The Effect of Intraoperative Labetalol on Time to Discharge

Study Overview
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Brief Summary
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Patients coming for surgery often receive opioid medications, like fentanyl, to treat pain. Opioids however have many unpleasant side effects including nausea and vomiting, itching, sedation, and decreased breathing. During laparoscopic surgery increases in heart and blood pressure are often attributed to pain. It has been shown that by treating these changes with medications such as esmolol, instead of opioids, side effects and time to discharge from hospital can be reduced. Labetalol is a drug that is similar to esmolol but may have advantages over it. It is more effective at controlling both heart rate and blood pressure and it is easier and less costly to use. This study is investigating labetalol in patients having laparoscopic gallbladder surgery and comparing it to esmolol and fentanyl. Patients will be treated with one of these drugs during surgery to control heart rate and blood pressure and the effects on time to discharge, pain scores, frequency of side effects, and narcotic requirements will be observed in the recovery room. It is thought that labetalol will be shown to be as effective as esmolol and that both drugs that minimize fentanyl will show reduced time to discharge, fewer side effects, and effective treatment of heart rate and blood pressure.

Official Title
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The Effect of Intraoperative Labetalol on Time to Discharge and Hemodynamic Stability in Laparoscopic Cholecystectomy

Conditions
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Bloodpressure, Heart Rate

Intervention / Treatment
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* Drug: Esmolol
* Drug: Labetalol
* Drug: Fentanyl
* Other: saline infusion
* Other: 1 ml saline infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: scheduled to undergo elective ambulatory laparoscopic cholecystectomy under general anesthesia American Society of Anesthesiologist's Status ASA) 1-3 able to understand and sign informed consent Exclusion Criteria: known allergy to any of the study medications including beta blockers, fentanyl, acetaminophen, non-steroidal anti-inflammatories or local anesthetics chronic use of beta-adrenergic receptor antagonists or opioids conversion to open cholecystectomy History of renal, hepatic or cardiac failure, reactive airway disease Medical history that in the investigator's judgement would interfere with the protocol or assessments Unable to understand pain assessment Failure to give informed consent pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Esmolol<br>Esmolol infusion and 1 ml saline infusion | Drug: Esmolol<br>* Following induction and intubation, any increase in heart rate (HR) or mean arterial pressure (MAP) >20% of baseline will be treated with an initial intravenous bolus of esmolol 30 mg IV (30 mg in 5 ml of normal saline). An intravenous esmolol infusion will be initiated at 5mcg/kg/min after the first intravenous bolus dose and will be titrated up by 5mcg/kg/min each time HR or MAP >20% of baseline. An intravenous bolus of placebo (normal saline 1 ml) will be administered whenever a change to the infusion rate is made.<br>Other: 1 ml saline infusion<br>* Every time the infusion rate of esmolol is changed, 1 ml of normal saline will be infused.<br>|
| Experimental: Labetalol<br>Labetalol Bolus and saline infusion | Drug: Labetalol<br>* Following induction and intubation, any increase in heart rate (HR) or mean arterial pressure (MAP) >20% of baseline will be treated with an initial intravenous bolus of labetalol 10 mg IV (10 mg in 5 ml of normal saline). Any further increases in HR or MAP >20% of baseline will be treated with intravenous boluses of labetalol 5 mg in 1 ml every 5 minutes as needed. An intravenous placebo infusion (normal saline) will be initiated at 5 mcg/kg/min after the first intravenous bolus dose and will be titrated up by 5 mcg/kg/min each time an additional intravenous bolus is given.<br>Other: saline infusion<br>* An intravenous placebo infusion (normal saline) will be initiated at 5 mcg/kg/min after the first intravenous bolus drug dose (fentanyl or labetalol depending upon randomization) and will be titrated up by 5 mcg/kg/min each time an additional intravenous bolus is given.<br>|
| Active Comparator: Fentanyl<br>Fentanyl Bolus and saline infusion | Drug: Fentanyl<br>* Following induction and intubation, any increase in heart rate (HR) or mean arterial pressure (MAP) >20% of baseline will be treated with an initial intravenous bolus of fentanyl 50 mcg IV (50 mcg in 5 ml of normal saline). Any further increases in HR or MAP >20% of baseline will be treated with intravenous boluses of fentanyl 25 mcg in 1 ml every 5 minutes as needed. An intravenous placebo infusion (normal saline) will be initiated at 5 mcg/kg/min after the first intravenous bolus dose and will be titrated up by 5 mcg/kg/min each time an additional intravenous bolus is given.<br>Other: saline infusion<br>* An intravenous placebo infusion (normal saline) will be initiated at 5 mcg/kg/min after the first intravenous bolus drug dose (fentanyl or labetalol depending upon randomization) and will be titrated up by 5 mcg/kg/min each time an additional intravenous bolus is given.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of stay in the post-anesthesia care unit (PACU) | time from arrival in PACU after surgery until discharge from PACU | The time-frame between entry to PACU and discharge from PACU (approximately 1.5 hours). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraoperative Heart Rate (HR) | heart rate (beats per min.) | intraoperatively-from anesthesia induction to the surgery completion (wound closure) -approximately 45 min. | 
| Intraoperative mean arterial pressure (MAP) | blood pressure (mmHg) | intraoperatively-from anesthesia induction to the surgery completion (wound closure)-approximately 45 min. | 
| postoperative nausea and vomiting (PONV) in PACU | incidence of nausea and vomiting | The time-frame between entry to PACU and discharge from PACU (approximately 1.5 hours). | 
| pain scores | pain scores visual analogue scale (VAS) | The time-frame between entry to PACU and discharge from PACU (approximately 1.5 hours). | 
| fentanyl required | total fentanyl required mcg | The time-frame between entry to PACU and discharge from PACU (approximately 1.5 hours). | 
| adverse effects | Any reported adverse effects or complications | The time-frame between entry to PACU and discharge from PACU (approximately 1.5 hours). | 
| postoperative heart rate | heart rate (beats per min) | The time-frame between entry to PACU and discharge from PACU (approximately 1.5 hours). | 
| postoperative mean arterial pressure (MAP) | blood pressure (mmHg) | The time-frame between entry to PACU and discharge from PACU (approximately 1.5 hours). |