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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

Status
Terminated
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01114997
Enrollment
32
Registered
2010-05-03
Start date
2010-04-30
Completion date
2015-06-30
Last updated
2016-11-03

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

Conditions

Constipation, Nausea, Pain, Vomiting

Keywords

Lidocaine Infusion, Esmolol Infusion, Anesthetic adjuvant, Abdominal surgery, Pain management, Hemodynamic stability, Perioperative outcomes

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.

Interventions

DRUGLidocaine

Pre-Induction: Lidocaine Loading: 1 mg/kg After Induction:Lidocaine Infusion: 12.5-25 mcg/kg/min 0.75-1.5 mg/kg/h)

DRUGEsmolol

Esmolol Pre-Induction: Loading dose 750 mcg/Kg (0.75 mg/kg) Esmolol Post Induction: Infusion dose 7.5 - 15 mcg /kg/min

DRUGLidocaine + 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)

Sponsors

Cedars-Sinai Medical Center
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

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

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

Design outcomes

Primary

MeasureTime frameDescription
Post Operative Pain1 dayOutcome 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 Surgery1 monthHighest 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

MeasureTime frameDescription
Return to Normal Activities of Daily Living Using Follow up Questionnaires1 monthDescription: return to normal activities of daily living(including dietary intake, bowel and bladder function, physical activities)
Opioid Consumption Obtained From the Recorded Data1 dayPostoperative use of opioid consumption inside hospital (recorded by study staff and data obtained from patient charts)
Post-anesthesia Care Unit (PACU) Stay1 day
Patient Satisfaction1 monthPatient satisfaction using a verbal rating scale from 0 to 10 0= Not satisfied 10= Excellent
Number of Participants With Postoperative Nausea One Day After Surgery1dayPostoperative nausea using a Verbal Rating Scale Outcomes measured at the first day after surgery

Countries

United States

Participant flow

Participants by arm

ArmCount
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)
11
Esmolol
Pre-Induction: Esmolol Loading dose: 750 mcg/Kg (0.75 mg/kg) Post-Induction: Infusion dose 7.5 - 15 mcg /kg/min
10
Lidocaine + Esmolol (Combo)
Pre-induction: Lidocaine Loading dose(1 mg/kg)+Esmolol Loading dose(750 mcg/Kg) Post-Induction (Maintenance Infusion): Lidocaine(12.5-25 mcg/kg/min) + Esmolol(7.5-15 mcg/kg/min)
11
Total32

Baseline characteristics

CharacteristicLidocaineEsmololLidocaine + Esmolol (Combo)Total
Age, Continuous42 years
STANDARD_DEVIATION 8
44 years
STANDARD_DEVIATION 3
38 years
STANDARD_DEVIATION 10
41 years
STANDARD_DEVIATION 9
Region of Enrollment
United States
11 participants10 participants11 participants32 participants
Sex: Female, Male
Female
11 Participants10 Participants11 Participants32 Participants
Sex: Female, Male
Male
0 Participants0 Participants0 Participants0 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —
other
Total, other adverse events
0 / 110 / 100 / 11
serious
Total, serious adverse events
0 / 110 / 100 / 10

Outcome results

Primary

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.

Time frame: 1 month

Population: Experience of pain at home

ArmMeasureValue (NUMBER)
LidocaineNumber of Participants With Post Operative Pain One Month After Surgery10 participants
EsmololNumber of Participants With Post Operative Pain One Month After Surgery8 participants
Lidocaine + Esmolol (Combo)Number of Participants With Post Operative Pain One Month After Surgery10 participants
Primary

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.

Time frame: 1 day

ArmMeasureValue (MEAN)Dispersion
LidocainePost Operative Pain4 Score on a scaleStandard Deviation 4
EsmololPost Operative Pain2 Score on a scaleStandard Deviation 2
Lidocaine + Esmolol (Combo)Post Operative Pain4 Score on a scaleStandard Deviation 3
Secondary

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

Time frame: 1day

ArmMeasureValue (NUMBER)
LidocaineNumber of Participants With Postoperative Nausea One Day After Surgery3 participants
EsmololNumber of Participants With Postoperative Nausea One Day After Surgery2 participants
Lidocaine + Esmolol (Combo)Number of Participants With Postoperative Nausea One Day After Surgery3 participants
Secondary

Opioid Consumption Obtained From the Recorded Data

Postoperative use of opioid consumption inside hospital (recorded by study staff and data obtained from patient charts)

Time frame: 1 day

Population: Opioid: Hydromorphone

ArmMeasureValue (MEAN)Dispersion
LidocaineOpioid Consumption Obtained From the Recorded Data1.5 mgStandard Deviation 1
EsmololOpioid Consumption Obtained From the Recorded Data1 mgStandard Deviation 0.8
Lidocaine + Esmolol (Combo)Opioid Consumption Obtained From the Recorded Data1.5 mgStandard Deviation 1
Secondary

Patient Satisfaction

Patient satisfaction using a verbal rating scale from 0 to 10 0= Not satisfied 10= Excellent

Time frame: 1 month

ArmMeasureValue (MEAN)Dispersion
LidocainePatient Satisfaction9.4 Score on a scaleStandard Deviation 0.8
EsmololPatient Satisfaction9.2 Score on a scaleStandard Deviation 1
Lidocaine + Esmolol (Combo)Patient Satisfaction8.3 Score on a scaleStandard Deviation 2
Secondary

Post-anesthesia Care Unit (PACU) Stay

Time frame: 1 day

ArmMeasureValue (MEAN)Dispersion
LidocainePost-anesthesia Care Unit (PACU) Stay236 MinutesStandard Deviation 147
EsmololPost-anesthesia Care Unit (PACU) Stay116 MinutesStandard Deviation 38
Lidocaine + Esmolol (Combo)Post-anesthesia Care Unit (PACU) Stay214 MinutesStandard Deviation 125
Secondary

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)

Time frame: 1 month

ArmMeasureValue (NUMBER)
LidocaineReturn to Normal Activities of Daily Living Using Follow up Questionnaires10 participants
EsmololReturn to Normal Activities of Daily Living Using Follow up Questionnaires8 participants
Lidocaine + Esmolol (Combo)Return to Normal Activities of Daily Living Using Follow up Questionnaires8 participants

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