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Labetalol and Esmolol: Vital Signs and Post Operative Pain Management

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
Information provided by (Responsible Party):
Ronald Wender, Cedars-Sinai Medical Center

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.


Condition or disease Intervention/treatment Phase
Laparoscopic Surgery Drug: Fentanyl Drug: Labetalol Drug: Esmolol Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Prevention
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
Actual Study Start Date : September 3, 2009
Actual Primary Completion Date : July 30, 2014
Actual Study Completion Date : July 31, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vital Signs

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 Name: 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: 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: 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

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: 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)




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 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

  2. Postoperative Nausea and Vomiting [ Time Frame: 1 day ]
    Nausea and vomiting will be measured at PACU

  3. Return to Feeling Normal [ Time Frame: 1 month ]
    Days to report to return to feeling normal, using follow up questionnaires

  4. 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

  5. Low Appetite [ Time Frame: 1 month ]
    Participant who experienced low appetite (follow up questionnaire)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01114971


Locations
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United States, California
Cedars Sinai Medical Center
Los Angeles, California, United States, 90048
Sponsors and Collaborators
Cedars-Sinai Medical Center
Investigators
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Principal Investigator: Ronald H Wender, MD Cedars-Sinai Medical Center
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Responsible Party: Ronald Wender, Chairman, Department of Anesthesiology, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT01114971    
Other Study ID Numbers: Pro00019328
First Posted: May 3, 2010    Key Record Dates
Results First Posted: February 20, 2020
Last Update Posted: February 20, 2020
Last Verified: February 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ronald Wender, Cedars-Sinai Medical Center:
Labetalol
Esmolol
Fentanyl
Anesthetic adjuvant
Ambulatory surgery
Outpatient surgery
Pain management
Hemodynamic stability
Perioperative outcomes
Additional relevant MeSH terms:
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Labetalol
Fentanyl
Esmolol
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adjuvants, Anesthesia
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Sympathomimetics
Autonomic Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists