Dextromethorphan Use in Multimodal Analgesia Regimens for Total Knee Arthroplasty

NCT ID: NCT02987920

Last Updated: 2019-05-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2018-01-31

Brief Summary

Total knee arthroplasty (TKA) is one of the most painful orthopedic procedures. After TKA surgery, postoperative pain relief may be achieved using a variety of techniques. Integral to recovery and improved outcomes is early ambulation and mobilization. Achieving adequate postoperative pain control while ensuring the ability to ambulate early can be quite challenging.

Currently, in our country there has been a call to address prescription opioid use and abuse due to a nationwide opioid epidemic. In light of this, improving our multimodal analgesic protocol will serve to decrease reliance of opioid medications for pain control. Multimodal analgesia is effective in decreasing total opioid consumption postoperatively. Dextromethorphan is a low-affinity noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. It has a long history of clinical use with an established safety record. Studies have shown that it has a positive effect as an analgesic.

In order to see if dextromethorphan will decrease opioid use, this study will look at two patient groups undergoing total knee arthroplasty with the same preoperative, intraoperative, and postoperative anesthetic plan with the exception of the addition of dextromethorphan to one groups multimodal analgesic regimen. This study is designed as a double-blinded, randomized, prospective cohort trial.

Detailed Description

Each subject will receive as part of their standard of care a spinal with sedation for intraoperative anesthesia.

Subjects will be randomly assigned using computer generated allotment. The group designation will be placed in sealed envelopes. The group listed will determine whether or not they will receive dextromethorphan as part of their preoperative preincisional analgesic regimen. Only the pharmacist dispensing the medication will be unblinded. The drug and placebo will then be concealed by the pharmacist and delivered to the patient to ingest in the preoperative area.

Group A: standard preop meds

Group B: standard preop meds + dextromethorphan

The standard preoperative analgesic regimen will include placement of an adductor canal catheter nerve block, acetaminophen 1000mg PO, oxycodone extended release 10mg PO, celecoxib 400mg PO (held if elevated creatinine), and pantoprazole 40mg PO

All blocks will be performed by resident trainees under the supervision of anesthesia regional and acute pain attendings. The continuous adductor canal nerve block will be placed using B-Braun "Contiplex Continuous Peripheral Nerve Block Tray", using 20g catheters.

Intraoperative anesthesia will be performed with spinal injection using local anesthestic only. No opioid will be given intrathecally. Intraoperative sedation will include standard sedation with propofol infusion. Postoperative nausea and vomiting prophylaxis will include ondansetron, propofol infusion, and dexamethasone 0.1mg/kg if not contraindicated. The postoperative recovery room pain protocol will include the following: starting the adductor canal catheter infusion with "On-Q" pump dispensing ropivicaine 0.1% at 4ml/hr, oxycodone 5 10mg po for moderate to severe pain, dilaudid 0.2mg IV q5min up to 2 mg, ketorolac 30mg intravenous (IV) once, and acetaminophen 1000mg intravenous once if greater than 6 hours has elapsed since initial preoperative dose.

Assessments of pain using the VAS pain score will be performed in postanesthesia care unit (PACU) at the time of spinal block cessation by a blinded observer (recovery room nurse), and then subsequently every 4 hours by a registered nurse and documented in the electronic medical record. Initial evaluation for resolution of the spinal blockade will be performed at the 1 hour timepoint in the PACU.

Assessments of opioid administration, will include all medications given and documented in the electronic medical record. The various time points analyzed will include intraoperative, PACU, and daily postoperative morphine equivalents administered to each patient.

Postoperative followup will be done by research personnel blinded to the group distribution. Visual Analog Scale for Pain (VAS Pain) will be performed every 4 hours until discharge.

On postoperative day (POD) #1, all patients will be given the Quality of Recovery (QoR) Questionnaire. This is recovery specific, patient rated questionnaire containing 40 items measuring 5 dimensions. The QoR 40 was specifically designed to measure a patient's health status after surgery and anesthesia, and its completion time generally ranges from 3 to 10 min. The five dimensions measured include: the physical comfort (12 items), emotional state (nine items), physical independence (five items), psychological support (seven items) and pain (seven items). The total score and subscales of the QoR 40 are measured using a five point Likert scale (for positive items: 1 = none of the time, 5 = all of the time; for negative items, the scoring was reversed) and individual scores are then added together, with the minimum score being 40 points and the maximum score being 200 points.

In addition, the study will require home follow up phone calls assessing the occurrence of any possible side effects or complications, pain, and postoperative opioid use. These phone calls will occur at POD#3 after discharge, POD #7, POD #14, and POD#28. Each of these phone assessments will require about 5 minutes of time. Authorized research personnel of the study project will be making the phone calls.

Conditions

Pain, Postoperative

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo - Concentrate

preoperative oral medications given one time: acetaminophen 1000mg tablet, oxycodone extended release 10mg tablet, celecoxib 400mg tablet, pantoprazole 40mg tablet, and Placebo - Concentrate by mouth.

postoperative medications given for 2 days: Acetaminophen 1000mg every 6hr, Ketorolac15mg IV q6hrs x4 doses, Oxycodone 5mg po q3hrs prn moderate pain, Oxycodone10mg po q3hrs prn severe pain, Gabapentin100-300mg once at night, Dilaudid 0.2mg IV q2hrs prn severe pain

Group Type: ACTIVE_COMPARATOR

Placebo - Concentrate

Intervention Type: DRUG

Additional medication to perioperative analgesic regimen to Group A

Acetaminophen

Intervention Type: DRUG

Multimodal analgesic regimen to Group A and Group B

Oxycodone

Intervention Type: DRUG

Multimodal analgesic regimen to Group A and Group B

Celecoxib

Intervention Type: DRUG

Multimodal analgesic regimen to Group A and Group B

Pantoprazole

Intervention Type: DRUG

Multimodal analgesic regimen to Group A and Group B

Ketorolac

Intervention Type: DRUG

Multimodal analgesic regimen to Group A and Group B

Gabapentin

Intervention Type: DRUG

Multimodal analgesic regimen to Group A and Group B

Hydromorphone

Intervention Type: DRUG

Multimodal analgesic regimen to Group A and Group B

Dextromethorphan

preoperative oral medications given one time: acetaminophen 1000mg tablet, oxycodone extended release 10mg tablet, celecoxib 400mg tablet, pantoprazole 40mg tablet, and Dextromethorphan 60mg tablet

postoperative medications given for 2 days: Acetaminophen 1000mg every 6hr, Ketorolac15mg IV q6hrs x4 doses, Oxycodone 5mg po q3hrs prn moderate pain, Oxycodone10mg po q3hrs prn severe pain, Gabapentin100-300mg once at night, Dilaudid 0.2mg IV q2hrs prn severe pain, and dextromethorphan 60mg by mouth twice daily

Group Type: EXPERIMENTAL

Dextromethorphan

Intervention Type: DRUG

Additional medication to perioperative analgesic regimen in Group B

Acetaminophen

Intervention Type: DRUG

Multimodal analgesic regimen to Group A and Group B

Oxycodone

Intervention Type: DRUG

Multimodal analgesic regimen to Group A and Group B

Celecoxib

Intervention Type: DRUG

Multimodal analgesic regimen to Group A and Group B

Pantoprazole

Intervention Type: DRUG

Multimodal analgesic regimen to Group A and Group B

Ketorolac

Intervention Type: DRUG

Multimodal analgesic regimen to Group A and Group B

Gabapentin

Intervention Type: DRUG

Multimodal analgesic regimen to Group A and Group B

Hydromorphone

Intervention Type: DRUG

Multimodal analgesic regimen to Group A and Group B

Interventions

Dextromethorphan

Additional medication to perioperative analgesic regimen in Group B

Intervention Type: DRUG

Placebo - Concentrate

Additional medication to perioperative analgesic regimen to Group A

Intervention Type: DRUG

Acetaminophen

Multimodal analgesic regimen to Group A and Group B

Intervention Type: DRUG

Oxycodone

Multimodal analgesic regimen to Group A and Group B

Intervention Type: DRUG

Celecoxib

Multimodal analgesic regimen to Group A and Group B

Intervention Type: DRUG

Pantoprazole

Multimodal analgesic regimen to Group A and Group B

Intervention Type: DRUG

Ketorolac

Multimodal analgesic regimen to Group A and Group B

Intervention Type: DRUG

Gabapentin

Multimodal analgesic regimen to Group A and Group B

Intervention Type: DRUG

Hydromorphone

Multimodal analgesic regimen to Group A and Group B

Intervention Type: DRUG

Other Intervention Names

delsym; placebo, placebos, sugar water; tylenol; oxycodone extended release; oxycontin; celebrex; protonix; toradol; neurontin; dilaudid

Eligibility Criteria

Inclusion Criteria

• Adult patients (>18 years of age, American Society of Anesthesiologists (ASA) > IIII) who are undergoing only elective primary total knee replacement will be included in the study.

Exclusion Criteria

• patient refusal to be included in the study, contraindications to regional anesthesia, history of allergy to amide local anesthetics, the presence of a progressive neurological deficit, chronic pain diagnoses, the presence of coagulopathy or infection, or pregnancy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Southern California

OTHER

Sponsor Role: lead

Responsible Party

Hanna Schittek

Clinical Assistance Professor of Anesthesiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hanna Schittek, MD

Role: PRINCIPAL_INVESTIGATOR

University of Southern California

Other Identifiers

HS-16-00739

Identifier Type: -

Identifier Source: org_study_id