Effect of Lidocaine and Esmolol to Improve the Quality of Recovery

Phase 4

Terminated

Conditions: Pain
Vomiting
Constipation
Nausea

Interventions: Drug: Lidocaine + Esmolol (Combo)
Drug: Lidocaine
Drug: Esmolol

Registration Number: NCT01114997

Lead Sponsor: Cedars-Sinai Medical Center

Brief Summary: 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

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: TERMINATED

Sex: All

Target Recruitment: 32

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 & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Lidocaine + Esmolol (Combo)	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)
Lidocaine	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)
Esmolol	Esmolol	Pre-Induction: Loading dose 750 mcg/Kg (0.75 mg/kg) Post-Induction: Infusion dose 7.5 - 15 mcg /kg/min

Primary Outcome Measures

Name	Time	Method
Post Operative Pain	1 day	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.
Number of Participants With Post Operative Pain One Month After Surgery	1 month	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.

Secondary Outcome Measures

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