61Pain Management 61

61 Pain Management

T. Deckmyn

61

Summary

Many patients experience severe pain after total knee arthroplasty (TKA) which can lead to several pathophys- iological responses, increasing morbidity and delaying prompt rehabilitation. Analgesic regimens, based on a multimodal approach including preemptive NSAIDs and opioids, neuraxial or regional peripheral nerve blockade, and patient-controlled opioid infusions,not only provide effective pain relief and high patient satisfaction but also result in improved functionality,decreased recovery time, and shortened hospital stay. Though epidural techniques provide the best results, use of this method is limited by increased risk of serious complications due to combina- tion with thromboembolism prophylaxis, and femoral three-in-one or lumbar plexus blocks may be preferable.

Introduction

Pain is a significant component of patients’experience af- ter total knee arthroplasty (TKA). It is severe in 60% of patients and moderate in 30%, which may hinder early physical therapy [1].The average worst pain during the 48 h before discharge was found to be moderate to severe, supporting the existence of an “analgesic gap” [2, 3]. Even treated with on-demand doses of narcotics, patients may experience severe pain as a result of delays, improper route of administration, underestimation of effective dose ranges, or overestimation of analgesic duration [3].

Acute pain, limiting mobility, may contribute to compli- cations such as pulmonary or urinary problems, throm- boembolism, hyperdynamic circulation, and increased oxygen consumption, through pathophysiological re- sponses including peripheral sensitization and neuroen- docrine and sympathoadrenal activation. It can also develop into chronic pain. Lack of pain control results in anxiety, sleeplessness, intensified reflex responses, and release of catecholamines, as well as inhibiting early mo- bilization of the knee, possibly leading to arthrofibrosis [3]. Pain assessment has also become a new standard im- plemented by the Joint Commission on Accreditation of Healthcare Organizations [2]. This emphasizes the im-

portance of recognizing recent therapeutic advance- ments, including the introduction of potent analgesics and more efficient and safe methods of administration.

Oral Analgesics: Oral Opioids

To achieve adequate pain control, an individualized pre- scription is needed, taking into account the physiological and psychological condition of the patient, the patho- physiological alterations resulting from surgery, and the technical and economic resources available. Oral admin- istration of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) should always be considered first, be- cause of their safety. However, despite their ease of use and combination,which reduces opioid consumption and related side effects, postoperative pain often remains severe [4]. The choice of oral analgesics is very wide, but alterations in gastrointestinal function after general anes- thesia may reduce efficacy.Orally administered morphine and meperidine undergo substantial enterohepatic me- tabolism, have late onset and duration, and may require high doses.Therefore,the sustained-release oxycodone is a better choice and can be used as a transition analgesic after discontinuation of epidural analgesics [3]. The sus- tained-release preparations provide superior pain control and reduce opioid-related side effects,but the risk of con- stipation or ileus is higher. Tramadol is a less potent anal- gesic but does not cause respiratory depression, so it may be a better choice for elderly or very young patients.

Oral Analgesics: Oral NSAIDs

NSAIDs are often prescribed for patients with painful os- teoarthritis, many of whom subsequently require total joint arthroplasty. Because of the increased risk of peri- operative bleeding,wound hematoma,and hemarthrosis, NSAIDs should be discontinued 7-10 days before surgery.

However,NSAID cessation can result in an arthritic flare-

up,leading to increased preoperative pain.The severity of

preoperative pain correlates directly with postoperative

pain and with the amount of opioid analgesic required

Chapter 61 · Pain Management – T. Deckmyn ³⁸⁵

61

[5]. The arthritic flare in other joints may interfere with postoperative physical therapy and rehabilitation. The concomitant use of NSAIDs with warfarin or low-molec- ular-weight heparin (LMWH) can lead to increased bleeding complications. However, the new COX-2 selec- tive inhibitors maintain platelet function and gastric mucosal integrity. Rueben et al. concluded that rofecoxib 50 mg or celecoxib 200 mg daily,can be used safely in TKA patients in combination with warfarin 5 mg daily without an increase in the INR [5, 6]. The preoperative use of rofe- coxib did not alter blood loss during surgery. Other COX-1 NSAIDs, such as ketoprofen (100 mg twice daily), indomethacin (100 mg twice daily), ibuprofen (600 mg every 8 h), diclofenac (50-100 mg), or ketorolac (30 mg every 6 h) are still used [4,7-9].However,concerns remain about the possible impairment of bone growth and higher non-union rates (in spine fusion) [3].

Parenteral Analgesics

Morphine (0.1 mg/kg every 4 h) is still commonly used for severe pain, although the relatively slow onset after intra- muscular or subcutaneous injection and side effects (nau- sea, pruritus, histamine release, and biliary colic) make it less favorable than meperidine, hydromorphone, or pir- itramide [3].Ketorolac is a potent NSAID available for par- enteral use but also carries an increased risk of causing hemorrhage, gastric ulcer, and renal toxicity. Parenteral selective COX-2 inhibitors would be expected to be safer.

Infusion devices allow the patient to receive small doses of parenteral medication without delay,within pre- scribed limits and lockout intervals. Patients’ control of frequency adjusts the total dose to meet the individual needs, differences in pain perception, and variability in pharmacokinetics. By minimizing the bolus amount and extending the lockout interval sufficiently, the technique avoids cycles of excessive sedation and ineffective pain control. Another advantage is the option of controlling the variations of analgesic requirements during day and night, or during physical therapy [10]. A loading dose should be titrated to achieve a baseline plasma concen- tration. Patients must be trained to treat pain before the stimulus becomes overwhelming and should understand that their pain will not be completely eliminated.

Epidural and Intrathecal Analgesia

Many studies confirm the superior efficacy of postoper- ative analgesia and accelerated rehabilitation with epidural and intrathecal analgesia [1, 6, 7]. Single in- trathecal boluses of opioids such as morphine (0.3 mg) provide an analgesic effect superior to i.v. patient-con- trolled analgesia (PCA) with morphine but also have a

high incidence of adverse effects,including late onset res-

piratory depression due to rostral cerebral spinal fluid

spread [3]. These problems have been overcome with the

use of continuous epidural infusion, avoiding high peak

cerebral fluid concentrations. Continuous epidural infu-

sion of local anesthetics offers reliable segmental analge-

sia and reduced opioid related side effects, but causes

more hypotension and urinary retention. The use of low-

dose bupivacaine (0.125%) or ropivacaine (0.2%) at rates

of 5-12 ml/h prevents motor block. The association of

lipophilic opioids with fast onset and short duration has

a synergistic effect and seems to further reduce the side

effects of both opioids and local anesthetics. The intro-

duction of patient-controlled epidural analgesia has im-

proved the efficacy, tolerability, and comfort and satisfac-

tion of the patient.Despite the fact that patient-controlled

epidural analgesia provides the best pain scores and bet-

ter revalidation, some patients prefer i.v. PCA. Probably

they favor a classical maintained, well-tolerated pain lev-

el,and they maintain control through self-administration

with fewer side effects [3, 7]. To reduce these side effects,

present research is focused on the addition of adjuvant

drugs. In Europe, the α2-agonist clonidine (1-2 µg/ml) is

added to obtain a longer duration of analgesia.It is known

to block conduction in C-fibers and provides better con-

trol of dynamic pain [1, 7, 8]. Activation of the NMDA re-

ceptors within the spinal cord is considered to be central

to the development of acute and chronic pain. Ketamine

may inhibit a facilitated state of excitability by suppress-

ing the progressive nociceptive response caused by wind-

up phenomena and long-term potentiation (anti-hyper-

algesic action). Once pain sensitization from incisional

and inflammatory injury is established,ketamine reduces

NMDA-receptor related altered pain transmission and

thus hyperalgesia. Small doses of ketamine (0.25 mg/kg

epidural) efficiently block injury-induced pain sensitiza-

tion without any side effects and provide supplemental

pain relief for an extended period of time [9]. Despite the

better pain relief and faster rehabilitation [7,11],reduction

in blood loss and deep vein thrombosis [6], and good

blockade of the ‘hidden’ endocrine response [12], some

occasionally serious side effects can occur. Clinically

relevant respiratory compromise is reported to occur in

between 0.1% and 0.4% of patients, and can be of late on-

set (after 8-12 h). It may develop slowly, often preceded by

nausea and sedation,and can be treated with naloxone in-

fusions (400 µg/l at 100 ml/h) [3]. Epidural analgesia can

mediate hypotension that is not always well tolerated. Bi-

lateral motor block and urinary retention impede func-

tional recovery and may increase the risk of infection

arising from urinary catheters. The risk for epidural

hematoma is a major concern in TKA patients who

receive LMWH for deep venous thrombosis prophylaxis

[6,11,13].The present guidelines do not guarantee against

the occurrence of epidural hematoma [6, 13].

Regional Blocks

Regional block techniques can provide analgesia equal to or better than epidural analgesia without the risk of epidural hematoma [1, 6, 7, 8]. The use of postoperative continuous femoral infusion is associated with a decrease in morphine consumption by up to 70%. This technique permits more rapid postoperative functional recovery [1], better immediate and secondary functional outcomes, and a reduction in length of hospital stay [6, 7]. However, the best technique for establishing blockade of the lumbar plexus is not clear. The knee joint is supplied by the femoral, obturator, and sciatic nerves, and some cuta- neous areas of surgical incision with the lateral femoral cutaneous nerve. The osteotomal segments of the femur and tibia at the knee are supplied by the sciatic nerve from the S1 root. Singelyn et al. reported excellent results with a three-in-one approach, first described by Winnie et al.

in which after neurostimulation,a catheter is inserted un- der the inguinal ligament 1.5 cm lateral to the femoral artery and then advanced proximally (12-20 cm) in the sheath of the femoral nerve alongside the psoas muscle, blocking the femoral, obturator, and lateral femoral cuta- neous nerves [14]. Because of the variable blockade of the obturator nerve (and the S1 root), Ganapathy et al. pro- posed a modification placing the catheter under the fas- cia lata and the fascia iliaca (double-pop technique) [8].

The most reliable method of accessing the lumbar plexus is through the posterior paravertebral approach. Howev- er, because of the increased risks of bleeding at the punc- ture site, psoas hematoma, renal subcapsular hematoma, and lumbar plexopathy, Bogoch et al. found insufficient justification for its use [14, 15]. Since the sciatic nerve sup- plies the posterior region of the knee joint, the combina- tion with a sciatic nerve block may be necessary [14].Oth- ers have noted that a single femoral block provides pain relief as satisfactory as that from a combined femoral and sciatic block, suggesting that the sciatic nerve provides a minor contribution to postoperative pain [4]. When con- centrations of local anesthetic are high enough (bupiva- caine and ropivacaine 0.2% or lidocaine 1% at rates of 10 ml/h) obturator and lateral femoral cutaneous nerve block can be achieved in 80% of patients [1, 7, 8]. Plasma levels remain below the toxic range, so even higher doses can be used [8]. With the admixture of clonidine (1-2 µg/ml) and/or opioids (sufentanil 0.1 µg/ml, morphine 0.03 mg/ml) pain relief can be further improved.

Regional blocks may also help reduce blood loss and subsequent transfusion requirements [14]. Two mecha- nisms can influence blood loss: a direct effect on vaso- constrictive sympathetic fibers contained in peripheral nerves (resulting in vasodilation in small and medium vessels, leading to reduced arterial and venous pressure), and an indirect effect mediated by antinociception and reduced systemic blood pressure [6].

The augmented analgesic effects of the regional tech- niques on pain permit early mobilization with continu- ous passive motion (CPM) [6, 7]. Pain after knee surgery can be associated with severe spasm of the quadriceps muscle, causing further pain, impaired muscle function, and hindering early rehabilitation. Regional anesthesia may block the massive afferent nociceptive input thought to trigger the increased excitability of the peripheral no- ciceptors, as well as the dorsal horn neurons. Muscle re- laxation can be enhanced by use of a local anesthetic such as lidocaine 1%,which offers greater motor blockade than bupivacaine 0.25% or ropivacaine 0.2%.

The control of postoperative pain may also indirectly influence the risk of wound infection.Patients with a con- tinuous femoral infusion have been reported to have few- er episodes of fever compared with patients who receive parenteral or epidural pain treatment.Morphine has been shown to depress the oxidative bactericidal function of neutrophils, so the reduction in morphine consumption may lead to a lower risk of immediate postoperative in- fection [6]. When the recovery of knee function is ham- pered by pain, patients must be identified, followed up closely, and treated with individualized pain therapy promptly [16].

New Concepts in Pain Management

Although most clinical studies have concentrated on de- creasing postoperative pain and acute disability,preemp- tive analgesia may also provide long-term benefits and either prevent or minimize the severity of chronic pain syndromes [3]. With the preoperative administration of pain therapy (NSAIDs, opioids, neuraxial or regional blocks) and extension of the treatment through surgery and the subsequent postoperative inflammatory re- sponse, the sensitization of the dorsal horn neurons may be prevented.

Peripheral neural infiltration techniques or intra-ar- ticular blocks can also be valuable adjuncts in pain man- agement. Both single-dose injections of local anesthetics and continuous-infiltration catheter techniques have been described. Injection into the wound requires surgi- cal infiltration of large volumes of concentrated local anesthetic solution into the skin,subcutaneous tissues,or joint capsule.Continuous infiltration techniques use mul- tihole 19-gauge catheters to continuously infuse either 0.125% or 0.25% bupivacaine under the skin and muscle layers of the incision. However, potential infection after implantation remains a concern [3].

No single analgesic technique or drug treatment can be expected to achieve complete abolition of postopera- tive pain.To avoid high dose requirements and adverse ef- fects,“balanced” or multimodal analgesic regimens have been advocated [3, 9]. At our institution, the regional

61

Chapter 61 · Pain Management – T. Deckmyn ³⁸⁷

61

block is routinely used with systematic administration of acetaminophen (1 g every 6 h) or propacetamol (2 g every 6 h) and perioperative NSAIDs (parecoxib 40 mg daily, ketorolac 15-30 mg every 6 h, or tenoxicam 40 mg daily).

We also use a combination of low-dose local anesthetics (levobupivacaine 0.2% at 8 ml/h), lipophilic opioids (sufentanil 0.5 µg/ml), and clonidine (1 µg/ml) in the re- gional block [1, 6].

After discontinuation of the regional infusion, opi- oids such as piritramide (0.25 mg/kg every 4 h), a syn- thetic µ-agonist opioid, or codeine (60 mg every 6 h) are prescribed. Others have used i.v. PCA of morphine (1- to 2-mg bolus with lockout of 6 min) [4, 6, 8] or sustained- release oxycodone PO (20 mg every 12 h) [12]. In the future a form of fentanyl (a synthetic lipophilic opioid), based on a transdermal release patch combined with a small electric current to facilitate dermal migration, but with short onset and duration, will become available.

Following the Clinical Practice Guidelines of the USA Veterans Health Administration, intrathecal opioids may be used but intra-articular opioids are not effective.These guidelines also confirm the value of non-pharmacologi- cal interventions such as cold therapy, transcutaneous electrical nerve stimulation (TENS), distraction, relax- ation, positioning, hypnosis, massage, and exercise. Cold application by means of continuous-flow or cold com- pression dressings reduces blood loss and pain [17].TENS may not relieve the most intense aspects of acute pain,but as an analgesic supplement it effectively reduces opioid use [3].

To provide prompt and adequate pain relief, neces- sary to achieve a rapid functional rehabilitation, and to avoid “analgesic gap”in delivering multimodal pain ther- apy,inpatient acute pain services can be helpful.The mul- tidisciplinary approach includes caregivers trained to for- mulate and provide safe and specialized therapy, develop standardized treatment protocols,and optimize methods of drug delivery. It also provides nursing education in as- sessing patients’ pain, in executing standard protocols, and in treating adverse side effects [2].

Appreciation of the severity and character of the pain stimulus and the importance of pain relief in the preven- tion of a longer rehabilitation or knee stiffness commands that optimal control be provided at each phase of the recovery process. Therapeutic gains are dramatic in pa- tients with underlying cardiovascular and pulmonary disease. Optimally administered regional blockade can suppress the release of catecholamines, maintain hemo-

dynamic stability, reduce myocardial oxygen require- ments, improve respiratory function, facilitate participa- tion in physical therapy, and reduce length of hospital stay. These advantages outweigh the greater invasiveness, potential side effects, and cost of indwelling catheters, drug preparation, and supervision.

References

1. Singelyn FJ et al (1998) Effects of intravenous patient-controlled analge- sia with morphine, continuous epidural analgesia, and continuous three- in-one block on postoperative pain and knee rehabilitation after unilat- eral total knee arthroplasty. Anesth Analg 87:88-92

2. Strassels SA et al (2002) Postoperative analgesia: economics, resource use, and patient satisfaction in an urban teaching hospital. Anesth Analg 94:130-137

3. Sinatra RS et al (2002) Pain management after major orthopaedic surgery: current strategies and new concepts. J Am Acad Orthop Surg 10:117-129

4. Allen HW et al (1998) Peripheral nerve blocks improve analgesia after total knee replacement surgery. Anesth Analg 87:93-97

5. Rueben SS et al (2002) Evaluation of the safety and efficacy of the peri- operative administration of rofecoxib for total knee arthroplasty. J Arthro- plasty 17:26-31

6. Chelly JE et al (2001) Continuous femoral blocks improve recovery and outcome of patients undergoing total knee arthroplasty. J Arthroplasty 16:436-445

7. Capdevilla X et al (1999) Effects of perioperative technique on the surgi- cal outcome and duration of rehabilitation after major knee surgery.

Anesthesiology 91:8-15

8. Ganapathy S et al (1999) Modified continuous femoral three-in-one block for postoperative pain after total knee arthroplasty. Anesth Analg 89:1197-1202

9. Himmelseher S et al (2001) Small-dose S(+)-ketamine reduces postoper- ative pain when applied with ropivacaine in epidural anesthesia for total knee arthroplasty. Anesth Analg 92:1290-1295

10. Sinatra RS et al (1992) Acute pain: mechanisms and management.

Mosby-Year Book, St. Louis, MO

11. Williams-Russo P et al (1996) Randomized trial of epidural versus gener- al anesthesia: outcomes after primary total knee replacement. Clin Orthop 331:199-208

12. Adams HA et al (2002) Postoperative pain management in orthopaedic patients: no differences in pain score, but improved stress control by epidural anaesthesia. Eur J Anaesthesiol 19:658-665

13. American Society of Regional Anesthesia and Pain Medicine. Consensus statements on neuraxial anesthesia and anticoagulation. Available at http://www.asra.com/

14. Chelly JE et al (2001) Continuous peripheral nerve block techniques.

Mosby, London

15. Bogoch ER et al (2002) Lumbar paravertebral nerve block in the man- agement of pain after total hip and knee arthroplasty. J Arthroplasty 17:398-401

16. Ranawat et al (2003) Total knee rehabilitation protocol. J Arthroplasty 18:27-30

17. Webb JM (1998) The use of cold compression dressings after total knee replacement: a randomized controlled trial. Orthopedics 21:59-61