Surgical Efficacy in Varicocele Ligation with Ephedrine-Assisted Blood Pressure Control

Introduction

Varicocele (VC) was a common disease of the male reproductive system, with a prevalence of 15–20%. Among male infertility patients, the incidence of VC is approximately 40% [1]. The pathogenesis of VC was characterized by dilation of the testicular veins due to increased resistance to blood flow in the spermatic veins, often exacerbated by venous valve dysfunction or hemodynamic changes [2]. Prolonged VC can lead to testicular atrophy and impaired spermatogenesis, thereby adversely affecting male fertility [3,4].

Surgical intervention remains the mainstay of treatment for patients presenting with abnormal semen parameters and testicular pain due to VC [5]. Surgery can effectively block the reflux route of the spermatic veins, significantly alleviating pain, and improving testicular spermatogenic function. Therefore, surgical management is considered the most direct and effective approach for treating VC. Various surgical techniques are employed to treat VC [6], including open surgery, laparoscopic spermatic vein ligation, and microscopic spermatic vein ligation (MSVL). MSVL offered significant advantages over open or laparoscopic methods, as it allows for complete ligation of both internal and external spermatic veins under high magnification, while preserving the testicular arteries (TAs) and lymphatic vessels. This approach is associated with a better prognosis, including a lower rate of postoperative recurrence and complications [7,8]. Moreover, it had been shown to be more effective in improving semen parameters in VC patients. As such, MSVL is regarded as the criterion standard technique for treatment of VC today [9,10].

However, it was noteworthy that many urologists are hesitant to adopt microscopic techniques [11]. Despite the use of high optical magnification, achieving complete ligation of the veins while maintaining the integrity of the TAs during surgery remains challenging [12]. The subinguinal region contains multiple internal spermatic veins and arteries, with an average of 12 unilateral internal spermatic veins, and in some patients, more than 1 TA [11,13]. Microscopic surgery is time-consuming and technically challenging for surgeons [6,14,15], especially in adolescent patients, where the small diameter of the vessels and lower blood pressure can complicate arterial identification [11]. Additionally, in 29–57% of cases, the testicular artery is surrounded by a network of varicose veins, making its identification difficult. In these cases, the TAs may be masked by neighboring veins, and isolating it becomes a challenging task [16]. This increases the risk of inadvertent damage to the TAs during MSVL [2]. Studies in humans and animal models had shown that ligation of the TAs can have detrimental effects on the germinal epithelium and spermatogenesis [17]. Therefore, earlier and more accurate identification of the TAs during the surgical procedure is essential to minimize the risk of arterial injury.

To more accurately identify the TAs, most surgeons commonly use an intraoperative lidocaine solution to cover the spermatic vein plexus. However, this approach is ineffective for identifying small arteries encircled by the vein [18,19]. For surgeons using micro-Doppler imaging, this is a more effective method for locating the TAs. However, the pulsations may be faint until the vessels are fully isolated, making it difficult to precisely locate the pulsating arteries. Moreover, micro-Doppler devices may not be available in all operating rooms, particularly in some hospitals [13,18]. Therefore, for experienced urologists, a simple and effective method is needed to ensure safe preservation of the TAs during surgery.

In patients with VC, it has been observed that most patients are younger, with an average systolic blood pressure of approximately 110 mmHg, and very few patients have a systolic blood pressure exceeding 130 mmHg. In patients with higher baseline blood pressure, the pulsation of the TAs tends to be more vigorous, which can assist in the identification and isolation of the artery, thereby aiding in its preservation.

Ephedrine, a sympathomimetic drug, stimulated the sympathetic nervous system and exerted an excitatory effect on both α and β receptors. This resulted in an increase in blood pressure and pulse pressure following administration [20,21]. The intraoperative use of ephedrine can safely and effectively elevate blood pressure, potentially aiding surgeons in more quickly locating the TAs.

Therefore, this retrospective observational clinical study included 52 patients undergoing MSVL for VC to compare outcomes between patients with and without medical ephedrine-induced blood pressure, with the goal of improving identification of the TAs.

Material and Methods

GENERAL INFORMATION:

The Ethics Committee of our hospital approved the study protocol (Ethics No. XZXY-LK-20240312-0041), and informed consent was obtained from all patients prior to participation. In this cross-sectional comparative study, a total of 25 patients underwent MSVL between January 2023 and June 2023, while 27 patients had their blood pressure transiently elevated to 140–160 mmHg using ephedrine during MSVL between July 2023 and December 2023 (Figure 1).

All procedures were performed by the same senior urologist. The diagnosis of VC was established based on physical examination (including the Valsalva maneuver) and ultrasound findings. Oligospermia and asthenospermia were diagnosed based on semen analysis results. Oligospermia was defined as a sperm concentration of less than 15×10⁶/ml, while asthenospermia was defined as a total sperm motility of less than 40%.

The inclusion criteria were as follows: (1) patients with VC combined with oligospermia and/or asthenospermia; (2) patients aged 18 to 45 years; (3) patients with scrotal Doppler ultrasound showing internal spermatic veins greater than 2 mm in diameter and venous reflux after the Valsalva maneuver (Figure 2); (4) patients with normal preoperative electrocardiograms, pulse, and blood pressure; (5) patients who were evaluated by anesthesiologists and were able to tolerate ephedrine-induced elevation of blood pressure; and (6) patients who volunteered to undergo follow-up and review of their condition within 6 months after surgery. The exclusion criteria were secondary VC or received medications that impair semen parameters. The study was planned in accordance with the STROBE guidelines and conducted in accordance with the principles of the Declaration of Helsinki.

OUTCOME MEASURES:

Intraoperative operative time was recorded. To minimize the potential errors associated with varying body mass index (BMI) and the time spent locating the spermatic cord, the operative time was defined as beginning from the incision of the outer fascia of the spermatic cord and ending after the skin was sutured. The following parameters were also documented: the number of spermatic veins ligated, the number of preserved TAs, and any damage to the TAs (including accidental ligation of the TAs and arterial wall injury).

Postoperative follow-up was conducted to assess the occurrence of headaches within 3 days of surgery, as well as any complications, including syringomyelia and testicular atrophy. Patients were also monitored for recurrence of VC and semen analysis was performed at 6 months postoperatively. All results were subsequently reviewed and evaluated by a second surgeon, using standardized criteria.

MONITORING OF BLOOD PRESSURE: After the patients in the EBP group entered the operating room, radial artery puncture and catheterization were performed under local anesthesia. A single-use pressure transducer was then connected to monitor invasive arterial blood pressure in real time. Figure 3 illustrates the tools used for blood pressure monitoring and their application.

ELEVATED BLOOD PRESSURE IDENTIFIES TAS:

After lumbar anesthesia, the patient was positioned supine, and a transverse incision of approximately 2–3 cm was made at the inferior portion of the outer ring of the groin. The skin was incised and the underlying tissues were carefully separated to expose the spermatic cord. Using tissue forceps, the spermatic cord was gently retracted through the incision, and a small hook was employed for further manipulation. A microscope was used to magnify the surgical field 10 times, facilitating dissection of the external spermatic fascia. Upon opening the external spermatic fascia, in the NEBP group we infiltrated the surface of the blood vessels with a lidocaine solution to identify the TAs, separating the lymphatic vessels and arteries for preservation.

In the EBP group, after opening the internal spermatic fascia, the anesthesiologist administered 3–6 ml of a 1 mg/ml ephedrine solution intravenously, based on the patient’s baseline blood pressure, to maintain systolic blood pressure within the range of 140–160 mmHg during the procedure. If there was a subsequent decrease in blood pressure, additional doses of ephedrine were given until the testicular artery was clearly identified. The total amount of ephedrine administered was recorded after completion of surgery. Figure 4 illustrates the varicocele in a patient and successful identification of the TAs.

LIGATION OF THE SPERMATIC VEINS: After freeing and protecting all the TAs, all the internal spermatic veins and their collateral branches were ligated sequentially and individually. Following the ligation of the spermatic veins, the severed ends were double ligated with 4-0 silk sutures. After thoroughly checking for any missed veins and visible bleeding points, the levator ani muscle and the external fascia of the spermatic cord were sutured. The spermatic cord was then returned to its original position, and the incision was closed layer by layer. Finally, the wound was dressed with a sterile dressing under pressure. In Figure 5, the operator fully preserved the TAs and lymphatic vessels, and ligated the severed ends of the spermatic veins.

STATISTICAL ANALYSIS:

Statistical analysis was performed using SPSS software version 26.0. The normality of data distribution was assessed using the Kolmogorov-Smirnov test. For normally distributed data, comparisons between groups were made using the t test; for non-normally distributed data, the Mann-Whitney U test was applied. Frequency data were compared using the chi-square test or Fisher’s exact test. Measurement data are presented as mean±standard deviation (SD) for normally distributed variables or as median (25^th, 75^th percentiles) for non-normally distributed variables. Count data are expressed as n/n. Statistical significance was set at P<0.05.

Results

DEMOGRAPHICS:

There was no statistically significant difference in the age of the patients between the 2 groups (26 (23.5, 32.5) vs 30 (25, 32)), P=0.659). Additionally, there was no statistically significant difference in the distribution of left and right lesions between the 2 groups (P=0.71). The mean systolic blood pressure was 115.6±6.5 mmHg in the NEBP group and 116.1±4.3 mmHg in the EBP group, with no statistically significant difference (P=0.738). Table 1 provides a summary of the demographic information for the patients in both groups.

SURGICAL PARAMETERS:

Intraoperative EBP significantly promoted TAs pulsation and effectively reduced the time required to isolate and protect the TAs. The time in the EBP group (36.48±4.53 minutes) was significantly less than that in the NEBP group (50.40±6.46 minutes) (P<0.001). Only 2 patients in the NEBP group had 2 TAs identified and successfully preserved, whereas 9 patients in the EBP group had 2 TAs identified and preserved. The number of TAs preserved intraoperatively in the EBP group (1.33±0.48) was significantly higher than in the NEBP group (0.96±0.45) (P=0.006). In the NEBP group, in 2 patients there was failure to successfully identify the TAs, and the TAs of 4 patients were damaged, while the TAs of all patients in the EBP group were successfully identified, and the TAs of 2 patients were damaged. There was no significant difference in the incidence of TA injury between the 2 groups (P>0.05). The average number of spermatic vein ligations in the NEBP group were 9.28±2.07, while the average number of spermatic vein ligations in the EBP group were 10.37±2.19, with no significant difference in the number of intraoperative spermatic vein ligations between the 2 groups (P=0.71) (Table 2).

COMPLICATIONS AND RECURRENCE:

No patients in the NEBP group experienced headaches, while 2 patients in the EBP group did, but this difference was not statistically significant (P=0.51). No complications, such as hydrocele or testicular atrophy, were observed in either group at the 6-month follow-up. The difference in complication rates was also not statistically significant. Additionally, 1 patient in each group had a recurrence of VC at 6 months postoperatively, with no significant difference between groups (P=1.00) (Table 2).

SEMEN PARAMETERS:

There was no significant difference in preoperative sperm density and motility between the 2 groups (P=0.34, P=0.38). However, a significant improvement in both sperm density and motility was observed at 6 months postoperatively compared to the preoperative period in both groups (both P<0.001). Furthermore, no significant difference in sperm density or motility was observed between the 2 groups after surgery (P=0.24, P=0.15) (Table 3).

To control for potential errors related to unsuccessful TAs preservation, we compared the semen parameters of the 2 groups after excluding patients with unsuccessful preservation of the TAs, showing there was no significant difference in preoperative sperm density or motility between the 2 groups (P=0.40, P=0.78). Additionally, no significant difference in postoperative sperm density or motility was found between the 2 groups (P=0.56, P=0.33) (Table 4).

Discussion

From the perspective of surgical duration, the use of EBP can significantly reduce the surgical time. This study clearly demonstrated that, with the assistance of EBP, the pulsatile area of the TAs becomes more distinct, which facilitated its dissection and protection, thereby significantly shortening the overall surgical time. The observed reduction in surgical time was consistent with the findings from Doppler ultrasound-assisted MSVL [6]. As surgical expertise and proficiency continued to improve, further reductions in surgical time may be achieved.

Most patients had 2 TAs in their spermatic cord, but in MSVL, often only 1 TA was successfully preserved, with the other frequently missed [17]. However, in EBP group, it was observed during surgery that a higher number of patients had both TAs successfully preserved. The number of TAs preserved in the EBP group was significantly higher than in the NEBP group. This can be attributed to the ability of EBP to more accurately identify small TAs. The American Urological Association recommends performing VC resection under optical magnification, emphasizing the importance of preserving any encountered arteries. The TAs are the primary source of blood flow to the testes, and maximizing the blood supply from the TAs may help improve postoperative sperm motility [22,23]. Furthermore, some studies suggest that in patients with VC, oligospermia, and/or asthenospermia, it is crucial to maintain maximal arterial blood flow to prevent testicular hypoxia and the reflux of toxic substances. Therefore, every effort should be made to preserve all TAs during MSVL [24,25].

Both groups had significant improvements in semen quality compared to preoperative levels, consistent with previous studies on MSVL [6]. Surprisingly, however, there was no significant difference in the improvement of semen parameters between the 2 groups. This may be due to the relatively small sample size of the current study, with a follow-up period of only 6 months. Thus, it remains uncertain whether the preservation of a greater number of TAs had a more substantial impact on fertility outcomes in patients with VC and oligospermia and/or asthenozoospermia. No relevant research reports have been published, and larger-cohort studies are needed to confirm this effect.

In our study, the recurrence rate and incidence of complications were the lowest for both EBP-assisted MSVL and traditional MSVL. During the 6-month follow-up after surgery, 1 patient in each group experienced recurrence, and neither group experienced any complications. These results were consistent with findings from other studies on MSVL performed under the inguinal canal [6,26,27]. No significant difference was observed in the number of spermatic veins ligated between the 2 groups, and EBP did not affect the number of veins ligated. This was likely because during the procedure, the arteries and lymphatic vessels within the spermatic vein plexus were freed, followed by ligation of the branches of the patient’s spermatic vein. In this study, in the NEBP group, there were 2 patients in whom we were unable to successfully identify the TAs, and there were also 6 other patients with intraoperative TA injury. Despite this, these 8 patients showed significant improvement in semen parameters 6 months after surgery compared to their preoperative values. This may be attributed to the healing of the injured TAs after surgery, or to collateral blood supply to the testes through other smaller arteries in the spermatic cord.

The use of medication for EBP management may be more cost-effective than the use of other auxiliary devices, such as Doppler ultrasound or indocyanine green angiography. The cost of medication for EBP is considerably lower than that of Doppler ultrasound [18]. Moreover, our hospital does not currently equip the operating room with micro-Doppler ultrasound devices. Prior to identifying methods for increasing blood pressure, lidocaine solution was employed to locate the TAs during surgery.

Ephedrine solution is commonly administered intravenously by anesthesiologists via an intravenous pump, which provides a simple and convenient method for surgical management. For most patients, a rapid and significant elevation in blood pressure (EBP) can be achieved with an average dosage of 6.52±1.28 mg. Some patients who have a less pronounced increase in blood pressure may require slightly higher doses. The duration of each blood pressure elevation was approximately 10–15 minutes, without prolonging the duration of surgery. Moreover, no significant adverse reactions were observed during the surgical procedure in the EBP group, and only a few patients reported mild headaches postoperatively, without any severe adverse effects. The patients’ vital signs remained stable both during and after the surgery.

In summary, intraoperative EBP can accurately free the TAs under direct visual conditions, which facilitates early identification and preservation of the TAs. This technique can significantly reduce the incidence of TAs injury during MSVL as the sample size increased. It has been shown to be both safe and effective. Furthermore, we suggest that such simple yet effective methods be applied in microsurgery to safeguard the TAs system, as this was crucial for postoperative testicular spermatogenic function recovery and the reduction of postoperative complications. However, this study had certain limitations. The retrospective design was a primary limitation, as clinical outcomes were determined based on the patient’s surgical records and follow-up results. Additionally, the sample size was relatively small, and the study did not include relevant case reports from adolescent patients, preventing the assessment of EBP’s applicability in adolescent VC cases. All surgeries were performed by an experienced urologist, which may limit the generalizability of the results to surgeons with varying levels of expertise.

Conclusions

The present study’s results suggest that the administration of ephedrine for EBP during MSVL can help surgeons safely and effectively identify and preserve the TAs, while also reducing the overall operation time. However, further research with larger sample sizes and extended follow-up periods is required to validate these findings and assess the clinical utility.