Labetalol and Esmolol: Vital Signs and Post Operative Pain Management

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Laparoscopic Surgery

Intervention / Treatment
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* Drug: Fentanyl
* Drug: Labetalol
* Drug: Esmolol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fentanyl<br>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<br>* 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)<br>Drug: Esmolol<br>* 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)<br>* Other names: Brevibloc;|
| Experimental: Labetalol<br>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<br>* 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)<br>Drug: Esmolol<br>* 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)<br>* Other names: Brevibloc;|
| Experimental: Esmolol<br>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<br>* 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)<br>Drug: Labetalol<br>* 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)<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Esmolol, Labetalol, Fentanyl, Anesthetic adjuvant, Ambulatory surgery, Outpatient surgery, Pain management, Hemodynamic stability, Perioperative outcomes