Clinical trial NCT03824808: Effect of Perioperative Intravenous Lidocaine Infusion in Robotic-Assisted Urologic Surgery
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Kidney Cancer
Prostate Cancer
Keywords: prostatectomy
partial nephrectomy
robotic surgery
intravenous lidocaine
lidocaine hydrochloride
Lead sponsor: University of Missouri-Columbia
Sponsor class: OTHER
First posted: 2019-01-31
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will receive either intraoperative 0.8% lidocaine or normal saline at 1 mg/kg/h when younger than 65 years and 0.5 mg/kg/h when greater than or equal to the age of 65 to be delivered by continuous infusion for 24 hours.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Difference in Post-operative Pain Scores Measured by Visual Analog Scale
timeFrame: 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 outcomes:
measure: Opioid Consumption
timeFrame: 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.
measure: Length of Hospital Stay
timeFrame: At participant discharge, assessed up to 14 days (+/-) 7 days
measure: Duration of Post-operative Ileus
timeFrame: 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.
measure: Post-operative PACU Time
timeFrame: During hospitalization, approximately 2 hours post-surgery
measure: Return of Flatus
timeFrame: During hospitalization at 1h, 2h, 4h, 6h, 12h, and 24h post operatively, then every 24 hours thereafter until discharge.
measure: Time to Out of Bed
timeFrame: During hospitalization regular intervals for the first 24 hours, then every 24 hours until discharge.
measure: First Ambulation in the Hallway
timeFrame: During hospitalization at 1h, 2h, 4h, 6h, 12h, and 24h post operatively, then every 24 hours until discharge.
Other outcomes:
Locations:
city: Columbia
country: United States
facility: University Hospital
state: Missouri
Study officials:
affiliation: University of Missouri-Columbia
name: Boris Mraovic, MD
role: PRINCIPAL_INVESTIGATOR
References:
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