Labetalol and Esmolol: Vital Signs and Post Operative Pain Management

NCT ID: NCT01114971

Last Updated: 2020-02-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-03
• Study Completion Date: 2018-07-31

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.

Conditions

Laparoscopic Surgery

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

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)

Group Type: ACTIVE_COMPARATOR

Labetalol

Intervention Type: DRUG

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)

Esmolol

Intervention Type: DRUG

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)

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)

Group Type: EXPERIMENTAL

Fentanyl

Intervention Type: DRUG

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)

Esmolol

Intervention Type: DRUG

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)

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)

Group Type: EXPERIMENTAL

Fentanyl

Intervention Type: DRUG

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)

Labetalol

Intervention Type: DRUG

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

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)

Intervention Type: 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)

Intervention Type: 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)

Intervention Type: DRUG

Other Intervention Names

Brevibloc

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cedars-Sinai Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Ronald Wender

Chairman, Department of Anesthesiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ronald H Wender, MD

Role: PRINCIPAL_INVESTIGATOR

Cedars-Sinai Medical Center

Locations

Cedars Sinai Medical Center

Los Angeles, California, United States

Countries

United States

Other Identifiers

Pro00019328

Identifier Type: -

Identifier Source: org_study_id