A nonopioid pain management regimen consisting of nonsteroidal anti-inflammatory drugs (NSAIDs), muscle relaxant, and gabapentin provided equivalent or better postoperative pain relief compared with standard opioid treatment, according to findings from 2 prospective randomized controlled trials of patients who underwent anterior cruciate ligament (ACL) reconstruction or rotator cuff surgery.  

Orthopedic and spine conditions account for approximately 30% of opioid prescriptions. Decreasing the opioid burden after these surgeries may help decrease the risk for opioid dependence and, ultimately, opioid-related deaths. The challenge is to minimize opioid use while optimizing patients’ pain control after surgery, said senior author of both studies Kelechi Okoroha, MD, who is an orthopedic surgeon and sports medicine specialist at Mayo Clinic’s sports medicine facility in Minneapolis, Minn.

“Nurse practitioners and PAs should be aware of alternative pain management strategies that reduce and/or eliminate opioids as they often deal with patients regarding pain and medication refills after surgery,” Dr Okoroha said in an interview. “It is also important to note that these common sports surgeries can be completed without the use of any opioids at all, especially in patients who have not used opioids before.”

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The multimodal nonopioid analgesic protocol use in both studies is shown in the Table.

Postoperative DaysMorningNoonAfternoonEvening
Days 1-5Ketorolac, 10 mg Gabapentin, 300 mg Diazepam, 5 mga Acetaminophen, 1000 mgKetorolac, 10 mg Gabapentin, 300 mg Diazepam, 5 mga Acetaminophen, 1000 mgKetorolac, 10 mg Gabapentin, 300 mg Diazepam, 5 mga Acetaminophen, 1000 mgKetorolac, 10 mg Diazepam, 5 mga  
Days 6-14Meloxicam, 7.5 mg Diazepam, 5 mga Acetaminophen, 1000 mg Meloxicam, 7.5 mg Diazepam, 5 mga Acetaminophen, 1000 mgDiazepam, 5 mga Acetaminophen, 1000 mg
aMethocarbamol was used in the rotator cuff surgery study but has since been replaced by diazepam in the nonopioid protocol to reduce side effects of drowsiness.
Table adapted from Moutzouros et al.

ACL Surgery

The first study compared outcomes in 62 patients undergoing primary ACL reconstruction randomly assigned to the multimodal nonopioid analgesic protocol or a standard opioid regimen (hydrocodone-acetaminophen). The primary outcome was postoperative visual analog scale (VAS) pain scores for 10 days.

Scores on the VAS were significantly lower among patients receiving the nonopioid regimen compared with those who received opioids (mean daily pain difference, 1.56; P <.05). After adjusting for graft type, age, BMI, sex, smoking status, and depression, mean daily pain scores remained significantly lower in the nonopioid group (mean difference, 1.71; P <.001). However, no significant between-group differences were found over time in either analysis.

No significant difference was found in patients’ scores on the Patient-Reported Outcomes Measurement and Information System Pain Interference Short Form preoperatively (58.6 vs. 57.5; P =.385) and at 1-week following surgery (66.3 vs 61.4; P =.147) in the opioid and multimodal nonopioid treatment arms, respectively.

Rotator Cuff Injury

In the second study, patients undergoing rotator cuff repair were randomly assigned to oxycodone (n=23) or the multimodal nonopioid pain regimen (n=17). Pain scores on the VAS on days 1 and 10 postoperatively were significantly higher in the opioid group than in the nonopioid group (Table).

Table. Visual Analog Scale Score on Postoperative Days 1 and 10 Following Rotator Cuff Surgery

OutcomeOpioid RegimenMultimodal Nonopioid RegimenP value
VAS Day 15.7 ± 23.7 ± 2.2.011
VAS Day 104.4 ± 2.72.4 ± 2.2.023

All patients in both studies receive a nerve block before surgery as well as a preoperative regimen of celecoxib, acetaminophen, tramadol, gabapentin, and dexamethasone.

In both studies, the most common side effects were drowsiness, dizziness, and gastrointestinal symptoms. In the rotator cuff study, patients who received opioids reported significantly more days with constipation and upset stomach than those in the nonopioid group. The researchers have since replaced diazepam with methocarbamol in the protocol to reduce drowsiness.

“I think this is really game-changing research,” Dr Okoroha said. “These studies demonstrate an alternative pain regimen that can manage postsurgical pain after common sports surgeries without the use of opioids.”

“We currently use this regimen for ACL reconstructions and rotator cuff surgery at Mayo Clinic,” Dr Okoroha concluded. “We would like to see the regimen used widely in other surgeries. I use it in my practice as long as there are no contraindications to its use.”


Jildeh TR, Abbas MJ, Hasan L, Moutzouros V, Okoroha KR. Multimodal nonopioid pain protocol provides better or equivalent pain control compared to opioid analgesia following arthroscopic rotator cuff surgery: a prospective randomized controlled trial. Arthroscopy. 2021 Nov 25:S0749-8063(21)01046-X. doi:10.1016/j.arthro.2021.11.028

Moutzouros V, Jildeh TR, Tramer JS, Meta F, Kuhlmann N, Cross A, Okoroha KR. Can we eliminate opioids after anterior cruciate ligament reconstruction? A prospective, randomized controlled trial. Am J Sports Med. 2021;49(14):3794-3801. doi:10.1177/03635465211045394