Studies have demonstrated that many patients report joint pain two weeks after TKA.² Given the status of the ongoing opioid epidemic, it is critical to study safe and effective alternative pain treatments.

“Previous research has shown us how to keep most patients relatively comfortable for the first one to two days after TKA. However, patients often have significant and troubling pain during the first two weeks, once the nerve blocks wear off. They often take large amounts of opioids,” said principal investigator Jacques Ya Deau, MD, PhD, an anesthesiologist at HSS. “It is important to reduce postoperative opioid use without increasing pain or worsening the patient experience.”

Finding alternative strategies for pain relief after TKA is imperative, as improved postoperative pain management is linked to improved patient satisfaction, faster rehabilitation, and reduced complications.

Dr. Ya Deau and colleagues enrolled 160 patients undergoing TKA into the study and randomized them into a duloxetine or placebo group. Patients took 60 mg of oral duloxetine or placebo once daily for 14 days after surgery and answered questions on postoperative days one, two, seven, 14, six weeks, and 90 days. Postoperative pain management also included acetaminophen, ketorolac, meloxicam, and oxycodone as needed.

The researchers collected data on numerical rating scale (NRS) scores for pain management, opioid consumption, patient satisfaction, and questions based on the Brief Pain Inventory.

Duloxetine was found to be better than placebo for reducing opioid use and was of equal efficacy to placebo for reducing pain. Duloxetine was also better than placebo for patient satisfaction and for the effect of pain on mood, walking, working, and sleeping.

“Duloxetine, given on the day of surgery and once daily for 14 days afterwards, reduces opioid use by about 30%. Patients receiving duloxetine are more satisfied with their pain management, and pain interferes less with their activities and mood,” Dr. Ya Deau said.

HSS is committed to patient safety and being a leader in effective pain management. Its Controlled Substances Task Force continues to make strides in patient education and safe prescribing.

In addition to this study, HSS is ramping up further research on opioids with the help of a $3 million grant from the Starr Foundation. “Future research could examine optimum duration of therapy and determine whether duloxetine is also useful for other orthopedic procedures. We also need to try to understand barriers to adoption of duloxetine as a postoperative analgesic,” Dr. Ya Deau concluded.

References

1. Danya A. DeMeo BS, Ejiro Gbaje MPH, Jacques T. YaDeau MD PhD, Kethy M. Jules-Elysee MD, Yi Lin MD PhD, Enrique A. Goytizolo MD, David Kim MD, Richard L Kahn MD, Stephen C. Haskins MD, David J. Mayman MD, Douglas E. Padgett MD, Thomas P. Sculco MD, Chad M. Brummett MD, Geoffrey Westrich MD. “Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty. A Double-Blinded Randomized Control Trial.” Presented at: 46th Annual Regional Anesthesiology and Acute Pain Medicine Meeting of the American Society of Regional Anesthesia and Pain Medicine (ASRA), May 13-15, 2021; Orlando, FL.

2. Lewis GN, Rice DA, McNair PJ, Kluger M. Predictors of persistent pain after total knee arthroplasty: a systematic review and meta-analysis. Br J Anaesthe 2015; 114: 551-61.

HSS Researchers Find Duloxetine May Reduce Opioid Use and Improve Pain Management After Total Knee Replacement

• Anesthesiologist Jacques Ya Deau, MD, PhD and colleagues investigated using duloxetine after surgery to reduce pain and opioid use. They found that duloxetine, given on the day of surgery and once daily for 14 days afterwards, reduced opioid use by about 30%. Patients receiving duloxetine were also more satisfied with their pain management.

Study Identifies Risk Factors for Pediatric Opioid Dependence After Surgery

• Anesthesiologist Kathryn (Kate) DelPizzo, MD and colleagues identified risk factors for persistent opioid use after surgery in pediatric patients. Understanding risk factors for opioid dependence could help develop strategies to prevent long-term opioid use in this vulnerable population.

Knowledge Gaps on Opioid Use and Pain Relief After Surgery Offer Opportunities for Improving Patient Education

• Anesthesiologist Bradley Lee, MD and colleagues identified gaps in patient knowledge about pain management and opioid use before total hip replacement, including misconceptions about how much pain relief to expect from opioids after surgery, how to use multiple modes of pain relief, and proper opioid storage and disposal. Improving patient education about opioids and pain management could lead to improvements in pain control and functional outcomes after surgery.

Interim Study Results Suggest Oral Tranexamic Acid (TXA) Is Equally Effective as Intravenous TXA in Preventing Blood Loss in Joint Replacement Surgery

• Anesthesiologist Stavros Memstoudis, MD, PhD, MBA and colleagues examined the efficacy and safety of oral TXA for joint replacement surgery. Using oral TXA versus intravenous TXA could translate to improvements in efficiency, cost and safety.

HSS Study Examines Hip Fracture Patient Characteristics and Outcomes Pre- and Post-COVID-19 Outbreak

• Anesthesiologist Stavros Memstoudis, MD, PhD, MBA and colleagues sought to compare characteristics and outcomes of hip fracture patients admitted during the COVID-19 outbreak to patients admitted before the outbreak. They also examined characteristics and outcomes of hip fracture patients with and without the virus.

The researchers found that both forms of acetaminophen worked equally well. The paper, titled, "IV vs. Oral Acetaminophen as a Component of Multimodal Analgesia After Total Hip Arthroplasty: A Randomized, Double Blinded, Controlled Trial," was presented today at the American Academy of Orthopaedic Surgeons Annual Meeting in Las Vegas. 

The study has also been published online in advance of print publication in the Journal of Arthroplasty. "At a time when health care costs are increasingly under the microscope, the study supports the use of oral acetaminophen, which is less costly and less invasive to administer," said Geoffrey H. Westrich, MD, the director of research for the Adult Reconstruction and Joint Replacement Service at HSS who presented the study.  

More than 500,000 hip replacements are performed in the United States each year. Although narcotic medication is often part of the pain management plan after surgery, the opioid epidemic has prompted researchers to look for ways to minimize their use.

"A multifaceted pain management plan is standard for all patients having joint replacement surgery at HSS," explained Dr. Westrich. "Known as 'multimodal analgesia', it entails the use of several different anesthetic agents and medications both during and after surgery to control pain and reduce side effects."
 
All 154 patients in the study had hip replacement surgery at HSS. They all received the standard multifaceted pain control protocol after surgery and were randomly assigned to one of two groups. One group received intravenous acetaminophen, while the other group was given the oral pill form. Neither the patients nor their doctors knew which individuals were receiving intravenous versus oral acetaminophen. Those getting IV acetaminophen also received a placebo in pill form, and those given oral acetaminophen received a placebo IV solution.

When they launched the study, the researchers thought intravenous acetaminophen might provide a benefit in terms of pain management, as it reaches the blood stream more quickly than the pill form. But the study found that both worked equally well. 

"Patients in both groups had low pain scores with activity, minimal opioid-related side effects, and limited opioid usage," Dr. Westrich said. "The big picture highlights multimodal analgesia overall as an effective method of pain control after joint replacement surgery."

"How to optimize multimodal therapy for a given patient remains a 'Holy Grail' of research for this field," said Jacques T. YaDeau, MD, PhD, an anesthesiologist at HSS and study author. "At HSS, there is ongoing research on this topic, including both randomized trials and 'big-data' analysis."

"We find that our current departmental protocol appears to give good pain control while patients are in the hospital, but we have limited information about their pain experience in the subacute time frame (two weeks after surgery)," explained co-author and anesthesiologist Jacques T. YaDeau, MD, PhD, and director of the Clinical Research Division within the Department of Anesthesiology, Critical Care & Pain Management. "There is a concern that early discharge may leave some patients vulnerable to excessive pain at home."

To measure pain outcomes in patients who underwent total shoulder arthroplasties using this specific multimodal approach to analgesia, a team of HSS researchers examined outcomes in 100 patients enrolled in a prospective cohort trial. This study presented at the 2018 World Congress used interim findings on the first 50 patients enrolled.

Before surgery, each patient answered questions about their pain levels. During surgery, patients received an interscalene block, a type of peripheral nerve block that desensitizes pain in the shoulder, using local anesthetic in combination with clonidine, dexamethasone and buprenorphine. These medications, when used as part of the interscalene block, are associated with superior pain relief in shoulder replacement patients and are part of the multimodal analgesia plan for many patients at HSS. After surgery, researchers measured patients’ pain scores on days 1, 3, 7, 14 and three months following surgery.

Post-operative pain, both at rest and with movement, was consistently less than pre-operative pain, reported the researchers. While opioid use peaked on day 1, the use of intravenous opioid was minimal – only 24 percent of patients used  more than four doses.

"We found most patients did not make extensive use of intravenous opioids, there was a steep decrease of opioid consumption per 24-hour period over the first two weeks, and a number of patients did not take any oral opioids after leaving the hospital," said Dr. YaDeau.

Patients reported minimal side effects and high satisfaction with their post-operative pain treatment on both 1 and 14 days after surgery.

"Overall, these benchmark results demonstrate excellent analgesia using our current multimodal analgesia pathway," concluded Dr. YaDeau. "These pain outcomes are much better than the published outcomes when patients are given opioids only. The outcomes in this preliminary study provide insight for future research into improving pain relief in patients undergoing shoulder replacements."

Reference

Schweitzer, A BA; Liu, S MD; Gordon M MD; Lin Y MD, PhD; Gulotta, L MD; Dines D MD; Field K MS; YaDeau, JT MD PhD. "Pain Trajectory after Total Shoulder Arthroplasty Conducted with Multimodal Analgesia." Presented at: 2018 World Congress on Regional Anesthesiology and Pain Medicine; April 19-21, 2018.