What are the guidelines for using morphine (opioid analgesic) for pain management?

Morphine for Pain Management: Clinical Guidelines

Oral morphine is the first-line strong opioid of choice for moderate to severe cancer pain and should be initiated without delay when pain is uncontrolled by non-opioid analgesics and weak opioids. 1

Indications and Patient Selection

• Morphine is indicated for moderate to severe pain not responsive to non-narcotic analgesics 2
• Start morphine immediately when step 1 (paracetamol/NSAIDs) and step 2 (weak opioids like codeine, tramadol) treatments fail to control pain 1
• The oral route should be the first choice for administration whenever possible 1

Dosing and Titration Strategy

Initial Dosing

• For opioid-naïve patients: Begin with immediate-release (IR) morphine 5-15 mg orally every 4 hours, with rescue doses available up to hourly for breakthrough pain 1
• For IV administration: Start with 0.1-0.2 mg/kg every 4 hours in adults, adjusting based on pain severity, adverse events, patient age, and size 2
• For severe pain requiring rapid titration: Use IV morphine 1.5 mg bolus every 10 minutes until pain relief is achieved (84% of patients achieve satisfactory relief within 1 hour versus 25% with oral IR morphine) 1

Conversion Ratios

• The oral to IV/subcutaneous morphine potency ratio is 1:2 to 1:3, meaning oral doses need to be 2-3 times higher than parenteral doses 1
• When switching from another strong opioid, calculate the starting morphine dose using equianalgesic ratios, but err on the side of caution by using the lower end of the conversion range and providing rescue doses 1

Maintenance and Breakthrough Pain

• After titration with IR morphine, transition to sustained-release formulations for around-the-clock dosing 1
• Always prescribe IR morphine concurrently as rescue medication for breakthrough pain episodes, typically 10-15% of the total daily dose 1
• If more than 4 rescue doses per day are needed, increase the baseline sustained-release dose accordingly 1
• For predictable pain episodes (movement, swallowing), administer IR morphine at least 20 minutes before the trigger 1

Special Populations and Contraindications

Renal Impairment

• Critical consideration: Use all opioids with caution and at reduced doses/frequency in renal impairment 1
• For chronic kidney disease stages 4-5 (eGFR <30 mL/min): Switch to fentanyl or buprenorphine via transdermal or IV routes, as these are the safest options due to lack of neurotoxic metabolite accumulation 1
• Morphine metabolites (morphine-3-glucuronide and morphine-6-glucuronide) accumulate in renal failure and cause neurotoxicity 3

Absolute Contraindications

• Known hypersensitivity or allergy to morphine 2
• Bronchial asthma or upper airway obstruction 2
• Respiratory depression without resuscitative equipment available 2
• Paralytic ileus 2

Relative Contraindications and Cautions

• Head injury/increased intracranial pressure: Morphine may increase respiratory depression and elevate cerebrospinal fluid pressure 2
• Biliary tract disorders: May cause sphincter of Oddi spasm 2
• Cardiovascular instability: High doses can cause sympathetic hyperactivity and increased catecholamines 2

Side Effect Management

Mandatory Prophylaxis

• Constipation: Laxatives must be routinely prescribed for both prophylaxis and management—this is the only side effect that does not resolve with continued use 1, 4, 5
• Provide dietary and hydration advice alongside laxative therapy 1

Common Side Effects Requiring Treatment

• Nausea/vomiting: Prescribe metoclopramide or antidopaminergic drugs for several days; exclude other causes first 1
• Sedation/drowsiness: Usually resolves within days during titration; if persistent, rule out metabolic disorders or drug interactions before reducing morphine dose 1, 4
• Dry mouth, dizziness, lightheadedness: Common but typically transient 2, 4

Serious Adverse Events

• Respiratory depression: Most likely with rapid IV administration, which can cause chest wall rigidity 2
• CNS toxicity: High doses may cause convulsions 2
• Hypotension: May occur in ambulatory patients 2

Opioid Rotation Strategy

When morphine causes intolerable side effects despite adequate symptomatic management:

1. First-line alternatives: Consider fentanyl (lower rates of constipation, nausea, vomiting), hydromorphone, or oxycodone 3
2. Calculate equianalgesic doses but use the lower end of the conversion range for safety 1
3. Main indications for rotation: Resistant side effects (cognitive dysfunction, hallucinations, myoclonus, nausea) despite treatment, especially at high doses 1
4. Never combine different opioid receptor types (pure agonists with partial agonists or mixed agonist-antagonists) as this can precipitate withdrawal 1, 3

Critical Safety Considerations

• Never stop morphine abruptly—taper by 30-50% over approximately one week to avoid withdrawal symptoms 1
• Avoid dosing errors: Take extreme care to distinguish between different concentrations and between mg and mL to prevent accidental overdose and death 2
• Drug interactions: CNS depressants, muscle relaxants, cimetidine, and anticholinergics can increase respiratory depression, neuromuscular blockade, or constipation 2
• Psychological addiction is rare in cancer pain patients when properly monitored 5
• Physical dependence and tolerance are not clinically problematic in chronic cancer pain management 1, 5, 6

Alternative Routes When Oral Administration Impossible

• Preferred alternatives: Transdermal fentanyl or continuous parenteral morphine with patient-controlled analgesia 1
• Other routes: Rarely indicated and should only be used after considering benefit-to-risk ratio, personnel training, and follow-up constraints 1