Study design and population
This study was a prospective stratified permuted block randomized controlled trial that compared the great saphenous vein's puncture effect using the ultrasound-assisted technique with the traditional anatomic landmark approach in the exclusive group of children with congenital heart defects. Eligible participants undergoing cardiac surgery in our hospital were recruited from June 2020 to September 2020. Ethics approval for the study was obtained by the Institutional Review Board of Shanghai Children's Medical Center (approval number: SCMCIRB-K2020049-1). The whole trial protocol was performed in accordance with the Declaration of Helsinki. Also, the study protocol was registered at http://www.chictr.org.cn (number: ChiCTR2000033368; principal investigator: Yue Huang; date of registration: May 29, 2020). The ultrasound equipment used in the study was licensed for clinical application.
We included participants from a convenience sample of all eligible children requiring congenital cardiac surgery. Infants and toddlers aged 0 ~ 3 years, with ASA scores ofⅠ-Ⅲand congenital heart disease, were all enrolled. Exclusion criteria included infection or hemangioma at or near the puncture site within one month previously, recent great saphenous venous puncture history, ASA score > Ⅲ, or an emergency surgery needed. The medical history was collected, including age, sex, height, weight, previous history of difficult access, comorbidity, and types of cardiac anomalies. Informed consent was obtained from parents or guardians of all children after the anaesthesiologists in the study explained the study protocol. Children were assessed for inclusion and were randomly assigned to the routine anatomic landmark group or the ultrasound-assisted group at the level of types of a pre-existing cardiac anomaly, including cyanotic or acyanotic congenital heart disease. Cyanotic congenital heart disease was defined as the presence of SpO2 < 85% at rest or after crying without oxygen supplement and coexisting mixing intracardiac pathology (e.g., right-to-left shunts at the atrial or ventricular level). Acyanotic congenital heart disease was defined as intracardiac pathology (e.g., left-to-right shunt at the atrial and ventricular levels) with SpO2 ≥ 85% in both static and crying conditions. The random numbers were automatically generated through the Excel operating program. A balanced Stratified block randomization assignment was adopted to ensure the equal size of comparison groups throughout the study. We used fixed block sizes of four with an overall block of 18 and an allocation ratio of 1:1 separately. The corresponding random Numbers were kept in sealed, opaque envelopes, which were employed in sequence according to the order of patient presentation. Children with cyanosis have the features of cardiovascular instability and poor peripheral circulation caused by long-term hypoxia. So this study was expected to find differences in the success rate of puncture between the subgroups. To reduce the influence of operators' confounding factors on the outcome judgment, the procedures in this study were performed only by one anesthesiologist of our hospital with 25 years of experience in anesthesia. Before the study, The anesthesiologist underwent theoretical training of ultrasound-assisted technique in the details of ultrasonic machine operation and image analysis by ultrasound professionals. Apart from theoretical training, a hands-on simulation of artificial limbs' real-time process was carried out to help the practitioner master this skill. Besides, clinical practice with the ultrasonic device was carried out for two weeks before the trial started.
Before getting into the operating room, the child was given 0.5 mg/kg midazolam orally by the sedative nurse. If Ramsay score ≥ 4 were met, the child would be brought into the operating room, and random numbers were extracted from the envelope to determine the group. If the participant did not sleep during the first 30 minutes, 1 µg/kg of dexmedetomidine would be added to avoid the child and family members' separation anxiety. After entering the operating room, the child's saphenous venous condition was graded using the venous grading criteria by the anesthesiologist conducting the venipuncture in this experiment. The grading criteria are shown in Table 1. The vein distance from the top of the vein to the skin(depth) and the maximum transverse vein diameter(width) of the bilateral saphenous vein at the level of medial malleolus were then measured by another anesthesiologist with extensive ultrasound experience using an 8–18 MHz Linear probe of a GE Healthcare ultrasound device (Venue 50, GE Healthcare) and the ultrasonic depth was standardized to 2 cm. The depths and widths of the vein in the same short-axis plane were measured three times to determine the final parameter by the average values of the measurements. The measurement legend of the great saphenous vein was shown in Fig. 1. All procedures were performed using water-soluble ultrasound transmission gel as a contact medium. The corresponding images were saved so that the operator could review the picture and the measurement results of the saphenous vein selected by the operator afterward.
The grading criteria of saphenous vein punctures
Ⅰ Visible bilateral saphenous veins, no difficulty in puncture
Ⅱ Only a saphenous vein visible, predictable difficult access
Ⅲ No visible or palpable bilateral saphenous veins
The ultrasound-assisted IV catheter placement was performed using a static ultrasonic technique. Briefly, the operator was permitted to apply a tourniquet to the proximal part of the ankle. For the ultrasound group, the operator performed ultrasonic equipment to scan the full field of both saphenous veins in the short axis view to select the better one for the cannulation with the tourniquet applied. In two points with 1 cm distance to each other in the short-axis plane, the overlying skins were marked with a straight line using a black marker. Once the puncture site was identified and the vein was marked, the field was prepared aseptically. Then the operator immediately used the skin marking as a landmark for subsequent IV access attempts. A cannula was chosen at the discretion of the study operator. Once a vein was selected, the operator was not permitted to change sides during the study. When a flash of blood was seen in the trocar, that is, the cannula penetrated the anterior wall of the vein, the needle angle was lowered, and afterward, the cannula was advanced into the vein over the needle. In contrast, for the landmark group, after the tourniquet was applied, the choice of the great saphenous vein was made by the experience of the operator, which included the visualization and the palpation of the great saphenous vein. After the puncture site was identified, regular disinfection was made. The operator performed the catheterization just anterior to the medial malleolus of the ankle. Subsequent operations were similar to the ultrasound group. If the first attempt failed, the choice of following puncture location was left at the discretion of the anesthetist. The overall puncture time and other parameters were recorded during the puncture process, and the specific definitions are described in the upcoming section. The overall puncture time and other parameters were recorded and calculated with a stopwatch by an anesthesiologist who was not involved in the anesthetic care of the child, and results were self-reported. The anesthesiologist was strictly trained about the procedure and time calculation to ensure the accuracy of the record. To avoid unnecessary body movement during puncture, inhalant sevoflurane (5%) in oxygen at 5 L/min was delivered to the child through a face mask. If the MAC reached 0.8, the puncture was performed. Standard monitoring was applied throughout the period, including blood pressure, heart rate, and pulse oxygen saturation. At the end of the surgery, the complications of the puncture site were recorded, such as skin swelling and whiteness, venous extravasation, hematoma. Because of the physical nature of the interventions, it was not possible to conceal the group allocation from the research assistants or the trial operator. Still, the random numbers were maintained separately by a nurse who was not involved in the study and data processing and was not revealed to the research investigators and statisticians until data entry and analyses were completed.
Outcome Measurements And Definitions
We recorded the age, sex, height, body weight, Previous history of difficult access, and any comorbidities that might render IV access difficult, including the chromosomal abnormality, severe intellectual disability, and the types of cardiac anomaly. BMI was measured by height and weight (BMI = weight/(height) 2).
The primary outcome was the success rate of the first attempt in either group. The successful venous cannulation was defined as catheter placement with reflux of blood into the catheter and subsequent ability to infuse 5 mL of standard saline flush without local infiltration. If the insertion of the first attempt was not successful, the procedure was considered as a failure of the first attempt. Unsuccessful venous cannulation after three attempts was described as a failure of overall punctures. The secondary outcomes included the overall numbers of attempts, the overall puncture time, overall numbers of needle redirections, the time to cannulation at the first attempt, numbers of needle redirections at the first attempt. One attempt was described as a puncture in which the needle enters the skin directly for intravenous catheterization, and the endpoint of an attempt was the withdrawal of the needle out of the skin. The time of one puncture was identified as the time starting from tourniquet placement to the end of confirmation of the flush of normal saline. The overall puncture time was calculated by accumulating the time of each puncture. A redirection was defined as the partial withdrawal of the catheter with subsequent advancement to change the direction of catheter placement. The numbers of needle redirections at the first attempt were counted. The overall numbers of needle redirections were calculated by accumulating total needle redirections of attempts. If the needle was redirected more than six times, no further adjustment would be made to avoid harm to children.
Statistical Analysis And Sample Size Calculation
All analyses in this study were performed on an intention to treat basis. Statistical package for social sciences(SPSS) version 24 for windows (SPSS Inc., Chicago, IL, USA) was used in the analysis of the data obtained. The normality of continuous data was tested by the Shapiro-Wilks method. Means ± standard deviations were computed for the continuous and normally distributed data. A two-sided independent sample t-test was used for intergroup comparison. Skewed distribution data were presented as medians with ranges. The Mann-Whitney tests were used for Skewed distribution data and ordered categorical variables. Proportions and associated 95% confidence intervals(CIs) were computed for categorical variables. Pearson chi-squared test or Fish's exact test was used for unordered categorical variables, and relative risks and differences in proportions (with 95% confidence intervals (CIs) were computed between groups to compare the difference. When taking into account the confounding factor (the types of cardiac anomaly), the Cochran-Mantel-Haenszel method was used for stratified data. A P-value of less than 0.05 was considered statistically significant. A multivariate logistic regression model was performed to test if the success rates at the first attempt were affected by possible confounders such as types of the cardiac anomaly, the puncture methods selected, age, sex, BMI, previous history of difficult access, comorbidities, saphenous veins grading, numbers of needle redirections at the first attempt, the diameter and depth of the saphenous veins. All variables above were analyzed firstly by univariate logistic regression. If P was less than 0.2, the variable was included in the multivariate logistic regression model for correlation analysis. Associations between two continuous covariates were assessed by the Pearson correlation coefficient. If correlation coefficients were less than 0.8, the more statistically significant variable was selected in the multivariate logistic regression model to avoid multicollinearity among the potential covariates. Finally, Receiver operating characteristic (ROC) curve and Hosmer-Lemeshow test were used to assess the discrimination and calibration of the logistic model.
The sample size required was calculated on the basis of the success rate of the first attempt. The previous study reported first-attempt success rates of about 51% with the conventional method for saphenous venous cannulation. We assumed that a 30% increase in the success rate of the first attempt using the ultrasound technique should be significantly different compared with the traditional anatomic landmark approach. This assumption required 60 participants in each group to detect a difference in the success rate of the first attempt between groups with a power of 80% and a significance level of 0.05 using a two-sided Chi-square test. Considering the balance of the random block and the 10% dropouts of the samples, the final sample size was raised to 72 cases in each group. This sample size also allowed us to effectively find the effects of stratified factors (types of cardiac anomaly).