Labetalol and Esmolol: Vital Signs and Post Operative Pain Management

Phase 4

Completed

Conditions: Laparoscopic Surgery

Interventions: Drug: Labetalol
Drug: Fentanyl
Drug: Esmolol

Registration Number: NCT01114971

Lead Sponsor: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 75

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 & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Fentanyl	Labetalol	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)
Fentanyl	Esmolol	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)
Labetalol	Fentanyl	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)
Labetalol	Esmolol	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	Labetalol	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	Fentanyl	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)

Primary Outcome Measures

Name	Time	Method
Postoperative Pain	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

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

Trial Locations

Locations (1): Cedars Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States