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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

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01114971
Enrollment
75
Registered
2010-05-03
Start date
2009-09-03
Completion date
2018-07-31
Last updated
2020-02-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Laparoscopic Surgery

Keywords

Labetalol, Esmolol, Fentanyl, Anesthetic adjuvant, Ambulatory surgery, Outpatient surgery, Pain management, Hemodynamic stability, Perioperative outcomes

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.

Interventions

DRUGFentanyl

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)

DRUGLabetalol

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)

DRUGEsmolol

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)

Sponsors

Cedars-Sinai Medical Center
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Caregiver)

Eligibility

Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Postoperative Painone dayPostoperative 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

MeasureTime frameDescription
Number of Participant With Opioid Consumption1 monthn=Post discharge use of opioid consumption NUMBER OF PARTICIPANTS WHO TOOK PAIN KILLER PILLS
Postoperative Nausea and Vomiting1 dayNausea and vomiting will be measured at PACU
Return to Feeling Normal1 monthDays to report to return to feeling normal, using follow up questionnaires
Patient Satisfaction Using a Verbal Rating Scale From 0 to 101 monthPatient 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 Appetite1 monthParticipant who experienced low appetite (follow up questionnaire)

Countries

United States

Participant flow

Participants by arm

ArmCount
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) 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) 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)
25
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) 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) 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)
25
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) 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) 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)
25
Total75

Baseline characteristics

CharacteristicFentanylLabetalolEsmololTotal
Age, Continuous46 years
STANDARD_DEVIATION 13
42 years
STANDARD_DEVIATION 14
49 years
STANDARD_DEVIATION 11
46 years
STANDARD_DEVIATION 13
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
3 Participants0 Participants1 Participants4 Participants
Race (NIH/OMB)
Black or African American
3 Participants6 Participants4 Participants13 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants1 Participants1 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
19 Participants19 Participants19 Participants57 Participants
Sex: Female, Male
Female
21 Participants21 Participants15 Participants57 Participants
Sex: Female, Male
Male
4 Participants4 Participants10 Participants18 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
0 / 250 / 250 / 25
other
Total, other adverse events
0 / 250 / 250 / 25
serious
Total, serious adverse events
0 / 250 / 250 / 25

Outcome results

Primary

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)

Time frame: one day

ArmMeasureValue (MEAN)Dispersion
FentanylPostoperative Pain3.2 Score on scale 0-10Standard Deviation 2
LabetalolPostoperative Pain3 Score on scale 0-10Standard Deviation 3
EsmololPostoperative Pain3.9 Score on scale 0-10Standard Deviation 2.5
Secondary

Low Appetite

Participant who experienced low appetite (follow up questionnaire)

Time frame: 1 month

ArmMeasureValue (NUMBER)
FentanylLow Appetite15 participants
LabetalolLow Appetite7 participants
EsmololLow Appetite9 participants
Secondary

Number of Participant With Opioid Consumption

n=Post discharge use of opioid consumption NUMBER OF PARTICIPANTS WHO TOOK PAIN KILLER PILLS

Time frame: 1 month

ArmMeasureValue (NUMBER)
FentanylNumber of Participant With Opioid Consumption15 participants
LabetalolNumber of Participant With Opioid Consumption14 participants
EsmololNumber of Participant With Opioid Consumption13 participants
Secondary

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

Time frame: 1 month

ArmMeasureValue (MEAN)Dispersion
FentanylPatient Satisfaction Using a Verbal Rating Scale From 0 to 109.1 score on a scale (0-10)Standard Deviation 1.6
LabetalolPatient Satisfaction Using a Verbal Rating Scale From 0 to 109 score on a scale (0-10)Standard Deviation 1.2
EsmololPatient Satisfaction Using a Verbal Rating Scale From 0 to 108 score on a scale (0-10)Standard Deviation 2.5
Secondary

Postoperative Nausea and Vomiting

Nausea and vomiting will be measured at PACU

Time frame: 1 day

ArmMeasureValue (NUMBER)
FentanylPostoperative Nausea and Vomiting9 participants
LabetalolPostoperative Nausea and Vomiting4 participants
EsmololPostoperative Nausea and Vomiting7 participants
Secondary

Return to Feeling Normal

Days to report to return to feeling normal, using follow up questionnaires

Time frame: 1 month

ArmMeasureValue (MEAN)Dispersion
FentanylReturn to Feeling Normal11 DaysStandard Deviation 9
LabetalolReturn to Feeling Normal10 DaysStandard Deviation 9
EsmololReturn to Feeling Normal12 DaysStandard Deviation 10

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026