Analgesia

High-Yield Tips

• Be conservative! You can always give more analgesia but you can't take it out of the patient.
• Be particularly cautious in: elderly patients, patients with renal impairment, patients with hepatic impairment, those with respiratory issues.
• Main adverse effects of opioids include: respiratory depression, sedation, constipation, nausea.
• Ensure the patient is well-monitored after any opioid administration.
• Use the WHO Pain Ladder as a framework for what level of analgesia may be required for the pain that the patient is experiencing.

WHO Pain Ladder

Principles

1. Start at the level most appropriate for the patient
   • e.g. acute pain in ED → can start at level 2
   • e.g. chronic pain on the wards → can start at level 1 (or non-pharmacological)
2. Re-evaluate patient’s response to therapy
3. Titrate dose and medication to patient’s response
4. Aim to have patient’s pain managed on the lowest step possible at the lowest dose
5. Aim for realistic goals
   • i.e. goal isn’t to remove pain entirely, but remove it enough that rehab and ADLs can be performed
6. Choose right dosing regimen
   • e.g. better to have regular paracetamol +/- NSAIDs, rather than PRN
   • Consider whether regular opioids are required or if only PRNs are required for acute flares of pain (”breakthrough” pain)
7. Choose the right drug
   • Consider what type of pain is present (e.g. neuropathic vs somatic), organ function (e.g. renal or hepatic impairment), response to prior therapy (e.g. allergies), duration of action required (e.g. short- vs long-acting)

Steps

Non-Pharmacological Therapies

• Note: in a patient with a fracture or dislocation, splinting/sling or reduction is another useful non-pharmacological pain management strategy

Pharmacological Therapies

Non-opioids

Paracetamol

• In addition to analgesic effects, also provides anti-pyretic effects
• MoA: ?
• Route of administration: PO, IV, PR
  • PO onset of action: 20-30 mins
• Dose: 1g QID or PRN q4-6h
  • Max dose: 4g in 24h
• Considerations:
  • Dose adjustment in: liver failure, low body weight (< 50kg), older age

NSAIDs

• In addition to analgesic effects, also provides anti-inflammatory, antiplatelet and anti-pyretic effects
• MoA: COX enzyme inhibition
• Classification:
  • Non-selective COX inhibitors (most) e.g. ibuprofen, aspirin, diclofenac, naproxen, indomethacin
  • Preferential COX-2 inhibitors e.g. meloxicam
  • Selective COX-2 inhibitors e.g. parecoxib, celecoxib
    • No platelet inhibition thus ↓ bleeding risk compared to other NSAIDs
    • Also ↓ GI toxicity compared to non-selective COX-inhibitors
• Route of administration: PO, IM, IV, PR, topical
• Dose (ibuprofen): 400mg PO TDS or 200-400mg PO PRN
  • Max dose: 1200mg in 24h
• Dose (celecoxib): 100-200mg PO BD
  • Max dose: 400mg in 24h
• Considerations:
  • Avoid in: elderly (> 75y), renal disease, use of ARBs/ACE-Is, peptic ulcer disease, cardiovascular disease, coagulation disorders, severe hepatic impairment, surgery
  • If patient is in pain, chart as regular as nursing staff may not give if it's PRN
• Risks:
  • Renal impairment (in dehydrated patients, those already on drugs that reduce GFR, post-surgical patients)
  • ↑ bleeding risk
  • Peptic ulcer disease or GI bleed
  • ↑ risk of cardiovascular events (in patients with pre-existing CVD)
  • NSAID-induced bronchospasm (in asthmatics)

Opioids

• All patients respond differently to different opioid drugs.
• Major problems of opioids include: respiratory depression, sedation, nausea (acutely), constipation, dependence, hypotension
• Think about dose adjustment in certain patient populations: elderly, low body weight, renal impairment, respiratory issues
• Ensure patients are being monitored regularly with pulse oximetry, BP measurements and nursing staff review

Weak Opioids

Codeine

• MoA: very weak μ-receptor agonist
  • Analgesic action depends on metabolism (~10% metabolised to morphine)
• Route of administration: PO
• Dose: 30-60mg q4h
  • Max dose: 240mg in 24h
• Duration of action: ~4h
• Considerations:
  • Interethnic differences in the variant CYP 2D6 alleles required for metabolism (ultrametabolisers vs poor metabolisers)
  • GI effects → always chart with aperients

Tramadol

• MoA (tramadol itself and its M1 metabolite): weak μ-receptor agonist + serotonin and noradrenaline reuptake inhibitor
• Route of administration: PO, IM
  • PO formulations: immediate-release and slow-release
• Dose: 50-100mg PRN q4-6h
  • Max dose: 400mg in 24h
• PO onset of action: ~1h post-administration
• Considerations:
  • Dose adjustment in: elderly, renal impairment, severe hepatic impairment
  • Less respiratory depression and GI effects than other opioids
• Risks:
  • Serotonin toxicity

Strong Opioids

Oxycodone

• Semi-synthetic opioid
• Good oral bioavailability with fast onset of action
• Route of administration: PO, IV, SC
  • PO formulations: immediate release tablet (Endone), controlled release tablet (OxyContin), immediate release cap (OxyNorm), tablet with naloxone (Targin)
    • The addition of naloxone (in Targin) is (theoretically) to ↓ constipation + ↓ diversion
    • As naloxone is metabolised by the liver, naloxone-based therapies are contraindicated in moderate to severe hepatic impairment
• PO dose: 2.5-15mg q4h + titrate to effect
• Duration of action: 3-6h (immediate release), 12h (controlled release)
• Considerations:
  • Dose adjustment in: elderly, renal impairment

Morphine

• Prototypical opiate → used as reference for all others
• Generally provides good 'quality' of analgesia
• Route of administration: PO, SC, IV
  • PO formulations: tablet (Sevredol), liquid (Ordine), controlled release tablet (MS Contin), controlled release cap (Kapanol)
• Poorly lipid soluble:
  • Onset of action: ~5 mins
  • Peak effect: ~20 mins
• Dose (age-dependent → refer to AMH): ~0.1-0.15mg/kg for most patients
• Duration of action: ~3-4h
• Metabolised into M3G (little analgesic effect, neuroexcitatory effects → myoclonus, allodynia, seizures) and M6G (potent analgesic effect)
• Considerations:
  • Nausea and sedation particularly problematic
  • Available on the ward in 10mg/1mL ampoules
  • Volume of distribution is important for initial dosing
  • Clearance affects duration of action → important for repeated dosing and infusions. Clearance is affected in renal impairment → accumulation of metabolites.

Fentanyl

• Synthetic opioid
• Extremely potent
• Highly lipophilic:
  • Onset of effect: 2-3 mins
  • Peak effect: ~3-5 mins
  • Duration of effect: 20-40 mins following a single dose
• No active metabolites → does not accumulate in renal dysfunction
• Route of administration: IM, SC, IV, TD, IN
• Dose: ~1-3 mcg/kg q4h for most adults
• Considerations
  • Unpredictable IM/SC/TD absorption → only IV administration suitable acutely
  • Present in 100mcg/2mL and 500mcg/10mL ampoules
  • Dose reduction from age > 40 (check AMH)
  • ↑ risk of serotonin toxicity (avoid with MAOI)

Hydromorphone

• Only indicated for patients intolerant of morphine and oxycodone
• Requires specialist supervision
• Dose reduction in renal and hepatic impairment
• About 5-6x more potent than morphine

IV Administration of Opioids

• Verify:
  • Patient details, drug, route
  • Allergy status of patient
  • Patency of cannula
  • Monitoring, oxygen, emergency plan, equipment
• Steps:
  1. Disinfect access port with alcohol wipe and allow to dry
  2. Administer initial dose and flush line to ensure it reaches the patient
  3. Monitor vital signs and response
  4. Do not administer more until magnitude of response apparent
  5. If more required, flush after each incremental dose

Sedation Score

• Aim to keep sedation score < 2.
• Score ≥ 2 suggests early respiratory depression → no further opioids should be given.
• If a patient is still in pain, but has a sedation score of ≥ 2, consider referral to Acute Pain Service (APS).

Adjuvant Therapies

Ketamine

TBA

Local & Regional Anaesthesia as Analgesia

• Contact the APS for this → only indicated after other initial treatments have been initiated.

Other Tips

• Patient Controlled Analgesia (PCAs) can only be initiated by the APS.
• In most cases, pre-surgical patients who are Nil By Mouth (NBM) can still be given oral medications up to 2h prior to surgery.

Resources

1. Lecture given by Dr Rebekah Potter
2. Practical Pain Management: The WHO Pain Ladder: Do We Need Another Step?
3. AMH
4. Australian Prescriber: How to adjust drug doses in chronic kidney disease
5. Australian Prescriber: Prescribing in renal disease
6. Opioid Metabolism