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
Term covers the key factors in ventilatory impairment e.g.
Decreased CO2 responsiveness
The elevated partial pressure of CO2 in arterial blood
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
Allows patient to determine when and how much analgesic medication they receive
Allows small regular boluses of opioids to be given 'as needed'
Helps keep patients within the 'analgesic corridor'
Easy flexibility to control dose and duration
Can be calculated over 24 hr period to allow conversion to oral requirements
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)
Morphine 1 mg
Oxycodone 1 mg
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
If SS = 2 halve the bolus dose and cease background infusion
If SS = 2 and RR <7 - halve dose, increase supervision and consider naloxone
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 ?
Have you had nightmares or thought about event when you don't want to?
Tried hard not to think about it or avoided things that remind you of it?
Were constantly on guard, watchful or easily startled?
Felt numb or detached from activities or your surroundings?
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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