Effect of Lidocaine and Esmolol to Improve the Quality of Recovery

Effect of Lidocaine and Esmolol Alone or in Combination to Improve the Quality of Recovery, Maintaining Hemodynamic Stability During Abdominal Surgery

The purpose of this prospective, randomized, double-blinded, active-controlled study is:

To assess the effectiveness of systemic administration of lidocaine and esmolol in combination (vs. either drug alone) will result in improved postoperative outcomes for patients undergoing abdominal surgery (e.g., less pain and postoperative constipation, nausea and vomiting, faster return of bowel function, resumption of normal activities of daily living), leading to a shorten length of hospital stay, maintaining hemodynamic stability during general anesthesia, when administered as intravenous adjuvants

Study Overview

• Status: Terminated
• Conditions: Pain; Nausea; Vomiting; Constipation
• Intervention / Treatment: Drug: Lidocaine; Drug: Esmolol; Drug: Lidocaine + Esmolol (Combo)

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients scheduled to undergo abdominal surgical 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: Class 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 or blood pregnancy test
• Patients with systolic blood pressure greater than 80 and less than 150 at baseline, diastolic blood pressure less than 100 at baseline.

Exclusion Criteria:

• Inability to comprehend the pain assessment tools.
• 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
• Patients with history of hepatic, renal, cardiac failure, organ transplant, or diabetes
• Patients with reactive airway disease (asthma)
• Patients with seizures
• Chronic use of ß-blocker or calcium channel blocker
• Morbid obesity (body mass index >40)
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lidocaine; Pre-Induction: Lidocaine Loading: 1 mg/kg Post- Induction:Lidocaine Infusion: 12.5-25 mcg/kg/min 0.75-1.5 mg/kg/h)	Drug: Lidocaine; Pre-Induction: Lidocaine Loading: 1 mg/kg After Induction:Lidocaine Infusion: 12.5-25 mcg/kg/min 0.75-1.5 mg/kg/h)
Active Comparator: Esmolol; Pre-Induction: Loading dose 750 mcg/Kg (0.75 mg/kg) Post-Induction: Infusion dose 7.5 - 15 mcg /kg/min	Drug: Esmolol; Esmolol Pre-Induction: Loading dose 750 mcg/Kg (0.75 mg/kg) Esmolol Post Induction: Infusion dose 7.5 - 15 mcg /kg/min
Experimental: Lidocaine + Esmolol (Combo); Performed with the administration of both drugs. Pre-induction: Lidocaine Loading dose(1 mg/kg)+Esmolol Loading dose(750 mcg/Kg) Post-induction: Infusion rate: Lidocaine(12.5-25 mcg/kg/min) + Esmolol(7.5-15 mcg/kg/min)	Drug: Lidocaine + Esmolol (Combo); Pre-induction: Lidocaine Loading dose(1 mg/kg) + Esmolol Loading dose(750 mcg/Kg) Maintenance Infusion rate after Induction: Lidocaine(12.5-25 mcg/kg/min) + Esmolol(7.5-15 mcg/kg/min)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post Operative Pain	Outcome had a duration of one day at post-anesthesia care unit (PACU) Postoperative pain measured using a Verbal Rating Scale (VRS) Postoperative pain VRS scores: 0 = none pain to 10 = intolerable pain.	1 day
Number of Participants With Post Operative Pain One Month After Surgery	Highest Post Operative pain one month after surgery, using a verbal rating score from 0 (no pain) to 10 (highest level of pain). Patient received a post-operative follow-up call one month after surgery.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid Consumption Obtained From the Recorded Data	Postoperative use of opioid consumption inside hospital (recorded by study staff and data obtained from patient charts)	1 day
Number of Participants With Postoperative Nausea One Day After Surgery	Postoperative nausea using a Verbal Rating Scale Outcomes measured at the first day after surgery	1day
Return to Normal Activities of Daily Living Using Follow up Questionnaires	Description: return to normal activities of daily living(including dietary intake, bowel and bladder function, physical activities)	1 month
Patient Satisfaction	Patient satisfaction using a verbal rating scale from 0 to 10 0= Not satisfied 10= Excellent	1 month
Post-anesthesia Care Unit (PACU) Stay		1 day

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: April 23, 2010
• First Submitted That Met QC Criteria: April 30, 2010
• First Posted (Estimate): May 3, 2010

Study Record Updates

• Last Update Posted (Estimate): November 3, 2016
• Last Update Submitted That Met QC Criteria: September 28, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Pain management; Anesthetic adjuvant; Hemodynamic stability; Perioperative outcomes; Abdominal surgery; Lidocaine Infusion; Esmolol Infusion
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Vomiting; Constipation; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Adrenergic beta-1 Receptor Antagonists; Lidocaine; Esmolol
• Other Study ID Numbers: Pro00020608

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES