Multimodal Pain Study in Free Flap Patients

Multimodal Management for Perioperative Analgesia in Otolaryngology - Head and Neck Free Flap Reconstructive Surgery: A Prospective Study

This study will be a randomized, prospective study comparing Pain Management Arm A and Pain Management Arm B. Arm A will have scheduled Tylenol with opioids available as needed (PRN) in the peri-operative period. Arm B will undergo scheduled Gabapentin, Ketorolac and Tylenol as well as the Anesthesiology team managing regional nerve blocks, with opioids available PRN in the peri-operative period. The amount of pain medication used by all patients will be recorded as well as pain scores documented on a pain scale (0-10 with 0 indicating no pain and 10 indicating worst pain ever) as well as ABC pain scale throughout the patients' hospital stay. Morphine equivalents for the opioids will be calculated for each arm while observing pain scores. Then, the investigators will compare these two groups to see if there is a difference in opioid pain medication used. The study team's hypothesis is that the use of Gabapentin, Ketorolac, and Tylenol in combination will significantly reduce (at least 30% of Mean Morphine Equivalents - MME) the use of opioid medication for patients undergoing head and neck free flap reconstruction with similar to improved pain scores.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer; Analgesia
• Intervention / Treatment: Drug: Tylenol; Drug: Oxycodone; Drug: Morphine; Drug: Gabapentin; Drug: toradol; Drug: Bupivacaine

Detailed Description

ABSTRACT

Objectives:

To apply implementation science principles to optimize the delivery of multimodal analgesia to patients undergoing major head and neck oncologic surgeries including free flap reconstruction, to reduce variability in opioid administration and decrease the need for opioids.

Methods:

A pilot prospective randomized controlled trial (RCT #1) followed by a hybrid type 1 effectiveness-implementation pragmatic randomized controlled trial (RCT #2).

RCT#1 included patients randomized to receive either scheduled acetaminophen and as needed opioids (control, Group 1) or scheduled acetaminophen, gabapentin, ketorolac, and as needed opioids (experimental, Group 2). The primary outcome was mean morphine milligram equivalents (MMEs) administered during the hospital stay. Secondary outcomes were hospital length of stay (LOS) and postoperative complications. We applied the principles of implementation science after identifying significant variability in healthcare professionals' approaches to administering opioids postoperatively during RCT#1.

RCT#2, a hybrid type 1 effectiveness-implementation pragmatic trial, was designed to test the effectiveness of the intervention and the penetrance of the implementation strategy. Arm A received standard regimen of scheduled acetaminophen and as needed opioids. Arm B received scheduled gabapentin, ketorolac, a regional nerve block at the free tissue donor site, scheduled acetaminophen and as needed opioids. Primary outcome was mean MMEs administered during the hospital stay (0-3 and 0-7 days). Secondary outcomes were LOS, complications, and functional pain scores (ABCs).

KEYWORDS: multimodal analgesia; head and neck; free flap reconstruction; dissemination and implementation

LEVEL OF EVIDENCE: 1B, Randomized Clinical Trial

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients over the age of 18 who are seen in the Department of Otolaryngology-Head and Neck Surgery clinic.
• Patients with a new H&N cancer diagnosis undergoing primary surgery (free flap) for their cancer treatment.

Exclusion Criteria:

• Prior treatment for head and neck cancer.
• Planned treatment with primary radiation or chemoradiation for their head and neck cancer.
• Pregnant or lactating women.
• Patients with a history of consistent or regular opioid use for greater than six months used pre-operatively.
• Chronic gabapentin, pregabalin, and other non-opioid pain medication use pre-operatively.
• Diagnoses with fibromyalgia, anxiety disorder and other pain syndromes.
• Patients with documented history of kidney or liver disease.
• Patients with pre-operative lab values concerning for kidney/liver disease such as increased creatinine or liver function tests.
• Patients with a history of a serious GI bleed, CAD, or history of ischemic stroke .

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of Care A; Randomized controlled prospective trial to compare two standards of care for head and neck surgery pain management. Arm A, will include: Scheduled Tylenol 1000 mg IV one time dose intra-operatively, then 650 mg via PEG tube or PO Q4H to a max dose of 4gm/24 hrs; Opioids prn based on Numeric Pain Scale (0-10, with 0 indicating no pain and 10 indicating worst pain ever):; 0-3: no prn meds, reassurance, listen to music, watch TV.; 4-7: Oxycodone 5 mg q4h prn via PEG tube or PO with a maximum of 30 mg/24 hours.; 8-10 Morphine 2 mg IV q2h prn breakthrough pain.	Drug: Tylenol; Used for both arms, scheduled; Drug: Oxycodone; Used for both arms PRN; Drug: Morphine; Used for both arms PRN
Experimental: Standard of Care B; Arm B, will include: Arm A description with addition..; Scheduled Ketorolac starting post-op day #1, 15 mg q6h (max 120 mg/day), for a total of 5 days; Scheduled Gabapentin starting 7 days preoperatively to continue postoperatively; Regional block per anesthesia protocol - Initial block: 0.5% bupivacaine, 20 ml Continuous infusion: 0.125% bupivacaine at 6 ml/hr with a 5 ml bolus available every 30 mins	Drug: Tylenol; Used for both arms, scheduled; Drug: Oxycodone; Used for both arms PRN; Drug: Morphine; Used for both arms PRN; Drug: Gabapentin; Used for Arm B; Drug: toradol; Used for Arm B; Drug: Bupivacaine; Used for Arm B - anesthesia block

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Morphine Equivalents During Stay	Mean morphine equivalents will be calculated after converting all opioids to morphine equivalents and then averaging them.	Duration of their initial post-operative hospital stay as defined as the interval between index surgery to post-operative day 7.
Mean Morphine Equivalents	Mean morphine equivalents prescribed outpatient after index surgery. Will be calculated after converting all opioids to morphine equivalents and then averaging them.	From day of index surgery to 1 year post-operatively.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of Stay	Length of stay in days	At end of stay, number of post-operative days spent in the hospital was recorded for each patient.
Number of Patients With Post-operative Complications	Monitor chart/EMR for bleeding, acute kidney injury, etc.	Analyze the first 7 post-operative days to confirm number of patients with post-operative complications
Patient Pain Percentage Compared to Baseline	Pain was measured on a Likert scale from 0 to 10 (i.e. 0 being the lowest and 10 being the greatest amount of pain). Baseline pain (P0) was measured on this scale for each patient in the preoperative setting. Pain was similarly assessed at regular intervals post-operatively during hospitalization (Pn). Patient pain percentage was subsequently defined as follows: { 100*[(P_n/P_0) -1]│ n∈N, n≥1} Where: P_0: the baseline (initial) measurement taken at time t=0. P_n: the measurement taken at the nth time interval after baseline, where n∈N, n≥1 Interpretation of "pain percentage compared to baseline": A value of 0% indicates no change from baseline pain; Negative values indicate lower pain than baseline; Positive values indicate higher pain than baseline; Therefore, lower values represent a better outcome and higher values represent a worse outcome	Pain level collected every 2 to 4 hours while inpatient. Daily pain percentage values were first averaged for each patient and then across all patients within each arm.
Patient Pain Assessment Percentage	Each of the domain of ABC pain index is weighted (mult_D) based on relative importance. For each domain D ∈{sleep, lying, sitting, oob, walk}, let: D_able∈{1,2,3}, (1 = able with pain; 2 = unable due to pain; 3 = unable for other reasons) D_pain∈[0, 5] (reported pain score) Then if: D_able = 1 numerator_D = D_pain × mult_D denominator_D = 1 +(5×mult_D) D_able=2 numerator_D = 1 + (5×mult_D) denominator_D= 1 + (5×mult_D ) D_able=3 numerator_D = 1 denominator_D = 1 For the site-specific domains D ∈{h&n,flap,graft}, let: D_present∈{1,2} (1=present; 2=absent) D_pain∈[0, 5] (reported pain score) Then if: D_present=1: numerator_D = D_pain × mult_D denominator_D = 5 × mult_D D_present=2: numerator_D = 0 denominator_D = 0 Patient Pain Assessment Percentage: ABC_numerator = sum(numerator_D) ABC_denominator = sum(denominator_D) ABC_percentage = ABC_numerator / ABC_denominator This ranges from 0-100%. Lower values are better, higher values are worse.	Daily. The ABC pain scale will be given once daily for the patient to fill out for the first seven days.

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Investigators: Principal Investigator: Lisa Shnayder, MD, KUMC

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Actual): June 1, 2021
• Study Completion (Actual): May 1, 2023

Study Registration Dates

• First Submitted: October 31, 2019
• First Submitted That Met QC Criteria: January 28, 2020
• First Posted (Actual): January 29, 2020

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neoplasms by Site; Neoplasms; Neurobehavioral Manifestations; Perceptual Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Head and Neck Neoplasms; Agnosia; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Acids, Acyclic; Carboxylic Acids; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Indomethacin; Indoles; Amino Acids; Heterocyclic Compounds, 4 or More Rings; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Carbocyclic; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Morphine Derivatives; Cyclohexanecarboxylic Acids; Codeine; Gabapentin; Bupivacaine; Acetaminophen; Morphine; Ketorolac Tromethamine; Oxycodone
• Other Study ID Numbers: 00025711

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No