pain and opioid management

Mechanism-guided pain classification, around-the-clock titration with breakthrough dosing, equianalgesic conversions, opioid rotation with cross-tolerance reduction, transdermal fentanyl rules, and recognition of opioid neurotoxicity vs overdose.

pain classification

nociceptive — somatic (well-localised, aching) or visceral (diffuse, crampy/pressure)
neuropathic — burning, lancinating, allodynia, dysaesthesia
mixed — most cancer pain; treat each component

baseline titration

initiate immediate-release (IR) opioids q4h around-the-clock (ATC)
titrate only after steady state (4–5 half-lives; ~24h for IR, ~48–60h for sustained-release)
new daily ATC dose = prior 24h baseline + total breakthrough doses consumed
breakthrough (BT) dose = ~10% of total 24h scheduled dose, q1h PRN
if ≥3 BT doses/24h consistently → increase ATC dose by 20–25% (or 50–100% if total daily oral morphine equivalent ≤60 mg)

dosing interval rationale

standing q4h — based on IR opioid duration of action (2–4h)
PRN q1–2h — based on time to peak effect (SC Cmax ~30 min; PO ~60 min)
reserve long-acting formulations until stable analgesia achieved on IR

incident pain

Pre-empt predictable procedural/movement pain: IR dose 30 min before (SC) or 60 min before (PO).

equianalgesic conversions

Agent	PO dose	SC/IV dose	PO:parenteral ratio
morphine	10 mg	5 mg	2:1
hydromorphone	2 mg	1 mg	2:1
oxycodone	5–7.5 mg	—	no standard SC form
codeine	100 mg	50 mg	2:1

opioid rotation protocol

indications

opioid-induced neurotoxicity (OIN)
refractory pain despite aggressive dose titration
intolerable adverse effects
route failure requiring parenteral conversion (e.g. CADD pump)

steps

calculate total 24h baseline dose
convert to target agent using equianalgesic ratios
reduce by 25–50% for incomplete cross-tolerance (use greater reduction in renal impairment or extreme frailty)
set new BT dose at 10% of new total

incomplete cross-tolerance

Different opioids have distinct affinity profiles across µ-receptor subtypes → patients are disproportionately sensitive to a newly introduced opioid. Always reduce the equianalgesic dose by 25–50% when rotating.

transdermal fentanyl

only for opioid-tolerant patients with stable baseline pain
25 µg/h patch ≈ 60–134 mg/day oral morphine equivalent
~72h to steady state; replace q72h (q48h for end-of-dose failure)
starting: continue oral IR opioid for 12h after patch placement
stopping: wait 6–12h after patch removal before initiating new scheduled oral opioid

opioid-induced neurotoxicity (OIN) vs overdose

OIN is a neuroexcitatory state driven by toxic polar metabolite accumulation (morphine-3-glucuronide, hydromorphone-3-glucuronide) — distinct from µ-receptor agonism.

Feature	Expected side effects	OIN	Overdose
mechanism	therapeutic µ-receptor effect	toxic metabolite accumulation (renal failure, dehydration)	excessive µ-receptor stimulation
signs	nausea, mild drowsiness, constipation	hyperalgesia, allodynia, myoclonus, visual/tactile hallucinations, agitated delirium	sedation, miosis, RR ≤8, coma
management	symptom-specific (laxatives, antiemetics)	IV/SC hydration, dose reduction, opioid rotation (resolves 24–48h)	naloxone, ventilatory support

neurotoxicity ≠ undertreated pain

Myoclonus + agitation + worsening pain in a patient on opioids with renal impairment → suspect OIN. Escalating the same opioid worsens it — rotate instead.

adjuvant analgesics

bone pain

localised: EBRT + NSAIDs + corticosteroids; 2nd-line — surgical stabilisation, epidural/intrathecal analgesia
disseminated: NSAIDs, corticosteroids, bisphosphonates (zoledronic acid, pamidronate), systemic radionuclides

neuropathic pain

Line	Agents
1st	gabapentinoids, TCAs, corticosteroids (acute compression)
2nd	SNRIs (duloxetine), carbamazepine, valproate, regional nerve blocks
3rd	NMDA antagonists (ketamine, methadone), lidocaine infusions, cordotomy/rhizotomy

opioid selection by organ function

Context	Preferred	Avoid
renal impairment	fentanyl, methadone (hepatic clearance, inactive metabolites)	morphine, codeine, meperidine; discontinue hydromorphone if acute H3G accumulation
hepatic impairment	hydromorphone, fentanyl (dose-adjust)	codeine (pro-drug, unpredictable), methadone (prolonged t½)

worked conversion: PO hydromorphone → SC morphine

Step	Calculation
1. total 24h oral dose	hydromorph contin 12 mg PO q12h = 24 mg PO/day
2. convert to oral morphine	ratio hydromorphone:morphine = 1:5 → 24 × 5 = 120 mg PO morphine/day
3. convert PO → SC	ratio 2:1 → 120 ÷ 2 = 60 mg SC morphine/day
4. reduce 50% for cross-tolerance	60 × 0.5 = 30 mg SC/day
5a. scheduled ATC (q4h = 6 doses)	30 ÷ 6 = 5 mg SC q4h
5b. BT dose (10% of daily)	30 × 0.1 = 3 mg SC q2h PRN