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The early report didn't show any benefit.
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lidocaine | Active Comparator | 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 | Active Comparator | Pre-Induction: Loading dose 750 mcg/Kg (0.75 mg/kg) Post-Induction: Infusion dose 7.5 - 15 mcg /kg/min |
|
| Lidocaine + Esmolol (Combo) | Experimental | 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lidocaine | Drug | Pre-Induction: Lidocaine Loading: 1 mg/kg After Induction:Lidocaine Infusion: 12.5-25 mcg/kg/min 0.75-1.5 mg/kg/h) |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Roya Yumul, MD, PhD | Cedars-Sinai Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cedars Sinai Medical Center | Los Angeles | California | 90048 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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) |
| FG001 | Esmolol | Pre-Induction: Esmolol Loading dose: 750 mcg/Kg (0.75 mg/kg) Post-Induction: Infusion dose 7.5 - 15 mcg /kg/min |
| FG002 | Lidocaine + Esmolol (Combo) | 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) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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) |
| BG001 | Esmolol | Pre-Induction: Esmolol Loading dose: 750 mcg/Kg (0.75 mg/kg) Post-Induction: Infusion dose 7.5 - 15 mcg /kg/min |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Deviation | Score on a scale | 1 day |
|
1 month
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Roya Yumul | Cedars Sinai Medical Center | 310-423-1682 | Roya.Yumul@cshs.org |
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| ID | Term |
|---|---|
| D010146 | Pain |
| D003248 | Constipation |
| D009325 | Nausea |
| D014839 | Vomiting |
| D000377 | Agnosia |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012817 | Signs and Symptoms, Digestive |
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| ID | Term |
|---|---|
| D008012 | Lidocaine |
| C036604 | esmolol |
| ID | Term |
|---|---|
| D000083 | Acetanilides |
| D000813 | Anilides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000814 |
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| Esmolol | Drug | Esmolol Pre-Induction: Loading dose 750 mcg/Kg (0.75 mg/kg) Esmolol Post Induction: Infusion dose 7.5 - 15 mcg /kg/min |
|
| Lidocaine + Esmolol (Combo) | Drug | 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) |
|
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 |
| BG002 | 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) |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | California, United States | Number | participants |
|
| Lidocaine + Esmolol (Combo) |
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) |
|
|
| 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. | Experience of pain at home | Posted | Number | participants | 1 month |
|
|
|
| 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) | Opioid: Hydromorphone | Posted | Mean | Standard Deviation | mg | 1 day |
|
|
|
| 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 | Posted | Number | participants | 1day |
|
|
|
| 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) | Posted | Number | participants | 1 month |
|
|
|
| Secondary | Patient Satisfaction | Patient satisfaction using a verbal rating scale from 0 to 10 0= Not satisfied 10= Excellent | Posted | Mean | Standard Deviation | Score on a scale | 1 month |
|
|
|
| Secondary | Post-anesthesia Care Unit (PACU) Stay | Posted | Mean | Standard Deviation | Minutes | 1 day |
|
|
|
| 0 |
| 11 |
| 0 |
| 11 |
| EG001 | Esmolol | Pre-Induction: Loading dose 750 mcg/Kg (0.75 mg/kg) Post-Induction: Infusion dose 7.5 - 15 mcg /kg/min | 0 | 10 | 0 | 10 |
| EG002 | Lidocaine + Esmolol (Combo) | 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) | 0 | 10 | 0 | 11 |
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| D010468 | Perceptual Disorders |
| D019954 | Neurobehavioral Manifestations |
| D009422 | Nervous System Diseases |
| Aniline Compounds |
| D000588 | Amines |