Effect of Perioperative Intravenous Lidocaine Infusion in Robotic-Assisted Urologic Surgery

Prostate Cancer Clinical Trial

Official 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03824808
• Other study ID #: 2012402
• Status: Terminated
• Phase: Phase 4
• Start date: February 26, 2019
• Est. completion date: March 26, 2020

Study information

• Verified date: October 2023
• Source: University of Missouri-Columbia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: March 26, 2020
• Est. primary completion date: March 26, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Undergoing robotic assisted prostatectomy or robotic assisted partial nephrectomy at University of Missouri Hospital for prostate cancer or kidney mass

• Age = 18 years

• ASA I-III

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Kidney Cancer
• Kidney Neoplasms
• Prostate Cancer

Intervention

Drug:
• Lidocaine Hydrochloride 0.8% in Dextrose 5% Solution
Lidocaine Hydrochloride and 5% Dextrose Injection, USP is a sterile, nonpyrogenic solution prepared from lidocaine hydrochloride and dextrose in water for injection.
• 0.9% Sodium Chloride Injection
Sodium Chloride Injection USP is sterile, nonpyrogenic, isotonic and contains no bacteriostatic or antimicrobial agents.

Locations

Country	Name	City	State
United States	University Hospital	Columbia	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
University of Missouri-Columbia

Country where clinical trial is conducted

United States, 

References & Publications (16)

Avulova S, Smith JA Jr. Is Comparison of Robotic to Open Radical Prostatectomy Still Relevant? Eur Urol. 2018 May;73(5):672-673. doi: 10.1016/j.eururo.2018.01.011. Epub 2018 Feb 3. No abstract available. — View Citation

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 Feb;185(2):551-5. doi: 10.1016/j.juro.2010.09.088. Epub 2010 Dec 18. — View Citation

Batley SE, Prasad V, Vasdev N, Mohan-S G. Post-Operative Pain Management in Patients Undergoing Robotic Urological Surgery. Curr Urol. 2016 Feb;9(1):5-11. doi: 10.1159/000442843. Epub 2016 Feb 10. — View Citation

Centers for Disease Control and Prevention (CDC). Vital signs: overdoses of prescription opioid pain relievers---United States, 1999--2008. MMWR Morb Mortal Wkly Rep. 2011 Nov 4;60(43):1487-92. — View Citation

Choi JE, You JH, Kim DK, Rha KH, Lee SH. Comparison of perioperative outcomes between robotic and laparoscopic partial nephrectomy: a systematic review and meta-analysis. Eur Urol. 2015 May;67(5):891-901. doi: 10.1016/j.eururo.2014.12.028. Epub 2015 Jan 6. — View Citation

D'Alonzo RC, Gan TJ, Moul JW, Albala DM, Polascik TJ, Robertson CN, Sun L, Dahm P, Habib AS. A retrospective comparison of anesthetic management of robot-assisted laparoscopic radical prostatectomy versus radical retropubic prostatectomy. J Clin Anesth. 2009 Aug;21(5):322-8. doi: 10.1016/j.jclinane.2008.09.005. Epub 2009 Aug 22. — View Citation

De Oliveira GS Jr, Fitzgerald P, Streicher LF, Marcus RJ, McCarthy RJ. Systemic lidocaine to improve postoperative quality of recovery after ambulatory laparoscopic surgery. Anesth Analg. 2012 Aug;115(2):262-7. doi: 10.1213/ANE.0b013e318257a380. Epub 2012 May 14. — View Citation

Dunn LK, Durieux ME. Perioperative Use of Intravenous Lidocaine. Anesthesiology. 2017 Apr;126(4):729-737. doi: 10.1097/ALN.0000000000001527. No abstract available. — View Citation

Hedegaard H, Warner M, Minino AM. Drug Overdose Deaths in the United States, 1999-2016. NCHS Data Brief. 2017 Dec;(294):1-8. — View Citation

Jendoubi A, Naceur IB, Bouzouita A, Trifa M, Ghedira S, Chebil M, Houissa M. A comparison between intravenous lidocaine and ketamine on acute and chronic pain after open nephrectomy: A prospective, double-blind, randomized, placebo-controlled study. Saudi J Anaesth. 2017 Apr-Jun;11(2):177-184. doi: 10.4103/1658-354X.203027. — View Citation

Joshi GP, Jaschinski T, Bonnet F, Kehlet H; PROSPECT collaboration. Optimal pain management for radical prostatectomy surgery: what is the evidence? BMC Anesthesiol. 2015 Nov 4;15:159. doi: 10.1186/s12871-015-0137-2. — View Citation

Marcus HJ, Hughes-Hallett A, Payne CJ, Cundy TP, Nandi D, Yang GZ, Darzi A. Trends in the diffusion of robotic surgery: A retrospective observational study. Int J Med Robot. 2017 Dec;13(4):e1870. doi: 10.1002/rcs.1870. Epub 2017 Nov 6. — View Citation

Naik BI, Tsang S, Knisely A, Yerra S, Durieux ME. Retrospective case-control non-inferiority analysis of intravenous lidocaine in a colorectal surgery enhanced recovery program. BMC Anesthesiol. 2017 Jan 31;17(1):16. doi: 10.1186/s12871-017-0306-6. — View Citation

Nakhli MS, Kahloul M, Guizani T, Zedini C, Chaouch A, Naija W. Intravenous lidocaine as adjuvant to general anesthesia in renal surgery. Libyan J Med. 2018 Dec;13(1):1433418. doi: 10.1080/19932820.2018.1433418. — View Citation

Wheeler M, Oderda GM, Ashburn MA, Lipman AG. Adverse events associated with postoperative opioid analgesia: a systematic review. J Pain. 2002 Jun;3(3):159-80. doi: 10.1054/jpai.2002.123652. No abstract available. — View Citation

Woldu SL, Weinberg AC, Bergman A, Shapiro EY, Korets R, Motamedinia P, Badani KK. Pain and analgesic use after robot-assisted radical prostatectomy. J Endourol. 2014 May;28(5):544-8. doi: 10.1089/end.2013.0783. Epub 2014 Jan 30. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in Post-operative Pain Scores Measured by Visual Analog Scale	10-cm Visual Analog Scale (VAS), score of 0 "no pain" to a score of 10 "worst pain ever"	Through study completion, assessed at 1h, 2h, 4h, 6h, 12h and 24h post operatively, then every 24 hours until discharge, and at the post operative visit which occurred within 21-days post-operatively.
Secondary	Opioid Consumption	Difference in opioid consumption in first 24 hours, discharge and 21 days post-operatively (morphine equivalents)	Through study completion, assessed for first 24-hours post operatively, then every 24 hours until discharge, and at the post operative visit which occurred within 21-days post-operatively.
Secondary	Length of Hospital Stay	Difference in length of hospital stay determined by surgeon excluding social factors that may delay discharge	At participant discharge, assessed up to 14 days (+/-) 7 days
Secondary	Duration of Post-operative Ileus	Difference in post-operative Ileus duration	Through study completion, assessed at 1h, 2h, 4h, 6h, 12h and 24h post operatively, then every 24 hours until discharge, and at the post operative visit which occurred within 21-days post-operatively.
Secondary	Post-operative PACU Time	Difference in time in the Post Anesthesia Care Unit (PACU) after surgery	During hospitalization, approximately 2 hours post-surgery
Secondary	Return of Flatus	Difference in return of flatus after surgery	During hospitalization at 1h, 2h, 4h, 6h, 12h, and 24h post operatively, then every 24 hours thereafter until discharge.
Secondary	Time to Out of Bed	Difference in time to out of bed to chair after surgery	During hospitalization regular intervals for the first 24 hours, then every 24 hours until discharge.
Secondary	First Ambulation in the Hallway	Difference in time to first ambulation in the hallway after surgery	During hospitalization at 1h, 2h, 4h, 6h, 12h, and 24h post operatively, then every 24 hours until discharge.