Perioperative Analgesia on Postoperative Opioid Usage and Pain Control in H&N Cancer Surgery

Study Overview
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Brief Summary
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The purpose of this study is to determine how a non-opioid pain control regimen, administered before and during surgery, will affect postoperative pain control and total opioid consumption in head and neck cancer participants undergoing cancer surgery with free flap reconstruction.

Detailed Description
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This study will help the study team determine how the experimental, non-opioid pain control regimen affects opioid-related side effects, participant satisfaction with pain management, PACU length of stay, hospital length of stay, chronic pain level, and chronic pain-related disability in participants, and to determine the safety and tolerability of the non-opioid pain control regimen in head and neck cancer patients undergoing cancer surgery with free flap reconstruction. Ketamine, Lidocaine, Acetaminophen, Gabapentin, and Celecoxib are FDA-approved drugs that have been approved for use individually, and have been used in combination for perioperative pain control. However, the use of these five drugs together in head and neck cancer patients undergoing free flap reconstruction has not been studied, which is why this study is experimental.

Official Title
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Investigating the Effect of a Perioperative Analgesia Protocol on Postoperative Opioid Usage and Pain Control in Patients Undergoing Major Head and Neck Cancer Surgery Requiring Microvascular Free Flap Reconstruction

Conditions
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Postoperative Pain Control, Opioid Consumption

Intervention / Treatment
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* Drug: Ketamine
* Drug: Placebo Ketamine
* Drug: Lidocaine
* Drug: Placebo Lidocaine
* Drug: Acetaminophen
* Drug: Placebo Acetaminophen
* Drug: Gabapentin
* Drug: Placebo Gabapentin
* Drug: Celecoxib
* Drug: Placebo Celecoxib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Undergoing head & neck free flap reconstruction at the Cleveland Clinic Main Campus Subjects must have the ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: History of allergy to lidocaine, ketamine, acetaminophen, gabapentin, and/or celecoxib History of allergic reactions attributed to compounds of similar chemical or biologic composition to Ketamine, Lidocaine or other agents used in this study Subjects receiving any other investigational agents Inadequate renal function (serum creatinine ≥ 2 mg/dl) within 30 days Inadequate hepatic function (total bilirubin ≥ 2 x the institutional ULN and/or AST or ALT ≥3 x the institutional ULN) within 30 days Known or suspected history of illicit drug abuse (including opioids but excluding tobacco and EtOH) within the past 6 months Pregnancy Contraindication to lidocaine (heart block, heart failure with EF < 30%) as determined by history of Congestive Heart Failure, or as determined by preoperative evaluation for surgical clearance In the opinion of the investigator, subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Ages Eligible for Study
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Minimum Age: 18 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>Perioperative intervention (preoperative acetaminophen, gabapentin, and celecoxib and intraoperative ketamine and lidocaine). The Investigational Drug Service will mix and prepare the study medications necessary for each participant. An Investigational Drug Service staff member will deliver the oral medications to the nursing team in the preoperative holding unit and the IV medications to the anesthesia team in the OR unit. | Drug: Ketamine<br>* 0.25 mg/kg IV bolus before incision, followed by 0.005 mg/kg/minute IV for the remainder of the surgical case excluding the final 30-45 minutes.<br>* Other names: USP;Drug: Lidocaine<br>* 1.5 mg/kg IV bolus before incision, followed by infusion of 1.5 mg/kg/hour ideal body weight (max 8 hours) during the case<br>* Other names: lidocaine hydrochloride injection;Drug: Acetaminophen<br>* 1,000 mg orally at time of check-in to the preoperative unit<br>* Other names: APAP;Drug: Gabapentin<br>* 600 mg orally at time of check in to the preoperative unit<br>* Other names: Neurontin;Drug: Celecoxib<br>* 200 mg orally at time of check in to the preoperative unit<br>* Other names: Celebrex;|
| Placebo Comparator: Control Group<br>Perioperative placebo Placebo oral drugs will be encapsulated versions provided by the Investigational Drug Service and will appear identical to the interventional oral drugs. Placebo IV infusions will be prepared by Investigational Drug Service as per institutional guidelines and will appear identical to the interventional IV drugs. | Drug: Placebo Ketamine<br>* 0.25 mg/kg IV bolus before incision, followed by 0.005 mg/kg/minute IV for the remainder of the surgical case excluding the final 30-45 minutes.<br>Drug: Placebo Lidocaine<br>* 1.5 mg/kg IV bolus before incision, followed by infusion of 1.5 mg/kg/hour ideal body weight (max 8 hours) during the case<br>Drug: Placebo Acetaminophen<br>* 1,000 mg orally at time of check-in to the preoperative unit<br>Drug: Placebo Gabapentin<br>* 600 mg orally at time of check in to the preoperative unit<br>Drug: Placebo Celecoxib<br>* 200 mg orally at time of check in to the preoperative unit<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total opioid consumption measured in daily morphine equivalent | Total opioid consumption measured in daily morphine equivalent | at 48 hours postop | 
| Pain levels on Visual Analog Scale (VAS) | Change in pain levels on Visual Analog Scale (VAS 0-100mm scale with higher scores corresponding to more pain) | Pre-Op, 24 hours postop, and 48 hours postop | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Opioid Related Symptom Distress Scale (ORSDS) scores | Average Opioid Related Symptom Distress Scale (ORSDS) scores The OR-SDS is used to assess subject-reported levels of severity concerning 12 symptoms known to be associated with opioid medication usage. Symptom frequency, severity, and how bothersome symptom was is rated from 1-4 with higher . The average score for each symptom is calculated by taking the mean of patient-reported score. Total possible severity score: 0 (less severe) to 4 (more severe). | at 96 hours after surgery, and at discharge (an average of 1 week) | 
| Average Patient satisfaction with pain management scores | Average scores for Internally-developed patient satisfaction with pain management questionnaire. Domains include pain expected vs experienced, frequency of severe pain, promptness of care team, effectiveness of treatment, and future preferences Domain scores range from 1-5 with higher scores mean worse outcomes (more severe pain, poor quality of care) Domains are distinct and are not summarized with a totalscore. | at the time of discharge (an average of 1 week) | 
| Time to first flatulence and defecation | Time to first flatulence and defecation from end of surgical case | an average of 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head & neck cancer, Microvascular free flap reconstruction