Clinical trial NCT02055053
Conditions: Post Operative Pain (Post Laparoscopic Hernia Repair)
Keywords: Post Operative Pain hernia repair
Sponsor: Lahey Clinic
Start date: 2013-08-01; Completion date: 2019-10-16
Enrollment: 70 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To assess effect of local anesthetic into the preperitoneal space during laparoscopic hernia repair on post-operative pain.

Detailed description:

Arms: arm 1: After deployment of therapeutic mesh in the preperitoneal space of the abdomen wall during the procedure, the treatment group will receive infusion of 15 cc 0.5% Bupivicaine. arm 2: After deployment of therapeutic mesh in the preperitoneal space of the abdomen wall during the procedure, the placebo group will receive the infusion of 15 cc 0.9% Saline.
Interventions: intervention 1: 0.5% Bupivicaine
Intervention descriptions: intervention 1: Local anesthetic

Protocol documents:
Prot_SAP_000.pdf: 
Effects of Local Anesthesia on Post-operative Pain During Laparoscopic Inguinal 
Hernia Repair 
 
 
NCT 02055053 
 
10/7/20 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
Revised Version 2- dated 6/17/13 post irb  
 
 
Protocol: 
A randomized, double-blinded, placebo-controlled trial of the effects of instilling local 
analgesia on post-operative pain during laparoscopic inguinal hernia repair. 
 
 
Principal Investigator:  
 
Dmitry Nepomnayshy, MD 
 
(781)-744-5636 
 
 
Co-Investigators: 
 
Desmond Birkett, MD 
 
Heather Ford, MD 
 
(781)-744-3982 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
Table of Contents: 
 
 Study Schematic 
 
 
 
 
 
 
 
 
2 
 
 Background 
 
 
 
 
 
 
 
 
 
3 
 
 Objectives 
 
 
 
 
 
 
 
 
 
4 
 
 Methods 
 
 
 
 
 
 
 
 
 
4 
 
 Human Protection Plan 
 
 
 
 
 
 
 
5 
 
 Subject Reimbursement 
 
 
 
 
 
 
 
5 
 
 Data Analysis  
 
 
 
 
 
 
 
 
5 
 
 Appendix 
 
 
 
 
 
 
 
 
 
6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Schematic 
 


 
 
 
Background:  
 
Controlling post-operative pain is a standard part of managing any post-operative patient. Laparoscopic Total 
Extraperitoneal (TEP) Herniorrhaphy is a widely accepted technique to repair inguinal hernias and is offered to 
patients in our practice.1  The surgery requires general anesthesia and patients typically experience a significant 
amount of pain during the first post-operative day, at the incision sites, but more-so in the abdominal wall.2 Local 
anesthetics such as Lidocaine and Bupivicaine are commonly used for regional anesthesia in most surgical settings. 
These agents block the voltage-gated sodium channels of neuronal membranes halting the rate of depolarization 
or conduction of pain response from pain receptors to the brain. They are widely used, very safe and highly 
effective. The use of these agents have been described to prevent post-operative pain in laparoscopic surgery for 
                                                          
1 McKernan JB, Laws HL. Laparoscopic repair of inguinal hernias using a total extraperitoneal prosthetic approach. 
Surg Endosc. 1993;7:26-28. 
2 Edelman DS, Misiakos EP, Moses K. Extraperitoneal laparoscopic hernia repair with local anesthesia. Surg 
Endosc. 2001; 15:976-980. 


cholecystectomy, appendectomy and gynecologic surgery.3,4,5  The TEP technique, in contrast to intra-abdominal 
surgeries, remains entirely in the anterior abdominal wall where a temporary space between the muscle and 
connective tissue is made to repair the defect and place a piece of mesh.  This site of surgical dissection and 
trauma is a potential target for use of local anesthetics to decrease post-operative pain. There have also been a 
small number of studies describing the use in laparoscopic hernia repair with contrasting conclusions, three 
reporting significant reductions in post-operative pain with the use of intraperitoneal anesthetic and four studies 
suggesting no difference.6,7,8,9,10,11,12  In addition, these reports are limited by small enrollment sizes in a wide 
variety of sample populations internationally, (only one conducted in the United States in 1998), using a broad 
range of analgesia and anesthetic practices. Thus, the utility of local anesthetic in this setting remains at the 
forefront of debate.  Clearly, a prospective, randomized, placebo-controlled study with a larger sample size in a 
more representative population is needed to draw practice-changing conclusions. 
 
 
Objectives: 
 
Primary Objective:  To assess effect of local anesthetic into the preperitoneal space during laparoscopic hernia 
repair on post-operative pain.   
 
Methods: 
 
Patients with the clinical diagnosis of inguinal hernia, consented for elective laparoscopic inguinal hernia repair 
with mesh at Lahey Clinic Burlington by one of the General Surgeons listed in this study, will be randomized to two 
groups: the placebo group and the treatment group. The surgeons and the patients will be blinded to the 
allocation into the treatment and placebo arms of the study. The surgical approach to all patients will be the 
standard approach for laparoscopic inguinal hernia repair with general anesthesia. This standard will include both 
groups receiving 5 cc of 0.5% bupivacaine with epinephrine instilled at the umbilical port site and 2.5 cc instilled at 
                                                          
3 Alkhamesi NA, Peck DH, Lomax D, Darzi AW. Intraperitoneal aerosolization of bupivicaine reduces 
postoperative pain in laparoscopic surgery: a randomized prospective controlled double-blinded clinical trial. Surg 
Endosc. 2007;21:602-606. 
4 Thanapal MR, Tata AJ, Subramaniam T, Tong JMG, Palayan K, Rampal S, Gurunathan R. Pre-emptive 
intraperitoneal local anaesthesia: an effective method in immediate post-operative pain management and metabolic 
stress response in laparoscopic appendectomy, a randomized, double blinded, placebo-controlled study. ANZ J Surg. 
2012, Oct 11. 
5 Sripada S, Roy S, Mathur M, Hamilton M, Cranfield K, Bhattacharya S. A prospective double-blinded randomized 
controlled trial of intraoperative pelvic instillation with bupivicaine for management of pain following laparoscopy 
and dye. Br J Obstet Gynaecol. 2006; 101:835-838. 
6 Deans GT, Wilson MS, Brough WA. Controlled trial of preperitoneal local anesthetic for reducing pain following 
laparoscopic hernia repair. British J Surg. 1998;85:1013-1014. 
7 O’Riordain DS, Kelly P, Horgan PG, Keane FBV, Tanner WA. A Randomized Controlled Trial of Extraperitoneal 
Bupivacaine Analgesia in Laparoscopic Hernia Repair. Amer J Surg. 1998; 176:254-257. 
8 Saff GN, Marks RA, Kuroda M, Rozan JP, Hertz R. Analgesic Effect of Bupivicaine on Extraperitoneal 
Laparoscopic Hernia Repair. Anesth Analg. 1998;87:377-81. 
9 Bar-Dayan A, Natour M, Bar-Zakai, Zmora O, Shabtai M, Ayalon A, Kuriansky J. Preperitoneal bupivicaine 
attenuates pain following laparoscopic inguinal hernia repair. Surg Endosc. 2004;18:1079-1081. 
10 Hon SF, Poon CM, Leong HT, Tang YC. Pre-emptive infiltration of Bupivicaine in laparoscopic total 
extraperitoneal hernioplasty: a randomized controlled trial. Hernia. 2009;13:53-56. 
11 Suvikapakornkul R, Valaivarangkul P, Noiwan P, Phansukphon T. A Randomized Controlled Trial of 
Preperitoneal Bupivicaine Instillation for Reducing Pain Following Laparoscopic Inguinal Herniorrhaphy. Surgical 
Innov. 2009;16:117-123. 
12 Abbas MH, Hamade A, Choudhry MN, Hamza N, Nadeem R, Ammori BJ. Infiltration of wounds and 
extraperitoneal space with local anesthetic in patients undergoing laparoscopic totally extraperitoneal repair of 
unilateral inguinal hernias: A randomized double-blinded placebo-controlled trial. Scand J Surg. 2010;99:18-23. 


each of the 5mm port sites prior to incision. After deployment of mesh in the preperitoneal space of the 
abdominal wall during the procedure, the placebo group will receive the infusion of the 10cc 0.9% Saline in this 
space, and the treatment group will receive instillation of 10cc 0.5% bupivacaine with epinephrine. Post-
operatively, the patient will receive the standard of care analgesia and post-operative care.  The patient will be 
asked to rate pain using the Visual Analog Scale (VAS) hourly post-operatively until discharge. The nurse assigned 
to the patient’s care in the Post-Anesthesia Care Unit (PACU) will administer the VAS score – they already do this 
as part of their practice – they will do it for every hour that the patient is in recovery room. The patient will be 
given a pain diary that they have been educated on during the pre-operative evaluation describing their pain and 
their management at home, to be returned at their post-operative follow-up visit in clinic within 4 weeks. . Pain 
will be self-assessed using the same VAS pain scale used in the immediate post-operative pain assessment. 
Analgesia dosages will be recorded post-operatively, and duration of analgesia taken at home will be recorded. 
 
Recruitment:  
The patients will be recruited and consented for the study in the clinics of the above listed General 
Surgeons.  We calculated the sample size required so we have a power of 90% with intention to treat of detecting 
at least a 27% reduction of pain score with a 2-tailed test at P  .05. This number came to 114. We added 10% to 
account for possible loss of subjects to achieve an enrollment target of 125.  
 
Inclusion Criteria: 
 
Age  18 with unilateral or bilateral inguinal hernia for laparoscopic repair 
 
American Society of Anesthesiology (ASA) Class I and II 
 
Exclusion Criteria: 
 
Conversion from laparoscopic to open surgery 
 
History of chronic pain or ongoing treatment for chronic pain 
 
Age <18 
 
Allergy to local anesthetics 
 
 
 
 
 
 
 
 
Human Protection Plan: 
 
Informed Consent:  
Informed consent will be obtained using attached form following the Standard Operating Procedures for 
Informed Consent (see attached form SOP#: IC607-S). Consent will be obtained by the principle investigator, co-
investigators or the research coordinator. Those subjects unable to read or sign will be consented with a witness 
and those unable to speak English will be consented with a translator, following Standard Operative Procedures 
(see attached forms SOP#: IC608-S and SOP#: IC605-S) 
 
Adverse effects and unanticipated problems: 


Adverse reactions are rare and dose-dependent. Serious reactions are extremely infrequent and 
preventable with proper dosage calculations. 13,14  Maximum Dose: 90mg for adult. 0.5% Bupivicaine 5mg/mL with 
epinephrine. (15 mL, a total of 75mg will be given) . 
 
Adverse effects of Local Anesthetic: 
 
Common:  (= to 10% or more)  None 
 
Less Common:  (= to 3-9%)  None 
 
Rare ( =2% or less) None 
 
Very Rare: (=1% or less) 
 
Local reactions (1.9/10,000) : local parasthesias (sensation of tingling, tickling, burning or numbness) 
 
Systemic Toxicity (7.5/10,000) 
o 
CNS toxicity: perioral/tongue parasthesias, tremors, dizziness, slurred speech, double 
vision, tinnitus (ringing in the ears), confusion, restlessness, convulsions, seizure 
o 
Methemoglobinemia 
o 
Cardiovascular toxicity: bradycardia (slow heart rate), arrhythmias (abnormal rhythm) 
o 
Allergic reaction: skin redness and swelling, itchy rash, shortness of breath, throat 
swelling, low blood pressure 
All internal adverse effects will be reported to the IRB using the Unancticipated Problem Report (see 
attached). If serious, this will be reported to the expedited IRB within 10 working days/14 calendar days. If non-
serious this will be reported to the full IRB within 20 working days/30 calendar days. 
 
Benefit: 
Local anesthetics are safe and effective agents widely-used in surgical specialties to induce absence of pain 
sensation.  0.5% is a standard dose of Bupivicaine used in surgery and will be used in this study. The anesthetic will 
be instilled through a laparoscopic port trocar into the preperitoneal space, the site of the majority of surgical 
dissection and location of mesh placement. The risks are almost negligent for local anesthetic as described and 
maximum doses of 175mg will not be exceeded. The potential benefit is improved post-operative pain, less post-
operative stress maximizing patient comfort and recovery while minimizing additional IV and oral analgesics 
necessary post-operatively. 
 
Subject Reimbursement:  
None 
 
 
Data Analysis: 
 
We calculated the sample size required so we have a power of 90% of detecting at least a 27% reduction of pain 
score with a 2-tailed test at P  .05. This was done using the data in our literature review, which described a mean 
post-operative VAS pain score in the placebo group of  3.57 with a standard deviation of 1.47, and a mean 
difference between groups of 1.23, calculating the effect size at 0.84 (1.23/1.47). At 90% power and an effect size 
of 0.84, a total of 64 total patients is needed for significant conclusions in a parallel study, 32 in each arm.  We 
added 10% to the total sample size for intended enrollment to account for potential lost subjects during the trial.  
                                                          
13 Cox B, Durieux ME, Marcus MA. Toxicity of local anesthetics. Best Pract Res Clin Anaesthesiol. 2003 
Mar;17(17(1):111-36  
 
14 Moore PA, Hersh EV. Local Anesthetics: Pharmacology and Toxicity. Dent Clin N Am. (2010) 587-599 


Our statistician will provide randomization to the inpatient pharmacy who will provide the OR with the blinded 
study solution. Statistical data will be based on an intention-to-treat principle.  Data collection will be managed by 
the Research Coordinator and entered in an identifier-free, password-protected database. The Mann-Whitney U 
test will be applied to data on pain score and analgesia required while Fisher’s exact test will be used to calculate 
association of secondary outcomes. 
 
 
 
Appendix: 
 
o Informed Consent Form 
o Standard Operating Procedures Informed Consent 
o Standard Operating Procedures Informed Consent Unable to sign/speak 
o Standard Operating Procedures Informed Consent Non-English Speaking 
o Unanticipated Problem Report Form