Vaginal Vault Infiltration with Bupivacaine for Postoperative Pain Control after Total Laparoscopic Hysterectomy: A Randomized control trial.

This was a prospective two-arm double-blinded randomized control trial conducted in the Department of Obstetrics and Gynecology at an Apical Center in North India. All patients who require TLH for benign condition were recruited from the gynecology outpatient department. Since there was no similar study conducted in this population, sample size could not be calculated. However, to ensure a minimum sample size of 30 in both the groups, the total sample size of 60 was kept. Ethical clearance was obtained from the institutional ethics committee (CTRI No.: CTRI/2020/05/024994.). Written informed consent was taken from all the participants. The patients were randomized into two groups using computer-generated randomization software. The allocation cards were sealed in a sequentially numbered envelope. The principal surgeon opened the envelopes in the operation theater prior to surgery. After randomization, patients were divided into two groups. Group I comprised the intervention group ( n = 30), wherein patients received bupivacaine infiltration of vaginal vault after TLH. Group II comprised the control group ( n = 30), who did not receive bupivacaine infiltration in vaginal vault. The inclusion criteria for the study were patients requiring TLH with or without bilateral salpingo-oophorectomy (BSO) for benign conditions and uterine size ≤12 weeks of pregnancy. The exclusion criteria were presence of malignancy, contraindication to any medication that was used in the study (Bupivacaine, paracetamol, diclofenac), history of chronic pelvic inflammatory disease, and history of previous multiple surgeries. The primary outcome measure was the postoperative pain measured in both the groups at 1, 3, 6, 12, and 24 h, using visual analog score. The secondary outcome measure was need for rescue analgesia. The study consort diagram is depicted in Flowchart 1 . Consort diagram of the study A complete workup of each patient in terms of demographic profile, body mass index (BMI), and eligibility criteria was performed. A complete general physical and gynecological examination was done. All the patients were interviewed and written informed consent was taken. In all the patients, preoperative investigations for fitness to general anesthesia were done. They underwent Papanicolaou test (PAP Smear) test and endometrial aspiration before surgery. All the surgeries were performed under general anesthesia as per the standard protocol. Patients were placed in the lithotomy position for the standardized laparoscopic procedure. A uterine manipulator was used to expose the uterus and pelvic structures. Pneumoperitoneum was created using a Veress needle through the umbilicus, and a 10 mm umbilical trocar and three 5 mm secondary ports were used. TLH was performed stepwise using LigaSure and harmonic scalpel as energy sources. The vaginal cuff was closed using a continuous barb suture laparoscopically. After vault closure, 10 ml of 0.25% bupivacaine was infiltrated laparoscopically using a fine tipped aspiration needle into the vaginal vault at two different points 2–3 cm apart, 5 ml at each point, and at a depth of 3–4 mm, in the study group. In the control group, the latter step was omitted. Figure 1 shows infiltration of bupivacaine into the vaginal vault laparoscopically using aspiration needle. Infiltration of bupivacaine in to the vaginal vault laparoscopically using aspiration needle Postoperative pain was treated using intravenous paracetamol 1 g six hourly for 24 h. All the patients were given NSAIDS (Diclofenac) three times a day for 5 days. Additional requirement of analgesics (opioids and NSAIDS) was recorded. The women were asked to scale their pain with VAS score. The severity of incisional pain using VAS score (0 indicated no pain and 10 indicated unbearable pain) at 1, 3, 6, 12, and 24 h after surgery was recorded. They received tramadol 50 mg IM if they report a VAS score >4 in the postanesthesia care unit and surgical ward. The operative time, amount of operative bleeding, uterine weight, and any complications were recorded. The length of hospital stay was counted from the end of surgery till discharge. Pain visual analog scale (VAS) was used to assess postoperative pain in our study. The VAS is a validated, subjective measure for acute and chronic pain. Scores were recorded by making a handwritten mark on a 10-cm line that represents a continuum between “no pain” and “worst pain.” Descriptive statistics such as standard deviation and range values were computed for normally distributed data and the mean value was compared using “ t independent” tests. Frequency of categorical data was compared using “Chi-square/Fisher’s exact” tests. Nonnormal data, median values, and interquartile range were computed using nonparametric “Mann–Whitney tests.” All statistical analyses were carried out using STATA software version 12.0 (STATA CORP, Texas, US). For all statistical tests, probability of P < 0.05 was considered statistically significant.

Total laparoscopic hysterectomy (TLH) has emerged as a viable alternative to total abdominal hysterectomy. TLH offers advantages over the abdominal route in women requiring total hysterectomy for benign diseases, particularly with respect to minor perioperative complications, blood loss, and hospital stay.[ 1 ] Laparoscopy ensures faster recovery, fewer complications, and less pain as compared to laparotomy. This mode is still not devoid of pain and better pain control in postoperative period is still sought. In addition to the discomfort at the port-site incisions, few authors report that 80% of the patients require opioid analgesia after laparoscopic surgery.[ 2 3 ] Opioid-related side effects might delay mobilization, increase the duration of hospital stay, and delay recovery, thereby diminishing the benefits of laparoscopic procedures. Therefore, the use of opioid analgesics should be minimized.[ 4 ] Excess use of nonsteroidal anti-inflammatory drugs (NSAIDS) is also not devoid of side effects. Systematic analgesics such as NSAIDs and opioids cannot directly block the visceral nociception despite dose regulation under patient-controlled analgesia. It is reasonable that direct block of the uterosacral plexus through injection of a prolonged half-life analgesic can improve pain relief to enhance recovery and reduce opioid-related systemic side effects.[ 5 ] Infiltration of local analgesia intraoperatively has been found to reduce postoperative pain in several studies.[ 4 6 7 ] Intraperitoneal local anesthetic was introduced in the early 1950s, and it has since been used in various surgical procedures. In gynecologic laparoscopy, local anesthetic instillation into the intraperitoneal space and local injection into the incision site are common. After uterine surgery, visceral pain intensity is maximal, and most patients complain of lower abdominal pain. Visceral pain is transmitted by the pelvic visceral plexus, which is derived from the hypogastric plexus associated with the uterus, vagina, rectum, and bladder. The uterus receives primary innervation from the uterosacral plexus (Lee–Frankenhauser plexus), which is located near the lateral side of the uterine cervix within the uterosacral ligament and which plays an important role in pain transmission. Infiltration of vaginal vault with 0.25% bupivacaine causes sensory blockade of uterosacral plexus and reduces postoperative pain. With this concept, vaginal vault infiltration with local anesthetic agent after TLH is expected to reduce postoperative pain and may decrease the requirement of opioid use. Therefore, this randomized control study was done to evaluate the efficacy of infiltration of bupivacaine in the vaginal vault after TLH to reduce postoperative pain.

In this study, 60 patients requiring TLH were randomized into two groups using a computer-generated randomization program. Group I (intervention group) received bupivacaine infiltration to vaginal vault after TLH, and Group II (Control group) did not receive bupivacaine infiltration to vaginal vault. The patients in the two groups were comparable in terms of age, BMI, parity, and other baseline characteristics. The baseline characteristics of both the groups are mentioned in Table 1 . Patient characteristics in both the groups *Failed medical management. BMI: Body mass index, PBAC: Pictorial blood assessment chart, AUB: Abnormal uterine bleeding, FIGO: International federation of gynecology and obstetrtics, CIN: Cervical intraepithelial neoplasia Most of the patients were operated for abnormal uterine bleeding with failed medical management, classification based on POLYP, Adenomyosis, Leiomyoma, Malignancy and hyperplasia, Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, and Not yet classified (PALMCOEIN) given by International Federation of Gynecology and Obstetrtics (FIGO), as mentioned in Table 1 . There are nine categories, which are arranged according to the acronym PALM-COEIN. One patient was operated for cervical intraepithelial neoplasia-3. The difference between mean values of estimated blood loss and operating time was not statistically significant in both the groups ( P > 0.005). The operative characteristics in both the groups are depicted in Table 2 . Intra operative findings in both the groups TLH: Total laparoscopic hysterectomy All the patients in Group I (intervention group) had a pain VAS score <4 when compared to around 93% of the patients in Group II (control group) at 1 h postsurgery ( P = 0.49). Similarly, all the patients in Group I had a VAS score <4 when compared to 86.6% of the patients in Group II at 3 h postsurgery ( P = 0.112). The VAS score was <4 in significantly more number of patients, in the intervention group as compared to the control group at 6 h postsurgery (97% vs. 30%), with the P = 0.001. Similarly, the VAS score of less than 4 was significantly more common in Group I (96.7%) as compared to patients in Group II (10%) at 12 h postsurgery ( P = 0.001). 36.7% of the patients in Group I had a VAS score <4 when compared to 3.3% of the patients in Group II ( P = 0.002) at 24 h postsurgery. The number of patients having VAS score <4 at 6 th , 12 th , and 24 th h of postoperative period was significantly more in the intervention group [ Table 3 ]. Hence, infiltration with local analgesia effectively reduced the intensity of postoperative pain in postoperative period. Comparison of number of patients having visual analog scale score <4 in both the groups VAS: Visual analog scale The mean value of VAS score at 1 st h after completion of surgery in Group I was 1.53 ± 0.507, whereas in Group II was 2.17 ± 0.74 ( P < 0.001). Similarly, the mean values of VAS score at 3 rd , 6 th , 12 th , and 24 th h were calculated and compared between the two groups and found to be statistically significant at all these times ( P 0.05). Visual analog scale score at 1 st , 3 rd , 6 th , 12 th and 24 th h in both the groups VAS: Visual analog scale Five patients in the intervention group (I) received additional opioid analgesia in the postoperative period, whereas 27 patients in the control group (II) required the same in postoperative period ( P < 0.05). In Group I, although there was an increase in the mean value of VAS score from 3 rd to 6 th , 12 th , and 24 th h, the mean value was 4 in Group II. Thus, additional requirement of opioid analgesia for postoperative pain was more in Group II as compared to Group I ( P < 0.05) [ Table 5 ]. Patients requiring rescue analgesia in both the groups VAS: Visual analog scale

Overall, the present randomized control trial demonstrates that vaginal cuff infiltration with local anesthetic is a feasible and safe option for postoperative pain relief. Infiltration of the vaginal vault with 10 ml of 0.25% bupivacaine, at the end of laparoscopic hysterectomy, significantly increases the number of women who experience minimal postoperative pain for the first 24 h after surgery, with no impairments in surgical outcome. It also diminishes the requirement of additional analgesia/opioid usage. Nil. There are no conflicts of interest.

TLH was established from 1989 onward.[ 8 ] While contemporary changes such as a shift to minimally invasive modalities have resulted in improved outcomes, it is still associated with significant postoperative discomfort. Recently, there have been multiple attempts to institute strategies that reduce postoperative pain after a hysterectomy. Preoperative transverse abdominis plane blocks, injection of local anesthetic to port sites, and reduced port caliber are few examples to control postoperative pain. Most of these approaches are focused on decreasing discomfort on the abdominal wall. However, anatomical sites that also undergo significant tissue manipulation, such as the vaginal cuff and pelvic dissection sites, are often overlooked for targeted pain control despite the presence of nociceptors in the region. We propose the vaginal cuff and parametria as sites for targeted pain control with the objective of reducing noxious stimuli from the pelvic dissection and vaginal cuff closure. The present study was a randomized controlled trial performed to assess the efficacy of bupivacaine, a long-acting amide local anesthetic, infiltration in the vaginal vault in reducing postoperative pain after TLH and to see if it decreases the requirement of opioid use. Severity of pain was recorded using VAS score (0 indicating no pain and 10 indicating unbearable pain) at 1 st , 3 rd , 6 th , 12 th , and 24 th h after surgery. It was reported that the vaginal vault infiltration with bupivacaine is effective in reducing postoperative pain and bypassing the requirement of opioid analgesia, thereby preventing opioid-related side effects in early postoperative period. Kilpiö et al . performed a single-center, randomized trial, in which women assigned to laparoscopic hysterectomy were randomly divided into two groups.[ 9 ] In the intervention group ( n = 41), the vaginal cuff was infiltrated with 10 ml of ropivacaine (7.5 mg/ml) at four points, in addition to trocar-site anesthesia. In the control group ( n = 40), only trocar incisions were infiltrated with local anesthetic. The primary outcomes were postoperative opioid (oxycodone) use and record postoperative pain at 1, 3, 6, 12, and 24 h of surgery using VAS. Secondary outcomes were emesis, bleeding, operative time, time to discharge, and complications. VAS scores for pain were less than 3 during the entire postoperative study period in 17 patients in the intervention group and 8 patients in the control group, which was statistically significant ( P = 0.04). Otherwise, there were no significant differences between the groups in VAS scores for pain, the use of opioids, or in any other variables. In contrast to this, our study showed significantly decreased requirement of additional analgesia apart from less VAS scores at all times in postoperative period in the intervention group. Kwack Young et al . compared postoperative pain intensity at 2 h after administration of ropivacaine or placebo solution into uterosacral ligaments at the end of laparoscopic-assisted vaginal hysterectomy.[ 5 ] The mean pain scores in the ropivacaine group ( n = 20) were significantly less as compared to the saline group ( P = 0.023). The patients who received saline required more opioid analgesia in comparison to those who received ropivacaine ( P = 0.025). Radtke et al .[ 10 ] performed a paracervical block before laparoscopic hysterectomy and compared postoperative pain scores. Postoperative pain scores (VAS scores) were significantly lower in the treatment group at 30 and 60 min ( P < 0.001). Other interventions which have been found to be effective are infiltration of the muscular fasciae at the wound side, by the end of the laparoscopic surgery with levo-bupivacain, as reported by Sugihara et al .[ 11 ] bupivacaine block after the trocar incision closure by Tam et al .;[ 12 ] cold nebulization with ropivacaine before and after surgery by Somain et al .;[ 13 ] and intraperitoneal bupivacaine infiltration by Roy et al .[ 14 ] Few patients could not reliably confirm their VAS score in 1 st h as the effect of general anesthesia took time to wean off. However, the mean VAS score at 1 st h postsurgery calculated in our study was statistically significant. Hence, this study shows that pain control is effective even in the first few hours of surgery, better than our anticipation. Similar studies performed by various authors like Radtke et al .[ 10 ] calculated VAS score at 30 and 60 min interval postsurgery and found to be statistically significant. All patients in group I required low quantities of postoperative opioid analgesics when compared to Group II ( P < 0.05). Therefore, this study highlights the beneficial use of local vault infiltration with bupivacaine after TLH in improving pain control from early postoperative hours till 24 h. The results are especially encouraging as this is the period when maximum additional analgesics are required. The results were similar whether or not, the additional procedure of BSO was performed. Hence, local vault infiltration with bupivacaine is recommended for TLH with or without BSO.