Acute Pain Management

Question 1

What are implications of inadequate acute pain management?

Answer 1

• CVS → ↑ HR, ↑ BP, ↑ PVR, MI, venous stasis, thrombosis
• Resp → diaphragmatic splinting, atelectasis, sputum retentions, hypoxaemia
• GI → delayed gastric emptying, ↓ intestinal motility
• GU → urinary retention
• Met/End → ↑ protein breakdown, impaired wound healing, sodium/water retention, ↑ metabolic rate
• Chronic Pain
• Psych → anxiety, sleeplessness, fatigue, distress

Question 2

What is the World Health Organisation Analgesic Ladder?

Answer 2

• Initially → paracetamol / NSAIDs
• Next → weak opioids
• Next → strong opioids

Question 3

How does paracetamol work?

Answer 3

• Number of central mechanisms
• Effects on PG production, serotonergic, opioid, NO + cannabinoid pathways
• Analgesic and antipyretic without anti-inflammatory activity
• Excreted renally, after flucuronide + sulphate conjugation in liver
• Hepatotoxic metabolite N-acetyl-p-benzoquinoneimine normally inactivated by conjugation with hepatic glutathione
• In paracetamol OD, pathway is overwhelmed → hepatic cell necrosis

Question 4

How is paracetamol administered?

Answer 4

• PO or PR
• Available as IV prep
• Particularly effective when IV

Question 5

What is the recommended dose of paracetamol?

Answer 5

• 4 g/d in adults
• Effective when prescribed regularly rather than PRN
• MRHA licensed dose of paracetamol is same for all routes of administration in adults 50kg+
• Dose in children weighing _<_10kg is now 7.5mg/kg (>10kg: 15 mg/kg)

Question 6

NSAIDs are, in general, more useful for superficial pain arising from the skin, buccal mucosa, joint surfaces and bone. What is the mechanism of action of NSAIDs?

Answer 6

• Analgesic, anti-inflammatory, antiplatelet and antipyretic
• Due to inhibition of COX → ↓PGs, ↓prostacyclins, ↓Tx A₂
• COX-1: kidney, GI mucosa, platelets (PGs contribute to normal fxn)
• COX-2: inflammatory mediators following tissue damage
• NSAID therapeutic effects (COX-2) and adverse effects (COX-1)
• Selective COX-2 inhibitors developed in attempt to reduce adverse effects of NSAIDs

Question 7

What are adverse effects of NSAIDs?

Answer 7

• GI toxicity
• Renal impairment (all)
• Increased risk of CV events (eg MI / stroke)
• Lowest GI effects → iboprufen
• Lowest CV events → naproxen and low-dose iboprufen
• COX-2 inhibitors have higher CV risk but lower GI effects
• Other adverse effects: hypersensitivity rxn, fluid retention

Question 8

What are differences between NSAIDs and COX-2 inhibitors?

Answer 8

Question 9

What are contraindications to NSAIDs?

Answer 9

Avoid in severe renal impairment, heart failure, liver failure and known NSAID hypersensitivity

Question 10

What is the treatment for neuropathic pain?

Answer 10

NICE Guidelines:

1. First line → amitriptyline (or imipramine if untolerated) or pregabalin
2. Second line → amitriptyline AND pregabalin
3. Third line → refer to pain specialist, tramadol in interim + avoid morphine
4. Diabetic neuropathic pain → duloxetine

Question 11

What are examples of inhaled analgesia?

Answer 11

• Entonox (50/50 N₂O, O₂) → quick-acting, potent, short duration, self-admin
• Isonox (isofluorane in entonox) → lower concs of isofluorane produce less drowsiness

Question 12

What are side-effects of inhaled analgesia?

Answer 12

• Ideal for short procedures (dressings, drain removal, catheter, labour pain, traction)
• Entonox:
  
  • Side-effects → drowsiness, nausea, excitability
  • Diffuses rapidly into + increases gas-containing cavities
  • CIs → pneumothorax, decompression sickness, intoxication, bowel obstruction, bullous emphysema + head injury

Question 13

Opioid drugs act as agonists at opioid receptors, found mainly in brain + spinal cord, but also peripherally.

What are the 3 principal classes of opioid receptor?

Answer 13

• μ (mu) → analgesia, n+v, bradycardia, resp depression, miosis, inhibition of gut motility, pruritus, endogenous agonists are b-endorphins
• κ (kappa) → analgesia, sedation, dysphoria, diuresis, endogenous agonists are dynorphins
• δ (delta) → analgesia, endogenous agonists are enkephalins

Question 14

What are features of morphine?

Answer 14

• Gold standard against which all new analgesics compared
• Least lipid-soluble opioid in common use
• Metabolised in liver, excreted by kidney
• Metabolite morphine-6-flucuronide is more potent than morphine
• Accumulation can occur after prolonged use in pts w/ impaired renal fxn
• Dose ranges and dose intervals vary according to route of admin

Question 15

What are features of diamorphine?

Answer 15

• A prodrug (diacetylmorphine)
• Rapidly hydrolysed to 6-monoacetylmorphine and then morphine
• Much more lipid-soluble than morphine
• More rapid onset of action than morphine when given by epidural or IV

Question 16

What are features of fentanyl?

Answer 16

• Highly lipid-soluble synthetic opioid
• Short-acting because of rapid tissue uptake
• Suitable for transdermal administration
• Commonly administered IV, epidurally, intrathecally, buccally, or via nasal spray

Question 17

What are features of pethidine?

Answer 17

• Analgesic w/ anticholinergic + some LA activity
• Metabolised in liver, excreted in kidney
• Main metabolite is norpethidine (a potent analgesic)
• High blood conc → CNS excitation
• Pts with impaired renal fxn are at risk
• Can be used to treatpost-op shivering associated w/ volatile anaesthetic agents, and epidural + spinal anaesthesia

Question 18

What are features of codeine?

Answer 18

• Prodrug for morphine
• For mild-mod pain
• About 10% of dose is converted to morphine
• Metabolism ⇒ morphine requires CYP2D6 enzyme (part of cytochrome p450 system)
• 8-10% of caucasians lack this enzyme, obtaining little or no benefit

Question 19

What are features of tramadol?

Answer 19

• Synthetic, centrally acting opioid-like drug
• < 50% analgesic activity is at μ-receptor
• Inhibits noradrenaline + serotonin uptake
• Compared to other opioids → ↓tolerance + abuse, ↓resp depression, ↓constipation
• Main metabolite more potent, also depends on cytochrome p450 enzyme (same as codeine)

Question 20

All opioids are equianalgesic if adjustments are made for the dose + route of admin. Allowance should be made for long-term opioid therapy, incomplete cross-tolerance between opioids, differing half-lives and interpatient variability.

What are the equianalgesic dosages?

Answer 20

Question 21

Opioids have a similar spectrum of side-effects. There is considerable interpatient variability, and some patients may suffer from more side-effects with one particular drug compared to another.

What are side-effects of opioids?

Answer 21

• Resp depression → reduced RR, V_T and irregular rhythm
• Sedation
• Euphoria + Dysphoria
• Nausea + Vomiting
• Muscle rigidity
• Miosis
• Bradycardia
• Myocardiac depression
• Vasodilatation
• Delayed gastric emptying
• Constipation
• Pruritus

Question 22

What do opioid antagonists do?

Answer 22

• Act at all opioid receptors
• Naloxone most commonly used
• Possible to reverse side-effects such as respiratory depression, N+V, sedation
• Without antagonising the analgesic effects
• Naloxone effective for _~60 min

Question 23

What are routes of administration for opioids?

Answer 23

• Oral → limited due to first-pass metabolism, immediate-release oral opioids (moprhine syrup, oxycodone) for early management of acute pain, oral fentanyl should be restrictred to treating breakthrough pain in pts receiving opioid therapy for chronic cancer pain
• SC or IM (intermittent) → 4hrly PRN, titrate for each pt
• IV (intermittent) → adequate pain relief w/out XS drowsiness + resp depression, suitable for recovery wards. Eg. 1-3mg morphine or 20-60mcg of fentanyl every 5 min, until pt comfortable
• IV (continuus) → close obs + monitoring essential
• Intrathecal → good for day-case arthroscopic surgeries, or post-elective C section
• Intransal → v effective in children (>1yr), for breakthrough pain
• Transmucosal → fentanyl lollipops for children
• Transdermal → for lipid-soluble opioids

Question 24

What are recommended doses of transdermal fentanyl, based on morphine doses?

Answer 24

Question 25

What is **patient-controlled analgesia**?

Answer 25

* Pts administer **own** IV analgesia + titrate dose to own end-point of pan relief using small microprocessor-controlled pump * **Morphine** most common (more pruritus w/ morphine) * Others: fentanyl, pethidine, tramadol * Equipment malfunction rare * Operator error more common

Question 26

How do you manage **nausea + vomiting** with opioids?

Answer 26

* Add an **antiemetic** → ondansetron 4mg, cyclizine 50-100mg, haloperidol 2mg * Prescribe on a **regular** basis * Change the opioid

Question 27

How do you manage **breakthrough** pain?

Answer 27

* Add regular **NSAID** + **paracetamol** (if not contraindicated) * Increase **bolus** dose * Consider background infusion if severe

Question 28

How do you manage **respiratory depression**, with opioids?

Answer 28

* All opioids have **same** **potential** for resp depression * Relatively **uncommon** * Early indicator → increasing **sedation** * Opioid doses adjusted so **sedation score** remains **\<2** * Resp depression (RR \< 8) is reversed with IV **naloxone** (100-400 micrograms)

Question 29

For **epidural** analgesia, an indwelling epidural catheter is inserted used to provide continuous infusion of analgesic agents. Provide excellent analgesia. What are **benefits** of **epidural** **analgesia**?

Answer 29

* Gold standard for **major** surgery * Prevent postoperative **respiratory compromise** resulting from pain * **Post-operative** complications **reduced** → **MI, atelectasis, pulmonary infection, DVT, ileus, blood transfusion requirements** * Improved intestinal motility → permitted earlier feeding

Question 30

What are the **disadvantages** and **contraindications** for epidural analgesia?

Answer 30

* **No survival benefit** in high-risk pts * Confine pts to **bed** (esp if motor block present) * Indwelling urinary catheter → **infection** risk * Epidural **haematoma** * Contraindicated with patient refusal and untrained staff * Other contraindications → **sepsis**, **hypovolaemia**, **coagulation** disorders, **anticoagulants**

Question 31

What are **complications** of epidural analgesia?

Answer 31

Question 32

Extreme vigilance is needed for all pts who have epidural analgesia, because of the risk of **spinal infection**. What are the **clinical features** of spinal infection?

Answer 32

* **Back pain** * **Fever** * **Leucocytosis** * **↑ ESR** Epidural catheter should be removed _immediately_ + sent to lab for cultures, ***Staph aureus*** most common (90%). **MRI** w/ gadolinium is investigation of choice - **_scan early!_** Once onset of muscle weakness, only 20% of pts regain full function even after surgery.

Question 33

Quality of analgesia is better w/ peripheral nerve blocks, compared with opioids. Incidence of post-operative side-effects is reduced. What are examples of continuous **peripheral** **nerve** **blocks**?

Answer 33

* **Interscalene** * **Axillary** * **Femoral / fascia illiaca** * **Sciatic** Complications → bruising, haematoma, LA toxicity, peripheral nerve damage, infection, catheter kinking, catheter migration

Question 34

**Physical opioid dependence** is a physiological phenomenon characterised by a withdrawal rxn when the drug is withdrawn or antagonist administered. What are **symptoms** of opioid withdrawal?

Answer 34

* Yawning * Sweating + Anxiety * Rhinorrhoea + Lacrimation * Tachycardia, hypertension * Diarrhoea, nausea + vomiting * Abdo pain + cramps Symptoms peak 26-72hr after last dose

Question 35

What is **buprenorphine**?

Answer 35

* **Partial opioid agonist** * Used in treatment of **opioid addiction** * Dose → **8-32mg**

Question 36

What are features of **ketamine**?

Answer 36

* **NMDA receptor antagonist** in CNS + peripheral NS * Major _adjuvant_ **analgesic** in variety of settings * Major side effects uncommon * Insufficient evidence to recommend ketamine as routine perioperative analgesic