12 Treatment of pain
1 Introduction
1.1 Pain in people with hemophilia
Among people with hemophilia (PWH) pain is a very common condition affecting the quality of life [1,2].
When evaluating pain, it is important to take the patient’s life situation into account. The pain could be acute and/or severe or chronic. Pain from joints or muscles is very common in PWH, especially if the patient has hemophilic arthropathy, in which case the pain often is chronic.
Basic pain treatment can be symptomatic and, in some cases, also directed against the underlying disorder.
Bleeding in a joint or muscle will cause acute pain and should be treated with relevant hemostatic drugs as soon as possible to stop the bleeding.
If the PWH is not on a prophylactic treatment regimen and has a target joint, prophylaxis should be offered to avoid recurrent bleeding, inflammation, and pain.
Several instruments exist for the evaluation of pain in PWH among which are the visual analogue scale (VAS), health-related quality of life (HRQoL), McGill Pain Questionnaire (arthritis), and others [3–5].
In many situations chronic pain should be managed by a multidisciplinary team where the patient is rehabilitated with the help of a specialized pain management team, physiotherapists, psychologists, doctors of other specialities (e.g., anesthesia, orthopedic surgery, physiatry), social workers, psychologists, in addition to hemophilia doctors and nurses [6].
1.2 RECOMMENDATION
For PWH with acute or chronic pain, the use of age-appropriate pain assessment tools such as VAS are recommended.
Acute pain due to a joint or muscle bleed should be immediately treated with relevant hemostatic drug in addition to pain medication and other measures such as immobilization, compression to minimize the pain.
Chronic pain should be managed by a multidisciplinary team consisting of specialized pain management teams in addition to the hemophilia comprehensive care centre’s team.
2 Analgesics
2.1 Managing mild to moderate pain
Mild analgesics are often used in the treatment of both acute and chronic pain. Paracetamol (acetaminophen) is the basic treatment and can if necessary be combined with tramadol or codeine.
The analgetic effect of codeine is caused by codeine conversion to morphine. However, one should keep in mind that in approximately 10% of the Caucasian population, codeine is without an analgetic effect, due to an inability to convert codeine to morphine.
Tramadol is a synthetic codeine analogue.
Common side effects of treatment with codeine, tramadol, and morphine are nausea, vomiting, constipation and drowsiness.
Codeine should be used with caution, especially in elderly patients because of the risk of cognitive side effects.
Information about dosing of analgesics is very important for the prevention of toxicity e.g., liver toxicity with paracetamol in patients with chronic hepatitis or HIV.
Aspirin inhibits platelet aggregation irreversibly and should not be used in the treatment of pain for PWH.
If the pain is caused by inflammation in a joint, COX-2 inhibitors (celecoxib or etoricoxib) can be considered in selected PWH. COX-2 inhibitors do not inhibit platelet aggregation. However, even COX-2 inhibitors can have serious side effects like COX-1 inhibitors and should be used with caution.
One of the most serious side effects is gastroduodenal ulcers.
The risk of gastrointestinal ulcers is lower with COX-2 inhibitors compared to COX-1 inhibitors.
H2-receptor antagonists or proton pump inhibitors can be used to minimize the risk of ulcers.
Both COX-1 and COX-2 inhibitors can have severe gastrointestinal, renal, and cardiovascular (MI, stroke, and other arterial thrombosis) side effects.
Among the NSAIDs COX-1 inhibitors e.g., ibuprofen has a reversible inhibition on platelet aggregation. COX-1 inhibitors should generally only be used on strong indications and with caution in the treatment of pain in PWH due to the increased risk of bleeding and other serious side effects. If there is a strong indication for the use of COX-1 inhibitors in PWH it is recommended to choose a drug with a short half-life. Ibuprofen has a short half-life, and the risk of side effects (gastrointestinal ulcers and cardiovascular events) is considered low when the daily total dosage is 1,200 mg and below.
Some patients may benefit from using analgesics with prolonged effects, especially for the treatment of pain at night. Also, transdermal formulas can benefit many patients with chronic pain issues.
2.2 Managing severe and complex pain
In the case of severe acute pain, morphine could be necessary to use at the start, but due to the risk of addiction, it should be given for a limited period.
Patients with severe complex chronic pain should be preferably managed at a multi professional pain clinic.
It is important to be aware that children often express pain in a different way than adults.
Before injections, it is common to apply anesthetic cream to the skin of the child to minimize pain.
In addition to the management of nociceptive pain, patients with chronic pain conditions can also benefit from medications aimed at modifying the pain response, such as serotonin and norepinephrine reuptake inhibitors (SNRI), gabapentinoids or tricyclic antidepressants.
The non-pharmacologic, complementary management options are an important part of pain treatment. Examples of psychologic methods include meditation, distraction, mindfulness, relaxation techniques and acceptance and commitment therapy (ACT).
ACT is a cognitive-behavioral therapy commonly used by psychologists and other healthcare professionals working with patients with chronic pain. The aim of the therapy is through mindfulness and acceptance increase valued action in the presence of pain [7].
Physical medicine techniques such as the use of cold, heat and electricity (e.g., transcutaneous electrical nerve stimulation (TENS) can also provide relief. Ice must be used with caution as it may interfere with coagulation.
Physiotherapist also aid in finding pain relief. Methods include home-based exercises, hydrotherapy, manual therapy techniques, laser therapy, orthotics and aids, and advice for modifying physical activity [8].
Pain in PWHs could be managed as described below [141,142]:
2.3 RECOMMENDATION
- Mild pain and/or chronic pain can be managed with paracetamol alone or combined with codeine or tramadol.
2.4 RECOMMENDATION
- Pain and joint inflammation can be managed with COX-2 inhibitors (celecoxib or etoricoxib) or in special circumstances with COX-1 inhibitor ibuprofen.
2.5 RECOMMENDATION
- Acute severe pain can be managed with morphine.
2.6 RECOMMENDATION
- Non-pharmacological methods are a useful complement to pain medications.
3 Orthopedic surgery and treatment by the orthopedist
Treatment by the orthopedic surgeon should always be considered if the pain is a symptom caused by joint damage and conservative management has failed to provide sufficient improvement in pain and function.
Synovectomy with removal of the synovial membrane can often be used if the patient has inflammation without severe cartilage or bone destruction in the joint.
If the joint is severely damaged a joint prosthesis is often the best solution to the pain problem.
In some cases, the physiotherapist or orthopedist can help the patient with orthosis or heightening of shoe heels.
4 Intraarticular corticosteroid injection in joints with hemophilic arthropathy
Intraarticular injection of corticosteroid for the treatment of inflammation and pain in joints with arthritis e.g. rheumatoid arthritis is a documented and established treatment modality [9].
If the PWH has a joint with inflammation, a corticosteroid injection into the joint can be used. It has been demonstrated in a few studies that intra-articular injection of corticosteroids can reduce pain in hemophilia joints with inflammation [10].
A prophylactic dose of factor concentrate should be given prior to the injection of corticosteroid unless the patient uses non-factor replacement therapy.
The intra-articular injection must be given under sterile conditions and if possible, effusions can be drawn from the joint.
In case of suspicion of infection, the synovial fluid must be sent to further investigation to rule out infection and injection of corticosteroid should not be given. The most serious but also very rare complication of intra-articular corticosteroid is infection.
The dose of corticosteroid depends on the size of the joint and the degree of inflammation. The dose of corticosteroid could be e.g. triamcinolone hexacetonide (Lederspan®) 10-40 mg or triamcinolone acetonide (Kenalog®) 20-80 mg.
As it is essential to the effect of the treatment, that the corticosteroid is given into the joint, it is recommended that the injection is given by a physician, trained in giving injections into the joints. If possible, the injection could be given guided by ultrasonography to increase the precision of injection.
After the injection the patient must avoid loading of the joint for at least 24 hours. When corticosteroid is used in arthritis the effect of the injection stays at least four to six weeks but usually for several months or even longer. Osteoporosis around the joint needs to be managed appropriately.
Mild side effect is experienced in up to 10% of cases as flushing of the face and increased sweating in minutes to hours after the injection.
In patients with arthritis, approximately 2% can experience worsening pain lasting the first 24 hours after the injection.
Although the systemic effects of the corticosteroid injection are minimal, measurements of blood glucose should be done in patients with diabetes mellitus, as the blood glucose in some cases can be elevated in the first days after the injection.
4.1 RECOMMENDATION
- Corticosteroid injections can be used in joints with inflammation.
4.2 RECOMMENDATION
- Care must be taken to avoid bleeding and that the treatment is given into the joint.
4.3 RECOMMENDATION
- Systemic effects of single corticosteroid injections are minimal.