Labetalol and Esmolol: Vital Signs and Post Operative Pain Management

• ClinicalTrials.gov Identifier: NCT01114971
• Recruitment Status: Completed
• First Posted: May 3, 2010
• Results First Posted: February 20, 2020
• Last Update Posted: February 20, 2020
• Sponsor: Cedars-Sinai Medical Center
• Information provided by (Responsible Party): Ronald Wender, Cedars-Sinai Medical Center

Tracking Information

• First Submitted Date: April 23, 2010
• First Posted Date: May 3, 2010
• Results First Submitted Date: November 22, 2019
• Results First Posted Date: February 20, 2020
• Last Update Posted Date: February 20, 2020
• Actual Study Start Date: September 3, 2009
• Actual Primary Completion Date: July 30, 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 7, 2020)

Postoperative Pain [ Time Frame: one day ]

Postoperative pain will be measured at PACU using a Verbal Rating Scale (VRS) from 0 to 10 VRS is a subjective measure in which individuals verbally rate their pain on an eleven-point numerical scale. The scale is composed of 0 (no pain at all) to 10 (worst imaginable pain)

Original Primary Outcome Measures (submitted: April 30, 2010)

Postoperative pain using a Verbal Rating Scale [ Time Frame: one month ]

Postoperative will be measured at 1, 2, or 3, then 7 and 30 days after surgery

Current Secondary Outcome Measures (submitted: February 7, 2020)

• Number of Participant With Opioid Consumption [ Time Frame: 1 month ]
  n=Post discharge use of opioid consumption NUMBER OF PARTICIPANTS WHO TOOK PAIN KILLER PILLS
• Postoperative Nausea and Vomiting [ Time Frame: 1 day ]
  Nausea and vomiting will be measured at PACU
• Return to Feeling Normal [ Time Frame: 1 month ]
  Days to report to return to feeling normal, using follow up questionnaires
• Patient Satisfaction Using a Verbal Rating Scale From 0 to 10 [ Time Frame: 1 month ]
  Patient satisfaction using a verbal rating scale from 0 to 10 Where a VRS is a subjective measure in which individuals verbally rated their level of satisfaction on an eleven-point numerical scale. The scale is composed of 0 (excellent satisfaction) to 10
• Low Appetite [ Time Frame: 1 month ]
  Participant who experienced low appetite (follow up questionnaire)

Original Secondary Outcome Measures (submitted: April 30, 2010)

• Opioid consumption obtained from the recorded data [ Time Frame: 1 month ]
  Perioperative use of opioid consumption inside hospital (recorded by study staff and data obtained from patient charts) Post discharge use of opioid consumption (data obtained from the follow up questionnaires at 1, 2, or 3, then 7 and 30 days after surgery)
• Postoperative nausea and vomiting using a Verbal Rating Scale [ Time Frame: 1 month ]
  Nausea and vomiting will be measured with follow up questionnaires at 1, 2, or 3, then 7 and 30 days after surgery
• Return to normal activities of daily living using follow up questionnaires [ Time Frame: 1 month ]
  Return to normal activities of daily living(including dietary intake, bowel and bladder function, physical activities)will be measured in both groups.
• Patient satisfaction using a verbal rating scale from 0 to 100 [ Time Frame: 1 month ]
  0= Not satisfied 100= Excellent
• Hospital stay [ Time Frame: 1 week ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Labetalol and Esmolol: Vital Signs and Post Operative Pain Management
• Official Title: Randomized, Double-Blinded, Active-Controlled Study to Evaluate the Intraoperative Use of Labetalol vs. Esmolol for Maintaining Hemodynamic Stability During Laparoscopic Surgery: Effect on Recovery and Postoperative Pain

Brief Summary

This study proposes to investigate the effects of labetalol or esmolol on managing the vital signs (like blood pressure and heart rate) during surgery, on pain management, and on the later recovery after surgery.

It will also assess the cost-effectiveness of Labetalol and esmolol for outpatient surgery.

Detailed Description

Finding the optimal combination of anesthetic adjuvant drugs for maintaining hemodynamic stability during surgery is a challenge (1-3). Traditionally, potent opioid analgesics like fentanyl and its newer analogs have been used for this purpose. However, use of opioid compounds is associated with well-known side effects (e.g., ventilatory depression, postoperative nausea and vomiting, constipation, ileus, bladder dysfunction, urinary retention, pruritus, drowsiness and sedation). All of these common side effects interfere with the early recovery process and contribute to a delayed resumption of normal activities (4, 5). Increasingly, non-opioid analgesics (e.g. β-blockers and local anesthetics) are being utilized as adjuvant drugs during surgery for treatment of acute hyperdynamic responses (increased catecholamine release) during surgery, as well as, facilitation of the recovery process after surgery because of their anesthetic and analgesic-sparing effects. The β-blocking drugs, esmolol and labetalol have been used as an alternative to short-acting opioid analgesics for controlling the transient, acute autonomic responses during surgery (5-8), They have been shown to reduce the anesthetic requirement during intravenous (propofol) or volatile-based anesthesia (6,7,10-13) and to decrease opioid consumption intraoperatively and in the PACU (8). They may also improve hemodynamic stability during induction and emergence from anesthesia in the perioperative and early postoperative period and facilitate the resumption of normal activities after major surgical procedures. The anesthetic and analgesic-sparing effects of β -blockers also lead to a faster emergence from anesthesia and reduce postoperative opioid side effects (e.g., PONV) (14-18). Perioperative intravenous esmolol has shown improvement in perioperative outcomes, decreases acute hemodynamic responses, reduces anesthetics and opioids use during anesthesia, facilitates a faster emergence from anesthesia, reduces intraoperative and postoperative opioid requirements, reduces side effects as such as pruritus, constipation, ileus, nausea and vomiting (PONV) and thereby shortens the hospital stay. (3, 7, 13, 18)

Local anesthetics like lidocaine possess analgesic, antihyperalgesic and anti-inflammatory properties. Perioperative intravenous lidocaine has shown improvement in perioperative outcomes in patients undergoing abdominal surgery to decrease intraoperative requirement of Inhalants/Intravenous agents, opioid consumption, postoperative pain, fatigue, nausea and vomiting scores, maintain hemodynamic stability, facilitate a more rapid recovery of gastrointestinal function, improve postoperative recovery, fast resumption of normal activities of daily living and shorten length of hospital stay, when administered as an adjuvant during surgery.(19,23-29,33)

Theoretically, it would be extremely beneficial to administer an adjuvant (to patients undergoing abdominal surgery) that is capable of effectively controlling autonomic responses during surgery, while providing a faster recovery with fewer side effects. Preliminary data suggests that the perioperative effects of systemic administration of lidocaine and esmolol is most effective in facilitating bowel recovery, decreasing opioid consumption in the intra/postoperative period, and shorten length of hospital stay with early recovery. Therefore, we designed this prospective, randomized, double-blinded, active-controlled study to test the hypothesis that systemic administration of lidocaine and esmolol in combination (vs. either drug alone) for maintenance of hemodynamic stability during surgery will result in improved postoperative outcomes for patients undergoing abdominal surgery (e.g., less pain and postoperative nausea and vomiting, and faster return of bowel function and resumption of normal activities of daily living); leading to a shorten length of hospital stay.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Factorial Assignment; Masking: Double (Participant, Care Provider); Primary Purpose: Prevention
• Condition: Laparoscopic Surgery

Intervention

• Drug: Fentanyl

  Fentanyl 50 micrograms/ml boluses will be given:

  • at the induction time
  • at the time before surgical incision, and
  • as needed to maintain hemodynamic stability during the intraoperative period (MAP within 15% of the pre-induction baseline value, and/or HR > 80 bpm)
• Drug: Labetalol

  Labetalol 5 mg/ml boluses will be given:

  • at the induction time
  • at the time before surgical incision, and
  • as needed to maintain hemodynamic stability during the intraoperative period (MAP within 15% of the pre-induction baseline value, and/or HR > 80 bpm)
• Drug: Esmolol

  Esmolol 10 mg/ml boluses will be given:

  • at the induction time
  • at the time before surgical incision, and
  • as needed to maintain hemodynamic stability during the intraoperative period (MAP within 15% of the pre-induction baseline value, and/or HR > 80 bpm)
  Other Name: Brevibloc

Study Arms

• Active Comparator: Fentanyl

  Fentanyl 50 micrograms/ml boluses will be given:

  • at the induction time
  • at the time before surgical incision, and
  • as needed to maintain hemodynamic stability during the intraoperative period (MAP within 15% of the pre-induction baseline value, and/or Heart Rate (HR) > 80 bpm)
  Interventions:

  • Drug: Labetalol
  • Drug: Esmolol
• Experimental: Labetalol

  Labetalol 5 mg/ml boluses will be given:

  • at the induction time
  • at the time before surgical incision, and
  • as needed to maintain hemodynamic stability during the intraoperative period (MAP within 15% of the pre-induction baseline value, and/or HR > 80 bpm)
  Interventions:

  • Drug: Fentanyl
  • Drug: Esmolol
• Experimental: Esmolol

  Esmolol 10 mg/ml boluses will be given:

  • at the induction time
  • at the time before surgical incision, and
  • as needed to maintain hemodynamic stability during the intraoperative period (MAP within 15% of the pre-induction baseline value, and/or HR > 80 bpm)
  Interventions:

  • Drug: Fentanyl
  • Drug: Labetalol

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 7, 2020): 75
• Original Estimated Enrollment (submitted: April 30, 2010): 120
• Actual Study Completion Date: July 31, 2018
• Actual Primary Completion Date: July 30, 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients scheduled to undergo outpatient surgery procedures
• Willingness and ability to sign an informed consent document
• No allergies to anesthetic or analgesic medications
• 18 - 80 years of age
• American Society of Anesthesiologists (ASA) physical status classification I - III adults of either sex
• Women of childbearing potential must be currently practicing an acceptable form of birth control, and have a negative urine pregnancy test

Exclusion Criteria:

• Patients with known allergy, hypersensitivity or contraindications to anesthetic or analgesic medications
• Patients with clinically-significant medical conditions, such as brain, heart, kidney, endocrine, or liver diseases, peptic ulcer disease or bleeding disorders
• Pregnant or lactating women
• Subjects with a history of alcohol or drug abuse within the past 3 months
• Any other conditions or use of any medication which may interfere with the conduct of the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01114971
• Other Study ID Numbers: Pro00019328
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Ronald Wender, Cedars-Sinai Medical Center
• Original Responsible Party: Ronald H Wender, Cedars Sinai Medical Center
• Current Study Sponsor: Cedars-Sinai Medical Center
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Ronald H Wender, MD; Cedars-Sinai Medical Center

• PRS Account: Cedars-Sinai Medical Center
• Verification Date: February 2020