Clinical trial NCT03824808
Conditions: Kidney Cancer Prostate Cancer
Keywords: prostatectomy partial nephrectomy robotic surgery intravenous lidocaine lidocaine hydrochloride
Sponsor: University of Missouri-Columbia
Start date: 2019-02-26; Completion date: 2020-03-26
Enrollment: 21 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Controlling pain is fundamental during and after surgical procedures. This study examines pain associated with robotic assisted surgery on prostate cancer or a kidney mass. In recent years, the risk of opioids in the postoperative period has gained interest due to the growing epidemic of addiction, dependence, and overdose. In this study, the investigators expect a continuous infusion of intravenous lidocaine during the perioperative period to result in less pain and less opioid use.

Detailed description:
In recent years, the risk of opioids in the post-operative period has gained interest due to the growing epidemic of addiction, dependence, and overdose. The rate of drug overdose secondary to opioids has continued to increase at an alarming rate. This has been a primary point of concern in all fields of medicine and Urology has not been an exception. This is also a nationwide government and public health concern. This has generated an increased focus on the use of non-opioid analgesics after surgery such as intravenous lidocaine.

Opioids remain the primary source of relief for postoperative pain and have the potential to lead to significant morbidity. Opioids may delay recovery following surgery and have many well-known adverse effects including, but not limited to, nausea, vomiting and prolonged post-operative ileus. Furthermore, in one study, they inadequately provided pain control in 50-60% of postoperative participants. This is a frequent report of participants because of the less than optimal utilization of the medications in fear of their dose dependent adverse effects and various contraindications. On the other hand, surplus medication following surgery is another prominent component of the opioid problem in Urologic practices. Bates et al. found that of the 586 participants that underwent a urological procedure that they reviewed, 67% of them had collected surplus medication. It is both necessary and beneficial for surgeons and participants to utilize dose-sparing strategies following surgery to decrease overall opioid usage and outpatient requirement.

One mechanism that has already been employed for overall improvement in prostatectomies and partial nephrectomies is the use of the robotic assisted approach. Robot assisted partial nephrectomies (RALPN) and robotic assisted laparoscopic prostatectomies (RALP) are becoming a mainstay in urologic surgery and increasing annually. This coincides with a continuous downward trend of laparoscopic and open urologic procedures. RALPN has been shown in a meta-analysis to be more favorable than laparoscopic partial nephrectomies and will continue to be the surgical procedure of choice in the near future. RALP is also now the dominant surgical approach while open and laparoscopic prostatectomies becoming less frequent. Robotic assisted surgery is associated with improved functional outcomes, pain scores, shorter hospital stays, and increases in participants satisfaction in many studies.

While there has been a pronounced increase in robotic surgery over the past 10 years that has demonstrated benefits for participants, there has been limited studies regarding the pain management for these participants. Robotic assisted surgery itself decreases pain levels compared to other approaches, but participants continue to experience mild to moderate pain levels in the postoperative period, which are classically managed with NSAIDs and opioids.

Recently, Enhanced Recovery after Surgery protocols (ERAS) have been implemented in an attempt to decrease pain and opioid use as one outcome. ERAS utilizes multimodal analgesia and has shown improvement of participant satisfaction and perioperative opioid use. Systemic lidocaine is becoming more popular and regularly applied through this protocol and, other practices, in due to its analgesic, anti-hyperalgesia and anti-inflammatory properties that it contains. Systemic lidocaine mechanism of action is not fully understood, but it appears to be multifaceted. Systemic lidocaine inhibits voltage-gated sodium channels in both the peripheral and central nervous system. This is believed to cause an additive effect when combined with inhaled anesthetics which also work on the voltage-gated sodium channels in the central nervous system. Despite this summative effect, this is likely not the primary mechanism of action. Instead, it is believed to predominantly act on anti-inflammatory signaling and through inhibiting neuronal effects. Additionally, it reduces nociception and cardiovascular response to surgical stress and pain.

This is a prospective, randomized, double-blinded, placebo-controlled clinical trial on lidocaine infusion for pain control and opioid consumption in participants undergoing either robotic-assisted laparoscopic prostatectomy or robotic-assisted laparoscopic partial nephrectomy at University of Missouri Hospital. Participants will be randomized in a 1:1 fashion and stratified by the type of surgery to receive a perioperative intravenous 0.8% lidocaine infusion at 1 mg/kg/h if \< age 65 and 0.5 mg/kg/h if ≥ age 65 or an equal volume and rate of normal saline as a placebo. The infusion will be started 15 minutes after endotracheal intubation and continue for 24 hours.

The study that the investigators propose targets an area of urology that is underrepresented in the current literature despite its increasing importance. To the best of the investigator's knowledge, this has not been directly studied before, although it has been utilized numerous times in the ERAS protocol at the University of Missouri Hospital throughout the Division of Urology and Anesthesiology \& Perioperative Medicine in participants undergoing robotic surgery. The benefits of intravenous lidocaine have been demonstrated in other areas and these results warrant a prospective, randomized, double-blinded, placebo controlled study to assess the lidocaine infusion effects for robot assisted laparoscopic prostatectomies and partial nephrectomies. As the number of robotic assisted surgeries and emphasis on opioid reduction continues, the evaluation of systemic lidocaine will be important in improving outcomes in urology.

Arms: arm 1: Lidocaine Hydrochloride 0.8% in Dextrose 5% Solution arm 2: 0.9% Sodium Chloride Injection
Interventions: intervention 1: Lidocaine Hydrochloride 0.8% in Dextrose 5% Solution intervention 2: 0.9% Sodium Chloride Injection
Intervention descriptions: intervention 1: Lidocaine Hydrochloride and 5% Dextrose Injection, USP is a sterile, nonpyrogenic solution prepared from lidocaine hydrochloride and dextrose in water for injection. intervention 2: Sodium Chloride Injection USP is sterile, nonpyrogenic, isotonic and contains no bacteriostatic or antimicrobial agents.

Protocol documents:
Prot_SAP_000.pdf: 
1 
 
 BIOMEDICAL RESEARCH PROTOCOL 
UNIVERSITY OF MISSOURI 
 
Project Title: A Prospective, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial 
                        Evaluating the Use of Perioperative Intravenous Lidocaine Infusion to Decrease  
                        Pain Scores and Opioid Consumption after Robotic-Assisted Prostatectomy and 
                        Robotic-Assisted Partial Nephrectomy 
 
IRB Number: 2012402 
Version Number: 1 
Version Date: 08/24/2018 
Principal Investigator: Katie Murray, DO 
Funding Source: Departmental   
Clinical Trial Phase: Phase IV  
Clinicaltrials.gov Number: Pending  
Study Drug/Study Device: Lidocaine Hydrochloride  
 
 
Principal Investigator 
Katie Murray, DO 
Department of Surgery Urology 
Division 
Co-Principal Investigator 
Boris Mraovic, MD 
Department of Anesthesiology 
& Perioperative Medicine 
Co-Investigator(s) 
Terri Monk, MD 
Department of Anesthesiology 
& Perioperative Medicine 
 
Research Personnel 
Noah Timko, BS, BHS 
Department of Anesthesiology 
& Perioperative Medicine 
Consenting Professional(s) 
Department 
Department of 
Anesthesiology & 
Perioperative Medicine and 
Surgery-Urology 
 
 
 
 
 
University of Missouri University Hospital 
Department of Surgery Urology Division 
1 Hospital Drive 
Columbia, MO 65212 
 
 


2 
 
Table of Contents 
PROTOCOL SUMMARY AND/OR SCHEMA ............................................................................... 4 
OBJECTIVES AND SCIENTIFIC AIMS ......................................................................................... 4 
BACKGROUND AND STUDY DESIGN/INTERVENTION ............................................................... 5 
CRITERIA FOR SUBJECT ELIGIBILITY ......................................................................................... 9 
Subject Population ..........................................................................................................................9 
Subject Inclusion ............................................................................................................................9 
Subject Exclusion ......................................................................................................................... 10 
OVERVIEW OF STUDY DESIGNATION .................................................................................... 10 
Design ......................................................................................................................................... 10 
Intervention................................................................................................................................. 11 
THERAPEUTIC AND DIAGNOSTIC AGENTS ............................................................................. 12 
RECRUITMENT PLAN ............................................................................................................ 12 
PRETREATMENT EVALUATION ............................................................................................. 12 
SURGICAL INTERVENTION PLAN ........................................................................................... 13 
EVALUATION DURING TREATMENT/INTERVENTION ............................................................. 13 
TOXICITIES/SIDE EFFECTS ..................................................................................................... 14 
CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT ........................................ 15 
CRITERIA FOR REMOVAL FROM STUDY................................................................................. 15 
BIOSTATISTICS ..................................................................................................................... 16 
Sample Size.................................................................................................................................. 16 
Unadjusted and Adjusted Analysis ................................................................................................ 16 
Proposed Analyses ....................................................................................................................... 16 
RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION PROCEDURES ..................... 16 
Research Participant Registration ................................................................................................. 16 
Randomization ............................................................................................................................ 17 
DATA MANAGEMENT ISSUES ............................................................................................... 17 
Quality Assurance ........................................................................................................................ 17 
Data and Safety Monitoring ......................................................................................................... 17 
PROTECTION OF HUMAN SUBJECTS ..................................................................................... 18 
Benefits and Risks ........................................................................................................................ 18 
Toxicities and side effects............................................................................................................. 18 
Alternatives / Therapeutic options ............................................................................................... 18 
Financial Costs and Burdens ......................................................................................................... 18 
Privacy and Confidentiality ........................................................................................................... 18 
Volunteering Nature of the Study ................................................................................................. 18 
Serious Adverse Event (SAE) Reporting ......................................................................................... 19 
INFORMED CONSENT PROCEDURES ..................................................................................... 19 


3 
 
REFERENCES ........................................................................................................................ 19 
APPENDECIES ...................................................................................................................... 22 
 
 
 
 


4 
 
PROTOCOL SUMMARY AND/OR SCHEMA 
We propose a prospective, randomized, double-blinded, placebo-controlled clinical trial on the 
use of perioperative intravenous lidocaine infusion in order to decrease pain scores and opioid 
consumption after robotic-assisted prostatectomy and robot assisted partial nephrectomy. 
Patients undergoing urological robotic assisted surgery will be randomized 1:1 to receive either 
intraoperative 0.8% lidocaine or normal saline at 1 mg/kg/h for patients younger than 65 years 
and 0.5 mg/kg/h for patients greater than or equal to the age of 65 to be delivered by 
continuous infusion for 24 hours intra- and post-operatively. Opioid use will be monitored for 
up to 14 days post-operatively as well as pain scores.  
OBJECTIVES AND SCIENTIFIC AIMS 
Clinical Hypotheses: 
 
Primary Hypothesis: 
We hypothesize that use of perioperative lidocaine infusion for 24 hours in urology robotic 
surgeries would result in less pain and less opioid use compared to the placebo.  
 
Exploratory Hypotheses: 
We hypothesize that the use of the lidocaine infusion compared to placebo would: 
1. result in less opioid consumption in first 24 hours and 14 days post-operatively  
2. decrease length of stay in the PACU and improve SpO2 levels in PACU 
3. decrease postoperative nausea and vomiting 
4. decrease time to first ambulation after the surgery 
5. improve recovery of bowel movements after surgery 
6. improve patient satisfaction levels after surgery 
7. decrease length of stay in hospital 
 
Therefore: 
 
Primary Endpoint is: 
- 
Difference in post-operative pain  
 
Secondary Endpoints are: 
- 
Difference in opioid consumption in first 24 hours, discharge and 14 days post-
operatively (utilizing morphine equivalents) 
- 
Difference in length of hospital stay determined by surgeon excluding social factors that 
may delay discharge (discharge readiness; hours) 
- 
Difference in post-operative Ileus duration (hours) 
- 
Difference in time in the Post Anesthesia Care Unit (PACU) after surgery (discharge 
readiness and actual discharge; minutes) 
- 
Difference in return of flatus after surgery (hours) 
- 
Difference in time to out of bed to chair after surgery (hours) 
- 
Difference in time to first ambulation in the hallway after surgery (hours) 


5 
 
BACKGROUND AND STUDY DESIGN/INTERVENTION 
In recent years, the risk of opioids in the post-operative period has gained interest due to the 
growing epidemic of addiction, dependence, and overdose1. The rate of drug overdose 
secondary to opioids has continued to increase at an alarming rate (Figure 1)2. This has been a 
primary point of concern in all fields of medicine and Urology has not been an exception3. This 
is also a nationwide government and public health concern.  This has generated an increased 
focus on the use of non-opioid analgesics after surgery such as intravenous lidocaine4. 
 
Figure 1: CDC report of age-adjusted drug overdose death rates, by opioid category: United 
states, 1999-2016. 
 
Opioids remain the primary source of relief for postoperative pain and have the potential to 
lead to significant morbidity5.  Opioids may delay recovery following surgery and have many 
well-known adverse effects including, but not limited to, nausea, vomiting and prolonged post-
operative ileus6,7. Furthermore, in one study, they inadequately provided pain control in 50-
60% of postoperative patients. This is a frequent report of patients because of the less than 
optimal utilization of the medications in fear of their dose dependent adverse effects and 
various contraindications7. On the other hand, surplus medication following surgery is another 
prominent component of the opioid problem in Urologic practices. Bates et al. found that of the 
586 patients that underwent a urological procedure that they reviewed, 67% of them had 
collected surplus medication1. It is both necessary and beneficial for surgeons and patients to 
utilize dose-sparing strategies following surgery to decrease overall opioid usage and outpatient 
requirement.  
 
One mechanism that has already been employed for overall improvement in prostatectomies 
and partial nephrectomies is the use of the robotic assisted approach. Robot assisted partial 


6 
 
nephrectomies (RALPN) and robotic assisted laparoscopic prostatectomies (RALP) are becoming 
a mainstay in urologic surgery and increasing annually. This coincides with a continuous 
downward trend of laparoscopic and open urologic procedures8. RALPN has been shown in a 
meta-analysis to be more favorable than laparoscopic partial nephrectomies and will continue 
to be the surgical procedure of choice in the near future9. RALP is also now the dominant 
surgical approach while open and laparoscopic prostatectomies becoming less frequent. 
Robotic assisted surgery is associated with improved functional outcomes, pain scores, shorter 
hospital stays, and increases in patients satisfaction in many studies 8,10–12.  
 
While there has been a pronounced increase in robotic surgery over the past 10 years that has 
demonstrated benefits for patients, there has been limited studies regarding the pain 
management for these patients. Robotic assisted surgery itself decreases pain levels compared 
to other approaches, but patients continue to experience mild to moderate pain levels in the 
postoperative period, which are classically managed with NSAIDs and opioids6,11,13.  
 
Recently, Enhanced Recovery after Surgery protocols (ERAS) have been implemented in an 
attempt to decrease pain and opioid use as one outcome. ERAS utilizes multimodal analgesia 
and has shown improvement of patient satisfaction and perioperative opioid use14. Systemic 
lidocaine is becoming more popular and regularly applied through this protocol and, other 
practices, in due to its analgesic, anti-hyperalgesia and anti-inflammatory properties that it 
contains15.  Systemic lidocaine mechanism of action is not fully understood, but it appears to be 
multifaceted16. Systemic lidocaine inhibits voltage-gated sodium channels in both the 
peripheral and central nervous system. This is believed to cause an additive effect when 
combined with inhaled anesthetics which also work on the voltage-gated sodium channels in 
the central nervous system17. Despite this summative effect, this is likely not the primary 
mechanism of action. Instead, it is believed to predominantly act on anti-inflammatory signaling 
and through inhibiting neuronal effects4.  Additionally, it reduces nociception and 
cardiovascular response to surgical stress and pain.16 
 
The use of perioperative lidocaine has been studied and shown beneficial effects in patients 
undergoing surgery4,14,25–29,17–24. Outcomes have included: improved postoperative pain scores, 
decreased nausea, postoperative ileus, shorter length of hospital stays and a reduction in 
opioid use 18–20. In addition to its positive effects, there is a significant lack of negative effects. 
Weibel et al. evaluated 45 small, randomized studies and found that there is no current 
evidence of any major toxicities with usage of systemic lidocaine21. There is no great evidence 
for optimal pain management in laparoscopic urological procedures, especially in robotic 
assisted laparoscopic surgery. However, evidence from laparoscopic surgeries in other fields 
should be extrapolated12.  
 
The systematic review by Weibel et al.21 in 2016, revealed that patients who received 
intravenous perioperative lidocaine had lower pain scores for the first 24 hours after surgery. 
The effects were seen in a broad spectrum of patients and demonstrated clear evidence of the 
positive effects of pain reduction and decreased amounts of opioid use. These were most 
pronounced in laparoscopic abdominal surgery. A similar meta-analysis was completed in 2012 


7 
 
and exhibited benefits consistent with the most recent data22. Dunn and Durieux4 reviewed the 
use of intravenous lidocaine and generated a table of results that clearly illustrates the studies 
that have investigated systemic lidocaine and the resultant effects until 2017 (Table 1).  
 
 
 
Table 1: Table from Dunn and Durieux in 20174 that shows the systemic lidocaine studies that 
have been conducted prior to 2017.  It includes the type of study, bolus, infusion, duration, 
results and evidence.  
 
Overall, the use of intravenous lidocaine in abdominal laparoscopic surgery was found to be 
beneficial in multiple studies. Kaba et al.24, Wongyingsinn et al.23 and Tikuisis et al.25 showed a 


8 
 
decrease in pain, opioid use and post-operative ileus in laparoscopic colectomies, along with 
decreased inhaled anesthetic usage during the surgery23,24. Lauwick et al.26 demonstrated a 
reduction of inhaled anesthetics and opioid usage in laparoscopic cholecystectomies. Kim et 
al.30 and De Oliveira et al.27 had consistent findings of improvements with pain, opioid use and 
duration of ileus in laparoscopic gastrectomies. Kim et al.28 further showed intravenous 
lidocaine to be an improvement in pain for laparoscopic appendectomies. All laparoscopic 
abdominal surgeries studies that have been conducted with intravenous lidocaine have 
exhibited patient benefits, which further suggest the value of intravenous lidocaine in 
laparoscopic abdominal surgeries.   
 
There have been no randomized, double-blinded trials on the proper analgesia for post-
operative course after robotic surgery.  There have only been a handful of studies conducted on 
the use of lidocaine infusions in urological surgeries, with a majority of the studies showing 
significant success with its use14,17–20,29,31. Joshi et al indicated in their review of pain 
management in prostatectomies, there is a need for randomized clinical trials to investigate 
intravenous lidocaine as well as enhanced rehabilitative protocols especially in minimally 
invasive procedures, as the studies were done in open surgical procedures6. 
 
Most recently in 2018, Nakhli et al.17 used adjunctive intravenous lidocaine in renal surgery in 
comparison to saline placebo. They infused 1.5mg/kg bolus followed by a continuous infusion 
of 2 mg/kg/h until skin closure. The lidocaine infusion patients had a reduction of 31% 
(p<0.001) in isoflurane concentration requirement and 27% (p<0.001) reduction in their 
intraoperative remifentanil. This reduction of intraoperative anesthetic has been shown before 
in other species including both cats and dogs32,33. They additionally found a significant recovery 
from anesthesia with shorter extubation time 5.8 ± 1.8 minutes compared to control of 7.9 ± 
2.0 minutes (p<0.001).  
 
Lauwick et al.18 investigated functional walking capacity as a measure of recovery from a 
laparoscopic prostatectomy and discovered that patients who received lidocaine infusion were 
able to walk further over a shorter amount of time (56 vs. 43.5 meters) compared to saline. 
They received 1.5mg/kg bolus, 2mg/kg during the operation and 1mg/kg in the PACU for 24 
hours after surgery. They also had 12% reduction (5.6 vs 6.3) of desflurane during the 
operation.  
 
Groudine et al.19  demonstrated value of intravenous lidocaine in patients undergoing radical 
retropubic prostatectomy after infusing 1.5mg/kg bolus, followed by 1.5mg/kg/h infusion from 
beginning of surgery until 1 hour postoperatively. Patients had quicker return of flatulence, 
regained of bowel function faster (p<0.05), 1.1 fewer days in the hospital (p <0.05), and 
decreased postoperative pain19.  
 
Jendoubi et al.14 looked at the use of intravenous lidocaine or ketamine compared to saline for 
acute and chronic pain following open nephrectomy. They gave 1.5 mg/kg bolus at anesthesia 
induction followed by infusion of 1 mg/kg/h intraoperatively and continued for 24 hours. They 
found that both ketamine and lidocaine significantly reduced morphine consumption by about 


9 
 
33% and 42%, respectively (p<0.001), improved 6-minute walk distance at discharge from a 
mean of 27 meters to 82.3 meters in the lidocaine group (0.001), and also reduced 
development of neuropathic pain at 3 months (p<0.05).  
 
Tauzin-Fin et al.29 found significant enhancement of recovery with several endpoints revealing 
reduction of morphine 8.5mg in lidocaine infusion vs 25mg control group, improved post-
operative pain (P<0.05), time to first flatus (P<0.001) and 6-minute walk time (p<0.001) after a 
nephrectomy. Effective analgesia in the post-operative period considerably improves 
rehabilitation.  
 
Weinberg et al.20 looked at radical prostatectomy patients with perioperative lidocaine 2% or 
saline. A pre-operative intravenous bolus of 0.075mg/kg followed by peri-operative and 24-
hour post-operative infusion of 0.075mg/kg/h. They found it decreased hospital stay an average 
of 1.3 days (P=0.017), reduced pain at rest by 1.8 hours (p=0.001), and morphine consumption 
by a mean of 13.9mg (p=0.021).  
  
Only one study, Wuethrich et al.31, did not find any benefit from the use of intravenous 
lidocaine in renal surgery. They were unable to identify significant difference in length of 
hospital stay, post-operative pain, return of bowel function, stress response, fentanyl dosage 
used or anesthetic sparing effect following intra-operative and 24-hour post-operative 
lidocaine31. This small study of 64 patients stands alone as the only urological operation to not 
show benefits.  
 
The study that we propose targets an area of urology that is underrepresented in the current 
literature despite its increasing importance. To the best of our knowledge, this has not been 
directly studied before, although it has been utilized numerous times in the ERAS protocol at 
the University of Missouri Hospital throughout the Division of Urology and Anesthesiology & 
Perioperative Medicine in patients undergoing robotic surgery. The benefits of intravenous 
lidocaine have been clearly demonstrated in other areas and these results warrant a 
prospective, randomized, double-blinded, placebo controlled study to assess the lidocaine 
infusion effects for robot assisted laparoscopic prostatectomies and partial nephrectomies. As 
the number of robotic assisted surgeries and emphasis on opioid reduction continues, the 
evaluation of systemic lidocaine will be important in improving patient outcomes in Urology.  
CRITERIA FOR SUBJECT ELIGIBILITY 
Subject Population 
- 
Undergoing robotic assisted prostatectomy or robotic assisted partial nephrectomy at 
University of Missouri Hospital for prostate cancer or kidney mass 
 
Subject Inclusion 
- 
Age  18 years 
- 
ASA I-III 
 


10 
 
Subject Exclusion 
- 
Inability to obtain written informed consent 
- 
Allergy to lidocaine or other amide local anesthetics 
- 
Atrioventricular conduction blocks 
- 
CV instability and concomitant use of alpha agonists or beta blockers 
- 
Recent myocardial infarction (≤ 6 months ago) 
- 
Cardiac arrhythmia disorders 
- 
Stokes-Adams syndrome 
- 
Wolff-Parkinson-White syndrome 
- 
Seizure disorders 
- 
Liver failure or hepatic dysfunction 
- 
Significant renal disease with a serum creatinine ≥ 2 mg/dl 
- 
A family history of malignant hyperthermia 
- 
Current use of opioids or documented history of opioid abuse 
- 
Typically, have less than 3 bowel movement per week  
- 
Combined surgical cases that include robotic prostatectomy or robotic partial 
nephrectomy 
OVERVIEW OF STUDY DESIGNATION 
Design 
This is a prospective, randomized, double-blinded, placebo-controlled clinical trial on lidocaine 
infusion for pain control and opioid consumption in patients undergoing either robotic-assisted 
laparoscopic prostatectomy or robotic-assisted laparoscopic partial nephrectomy at University 
of Missouri Hospital. Patients will be randomized in a 1:1 fashion and stratified by the type of 
surgery to receive a perioperative intravenous 0.8% lidocaine infusion at 1 mg/kg/h if < age 65 
and 0.5 mg/kg/h if ≥ age 65 or an equal volume and rate of normal saline as a placebo. The 
infusion will be started 15 minutes after endotracheal intubation and continue for 24 hours.  
 
After obtaining written consent, subjects will be randomized to receive lidocaine or normal 
saline.  The anesthesiologist, surgeon, nurses, research staff, and patient will be blinded to the 
intervention. Masked infusion bags of 0.8% lidocaine or normal saline will be prepared by the 
investigational pharmacy at University of Missouri Hospital. To avoid any compromise in the 
blinding process, the investigational pharmacist will enter “Study Medication” in the medical 
record.   
 
Perioperative care, surgery and anesthesia, for all subjects will be per standard hospital 
protocol.  
 
In short: 
Upon arrival to the operating room, patients will be placed supine on the operating table and 
intravenous (IV) lines connected to allow initiation of IV lidocaine or saline following anesthetic 
induction. IV antibiotics will be utilized if clinical necessary based on the discretion of the 
anesthesiologist and attending surgeon. Standard perioperative monitoring including a 


11 
 
continuous electrocardiogram, pulse oximetry, urine output, non-invasive arterial pressure 
measurement, end-tidal CO2 and temperature will be utilized. Intravenous fluid use during 
surgery will be provided by the anesthesiology team as clinically indicated. Anesthesia will be 
standardized. Induction will be with lidocaine 1.5 mg/kg, fentanyl 1 mcg/kg, propofol 1.5 to 2 
mg/kg, and rocuronium 0.6 mg/kg. Patient will then be prepared and draped in sterile fashion. 
Timeout will be performed.  
 
Anesthesia will be maintained with 1 MAC sevoflurane, additional fentanyl and rocuronium will 
be given per anesthesia discretion. Quantity of all anesthetic and analgesic medications during 
the operation will be documented. Local 0.25% bupivacaine (10mL) without epinephrine 
injection will be used post-operatively during closure in all patients regardless of being in the 
study group or control group as a part of normal operational procedure. Reversal of 
neuromuscular blockade will be with sugammadex 2 mg/kg. When standard extubation criteria 
are met the subject will be extubated and transported to PACU. 
 
Intervention 
Fifteen minutes following endotracheal intubation, subjects will be intravenously infused with 
either 0.8% lidocaine at 1 mg/kg/h if < age 65 and 0.5 mg/kg/h if ≥ age 65 or an equal volume 
and rate of normal saline placebo as determined by the randomization table. The infusion will 
be continued for 24 hours after surgery. Masked infusion bags of 0.8% lidocaine or normal 
saline will be prepared by the Investigational Pharmacy at the University of Missouri Hospital 
according to the subject randomization table. Infusion preparation will occur in a blinded 
fashion to all clinical and research personal involved with the study case. To maintain blinding, 
the investigational pharmacist will enter “Study Medication” in the medical record. 
 
In PACU patient will receive additional fentanyl or hydromorphone. Postoperative pain scores, 
vital measures, and opioid use will be documented. Once patient is able to tolerate oral intake, 
they will be switched to oral narcotics. Patient fentanyl consumption and 10 cm visual analog 
scale (VAS) will be utilized. VAS will be scored from a 0 “no pain” to a 10 “worst pain ever” and 
will be recorded by blinded research staff at 1, 2, 4, 6, 12, 24 hours post-operatively, postop day 
2, any additional day during hospitalization, at time of discharge and 14-day follow up. The 
nurse that will be caring for these patients will document the time of first bowel movement, 
return of flatus and any adverse reactions per standard of care. Post-Anesthesia Patient 
Satisfaction Assessment will be performed at 24 h post-surgery. 
 
Patient may go to the floor or ICU with the infusion. Orders will be included in surgeon's post-
operative orders including the stop time at 24 hours. The infusion pump will be programmed 
using Guardrails settings, it will be on separate infusion pump from IV fluids with sign for pump 
- local toxicity, obtained from anesthesia pain nurse. 
 
Patients will be monitored clinically for toxicities during the postoperative period. Per standard 
of care the nurse caring for the patient will be required to document any adverse events to 
lidocaine every four hours and anesthesiology pain nurses will monitor these reports. If patients 
experience the presence of perioral paresthesia, metallic taste, tinnitus, confusion, agitation, 


12 
 
muscle spasms, and seizures, the lidocaine infusion will be stopped and a lidocaine toxicity 
protocol will start by the standard of care. The subject will be removed from the study. 
 
At initial follow-up appointment, patient will be asked to bring in prescribed opioids, if 
applicable, to determine how much was required in their outpatient recovery. Pill count will be 
done and compared to distributed quantity. VAS score will be also assessed.  
THERAPEUTIC AND DIAGNOSTIC AGENTS 
Lidocaine is the intravenous analgesic. Lidocaine infusion will be stored and dispensed by the 
Investigational Pharmacy at University Hospital. A 0.8% Lidocaine infusion will be injected 
intravenously using an administration set with a filter at a constant rate of 1 mg/kg/h for ages < 
65 and 0.5 mg/kg/h for ages ≥ 65. Patients with BMI ≥ 40 will be dosed using ideal body weight. 
RECRUITMENT PLAN 
Patients will be recruited from the practices of the Division of Urology, Department of Surgery. 
The study will be introduced to every eligible patient scheduled for robot assisted laparoscopic 
prostatectomy and robot assisted laparoscopic partial nephrectomy by the participating 
consenting physicians from the Department of Surgery-Urology Division and a written consent 
obtained prior to surgery by the consenting research personnel. Candidate subjects will be 
provided time to consider the study, to read the informed consent document at their 
convenience, and discuss the study with family and others, as desired.  
PRETREATMENT EVALUATION 
This study does not require any additional pretreatment evaluations other than those which are 
part of current clinical care standards for a patient undergoing RALP or RALPN at University of 
Missouri. Preoperative evaluations follow recommendations from the NICE34,35.  
 
For RALP these include: 
- 
Routine history and physical examination to include documentation of any 
comorbidities, medications (including complementary and alternative medications), 
family history, social history (alcohol and tobacco usage), height, body weight, Karnofsky 
performance status within 30 days of surgery 
- 
Chest X-ray or CT scan of the Chest within 30 days of surgery 
- 
Pre-operative laboratory investigations: CBC, BMP, urinalysis (dipstick, microalbumin, 
creatinine, microscopic evaluation if indicated), urine culture if indicated within 30 days 
of surgery 
- 
Baseline EKG 
 
For RALPN these include: 
- 
Routine history and physical examination to include documentation of any 
comorbidities, medications (including complementary and alternative medications), 
family history, social history (alcohol and tobacco usage), height, body weight, Karnofsky 
performance status within 30 days of surgery 


13 
 
- 
Abdominal and pelvic CT scan and/or MRI and/or renal ultrasound within 60 days of 
surgery.  
- 
Chest X-ray or CT scan of the Chest within 30 days of surgery 
- 
Pre-operative laboratory investigations: CBC, BMP, urinalysis (dipstick, microalbumin, 
creatinine, microscopic evaluation if indicated), urine culture if indicated within 30 days 
of surgery 
- 
Baseline creatinine values will be converted to eGFR using the CKD-EPI equation 
o This value will be recorded from the MU pre-surgical testing blood work 
mandatory for all patients undergoing surgery at MU. 
SURGICAL INTERVENTION PLAN 
The technique of surgery will have been determined to be robotic assisted laparoscopy based 
on the discretion of the surgeon and patient. None of the techniques utilized in the study are 
considered experimental and all are considered standard therapeutic options for the patient 
with either a prostate cancer or a renal mass concerning for cancer amenable to prostatectomy 
or partial nephrectomy, respectively. Since patients will be undergoing the same approach, 
impact from physiologic differences between the 2 approaches are expected to be equally 
distributed between the 2 arms and the randomization will be additionally stratified by the type 
of the surgery. Patient medications will be recorded from the home medications list and 
managed perioperatively per institutional standards. 
 
The operating team will consist of surgeons on faculty at University of Missouri Department of 
Surgery-Urology Division. The procedures are performed under standardized general anesthesia 
with standard intraoperative vital sign monitoring. 
EVALUATION DURING TREATMENT/INTERVENTION 
This protocol does not require any additional evaluations after the subject is admitted for 
surgery other than those routinely part of clinical care for a patient undergoing robot assisted 
laparoscopic prostatectomy or robot assisted laparoscopic partial nephrectomy other than 
inquiring for subjects’ satisfaction on postop day one and monitoring for signs of lidocaine 
toxicity during inpatient hospitalization. Signs of possible lidocaine toxicity include the presence 
of perioral paresthesia, metallic taste, tinnitus, confusion, agitation, muscle spasms, and 
seizures. If toxicity is suspected the infusion will be stopped per the standard of care at 
University Hospital. 
 
Routine evaluation and management for those undergoing robot assisted laparoscopic 
prostatectomy include: 
- 
ASA classification, assigned by the anesthesiologist  
- 
Deep venous thrombosis prophylaxis per standardized pathway 
- 
Estimated blood loss 
- 
Use of intraoperative fluids (crystalloid, colloid, blood products) 
 


14 
 
Routine evaluation and management for those undergoing robot assisted laparoscopic partial 
nephrectomy, these include:  
- 
ASA classification, assigned by the anesthesiologist  
- 
Deep venous thrombosis prophylaxis per standardized pathway 
- 
Duration of warm ischemia time 
- 
Estimated blood loss 
- 
Use of intraoperative fluids (crystalloid, colloid, blood products) 
TOXICITIES/SIDE EFFECTS 
Various symptoms including perioral paresthesia, metallic taste, tinnitus, confusion, agitation, 
muscle spasms, and seizures have been described when the plasma lidocaine was higher than 5 
g/mL. While under general anesthesia, evidence of toxicity may be evident through 
bradycardia, increased intervals and widening QRS complex and may be increased with 
hypercapnia.16 However, it has been shown to be more cardio-protective, rather than cardio-
toxic in prospective randomized study36. The toxic levels of lidocaine are unlikely to be 
experienced at the levels used in our protocol. Our study is using the low end of the 
recommended dose and rate of 1-2 mg/kg/h. We additionally are utilizing a bolus only as a part 
of routine anesthesia induction, which is recommended to be 1-2 mg/kg and start the infusion 
15 minutes after the endotracheal intubation. 
 
Signs of lidocaine toxicity will be monitored per University Hospital standard of care protocol. 
This includes assessment and documentation by floor nursing staff, every 4 hours, of the signs 
and symptoms of lidocaine toxicity. The presence or lack of toxicity is reported in the medical 
record at these time points and pain nurse with the Department of Anesthesiology and 
Perioperative Medicine review this information. Management and review of medications will 
also be performed by the surgical and inpatient care teams per standard of care. Toxicity in our 
study will be evaluated clinically postoperatively by the presence of perioral paresthesia, 
metallic taste, tinnitus, confusion, agitation, muscle spasms, and seizures. Following standard of 
care, if there is concern of possible toxicity a lidocaine level may be ordered per standard of 
care. 
 
Surgical complications will be assessed prospectively and retrospectively and reviewed using 
the institutional standard for complications reporting for all surgical patients as followed by the 
Department of Surgery. Standardized graded complications and adverse effects at UM utilize 
the five-point modified Clavien-Dindo system. Grade I include complications requiring 
monitoring but no intervention; Grade II requires bedside or medical treatment; Grade III 
constitute adverse events requiring surgical or procedural intervention with return to normal 
functioning; Grade IV includes disabling, life-threatening complications with resulting functional 
loss and grade V is death of the patient. This is a modification of the Clavien-Dindo system for 
reporting complications with defined, categorized and classified events that will be segregated 
into time periods of ≤30 days, 31-90 days and > 90 days after surgery and includes medication 
complications following NCI CTCAE version 5 guidelines. 


15 
 
CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT 
If the surgery is aborted for any reason before attempted excision of the mass or intravenous 
infusion fails for any reason, the patient will be removed from the study and replaced. Based on 
past experience these issues are rare events. If a partial nephrectomy converts to radical 
nephrectomy, infusion will be continued and the data will be collected. If any robotic procedure 
converts to an open procedure, the subject will be excluded from the study. Lidocaine infusion 
will be continued or started (if subject is receiving normal saline) per surgeon request.    
 
The intraoperative period is defined as the period from anesthesia induction to the extubation 
of the trachea. The surgical time is determined from the incision to the final skin closure. 
 
The postoperative period is defined as the period from the extubation to the study endpoint at 
14 days ± 7 days.   
 
Blood loss is defined as the estimate accounted from the suction device and absorptive sponges 
during the procedure, as described and agreed upon by the surgeon, anesthesiologist, 
circulating nurse, and surgical technician as covered by institutional guidelines. 
 
Post-operative pain will be defined by the patient through the use of a 10 cm visual analog scale 
(VAS) and 11 point numeric scale (0-10).   
 
Length of hospital stay will be defined as the time the subject leaves the OR until subject meets 
standardized discharge criteria according to the surgeons' protocol, which will exclude social 
factors delaying real discharge times. 
 
Post-operative Ileus duration is defined as return of bowel function in hours from extubation 
per patients recall following nursing inquiry. Documentation will be done per standard of care 
by the nurse caring for study patient. 
 
Flatus return is defined as return of flatus in hours from extubation per patients recall following 
nursing inquiry. Documentation will be done by nurse caring for patient following standard of 
care. 
 
Patient satisfaction will be assessed 24 hours post-operative by Post Anesthesia Patient 
Satisfaction Assessment by research staff.  
 
CRITERIA FOR REMOVAL FROM STUDY 
Patients will be withdrawn from the study if they express a desire to do so, if it is determined to 
be in the patient’s best interest to do so, or if they do not undergo initiation of their surgical 
procedure as stipulated previously. If lidocaine infusion is stopped subject will be excluded from 
analysis. If surgery is converted from robotic assisted to open the subject will be excluded from 
analysis. Patients who are not evaluable for the study primary endpoint by failure to obtain 


16 
 
data for the primary endpoint will be excluded from the study and further analysis will not be 
performed.   
BIOSTATISTICS 
Sample Size 
The primary outcome for the study is the patient’s pain score at discharge. Although additional 
analyses are planned, the sample size estimate is based on this outcome. Assuming a common 
standard deviation of two-points, a sample size of 40 with 20 per treatment arm will provide 
80% power to detect a 2-point difference between groups when testing a two-sided alternative 
at the 5% level of significance using Wilcoxon Rank Sum Test. To take into account the loss to 
follow up, the drop-out inflated enrollment will be 46 subject with 23 subjects in each group 
assuming the same power. 
 
Unadjusted and Adjusted Analysis 
The unadjusted analysis will be designated as primary analysis and it will be performed to 
assess the pain level difference between the two groups. The adjusted analysis which will be 
designated as secondary analysis will incorporate other covariates like type of surgery in 
addition to the treatment assignments as covariate.  
 
Proposed Analyses 
Two statistical analysis methods will be used to make a comparison between the two treatment 
groups with regard to the primary end point: (i) to assess the difference of pain level between 
the two groups at specific time point, Wilcoxon Rank Sum Test will be used, (ii) to assess the 
pattern of change in pain level over the study period between the two groups, a Generalized 
Estimation Equation (GEE) model will be used.  
 
*A dropout rate of 10% was considered here. A Two Sample T-test using effect size sample size 
method was used to get an estimate of the samples needed from the PASS program.  
 
Table 2: Sample size assuming 80% and 90% power. 
RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION 
PROCEDURES 
Research Participant Registration 
Confirm eligibility as defined in the section entitled Criteria for Patient/Subject Eligibility.  
 
Obtain informed consent, by following procedures defined in section entitled Informed Consent 
Procedures. 
Sample Size 
  
  
  
Drop-out Inflated Enrollment  
 Treatment 
 Placebo  Effect Size  
SD 
Power 
 Treatment  
 Placebo 
20 
20 
2 
2 
80% 
23 
23 
27 
27 
2 
2 
90% 
30 
30 


17 
 
 
Randomization 
Randomization will be accomplished by the method of random permuted block and stratified 
by the type of the surgery and subject age. Since this is a double-blind study, the subjects’ 
treatment assignments will be kept in a blinded randomization table. The Excel column 
containing treatment designation assigned by a biostatistician will be occluded from view to 
maintain blinding. The investigational pharmacist will not be blinded and will have the 
randomization table. After recruitment, research staff will randomize the patient into the 
correct stratification and the Investigation Pharmacy will be notified. If it is clinically necessary 
to unblind a subjects’ treatment allocation this will be done using the randomization table.   
DATA MANAGEMENT ISSUES 
A Research Specialist (RS) from the Department of Anesthesiology and Perioperative Medicine 
will be assigned to the study who will provide data management support. The responsibilities of 
the RS include project compliance, data collection, abstraction and entry, data reporting, IRB 
correspondence, problem resolution and prioritization and coordination of the protocol study 
team activities. The data collected for this study will be entered into a secure departmental 
server. Source documentation and regulatory binders will be stored in a locked filing cabinet 
within a locked department office space. These sites are exclusively used for research 
documents and only members of the research team will have access to files for this study.  
 
Quality Assurance 
Registration reports will be generated every 6 months to monitor patient accrual and 
completeness of registration data. Routine data quality reports will be generated to assess 
missing data and inconsistencies. Accrual rates, and extent and accuracy of evaluations will be 
monitored throughout the study period. Potential problems will be brought to the attention of 
the study team for discussion and action.  
 
Data and Safety Monitoring 
The plans address the policies set forth by the NCI in the document entitled “Policy of the 
National Cancer Institute for Data and Safety Monitoring of Clinical trials” which can found at 
http://cancertrials.nci.nih.gov/researchers/dsm/index.html. The MU Health Care Data and 
Safety Monitoring Plans can be found online.  
 
There are several different mechanisms by which clinical trials are monitored for data, safety 
and quality. There are institutional processes in place for quality assurance (e.g., protocol 
monitoring, compliance and data verification audits, therapeutic response and staff education 
on clinical research QA) and departmental procedures for quality control, plus institutional 
committees that are responsible for monitoring the activities of the clinical trials program.  


18 
 
PROTECTION OF HUMAN SUBJECTS 
Benefits and Risks 
The experimental intervention (intravenous lidocaine infusion) is currently used at University of 
Missouri Hospital through the ERAS protocol. Numerous studies have shown significant patient 
benefits in all fields, including Urology. A review of 45, randomized studies demonstrated no 
major adverse events secondary to its usage. Therefore, we do not believe that the therapeutic 
aspects of this trail pose any risk different from patients undergoing robot assisted laparoscopic 
prostatectomy or a robot assisted laparoscopic partial nephrectomy. 
  
Toxicities and side effects 
Adverse outcomes are not anticipated with the doses of lidocaine being used in the protocol. 
Signs of lidocaine toxicity will be monitored per University Hospital standard of care protocol. 
This includes assessment and documentation by floor nursing staff, every 4 hours, of the signs 
and symptoms of lidocaine toxicity. The presence or lack of toxicity is reported in the medical 
record at these time points and pain nurse with the Department of Anesthesiology and 
Perioperative Medicine review this information. Management and review of medications will 
also be performed by the surgical and inpatient care teams per standard of care. Toxicity in our 
study will be evaluated clinically postoperatively by the presence of perioral paresthesia, 
metallic taste, tinnitus, confusion, agitation, muscle spasms, and seizures. Following standard of 
care, if there is concern of possible toxicity a lidocaine level may be ordered per standard of 
care. 
 
Alternatives / Therapeutic options 
The alternative to participation in the trial would be to undergo robot assisted laparoscopic 
prostatectomy or a robot assisted laparoscopic partial nephrectomy according to the surgeon’s 
standard practice and not to participate in the study.  No other aspect of patient care would 
differ. 
 
Financial Costs and Burdens 
Subjects will not be compensated for their participation and there are not costs involved in 
participation. Cost of the study medications, delivery from pharmacy, and administration will 
not be charged to the subject. The study is internally funded by the Department of Surgery – 
Urology Division and Department of Anesthesiology and Perioperative Medicine.   
 
Privacy and Confidentiality 
We will keep the study records confidential. No identifiers will be used in any reports or 
publications resulting from the study.  
 
Volunteering Nature of the Study 
Participation is entirely voluntary. All aspects of patient’s care and monitoring will be 
unaffected by whether the patient chooses to consent for the study. 


19 
 
Serious Adverse Event (SAE) Reporting 
Any SAE will be reported to the IRB as soon as possible, but no later than 5 calendar days. The 
reporting procedure will be followed as outlined in the University of Missouri protocol found in 
the “Core Standard Operating Procedure for Event Reporting.”.  
INFORMED CONSENT PROCEDURES 
Before protocol-specified procedures are carried out, consenting professionals will explain full 
details of the protocol and study procedures as well as the risks involved to participants prior to 
their inclusion in the study. Participants will also be informed that they are free to withdraw at 
any time. All participants must sign and date an IRB approved informed consent form indicating 
their consent to participate. This consent form meets the requirements of the Code of Federal 
Regulations and the Institutional Review Board.  
 
Before any protocol-specific procedures can be carried out, the consenting professional will 
fully explain the aspects of patient privacy concerning research specific information. In addition 
to signing the IRB Informed consent, all patients must agree to the Research Authorization 
component of the informed consent form. 
 
Each participant and consenting professional will sign the consent form. The participant will 
receive a copy of the signed informed consent form. A copy of the signed informed consent 
form will be placed in the participant’s chart and subsequently scanned into the electronic 
medical record under Research Consents.   
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1.  
Bates C, Laciak R, Southwick A, Bishoff J. Overprescription of Postoperative Narcotics: A 
Look at Postoperative Pain Medication Delivery, Consumption and Disposal in Urological 
Practice. J Urol. 2011;185(2):551-555. doi:10.1016/j.juro.2010.09.088 
2.  
Hedegaard H, Warner M, Miniño AM. Drug Overdose Deaths in the United States, 1999–
2016. 1999. https://www.cdc.gov/nchs/data/databriefs/db294.pdf. Accessed May 25, 
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Centers for Disease Control and Prevention (CDC). Vital signs: overdoses of prescription 
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Dunn LK, Durieux ME. Perioperative Use of Intravenous Lidocaine. Anesthesiology. 
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De Oliveira GS, Fitzgerald P, Streicher LF, Marcus R-J, McCarthy RJ. Systemic Lidocaine to 
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Joshi GP, Jaschinski T, Bonnet F, Kehlet H, PROSPECT collaboration. Optimal pain 
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Wheeler M, Oderda GM, Ashburn MA, Lipman AG. Adverse Events Associated With 


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Postoperative Opioid Analgesia: A Systematic Review. doi:10.1054/jpai.2002.123652 
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Marcus HJ, Hughes-Hallett A, Payne CJ, et al. Trends in the diffusion of robotic surgery: A 
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Choi JE, You JH, Kim DK, Rha KH, Lee SH. Comparison of Perioperative Outcomes 
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Avulova S, Smith JA. Is Comparison of Robotic to Open Radical Prostatectomy Still 
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D’Alonzo RC, Gan TJ, Moul JW, et al. A retrospective comparison of anesthetic 
management of robot-assisted laparoscopic radical prostatectomy versus radical 
retropubic prostatectomy. J Clin Anesth. 2009;21(5):322-328. 
doi:10.1016/j.jclinane.2008.09.005 
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Batley SE, Prasad V, Vasdev N, Mohan-S G. Post-Operative Pain Management in Patients 
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Woldu SL, Weinberg AC, Bergman A, et al. Pain and Analgesic Use After Robot-Assisted 
Radical Prostatectomy. J Endourol. 2014;28(5):544-548. doi:10.1089/end.2013.0783 
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Jendoubi A, Naceur I Ben, Bouzouita A, et al. A comparison between intravenous 
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2017;11(2):177-184. doi:10.4103/1658-354X.203027 
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Naik BI, Tsang S, Knisely A, Yerra S, Durieux ME. Retrospective case-control non-
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Estebe J-P. Intravenous lidocaine. doi:10.1016/j.bpa.2017.05.005 
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Nakhli MS, Kahloul M, Guizani T, Zedini C, Chaouch A, Naija W. Intravenous lidocaine as 
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Lauwick S, Kim DJ, Mistraletti G, Carli F. Functional walking capacity as an outcome 
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Groudine SB, Fisher HA, Kaufman RP, et al. Intravenous lidocaine speeds the return of 
bowel function, decreases postoperative pain, and shortens hospital stay in patients 
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http://www.ncbi.nlm.nih.gov/pubmed/9459225. Accessed April 24, 2018. 
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Weinberg L, Rachbuch C, Ting S, et al. A randomised controlled trial of peri-operative 
lidocaine infusions for open radical prostatectomy*. doi:10.1111/anae.13368 
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Weibel S, Jokinen J, Pace NL, et al. Efficacy and safety of intravenous lidocaine for 
postoperative analgesia and recovery after surgery: a systematic review with trial 
sequential analysis. Br J Anesth. 2016;116(6):770-783. doi:10.1093/bja/aew101 
22.  
Sun Y, Li T, Wang N, Yun Y, Gan TJ. Perioperative Systemic Lidocaine for Postoperative 
Analgesia and Recovery after Abdominal Surgery. Dis Colon Rectum. 2012;55(11):1183-
1194. doi:10.1097/DCR.0b013e318259bcd8 
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Wongyingsinn M, Baldini G, Charlebois P, Liberman S, Stein B, Carli F. Intravenous 


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Lidocaine Versus Thoracic Epidural Analgesia. Reg Anesth Pain Med. 2011;36(3):241-248. 
doi:10.1097/AAP.0b013e31820d4362 
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106. [American Society of Anesthesiologists, etc.]; 2007. 
http://anesthesiology.pubs.asahq.org/article.aspx?articleid=1923374. Accessed May 25, 
2018. 
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Tikuišis R, Miliauskas P, Samalavičius NE, Žurauskas A, Samalavičius R, Zabulis V. 
Intravenous lidocaine for post-operative pain relief after hand-assisted laparoscopic 
colon surgery: a randomized, placebo-controlled clinical trial. Tech Coloproctol. 
2014;18(4):373-380. doi:10.1007/s10151-013-1065-0 
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Lauwick S, Kim DJ, Michelagnoli G, et al. Intraoperative infusion of lidocaine reduces 
postoperative fentanyl requirements in patients undergoing laparoscopic 
cholecystectomy. Can J Anaesth. 2008;55(11):754-760. 
http://www.ncbi.nlm.nih.gov/pubmed/19138915. Accessed May 25, 2018. 
27.  
De Oliveira GS, Duncan K, Fitzgerald P, Nader A, Gould RW, McCarthy RJ. Systemic 
Lidocaine to Improve Quality of Recovery after Laparoscopic Bariatric Surgery: A 
Randomized Double-Blinded Placebo-Controlled Trial. Obes Surg. 2014;24(2):212-218. 
doi:10.1007/s11695-013-1077-x 
28.  
Kim TH, Kang H, Hong JH, et al. Intraperitoneal and intravenous lidocaine for effective 
pain relief after laparoscopic appendectomy: a prospective, randomized, double-blind, 
placebo-controlled study. Surg Endosc. 2011;25(10):3183-3190. doi:10.1007/s00464-011-
1684-3 
29.  
Tauzin-Fin P, Bernard O, Sesay M, et al. Benefits of intravenous lidocaine on post-
operative pain and acute rehabilitation after laparoscopic nephrectomy. J Anaesthesiol 
Clin Pharmacol. 2014;30(3):366-372. doi:10.4103/0970-9185.137269 
30.  
Kim TH, Kang H, Choi YS, et al. Pre- and Intraoperative Lidocaine Injection for Preemptive 
Analgesics in Laparoscopic Gastrectomy: A Prospective, Randomized, Double-Blind, 
Placebo-Controlled Study. J Laparoendosc Adv Surg Tech. 2013;23(8):663-668. 
doi:10.1089/lap.2012.0542 
31.  
Wuethrich PY, Romero J, Burkhard FC, Curatolo M. No benefit from perioperative 
intravenous lidocaine in laparoscopic renal surgery. Eur J Anaesthesiol. 2012;29(11):537-
543. doi:10.1097/EJA.0b013e328356bad6 
32.  
Acevedo-Arcique CM, Ibancovichi JA, Chavez JR, et al. Lidocaine, Dexmedetomidine and 
Their Combination Reduce Isoflurane Minimum Alveolar Concentration in Dogs. Thamm 
D, ed. PLoS One. 2014;9(9):e106620. doi:10.1371/journal.pone.0106620 
33.  
Pypendop BH, Ilkiw JE. The Effects of Intravenous Lidocaine Administration on the 
Minimum Alveolar Concentration of Isoflurane in Cats. Anesth Analg. 2005;100(1):97-
101. doi:10.1213/01.ANE.0000139350.88158.38 
34.  
Cui HW, Turney BW, Griffiths J. The Preoperative Assessment and Optimization of 
Patients Undergoing Major Urological Surgery. Curr Urol Rep. 2017;18(7):54. 
doi:10.1007/s11934-017-0701-z 
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Routine preoperative tests for elective surgery | Guidance and guidelines | NICE. 
https://www.nice.org.uk/guidance/ng45. Accessed May 27, 2018. 
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Kim H-J, Kim WH, Kim G, et al. A comparison among infusion of lidocaine and 


22 
 
dexmedetomidine alone and in combination in subjects undergoing coronary artery 
bypass graft: a randomized trial. Contemp Clin Trials. 2014;39(2):303-309. 
doi:10.1016/j.cct.2014.10.005 
37.  
Song X, Sun Y, Zhang X, Li T, Yang B. Effect of perioperative intravenous lidocaine infusion 
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APPENDECIES 
No appendices 
 
 

ICF_004.pdf: 
1 of 11 
 
 
 
CONSENT FORM TO PARTICIPATE IN A RESEARCH STUDY 
 
INVESTIGATOR’S NAME: KATIE MURRAY, DO, MS 
PROJECT #: 2012402 
Version #: 3 
STUDY TITLE: A PROSPECTIVE, RANDOMIZED, DOUBLE-BLINDED, PLACEBO-CONTROLLED 
CLINICAL TRIAL EVALUATING THE USE OF PERIOPERATIVE INTRAVENOUS 
LIDOCAINE INFUSION TO DECREASE PAIN SCORES AND OPIOID CONSUMPTION 
AFTER ROBOTIC-ASSISTED PROSTATECTOMY AND ROBOTIC-ASSISTED 
PARTIAL NEPHRECTOMY 
 
We invite you to take part in this research study. This consent form tells you why we are doing the study, 
what will happen if you join the study, and other important information about the study. 
 
Please take as much time as you need to read this consent form. You can discuss it with your family, 
friends, or personal doctor. If there is anything you do not understand, please ask us to explain. Then you 
can decide if you want to take part in the study or not. 
 
The Principle Investigator (also called the study doctor) is Dr. Katie Murray. The people working with 
Dr. Murray on this study are called the study team. 
 
WHAT SHOULD I KNOW BEFORE I DECIDE WHETHER TO TAKE PART IN THIS STUDY? 
• Research studies help us to learn new things and test new ideas about treating certain 
conditions/diseases. 
• Taking part in a research study is voluntary. You decide if you want to take part, and you can stop 
taking part at any time. Your regular medical care at the University of Missouri Hospitals and 
Clinics will not be affected now or in the future if you decide you do not want to be in this study. 
• We are doing this study because the use of continuous lidocaine infusions in patients undergoing 
robotic-assisted surgeries has not been well studied. We hope to learn how to better guide 
clinicians on the use of this treatment for robotic surgeries. 
• We invite you to take part in this study because you are scheduled to have elective robotic 
urologic surgery at University Hospital in Columbia Missouri. 
IRB Approval Date: Aug 10, 2022; Written Consent Form ID #603072; Annual Update ID #380272
ClinicalTrials.gov - NCT03824808
Version date: 08/28/2018


2 of 11 
 
 
• About 46 people will take part in this study. All cases will be at the University of Missouri. 
• If you take part in this study, all your study visits will occur at University Hospital. You will come 
for your scheduled surgery, be monitored by study staff during your hospital stay, and at your two- 
week clinic visit. You will be asked questions about your pain, surgical recovery, and satisfaction 
during these visits. We will explain these procedures in this form. 
• If you join this study, you will not have to stop your planned surgical procedure or regular pain 
management treatment for as long as you are in the study. 
• The total amount of time you could be in this study is about three weeks. 
• Taking part in this study may or may not make your health better. We hope that the information 
we learn from this study will help in the future treatment of people who choose to have robot 
assisted urologic surgery. There is no guarantee that taking part in this research will result in 
any improvement in your condition. 
• As with any research study, there are risks that we know about and there may be some we don’t 
know about. We will explain these risks in this form. 
• We will only include you in this study if you give us your permission first by signing this consent 
form. 
 
WHY IS THIS STUDY BEING DONE? 
 
Once a patient undergoes a robotic-assisted urological surgery it is necessary to control surgery-related 
pain. The purpose of this study is to determine if a continuous intravenous infusion of the medication 
lidocaine over the twenty-four-hour period following robotic-assisted urological surgeries will help to 
decrease postoperative pain. 
 
Continuous infusions are performed using devices called infusion pumps. For this study, an infusion 
pump will be mounted on a pole located near your bed. The infusion will be started while you are asleep 
for your surgery and last for 24 hours. 
 
This research is being done because the use of continuous lidocaine infusions in patients undergoing 
robotic-assisted urological surgeries has not been well studied. The benefit of continuous lidocaine 
infusions have been demonstrated to help patients’ pain management in different surgeries. 
IRB Approval Date: Aug 10, 2022; Written Consent Form ID #603072; Annual Update ID #380272


3 of 11 
 
 
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY? 
 
We plan to enroll 46 patients so that 40 people will take part in this study performed in University 
Hospital at the University of Missouri. 
 
WHAT IS INVOLVED IN THE STUDY? 
 
Whether or not you are in the study, you will receive the same medical care before, during and after your 
surgery. The type of medications used for the general anesthesia in this study will be the same in both 
groups and are the same medications used for general anesthesia for robotic-assisted urological surgery if 
you are not in the study. Your robotic-assisted urological surgery will be performed in the same manner 
that it would be done if you were not in the study. 
 
If you are in the study, you will be “randomized” into one of the study groups described below. 
Randomization means that you are put into a group by chance. It is like flipping a coin. Neither you nor 
the researcher will choose what group you will be in. You will have an equal chance of being placed in 
one of the groups, including a placebo. If you are in the placebo group you will not receive the study 
medication. Placebos are commonly used in studies involving medications 
 
Intravenous lidocaine is currently approved for use in correction irregular heartbeats and it is commonly 
used as a numbing agent. It is still being investigated for use in the proposed manner in this study. 
 
In this study, one group will receive intravenous lidocaine and the other group will receive an intravenous 
normal saline as a placebo. Lidocaine is a numbing medication used for pain relief. Normal saline is a 
salt water solution. Both medication treatments are routinely used today.  Neither you nor your doctor 
will know which drug you actually received until the end of the study. This “blinding” is usually used in 
clinical trials to get objective answers. In the case of unforeseen complications, on request your doctor 
will be told which medication you received. 
 
If you take part in this study, you will have the following tests and procedures: 
 
 
• There are no additional laboratory tests or medical scans if you take part in the study. 
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• As part of the study, one group will receive the medication lidocaine and the other group will receive 
a placebo of normal saline. 
• At the end of your surgery, you will leave the operating room with a blinded intravenous infusion 
providing either lidocaine or normal saline. This infusion will be started when you are asleep for your 
surgery and continue for twenty-four hours. 
• We will visit you every day following your surgery until you are discharged from the hospital and ask 
you to rate your level of pain using a Visual Analog Scale (a four inch line on which you will mark 
your pain) and a scale of 1 (no pain) to 10 (worst imaginable pain). This will also occur at your 14 
day follow-up visit. We will also record the amount of pain medication that you use each day. 
• You will be monitored for side effects during your hospital stay. 
• Your satisfaction with anesthesia will be evaluated using a questionnaire on the first day after surgery. 
 
If you are not in the study, the drugs you will receive will be determined by your doctors as part of the 
standard of care. You may receive an intravenous lidocaine infusion regardless of participating in this 
study. This will be determined by your doctor. 
 
The information we collect from you for this study will not be used or shared with other investigators for 
future research studies. This applies even if we remove all information that could identify you from the 
data. 
 
HOW LONG WILL I BE IN THE STUDY? 
 
You will be in this study from the time you sign the research informed consent form until your post- 
operative Urology Clinic visit. 
 
The investigator and/or your doctor may decide to take you off this study if one of the study medications 
is not available, if your surgery is stopped before attempting to remove your cancer, or if the intravenous 
infusion fails for any reason. 
 
You can stop participating at any time. Your decision to withdraw from the study will not affect in 
any way your medical care and/or benefits. If you decide to stop participating in the study, you are 
encouraged to discuss your decision with your doctor. 
 
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WHAT ARE THE RISKS OF THE STUDY? 
 
While on the study, you are at risk for the side effects described below. You should discuss these with the 
investigator and/or your doctor. There may also be other side effects that we cannot predict. You may 
receive other drugs to make side effects less severe and uncomfortable.  Many side effects go away 
shortly after the drugs are stopped, but in some cases side effects can be serious or long-lasting or 
permanent. 
 
All of the surgical procedures used are standard procedures and will be done whether you are in the study 
or not so they will not increase the risk. The medications that are used for general anesthesia in the study 
are the same as the medications used for anesthesia if you are not in the study. As such, there are no 
increased risks from the general anesthesia medication used or the procedures performed in the study. 
 
We will be using one medication, lidocaine, and a placebo of normal saline. Both medications will be 
delivered by continuous intravenous infusion. Toxic levels of intravenous lidocaine are unlikely to be 
experienced following the dosage used in our protocol. The risks for both intravenous lidocaine and 
normal saline will be explained by our doctor. 
 
Systemic reactions of the following types have been reported for intravenous lidocaine: 
 
• Nervous System Disorders: respiratory depression (slow breathing) and arrest (stopped 
breathing); unconsciousness; convulsions (seizures); tremors (unintentional shaking); 
twitching; vomiting; blurred or double vision; drowsiness; dizziness; light-headedness; 
tinnitus (ringing in the ears); sensation of heat, cold or numbness; euphoria (feeling of 
intense happiness); apprehension (feeling that something bad will happen); agitation 
(anxiety and nervous excitement); confusion; paresthesia (burning or prickling sensation on 
body parts); dysarthria (damage to muscles used to produce speech). 
• Cardiovascular System: cardiovascular arrest (stop in heart beat); bradycardia (slow heart 
rate) which may lead to cardiac arrest; hypotension (low blood pressure), Ventricular 
fibrillation (irregular heartbeat with quiver in the heart), Ventricular tachycardia (fast, 
abnormal heart rate), Ventricular arrhythmia (abnormal heartbeat), Asystole (stop in heart 
with no electrical activity). 
• Gastrointestinal Disorders: Hypoesthesia oral (numbness in mouth), Nausea. 
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• Hematologic Effects: methemoglobinemia (blood disorder with low oxygen delivered to cells) 
 
• Psychiatric Disorders: Disorientation (confusion) 
 
• Allergic reactions, including anaphylactic (serious, life-threatening) reactions, may occur but are 
infrequent. There have been no reports of cross sensitivity (reaction to a drug) between lidocaine 
hydrochloride and procainamide or quinidine (both drugs used to treat abnormal heart rhythms). 
 
Reactions which may occur because of the solution or the technique of administration of Normal Saline: 
 
• Fever (temporary increase in body temperature) 
 
• Infection at the site of injection 
 
• Venous thrombosis (blood clot) or phlebitis (vein inflammation) extending from the site of injection 
 
• Extravasation (leakage of intravenously infused fluid into tissue around site of infusion) 
 
• Hypervolemia (fluid overload in blood) 
 
In clinical trials where you and the investigator do not know what drugs you are given, there will be a 
mechanism to discover which treatment you are receiving if your condition worsens. Research personnel 
will disclose which medication you receive on your physician request. 
 
For the reasons stated above the investigator will observe you closely while giving the treatment described 
and, if you have any worrisome symptoms or symptoms that the investigator or her associates have described 
to you, notify the investigator immediately. Dr. Murray can be reached by telephone at 573-884-2384 / 573- 
884-8768 / 573-884-4057. For more information about risks and side effects, ask the investigator or 
contact Kate Muzzey, RN, BSN (Urology Nurse Navigator) at 573-884-2384. 
 
ARE THERE BENEFITS TO TAKING PART IN THE STUDY? 
 
If you agree to take part in this study, there may or may not be direct medical benefit to you. You may 
expect to benefit from taking part in this research to the extent that you are contributing to medical 
knowledge. We hope the information learned from this study will benefit other patients who are having 
robotic-assisted urologic surgery in the future. 
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There is no guarantee that taking part in this research will result in any improvement in your condition. 
However, the information gained in this study may be used to improve the care of adults who need 
robotic-assisted urologic surgery in the future. 
 
WHAT OTHER OPTIONS ARE THERE? 
 
Instead of being in this study, you have these options: 
 
 
An alternative is to not participate in this research study. You can have your robotic-assisted urologic 
surgery performed with general anesthesia. 
 
You may receive an intravenous lidocaine infusion even if you do not take part in this study. 
Please discuss these and other options with the investigator and your doctor. 
WHAT ABOUT CONFIDENTIALITY? 
 
A copy of this consent will be placed in the medical record. Anyone accessing your record will be able to 
view the document and see that you have agreed to participate in the study.  Medical information 
produced by this study will become part of your hospital medical record. Information that does not 
become part of your medical record will be stored in the investigator’s file and identified by a code 
number only. The code key connecting your name to specific information about you will be kept in a 
separate, secure location. Information contained in your records may not be given to anyone unaffiliated 
with the University Hospital in a form that could identify you without your written consent, except as 
required by law. If the investigator conducting this study is not your primary, or regular doctor, the 
investigator must obtain your permission before contacting your regular doctor for information about your 
past medical history or to inform them that you are in this trial. 
 
It is possible that your medical and/or research record, including sensitive information and/or identifying 
information, may be inspected and/or copied by the study sponsor (and/or its agent), the Food and Drug 
Administration (FDA), federal or state government agencies, or hospital accrediting agencies, in the 
course of carrying out their duties. If your record is inspected or copied by the study sponsor (and/or its 
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agents), or by any of these agencies, the University Hospital will use reasonable efforts to protect your 
privacy and the confidentiality of your medical information. 
 
The results of this study may be published in a medical book or journal or used for teaching purposes. 
However, your name or other identifying information will not be used in any publication or teaching 
materials without your specific permission. 
 
 
WHAT ARE THE COSTS? 
 
There is no cost to you for the study drug itself. However, you will be paying for the normal cost of your 
routine medical care. Any procedure related solely to research that would not otherwise be necessary will 
be explained. Your doctor will discuss these with you. 
 
In addition, the use of other medications to help control side effects could result in added costs that may 
or may not be covered by your medical insurance. 
 
You will not be charged for the questionnaires that are part of this research study. You or your insurance 
company will, however, be charged for any other portion of your care that is considered standard care. 
 
You or your insurance company will be charged for continuing medical care and/or hospitalization. 
 
 
A social worker and financial counselor are available to discuss medical/financial concerns with you such 
as insurance coverage. Please let the study staff know if you would like to visit with these individuals and 
they will arrange an appointment. 
 
WILL I BE PAID FOR PARTICIPATING IN THE STUDY? 
 
You will receive no payment for taking part in this study. 
 
 
WHAT IF I AM INJURED? 
 
It is not the policy of the University of Missouri to compensate human subjects in the event the research 
results in injury. The University of Missouri, in fulfilling its public responsibility, has provided medical, 
professional and general liability insurance coverage for any injury in the event such injury is caused by the 
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negligence of the University of Missouri, its faculty and staff. The University of Missouri also will provide, 
within the limitations of the laws of the State of Missouri, facilities and medical attention to subjects who 
suffer injuries while participating in the research projects of the University of Missouri. In the event you 
have suffered injury as the result of participation in this research program, you are to contact the Risk 
Management Officer, telephone number (573) 882-1181, at the Health Sciences Center, who can review the 
matter and provide further information. This statement is not to be construed as an admission of liability. 
 
WHAT ARE MY RIGHTS AS A PARTICIPANT? 
 
Participation in this study is voluntary. You do not have to participate in this study. Your present 
or future care will not be affected should you choose not to participate. If you decide to participate, 
you can change your mind and drop out of the study at any time without affecting your present or future 
care in the University Hospital at the University of Missouri. Leaving the study will not result in any 
penalty or loss of benefits to which you are entitled. In addition, the investigator of this study may decide 
to end your participation in this study at any time after she has explained the reasons for doing so and has 
helped arrange for your continued care by your own doctor, if needed. 
 
You will be informed of any significant new findings discovered during the course of this study that 
might influence your health, welfare, or willingness to continue participation in this study. 
 
Where Can I Get More Information About This Study? 
 
A description of this clinical trial will be available on www.ClinicalTrials.gov, as required by U.S. law. 
This Web site will not include information that can identify you. At most, the Web site will include a 
summary of the results. You can search this Web site at any time. 
 
Who Can Answer My Questions About The  Study? 
 
If you have more questions about this study at any time, you can call Dr. Murray or Kate Muzzey, RN, 
BSN (Urology Nurse Navigator) at 573-884-2384. Dr. Murray can also be contacted at any time at 573- 
884-4057 or 573-884-8768. 
 
You may also contact the University of Missouri Institutional Review Board (IRB) if you: 
• Have any questions about your rights as a study participant; 
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• Want to report any problems or complaints; or 
• Feel under any pressure to take part or stay in this study. 
 
The IRB is a group of people who review research studies to make sure the rights of participants are 
protected. Their phone number is 573-882-3181. 
 
If you want to talk privately about your rights or any issues related to your participation in this study, you 
can contact University of Missouri Research Participant Advocacy by calling 888-280-5002 (a free call), 
or emailing MUResearchRPA@missouri.edu. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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WE WILL GIVE YOU A COPY OF THIS CONSENT FORM. PLEASE KEEP IT WHERE YOU CAN FIND IT EASILY. IT WILL 
HELP YOU TO REMEMBER WHAT WE DISCUSSED TODAY. 
SIGNATURE 
 
I confirm that the purpose of the research, the study procedures, the possible risks and discomforts as well 
as potential benefits that I may experience have been explained to me. Alternatives to my participation in 
the study also have been discussed. I have read this consent form and my questions have been answered. 
My signature below indicates my willingness to participate in this study. 
 
 
 
Subject/Patient* 
Date 
 
 
 
Legal Guardian/Advocate/Witness (if required)** 
Date 
 
 
 
Additional Signature (if required) (identify relationship to subject)*** 
Date 
 
*A minor’s signature on this line indicates his/her assent to participate in this study. A minor’s signature is not 
required if he/she is under 7 years old. Use the “Legal Guardian/Advocate/Witness” line for the parent’s signature, 
and you may use the "Additional Signature" line for the second parent’s signature, if required. 
 
**The presence and signature of an impartial witness is required during the entire informed consent discussion if 
the patient or patient’s legally authorized representative is unable to read. 
 
***The "Additional Signature" line may be used for the second parent’s signature, if required. This line may also 
be used for any other signature which is required as per federal, state, local, sponsor and/or any other entity 
requirements. 
 
“If required” means that the signature line is signed only if it is required as per federal, state, local, sponsor and/or 
any other entity requirements. 
 
SIGNATURE OF STUDY REPRESENTATIVE 
I have explained the purpose of the research, the study procedures, identifying those that are 
investigational, the possible risks and discomforts as well as potential benefits and have answered 
questions regarding the study to the best of my ability. 
 
 
 
Study Representative**** 
Date 
 
****Study Representative is a person authorized to obtain consent. Per the policies of the University of Missouri 
Health Care, for any 'significant risk/treatment' study, the Study Representative must be a physician who is either 
the Principal or Co-Investigator. If the study is deemed either 'significant risk/non-treatment' or 'minimal risk,' the 
Study Representative may be a non-physician study investigator. 
IRB Approval Date: Aug 10, 2022; Written Consent Form ID #603072; Annual Update ID #380272