Minimal Opioid Use After Total Hip Replacement (THR)

Minimal Opioid Use After Total Hip Replacement (THR): a Blinded Randomized Placebo-controlled Study

Total hip arthroplasty can be associated with significant postoperative pain. Side effects of pain management may impair participation in physical therapy and slow readiness for discharge from the hospital. In a previous study done by the investigators' group, epidural patient controlled analgesia (EPCA) with a hydromorphone containing solution appeared to have a more favorable pain profile with ambulation, but greater side effects compared to injection of a peri-articular cocktail. The use of opioid was greater in the peri-articular injection group (PAI). There was no difference in length of stay. In view of the controversy over opioid use, the investigators would like to develop an optimal opioid sparing pain management approach by comparing 3 different protocols 1) Plain local anesthetic EPCA; 2) PAI; 3) EPCA + PAI; all in conjunction with a multimodal opioid sparing pain regimen. The goal would be to maximize pain control while minimizing opioid use and side-effects.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis, Hip
• Intervention / Treatment: Procedure: Periarticular injection (Deep injection); Procedure: Periarticular injection (Superficial injection); Drug: Placebo; Drug: Bupivacaine

Detailed Description

Long acting narcotics or scheduled doses of narcotics are often used as part of a multimodal pain regimen. In this study, this is eliminated. Instead, it uses a cocktail of different drugs including intraoperative Ketamine use (NMDA receptor antagonist), intra-op Benadryl (to decrease excitation of nociceptors) and IV Tylenol. The narcotic free regimen starts preoperatively with the use of Aspirin,Clonidine patch, Cymbalta (Duloxetine), and is maintained both intraoperatively and post operatively. Baby ASA (81mg) is being used as an anti-inflammatory agent. A number of studies including the one by Morris et al. (2009), have shown via in vitro experiments that low dose aspirin decreases polymorphonuclear leukocyte and macrophage accumulation. It inhibits thromboxane making it an antithrombotic agent as well. The concern with aspirin has been major bleeding. Several studies in the orthopedic patient population using ≤81 mg of aspirin have shown that it does not increase bleeding (Cuellar, Mantz). At HSS, patients are routinely continued on baby aspirin when needed for its cardio protective effect. Devereaux in the POISE trial did show an increased risk of bleeding when ASA was given preoperatively at a dose of 200 mg. In our study, all patients will be given intravenous tranexamic acid which should mitigate against the risk of bleeding. Duloxetine is also being added. In a recent study done at HSS. Duloxetine was found to decrease the amount of opioid use and nausea. If found to be more effective with the use of EPCA vs. PAI or combination of the two, a new way of managing postop pain while minimizing Nnartcuoreti co fu Ssetu adsy per CDC recommendation will be helpful in managing patients post-operatively.

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Hospital for Special Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Any patient with osteoarthritis scheduled for primary total hip arthroplasty with a participating surgeon
• Planned use of regional anesthesia
• Planned posterolateral surgical approach
• Age Range 45-80
• Ability to follow study protocol

Exclusion Criteria:

• Any patient with age <45 or >80
• Any patient with planned anterior surgical approach
• Any patient with prior major ipsilateral hip surgery
• Any patient intending to receive general anesthesia
• Any patient with an ASA of IV
• Any patient with insulin-dependent diabetes
• Any patient with hepatic (liver) failure (history of cirrhosis or elevated LFT's)
• Any patient with chronic renal (kidney) failure (formal diagnosis of renal disease of elevated creatinine)
• Any patient with history of gastric (stomach) ulcer
• Chronic opioid use (taking opioids for >3 mo duration on a daily basis)
• Chronic analgesic use (i.e. lyrica, gabapentin) for >3 mo duration
• Stress dose steroids
• Use of antidepressants
• Contraindications to aspirin
• Allergy to any of the medications (or adhesives) involved in the study protocol
• Dementia
• Non-English speakers.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Periarticular Injection (PAI); Aspirin and nerve pain medications including duloxetine and clonidine patch prior to surgery.; Peri-articular injection in the operating room; Combined Spinal Epidural with 1.5% Mepivacaine 4cc; A pain regimen while in the hospital that includes EPCA (saline) Duloxetine (Cymbalta) - by mouth Ketorolac (Toradol) - IV Celecoxib (Celebrex) - by mouth Acetaminophen (Tylenol) - IV; Acetaminophen and celecoxib for pain control once out of the hospital. Patients will also receive a prescription for an opioid medication in case they need it.	Procedure: Periarticular injection (Deep injection); Deep injection of "cocktail" containing Bupivacaine with Epi, 30mL; Morphine, 8mg/mL, 1mL; Methyprednislone, 40mg/mL, 1mL; Cefazolin, 500mg in 10 mL; saline, 22mL into the anterior capsule, the periosteum, the gluteus maximus, and the abductor muscles and fascia lata.; Procedure: Periarticular injection (Superficial injection); Superficial injection of 40mL 0.25% Bupivacaine into subcutaneous tissue prior to wound closure.; Drug: Placebo; EPCA: Saline.
Active Comparator: Epidural Patient-Controlled Analg (EPCA); Aspirin and nerve pain medications including duloxetine and clonidine patch prior to surgery.; Combined Spinal Epidural with 1.5% Mepivacaine 4cc; A pain regimen while in the hospital that consists of Epidural PCA (EPCA) with 0.06% bupivacaine. Duloxetine (Cymbalta) - by mouth Ketorolac (Toradol) - IV Celecoxib (Celebrex) - by mouth Acetaminophen (Tylenol) - IV The EPCA will be removed when pain is well-controlled. Other medications, including opioids, will be available.; Acetaminophen and celecoxib for pain control once out of the hospital. Patients will also receive a prescription for an opioid medication in case they need it.	Drug: Bupivacaine; EPCA: Bupivacaine 0.06%.
Experimental: PAI + EPCA; Aspirin and nerve pain medications including duloxetine and clonidine; Combined Spinal Epidural with 1.5% Mepivacaine 4cc; Anesthetic, Antiemetic and peri-articular injection in the operating room; A pain regimen while in the hospital that consists of EPCA (with 0.06% bupivacaine) Duloxetine (Cymbalta) - by mouth Ketorolac (Toradol) - IV Celecoxib (Celebrex) - by mouth Acetaminophen (Tylenol) - IV The EPCA will be removed when pain is well-controlled. Other medications, including opioids, will be available.; Acetaminophen and celecoxib for pain control once out of the hospital. Patients will also receive a prescription for an opioid medication in case they need it.	Procedure: Periarticular injection (Deep injection); Deep injection of "cocktail" containing Bupivacaine with Epi, 30mL; Morphine, 8mg/mL, 1mL; Methyprednislone, 40mg/mL, 1mL; Cefazolin, 500mg in 10 mL; saline, 22mL into the anterior capsule, the periosteum, the gluteus maximus, and the abductor muscles and fascia lata.; Procedure: Periarticular injection (Superficial injection); Superficial injection of 40mL 0.25% Bupivacaine into subcutaneous tissue prior to wound closure.; Drug: Bupivacaine; EPCA: Bupivacaine 0.06%.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid Use	Oral morphine equivalents, cumulative	within 24 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain at Rest	NRS (Numeric Pain Rating Scale). 0 means no pain, 10 means worst pain imaginable. A lower score is a better outcome.	Postoperative Day 1,2,3,7,90
Pain With Activity	NRS (Numeric Pain Rating Scale). 0 means no pain, 10 means worst pain imaginable. A lower score is a better outcome.	Postoperative Day 1,2,3,7,90
Opioid Side Effects	via ORSDS (Opioid-Related Symptom Distress Scale). Each symptom was rated on a 4 point scale from 0-4. A lower score is a better outcome.	Postoperative Day 1,2
Patient Satisfaction	via Likert scale. A higher score is a better outcome. the scale is from 0-10.	Postoperative Day 1,2,3,7
Post-operative Pain	via PAINOUT (Improvement in postoperative PAIN OUTcome) Minumum value is zero, maximum is ten. Higher scores mean worse outcomes.	Postoperative Day 1
Neuropathic Pain Assessed With S-LANSS	via S-LANSS (Self-report Leeds Assessment of Neuropathic Symptoms and Signs). Scores range from 0-24. A lower score is a better outcome.	Postoperative Day 7, Postoperative Day 90
Quality of Recovery	Via QoR-40 (Quality of Recovery). Minimum value of 40, maximum of 200. Higher values mean better outcome	Postoperative Day 1,2,3
Readiness for Discharge Time	When patient meets all readiness for discharge criteria	From end of surgery until the date/time of first documented clearance for discharge, assessed up to 1 week.
Blinding Assessment	What group do you think you were in	Assessed on day of discharge and on seventh post operative day
Opioid Consumption During the First 3 Days Post-op	Opioids consumed in the first 3 after surgery (cumulative consumption).	Postoperative day 0,1,2,3
No Opioids Consumed	Number of patients who did not consume any opioids	0 to 24 hours post-operatively

Collaborators and Investigators

• Sponsor: Hospital for Special Surgery, New York
• Investigators: Principal Investigator: Kethy Jules-Elysee, MD, Hospital for Special Surgery, New York

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2017
• Primary Completion (Actual): June 28, 2019
• Study Completion (Actual): September 27, 2019

Study Registration Dates

• First Submitted: March 13, 2017
• First Submitted That Met QC Criteria: March 20, 2017
• First Posted (Actual): March 24, 2017

Study Record Updates

• Last Update Posted (Actual): July 27, 2022
• Last Update Submitted That Met QC Criteria: July 26, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Total Hip Arthroplasty; Total Hip Replacement
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Hip; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: 2016-0721

Drug and device information, study documents

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