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Acute Pain - Management (3.2.14 - 3.2.24)

Updated: Mar 7, 2022




3.2.14 - Compare and contrast the evidence for efficacy and adverse effects in the

management of acute pain with:


Remember - the target is a reduction of pain intensity of 30-35% that has been rated as clinically meaningful


Opioids

Oxycodone 15 mg = NNT = 4.6

Morphine IM = NNT = 2.9


Paracetamol

MOA - ?? - Serotinergic effects, cannabinoid effects, COX2 effects ?

Bioavailability high (60-90%)


Efficacy for acute pain - Paracetamol 500 mg NNT 3.5


Non-steroidal anti-inflammatory drugs

Diclofenac 100 mg - Efficacy NNT - 2.3

Ibuprofen 200 mg - Efficacy NNT - 2.1

Celecoxib 400 mg - Efficacy NNT - 2.6


Tramadol 150 mg - NNT = 2.9


Tapentadol - Could not find an NNT for acute pain

Lower rates of doctor shopping

Reduced GI adverse effects

Unlikely to get serotonin syndrome

Mu load approximately 40% (compared to 100% for typical opioid)

Very very rare in drug overdose


Gabapentin 250 mg - NNT = 11

 

3.2.15 - Critically discuss the evidence-based for indications, efficacy and adverse

effects of the following drugs in the management of acute pain:


NMDA-receptor antagonists

  • MOA - Ionotropic receptors block glutaminergic neurotransmission. Moderates central sensitisation

  • Reduces opioids, pain intensity and postoperative N&V - Level 1

  • Reduces risk of chronic post surgical pain - Level 1

  • Reduced OIH and tolerance associated with remifentanil - Level 1

  • Useful in neuropathic pain following spinal cord injury - Level 1

  • Reduces post operative pain and opioid requirement in opioid-tolerant patients - Level 2


Anticonvulsants

  • Perioperative gabapentinoids reduce postoperative pain and opioid requirements (lvl Q)

  • Reduce postoperative nausea and vomiting and pruritis (S)

  • Increased risk of sedation and visual disturbance


Antidepressants

  • Minimal role acutely


Alpha-2 adrenergic agonists

  • Evidence for their use in opioid-withdrawal symptoms

  • Perioperative use does NOT reduce pain intensity but reduces opioid consumption and postoperative N&V (Level 1)

  • Clonidine can exten effects of opioid when used neuraxially (level 1)


Inhalational agents

  • Some small benefit shown in labour vs placebo (level 1)

  • Evidence of benefit in other procedures and acute pain settings show minimal improvement

  • Oxidisese Vitamin B12 preventing it from acting as a coenzyme in methionine synthetase

  • Some concerns regarding bone marrow suppression effects

Calcitonin

  • Salmon calcitonin has a role in improving mobilisation following osteoporosis-related vertebral compression fractures (level 1)

  • Reduces acute (but NOT chronic) phantom limb pain (level 2)


Corticosteroids

  • Increases blood glucose in diabetics

  • Does NOT increase risk of infection

  • Dexamethasone perioperatively reduced opioid requirement and also PONV, fatigue and improves quality of recovery (level 1) (Preop is better than later)

  • No increased risk of infections, anastomotic leak, or postoperative haemorrhage (Level 1)

  • Long term data is unclear

Regional corticosteroids

  • Addition of corticosteroids to block prolongs effecgt and may improve analgesia and PONV (level 1)

  • Epidural steroid prolongs duration of block, improves analgesia and reduces PONV (level 1)

  • Acute radicular pain - lumbar epidural is effective for short-term relief (level 1)

  • Intraarticular steroids with local anaesthetic or opioids reduces pain, analgesic consumption, and duration of immobilisation (level 2)

  • Repeat epidural injections are associated with reduced bone mineral density and increased risk of vertebral fractures

Bisphosphonates

  • Reduce pain in CRPS type 1 in early phase of disease (level 1)

  • Pamidronate has been snown to reduce pain with osteoporotic vertebral compression fractures (level 2)

Systemic lignocaine

  • Perioperative IV lignocaine reduces pain and opioid requirements to a limited extent (Level 1)

  • It reduces nausea, but NOT vomiting, incidence, and duration of ileus, and hospital stay duration (level 1)

  • Perioperative lignocaine has effects beyond its half-life (level 1)

  • Perioperative lignocaine reduces chronic post surgical pain at 3 mths vs placebo (level 1)


Cannabis

  • Significant adverse effecst of dizziness, cognitive changes and psychiatric symptoms limit its use acutely (level 1 cochrane)

  • No evidence for its use in acute pain management (level 1 cochrane)

  • Possibly evidence for neuropathic pain in AIDS

  • Possibly evidence for pain and spasticity with MS and HIV

  • Smoked Cannabis increases risk of ACS and chronic cardiovascular disease (level 1)

 


3.2.16 - Assess and manage all adverse effects related to pharmacological therapies

in acute pain management, including but not limited to:


Opioid-induced ventilatory impairment (OIVI) and excessive sedation

  1. Term covers the key factors in ventilatory impairment e.g.

  2. Decreased CO2 responsiveness

  3. The elevated partial pressure of CO2 in arterial blood

  4. Depressed consciousness with subsequent upper airway obstruction with lower airway motor tone reduction

Risk factors

  • Older age

  • Female gender

  • Sleep-disordered breathing

  • Obesity

  • Renal impairment

  • Pulmonary disease

  • Cardiovascular disease

  • Diabetes

  • Hypertension

  • Neuro diseases

  • Concomitant sedatives

  • Multiple routes of opioid admin

Contributing factors

  • Administration of sedatives

  • Administration of opioids by multiple routes

  • Continuous infusion of opioids

  • Multiple prescribes

Monitoring

  • Respiratory rate-limited value

  • Sedation score is better

Management

Sedation is nearly always the first significant sign


Sedation score: (aim for less than 2) (10 secs)

  • 0 Wide awake

  • 1 Easy to rouse

  • 2 Easy to rouse but doesn’t stay awake

  • 3 Difficult to rouse

When NOT to use naloxone

  • Somnolent but easily rousable patients

  • If peak of opioid concentration has passed

  • Severity of respiratory compromise is not severe

Naloxone use

Small bolus doses 0.4mg (in 1 Ml) with 9 mls of NS = 10 mLs

0.04mg/mL is then the dose - and 1 - 2ml given every 45 mins is often sufficienct


Nausea and vomiting (Stimulation of chemoreceptor trigger zone (CTZ))

  • Consider changing to another opioid

  • Use opioid-sparing agents

  • 5Ht3 Agents can be used but consider secondary constipation (E.g. Ondansetron)

  • Dopamine receptor antagonists (haloperidol and droperidol, metoclopramide (thought to be less efficacious at 10 mg dosing))

  • Dexamethasone can be used but its mechanism remains unclear

Opioid-induced pruritus

  • Does not always require treatment

  • Simple measures such as avoiding itchy clothing and heat can help

  • Naloxone, naltrexone, droperidol, and ondansetron have been shown to be helpful

  • Pregabalin can also be used

  • Histamines seem to play little role in opioid-induced pruritis

Constipation (Opioid-induced GI dysfunction)

  • There is no evidence suggesting treatment with one laxative agent over another (Cochrane)

  • Sennakot may be cheaper than lactulose

  • Probiotics may be helpful

  • Enema may be required in prolonged constipation

Opioid-induced cognitive dysfunction

 

3.2.17 - Describe the complications that may be associated with neuraxial analgesia

and other regional analgesia (including secondary to needle/catheter insertion

and drug administration) and how these may be mitigated and managed.


Contraindications to Neuraxial block

  • Local or systemic infection

  • CNS disease e.g. MS (may exacerbate disease)

  • Hypovolemia (therapies often block sympathetic drive)

  • Coagulation disorders (risk of epidural haematoma)

  • Presence of dural puncture (drug can gain direct access to CSF)

Complications of local anaesthetics

  • Respiratory problems with dense diaphragmatic block if C3-5 involved

  • Hypotension - Sympathetic block causing reducing resting tone (Particularly if epidural block is dense and above T4)

  • Sedation (though usually at excessive doses)

  • Motor blockade (lower doses used to try and preferentially affect small afferent fibres and not the larger motor fibres)

  • Urinary retention

  • GI (actually INCREASES gastric motility - which can be useful)

Complications of epidural analgesia


Insertion site issues

  • Postdural puncture headache

  • Nerve or spinal cord injury

  • Epidural haematoma

  • Epidural abscess/meningitis

  • Catheter migration

Equipment issues

  • Catheter/filter - Leakage/disconnection

  • Infusion pumps - Malfunction, incorrect program, gravity flow


Epidural haematoma

Protocols should be in place regarding relationship to anticoagulants

High index of suspicion always considered


Epidural infection

MRI is best

Similar symptoms to haematoma but much slower onset and systemic infection symptoms/signs

Treatment depends on site

Antibiotics are critical


Epidural on blood thinners

Warfarin - evidence is unclear - ideally INR <1.5 when removing catheter

IV Heparin - Delay starting heparin til >1 hr after, and only remove after heparin has been stopped for 4-6 hrs.

LMWH - placed at least 12 hrs after prophylatic dose of heparin and 24 hrs after a high therapeutic dose. Removed only after 12 hrs after dose and not given any more for at least 4 hrs.

DOACs - Dabigatran (5 days cessation before), Rivaroxaban (3 days), Apixaban (3 days)

NSAIDs - not been shown to be a risk factor for epidural haematoma

Clopidogrel - 5-7 days cessation

 

Dural puncture headache

  • Bed rest for patient comfort

  • Hydration

  • Analgesia +/- caffeine +/- Sphenopalatine block

  • Blood patch if required

Spinal injury - full neuro assessment


Epidural space infection or haematoma - MRI - Surgical decompression

(Onset can be sudden for haematoma. Muscle weakness is commonly the first sign. Motor, sensory, bladder or bowel can then progress). Can have sharp or nerve root pain. Can present as a patchy blockade and is slow to resolve.

Cease the infusion but do NOT pull out the catheter.

Urgent MRI and surgical review.


Epidural catheter migration - Remove. Treat drug effects

Leaking - can continue if not infection concerns


Managing side effects

N&V - Antiemetics, consider other causes e.g. ileus.

Pruritis - Small doses of naloxone, consider ondansetron, omit opioids from epidural

Sedation/Resp depression - As elsewhere (below) on this page

Urinary retention - Consider small doses of IV naloxone and/or catheterise

Hypotension - IV fluids +/- vasopressors

Numbness/Weakness - Check for catheter migration into CSF, cease infusion and restart when resolution of sensory/motor blockade, reduce local anaesthetic strength, consider MRI if indicated


 

3.2.18 - Outline a plan to transition patients to oral analgesia from patient-controlled

analgesia (PCA), epidural or regional analgesia for the management of acute

pain.


Benefits of PCA

  1. Allows patient to determine when and how much analgesic medication they receive

  2. Allows small regular boluses of opioids to be given 'as needed'

  3. Helps keep patients within the 'analgesic corridor'

  4. Easy flexibility to control dose and duration

  5. Can be calculated over 24 hr period to allow conversion to oral requirements

  6. May reduce nursing staff workload though this is not a primary reason to perform a clinical decision

Equipment

Modes

  • PCA demand mode

  • Continuous

  • Demand and continuous

Safety

  • There is an inherent safety of PCA in that as long as the machine is PCA only, if patient becomes excessively sedated, they can no longer make further opioid demands

  • Errors can occur through programming - this is reduced with 'smart pumps'

  • Antireflux valves stop back flow of opioid into the primary IV line

  • Antisiphon valves prevent emptying by gravity

  • Appropriate patient selection is required

  • Appropriate patient education given

Patient selection

  • Happy to take control of their pain relief

  • Wants to use PCA

  • Can understand ow to use it appropriately


Programming

  • Loading dose - can be done by machine but better through external means

  • Bolus dose (remember to reduce by half if >70 yo)

  1. Morphine 1 mg

  2. Oxycodone 1 mg

  3. Fentanyl 20 mcg

  • Concentration

  • Dose duration (often not adjustable)

  • Lockout interval - 5-10 mins standard

  • Background infusion - Rare to use particularly in opioid-naive patients

  • Hourly limits (no point... evidence shows unhelpful)

What to do if 'inadequate' analgesia provided


Reassess the patient

  • New cause for pain? Complications?

  • Poorly responsive to opioids?

  • Treat opioid-related side effects

  • Consider patient may not be opioid naive

  • Ensure patient understands the principles of PCA

Check other components of multimodal analgesia have been given

Give additional opioid to 'reload' patient

If patient under-pressing - suggest re-education

Can consider bolus dose increase if required


Complications of PCA


  • N&V - Consider antiemetics or change bolus dose, opioid type

  • Pruritis - Consider another type of opioid (antihistamines not overly helpful)

  • Sedated

  1. If SS = 2 halve the bolus dose and cease background infusion

  2. If SS = 2 and RR <7 - halve dose, increase supervision and consider naloxone

  3. If SS = 3 - attempt to wake patient. If not, give 40-100 mcg IV of naloxone every 2 minutes PRN. Cease PCA until the patient is more awake. Restart at half the dose


 

3.2.19 - Discuss the use of ultrasound imaging in the performance of regional

analgesic techniques


Benefits

  • Faster block performance

  • Fewer needle passes

  • Greater success of blockade

  • Reduced dose of anaesthetic

  • Reduced risk of nerve injury

 

3.2.20 - For patients receiving:

• PCA

• Epidural analgesia (including patient-controlled epidural analgesia)

• Intrathecal analgesia

• Plexus analgesia (including patient-controlled regional analgesia)

• Major peripheral nerve analgesia

• Paravertebral analgesia

Outline:

1. Risk-benefit analysis

2. Monitoring of efficacy

3. Safety considerations

 

3.2.21 - Discuss issues specific to the management of acute pain in patients with:


Spinal cord injury

  • No clear evidence to guide choices

  • At level pain occurs at the level and within 3 dermatomes below

  • Nociceptive pain treatment is the same as any other however being aware of increased risk of GI complications including gastric ulceration and their masking from lack of awareness

  • Baclofen is preferred to diazepam for acute spasm pain

  • Very little evidence for neuropathic pain in SCI

  • Can consider: Duloxetine, amitriptyline, gabapentinoids, tramadol, ketamine and lidocaine

  • Gastric stasis may affect oral absorption of medications


Burns - Acute (Be aware repleting magnesium is useful (NMDA)

  • IV opioids are commonly required

  • SC or IM can be used

  • Concerns about gastric emptying after major burns precludes oral medication

  • Paracetamol given if no contraindication

  • NSAIDs may not be appropriate particularly if renal risks/concerns and GI concerns

  • Coxibs can be used but again GI concerns should be considered

  • PCA for opioids can be used Morphine 1 mg with 5 mins lockout

  • Antihyperalgesia and antineuropathic agents are important to consider given sensitisation and neuropathic pain

  • Ketamine can be useful

  • Pregabalin/Gabapentin can help background and procedural pain

  • (These are also useful in the setting of itch)

Burns - Procedural

Oral options

  • Lorazapam 1-2 mg

  • Morphine 10 mg SCut


PCA options

  • Ketamine 10mg/ml and midazolam 0.5 mg/ml PCA 5 mins lockout

  • Fentanyl PCA

  • Slow-release opioid - particularly an atypical or methadone, can be useful for ongoing care

Burns itch

  • Pregabalin 75 mg BD

  • Clonidine 25 mcg TDS

  • (Stop smoking)

Burns - Chronic pointers (as an extra...)

  • NMDA is activated after a period of time of persistent pain stimulation

  • This is particularly common in Burns as sensitisation occurs in almost 100%

  • Remember to ensure patients are magnesium replete to reduce NMDA receptor activation

  • Catabolism lasts for some time - make sure nutrients and vitamins are replaced

  • PTSD is the key for many - ensure you ask the 4 question PTSD screen

PTSD screening questions in burns - 5 questions (3 or more YES = likely PTSD)

Have you gone through a traumatic event ?

  1. Have you had nightmares or thought about event when you don't want to?

  2. Tried hard not to think about it or avoided things that remind you of it?

  3. Were constantly on guard, watchful or easily startled?

  4. Felt numb or detached from activities or your surroundings?

  5. Felt guilty or unable to stop blaming yourself or others for the event?


Trauma

Rib fractures

  • Multi-modal analgesia should be the aim

  • Important to not just maximise opioids to cover incident pain as the opioid dose may be too high than when at rest leading to sedation and lack of movement

  • Epidural and regional options are helpful but no large studies showing reduced complications or mortality

  • Erector spinae blocks may be preferred over epidural and paravertebral blocks in setting of risk of hypotension with epidural local anaesthetics in patients with possibly unstable haemodynamics

  • Serratus anterior blocks do not cover posterior rib fractures well

  • Anticoagulants may not be an absolute contraindication to superficial, compressible block sites

Crush injuries and ischaemic limbs with a risk of compartment

syndrome

  • Spinal cord stimulation has some evidence in chronic ischaemic tissue

  • Surgical management takes priority for appropriate pain relief - treating the cause

  • E.g. Fasciotomy

  • No other specific factors - opioids and/or ketamine

  • Consider sequelae such as liver/renal damage and fluid issues

Post amputation

  • Non-pharmacological - Rigid removable dressing to reduce oedema and wound protection

  • Regional anaesthesia as able.

  • Ketamine, opioids, tramadol, gabapentinoids, amitriptyline

Acute phantom limb pain - Calcitonin (within 7 days), epidural benefits. -possibly regional benefits also. The rest of the evidence is somewhat low or conflicting.


Patients with obstructive sleep apnoea

  • OSA has increased sensitivity to opioid analgesia

  • Possibly due to upregulation of opioid receptors secondary to recurrent hypoxia and increased sensitivity to pain

  • CPAP treatment reduces pain severity in patients with OSA

  • OSA status did not correlate with increased opioid use

  • Morphine causes OSA worsening of severe hypoxaemia

  • Risk factor for OIVI

  • Buprenorphine in the acute setting was not shown to have a respiratory ceiling effect

  • Generally, maximise non-opioid therapies and regional techniques to limit opioid use

 

Patients who are pregnant or breast-feeding

  • The highest risk times are in organogenesis (week 4 to 10) and just before birth

  • Non-pharmacological should be maximised before pharmacological

  • Almost all drugs will cross the placenta

  • Lack of known risk for short-term exposure such as in acute pain settings

  • Studies are also significantly impacted by indication, recall bias and lack of an active comparator

  • NB: Grading is not necessarily indicative of risk of harm - but at times is more an indicator of the strength of evidence

  • NB: Neither methadone or buprenorphine have been shown to be clearly teratogenic. Buprenorphine may be preferable for resp protection. Bup also has less risk of preterm birth, higher birth weight, larger head, and less severe Neonatal abstinence syndrome (NAS).

Paracetamol - A

NSAIDs

  • B (Celecoxib is B3) - should definitely not be used after 32 weeks - the risk of premature closure of ductus arteriosus. Uncertain about the first trimester - possible confounder in studies as NSAIDs often taken in miscarriage

Opioids

  • Possibly increased risk of congenital malformations - orofacial cleft, ventricular and atrial septal defects, club foot

  • Neonatal abstinence syndrome particularly in the last 3 mths of pregnancy

  • Long term outcomes are uncertain as studies have significant confounders

  • Neonatal hypoxaemia is more common

  • Possibly behavioural long term complications however again this result may be more confounded by psychosocial comorbidities

Alpha-2-delta ligands - Gabapentin is B1, Pregablin is B3

Evidence is scant.

 

Patients with renal impairment (including those on dialysis)


Dialysis

Removes molecules that have a low molecular weight, greater water solubility, and lower volume of distribution

Drugs with higher protein binding and lower-efficiency dialysis techniques will reduce removal.


Medications you can use normally

  • Alfentanil/Sufentanil

  • Buprenorphine

  • Fentanyl

  • Ketamine

  • Paracetamol

  • Oxycodone

Medications for dose adjustment

  • Amitriptyline

  • Bupivacaine

  • Lignocaine

  • Clonidine

  • Gabapentin

  • Pregabalin

  • Codeine

  • Hydromorphone

  • Methadone

  • Morphine

  • Tramadol

  • Tapentadol

Should not be used

  • NSAIDS (all)

 

Opioid-tolerant patients / Patients with chronic pain


Methadone may be split into two or three divided doses to give a more stable background analgesia

Methadone can be given parenterally but dosing will need to be adjusted

Changes should only occur with liaison with the authorised prescriber or an addiction medicine specialist


Buprenorphine can be split into multiple doses throughout the day for background analgesia while additional opioid is being given

Concerns about buprenorphine blocking the analgesic effects of pure opioid agonists do not seem to occur in clinical practice

Continuing the buprenorphine tends to reduce the amount of the alternative opioid required


Maximise non-opioid agents and consider ketamine

 

Patients with past or present substance abuse disorder

They need to be reassured about the importance of treating pain appropriately and address their anxiety and concerns about re-instigating dependence and addiction behaviours


OSA patients

The key is appropriate monitoring as should be the case in all settings

Nasal oxygen has been shown to be as effective as CPAP and could be considered in situations of concern

 

3.2.22 - Discuss the management of patients who are taking anticoagulants or antiplatelet agents and who have or are about to receive catheters in situ for

neuraxial or major peripheral nerve analgesia.


Warfarin - evidence is unclear - ideally INR <1.5 when removing catheter

IV Heparin - Delay starting heparin til >1 hr after, and only remove after heparin has been stopped for 4-6 hrs.

LMWH - placed at least 12 hrs after prophylatic dose of heparin and 24 hrs after a high therapeutic dose. Removed only after 12 hrs after dose and not given any more for at least 4 hrs.

DOACs - Dabigatran (5 days cessation before), Rivaroxaban (3 days), Apixaban (3 days)

NSAIDs - not been shown to be a risk factor for epidural haematoma

Clopidogrel - 5-7 days cessation

 

3.2.23 - Discuss the potential complications specific to the concurrent use of

anticoagulant and antiplatelet agents in patients undergoing central neuraxial

and major regional nerve blockade


As discussed above - Epidural haematoma

 

3.2.24 - Discuss the management of patients undergoing repeated painful

procedures.


See discussion on burns management as an example

 


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