Comparison of the proximal and distal approaches for axillary vein catheterization under ultrasound guidance (PANDA) in cardiac surgery patients susceptible to bleeding: a randomized controlled trial

The PANDA (comparison of the proximal and distal approaches of axillary vein catheterization under ultrasound guidance) trial was a single-center prospective randomized controlled trial. The protocol of the PANDA study was approved by the Ethics Committee of Zhongshan Hospital, Fudan University (Shanghai, China, IRB No. B2017-140) and registered at ClinicalTrials.gov (ID: NCT03395691). Written informed consent was obtained from legal representatives in accordance with the Declaration of Helsinki.

Cardiac surgery patients of age > 18 years and requiring AVC for any clinical reason were screened. Patients susceptible to bleeding were defined as those who received oral antiplatelet drugs and/or anticoagulants for at least 3 days.

Patients meeting one of the following criteria were excluded: (1) the proximal and/or distal axillary vein was not clearly visualized or potentially unavailable for catheterization; (2) did not receive or had not received oral antiplatelet drugs and/or anticoagulants for less than 3 days; (3) already had presence of subclavian or axillary vein catheter; (4) required an emergency AVC; (5) had fracture of the ipsilateral clavicle or anterior proximal ribs; (6) had subclavian and/or axillary vein thrombosis; and (7) had local infection of the puncture area.

Patients were randomized to the proximal approach (PA) or distal approach (DA) group in a 1:1 ratio by using a computerized system. The allocation process was intensively managed by an allocation group using sequentially numbered containers, and the allocation result was concealed until it was implemented. When a patient was eligible, the investigator informed the allocation group to allocate the patient to the intervention group: PA or DA group. Because of feasibility issues, operators were not blinded to the assignment.

All procedures were performed in the Cardiac Surgery Intensive Care Unit (n = 39 beds) by five physicians with 3 to 18 months of experience in US-guided AVC. All operators underwent a protocolized training program to minimize variations in procedures before the initiation of this study [19]. A Philips CX50 system (Philips Healthcare, Eindhoven, Netherlands) equipped with a 3–12 MHz, linear array probe in the vascular mode was used for all CVCs. An 8 Fr two-lumen central venous catheter (Arrow International Inc., Reading, PA, USA) was chosen.

The proximal approach refers to the mid-infraclavicular axillary vein access (often termed as US-guided SVC in previous literature), in which the entry of the needle is close to the mid-clavicle (Fig. 1a). The distal approach refers to the more distal axillary vein access, in which the entry of the needle is distant from the artery and pleural cavity in the axilla (Fig. 1b). The patients were placed in the supine position with arms in the neutral position. A preoperative scanning was conducted to examine the axillary vein and the surrounding structures in the long-axis and short-axis view. Color Doppler imaging and flow measurements were used to confirm patency of the axillary vein. Lung sliding was examined to provide a comparison for post-procedure assessment. The operating field including the neck area was prepared with iodine disinfectant. The probe was wrapped in a sterile sleeve, with a sterile gel applied outside and inside the sleeve. The longitudinal axis/in-plane approach was used in which the target vein and the entire needle including the tip were simultaneously visualized during catheterization. The operators held the probe with the left (nondominant) hand and the needle with the right (dominant) hand. The probe was gently placed on the skin with the least amount of pressure to obtain the optimal image. The skin and subcutaneous tissues were infiltrated with lignocaine before venipuncture. When introducing the needle, the progression of the needle into the vein was visualized in real time. Although the US beam and needle advances could not be clearly viewed, the needle could be aligned slightly to visualize the needle tip clearly. The needle tip in the US image was manifested as a moving bright spot associated with distortion of the surrounding tissues. The transducer could be slid or tilted to follow the needle tip, if necessary. When the needle tip punctured the target vein successfully, blood was freely pulled into a syringe. The wire was then advanced carefully. The wire position was confirmed by the longitudinal axis image before vessel dilation. The length of catheter insertion was at the discretion of operators. Generally, a 14-cm to 16-cm catheter was used for the proximal approach and an 18-cm to 20-cm catheter was used for the distal approach according to the patient’s features. If the first two attempts of venipuncture failed, the procedure was converted to the other approach in the next two attempts. When both approaches (four attempts) failed, another site (the other axillary or the internal jugular vein) was chosen for cannulation by an experienced operator (G.W.T); this was regarded as failure. After successful catheterization, the presence of complications was assessed by US. The depth of the axillary vein (the distance between skin surface and the anterior wall of the vein) and the vessel diameters were measured in the longitudinal axis image by using software of the US machine (Fig. 1c, d). At least one chest X-ray or CT scan was performed within the following 24 h.

The primary outcome was the first puncture success rate defined as the number of successful catheterization in the first attempt. The secondary outcomes were the site success rate (defined as the number of successful cannulation within the first two attempts), overall success rate [defined as the number of successful cannulation in the targeted axillary vein within four attempts (the first two attempts using the randomized approach and the third and fourth attempts using the nonrandomized approach)], access time (defined as the time between penetration of skin and aspiration of venous blood into the syringe), time to successful catheterization (defined as the time from skin puncture until the completion of catheter insertion), number of attempts (one attempt was defined as the passage of the skin with the needle and one venipuncture), and mechanical complications occurring within the 24-h follow-up period (major bleeding, minor bleeding, arterial puncture, pneumothorax, nerve injuries, and catheter misplacement). Major bleeding was defined as a decrease in hemoglobin to > 1.6 g/dL or a need for transfusion or hemodynamic instability due to bleeding or hemothorax after the procedure. Minor bleeding was defined as the development of swelling > 2 cm around the skin puncture site under ultrasonography imaging after 5 min of manual compression. Catheter misplacement was defined as placement of the catheter’s tip outside the right atrium or the superior vena cava. The number of attempts, access time, insertion time, and immediate complications were recorded by a designated investigator. A physician blinded to the study data read all chest X-ray/CT scans to determine mechanical complications such as hemothorax, pneumothorax, and catheter misplacement.

The expected first puncture success rate in the DA group ranged from 67% to 76% based on the literature [10, 15, 20]. Considering the low experience of operators, the anticipated first puncture success rate was set as 67%. Assuming a difference of not less than 20% in the proportion of the first puncture success rate between the groups and a 10% attrition rate, we estimated that 198 patients (99 per group) were required to provide 90% power at a two-sided alpha level of 0.05.

All analyses were performed by the intention-to-treat method. Categorical variables were expressed as numbers and percentages. For continuous variables, the normality of distribution was evaluated using the Kolmogorov–Smirnov test. Continuous variables were expressed as mean and standard deviations (SD) or median and interquartile ranges (IQR). Categorical variables were compared using the Chi-square test or Fisher’s exact test, and continuous variables were compared using Student’s t test or the Mann–Whitney U test as appropriate. Statistical analyses were performed with SPSS 13.0 (IBM Inc., Armonk, NY, USA). Two-sided p values of less than 0.05 were considered statistically significant.