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C OPYRIGHT Ó 2020 BY T HE J OURNAL OF B ONE AND J OINT S URGERY, I NCORPORATED

Total Knee Arthroplasty: Opioid-Free Analgesia in a

Patient with Opioid-Induced Hyperalgesia
A Case Report
Allen Kadado, MD, Steven Slotkin, MD, Noel Osereimen Akioyamen, BS, Andrew El-Alam, BS, and Wayne Trevor North, MD

Investigation performed at Henry Ford Hospital, Detroit, Michigan

Abstract
Case: Pain control after total knee arthroplasty (TKA) remains a significant challenge, especially in the context of certain
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patient-specific factors. We present a case of a 59-year-old woman with opioid-induced hyperalgesia who was referred for
left knee pain and end-stage tricompartmental degenerative joint disease after failure of conservative management. We
outline an approach to control postoperative pain in patients undergoing TKA who have severe opioid contraindications.
Conclusions: TKA and rehabilitation with a 6-year follow-up period was accomplished using a multimodal nonopioid
approach, consisting of a combination of gabapentin, acetaminophen, ketorolac, meloxicam, methocarbamol, a tunneled
femoral nerve catheter, and periarticular injection.

T
otal knee arthroplasty (TKA) is commonly performed
in adult orthopaedic reconstruction surgery, with an
annual incidence of over 600,000 in the United States1. Its
objective is to eliminate pain, improve joint range of motion,
function, and thereby the quality of life. Postoperative pain may
decrease patient mobility, delay hospital discharge, and impede
the overall success of surgery2. Thus, adequate postoperative pain
control is critical to rehabilitation and recovery.
Recently, opioids have come under scrutiny because of asso-
ciated hindrances and risks posed to society. Aside from an intolerance
to opioids, there remain concerns such as diversion, abuse, and
addiction. In recent years, the United States has seen a 200% increase
in opioid-related overdose deaths with prescription opioids being a
major contributor3,4. In response, there has been a shift in practice to
reduce the number of opioid prescriptions being doled out. Con-
currently, we have seen a decline in federal funding for pain research5.
These findings underscore the importance of preventing opioid abuse
and identifying effective nonopioid pain management modalities.
Multimodal pain control strategies used for TKA include
intravenous and oral analgesia, neuraxial methods such as
epidural catheters, and regional block techniques. Multimodal
analgesia may be beneficial. In a population study including
over 1,500,000 arthroplasties, Memtsoudis et al. concluded that
patients receiving multimodal analgesia rather than opioids
alone experienced fewer respiratory and gastrointestinal com-
plications, shorter lengths of stay, and decreased opioid pre-
scriptions6. Although opioids remain a mainstay of pain relief,
they may not be used in all patients undergoing TKA.
In this study, we present a framework of an opioid
sparing TKA pathway using a multimodal pain management
strategy that others can modify.
The patient was informed that data concerning the case
would be submitted for publication, and she provided consent.
Case Report
A 59-year-old woman with opioid-induced hyperalgesia and a
history of osteochondral grafting in left knee at the age of 25
was referred for left knee pain and end-stage tricompartmental
degenerative joint disease. At the age of 55, the patient underwent
decompressive L4-5 laminectomy for lumbar radiculopathy asso-
ciated with multilevel degenerative changes and foraminal stenosis.
Postoperatively, the pain worsened. Between this procedure and her
current presentation, the patient had been prescribed morphine,
hydromorphone, fentanyl patches, hydrocodone/acetaminophen,
and oxycodone, none of which ameliorated her pain. She instead
experienced severe nausea, dizziness, diffusion, and increased pain.
Based on this new yet persistent reaction to opioids, a diagnosis of
opioid-induced hyperalgesia was established. It is unknown exactly
which medication caused hyperalgesia.
Before TKA, postoperative pain control strategies were
discussed with the patient and pain management team. We
decided to trial 2 weeks of low-dose methadone. Evidence has
shown that methadone has N-Methyl-d-aspartic acid antago-
nistic properties, which limits opioid-induced hyperalgesia7. At
the follow-up appointment, the patient reported discontinuing
methadone after 1 week because of exacerbating symptoms of

Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/B181).

JBJS Case Connect 2020;10:e20.00024 d http://dx.doi.org/10.2106/JBJS.CC.20.00024

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opioid-induced hyperalgesia and subsequent mood instability.
The joint decision was then made to proceed with an opioid-free
arthroplasty. The predetermined perioperative pain plan involved
the use of gabapentin, acetaminophen, ketorolac, meloxicam,
methocarbamol, a tunneled femoral nerve catheter, and intra-
operative capsular and retinacular injection.
The patient was instructed to begin taking oral gabapentin
300 mg 3 times daily in the 2 weeks leading up to surgery. This
decision was made considering the patient had previously taken
this medication for lumbar radiculopathy and experienced relief.
Immediately preoperatively, a tunneled femoral nerve catheter
was placed on the surgical side and 20 mL of 0.375% ropivacaine
was administered. Intra-articular, capsular, and soft-tissue injec-
tion of the knee was performed intraoperatively with a solution
containing 40 mL (200 mg) of 0.5% bupivacaine, 0.3 mL (0.3 mg)
of epinephrine (1/1,000), and 1 mL (40 mg) of methylpredniso-
lone acetate diluted with 18.7 mL normal saline to a total of
60 mL. Postoperatively, 0.2% ropivacaine was administered at a
rate of 8 mL/h via the peripheral nerve catheter. Oral postoper-
ative pain control regimen included gabapentin 800 mg 3 times
daily, meloxicam 15 mg once daily, acetaminophen 1 g 4 times
daily, and methocarbamol 750 mg 3 times daily as needed.
During her hospital course, the patient’s pain was well-
controlled via the described regimen, with an average visual
analog scale (VAS) pain score of 4.83/10. Her recovery, how-
ever, was complicated by quadriceps weakness leading to knee
buckling during ambulation. She intermittently used a knee
immobilizer during physical therapy to minimize fall risk. Evalu-
ation on postoperative day 3 revealed that the patient’s pain was
well-controlled on the previously described oral postoperative pain
control regimen. She was deemed stable and suitable for discharge.
Immediately before discharge, the tunneled femoral nerve catheter
was transitioned from continuous analgesia to On-Q PainBuster
using 0.2% ropivacaine delivered at 8 mL/h. The patient was in-
structed to continue the oral pain regimen for 30 days.
On postoperative day 7, the patient had a follow-up pain
clinic appointment. Six hours earlier, she stopped the peripheral
nerve medication and now reported 3/10 pain on VAS. The
catheter was removed and, in replacement of meloxicam, a 3-day
course of oral ketorolac 10 mg 3 times daily was prescribed for
the associated pain. At the 3-week follow-up in orthopaedics
clinic, the patient reported excellent control of pain without
narcotics. She was tolerating activities and physical therapy and
using a cane occasionally for support. She demonstrated active
range of motion from 5° to 80° and passive motion from 0° to
90°. Six years postoperatively, the patient remains pain-free in
her left knee, with range of motion from 0° to 115°.
Discussion
D isabling postoperative pain is associated with higher com-
plication rates, slower rehabilitation, delayed hospital dis-
charge, higher readmission rates, and greater economic burden8.
Opioids remain the cornerstone of pain control for moderate to
severe pain and are second only to nonsteroidal anti-inflammatory
medications in treatment of chronic pain9. However, the effec-
tiveness of opioids has become overshadowed by rampant overuse.
T O TA L K N E E A R T H R O P L A S T Y
In fact, America consumes 80% of the world’s opioid supply while
housing <5% of the world population10. The nontherapeutic use of
opioids and their consequences have spurred a national epidemic
and prompted a hard look at prescribing practices. In recent years,
orthopaedic surgeons have been the third highest prescribers of
opioids11. Resultantly, orthopaedic patients face risks associated
with both therapeutic and nontherapeutic opioid use. In response
to the opioid epidemic, orthopaedic surgeons must find ways to
effectively treat pain while minimizing exposure to opioids.
Our patient presented with a history of opioid-induced
hyperalgesia, a condition in which opioids paradoxically increase
pain sensitivity and may even exacerbate pre-existing pain symp-
toms although the exact mechanism has not been elucidated12.
Horlocker et al. outline a case in which opioid-free perioperative
analgesia following TKA was used because of the patient’s history
of intractable nausea/vomiting after receiving opioids13. Although
our rationale for evading opioids was different, the multimodal
and team-based approach they described helped guide our pre-
operative planning for management.
Methadone has been shown to be therapeutic in treating
of opioid-induced hyperalgesia14,15. Thus, before surgery, an
attempt was made to desensitize the patient to opioids. In our
patient, however, the trial failed because of worsening effects of
opioid-induced hyperalgesia. Interestingly, worsening of symp-
toms with methadone has been described16.
Various sources claim that perioperative use of gabapentin
decreases postoperative consumption of opioids17, postoperative
pain, and morbidity after TKA18. The literature, however, currently
provides conflicting evidence on the efficacy of perioperative ga-
bapentin19,20. Because methadone exacerbated her symptoms, the
patient was instructed to take gabapentin for 2 weeks preopera-
tively and continue after surgery. The favorable risk-benefit ratio
led us to use gabapentin, and we believe it helped control her pain.
The case report describing opioid-free analgesia following
TKA by Horlocker et al. provided regional analgesia with a con-
tinuous psoas compartment lumbar plexus block13. Although a
psoas block may theoretically provide more comprehensive anal-
gesia for TKA, minimal evidence currently compares efficacy of
psoas block versus femoral nerve block (FNB)21,22. After exploring
all options, we proceeded with a tunneled femoral nerve catheter,
which remains a good option for regional analgesia in the lower
extremity23,24. Adductor canal block (ACB) is currently preferred
over FNB for postoperative analgesia following TKA. It provides
similar analgesia as FNB and does so with lesser incidence of
quadriceps weakness25-27. Considering our patient’s recovery was
complicated by quadriceps weakness and difficulty ambulating,
ACB was the better option. However, at the time of the surgery
FNB was the preferred peripheral nerve block.
Periarticular injection with a multimodal drug cocktail is
becoming increasingly useful in perioperative pain management
after TKA28. It has been shown to be beneficial in decreasing
postoperative pain scores and analgesic requirements29. Since the
injection is performed intraoperatively, it offers no procedural
dilemma. Although immediate postoperative pain relief has
been shown, there is no definitive evidence demonstrating the
effects on the duration of hospitalization and rehabilitation30.
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Intra-articular, capsular, and soft-tissue injection was performed
intraoperatively in our case. Since it has been shown to decrease
postoperative analgesic requirements, it was rendered useful in
our patient with opioid-induced hyperalgesia.
In summary, we present a case in which we successfully
eliminated opioids from an elective TKA using a multimodal
pain regimen. This can serve as a template for others to adopt
and provides the potential to limit opioid-related adverse effects
and complications. n
Allen Kadado, MD1
Steven Slotkin, MD1
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T O TA L K N E E A R T H R O P L A S T Y
Noel Osereimen Akioyamen, BS2
Andrew El-Alam, BS2
Wayne Trevor North, MD1
1Department of Orthopaedic Surgery, Henry Ford Hospital, Detroit,
Michigan
2Wayne State University School of Medicine, Detroit, Michigan
E-mail address for A. Kadado: allenkadado@gmail.com
ORCID iD for A. Kadado: 0000-0002-8383-3192
ORCID iD for S. Slotkin: 0000-0001-6353-3240
ORCID iD for N.O. Akioyamen: 0000-0001-7617-5200
ORCID iD for A. El-Alam: 0000-0003-4242-8454
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