose bulk IV contrast agent is more time-saving and efcient for Chinese nurses and medical institutions compared with that of a single-dose package. Tese results may provide important references for clinical and hospital-based decisions involving contrast media utilization in China.

Data Availability
Te data used to support the fndings of this study are available from the corresponding author upon request.

Conflicts of Interest
Te authors declare that they have no conficts of interest.