- Email: [email protected]
Paracervical Block as a Strategy to Reduce Postoperative Pain after Laparoscopic Hysterectomy: A Randomized Controlled Trial
Accepted Manuscript
Para-cervical block as a strategy to reduce postoperative pain after laparoscopic hysterectomy: A randomized controlled trial Steven RADTKE MD , Todd BOREN MD , Stephen DEPASQUALE MD PII: DOI: Reference:
S1553-4650(18)31401-8 https://doi.org/10.1016/j.jmig.2018.12.001 JMIG 3699
To appear in:
The Journal of Minimally Invasive Gynecology
Received date: Revised date: Accepted date:
28 September 2018 19 November 2018 3 December 2018
Please cite this article as: Steven RADTKE MD , Todd BOREN MD , Stephen DEPASQUALE MD , Para-cervical block as a strategy to reduce postoperative pain after laparoscopic hysterectomy: A randomized controlled trial, The Journal of Minimally Invasive Gynecology (2018), doi: https://doi.org/10.1016/j.jmig.2018.12.001
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title page Para-cervical block as a strategy to reduce postoperative pain after laparoscopic hysterectomy:
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A randomized controlled trial
Authors: Steven RADTKE, MD1 ; Todd BOREN, MD1 ; Stephen DEPASQUALE, MD1
Affiliations: 1: University of Tennessee College of Medicine, Chattanooga. Department of
The authors report no conflict of interest. This study received no funding.
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Obstetrics and Gynecology. 979 E. 3rd Street – Suite C720. Chattanooga, TN 37403
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Abstract accepted to the 2018 AAGL meeting in Las Vegas, NV for an open communication
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session.
Corresponding Author: Steven Radtke, MD. Work address: Department of Ob/Gyn. 4801 Email: [email protected]
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Alberta Ave. El Paso, Texas 79905 Cellphone: 217-725-4940
Registered on ClinicalTrials.gov. Registration date 1/23/2017. Enrollment started 8/1/2017, ID
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number NCT03027661 URL: https://clinicaltrials.gov
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IRB# 16-130. Initial date of approval Dec 2016. Abstract word count: 390 Body word count: 1572 Short title: Para-cervical block for pain reduction after laparoscopic hysterectomy Keywords: block ; bupivacaine ; discomfort ; hysterectomy ; nerve Word count Abstract: 285
Body: 1917
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PRECIS Performing a para-cervical block using 10mL of 0.5% bupivacaine prior to total laparoscopic
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hysterectomy significantly reduces immediate postoperative pain.
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Abstract: Study Objective: To determine if performing a para-cervical block with 0.5% bupivacaine prior to laparoscopic hysterectomy reduces post-operative pain.
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Design: Double-blind randomized controlled trial (Canadian Task Force classification I). Setting: University affiliated hospital.
Patients: Between 18 and 65 years of age scheduled to undergo total laparoscopic hysterectomy for benign indications.
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Interventions: Eligible patients were allocated to control or treatment groups using block
randomization. Surgeon administered injection of either 0.9% NaCl or 0.5% bupivacaine into the cervical stroma at 3 and 9 o’clock after general anesthesia was established. Pain was assessed using a visual analogue scale with a range from 0 to 10 at 30 and 60 minutes after
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extubation.
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Measurements and results: 41 patients met criteria for analysis. Based on randomization, n=20 were allocated to the control arm and n=21 to treatment arm. We used T-student and Pearson
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Chi-Square to ensure both groups were homogenous to age (46.5 v 46 p=.87), BMI (35 v 32.7 p=.45), minutes of operating time (132.5 v 119.7 p=.11), specimen weight (138.8g v 160.6g
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p=.44), and history of cesarean (p=.58). Pain scores at 30 minutes (5.7 v 3.2 p=.01) and 60 minutes (5.9 v 2.3 p<.001) were significantly lower in the treatment arm. We dichotomized
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results depending on whether patients had successful postoperative pain control, defined as an average pain score of 4 or less. Chi-square test was used for comparison. Using this definition, 25% of patients had successful pain control in the placebo group versus 71.4% in the treatment group. This was statistically significant (p=.003). Mean length of hospital stay (0.65 v 0.86 p=.44) was not statistically different.
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Conclusion: Performing a para-cervical block with 0.5% bupivacaine prior to laparoscopic hysterectomy significantly reduces immediate postoperative pain.
number NCT03027661 URL: https://clinicaltrials.gov
Introduction
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Registered on ClinicalTrials.gov. Registration date 1/23/2017. Enrollment started 8/1/2017, ID
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Pain control after surgery is of paramount importance. Not only it is a key factor in enhanced postoperative recovery protocols, but it also plays a significant role in patient satisfaction. 1 Hysterectomy is one of the most common surgical procedures in the United States, with over 600,000 performed annually. 2,3 While contemporary changes such as a shift to minimally
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invasive modalities have resulted in improved outcomes, it is still associated with significant postoperative discomfort. 4 Recently, there have been multiple attempts to institute strategies
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that reduce postoperative pain after a hysterectomy. Examples of these include preoperative transverse abdominis plane (TAP) blocks, injection of local anesthetic to port sites, reduced port
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caliber, etc. 5-8 Most of these approaches are focused on decreasing discomfort on the
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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
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control despite the presence of nociceptors in the region.9 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. To achieve this, we suggest utilizing a paracervical block with 0.5% bupivacaine before scheduled total laparoscopic hysterectomies. The diffusion pathway of substances injected into the cervix has been previously described by Kimmig et al. and has shown to be a promising inoculation site to reach our proposed anatomic
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regions. 10 We chose bupivacaine given its pharmacokinetic profile with onset of action within 15 minutes and duration for up to 9 hours. 11 We hypothesize that immediate postoperative pain will be reduced when using this technique. Materials and Methods
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Approval from the institutional review board was obtained and registration to
clinicaltrials.gov was completed. The setting for the study was a university affiliated community hospital with a high volume of gynecologic surgery, and the site to an Obstetrics and
Gynecology residency program and a Minimally Invasive Gynecologic Surgery fellowship. A
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randomized double blind controlled trial was designed. Enrollment began in August, 2017.
Eligible patients included those between 18 and 65 years of age undergoing a total laparoscopic hysterectomy for benign indications, with or without salpingo-oophorectomy. Acceptable concomitant procedures included excision of endometriosis and appendectomy. Scheduled
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procedures in addition to the hysterectomy that deemed patients ineligible included those
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involving extensive additional tissue manipulation such as pelvic lymph node dissection (LND), laparoscopic pelvic floor repair procedures (uterosacral ligament suspension and
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sacrocolpopexy) or any vaginal procedures (anterior or posterior repair, mid-urethral slings, etc.). Patients who underwent intraoperative conversion to laparotomy were excluded.
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Additional exclusion criteria involved patients in which malignancy was detected intraoperatively resulting in an unscheduled LND, inability to perform the para-cervical block due to anatomic
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abnormalities (absent/flush cervix), known allergy to amide anesthetics and intraoperative inadvertent injury to gastrointestinal or urologic tract that necessitated repair. An invitation to participate in the study was extended to all eligible patients in the preoperative area by one of the research team members. Patients who consented to participate were allocated to either a treatment or placebo group in a sequential fashion using a previously generated masked list that was created via block randomization with block sizes 4:6. A numerically sequenced sealed and
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opaque envelope containing the assigned group based on the original randomization list was handed to the circulating nurse, who prepared a 10mL syringe labeled “Research” filled with either 10mL of 0.5% bupivacaine with epinephrine or 10mL of normal saline. The solutions were visually indistinguishable after preparation. The envelope was then resealed and kept with
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the data collection sheet. Patient, surgeon, anesthesiologist, research staff and PACU personnel were all blinded to allocation. The intervention was performed under general
anesthesia, prior to starting the surgery. The contents of the “Research” syringe were injected by the primary surgeon into the cervical stroma at 3 and 9 o’clock with a depth of 2 to 3 cm.
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Each side was injected with 5 mL of the solution. Because the assistant surgeon was working on trocar insertion simultaneously as the primary surgeon injected the cervix, there was no measurable interval between injection time and surgery start. A RUMI II (Cooper Surgical, CT, USA) uterine manipulator was then inserted and the remainder of the procedure was carried
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out. All hysterectomies were performed by two high-volume surgeons with subspecialty training in gynecologic oncology using the same operative technique. Cases were performed using an
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initial 12 mm trocar in the left upper quadrant that was inserted using open technique, and three accessory 8 mm trocars inserted under direct laparoscopic visualization. Port sites were
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injected with local anesthetic prior to incision. Pneumoperitoneum was maintained at 15mmHg. We routinely dissect the retroperitoneal space to identify the ureters, and subsequently ligate
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the uterine artery at its origin bilaterally. This was done for all cases in the cohort. Every colpotomy was created using monopolar energy and closed horizontally using barbed suture in
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a running fashion. A tensiometer was not used for this trial. All suture was tightened using visual cues, until there was no further give from sutured tissue. Extubation time was noted and a stopwatch was started at this point. Pain was assessed by a member of the research team at 30 and 60 minutes post-extubation via the visual analogue scale (VAS), which had also been presented and described to patients preoperatively through a standard script that included the explanation of 0 being no pain at all and 10 being the worst pain ever. Intraoperative and
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postoperative medication management per anesthesia personnel was not modified because of the trial and all patients underwent the same care protocol. Based on previous publications, it was determined that the expected mean pain score on postoperative day 0 after a TLH was 6 on the VAS, with a standard deviation (SD) of 2. 12,13 In
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order to detect at least a 40% reduction in postoperative pain between groups, with a
significance level of 5% and a power of 80%, a sample of 32 was required. Data collected for each patient included age, BMI, number of previous cesarean sections (CS), indication for surgery, other procedures performed, total operating time, final pathology, and weight of
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specimen. At the end of the accrual period, all envelopes containing patient groups were
unsealed and group allocation was attached to the data set. After separating subjects by allocation, T-Student was used to ensure both groups were homogenous to age, BMI, uterine weight and operating time. Pearson Chi-square cross tabulation was used to warrant that
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groups did not differ significantly regarding number of CS performed. This measure was taken due to the association between history of CS and the presence of pelvic adhesions which may
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lead to longer operating times and could have an effect on postoperative pain.
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Pain scores from the VAS were compared between groups using T-Student. We performed comparisons between the scores at 30 and 60 minutes. Additionally, prior to
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commencing accrual we had arbitrarily defined successful postoperative pain control as an average of the two measured pain scores of 4 or less, and analyzed this as a binary outcome
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using Pearson Chi-square. Univariate linear regression was also performed using preoperative diagnosis of pelvic pain as a covariate. Overnight admission to the hospital was analyzed as a binary variable using Pearson Chi-square All statistical analysis was performed using SPSS version 24 (IBM, Armonk, NY, USA).
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Results Accrual commenced in August 2017 and was completed on June 2018. During the recruitment period, 50 patients were found to be eligible out of which 3 declined to participate and 6 were excluded (see figure 1). The remaining 41 cases were separated into groups depending on
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treatment allocation, with 20 being in the placebo (NaCl) group and 21 in the bupivacaine group. Both groups were homogenous to mean age (46.5 v 46 p =.87), BMI (35.0 v 32.7 p=.45),
minutes of operating time (132.5 v 119.7 p = .11), specimen weight (138.8g v 160.6g p=.44), and number of CS (p=.58). Indications for surgery by group are listed in table 1. Postoperative
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pain scores were significantly lower in the treatment group in both comparisons which included an evaluation at 30 minutes (5.7 v 3.2 p=.01), and 60 minutes (5.9 v 2.3 p<.001) (see figure 2). When analyzing successful pain control using our predefined criteria of an average pain score of 4 or less, 25% met criteria in the placebo group, versus 71.4% in the treatment group. This
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was statistically significant (p=.003) (see figure 3). The effect of the diagnosis of preoperative pelvic pain as a covariate on this comparison was not significant (p=.28). Mean length of
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hospital stay in days was not significantly different between groups (0.65 v 0.86 p=.44). When analyzing this outcome in a binary fashion on whether patients stayed overnight or not, there
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either group.
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was also no difference (65% v 61.9% p =.83) (see table 2). There were no loss of patients from
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Discussion
We found a significant reduction of immediate postoperative pain in the treatment group. Much of the recent literature has focused on strategies to decrease pain in the abdominal wall. For TLHs specifically, a significant portion of the tissue insults originate from the parametrial dissection, creation of the vaginal cuff, and cuff closure. These areas can be readily reached
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with local anesthetic by infiltrating the cervix preoperatively. Our results suggest that this anatomic location is a promising option for targeted pain control. Although we did not detect a difference in length of hospital stay between groups, it is important to note that in the majority of cases decision for overnight admission is not based on pain and is already predetermined prior
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to surgery. For this study, we chose bupivacaine instead of its liposomal counterpart because of lower cost and ease of blinding. Additionally, our main objective was to investigate pain reduction in the immediate postoperative period. Taking the half-life of bupivacaine into
consideration, we did not expect to see any changes beyond postoperative day 1. However, the
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results from this study can serve as justification to perform further research using the higher costing liposomal bupivacaine.
Procedures that could potentially benefit by using this technique include the other routes of hysterectomy, as well as cases in which a posterior colpotomy is created for tissue extraction.
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Further research is warranted.
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The results presented in this study are strong given the double-blind methodology and the use of block randomization. Also, the surgical technique was standardized in every case, which is an
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important aspect when analyzing outcomes after surgery. Furthermore, excluding patients undergoing concomitant major pelvic procedures allowed for isolation of the pain generated
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from the hysterectomy, reducing potential confounding factors and facilitating comparisons. Potential limitations encompass the fact that we used VAS scores as the primary outcome,
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which although a validated pain assessment tool, is still a subjective measurement.14-16 Also, despite the results clearly demonstrating a reduction in immediate postoperative pain, data regarding pain scores or narcotic use beyond the first postoperative hour was not collected for this trial. Additionally, the fact that surgical technique was standardized in all cases may limit the generalizability of the results. However, we believe that this first step is important in order to avoid confounders resulting from variations in operative method. Further direction would include
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expanding the pool of participating surgeons, utilizing a longer-acting local anesthetic such as the liposomal form of bupivacaine, and analyzing outcomes including opioid use beyond postoperative day 1.
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Conclusion
Performing a para-cervical block with 0.5% bupivacaine before a total laparoscopic
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hysterectomy significantly reduces immediate postoperative pain.
Acknowledgments
Miranda Blevins DO : University of Tennessee College of Medicine, Chattanooga. No funding.
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Zineb Green MD: University of Tennessee College of Medicine, Chattanooga. No funding.
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Sarah Boyd MD: University of Tennessee College of Medicine, Chattanooga. No funding.
1.
Maher DP, Wong W, Woo P, et al. Perioperative factors associated with HCAHPS responses of 2,758 surgical patients. Pain Med. 2015;16(4):791-801. ACOG Committee Opinion No. 444: choosing the route of hysterectomy for benign disease. Obstet Gynecol. 2009;114(5):1156-1158. Whiteman MK, Hillis SD, Jamieson DJ, et al. Inpatient hysterectomy surveillance in the United States, 2000-2004. Am J Obstet Gynecol. 2008;198(1):34 e31-37. Schindlbeck C, Klauser K, Dian D, Janni W, Friese K. Comparison of total laparoscopic, vaginal and abdominal hysterectomy. Arch Gynecol Obstet. 2008;277(4):331-337. Acton JN, Salfinger SG, Tan J, Cohen PA. Outcomes of Total Laparoscopic Hysterectomy Using a 5-mm Versus 10-mm Laparoscope: A Randomized Control Trial. J Minim Invasive Gynecol. 2016;23(1):101-106.
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2.
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References
3. 4. 5.
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Andrea Humphrey-Nelson CST: Erlanger Hospital. No funding.
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9.
10.
11.
12.
13. 14.
15.
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16.
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8.
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7.
Bacal V, Rana U, McIsaac DI, Chen I. Transversus Abdominis Plane Block for Post Hysterectomy Pain: A Systematic Review and Meta-Analysis. J Minim Invasive Gynecol. 2018. Charlton S, Cyna AM, Middleton P, Griffiths JD. Perioperative transversus abdominis plane (TAP) blocks for analgesia after abdominal surgery. Cochrane Database Syst Rev. 2010(12):CD007705. Torup H, Bogeskov M, Hansen EG, et al. Transversus abdominis plane (TAP) block after robotassisted laparoscopic hysterectomy: a randomised clinical trial. Acta Anaesthesiol Scand. 2015;59(7):928-935. Ripperda CM, Jackson LA, Phelan JN, Carrick KS, Corton MM. Anatomic relationships of the pelvic autonomic nervous system in female cadavers: clinical applications to pelvic surgery. Am J Obstet Gynecol. 2017;216(4):388 e381-388 e387. Kimmig R, Aktas B, Buderath P, Rusch P, Heubner M. Intraoperative navigation in robotically assisted compartmental surgery of uterine cancer by visualisation of embryologically derived lymphatic networks with indocyanine-green (ICG). J Surg Oncol. 2016;113(5):554-559. Jain S, Nazir N, Singh S, Sharma S. A prospective randomised controlled study for evaluation of high-volume low-concentration intraperitoneal bupivacaine for post-laparoscopic cholecystectomy analgesia. Indian J Anaesth. 2018;62(2):109-114. Chung JH, Baek JM, Chung K, et al. A comparison of postoperative pain after transumbilical single-port access and conventional three-port total laparoscopic hysterectomy: a randomized controlled trial. Acta Obstet Gynecol Scand. 2015;94(12):1290-1296. Choi JB, Kang K, Song MK, Seok S, Kim YH, Kim JE. Pain Characteristics after Total Laparoscopic Hysterectomy. Int J Med Sci. 2016;13(8):562-568. Page MG, Katz J, Stinson J, Isaac L, Martin-Pichora AL, Campbell F. Validation of the numerical rating scale for pain intensity and unpleasantness in pediatric acute postoperative pain: sensitivity to change over time. J Pain. 2012;13(4):359-369. Thong ISK, Jensen MP, Miro J, Tan G. The validity of pain intensity measures: what do the NRS, VAS, VRS, and FPS-R measure? Scand J Pain. 2018;18(1):99-107. Karcioglu O, Topacoglu H, Dikme O, Dikme O. A systematic review of the pain scales in adults: Which to use? Am J Emerg Med. 2018;36(4):707-714.
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Figure legends
Figure 1: Research cohort flow diagram. * Intraoperative conversion to open (n=1), Unable to find cervix (n=3), Age above limit after randomization (n=1). **Inadvertently did not inject cervix
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(n=1).
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Figure 2: Mean pain scores at 30 and 60 minutes postoperatively
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Figure 3: Percentage of successful pain control within each group. Successful pain control
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defined as an average postoperative pain score of 4 or less.
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Table 1: Indications for procedure separated by group Control
Treatment
AUB
11
11
Pelvic Pain
3
1
Leiomyoma
2
6
Cervical Dysplasia
0
Pelvic mass
8
Other
3
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Indication
4 4
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1
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AUB = Abnormal uterine bleeding. Some patients had more than one indication.
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Table 2: Summary of data Treatment (SD)
P value
Age
46.5 (9.8)
43.0 (10.4)
p=.87
BMI
30.0 (9.8)
32.7 (9.8)
p=.45
Operating time
132.5 (33.1)
119.7 (15.5)
p=.11
Specimen weight
138.8 (82.2)
160.6 (97.8)
Length of hospital
0.65 (0.48)
0.86 (1.10)
Pain at 30 minutes
5.7 (2.8)
3.2 (3.4)
Pain at 60 minutes
5.9 (3.0)
Average pain
5.8 (2.7)
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stay
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Control (SD)
p=.44 p=.44
p=.01
2.3 (2.8)
P<.001
2.8 (2.8)
P=.002
BMI = Body mass index. Operating time in minutes. Specimen weight in grams. Length of
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hospital stay in nights spent in hospital. Pain represented by 0-10 score in the visual analogue
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scale.
Para-cervical block as a strategy to reduce postoperative pain after laparoscopic hysterectomy: A randomized controlled trial Steven RADTKE MD , Todd BOREN MD , Stephen DEPASQUALE MD PII: DOI: Reference:
S1553-4650(18)31401-8 https://doi.org/10.1016/j.jmig.2018.12.001 JMIG 3699
To appear in:
The Journal of Minimally Invasive Gynecology
Received date: Revised date: Accepted date:
28 September 2018 19 November 2018 3 December 2018
Please cite this article as: Steven RADTKE MD , Todd BOREN MD , Stephen DEPASQUALE MD , Para-cervical block as a strategy to reduce postoperative pain after laparoscopic hysterectomy: A randomized controlled trial, The Journal of Minimally Invasive Gynecology (2018), doi: https://doi.org/10.1016/j.jmig.2018.12.001
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title page Para-cervical block as a strategy to reduce postoperative pain after laparoscopic hysterectomy:
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A randomized controlled trial
Authors: Steven RADTKE, MD1 ; Todd BOREN, MD1 ; Stephen DEPASQUALE, MD1
Affiliations: 1: University of Tennessee College of Medicine, Chattanooga. Department of
The authors report no conflict of interest. This study received no funding.
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Obstetrics and Gynecology. 979 E. 3rd Street – Suite C720. Chattanooga, TN 37403
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Abstract accepted to the 2018 AAGL meeting in Las Vegas, NV for an open communication
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session.
Corresponding Author: Steven Radtke, MD. Work address: Department of Ob/Gyn. 4801 Email: [email protected]
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Alberta Ave. El Paso, Texas 79905 Cellphone: 217-725-4940
Registered on ClinicalTrials.gov. Registration date 1/23/2017. Enrollment started 8/1/2017, ID
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number NCT03027661 URL: https://clinicaltrials.gov
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IRB# 16-130. Initial date of approval Dec 2016. Abstract word count: 390 Body word count: 1572 Short title: Para-cervical block for pain reduction after laparoscopic hysterectomy Keywords: block ; bupivacaine ; discomfort ; hysterectomy ; nerve Word count Abstract: 285
Body: 1917
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PRECIS Performing a para-cervical block using 10mL of 0.5% bupivacaine prior to total laparoscopic
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PT
ED
M
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CR IP T
hysterectomy significantly reduces immediate postoperative pain.
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Abstract: Study Objective: To determine if performing a para-cervical block with 0.5% bupivacaine prior to laparoscopic hysterectomy reduces post-operative pain.
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Design: Double-blind randomized controlled trial (Canadian Task Force classification I). Setting: University affiliated hospital.
Patients: Between 18 and 65 years of age scheduled to undergo total laparoscopic hysterectomy for benign indications.
AN US
Interventions: Eligible patients were allocated to control or treatment groups using block
randomization. Surgeon administered injection of either 0.9% NaCl or 0.5% bupivacaine into the cervical stroma at 3 and 9 o’clock after general anesthesia was established. Pain was assessed using a visual analogue scale with a range from 0 to 10 at 30 and 60 minutes after
M
extubation.
ED
Measurements and results: 41 patients met criteria for analysis. Based on randomization, n=20 were allocated to the control arm and n=21 to treatment arm. We used T-student and Pearson
PT
Chi-Square to ensure both groups were homogenous to age (46.5 v 46 p=.87), BMI (35 v 32.7 p=.45), minutes of operating time (132.5 v 119.7 p=.11), specimen weight (138.8g v 160.6g
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p=.44), and history of cesarean (p=.58). Pain scores at 30 minutes (5.7 v 3.2 p=.01) and 60 minutes (5.9 v 2.3 p<.001) were significantly lower in the treatment arm. We dichotomized
AC
results depending on whether patients had successful postoperative pain control, defined as an average pain score of 4 or less. Chi-square test was used for comparison. Using this definition, 25% of patients had successful pain control in the placebo group versus 71.4% in the treatment group. This was statistically significant (p=.003). Mean length of hospital stay (0.65 v 0.86 p=.44) was not statistically different.
ACCEPTED MANUSCRIPT
Conclusion: Performing a para-cervical block with 0.5% bupivacaine prior to laparoscopic hysterectomy significantly reduces immediate postoperative pain.
number NCT03027661 URL: https://clinicaltrials.gov
Introduction
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Registered on ClinicalTrials.gov. Registration date 1/23/2017. Enrollment started 8/1/2017, ID
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Pain control after surgery is of paramount importance. Not only it is a key factor in enhanced postoperative recovery protocols, but it also plays a significant role in patient satisfaction. 1 Hysterectomy is one of the most common surgical procedures in the United States, with over 600,000 performed annually. 2,3 While contemporary changes such as a shift to minimally
M
invasive modalities have resulted in improved outcomes, it is still associated with significant postoperative discomfort. 4 Recently, there have been multiple attempts to institute strategies
ED
that reduce postoperative pain after a hysterectomy. Examples of these include preoperative transverse abdominis plane (TAP) blocks, injection of local anesthetic to port sites, reduced port
PT
caliber, etc. 5-8 Most of these approaches are focused on decreasing discomfort on the
CE
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
AC
control despite the presence of nociceptors in the region.9 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. To achieve this, we suggest utilizing a paracervical block with 0.5% bupivacaine before scheduled total laparoscopic hysterectomies. The diffusion pathway of substances injected into the cervix has been previously described by Kimmig et al. and has shown to be a promising inoculation site to reach our proposed anatomic
ACCEPTED MANUSCRIPT
regions. 10 We chose bupivacaine given its pharmacokinetic profile with onset of action within 15 minutes and duration for up to 9 hours. 11 We hypothesize that immediate postoperative pain will be reduced when using this technique. Materials and Methods
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Approval from the institutional review board was obtained and registration to
clinicaltrials.gov was completed. The setting for the study was a university affiliated community hospital with a high volume of gynecologic surgery, and the site to an Obstetrics and
Gynecology residency program and a Minimally Invasive Gynecologic Surgery fellowship. A
AN US
randomized double blind controlled trial was designed. Enrollment began in August, 2017.
Eligible patients included those between 18 and 65 years of age undergoing a total laparoscopic hysterectomy for benign indications, with or without salpingo-oophorectomy. Acceptable concomitant procedures included excision of endometriosis and appendectomy. Scheduled
M
procedures in addition to the hysterectomy that deemed patients ineligible included those
ED
involving extensive additional tissue manipulation such as pelvic lymph node dissection (LND), laparoscopic pelvic floor repair procedures (uterosacral ligament suspension and
PT
sacrocolpopexy) or any vaginal procedures (anterior or posterior repair, mid-urethral slings, etc.). Patients who underwent intraoperative conversion to laparotomy were excluded.
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Additional exclusion criteria involved patients in which malignancy was detected intraoperatively resulting in an unscheduled LND, inability to perform the para-cervical block due to anatomic
AC
abnormalities (absent/flush cervix), known allergy to amide anesthetics and intraoperative inadvertent injury to gastrointestinal or urologic tract that necessitated repair. An invitation to participate in the study was extended to all eligible patients in the preoperative area by one of the research team members. Patients who consented to participate were allocated to either a treatment or placebo group in a sequential fashion using a previously generated masked list that was created via block randomization with block sizes 4:6. A numerically sequenced sealed and
ACCEPTED MANUSCRIPT
opaque envelope containing the assigned group based on the original randomization list was handed to the circulating nurse, who prepared a 10mL syringe labeled “Research” filled with either 10mL of 0.5% bupivacaine with epinephrine or 10mL of normal saline. The solutions were visually indistinguishable after preparation. The envelope was then resealed and kept with
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the data collection sheet. Patient, surgeon, anesthesiologist, research staff and PACU personnel were all blinded to allocation. The intervention was performed under general
anesthesia, prior to starting the surgery. The contents of the “Research” syringe were injected by the primary surgeon into the cervical stroma at 3 and 9 o’clock with a depth of 2 to 3 cm.
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Each side was injected with 5 mL of the solution. Because the assistant surgeon was working on trocar insertion simultaneously as the primary surgeon injected the cervix, there was no measurable interval between injection time and surgery start. A RUMI II (Cooper Surgical, CT, USA) uterine manipulator was then inserted and the remainder of the procedure was carried
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out. All hysterectomies were performed by two high-volume surgeons with subspecialty training in gynecologic oncology using the same operative technique. Cases were performed using an
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initial 12 mm trocar in the left upper quadrant that was inserted using open technique, and three accessory 8 mm trocars inserted under direct laparoscopic visualization. Port sites were
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injected with local anesthetic prior to incision. Pneumoperitoneum was maintained at 15mmHg. We routinely dissect the retroperitoneal space to identify the ureters, and subsequently ligate
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the uterine artery at its origin bilaterally. This was done for all cases in the cohort. Every colpotomy was created using monopolar energy and closed horizontally using barbed suture in
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a running fashion. A tensiometer was not used for this trial. All suture was tightened using visual cues, until there was no further give from sutured tissue. Extubation time was noted and a stopwatch was started at this point. Pain was assessed by a member of the research team at 30 and 60 minutes post-extubation via the visual analogue scale (VAS), which had also been presented and described to patients preoperatively through a standard script that included the explanation of 0 being no pain at all and 10 being the worst pain ever. Intraoperative and
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postoperative medication management per anesthesia personnel was not modified because of the trial and all patients underwent the same care protocol. Based on previous publications, it was determined that the expected mean pain score on postoperative day 0 after a TLH was 6 on the VAS, with a standard deviation (SD) of 2. 12,13 In
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order to detect at least a 40% reduction in postoperative pain between groups, with a
significance level of 5% and a power of 80%, a sample of 32 was required. Data collected for each patient included age, BMI, number of previous cesarean sections (CS), indication for surgery, other procedures performed, total operating time, final pathology, and weight of
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specimen. At the end of the accrual period, all envelopes containing patient groups were
unsealed and group allocation was attached to the data set. After separating subjects by allocation, T-Student was used to ensure both groups were homogenous to age, BMI, uterine weight and operating time. Pearson Chi-square cross tabulation was used to warrant that
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groups did not differ significantly regarding number of CS performed. This measure was taken due to the association between history of CS and the presence of pelvic adhesions which may
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lead to longer operating times and could have an effect on postoperative pain.
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Pain scores from the VAS were compared between groups using T-Student. We performed comparisons between the scores at 30 and 60 minutes. Additionally, prior to
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commencing accrual we had arbitrarily defined successful postoperative pain control as an average of the two measured pain scores of 4 or less, and analyzed this as a binary outcome
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using Pearson Chi-square. Univariate linear regression was also performed using preoperative diagnosis of pelvic pain as a covariate. Overnight admission to the hospital was analyzed as a binary variable using Pearson Chi-square All statistical analysis was performed using SPSS version 24 (IBM, Armonk, NY, USA).
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Results Accrual commenced in August 2017 and was completed on June 2018. During the recruitment period, 50 patients were found to be eligible out of which 3 declined to participate and 6 were excluded (see figure 1). The remaining 41 cases were separated into groups depending on
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treatment allocation, with 20 being in the placebo (NaCl) group and 21 in the bupivacaine group. Both groups were homogenous to mean age (46.5 v 46 p =.87), BMI (35.0 v 32.7 p=.45),
minutes of operating time (132.5 v 119.7 p = .11), specimen weight (138.8g v 160.6g p=.44), and number of CS (p=.58). Indications for surgery by group are listed in table 1. Postoperative
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pain scores were significantly lower in the treatment group in both comparisons which included an evaluation at 30 minutes (5.7 v 3.2 p=.01), and 60 minutes (5.9 v 2.3 p<.001) (see figure 2). When analyzing successful pain control using our predefined criteria of an average pain score of 4 or less, 25% met criteria in the placebo group, versus 71.4% in the treatment group. This
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was statistically significant (p=.003) (see figure 3). The effect of the diagnosis of preoperative pelvic pain as a covariate on this comparison was not significant (p=.28). Mean length of
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hospital stay in days was not significantly different between groups (0.65 v 0.86 p=.44). When analyzing this outcome in a binary fashion on whether patients stayed overnight or not, there
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either group.
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was also no difference (65% v 61.9% p =.83) (see table 2). There were no loss of patients from
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Discussion
We found a significant reduction of immediate postoperative pain in the treatment group. Much of the recent literature has focused on strategies to decrease pain in the abdominal wall. For TLHs specifically, a significant portion of the tissue insults originate from the parametrial dissection, creation of the vaginal cuff, and cuff closure. These areas can be readily reached
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with local anesthetic by infiltrating the cervix preoperatively. Our results suggest that this anatomic location is a promising option for targeted pain control. Although we did not detect a difference in length of hospital stay between groups, it is important to note that in the majority of cases decision for overnight admission is not based on pain and is already predetermined prior
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to surgery. For this study, we chose bupivacaine instead of its liposomal counterpart because of lower cost and ease of blinding. Additionally, our main objective was to investigate pain reduction in the immediate postoperative period. Taking the half-life of bupivacaine into
consideration, we did not expect to see any changes beyond postoperative day 1. However, the
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results from this study can serve as justification to perform further research using the higher costing liposomal bupivacaine.
Procedures that could potentially benefit by using this technique include the other routes of hysterectomy, as well as cases in which a posterior colpotomy is created for tissue extraction.
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Further research is warranted.
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The results presented in this study are strong given the double-blind methodology and the use of block randomization. Also, the surgical technique was standardized in every case, which is an
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important aspect when analyzing outcomes after surgery. Furthermore, excluding patients undergoing concomitant major pelvic procedures allowed for isolation of the pain generated
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from the hysterectomy, reducing potential confounding factors and facilitating comparisons. Potential limitations encompass the fact that we used VAS scores as the primary outcome,
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which although a validated pain assessment tool, is still a subjective measurement.14-16 Also, despite the results clearly demonstrating a reduction in immediate postoperative pain, data regarding pain scores or narcotic use beyond the first postoperative hour was not collected for this trial. Additionally, the fact that surgical technique was standardized in all cases may limit the generalizability of the results. However, we believe that this first step is important in order to avoid confounders resulting from variations in operative method. Further direction would include
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expanding the pool of participating surgeons, utilizing a longer-acting local anesthetic such as the liposomal form of bupivacaine, and analyzing outcomes including opioid use beyond postoperative day 1.
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Conclusion
Performing a para-cervical block with 0.5% bupivacaine before a total laparoscopic
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hysterectomy significantly reduces immediate postoperative pain.
Acknowledgments
Miranda Blevins DO : University of Tennessee College of Medicine, Chattanooga. No funding.
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Zineb Green MD: University of Tennessee College of Medicine, Chattanooga. No funding.
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Sarah Boyd MD: University of Tennessee College of Medicine, Chattanooga. No funding.
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Maher DP, Wong W, Woo P, et al. Perioperative factors associated with HCAHPS responses of 2,758 surgical patients. Pain Med. 2015;16(4):791-801. ACOG Committee Opinion No. 444: choosing the route of hysterectomy for benign disease. Obstet Gynecol. 2009;114(5):1156-1158. Whiteman MK, Hillis SD, Jamieson DJ, et al. Inpatient hysterectomy surveillance in the United States, 2000-2004. Am J Obstet Gynecol. 2008;198(1):34 e31-37. Schindlbeck C, Klauser K, Dian D, Janni W, Friese K. Comparison of total laparoscopic, vaginal and abdominal hysterectomy. Arch Gynecol Obstet. 2008;277(4):331-337. Acton JN, Salfinger SG, Tan J, Cohen PA. Outcomes of Total Laparoscopic Hysterectomy Using a 5-mm Versus 10-mm Laparoscope: A Randomized Control Trial. J Minim Invasive Gynecol. 2016;23(1):101-106.
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2.
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References
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Andrea Humphrey-Nelson CST: Erlanger Hospital. No funding.
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Bacal V, Rana U, McIsaac DI, Chen I. Transversus Abdominis Plane Block for Post Hysterectomy Pain: A Systematic Review and Meta-Analysis. J Minim Invasive Gynecol. 2018. Charlton S, Cyna AM, Middleton P, Griffiths JD. Perioperative transversus abdominis plane (TAP) blocks for analgesia after abdominal surgery. Cochrane Database Syst Rev. 2010(12):CD007705. Torup H, Bogeskov M, Hansen EG, et al. Transversus abdominis plane (TAP) block after robotassisted laparoscopic hysterectomy: a randomised clinical trial. Acta Anaesthesiol Scand. 2015;59(7):928-935. Ripperda CM, Jackson LA, Phelan JN, Carrick KS, Corton MM. Anatomic relationships of the pelvic autonomic nervous system in female cadavers: clinical applications to pelvic surgery. Am J Obstet Gynecol. 2017;216(4):388 e381-388 e387. Kimmig R, Aktas B, Buderath P, Rusch P, Heubner M. Intraoperative navigation in robotically assisted compartmental surgery of uterine cancer by visualisation of embryologically derived lymphatic networks with indocyanine-green (ICG). J Surg Oncol. 2016;113(5):554-559. Jain S, Nazir N, Singh S, Sharma S. A prospective randomised controlled study for evaluation of high-volume low-concentration intraperitoneal bupivacaine for post-laparoscopic cholecystectomy analgesia. Indian J Anaesth. 2018;62(2):109-114. Chung JH, Baek JM, Chung K, et al. A comparison of postoperative pain after transumbilical single-port access and conventional three-port total laparoscopic hysterectomy: a randomized controlled trial. Acta Obstet Gynecol Scand. 2015;94(12):1290-1296. Choi JB, Kang K, Song MK, Seok S, Kim YH, Kim JE. Pain Characteristics after Total Laparoscopic Hysterectomy. Int J Med Sci. 2016;13(8):562-568. Page MG, Katz J, Stinson J, Isaac L, Martin-Pichora AL, Campbell F. Validation of the numerical rating scale for pain intensity and unpleasantness in pediatric acute postoperative pain: sensitivity to change over time. J Pain. 2012;13(4):359-369. Thong ISK, Jensen MP, Miro J, Tan G. The validity of pain intensity measures: what do the NRS, VAS, VRS, and FPS-R measure? Scand J Pain. 2018;18(1):99-107. Karcioglu O, Topacoglu H, Dikme O, Dikme O. A systematic review of the pain scales in adults: Which to use? Am J Emerg Med. 2018;36(4):707-714.
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Figure legends
Figure 1: Research cohort flow diagram. * Intraoperative conversion to open (n=1), Unable to find cervix (n=3), Age above limit after randomization (n=1). **Inadvertently did not inject cervix
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(n=1).
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Figure 2: Mean pain scores at 30 and 60 minutes postoperatively
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Figure 3: Percentage of successful pain control within each group. Successful pain control
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defined as an average postoperative pain score of 4 or less.
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Table 1: Indications for procedure separated by group Control
Treatment
AUB
11
11
Pelvic Pain
3
1
Leiomyoma
2
6
Cervical Dysplasia
0
Pelvic mass
8
Other
3
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Indication
4 4
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1
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AUB = Abnormal uterine bleeding. Some patients had more than one indication.
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Table 2: Summary of data Treatment (SD)
P value
Age
46.5 (9.8)
43.0 (10.4)
p=.87
BMI
30.0 (9.8)
32.7 (9.8)
p=.45
Operating time
132.5 (33.1)
119.7 (15.5)
p=.11
Specimen weight
138.8 (82.2)
160.6 (97.8)
Length of hospital
0.65 (0.48)
0.86 (1.10)
Pain at 30 minutes
5.7 (2.8)
3.2 (3.4)
Pain at 60 minutes
5.9 (3.0)
Average pain
5.8 (2.7)
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stay
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Control (SD)
p=.44 p=.44
p=.01
2.3 (2.8)
P<.001
2.8 (2.8)
P=.002
BMI = Body mass index. Operating time in minutes. Specimen weight in grams. Length of
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hospital stay in nights spent in hospital. Pain represented by 0-10 score in the visual analogue
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scale.