Neobook — clinical reference

Treatment of adverse effects of chronic opioid use

PAIN, CHRONIC

R52.1/R52.2/R52.9

DESCRIPTION

An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage. The relationship between pain (a subjective experience) and tissue damage (which may be assessed directly by others) is moderated by socio-cultural context as well as the nervous system. Acute pain is defined as pain present for less than 4 weeks and usually occurs in response to tissue damage. Chronic pain is pain present for more than 3 months.
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The goals of pain management include pain reduction and improved function, sleep, and well-being. Family members play an important part in the patient’s treatment and should be included where possible.

Measure care outcomes by evaluating pain severity, quality of life, and functionality, e.g. Pain, Enjoyment and General Activity (PEG) scale, https://health.gov/hcq/trainings/pathways/assets/pdfs/PEG_scale.pdf

ANALGESIA FOR CHRONIC NON-CANCER PAIN

Assessment of chronic non-cancer pain

A biopsychosocial assessment is necessary to inform effective pain management.
Ascertain the aetiology and perpetuating factors and manage accordingly.
Note that there may be overlap between different aetiologies, and condition-specific pain management may be required.
- Nocioceptive pain, e.g. rheumatoid arthritis; osteoarthritis; gout; spondylarthritis; chronic post-surgical or injury pain; visceral pain, e.g. chronic pancreatitis; chronic cancer pain; endometriosis
- Neuropathic pain
- Fibromyalgia and irritable bowel syndrome (see PHC STGs and EML, Irritable bowel syndrome)
- Mental illness, e.g. mood disorders (depression and bipolar disorder), anxiety, post-traumatic stress disorder (See chapter: Mental health conditions), somatic symptoms, and related disorders.
- Substance abuse disorders, including over the counter analgesics, opioids, benzodiazepines, and alcohol.
Ascertain the patient's beliefs about their pain and hopes of care. Common issues to address are:
- Patients’ perception of pain and the idealised nature of reality, e.g. that life must be pain-free.
- That pain means exercise and physical activity must be avoided.
- Catastrophic thinking regarding the pain.
- A need to be unwell to be cared for by others.
- Fear of work and responsibility, for various reasons.
- Stigma, with denial of mental illness or interpersonal conflict.
Social stressors, trauma, interpersonal conflict or violence may predispose to and perpetuate chronic pain.

GENERAL AND SUPPORTIVE MEASURES

Patients with chronic pain should be treated with a biospsychosocial approach, according to findings of a comprehensive assessment. Note that those with greater subjective pain complaints may also be at higher risk of an opioid use disorder.
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Validate the pain experienced and manage with empathy.
Explore and manage exacerbating factors for pain. See: Chronic pain.
Educate regarding the cause of pain, prognosis (including that pain may not be fully relieved), and realistic expectations regarding pain reduction.
Establish goals of care with the patient and select a measure of effectiveness e.g. Pain, Enjoyment and General Activity (PEG) scale.
Treat the underlying physical cause of pain. Refer for specialist care (e.g. rheumatologist, orthopaedic surgeon) where necessary.
Treat underlying or comorbid mental illness.
Manage substance use, refer to SANCA/ rehabilitative services.
Encourage physical activity; refer to Physiotherapy and Occupational Therapy (OT).
Address self-esteem, motivation, daily function, and social skills; refer to OT.
Address social stressors and interpersonal conflicts; refer to social worker, counselling services, psychologist, social welfare organisations, NGOs (e.g. FAMSA, or POWA if domestic violence is reported).

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MEDICINE TREATMENT

Paracetamol, ibuprofen and tramadol may be used alone or in combination according to the severity of pain.

Mild/moderate pain:

Paracetamol, oral, 500 mg–1 g, 4–6 hourly as required (to a maximum of 4 g in 24 hours).
- Maximum dose: 15 mg/kg/dose.

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NSAID, e.g.:
Ibuprofen, oral, 400 mg 8 hourly with meals.
- May be used in combination with paracetamol and/or opioids.

CAUTION

- Avoid long-term use of NSAIDs (e.g. ibuprofen) as they are associated with an increased risk of arterial thrombosis, renal impairment and GI bleeding.
- Concomitant use of more than one oral NSAID has no additional clinical benefit and only increases toxicity.
- All NSAIDs are associated with increased risks of gastrointestinal bleeding, renal dysfunction, and cardiovascular events (stroke and myocardial infarction).
- Use NSAIDs judiciously at the lowest effective dose and for the shortest duration.
- Do not use NSAID in pregnancy or while breastfeeding.

In high-risk patients: i.e. patients > 65 years of age, or with a history of peptic ulcer disease, or on concomitant warfarin, aspirin or corticosteroids:

ADD

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PPI, e.g.:
- Lansoprazole, oral, 30 mg daily.

Moderate pain unresponsive to simple analgesia:

Tramadol, oral, 50–100 mg, 6 hourly; may be increased to a maximum of 400 mg daily.
- Warn patient of adverse effects and risk of addiction. Advise not to operate machinery/drive initially and after dosage increases.
- Evaluate response to treatment using a pain rating scale at 2 weeks and every 4 weeks afterwards: taper and stop tramadol if not reducing pain. See PHC STG & EML: Pain control for rating scales.
- In patients with uncontrolled pain, the dose can be increased to a maximum of 100 mg 6 hourly.
- Improved effect when given with paracetamol.

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CAUTION – TRAMADOL

- Tramadol causes respiratory depression and may be fatal in overdose.
- Avoid concurrent prescribing of opioid pain medication, benzodiazepines or other respiratory depressants.
- After a period of no treatment, re-initiate at 50 mg. Treat overdose as in Opioid poisoning.
- Avoid use in those at high risk of opioid addiction (a personal or family history of any substance use disorder, comorbid mental illness, high levels of subjective pain and younger people). The Opioid Risk Tool (ORT) is a brief, self-report screening tool used to assess risk for opioid abuse among adults prescribed opioids for treatment of chronic pain. https://nida.nih.gov/sites/default/files/opioidrisktool.pdf
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- Tramadol inhibits reuptake of noradrenaline and serotonin – increases risk of seizures, of serotonin syndrome, and mania or hypomania. Use with caution in high-risk patient groups (e.g. epilepsy, severe head injury, if taking antidepressants, bipolar disorder). Educate the patient, optimise treatment of primary condition, avoid polypharmacy, and monitor closely.
- Other adverse effects include constipation, dry mouth, drowsiness, and confusion.
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Morphine solution (Mist morphine), oral.
- Starting dose: 5–10 mg (maximum 0.2 mg/kg) 4 hourly.
- Elderly or frail patients: 2.5–5 mg oral (maximum 0.1 mg/kg) 4 hourly.
- Increase total daily dose by 30% every 24 hours if pain control is inadequate.
- Increase the dosing interval in patients with renal or liver impairment.

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When stable on morphine solution, the morphine solution can be changed to an equivalent dose of long-acting, slow-release morphine:

Morphine, slow-release, oral, 12 hourly.
- Available in tablets of 10 mg, 30 mg, and 60 mg.
- Duration of action: 12 hours.
- Dose according to previous morphine solution requirements, e.g. a patient whose pain is controlled by 6 doses of 10 mg morphine solution per 24 hours (i.e. 60 mg morphine per day) can be converted to receive slow-release morphine tablets, 30 mg 12 hourly, oral.
- Maximum dose for non-cancer pain is usually 60 mg 12 hourly.

Note:

- When morphine is used for chronic non-cancer pain, discuss potential side-effects with the patient, the maximum dose of opioids that will be prescribed, and anticipated duration of treatment. Address all fears and concerns with the patient to alleviate fear. Provide support and education for caregivers and family.
- Patients with breakthrough pain should be treated appropriately. See PHC STG & EML: Breakthrough Pain.
- Avoid in patients with history of alcohol or other drug addiction, where possible.

ANALGESIA FOR CHRONIC CANCER PAIN

DESCRIPTION

The term “cancer pain” also includes pain due to “palliative care needs/ serious illness”.

GENERAL MEASURES

Follow the same steps as provided in: Analgesia for chronic non-cancer pain, with the following exceptions:

Morphine
- There is no maximum dose of morphine – Titrate as needed.
- Concerns regarding addiction/dependency should not compromise adequate pain control with opioids when used to treat “palliative care needs/serious illness”.
- For patients on slow-release morphine, it is advisable to still prescribe morphine solution for breakthrough pain or for painful procedures.
- Breakthrough pain is a transient exacerbation of pain which occurs either spontaneously or in relation to a specific trigger despite relatively stable and adequately controlled background pain. It may or may not be at the same location as the background/controlled pain.
- Treat breakthrough pain by giving an extra dose of immediate-release morphine equal to the regular 4-hour dose (i.e. one sixth of the total daily dose).
- The next regular dose of morphine must still be given at the prescribed time, and not be delayed because of the additional dose.

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The regular 4-hourly dosage should be titrated upward against the effect on pain in the following way:

Add up the amount of “breakthrough morphine” needed in 24 hours.
Divide this amount by 6 (the number of 4 hourly doses in 24 hours).
The next day increase maintenance dose by that amount.

Example:

Patient receives 10 mg morphine every four hours.
The patient has 3 episodes of breakthrough pain over 24 hours and is given an additional 10 mg during each episode:
- Total breakthrough pain dosage: 3 x 10 mg = 30 mg.
- Dose to add to maintenance dose the following day: 30 mg ÷ 6 = 5 mg.
The day following the breakthrough pain, the regular 4 hourly dose of 10 mg will be increased by 5 mg, i.e. 10 mg + 5 mg = 15 mg.
The new morphine dose will be 15 mg 4 hourly.

Note

- Opioid–induced hyperalgesia is defined as increasing pain sensitivity in patients chronically exposed to opioids without any new causes for pain. Increasing doses of morphine paradoxically result in increased pain, often with features of neuropathic pain such as hyperalgesia or allodynia (consult with a pain clinician/specialist).

Bisphosphonates may be considered for metastatic bone pain – refer to the Tertiary and Quaternary EML (specialist management/consultation).

TREATMENT OF ADVERSE EFFECTS OF CHRONIC OPIOID USE

Y45.0

MEDICINE TREATMENT

Constipation: (K59.0)

Patients on chronic opioids should routinely be prescribed a laxative.

Sennosides A and B, oral, 13.5 mg, 1-2 tablets at night.
- Contraindicated in patients with potentially obstructive lesions.

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In patients with potentially obstructive lesions:

Lactulose, oral, 10–20 mL 12–24 hourly.

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Nausea and vomiting:

Metoclopramide, oral/IM/slow IV, 10 mg 8 hourly (See Treatment of PONV)

Promethazine, oral, 25 mg 8 hourly.

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Ondansetron, oral, 8 mg 12 hourly.

NEUROPATHIC PAIN

G62.9

DESCRIPTION

Pain caused by a lesion or disease of the somatosensory nervous system.
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Different patterns are noted, i.e. polyneuropathy, mononeuritis multiplex, and mononeuropathy, each of which may be caused by axonal degeneration or demyelination or a combination of the above. Clinical features may be predominantly of a sensory, sensorimotor, or motor nature.
Important causes of a predominantly sensory neuropathy include:
- alcohol;
- diabetes;
- HIV infection;
- Vitamin deficiency: thiamine, vitamin B12 (although the latter more commonly presents as subacute combined degeneration of the cord);
- medicines (e.g. isoniazid, stavudine, metronidazole, amiodarone, certain chemotherapeutic agents).
Important causes of a predominantly motor neuropathy include:
- Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP – also known as Guillain-Barrè syndrome),
- Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP),
- Acute porphyrias

GENERAL MEASURES

If there is a history of rapid progression, particularly in patients with features suggestive of AIDP, (e.g. rapid progression with stabilisation within 4 weeks) admit the patient and monitor vital capacity carefully with spirometry, as intubation and ventilatory support may be required.
Manage the cause where possible.
Specialised nursing care and dedicated physiotherapy may be indicated. If not managed appropriately, chronic cases may develop contractures, weakness affecting gait, and chronic bedsores, and they may become wheel chair-bound.
Encourage activity, with referral to OT and physiotherapy.
Address psychosocial stressors and enhance perceived social support, and refer to social worker as required.
Treat comorbid mental illness (see chapter: Mental health conditions).
Assess outcome of treatment with objective measures of function, e.g. Pain, Enjoyment and General Activity (PEG) scale.

MEDICINE TREATMENT

Most cases respond to management of the underlying disease process or removal of the aetiological agent.

In addition to the analgesics for chronic nociceptive pain (see for analgesia for chronic non-cancer pain), anti-neuropathic pain medicines to stabilise affected sensory nerves can be used.

Amitriptyline, oral, 10 mg, two hours before usual sleep time.
- Titrate up to 75 mg (to a maximum of 150 mg) at night if needed.
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- In the elderly: 10–25 mg daily, increasing gradually up to 50–100 mg daily, if required and tolerated. A single bedtime dose is optimal for most patients.
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- Use regularly, as it takes 2-6 weeks for maximal effect.
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Post-herpetic neuralgia: (G53.0)

Initiate treatment with adjuvant amitriptyline therapy early.

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If no response after 2-4 weeks to amitriptyline:

ADD

Carbamazepine, oral, 100mg 12 hourly for 2 weeks.
- If response is inadequate, increase the dose every 2 weeks to a maximum dose of 600 mg 12 hourly.
- Monitor for possible drug interactions in patients on ART.

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If amitriptyline is contraindicated:

REPLACE WITH

Carbamazepine, oral, 100mg 12 hourly for 2 weeks.
- If response is inadequate, increase the dose every 2 weeks to a maximum dose of 600 mg 12 hourly.
- Monitor for possible drug interactions in patients on ART.

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Note

Aciclovir is not beneficial in treating post-herpes zoster neuropathy.

Isoniazid-induced polyneuropathy: (G62.9 + Y41.1)

Pyridoxine, oral, 75 mg daily for 3 weeks.
- Follow with 25-50 mg daily.

Trigeminal neuralgia (G50.0)

Sudden, usually unilateral, severe, brief, stabbing, recurrent episodes of pain in the distribution of one or more branches of the trigeminal nerve.

Carbamazepine, oral, 100 mg 12 hourly, initial dose.
- Increase dose slowly. Doses of up to 1 200 mg daily may be required.
- After exacerbation, reduce to maintenance dose of 400-800 mg daily.

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REFERRAL

Neuropathic pain unresponsive to these medicines, refer patient to an experienced pain clinician.

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Standard Treatment Guidelines and Essential Medicines List for South Africa, Adult Hospital Level, 2020-2024_Version 1.0_07 November 2024

Chapter 25: Pain_25.1 Pain, Chronic

Pain, Chronic

Drugs mentioned

ICD-10 codes