Pharmacologic, Physical, and Cognitive Pain Alleviation for Musculoskeletal Extremity/Pelvis Surgery
This guideline was produced in collaboration with METRC, with funding provided by the US Department of Defense. Endorsed by: SOMOS, OTA
Acupuncture
Limited evidence suggests that acupuncture may be used with standard treatment for improved pain scores; however, there were no significant differences in function.
Limited Evidence Limited Evidence

Three high quality (Crawford 2019, Wetzel 2011, Usichenko 2007) papers focusing on auricular acupuncture were evaluated.  One paper showed improved pain with acupuncture versus sham; a second paper showed decreased opioid consumption with acupuncture versus sham; a third paper showed no difference.

One high quality (Petersen 2018) and one moderate (Mikashima 2012) quality papers evaluated acupuncture on various body areas and showed no difference or improvement in pain.  One paper showed improved function after acupuncture, but the other showed no difference or slight improvement with standard care. 

One high quality (Chen 2015) paper combined auricular and acupuncture on the body and compared it against sham acupuncture. The results showed an improvement in pain and decreased opioid use with fewer side effects in the acupuncture group.

The Acupuncture recommendation has been downgraded two levels because of inconsistent evidence.

Benefits/Harms of Implementation

Overall, effect size is limited with these studies, however the low cost and risk to the patient of acupuncture weigh positively in considering use of this physical treatment.  

Cost Effectiveness/Resource Utilization

Minimal cost and resource utilization, however acupuncture-trained professional would have to be hired/available.

Acceptability

May have some challenge gaining acceptability in Western medicine, however acupuncture is more widely acknowledged as a reasonable medical treatment than in prior decades.

Feasibility

Most patients would have no limitation in receiving this treatment, however feasibility may be limited by the number of skilled acupuncture professionals available.

Future Research

Increased studies comparing auricular with other body acupuncture, better examination of pain and opioid consumption after these interventions, better examination of functional scores and outcomes after this intervention.

 

 

Acupuncture
Limited evidence suggests no significant difference in patient pain and function outcomes between auricular or other acupuncture and sham.
Limited Evidence Limited Evidence

Three high quality (Crawford 2019, Wetzel 2011, Usichenko 2007) papers focusing on auricular acupuncture were evaluated.  One paper showed improved pain with acupuncture versus sham; a second paper showed decreased opioid consumption with acupuncture versus sham; a third paper showed no difference.

One high quality (Petersen 2018) and one moderate (Mikashima 2012) quality papers evaluated acupuncture on various body areas and showed no difference or improvement in pain.  One paper showed improved function after acupuncture, but the other showed no difference or slight improvement with standard care. 

One high quality (Chen 2015) paper combined auricular and acupuncture on the body and compared it against sham acupuncture. The results showed an improvement in pain and decreased opioid use with fewer side effects in the acupuncture group.

The Acupuncture recommendation has been downgraded two levels because of inconsistent evidence.

Benefits/Harms of Implementation

Overall, effect size is limited with these studies, however the low cost and risk to the patient of acupuncture weigh positively in considering use of this physical treatment.  

Cost Effectiveness/Resource Utilization

Minimal cost and resource utilization, however acupuncture-trained professional would have to be hired/available.

Acceptability

May have some challenge gaining acceptability in Western medicine, however acupuncture is more widely acknowledged as a reasonable medical treatment than in prior decades.

Feasibility

Most patients would have no limitation in receiving this treatment, however feasibility may be limited by the number of skilled acupuncture professionals available.

Future Research

Increased studies comparing auricular with other body acupuncture, better examination of pain and opioid consumption after these interventions, better examination of functional scores and outcomes after this intervention.

 

 

Acupressure
Limited evidence suggests that auricular acupressure may be used with standard treatment for opioid reduction and improved function; however, there was no difference in pain.
Limited Evidence Limited Evidence

Three high quality (Feng 2017, He 2013, Chang 2012) papers focusing on acupressure were evaluated.  Two papers showed decreased opioid consumption and improved function with acupressure versus sham; one of these also showed improved pain and decreased side effects (nausea, vomiting, and dizziness) with acupressure versus sham.  A third paper showed no difference in side effects with acupressure versus sham.

The Acupressure recommendation has been downgraded two levels because of inconsistent evidence.

Benefits/Harms of Implementation

Overall, effect size is limited with these studies, however the low cost and risk to the patient of acupressure weigh positively in considering use of this physical treatment. 

Cost Effectiveness/Resource Utilization

Minimal cost and resource utilization, however acupressure-trained professional would have to be hired/available.

Acceptability

May have some challenge gaining acceptability in Western medicine, however acupuncture is more widely acknowledged as a reasonable medical treatment than in prior decades.

Feasibility

Most patients would have no limitation in receiving this treatment, however feasibility may be limited by the number of skilled acupressure professionals available.

Future Research

Increased studies with larger patient populations evaluating acupressure with better examination of pain and opioid consumption after these interventions, better examination of functional scores and outcomes after this intervention

Compression
Limited evidence suggests no significant differences in pain or function with compression.
Limited Evidence Limited Evidence

Three high quality studies (Grubhofer 2018, Snyder 2017, Pornrattanamaneewong 2019) and two moderate quality (Windisch 2011, Pornrattanamaneewong 2018) were evaluated with inconsistent results.  In most cases, compression versus standard care showed no significant differences for pain or function.  In one study, prolonged use of compression for six weeks had improved VAS and decreased DVT rate.  A separate study had decreased opioid use on post-operative day one with compression.

The Compression recommendation has been downgraded two levels because of inconsistent evidence.

Benefits/Harms of Implementation

Overall, effect size is limited with these studies, however the low cost and risk to the patient of compression weigh positively in considering use of this physical treatment.  A decreased rate of DVT could have a benefit to the patient.

Cost Effectiveness/Resource Utilization

Use of compression in these studies required a specific machine which itself would be a large cost if a treating facility had not already invested in these devices.  Otherwise, resource utilization is low.

Acceptability

Compression is already widely used in hospitals and would have no concerns with acceptability.

Feasibility

Compression is already widely used in hospitals and would have no concerns with feasibility.  For an extended use of compression (after discharge), feasibility would be more challenging to gain resources from payers to distribute portable devices.

Future Research

Increased studies with larger patient populations evaluating compression with better examination of pain and opioid consumption after these interventions, better examination of functional scores and outcomes after this intervention.

Cryotherapy
Limited evidence suggests no significant difference in patient pain, function and opioid use between cryo-compression and control/ice/circulating water.
Limited Evidence Limited Evidence

Nine high (Levy 1993, Schinsky 2016, Ivey 1994, Li 2016, Thijs 2019, Kullenberg 2006, Smith 2002, Sadoghi 2018, Park 2019) and seven moderate quality articles (Gibbons 2002, Karaduman 2019, Thienpont 2014, Bech 2015, Leegwater 2017, Dervin 1998, Su 2012, Pan 2015) were reviewed regarding cryotherapy.  Of the five studies evaluating pain, three showed improved pain with cryotherapy and one of these also showed decreased opioid consumption.  Of the seven studies evaluating function after cryotherapy, five showed improved range of motion with cryotherapy. 

The Cryotherapy recommendation has been downgraded two levels because of inconsistent evidence.

Benefits/Harms of Implementation

Prolonged cryotherapy could potentially harm the patient with skin contact damage in certain sensitive population, but overall low risk intervention.

Cost Effectiveness/Resource Utilization

Use of a cryotherapy machine would be a large cost if a treating facility had not already invested in these devices.  In addition, large cost for patient to take this device home if indicated.  Potentially large resource utilization in donning/doffing if needing assistance from nursing.

Acceptability

Would require increased resource utilization which may have some concerns with acceptability.

Feasibility

For an extended use of cryotherapy (after discharge), feasibility would be more challenging to gain resources from payers to distribute portable devices.

Future Research

Increased studies with larger patient populations evaluating cryotherapy with better examination of pain and opioid consumption after these interventions, better examination of functional scores and outcomes after this intervention.

Early Mobilization
Limited evidence suggests no difference in patient pain, function and opioid use between earlier mobilization and standard treatment.
Limited Evidence Limited Evidence

Twenty high quality (Christersson 2018, Sheps 2015, Bohl 2019, Paschos 2013, Jenssen 2018, Beaupre 2001, Aufwerber 2020, Kimmel 2012, Lehtonen 2003, Hagen 2020, Okamoto 2016, Schroter 2017, Aufwerber 2019, Keener 2014, Dehghan 2016, Iwakiri 2020, Sheps 2019, Mazzocca 2017, Smeeling 2018, Sherrington 2003) and thirteen moderate quality studies (Yashar 1997, Bennett 2005, Kumar 1996, Lee 2012, Johnson 1990, MacDonald 2000, Gross 2016, Liow 2002, De Roo 2015, Zhang 2017, Arndt 2012, Cuff 2012, Mortensen 1999, Suchak 2008) were reviewed. Most studies showed no significant difference in improvement in pain, patient reported outcomes or opioid use. Three high quality and one moderate quality studies showed worsened pain, while one high quality and one moderate quality study showed improved pain. Seven high quality and five moderate quality studies showed improved function, while two high quality and two moderate quality studies showed worsened function.

The Early Mobilization recommendation has been downgraded two levels because of inconsistent evidence.

Benefits/Harms of Implementation

Despite the large number of studies, only one showed significant negative adverse events for this intervention.

Cost Effectiveness/Resource Utilization

Potentially large resource utilization in delivering this level of care in the hospital setting

Acceptability

Would require increased resource utilization which may have some concerns with acceptability.

Feasibility

Intervention has been used extensively and is clearly feasible.

Future Research

Inconsistent results highlight the need for larger studies with an emphasis on heterogenous treatment effects

Massage
Massage may be used with standard treatment for improved pain outcomes.
Moderate Evidence Moderate Evidence

One high quality (Pasyar 2018) and three moderate quality (Forward 2015, Eghbali 2010, Buyukyilmaz 2013) studies were reviewed. All studies showed improvements in pain. Only one study measured opioid use and did not report improvement, and no studies measured function.

Benefits/Harms of Implementation

No studies reported adverse events, but the level of risk associated with this intervention is low.

Cost Effectiveness/Resource Utilization

Potentially moderate to high resource utilization in delivering this level of care in the hospital setting.

Acceptability

Would require increased resource utilization and specialized staff which may have some concerns with acceptability

Feasibility

Intervention has been used extensively and is clearly feasible.

Future Research

Further research into the effect of this intervention on opioid use and function are needed, as well as cost effectiveness studies.

Neuromuscular Electrical Stimulation
Neuromuscular electrical stimulation should be used with standard treatment to improve function, but no significant difference is seen in pain.
Strong Evidence Strong Evidence

Two high quality (Stevens-Lapsley 2012, Feil 2011) and one moderate quality (Skowron 2019) study were reviewed. The two high quality studies showed improved function for Neuromuscular electrical stimulation (NMES) over standard of care, and one high quality study also showed improved function over Transcutaneous electrical nerve stimulation (TENS). The single moderate quality study showed decreased ROM and no change on QOL outcomes for NMES compared to standard treatment. Two studies (one high and one moderate quality) showed no changes in pain.

Benefits/Harms of Implementation

No studies reported adverse events and this technology is in widespread use. Risks appear to be low.

Cost Effectiveness/Resource Utilization

NEMS units are economical and may have low resource utilization in the hospital setting.

Feasibility

Intervention has been used extensively and is clearly feasible.

Future Research

Inconsistent results highlight the need for larger studies with an emphasis on heterogenous treatment effects. Further research into the effect of this intervention on opioid use and pain are needed, as well as cost effectiveness studies.

Transcutaneous Electrical Nerve Stimulation
Moderate evidence supports no significant difference in functional outcomes, pain or opioid use between transcutaneous electrical nerve stimulation and standard treatment or sham.
Moderate Evidence Moderate Evidence

Eight high quality (Kadi 2019, Gorodestskyi 2017, Ramanathan 2017, Feil 2011, Avramidis 2011, Izumi 2015, Forogh 2019, Rakel 2014) and three moderate quality (Goyal 2012, Lan 2012, Gorodetskyi 2010) studies were reviewed. Only one of these eleven studies reported improvements in function (over standard treatment), and two additional studies reported improvement in ROM. Only one moderate quality study reported reductions in opioid use. Three of nine studies reporting on pain outcomes showed improvement.

The Transcutaneous Electrical Nerve Stimulation recommendation has been downgraded one level because of inconsistent evidence.

Benefits/Harms of Implementation

No studies reported adverse events and this technology is in widespread use. Risks appear to be low.

Cost Effectiveness/Resource Utilization

Transcutaneous electrical nerve stimulation (TENS) units are economical and may have low resource utilization in the hospital setting.

Future Research

Inconsistent results highlight the need for larger studies with an emphasis on heterogenous treatment effects, particularly around pain outcomes and cost effectiveness studies.

 

Peri-op Injections
Moderate evidence suggests no difference in patient outcomes between local and regional anesthesia for patients undergoing total knee and hip arthroplasty.
Moderate Evidence Moderate Evidence

Six high quality (Kuchalik 2017 (a), Kuchalik 2017 (b), Kuchalik 2013, Jules-Elysee 2015, Johnson 2017, Fahs 2018) total hip arthroplasty and twenty-six total knee arthroplasty (Tong 2018, Runge 2016, Zhou 2018, Kampitak 2018, Mayr 2019, Varshney 2019, Chaubey 2017, McDonald 2016, Tanikawa 2014, Fan 2016, McCarthy 2019, Safa 2014, Rizk 2017, Affas 2011, Meftah 2019, Sogbein 2017, Carli 2010, Chandy 2019, Chaumeron 2017, Tammachote 2013, Mahadevan 2012, Li 2017, Ukai 2020, Gi 2014, Uesugi 2014, Tanikawa 2017) showed no difference in patient outcomes.

The Peri-Op Injection recommendation has been downgraded one level because of inconsistent evidence.

Benefits/Harms of Implementation

Improved pain control can improve patient satisfaction and reduce patient morbidity by mitigating the systemic stress response. Reducing opioid use in the post-op period mitigates their well-known side-effects such as nausea/vomiting, respiratory depression, tolerance, etc. Local anesthetic systemic toxicity is always a concern when using local anesthetics. Proximal brachial plexus regional anesthesia may cause hemidiaphragm paresis which may not be tolerated in those with severe pulmonary disease.

Outcome Importance

Postoperative pain control is an important concern to patients, and when poorly managed is associated with delays in achieving functional milestones, greater opioid use, and increased morbidity. The US is in the midst of an opioid epidemic known to contribute to the development of hyperalgesia, tolerance, dependence, addiction, and abuse. Therefore, reducing opioid use is a national priority.

Cost Effectiveness/Resource Utilization

Bupivacaine and ropivacaine, the most used long-acting local anesthetics in regional anesthesia, are both inexpensive and available in generic formulations. The peri-operative use of continuous regional anesthesia requires the assistance of a qualified anesthesia provider, an infusion pump system, and close patient follow-up

Acceptability

Continuous regional anesthesia has been widely used for orthopaedic surgery patients for over 30 years.

Feasibility

Continuous regional anesthesia may not be available in smaller medical centers or ambulatory surgery centers

Future Research

Local anesthetics have a key role in treating surgical pain. Future studies should explore novel local anesthetics and adjuvant agents that prolong the duration of pain relief, as well as motor-sparing regimens. These studies should also examine the optimal combination of both local and regional anesthetics versus either technique alone.

Peri-op Injections Total Shoulder Arthroplasty
Strong evidence supports the use of continuous regional anesthesia over local anesthesia in total shoulder arthroplasty to reduce pain and opioid use in the first 24hrs after surgery.
Strong Evidence Strong Evidence

One high quality study (Panchamia 2019) demonstrated that a continuous interscalene brachial plexus catheter was associated with reduced pain and less opioid use thru noon on post-operative day 1 after Total Shoulder Arthroplasty.

One moderate quality study (Bjornholdt 2015) demonstrated that a continuous interscalene brachial plexus catheter was associated with reduced pain thru 8 hours post-operatively and less opioid use in the first 24 hours after Total Shoulder Arthroplasty.

The Peri-Op Shoulder Injection recommendation has been upgraded one level due to the large magnitude of treatment effects for the critical outcomes of pain and opioid consumption.

Benefits/Harms of Implementation

Improved pain control can improve patient satisfaction and reduce patient morbidity by mitigating the systemic stress response. Reducing opioid use in the post-op period mitigates their well-known side-effects such as nausea/vomiting, respiratory depression, tolerance, etc. Local anesthetic systemic toxicity is always a concern when using local anesthetics. Proximal brachial plexus regional anesthesia may cause hemidiaphragm paresis which may not be tolerated in those with severe pulmonary disease.

Outcome Importance

Postoperative pain control is an important concern to patients, and when poorly managed is associated with delays in achieving functional milestones, greater opioid use, and increased morbidity. The US is in the midst of an opioid epidemic known to contribute to the development of hyperalgesia, tolerance, dependence, addiction, and abuse. Therefore, reducing opioid use is a national priority.

Cost Effectiveness/Resource Utilization

Bupivacaine and ropivacaine, the most used long-acting local anesthetics in regional anesthesia, are both inexpensive and available in generic formulations. The peri-operative use of continuous regional anesthesia requires the assistance of a qualified anesthesia provider, an infusion pump system, and close patient follow-up

Acceptability

Continuous regional anesthesia has been widely used for orthopaedic surgery patients for over 30 years.

Feasibility

Continuous regional anesthesia may not be available in smaller medical centers or ambulatory surgery centers.

Future Research

Local anesthetics have a key role in treating surgical pain. Future studies should explore novel local anesthetics and adjuvant agents that prolong the duration of pain relief, as well as motor-sparing regimens. These studies should also examine the optimal combination of both local and regional anesthetics versus either technique alone.

Cognitive/Behavioral Treatment
Limited evidence suggests no difference in patient function or pain outcomes between cognitive behavioral therapy and standard treatment for patients undergoing total knee arthroplasty.
Limited Evidence Limited Evidence

One high quality (Riddle 2019) and one moderate quality study (Cai 2018) met inclusion criteria. Multiple studies of CBT are present in the orthopaedic literature; however, the lack of randomization and robust data analysis limit the current analysis to two studies. Furthermore, the various methods of CBT available and different methods of delivery make interpretation of the literature challenging.

One high quality study (Riddle 2019) demonstrated no differences in WOMAC scores among patients undergoing TKA for those who had or who had not received pain coping skills cognitive behavioral interventions.   However, this study included only those patients with moderate to high levels of catastrophizing, an area not routinely measured among those undergoing musculoskeletal surgery.

One moderate quality study (Cai 2018) noted that patients with high levels of kinesiophobia undergoing TKA who were in the intervention arm experienced decreased pain and improved function, but noted decreased kinesiophobia, after surgery.  However, this study is limited in its applicability, given the limitation of the patient population to only those with high levels of kinesiophobia, a characteristic not routinely measured in patients undergoing musculoskeletal surgery. 

The Cognitive/Behavioral Treatment recommendation has been downgraded one level because of inconsistent evidence.

Benefits/Harms of Implementation

While cognitive behavioral therapy may be a promising non-pharmacologic modality to improve post-operative pain control and function, there is not enough evidence to recommend its use at this point.  There are limited risks to using CBT, primarily emotional discomfort, although this may be more severe in some patients.  Only one of the studies (Cai 2018) focused on differences in treatment efficacy between genders and found none, and none of the studies specifically evaluated the effect of education level on outcomes.

Cost Effectiveness/Resource Utilization

Costs and resource utilization depend on the method of CBT chosen. In some studies, noted above, CBT is performed by trained clinical psychologists, whereas in others physical therapists are trained in CBT techniques. The costs and use of resources may vary substantially depending on the method of delivery chosen.

If personnel other than behavioral health professionals are performing this intervention they would need to be identified and receive appropriate training.  Presumably, they would be people already working with patients undergoing surgery, without need for additional hires.  The availability and cost of this training is 

not known.  However, once this training is received, this would seem to be a more cost-effective measure than pharmacologic options if training costs were offset by savings in other areas (e.g,, fewer opioids prescriptions, better function resulting in shorter lengths of stay).

Acceptability

CBT is receiving increased attention as a mechanism to improve pain and function.  However, cost, resource utilization, and time management concerns may hinder the delivery of CBT to patients.  The studies available for review were limited in either the patient population included (levels of kinesiophobia or pain catastrophizing) or because they were performed outside of the US.  Given the significant cultural implications of pain expression and opioid use, it is difficult to extrapolate results found among patients in a different culture to patients from the broad range of backgrounds found in the US. 

Feasibility

CBT may not be available to all patients due to limited access to or availability of behavioral health services, non-availability of CBT for outpatient surgical patients, and time constraints. Providing access to physical therapists and/or psychologist with training in CBT related to surgical outcomes may be challenging, especially in rural/frontier or smaller hospitals, where access to mental health services is already limited. While tele-mental health could be utilized for this, half of the US population does not have access to sufficient broad band internet access for this type of patient visit, and future studies would need to assess whether phone consultation in their circumstances is equivalent to in-person or virtual (audio and visual) interactions.

Future Research

Additional research is needed to better determine the impact of CBT on patient function and opioid use after musculoskeletal surgery.  This would seem to be a promising non-pharmacologic intervention, given the significant impact of mental health on the pain experience and opioid use, but there is currently insufficient evidence to recommend its routine use.  In addition, current evidence is limited to specific populations, and the efficacy of CBT has not been established for heterogeneous groups.   While 2 of the included studies found no differences in outcome based on patient sex or gender, future studies should include this as a routine variable.  Further research should investigate the effect of culture, education status, socioeconomic status, sex, gender, and other demographic variables on the efficacy of CBT after orthopaedic surgery. Furthermore, the optimal timing and method of delivery of CBT has not been established and merits further study.

 

Guided Relaxation Therapy
There is no significant difference in pain and opioid use outcomes between guided relaxation therapy and standard treatment.
Moderate Evidence Moderate Evidence

Guided relaxation therapy includes progressive muscle relaxation and guided imagery with or without therapeutic touch.  Three moderate quality studies (Forward 2015, Wang 2015, Lin 2012) met inclusion criteria.

In patients undergoing joint arthroplasty Lin et al (Lin 2012) found no differences in average pain score when comparing bed rest to relaxation interventions (in person and recorded), but patients in the intervention arm noted decreased anxiety and better sleep.  Wang (2014) noted less pain after CPM use among patients receiving biofeedback, compared to control patients.  However, no mention was made of differences in opioid use.  Forward (2015) found no differences in reported pain or opioid use among patients receiving guided imagery or therapeutic touch, compared to patients receiving usual care.

Benefits/Harms of Implementation

There seem to be no obvious harms from use of these modalities, and, if future research supports its use, there is the potential benefit of improved patient outcomes and lower opioid use.

Cost Effectiveness/Resource Utilization

The interventions in the noted studies were provided by a variety of healthcare professionals and researchers.  There would be costs associated with the use of this modality for initial and continued training of those involved, and these costs would need to be balanced with improvements in patient outcomes (and decreased lengths of stay) and opioid use. 

Acceptability

Patients are accustomed to interventions or medications for pain control.  There would need to be assessment of acceptance of these techniques among patients undergoing surgical treatment in the US.  There would also need to be education among healthcare professionals in the US about the potential use and impact of these techniques. 

Feasibility

Guided relaxation therapy may not be available to patients undergoing outpatient surgery or in locations where the availability of therapists/biofeedback machines are limited. The cost of these technique and need to have access to appropriately trained personnel could limit use of these modalities, especially in rural/frontier or smaller hospitals.  Given the time constraints of those in most healthcare systems, finding the time needed for patient interaction with this type of intervention may be challenging.  There would need to be more and better data on its effectiveness before most systems would invest the time and resources needed. 

Future Research

The efficacy of guided relaxation therapy has not been established for heterogeneous groups, none of the studies reported results based on sex, and there was inconsistent reporting of what constituted “standard treatment.  Further research should investigate the effect of culture, education status, socioeconomic status, sex, gender, and other demographic variables on the efficacy of guided relaxation therapy after orthopaedic surgery. Furthermore, the optimal timing and method of delivery of guided relaxation therapy has not been established and merits further study. Current studies in this area are limited to specific patient populations (e.g. patients using CPM after joint arthroplasty).  Future studies should include patient undergoing a wider range of procedures.  In addition, given the significant impact of cultural expectations, it is difficult to extrapolate results from other countries to the US.  Additional studies would be required in the US, involving patients from a broad range of gender and racial/ethnic backgrounds, to determine applicability of this technique in the US.  Given the limited access to needed resources to implement relaxation strategies, future research could also assess the impact of providing these virtually to patients in smaller hospitals.

Music Therapy
Music therapy might be used with standard treatment to decrease post-operative pain and opioid use.
Limited Evidence Limited Evidence

Three moderate studies (Gallagher2018, McCaffrey 2004 and McCaffrey 2006) assessed the impact of use of music therapy after musculoskeletal surgery.  The study by Gallagher also included use of relaxation and imagery strategies, making the impact of music therapy alone difficult to determine.  The authors found no change in opioid or anti-emetic use of length of stay with the use of music therapy but noted decreased pain, anxiety, nausea, and mood up to POD 2 with the intervention. The studies by McCaffrey were designed to assess the impact of music therapy on cognitive function, with pain and function as secondary outcomes.  The authors found that patients in the intervention arm demonstrated greater readiness to ambulate and less pain and opioid use, as well as higher satisfaction.

The Music Therapy recommendation has been downgraded one level because of feasibility issues.

Benefits/Harms of Implementation

The impact of MT on post-operative pain and function requires additional study but may be a useful addition to standard treatment.  No potential harms were noted in either study, but this needs additional research.

Cost Effectiveness/Resource Utilization

Current studies of MT utilize either a board-certified music therapist (Gallagher) or CDs at the patient bedside.  For hospitals not currently employing the former, this could be an added cost.  CDs or other devices with recorded music could be costly, if they need to be replaced frequently.  In-person therapists and biofeedback machines may present substantial cost and time barriers. The delivery of this therapy to outpatients remains to be studied.

Acceptability

Use of music for relaxation is accepted, but its use for pain control and improved function is less so.  Acceptability would need to be evaluated in the setting of multi-patient rooms if the delivery method available did now allow for private sessions. 

Feasibility

The ability to and cost of hiring a music therapist or train current healthcare professionals in this area could limit use of this technique, especially in rural/frontier or smaller hospitals.  Hearing impaired patients may not benefit from pre-recorded relaxation sessions.  MT is currently only studied in inpatients, although the listening only therapy may be available to outpatients as well.

Future Research

Music therapy may be a useful non-pharmacologic adjunct to improve post-operative pain and function.   However, additional research is needed in this area.  The impact of music therapy alone, without the addition of PMR and guided imagery, is needed to determine the relative impact of only music therapy.  The first 2 modalities can be provided by other staff, without needing to have access to a music therapist, making the intervention less costly.  If, however, the most important intervention is music therapy, the relative cost of hiring a therapist or training additional personnel in this technique (and accounting for the time that this would take from their usual duties) compared to usual care and any cost savings in terms of patient pain control and complications would need to be assessed.  Additional research could also assess the impact of virtual or remote applications. Interventions for those deaf or hard of hearing also need to be evaluated.  Sex-based differences in outcome need to be assessed.

Patient Education
Limited evidence suggests patient education can be used to improve patient function and earlier cessation of opioid use.
Limited Evidence Limited Evidence

Patient education encompasses a broad range of topics and may be delivered in multiple ways. In addition, studies in this area used a wide variety of outcome measures, from pain scores, to opioid use, to measures of patient knowledge and self-efficacy, making the identification of consistent impact of this intervention challenging. One high quality study found improved pain scores, earlier discontinuation of opioids and decreased opioid consumption up to three months after rotator cuff repair in patients who received dedicated opioid education preoperatively compared to standard counseling (Syed 2018).

One high quality study (Riddle 2019) demonstrated that among patients with high catastrophizing scores undergoing TKA, training in pain coping skills or pre-operative arthritis education resulted in no differences in WOMAC scores or level of reported pain, compared to usual care.  Given that this study focused only on those with high pain catastrophizing scores, the utility of this intervention for all patients undergoing TKA is unknown. 

One high quality study (Huang 2017) found that patients undergoing empowerment education related to their THA allowed patients to become more knowledgeable about the procedure, developed greater self-efficacy had improved Tinetti Mobility scores, and improved SF-36 quality of life scores.  No indication in this study regarding who provides this education.

One high quality study (Wong 1990) demonstrated that viewing a video, reviewing a handout and then frequent discussions with nurses after THA after anticipated changes in function led to no differences in function or psychosocial status, compared to controls, after surgery.  This video was shown to patients at 6 days (and beyond) in the hospital after surgery.  Given the current limited length of stay after THA, this study design has limited utility. 

One high quality study (von Eck 2018) demonstrated improved satisfaction with recovery after knee or shoulder arthroscopic procedures among patients who underwent web-based education prior to and after surgery.  However, the differences in satisfaction scores do not seem to be clinically significant.

One moderate quality study (van den Akker Scheek 2007) demonstrated that a 6-month home-based support program after THA and TKA had no impact on physical function or self-efficacy.  A portion of the intervention included newsletters that were mailed to participants, but there is no indication that there was confirmation that patients receive or read these. 

The Patient Education recommendation has been downgraded two levels because of inconsistent evidence.

Benefits/Harms of Implementation

There are no known harms from this intervention.  These interventions may be of interest to patients interested in non-pharmacologic or non-invasive methods of pain control.  These interventions also address function and self-efficacy, in addition to pain and opioid use.  Providing education about opioids seems to impact amount and length of opioid use after surgery. 

Cost Effectiveness/Resource Utilization

Costs and resource utilization vary with method of delivery. Web-based education platforms may require additional expertise to design and maintain the website. Education provided by dedicated clinical personnel may require additional staffing and training. Some of the interventions described involve extensive human resources in terms of home visits, frequent follow-up phone calls, teaching in patient education modules, etc.  Additional research is needed to better determine the cost/benefit impact of this intervention.

Acceptability

Patient education is a well-accepted component of standard surgical practice. Specific to pain alleviation strategies, patients are accustomed to interventions or medications for pain control.  There would need to be assessment of acceptance of these techniques among patients undergoing surgical treatment in the US.  There would also need to be education among healthcare professionals in the US about the potential use and impact of these techniques.

Feasibility

Formalized patient education may require additional staffing, resources (websites, cellphone applications, etc.), and translating services. Patient’s own education level may affect the success of patient education efforts. Given the human resources needed for this intervention, there may be limited options for this in small or rural hospitals.  However, interactive telehealth could allow patient education classes to be taught over the internet, among different hospitals.  Use of this modality for individual teaching in patient homes or using telemedicine, rather than in-person, for follow-up is limited to those with adequate access to broadband internet.

Future Research

The optimal delivery method and timing of patient education has yet to be determined and may be specific to the topic of interest. Social and demographic variables may influence the effect of patient education efforts. Further research should seek to determine the ideal timeline and delivery platform of patient education efforts, with sub-group analyses to determine if gender- and race/ethnicity-based differences affect the acceptance and outcomes of this intervention. Future research needs to focus on relative impact of specific interventions (e.g., teaching self-efficacy vs learning more about a procedure vs learning more about post-operative limitations vs learning more about opioids and addiction).

Virtual Reality
Limited evidence suggests no difference in patient outcomes between use of virtual reality and standard treatment.
Limited Evidence Limited Evidence

Two moderate quality studies (Jin 2018 and Gianola 2020) addressed use of virtual reality.  Jin et al utilized psychologic interventions, along with VR (simulated rowing), and found lower WOMAC scores up to 6 months and lower VAS scores up to 7 days among patients in the intervention group.  However, the use of 2 modalities makes the effect of VR alone difficult to discern.  Gianola found no differences in VAS, WOMAC, opioid use, knee range of motion, strength, or QoL but improve proprioception among patients who utilized VR, but the authors did not describe the intervention used. 

The Virtual Reality recommendation has been downgraded one level because of feasibility and inconsistent evidence.

Benefits/Harms of Implementation

No benefits or harms were noted in either of the cited studies.  However, there is insufficient evidence with this relatively new technology to understand potential risks. 

Cost Effectiveness/Resource Utilization

The cost of VR was not discussed in either cited study.  This will need additional evaluation, to assure that the cost of VR is offset by savings in terms of patient outcome (and length of stay) and opioid use. 

Acceptability

While VR is used for recreation, its use in a medical setting is not widely discussed at this point.  The acceptance of use of this technology among patients and surgeons will need additional input and research.   

Feasibility

While VR is becoming more accessible, use may be limited in rural/frontier and smaller hospitals.  In addition, training of healthcare professionals regarding the appropriate use of this technology may limit its translation into routine patient care. 

Future Research

Virtual reality may prove to be an effective non-pharmacologic intervention to improve patient pain and function after musculoskeletal surgery.  However, there is currently insufficient evidence to recommend its use.  Further research is needed to identify the benefits, potentials harms, and associated costs with this modality.  Research should include patients with a spectrum of genders and racial/ethnic backgrounds, to reflect the patient population in the US.

Intra-Articular Opioids vs NSAIDs
Limited evidence suggests there is no difference in patient outcomes between intra-articular opioids and NSAIDs administered intraoperatively for post-operative pain control.
Limited Evidence Limited Evidence

There are 2 moderate quality studies (Kim 2015, Sanel 2016) with inconsistent evidence suggesting no difference in outcomes in patients who receive intraarticular opioid versus NSAIDs.

The Intra-Articular Opioid vs NSAID recommendation has been downgraded one level because of inconsistent evidence.

Benefits/Harms of Implementation

Uncontrolled pain after total joint arthroplasty can lead to limited post-operative range of motion, poor functional outcomes, and patient’s dissatisfaction. There are many analgesic modalities that can be used in the perioperative period, such as intravenous and oral opioids, epidural analgesia, and peripheral nerve blockade. Each method has its own risks and side effects, intravenous opioids cause nausea, vomiting, and urinary retention. Epidural analgesia is associated with urinary retention, respiratory depression, delayed ambulation and is complicated by perioperative thromboprophylaxis. Peripheral nerve blockade may cause muscle weakness resulting in delayed ambulation. There is also the risk of local anesthetic toxicity and nerve injury. Periarticular injection involves injection of a combination of analgesic drugs into the synovium, joint capsule, and subcutaneous tissues during orthopedic surgery. Periarticular injection after total joint arthroplasty has been reported to have good analgesic efficacy, cost-effectiveness, and few side effects. The main side effects are associated with local anesthetic toxicity. Adherence to dosing guidelines in conjunction with appropriate patient monitoring during and after injection will decrease the potential for harm.

Outcome Importance

Opioid-related side effects such as dizziness, nausea and vomiting can result in delayed ambulation and subsequently delay discharge from the hospital. Using a combination of periarticular local anesthetics, opioids, NSAIDs, and other agents has been shown to decrease opioid use.

Cost Effectiveness/Resource Utilization

Periarticular infiltration is generally performed by the surgeon during the procedure, which other than the medication costs, results in little added expense. It is recommended that these medications are prepared in a controlled, sterile manner. Intra articular opioids alone or in combination require chain of control processes to ensure there is no opioid misuse or abuse potential.

Acceptability

Surgeon training and acceptance of peri articular infiltration is increasing. Anesthesiologists are also learning how to incorporate peri articular infiltration into perioperative multimodal analgesic plans.

Feasibility

The inclusion of periarticular infiltration into practice is feasible. It will require surgeon education, pharmacy preparation of sterile combination of medications, and recognition of side effects associated with its use.

Future Research

Although the analgesic effect of various drug combinations for periarticular infiltration during orthopedic surgery has been well documented, the gold standard for drug combination has not yet been established. Future research should focus on the ideal combination and dose of medications.

 

Opioid Combo vs NSAID
Limited evidence suggests opioid/NSAID combination treatment may be used over NSAIDs to improve pain.
Limited Evidence Limited Evidence

There is one high quality study (Bali 2016) showing limited significant difference in pain or opioid use between opioid combinations and NSAIDs.

The Opioid Combination/NSAID recommendation has been downgraded one level because of inconsistent evidence and the harm of opioids.

Benefits/Harms of Implementation

Multimodal analgesia incorporating oral opioids and NSAIDs is standard of care for managing orthopedic postoperative pain. Using a combination of oral opioids and NSAIDs will decrease parenteral opioid use and subsequently decrease opioid-related side effects, such as nausea, vomiting, and respiratory depression. There are no obvious harms to implementing this practice.

Outcome Importance

Targeting multiple pain pathways with multimodal analgesics including oral opioids and NSAIDs will decrease parenteral opioid use and side effects. In addition, it may decrease the amount of NSAIDs needed which could decrease the risks associated with NSAID use, such as renal and GI dysfunction.  

Cost Effectiveness/Resource Utilization

Oral opioids and NSAIDs are commonly used and are both relatively inexpensive medications. Oral route of administration is significantly less expensive than parenteral medication administration.

Acceptability

Oral opioids and NSAIDs are both widely accepted medications for treating postoperative pain

Feasibility

This recommendation does not significantly change clinical practice as these medications are both widely used.

Future Research

Future research should focus on determining the most effective combination and dose of medications.

 

 

Tramadol Combo vs NSAID
Limited evidence suggests no difference in patient outcomes between tramadol combinations and NSAIDs.
Limited Evidence Limited Evidence

One moderate quality study (Mochizuki 2016) looking at combo tramadol/acetaminophen vs NSAID in 1551 TKA patients demonstrated decreased VAS scores and independence from the need for walker in the tramadol/acetaminophen group.

Benefits/Harms of Implementation

Tramadol causes less respiratory depression, cardiac depression, dizziness, and drowsiness than morphine; therefore, it has been used as a first-line analgesic for postoperative pain. Combination therapy with acetaminophen and Tramadol results in less pain than when the medications are used alone.

Outcome Importance

Targeting multiple pain pathways with multimodal analgesics including Tramadol, acetaminophen and NSAIDs will decrease parenteral opioid use and side effects. In addition, using Tramadol in conjunction with acetaminophen may decrease the dose of Tramadol required, subsequently decreasing side effects.

Cost Effectiveness/Resource Utilization

Tramadol is a centrally acting, oral analgesic that contains an opioid and is therefore considered a controlled substance. Side effects such as nausea, vomiting and dizziness are associated with Tramadol, although unlike other opioids, respiratory depression is rare.

Acceptability

Tramadol, acetaminophen and NSAIDs are all commonly used medications for postoperative orthopedic pain.

Feasibility

This recommendation does not significantly change clinical practice as all of these medications are widely used.

Future Research

Future research should focus on determining the most effective combination and dose of medications.

Fentanyl Patch vs Morphine
Limited evidence suggests no significant difference in patient outcomes between fentanyl patch and morphine.
Limited Evidence Limited Evidence

One moderate quality study (Mattia 2010) compared fentanyl patch to MSO4 IV PCA. The authors concluded that the fentanyl patch and morphine IV PCA are both well tolerated and effective methods of pain control. Discontinuation rates and the incidence of adverse events were also evaluated.

Benefits/Harms of Implementation

All opioid medications are associated with similar side effects, consisting of nausea, vomiting, dizziness, and respiratory depression. Changing the route of administration from intravenous to an iontophoretic transdermal system (patch) eliminates some of the risks associated with intravenous administration and also allow for opioid administration after hospital dismissal.

Outcome Importance

In the setting of the current US opioid epidemic, the use of multimodal, non-opioid medications is the goal right now. Moving away from the routine use of opioids such as Fentanyl and Morphine has been a priority for surgeons, anesthesiologists and patients. The ability to provide opioid medications in the postoperative period without maintenance of intravenous access may be appealing as the number of ambulatory total joint arthroplasties increase.

Cost Effectiveness/Resource Utilization

There is limited evidence comparing cost of Morphine PCA to fentanyl patch, although removing the administration costs (pumps, tubing, nursing support, etc) is likely to make the fentanyl patch more cost-effective.

Acceptability

Iontophoretic transdermal systems have historically been used by physicians trained in chronic pain management. It is unlikely that orthopedic surgeons will be comfortable ordering and managing this route of opioid administration.

Feasibility

Both Fentanyl patch and Morphine PCA require significant physician oversight to prevent overdose or misuse. This makes both treatment options less feasible than multimodal oral analgesics.

Future Research

Future research should be focused on patients who may benefit from Fentanyl patch or Morphine PCA in the postoperative period such as chronic pain patients or those who have uncontrolled pain in the setting of aggressive multimodal oral analgesia.

Tramadol vs NSAID
Limited evidence suggests no significant difference in patient outcomes between tramadol and NSAIDs.
Limited Evidence Limited Evidence

There is one moderate quality study (Oh 2018) that compared cox-2 inhibitors, ibuprofen and tramadol. There was no significant difference in terms of pain intensity, incidence of adverse effects or dosage of rescue medications at 3 days or 2 weeks.

Benefits/Harms of Implementation

Tramadol is a centrally acting, oral analgesic that contains an opioid and is therefore considered a controlled substance. Side effects such as nausea, vomiting and dizziness are associated with Tramadol, although unlike other opioids, respiratory depression is rare. Traditional NSAIDs inhibit cyclooxygenase COX-1 and may inhibit platelet function or lead to gastrointestinal or renal toxicity. They have minimal side effects in most patients and are safe if avoided in patients considered high risk. Selective COX-2 inhibitors are thought to have fewer side effects.  There have been some recent evidence to suggest that COX-2 medications may impair muscle regeneration or weaken tendon-bone healing.

Outcome Importance

In patients without significant kidney disease or gastrointestinal diseases in the setting of equal outcomes ibuprofen would be an inexpensive, easily obtainable option for postoperative pain control compared to Tramadol or COX-2 inhibitors. Targeting multiple pain pathways with multimodal analgesics including a combination of Tramadol and NSAIDs will decrease parenteral opioid use and side effects. In addition, using Tramadol in conjunction with NSAIDs may decrease the dose of Tramadol required, subsequently decreasing side effects.

Cost Effectiveness/Resource Utilization

 Ibuprofen is an over the counter medication which is inexpensive and easily available to all patients. COX-2 inhibitors require a prescription and often require approval for insurance coverage. Tramadol is a controlled substance and requires a prescription.

Acceptability

Tramadol and NSAIDs are all commonly used medications for postoperative orthopedic pain.

Feasibility

This recommendation does not significantly change clinical practice as all of these medications are widely used.

Future Research

Future research should focus on determining the most effective combination and dose of medications.

Anti-Depressants
In the absence of reliable evidence, it is the opinion of the workgroup that a recommendation for or against the use of duloxetine cannot be made given the limited evidence and safety concerns.
Consensus Consensus

There is lack of evidence for the use of duloxetine with only one moderate quality study (YaDeau 2016) included which demonstrated a reduction in opioid consumption but did not demonstrate an improvement in pain after surgery, the primary study outcome.

Benefits/Harms of Implementation

Reducing opioid use in the post-op period mitigates their well-known side-effects such as nausea/vomiting, respiratory depression, tolerance, etc. Pain and symptoms of depression/anxiety are well known to interact clinically such that it is difficult to treat pain when symptoms of depression/anxiety are poorly controlled, and vice versa. There is an FDA Black Box Warning on prescribing duloxetine to patients younger than 25 years old as there is an increased risk of suicidality in this population. Duloxetine may negatively interact with pre-existing therapies for those with mental health disease.

Outcome Importance

The US is in the midst of an opioid epidemic known to contribute to the development of hyperalgesia, tolerance, dependence, addiction, and abuse. Therefore, reducing opioid use is a national priority. Patients with mental health disease can face significant challenges in symptom control after surgery, and maintaining control is essential to pain management and functional improvement.

Cost Effectiveness/Resource Utilization

Duloxetine is a generic medication not requiring significant resources over other medications.

Acceptability

Some orthopaedic surgeons may be hesitant to prescribe duloxetine for pain given its use in anxiety and depression, concern for interference with pre-existing medications, or lack of clinical familiarity with medication treatments for mental health diseases.

Feasibility

Duloxetine is currently widely prescribed in the US and is FDA indicated for chronic musculoskeletal pain, fibromyalgia, diabetic peripheral neuropathic pain, generalized anxiety disorder, and major depressive disorder.

Future Research

Future pain outcomes should be investigated in patients with chronic pain, pre-operative opioid use, generalized anxiety disorder, major depressive disorder.

COX-2
Cox2 agents should be used to limit patient opioid consumption, improve pain and function; however, there is no difference in adverse events.
Strong Evidence Strong Evidence

There are eight high quality (Schroer 2011, Boonrioing 2010, Chen 2015, Xu 2018, Kahlenberg 2017, Mardani-Kivi 2013, Zhu 2018, Gong 2013) and four moderate quality studies (Ittichaikulthol 2010, Jianda 2016, Zhu 2014, Zhu 2016) that met inclusion criteria for this recommendation.

In a randomized double-blind placebo-controlled trial in patients undergoing TKA, Schroer et al (2011) studied celecoxib given twice daily for 6 weeks after discharge vs. placebo. Patients in the study group took significantly fewer opioids over the course of 12 months. Pain scores at rest and with activity were significantly lower in the celecoxib group out to 3 weeks after surgery, and pain scores at night were significantly lower out to 6 weeks after surgery. Patients in the celecoxib group had a significant increase in function across multiple patient reported outcome measures/functional domains (Knee Society Score – Function, Oxford, SF-12 – physical) at 6 weeks.  No differences were noted in adverse events.

Boonriong et al (2010) evaluated preoperative celecoxib and placebo as one-time dose in patients undergoing anterior cruciate ligament reconstruction (ACLR). No significant differences were found between pain, narcotic use, or function between celecoxib and placebo. There were no other differences found to include adverse events between groups.

Chen et al (2015) evaluated patients after total hip arthroplasty receiving oral celecoxib preoperatively and postoperatively through day 5 vs placebo. Patients in the celecoxib group had improved VAS pain scores through 72 hours postop, but no difference in Harris Hip Scores. Patients in the celecoxib group were noted to ambulate more than 1 day earlier than the placebo group however the mean times to ambulation were 4.5 +1.2 days vs. 5.83 +2.04 days in the celecoxib vs. control group which calls into question the applicability of this outcome in most modern rapid recovery protcols.  There were no differences in adverse events between groups.

Xu et al (2018) evaluated markers of inflammation in patients taking celecoxib with tramadol vs. tramadol alone after TKA. Indicators of aseptic inflammation (skin temperature, WBC, ESR and CRP) were all significantly reduced in the celecoxib group and Knee Society Scores were improved. Pain was not assessed.

Kahlenberg (2017) performed a randomized double-blind placebo-controlled trial evaluating preoperative celecoxib vs. placebo when given as 1 preoperative dose prior to hip arthroscopy. There were significant improvements in postoperative pain scores up to 2 hours after surgery. There were no differences noted in opioid consumption and small but not significant decreases in PACU time were found in the celecoxib group.

Mardani-Kivi (2013) performed a randomized triple blind placebo-controlled trial evaluating one dose of preoperative celecoxib vs. placebo for patients undergoing isolated ACLR or partial meniscectomy. Pain scores were significantly lower in the celecoxib group for both ACLR and partial meniscectomy at 6 and 24 hours after surgery. Opioid usage was significantly less in the celecoxib group for partial meniscectomy at 6 and 24 hours and for the ACLR group at 6 hours.  Function was not evaluated.  There were no significant differences in adverse events.

Ittichaikulthol et al (2010) performed a randomized double-blind placebo-controlled trial in patients undergoing TKA/THA comparing 1 dose of preoperative celecoxib vs parecoxib vs placebo. Decreased opioid consumption was found in the first 24 hours in both celecoxib and parecoxib groups vs placebo. There were improved pain scores in the parecoxib group through 12 hours compared to both celecoxib and placebo but no difference in pain scores between celecoxib and placebo. Function was not assessed. There was less sedation in the parecoxib group but otherwise no difference in adverse events.

Jianda (2016) performed a randomized placebo-controlled trial looking at one dose of celecoxib preoperatively vs placebo in patients undergoing TKA. All patients received multimodal analgesia throughout hospital stay and the same postoperative discharge medications (to include celecoxib). Two-minute walking test at 3 days after surgery was better in the celecoxib group. Significant improvements in pain scores and decreased opioid consumption were found in the celecoxib group.

Zhu et al (2018) performed a randomized double-blind placebo-controlled trial evaluating the use of celecoxib in patients undergoing TKA. The primary outcome evaluated postoperative cognitive deficiencies, with pain scores evaluated as a secondary outcome. Postoperatively they noted statistically lower pain scores out to 7 days after surgery and less cognitive dysfunction in the celecoxib group.

Benefits/Harms of Implementation

Use of Cox-2 selective agents carries the risks associated with the known side effect profile of these medications, with the possible benefit of decreased gastrointestinal irritation and effect known to occur with non-cox-2 selective agents. Special caution should be exercised in patients with renal insufficiency and a known history of cardiovascular disease, as these medications may be contraindicated in this patient population.

Cost Effectiveness/Resource Utilization

Cox-2 agents may cost more than their non-selective counterparts, but as generic formulations come to market the differences in cost may gradually decrease.

Acceptability

The use of cox-2 selective agents is well accepted under conditions in which NSAIDs are typically used. Patients and clinicians should be aware of the potential risks of these medications and understand the presentation and treatment of potential adverse events.

Feasibility

As cox-2 selective agents become available in generic formulations, their availability to clinicians should become more common and encouraged.

Future Research

Cox-2 selective agents may play an important role in pain alleviation strategies after orthopaedic surgery. Further research into the ideal combination of medications to minimize opioid requirements and consumption after surgery are warranted. Future research should focus on non-arthroplasty surgery and evaluate outcomes and adverse events for longer periods to determine the safety of these medications in orthopaedic surgery patients’ long term.

Oral Acetaminophen
There is no significant difference in pain intensity and opioid use between oral acetaminophen and intravenous acetaminophen.
Strong Evidence Strong Evidence

There are 2 high quality (Westrich 2019, Hickman 2018) 1 moderate quality studies (Politi 2017) and one low quality (Suarez 2018) showing no difference in pain scores or opioid use in patients receiving intravenous versus oral acetaminophen. There are 2 high quality studies showing no difference in adverse events between IV and oral acetaminophen.

Benefits/Harms of Implementation

Reducing opioid use in the post-op period reduces opioid-related side-effects such as nausea/vomiting, respiratory depression, opioid tolerance/abuse, etc. Acetaminophen is a well-accepted as a safe analgesic with minimal to no side effects in the vast majority of patients. The safety of oral and intravenous formulations is well established and widely accepted.

Outcome Importance

The US is in the midst of an opioid epidemic known to contribute to the development of hyperalgesia, tolerance, dependence, addiction, and abuse. Therefore, reducing opioid use is a national priority.

Cost Effectiveness/Resource Utilization

Oral acetaminophen is a widely available, inexpensive, generic, over the counter analgesic that does not require significant resources compared to opioids. Intravenous acetaminophen is much more costly than the oral route of administration with no difference in pain relief or side effects. If patients are able to take oral medications using acetaminophen po will result in decreased costs and similar analgesia.

Acceptability

Acetaminophen is widely accepted as an analgesic by orthopedic surgeons, anesthesiologists as well as patients. The tolerance of oral acetaminophen is extremely high with very few contraindications.

Feasibility

Acetaminophen is a widely used analgesic in the United States. Intravenous acetaminophen requires the presences of intravenous access but should be considered an excellent option for patients unable to take oral medications.

Future Research

It is well established that acetaminophen po vs. the intravenous route is similar in efficacy with regard to onset and pain relief. Future research should consist of analgesic combinations and the degree of opioid sparring. Future pain outcomes should be investigated in patients with chronic pain, pre-operative opioid use.

Acetaminophen
Acetaminophen should be used to improve patient pain and decrease opioid use.
Strong Evidence Strong Evidence

There is one high quality (Murata-Ooiwa 2017) and 2 moderate quality studies (Sinatra 2012, Takeda 2019) that demonstrate improved pain at rest in patients receiving acetaminophen. There are 3 high quality studies and 2 moderate quality studies demonstrating reduced opioid consumption in patients receiving acetaminophen.

Benefits/Harms of Implementation

Reducing opioid use in the post-op period reduces opioid-related side-effects such as nausea/vomiting, respiratory depression, opioid tolerance/abuse, etc. Acetaminophen is a well-accepted as a safe analgesic with minimal to no side effects in the vast majority of patients.

Outcome Importance

The US is in the midst of an opioid epidemic known to contribute to the development of hyperalgesia, tolerance, dependence, addiction, and abuse. Therefore, reducing opioid use is a national priority.

Cost Effectiveness/Resource Utilization

Acetaminophen is a widely available, inexpensive, generic, over the counter analgesic that does not require significant resources compared to opioids.

Acceptability

Acetaminophen is widely accepted as an analgesic by orthopedic surgeons, anesthesiologists as well as patients. The tolerance of acetaminophen is extremely high with very few contraindications.

Feasibility

Acetaminophen is a widely used analgesic in the United States.

Future Research

Superiority to placebo is well established. Future research should consist of analgesic combinations and the degree of opioid sparring. Future pain outcomes should be investigated in patients with chronic pain, pre-operative opioid use.

Acetaminophen/NSAID Combination Treatment vs NSAID
Acetaminophen/NSAID combination treatments may be used over NSAIDs for reduction in pain; however, no significant difference in reduction of opioid use.
Limited Evidence Limited Evidence

One high quality study (Thybo 2019) and one moderate quality study (Gupta 2016) evaluated the effect of combination acetaminophen with NSAID vs. NSAID alone. In a multi-center study evaluating morphine use after THA, the authors noted statistically significant reductions in morphine usage in the combination group vs. NSAIDs alone, however this did not meet the pre-defined MCID of 10mg (Thybo 2019). 

A moderate quality study evaluating combination therapy after TKA or THA found significantly lower pain scores up to day 3 and decreased opioid consumption in the combination ibuprofen/acetaminophen group vs. ibuprofen alone (Gupta).

The Acetaminophen/NSAID Combination recommendation has been downgraded one level because of inconsistent evidence.

Benefits/Harms of Implementation

Potential harms are related to the risk profile of the individual medications. Combination therapy does not offer additional risk of harm to the medications given in isolation.

Cost Effectiveness/Resource Utilization

There are minimal additional costs associated with this intervention. The use of acetaminophen and NSAIDs are commonplace and most medications are now generic. Combination therapy does not require a novel combination medication.

Acceptability

No anticipated issues. Patients and clinicians should be aware of the presenting signs and treatments required for adverse events related to both classes of medications.

Feasibility

Both acetaminophen and NSAIDs are used commonly and are readily available in most pharmacies.

Future Research

The ideal combination and dosing strategy are unclear at this point. Future research should focus on identifying the most efficacious and safest combination medication strategy and expand studies to include orthopaedic surgery patients undergoing non-arthroplasty procedures.

Gabapentin
There is no significant difference in patient outcome between single-dose gabapentin and placebo; however, additional concerns for adverse events such as sedation and respiratory depression should be recognized with its use.
Strong Evidence Strong Evidence

Four high level studies (Lunn 2015; Paul 2013; Paul 2015; Clarke 2014) evaluated multi-dosed perioperative oral gabapentin.  Lunn 2015 looked at high dose (1300mg/d) and low dose (900mg/d) gabapentin protocol consisting of a single preoperative dose through 7 days post operatively in TKA.  Sleep quality was better in the first 48 hrs. in both gabapentin groups, but no differences were seen in overall pain (only VAS pain at rest) or morphine used.  Furthermore, dizziness was more frequently observed in both gabapentin groups leading the authors to conclude that gabapentin may have a limited role in multimodal TKA pain control and should not be recommended as standard of care. The CPG group agrees with the authors of these studies that routine clinical use of gabapentin should be avoided outside of controlled clinical research scenarios allowing for gabapentin’s potential use in future multimodal pain regimens.

Paul evaluated pre- (600mg) and post-operative (200mg TID) gabapentin in both TKA (2013) and THA (2015) and found no differences in pain, ROM, morphine consumption, satisfaction, or length of stay in either cohort.  It is worth noting that Paul 2013 did not use any femoral or adductor canal nerve blocks and but did utilize post-operative PCA and spinal anesthesia.

Clarke 2014 utilized a PCA, spinal anesthesia, femoral and sciatic nerve blocks in addition to 600mg pre- and 200mg TID post-operative gabapentin (or placebo) for 4 days in a TKA population.  The gabapentin group used significantly less morphine in the first 24 hrs. and increased in hospital knee ROM (secondary outcomes).  No differences were seen in pain or physical function at 4 days, 6 wks., and 3 months after surgery (WOMAC score was primary outcome).  The placebo group had significantly more nausea and pruritus (possible opioid side effect) compared to the gabapentin group on POD 1 and dizziness on POD 3.

Two high quality studies (Clarke 2009; Panah Khahi 2012) looked at single dose gabapentin given either before or after surgery.  Clarke (2009) looked at single dose gabapentin (600 mg) either before or after THA and found no difference in pain scores or morphine consumption.  Similarly, Panah Khahi (2012) looked at single dose gabapentin (300 mg) following ORIF of a tibia fracture and found no difference in pain or morphine consumption.

Feasibility

Gabapentin is FDA off label use for perioperative pain.

Future Research

Research would benefit from further well-constructed trial looking at gabapentin in the TKA population in the presence of adductor canal blocks, dosed both pre-and post-operatively in a variety of patient populations beyond TJA, and with studies powered for primary outcomes looking at pain, narcotic use, adverse events, sleep quality, and function.

Gabapentin
There is no significant difference in patient outcome between multi-dose gabapentin and placebo; however, additional concerns for adverse events such as sedation and respiratory depression should be recognized with its use.
Strong Evidence Strong Evidence

Four high level studies (Lunn 2015; Paul 2013; Paul 2015; Clarke 2014) evaluated multi-dosed perioperative oral gabapentin.  Lunn 2015 looked at high dose (1300mg/d) and low dose (900mg/d) gabapentin protocol consisting of a single preoperative dose through 7 days post operatively in TKA.  Sleep quality was better in the first 48 hrs. in both gabapentin groups, but no differences were seen in overall pain (only VAS pain at rest) or morphine used.  Furthermore, dizziness was more frequently observed in both gabapentin groups leading the authors to conclude that gabapentin may have a limited role in multimodal TKA pain control and should not be recommended as standard of care. The CPG group agrees with the authors of these studies that routine clinical use of gabapentin should be avoided outside of controlled clinical research scenarios allowing for gabapentin’s potential use in future multimodal pain regimens.

Paul evaluated pre- (600mg) and post-operative (200mg TID) gabapentin in both TKA (2013) and THA (2015) and found no differences in pain, ROM, morphine consumption, satisfaction, or length of stay in either cohort.  It is worth noting that Paul 2013 did not use any femoral or adductor canal nerve blocks and but did utilize post-operative PCA and spinal anesthesia.

Clarke 2014 utilized a PCA, spinal anesthesia, femoral and sciatic nerve blocks in addition to 600mg pre- and 200mg TID post-operative gabapentin (or placebo) for 4 days in a TKA population.  The gabapentin group used significantly less morphine in the first 24 hrs. and increased in hospital knee ROM (secondary outcomes).  No differences were seen in pain or physical function at 4 days, 6 wks., and 3 months after surgery (WOMAC score was primary outcome).  The placebo group had significantly more nausea and pruritus (possible opioid side effect) compared to the gabapentin group on POD 1 and dizziness on POD 3.

Two high quality studies (Clarke 2009; Panah Khahi 2012) looked at single dose gabapentin given either before or after surgery.  Clarke (2009) looked at single dose gabapentin (600 mg) either before or after THA and found no difference in pain scores or morphine consumption.  Similarly, Panah Khahi (2012) looked at single dose gabapentin (300 mg) following ORIF of a tibia fracture and found no difference in pain or morphine consumption.

Feasibility

Gabapentin is FDA off label use for perioperative pain.

Future Research

Research would benefit from further well-constructed trial looking at gabapentin in the TKA population in the presence of adductor canal blocks, dosed both pre-and post-operatively in a variety of patient populations beyond TJA, and with studies powered for primary outcomes looking at pain, narcotic use, adverse events, sleep quality, and function.

Pregabalin
Moderate evidence suggests single or multi-dose pregabalin could be used to improve patient pain and opioid consumption outcomes; however, additional concerns for adverse events such as dizziness and sedation should be recognized with its use.
Moderate Evidence Moderate Evidence

Single Dose:

Lee (TKA & THA) 43 min, Omara (femur fracture with intramedullary nail) 140 min, Sebastian (“lower limb orthopedic surgeries”) 70 min, Ahn (arthroscopic shoulder surgery) decreased incidence at 24 hr (40% vs. 13%) and 48 hr (40% vs. 10%) of rescue IV ketorolac in control vs. pregabalin group respectively. Line 2000 – Lee, Omara, Sebastian – same study population as above for line 1997.  Lee regression of sensory & motor block was 15 min and 11 min longer for pregabalin, respectively; Omara regression of sensory & motor block was 14 min and 15 min longer for pregabalin, respectively; Sebastian regression of sensory block was 20 min longer for pregabalin.  For Rahat the population was “orthopedic surgeries for tibial fractures” and the “duration for analgesia” was 148 min longer for the pregabalin group.

Three high quality (Lee, 2018; Omara, 2019; Sebastian, 2016) studies and one moderate quality (Rahat, 2018) study found an increased duration of spinal anesthetic.  Omara and Lee also found an increased duration of motor block.

Lee, Ahn, Omara population groups (orthopaedic surgeries) are all the same as previously listed.  The only new study is Akhavanakbari with a study population only detailed as “lower limb orthopedic surgery.

Three high quality studies (Lee, 2018; Ahn, 2016; Akhavanakbari, 2013) found improved pain scores on VAS or NRS.

Omara (2019) found sleep quality was improved in the first 24 hours as a secondary outcome.

Significant side effects included dizziness (Rahat, 2018, Akhavanakbari, 2013; Sebastian, 2016), sedation (Sebastian, 2016; Lee, 2018), hypotension (Sebastian, 2016), and blurred vision (Lee, 2018).

Multi-dose:

Two high quality studies (Clarke, 2015; Cho, 2019) and one moderate quality study (Eskander, 2013) of multi-dose pregabalin found that pain was lower on post-op day 7 by numerical rating scale, 14 days by visual analogue scale (VAS), and through 8 hours by VAS in TKA, ACL, and shoulder arthroscopy cohorts respectively.  However, pain in the Clarke study in a TKA population was a secondary outcome measure.

One high quality study (Buvanendran, 2015) suggests improvement in neuropathic pain at 3 and 6 months (primary measure) and sleep quality in the first 24 hours (secondary measure) with multi-dose pregabalin in a TKA population.

Two high quality studies (Buvanendran, 2015; Singla, 2015) suggest multidose pregabalin may increase ROM in the first 30 and 3 days respectively (secondary measures) in a TKA population.

Two high quality (Clarke, 2015; Singla, 2015) studies in TKA populations and one moderate quality (Eskandar 2013) study in shoulder arthroplasty found a decrease in opioid consumption within the first week in pregabalin groups on secondary measures.

One high quality study (Yik, 2019) found no difference in any primary (morphine equivalents) or secondary (VAS, ROM, KSS, WOMAC, SF-36) measures in a TKA population.

The Pregabalin recommendation has been downgraded one level because of inconsistent evidence.

Feasibility

Pregabalin is NOT FDA approved for perioperative use.

Future Research

The literature would benefit from high level studies addressing outcomes on function, standardization of dosing (timing, strength and duration),  as well has having non-industry backed studies as 3 studies (Bhuvanendran, 2010; Clarke, 2015; Signla, 2015) with supportive findings disclosed industry support.  Many of the statistically significant findings in support of pregabalin were in secondary measures.  These findings need to be replicated in studies powered with these outcomes as primary measures.

Ketamine
Strong evidence supports the use of intravenous ketamine in the peri-operative period to reduce opioid use in the first 24hrs after hip and knee arthroplasty.
Strong Evidence Strong Evidence

Two high quality studies (Remerand 2009, Cengiz 2014) demonstrated that peri-operative intravenous ketamine was associated with less morphine use in the first 24 hours after THA & TKA respectively.

Benefits/Harms of Implementation

Reducing opioid use in the post-op period mitigates their well-known side-effects such as nausea/vomiting, respiratory depression, tolerance, etc. Ketamine can produce many side-effects however they are mostly associated with anesthetic-level dosing. Low-dose, i.e. sub-anesthetic, ketamine used as an adjunct pain medicine has been associated with vivid dreams and hallucinations.

Outcome Importance

The US is in the midst of an opioid epidemic known to contribute to the development of hyperalgesia, tolerance, dependence, addiction, and abuse. Therefore, reducing opioid use is a national priority.

Cost Effectiveness/Resource Utilization

Ketamine is an inexpensive, generic medication on the WHO Model List of Essential Medicines, 21st List (2019). The peri-operative use of ketamine requires the assistance of a qualified anesthesia provider.

Acceptability

Ketamine is already widely used as an adjunctive pain medicine for patients undergoing surgery.

Feasibility

Intravenous ketamine can be easily administered by intermittent manual bolus, gravity infusion, or mechanical pump infusion.

Future Research

Ketamine is an NMDA receptor antagonist, and the NMDA receptor is the nexus of pathways leading to hyperalgesia from poorly controlled pain and opioid use. Future studies should explore longer term outcomes associated with the perioperative use of ketamine such as the development of chronic pain, persistent opioid use, and opioid use disorder.

 

 

Oral Relaxants
There is no significant difference in patient outcomes, pain intensity or opioid use between oral relaxants and placebo given postoperatively.
Moderate Evidence Moderate Evidence

One high quality article (Skrejborg 2020) evaluated the use of an oral relaxant (Chlorzoxazone) compared to placebo, administered for the first 7 days after TKA or THA.  No significant differences were found in pain after a 5-minute walk on POD 1 or pain at rest during the first 24 hours after surgery.  No significant differences were found in Oxford Hip Score or Oxford Knee Score at 7 days or 12 months after surgery.  There were also no significant differences found in opioid consumption during the first 7 days after surgery or for side effects, such as fatigue, dizziness, nausea, or vomiting while hospitalized after surgery.  

Benefits/Harms of Implementation

While there are multiple potential side effects of relaxants, such as drowsiness, dizziness, lightheadedness, headaches, and gastrointestinal upset, none were identified in this study.  These should be evaluated in any future research in this area.  In addition, this study did not assess for differences based on patient sex or gender, so differences in potential harms among sexes is not known. 

Cost Effectiveness/Resource Utilization

While approved in the US and available for relatively low cost, the lack of efficacy noted in this study does not support the use of Chlorzoxazone for this indication, and the additional cost is not offset by lower use of opioids. 

Acceptability

Chlorzoxazone is also approved for use in the US but based on one-high quality study, does not seem to improve post-operative pain or function or lower opioid use.

Feasibility

Chlorzoxazone appears to be a readily available medication in the US, but additional research is needed to determine if this, or other oral relaxants, given during the perioperative period have significant benefit in terms of pain, opioid use, or function, before recommending their routine use. 

Future Research

With the need to decrease opioid prescribing and the trend of shorter hospital stays, use of non-opioid oral medications after TKA and THA to improve patient function with lower risks of side effects needs additional investigation.  This could include the use of oral muscle relaxants.  Given the differences in nociception and pharmacokinetics and pharmacodynamics among the sexes, future research on the use of relaxants in this setting should include assessments of outcomes based on patient sex.


ACKNOWLEDGEMENTS

Guideline Work Group:

  • David Ring, MD, FAAOS, Co-Chair
  • Joseph R. Hsu, MD, FAAOS, Co-Chair 
  • Renan Castillo, PhD
  • Anna Miller, MD, FAAOS
  • Jeanne Patzkowski, MD, FAAOS
  • Sandra Kopp, MD
  • Michael Patzkowski, MD
  • Kimberly Templeton, MD, FAAOS
  • Thomas Myers, MD, FAAOS

Oversight Chair:
Yale Fillingham, MD, PhD, MPH

AAOS/METRC Staff:

  • Ellen MacKenzie, PhD, Dean of Bloomberg School of Public Health
  • Jayson N. Murray, MA - Director, Clinical Quality & Value
  • Kaitlyn Sevarino, MBA, CAE, Director, Clinical Quality & Value
  • Nicole Nelson, MPH, Manager, Clinical Quality & Value
  • Connor Riley, MPH, Research Analyst, Clinical Quality & Value
  • Jennifer Rodriguez, Administrative Assistant, Clinical Quality & Value
  • Tyler Verity, Medical Librarian, Clinical Quality & Value