Comparison of different approaches to combined spinal epidural anesthesia (CSEA) under the guidance of ultrasound in cesarean delivery obese patients: A randomized controlled trial


 Background: Combined spinal epidural anesthesia (CSEA) is commonly performed in cesarean deliveries. However, it is difficult to perform in obese parturients because of positioning challenges. The aim of this study was to compare the effect of different approaches to CSEA under the guidance of ultrasound.Methods: One hundred obese patients (BMI≧30 kg/m2) who underwent elective cesarean section were randomly enrolled. Patients were assigned to a median approach group and a paramedian approach group randomly. Clinical characteristics were compared between groups. First puncture success rate, ultrasonic time needed for positioning and puncture time, ultrasonic predicted anesthesia puncture depth, actual puncture depth, adverse reactions to anesthesia, complications after anesthesia, and patient satisfaction with the epidural puncture were recorded.Results: The first puncture success rate was significantly different between the two groups (92% vs 86%, P <0.05). The positioning time and total puncture time in the paramedian approach group were higher than those in the median approach group (217.7 s vs 201.6 s, P <0.05; 251.3 s vs 247.4 s, P＞0.05). The incidence of postanesthesia complications in the paramedian approach group was significantly lower than that in the median approach group (2% vs 12%, P <0.05), and patient satisfaction was higher in the paramedian approach group than in the median approach group (P <0.05).Conclusion: The ultrasound-guided paracentesis approach for intrauterine spinal anesthesia for cesarean section patients is time-consuming, but it can effectively improve the success rate of the first puncture, reduce the incidence of anesthesia-related adverse reactions, and improve patient satisfaction.Trial registration: This study was registered with the Chinese Clinical Trial Registry (ChiCTR1900024722) on July 24, 2019.

section patients is time-consuming, but it can effectively improve the success rate of the rst puncture, reduce the incidence of anesthesia-related adverse reactions, and improve patient satisfaction.
Trial registration: This study was registered with the Chinese Clinical Trial Registry (ChiCTR1900024722) on July 24, 2019.

Background
Combined spinal epidural anesthesia (CSEA) has the advantages of quick onset, good effect and controllable action time. It has been widely used in clinical practice and has become the preferred anesthesia method for cesarean section [1]. However, failure of intraspinal anesthesia puncture caused by a large abdominal circumference, a nonideal anesthesia position, obesity and tissue edema, as well as anesthesia-related complications, such as nerve injury, unsatisfactory anesthetic effect and postpartum lumbago, are not uncommon [2]. Therefore, it is particularly important to improve the success rate of CSEA for pregnant women, especially for obese patients.
Ultrasound technology has the advantages of easy operation and noninvasiveness and has been widely valued in clinical practice. Previous studies have shown that ultrasound imaging of the spine has the ability to assist in locating the epidural space [3,4] and can also be used to measure the distance from the skin to the epidural space to predict the penetration depth of the puncture needle to avoid the o puncture of the dura mater caused by a too-deep puncture. Some studies have shown that although there is a certain difference between the ultrasonic prediction of puncture depth and the actual operation of epidural puncture depth, there is still a good correlation between them [5]. This provides some guidance for anesthesiologists for conducting ultrasound-guided epidural puncture.
Epidural puncture by anesthesiologists under the guidance of ultrasound has become one of the hot topics of clinical anesthesia and pain treatment research [6]. Studies have found that there may be no signi cant difference in the timing between traditional intraspinal puncture by experienced anesthesiologists and ultrasound-guided epidural puncture [7][8][9], which does not re ect the application advantage of ultrasound in epidural puncture. However, ultrasound localization is helpful for epidural puncture in patients with di cult surface localization or abnormal anatomical markers. A recent study found that ultrasound positioning can be used for intraspinal anesthesia in cesarean section of obese pregnant women [10]. The rst puncture success rate in the ultrasound group was signi cantly improved, the number of punctures was signi cantly reduced, the incidence of postoperative low back pain of parturients was reduced, and the safety of anesthesia was increased. These ndings are consistent with the conclusions of other researchers [11].
However, some studies have found that the incidence of postpartum low back pain was high in overweight or obese women after spinal anesthesia [12], and the incidence of postpartum low back degeneration was high in obese women [13]. There are two puncture approaches for combined spinal epidural anesthesia: median approach puncture and paramedian approach puncture. Early studies have noted that the success rate of paramedian approach puncture was higher than that of median approach puncture and that it is associated with fewer complications and postoperative complications [14]. To date, we found that all the relevant studies on intraspinal anesthesia have used the median approach puncture by ultrasound; however, it is still unknown whether the paramedian approach under ultrasound can improve the success rate of puncture and reduce complications when compared with the median approach.

Materials And Methods
This study was approved by the Ethics Committee of Shanghai First Maternity and Infant Hospital and was registered with the Chinese Clinical Trial Registry (ChiCTR1900024722). A total of one hundred obese pregnant women who underwent elective cesarean section in Shanghai First Maternity and Infant Hospital from August 2019 to March 2020 were selected. The inclusion criteria were as follows: age ≥ 18 years, normal singleton pregnancy, gestational age ≥ 37 weeks, and body mass index (BMI) ≥ 30 kg/m 2 (based on weight measured the day before delivery). The exclusion criteria were as follows: rejection of spinal anesthesia; twins; a history of spinal deformity or spinal surgery; contraindications to spinal anesthesia (infection of the puncture site, coagulation dysfunction, allergy to local anesthesia, insu cient blood volume or abnormal spinal anatomy); and emergency cesarean section. Combined spinal epidural anesthesia was performed on all patients, and the L3-4 or L2-3 interspace was selected.
According to the different puncture approaches, 50 patients were divided into a median approach group and a paramedian approach group. No sedation was provided before or during anesthesia. One anesthesiologist with more than three years of clinical experience in spinal anesthesia was selected as the operator. Ultrasound was performed by a single researcher trained in the technique, and more than 150 ultrasound-guided spinal block experiences were performed.

Anesthesia care
The patient was placed in the right-side position with the arms embracing the knees and the back arched.
A Sonosite convex array probe was used for ultrasonic scanning. The ultrasonic probe was placed at the middle level of the sacrococcygeal region, and a scan was performed horizontally and moved to the lumbosacral region. The L3 vertebra, L4 vertebra and L3-L4 interspace were identi ed, the skin was marked, and the probe was turned to the horizontal position while keeping it centered. Then, the position of the L3 vertebra was determined and marked, and the intersection of the longitudinal and transverse lines at the L3-L4 interspace was determined as the puncture point for the median approach. In longitudinal sagittal ultrasound imaging, it is necessary to identify the L3 and L4 articular processes and the ligamentum avum in the middle of the articular processes and to measure the distance between the skin and ligamentum avum to predict the puncture depth (Fig. 1A). In the paramedian approach group, the L3-L4 interspace was selected, and the puncture point was 1.5 cm below this area in the median vertical paracentesis. And the distance between the skin and the ligamentum avum was measured by ultrasound at the puncture point to predict the depth of anesthesia puncture (Fig. 1B).
After the skin was marked, the skin was disinfected, a towel was spread, 1% lidocaine was injected into the skin for local anesthesia, and it was con rmed that the 16G epidural puncture needle had entered into the epidural space (negative pressure method). The patient was instructed to keep still, and the subarachnoid cavity was entered through the epidural needle cavity with a 25G lumbar anesthesia needle. After cerebrospinal uid appeared in the lumbar puncture needle, the needle tip was pointed toward the patient's head, and 0.5% ropivacaine 2 ~ 3 mL was injected at rate of approximately 0.1 mL/s. After injection, the spinal needle was pulled out, an epidural catheter was placed, and the patient was moved to left supine position. In the paramedian approach group, the angle between the needle and the skin was 75°, and other steps were as the same as in the median approach group.
The L3-L4 interspace was the rst choice for puncture, and the L2-L3 interspace was used for the followup attempt. A maximum of 3 skin puncture attempts (needle withdrawn from the skin and then readvanced) were allowed for one interspace and a maximum of 5 needle passes (needle withdrawn and readvanced without complete withdrawal from the skin) were allowed for each skin puncture attempt. If dural puncture was unsuccessful after attempts at the L2-L3 interspace, the operator was allowed to use other means to perform anesthesia, including changing the operator or anesthesia mode. Successful spinal anesthesia was de ned by a bilateral T4 block ve minutes after injection. The incidence of hypotension (mean blood pressure below 90 mmHg or systolic pressure reduction of > 25% from the initial value) was recorded. Other complications, such as bloody tap or paresthesia, were also recorded by an independent observer blinded to the group allocation. A blinded attending anesthesiologist recorded all the outcomes.

Measurement
The clinical data of the patients, including age, gestational age, height, weight and BMI, were recorded.
The primary outcome was the rate of successful dural puncture on the rst attempt. Secondary outcomes were the location time (from the time the operator placed the ultrasonic probe on the back of the patient to the end of positioning), puncture time (total operation time, location time), adverse reactions during puncture (incidence of nerve stimulation, bleeding), total operation time (the time from disinfection to the time when the patient changed to supine position), and complications after anesthesia (incidence of postoperative low back pain).

Statistical analysis
Statistical analysis was performed using SPSS Version 22.0 (IBM, Armonk, NY). Continuous data were tested for normality using Q-Q plots and the Shapiro-Wilk W statistic. Normally distributed outcome data were summarized as the mean (standard deviation) values and were compared between groups using independent measures t test. Categorical data were analyzed using the χ 2 test or Fisher's exact test. The primary outcome (the rst-attempt success rate) was analyzed using the χ2 test, while Fisher's exact test was used for subgroup analyses for subgroups with P values considered statistically signi cant.

Results
A total of 133 women were recruited for the study from August 2019 to March 2020,after exclusion there were 100 patient in analysis.There were fty patients in the paramedian approach group and fty patients in the median approach group. No patients were excluded due to loss of data or failed follow-up (Fig. 2). There were no signi cant differences in age, gestational age, height, weight, BMI, ASA grade or operation time between the two groups (Table 1). Data related to intraspinal anesthesia from the two groups are shown in Table 2. The success rate of the rst attempt in the paramedian approach group was signi cantly higher (92% vs 86%, P < 0.05) than that in the median approach group. Two groups of patients achieved bilateral T4 block after successful anesthesia, and there were no cases in which the mode of anesthesia of changed. There was no signi cant difference between the two groups in the total operation time of puncture (time from disinfection to supine position) (P > 0.05), but the location time of the paramedian approach group was signi cantly longer than that of the median approach group (P < 0.05). In addition, there were some differences in anesthesia-related adverse reactions between the two groups. Compared with that in the median approach group, lower nerve stimulation occurred during anesthesia puncture (1/50 vs 2/50, P > 0.05) in the paramedian approach group. Blood returned after epidural catheter implantation (2/50 vs 3/50, P > 0.05), and there was a signi cant difference in the incidence of postoperative lumbar back pain between the two groups (1/50 vs 6/50, P < 0.05). Patients in the paramedian approach group had higher satisfaction (P < 0.05) than those in the median approach group.  Table 3 shows the data of the ultrasonic predicted anesthesia puncture depth and actual puncture depth in the two groups. There was no signi cant difference in the actual puncture depth between the two groups (in the median approach group, P = 0.927; in the paracentral approach group, P = 0.726).

Discussion
In this randomized controlled study, we found that the rst puncture success rate in the paramedian approach group was 92%, which was signi cantly higher than the 86% in the median approach group (P < 0.05). In the paramedian approach, the superior and interspinous ligaments were avoided so that the epidural space was entered directly from the ligamentum avum. There were fewer ligaments and other anatomical structures; therefore, the rst puncture success rate was higher in the paramedian approach group than in the median approach group. In addition, based on the analysis of the anatomical structure of the spine, the paramedian approach is not limited by the inclination of the spinous process and the bone structure. When entering the epidural space, the end of the puncture needle is more inclined to form an angle on the side of the head, the cerebrospinal uid returns smoothly after the insertion of the lumbar anesthesia needle, and it is easier to place the epidural catheter after the completion of the lumbar anesthesia. Some studies have con rmed that the puncture interspace of the paramedian approach is wider than that of median approach, which reduces the di culty of puncture, avoids repeated puncture and increases the success rate of puncture [15].
At the same time, the controversy over the use of ultrasound to assess the distance between the skin and the epidural space should be considered. In theory, the actual puncture depth is deeper than that predicted by ultrasound. Our study found that the actual depth of extradural puncture was deeper than that predicted by ultrasound, but there was no signi cant difference between groups (P < 0.05). The reason may be that when the operator evaluates the success of epidural puncture, the needle insertion is stopped immediately when negative pressure is felt during the puncture to avoid placing the puncture needle too deeply, especially for anesthesiologists with more puncture experience. There was no signi cant difference between the predicted puncture depth and the actual puncture depth in the median approach group, which suggested that ultrasound could effectively predict the epidural puncture depth in different approaches of combined spinal epidural anesthesia. However, it should be pointed out that the actual puncture depth of both groups of data was deeper than that predicted by ultrasound. Considering the possible in uence of fat thickness or tissue edema on the backs of obese pregnant women, our study compressed the maternal skin to avoid its in uence when ultrasound placed the puncture point.
In this study, a high-frequency convex array probe was used to accurately determine the best puncture point of anesthesia in the median approach group. The selection of puncture point in the paramedian approach group was based on the lateral paracentesis of 1.5 cm at the median approach puncture point, and on this basis, ultrasound was used to predict the puncture depth. Therefore, it was found that the positioning time of the paramedian group was higher than that of the median group (P < 0.05). However, there was no signi cant difference in the total operation time between the two groups (P > 0.05).
Considering that the rst puncture success rate of the two groups was high, the number of attempts was small, and the skilled operation of anesthesiologists had a certain relationship.
Anesthesia safety is also an important factor in this study. Among the one hundred obese pregnant women included in this study, there were adverse effects of anesthesia in both groups, such as epidural catheter bleeding, nerve stimulation signs and the occurrence of low back pain after anesthesia, and there were signi cant differences between the two groups in the occurrence of low back pain (P < 0.05). We considered that the paramedian approach group could avoid the supraspinous ligament and part of the interspinous ligament and allow entrance into the epidural space through the ligamentum avum in the process of puncture. The analysis shows that the main reason for the difference in the incidence of low back pain between the two groups is the difference in ligament injury caused by the dural puncture needle. There was no signi cant difference in nerve stimulation between the two groups. It is worth mentioning that there were no cases of unexpected dural puncture in the either of the groups, further suggesting the advantage of ultrasound in obese women. There was a higher degree of satisfaction in the paramedian approach group than in the median approach group (P < 0.05).
Previous studies have found that there is no signi cant difference in the success rate of traditional intraspinal puncture when ultrasound is used and when it is not in normal pregnant patient[16], which does not re ect the application advantages of ultrasound in epidural puncture. Therefore, this study is more valuable for the application of ultrasound-guided epidural puncture in obese cesarean section women. In addition, it should be pointed out that the technology of ultrasound intervention in epidural puncture can be divided into prepuncture positioning and real-time guiding operation, but the real-time guiding requires aseptic treatment of the probe, the operation process is complex, and the advantage is not obvious compared with the prepuncture ultrasound positioning; additionally, in the operation process, elimination of air/liquid resistance is still used to determine whether the tip of the needle reaches the epidural cavity [17]. Therefore, in this study, we chose to place the epidural catheter before ultrasoundguided puncture rather than under real-time ultrasound-guided puncture. Of course, there are some limitations in our research. First, although we used the same anesthesiologist with much experience in using spinal ultrasound, the results are still controversial. Second, we had a relatively small number of cases and fewer positive results. More samples are needed for further study.

Conclusion
Our conclusion is that the ultrasound-guided paramedian approach puncture for combined spinal anesthesia for cesarean section patients is more time-consuming, but it can effectively improve the success rate of the rst puncture, reduce the incidence of anesthesia-related adverse reactions, and improve patient satisfaction.
Abbreviations CSEA: Combined spinal epidural anesthesia; BMI: Body mass index; ASA: American Society of Anesthesiologists classi cation Declarations Zhiqiang Liu designed the study and drafted the manuscript.Yilu Zhou participated in the design of the study and interpreted the results. Zhendong Xu participated in the interpretation of the results. All authors read and approved the nal manuscript.

Funding
This study received no funding from the public, commercial or nonpro t sectors that provide special grants for this research.
Availability of data and materials All data generated or analyzed during this study are presented in this manuscript and/or additional supporting les. The additional datasets are also available from the corresponding author on reasonable request.

Ethics approval and consent to participate
This study was approved by the Ethics Committee of Shanghai First Maternity and Infant Hospital and was registered in the Chinese Clinical Trial Registry (ChiCTR1900024722) on July 24, 2019.The registry can be monitored at this link http://www.chictr.org.cn/index.aspx. Written informed consent to participate was obtained from each participant.

Consent for publication
Not applicable.

Competing interests
There was no con ict of interest in this study.