Labetalol and Esmolol: Vital Signs and Post Operative Pain Management

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

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.

Study Overview

• Status: Completed
• Conditions: Laparoscopic Surgery
• Intervention / Treatment: Drug: Labetalol; Drug: Esmolol; Drug: Fentanyl

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
• Enrollment (Actual): 75
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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)	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 Names: Brevibloc
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)	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 Names: Brevibloc; 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)
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)	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: 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Pain	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)	one day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participant With Opioid Consumption	n=Post discharge use of opioid consumption NUMBER OF PARTICIPANTS WHO TOOK PAIN KILLER PILLS	1 month
Postoperative Nausea and Vomiting	Nausea and vomiting will be measured at PACU	1 day
Return to Feeling Normal	Days to report to return to feeling normal, using follow up questionnaires	1 month
Patient Satisfaction Using a Verbal Rating Scale From 0 to 10	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	1 month
Low Appetite	Participant who experienced low appetite (follow up questionnaire)	1 month

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2009
• Primary Completion (Actual): July 30, 2014
• Study Completion (Actual): July 31, 2018

Study Registration Dates

• First Submitted: April 23, 2010
• First Submitted That Met QC Criteria: April 30, 2010
• First Posted (Estimate): May 3, 2010

Study Record Updates

• Last Update Posted (Actual): February 20, 2020
• Last Update Submitted That Met QC Criteria: February 7, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Pain management; Fentanyl; Labetalol; Esmolol; Anesthetic adjuvant; Ambulatory surgery; Outpatient surgery; Hemodynamic stability; Perioperative outcomes
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Sympathomimetics; Adrenergic beta-1 Receptor Antagonists; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Fentanyl; Labetalol; Esmolol
• Other Study ID Numbers: Pro00019328

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No