Laparascopic TAP and Hysterectomy Trial #2
Condition: Anesthesia
Study type: Interventional

Summary: 
      More than 600,000 hysterectomies are performed in the United States each year, making it the
      most common non-obstetric major surgery performed on women1. Estimates suggest that at least
      30% of hysterectomies are performed laparoscopically or robotically with an increasing trend
      toward minimally invasive approaches2. While a minimally invasive approach certainly provides
      improved recovery, patients still experience substantial pain and most require opiate
      medications for pain control. Incorporating a multimodal approach to postoperative pain
      management through the use of field nerve blocks is potentially an ideal way to enhance
      recovery and minimize the need for narcotic pain medications.

      Over the past decade, the use of Transversus Abdominis Plane (TAP) blocks as an adjunct for
      postoperative pain management has gained in popularity. First described in 2001 by Dr. Rafi
      of Limerick3, Ireland, TAP blocks are now typically performed by an anesthesiologist with the
      use of ultrasound guidance. The transversus abdominis plane is the neurovascular plane
      between the aponeurosis of the internal oblique and transversus abdominis muscles. Herein lie
      the afferent nociceptor nerve endings of T7-L1. Injection of a 20-30cc volume of anesthetic
      into this plane causes a sensory nerve block to the ipsilateral antero-abdominal wall from
      the costal margin to the symphysis pubis4.

      Clinical trials have documented the validity of using TAP blocks for both open and
      laparoscopic procedures and verified their use for postsurgical pain relief. Studies have
      demonstrated that TAP blocks for both open and laparoscopic hysterectomies are safe and
      efficacious5, 6. In 2011, De Oliveira et al. demonstrated improved quality of recovery for
      women undergoing preoperative ultrasound guided TAP infiltration with ropivacaine at the time
      of laparoscopic hysterectomy7.
    

Detailed description: 
      The primary goal of our study is to demonstrate that laparoscopically assisted bilateral
      Transversus Abdominis Plane (TAP) block using liposomal bupivacaine is superior to
      pre-incisional injection of bupivacaine in terms of peri-operative opiate use, pain scores
      and overall patient satisfaction up to one week following surgery. Our recent research has
      already demonstrated the safety of performing Laparoscopic assisted TAP blocks using
      liposomal bupivacaine.

      This trial will evaluate the efficacy of laparoscopic TAP blocks with liposomal bupivacaine
      by using VAS/numeric pain scores at rest and with cough in recovery at 1 and 2 hours post-op.
      The trial will also utilize an OBAS patient survey, document peri-operative opioid pain
      medication used intraoperatively, in PACU and overnight (if admitted), and assess length of
      time in PACU and same-day discharge versus admission. Opioid pain medication use at home up
      to one week will also be recorded.

      HYPOTHESES/SPECIFIC AIMS The goal of this research project is to prove that a
      laparoscopically delivered TAP block using a combination of Liposomal bupivacaine (Exparel)
      and Bupivacaine is an effective and feasible means for decreasing post-operative pain from
      the immediate post-operative period up to one week.

      The research aims to demonstrate that TAP blocks, when delivered laparoscopically and by
      using Liposomal bupivacaine will show a 20% benefit in post-operative QoR-15 scores on
      post-operative days 1,2 and 7. Other objectives of our study will be to evaluate
      peri-operative narcotic medication dosing, VAS/Numeric pain scores with cough at 1 and 2
      hours in PACU, overnight narcotic use for patients who are admitted and narcotic pain pill
      use at home up to 7 days. Finally, the study aims to confirm that this technique is simple to
      perform, easy to implement and would offer a multi-modal anesthetic alternative to the
      excessive use of post-operative opioid pain medications.

      Patients scheduled for laparoscopic or robotic hysterectomy are screened in the
      pre-anesthesia care unit and if eligible are invited to enroll in the trial. Primary
      Attendings for each surgery will advise patients of the option for the trial at pre-operative
      appointments. Patients who agree to enrollment are appropriately consented and then
      randomized to either control (pre-incisional anesthetic) or study (TAP) group. The patient
      remains blinded to the arm of the study, but OR personnel are advised so as to prepare
      medications and syringes.

      Following induction of anesthesia, the patients in the TAP block arm are prepared and draped
      for surgery allowing for mid-axillary access along the flank bilaterally. Once
      pneumoperitoneum and a port for the laparoscope were established, TAP block is performed
      bilaterally by first palpating the external landmark within the Triangle of Petit, 2 cm above
      the iliac crest. A 21-gauge Stimuplex ® A insulated needle (Braun, Melsungen, Germany) is
      used to enter the transversus abdominis neurovascular plane. Bilaterally, TAP block patients
      receive 10cc of liposomal bupivacaine combined with 10cc of 0.25% bupivacaine and 10cc normal
      saline. Patients in the pre-incisional injection arm of the study receive a total of 20cc of
      0.25% bupivacaine total, equally distributed between the incisions. All patients receive
      routine general anesthesia with opiate use adjusted as determined by the anesthesia provider.
      The anesthesia team is neither blinded nor given specialized protocol instructions. At the
      end of each case, narcotic dosage used is documented.

      All of the patients will receive phone calls on post-operative days 1,2 and 7. They will be
      asked their opiate pain medication usage, number of pills used and "Overall Benefit of
      Anesthesia" (OBAS) scores will be obtained. The OBAS is a simple quality assessment
      instrument shown to reliably measure benefit from post-operative pain therapy16 (Table 1).

      Table 1. Overall Benefit of Analgesia Score

        1. Please rate your current pain at rest on a scale between 0=minimal pain and 10=maximum
           imaginable pain

        2. Please grade any distress and bother from vomiting in the past 24 h (0=not at all to
           10=very much)

        3. Please grade any distress and bother from itching in the past 24 h (0=not at all to
           10=very much)

        4. Please grade any distress and bother from sweating in the past 24 h (0=not at all to
           10=very much)

        5. Please grade any distress and bother from freezing in the past 24 h (0=not at all to
           10=very much)

        6. Please grade any distress and bother from dizziness in the past 24 h (0=not at all to
           10=very much)

        7. How satisfied are you with your pain treatment during the past 24 h (0=not at all to 10=
           very much)

           OBJECTIVES The primary goal of our study is to demonstrate that laparoscopically
           assisted bilateral Transversus Abdominis Plane (TAP) block using liposomal bupivacaine
           is superior to pre-incisional injection of bupivacaine in terms of peri-operative opiate
           use, pain scores and overall patient satisfaction up to one week following surgery. Our
           recent research has already demonstrated the safety of performing Laparoscopic assisted
           TAP blocks using liposomal bupivacaine.

           This trial will evaluate the efficacy of laparoscopic TAP blocks with liposomal
           bupivacaine by using VAS/numeric pain scores at rest and with cough in recovery at 1 and
           2 hours post-op. The trial will also utilize an OBAS patient survey, document
           peri-operative opioid pain medication used intraoperatively, in PACU and overnight (if
           admitted), and assess length of time in PACU and same-day discharge versus admission.
           Opioid pain medication use at home up to one week will also be recorded.

           HYPOTHESES/SPECIFIC AIMS The goal of this research project is to prove that a
           laparoscopically delivered TAP block using a combination of Liposomal bupivacaine
           (Exparel) and Bupivacaine is an effective and feasible means for decreasing
           post-operative pain from the immediate post-operative period up to one week.

           The research aims to demonstrate that TAP blocks, when delivered laparoscopically and by
           using Liposomal bupivacaine will show a 20% benefit in post-operative QoR-15 scores on
           post-operative days 1,2 and 7. Other objectives of our study will be to evaluate
           peri-operative narcotic medication dosing, VAS/Numeric pain scores with cough at 1 and 2
           hours in PACU, overnight narcotic use for patients who are admitted and narcotic pain
           pill use at home up to 7 days. Finally, the study aims to confirm that this technique is
           simple to perform, easy to implement and would offer a multi-modal anesthetic
           alternative to the excessive use of post-operative opioid pain medications.

           PRELIMINARY WORK IRB protocol #14-132 was discontinued 12/14/15 due to a protocol
           violation. Because the study could not be completed with its original objectives, we are
           seeking to repeat the study with a very similar protocol. While talking with patients
           during the audit of their post-operative phone calls, it became clear that the
           experimental arm of the study might, in fact, have had a beneficial impact on
           post-operative recovery. As we do not have that portion of the data, we are seeking to
           repeat the study with a few minor modifications.

           METHODS

             1. Study Design Proposed study design is for a Prospective Single blinded Randomized
                Clinical Trial. The study aims to evaluate two arms and compare them: All patients
                would undergo laparoscopic total hysterectomy or Robotic assisted laparoscopic
                total hysterectomy with or without removal of adnexa. Patients would not be
                excluded for having other simultaneous procedures such as appendectomy, excision of
                endometriosis or pelvic lymph node dissection. Patients in one arm of the study
                would receive a bilateral Laparoscopic Assisted TAP block with 10cc Liposomal
                bupivacaine, 10cc 0.25% bupivacaine and 10cc normal saline each bilaterally at the
                beginning of their surgery. The patients in the control arm of the study would
                receive pre-incisional injections at the trocar incision sites using a total of
                20cc 0.25% bupivacaine.

             2. Study Subjects

             1. Women undergoing laparoscopic hysterectomy or robotic assisted laparoscopic
                hysterectomy with or without removal of adnexa would be eligible. Patients will be
                randomized.

             2. Inclusion Criteria: Women undergoing TLH at Erlanger Hospital. They must be 18
                years or older due to restrictions on Exparel. Women undergoing simultaneous lymph
                node dissection, appendectomy, adhesiolysis or other incidental procedures would
                not be excluded.

             3. Exclusion Criteria: Patient refusal. Soft tissue infection of the abdominal wall
                and skin. Abnormality at the needle insertion site. Chronic opiate use within 3
                months prior to surgery. Age less than 18 years. Anticipated need for extension of
                incision greater than 2cm. Hepatic or renal impairment, current pregnancy or BMI
                >50.

           c. Sample Size: 100 patients, 50 in each arm of the study. The sample size calculation
           is based on an assumption that a 24% difference in VAS pain scores would be clinically
           meaningful. A sample size of 41 patients in each cohort would be able to detect a 20%
           difference in post-operative QoR-15 quality of life post-surgery scores with a power of
           80%. This calculation was done with the assistance of Jenny Holcomb, PhD (See
           accompanying paperwork).

           d. Data Collection: Each patient will have paperwork designating name, demographics,
           telephone numbers as well as pertinent PHI. Documentation of VAS scores, time-frame to
           first request for opiate pain medications, post-operative pill counts and follow-up
           phone questionnaire (OBAS) will be collected on accompanying forms.

           e. Data Handling: A file, with the paper work on each patient, will be handled by the
           Principal Investigator, Shanti Mohling, MD and primary Co-investigator, Rayan Elkattah,
           MD. Two personnel will be recruited to handle post-operative phone calls. They will be
           carefully screened for reliability and phone-calls assessments will be periodically
           audited to avoid the concerns occurring with #14-132. The charts will be stored in the
           primary investigator's private office or in the research specialist's office (Patricia
           Bush) during analysis.

           f. Data Analysis: Following collection of data and collation of all data, the results
           will be statistically analyzed with the help of statistician Jenny Holcomb, PhD.

           g. Time Frame:

      1. 12 months for data collection. 2. 18 months time for completion of study including
      analysis. h. Strengths/Innovation: Adding a simple technique for post-operative pain control
      to the armamentarium of multi-modal anesthesia techniques will greatly enhance the options
      for caring for patients around the time of laparoscopic surgery. Currently, I believe the
      laparoscopic TAP block is a valuable, yet underutilized tool in the field of Minimally
      Invasive Surgery.

      i. Limitations:

        1. Liposomal bupivacaine is a milky white color and it would have been very difficult to
           blind the surgeons infiltrating it as opposed to a placebo.

        2. There is a learning curve with developing an ability to do the TAP block
           laparoscopically, however this technique has now been well practiced by our team.

        3. BMI, additional procedures, history of other pain issues, such as fibromyalgia, may all
           be confounders to this study. All of these will be documented and hopefully averaged in
           the randomization.

      VII. RISKS/BENEFITS

        1. Risks and side effects related to the TAP Block with liposomal bupivacaine include
           bruising at the site of the injections, soreness, and a rare potential for intravascular
           injection causing cardiac arrhythmia. These risks are similar to the risk of routine
           bupivacaine in the trocar sites routinely used anyway. Of note, there were no
           complications of laparoscopic TAP blocks during the course of our recent trial #14-132.

        2. There are no known direct benefits to study subjects.

        3. If the study demonstrates a benefit of the TAP block in controlling post-operative pain
           better than simply using pre-incisional injections and decreases patient need for opiate
           analgesia this will undoubtedly benefit patients in future.

        4. There are no potential ethical concerns with this study, especially given that it will
           be randomized.

      BUDGET Primary costs incurred will be files and paper products for VAS scores, charting on
      recovery and post-op questionnaires. The cost of the procedural medications will be rolled
      into the global surgical charge as pre-incisional anesthetics are already routinely billed
      for.

      RESEARCH ENVIRONMENT All procedures will all take place at the time of surgery in the
      operating room. Patients will receive information on the study in pre-op consultation or at
      the time of arrival to the Pre-op arena.
    

Intervention name(s): TAP Block
Intervention type(s): Procedure
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Patients in one arm of the study would receive a bilateral Laparoscopic Assisted TAP block with 10cc Liposomal bupivacaine, 10cc 0.25% bupivacaine and 10cc normal saline each bilaterally at the beginning of their surgery. The patients in the control arm of the study would receive pre-incisional injections at the trocar incision sites using a total of 20cc 0.25% bupivacaine.
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: laparascopic, surgery, anesthesia