Acute pain management

Introduction

• Primary presenting complaint in 75-80% of ED patients
• Oligoanalgesia more likely in
  • The aged
  • The very young
  • Cognitively impaired
  • Ethnic minorities
• Should treat pain and underlying cause simultaneously
• Mechanistic approach is always preferred i.e. targeting cause of pain vs. masking pain with opioids

Pathophysiology

• Pain
  • The physiological response to noxious stimulus
• Suffering
  • The expression of pain modified by complex cognitive, behavioural, cultural dimensions
• Somatic pain
  • Peripheral nervous system (nociceptors, C fibres, A-delta fibres and free nerve endings)
  • Initiate sensation of somatic pain by responding to noxious stimulus and sending neuronal discharge to dorsal root ganglion of spinal cord
  • Transmission up to hypothalamus, thamalic nuclei, limbic system and RAS
• Visceral pain pathways differ to this in integration and poor localisation

Opioid receptors

• Spinal cord, GI tract and brain receptors
• Delta, kappa, mu and nociceptin
• Physiological function is to interact with endogenous dysnorphins, enkephalins, endomorphins, endorphins and nociceptin
• Mu-1: Supraspinal analgesia
• Mu-2: Euphoria, miosis, respiratory depression and reduced GI motility
• Delta – Analgesia (<mu-1) and antidepressant effect
• Kappa – Dysphoria, dissociation, delirium and diuresis (inhibits ADH release)

Evaluation

• Pain scales are primarily for research purposes and often just asking if patient requires more analgesia is as effective and more practical
• Pain scales can be used to quantitate severity and guide further therapy and are a reference point based on past personal experience rather than an absolute value
• The elderly may experience a decrease in the minimum clinically signficant noticeable difference in acute pain over time when using numerical scales
• Trauma patients and those with acute intoxication do not perform as reliably on pain scales
• Women are more likely to express pain and actively seek treatment
  • Yet there is a tendency to underestimate and undertreat pain in women
• Visual analog scale is preferred for language or cross-cultural difficulties in assessment

Pain scales

• Adjective rating scale
  • No pain to worst possible pain
• Pieces of hurt (3-6yo)
• FACES pain scale (4+)
• Visual analogue scale (6+)
  • Mark along 10cm linear scale from no pain to worst
  • Difference of 13mm is the minimum clinically significant change noticeable by patients
  • Difference of 30mm is the minimum acceptable change for pain control
• Numeric rating scale (8+)
  • 0-10 with descriptors. Not as discriminating as VAS
  • Recommended if over 8yo
  • Proportional change in pain score is probably more valuable than absolute change
• 5-point global scale
  • 0-4 (worst). Change of 1 point is a large change and so not as sensitive to small changes
• Verbal quantitative scale
  • 0-10 without descriptors

Pain scales

• Graded scoring (mild, moderate, severe) more effective if:
  • Distracting injury
  • Altered mental state
  • Intellectual disability
  • Communication difficulties
• FLACC score
  • Used in pre-verbal children
  • 5 elements: Facial expression, leg movement, movement, crying, consolability
  • Total score 0-10
  • Validated in children with cognitive impairment but not for procedures

Non-pharmacological

• Explanation of procedure and showing on doll
• Caregivers on side and relieve their anxiety first
• Caregivers providing assistance rather than spectators
• Behaviours that do NOT help
  • Reassuring ‘you’ll be okay’
  • Apologising
  • Bargaining
  • Criticising ‘you’re being a baby’
  • Giving child control over when to start procedure

Pharmacological pain treatment

• Need appropriate agent for intensity, time to onset, ease of administration, safety and efficacy
• Tiered approach unnecessarily subjects patients to more prolonged suffering so should try and match intensity with agent
• NSAID
  • Mild/moderate somatic pain plus severe colicky pain
  • Use caution in elderly, renal, GI and haematological disorders
  • Parenteral no more effective and more costly
  • Rectal route no more effective either or any less complications
• Opioids
  • PO: Effective if adequately dosed. Variable absorption and slower onset
  • IM: Painful injections and unreliable absorption
  • IV: Easily titrated but need IV access
• Local anaesthetics
  • Infiltration has limited duration of action
  • Nerve block can be opioid sparing but may be technically difficult

Paracetamol

• No evidence of hypotension following IV administration
• Dose limit of 3g if compensated chronic hepatic disease
• CI if uncompensated chronic hepatic disease
• CI if acute hepatic disease

NSAID’s

• Decrease prostanoid and arachidonic acid-mediated inflammatory peptides
• Do not actually inhibit inflammation per-se but provide symptomatic relief
• Inhibition of COX-2 in spinal cord decreases excitability of dorsal horn neurons
• Indomethacin may have more uricosuric action and is agent of choice in gout
• Opioid dose-sparing effect
• Aspirin and traditional NSAID’s are non-specific COX inhibitors that reduce both PGI2 and thromboxane A2
• PGI2
  • Predominant COX-2 product in endothelium that inhibits platelet aggregation, causes vasodilation and prevents proliferation of vascular smooth muscle cells (hence COX-2 inhibitors increase CVD risk)
• Thromboxane A2
  • Predominant COX-1 product of platelets that causes platelet aggregation, vasoconstriction and vascular proliferation
• Adverse effects (6x paracetamol)
  • Platelet dysfunction, GI irritation/bleeding, nephropathy, headaches and dizziness
  • All increase risk of cardiac death in patients with IHD
    • COX-2 specific agents have highest risk
  • Renal impairment more common in elderly or volume deplete, pre-existing renal/cardiac disease or are on loop diuretics and is due to inhibition of vasodilatory PGE2 (COX-1 and COX-2 inhibition effect)
  • Bronchospasm
  • Do not appear to inhibit wound healing despite previous concerns

NSAID’S

• Ibuprofen 400-800mg q4-6h; max 2400mg per day
• Naproxen 250-500mg q8-12h; max 1250mg per day
• Indomethacin 25-50mg q8h; max 200mg per day
• Ketorolac
  • Single dose therapy: 60mg IM or 30mg IV (half dose if age > 65 or <50kg)
  • Multi-dose therapy: 30mg IV/IM q6h (half dose if age >65 or <50kg)
  • 10mg PO q4-6h (max 40mg per day and 3 days IV/5 days PO)
  • High risk of GI bleeding than ibuprofen

Opioid analgesics

• Opiate = Structurally related to natural alkaloids found in opium
• Opioid = Any compound with pharmacological activity similar to an opiate regardless of structure
• Variation in response to opioids depends on:
  • Age
  • Initial pain severity
  • Previous or chronic exposure to opioids
  • NOT WEIGHT OR GENDER
• Allergy is uncommon and minimal cross-reactivity (aside from among piperidines e.g. fentanyl, alfentanil, sufentanil)
• No compelling evidence than one agent is better than another

Opioids

• Morphine
  • Direct histamine release prevented by slow administration and dilution
  • Hepatically metabolised to morphine-6-glucuronide (active)
    • Half-life of morphine-6-glucuronide is 2.6-5.7 hours
    • Reduced renal clearance of the metabolite causes prolonged activity in the elderly and renal patients
  • CI in severe haemodynamic instability or renal impairment
  • Opioid sensitivity directly related to age (vs. weight)
  • 5mg in adults, 2.5mg if over 70yo, 0.1mg/kg for children
• Fentanyl
  • More rapid onset and fewer haemodynamic effects than morphine
  • Shorter duration of action due to rapid redistribution
  • 40-80mcg in adults, 1.5mcg/kg IV in children
  • IN dose 1.5-3mcg/kg (repeat 1.5mcg/kg q5min for effect)
  • Lasts 40-60 minutes with peak at 4-6 minutes and onset within 2 minutes

Opioid analgesics

• Meperidine/Pethidine
  • Not recommended as often under-dosed, interacts with other drugs to cause serotonin syndrome and parent drug is metabolised to norpethidine (neuroexcitatory/seizure and long half-life 24-48 hours)
  • Can produce toxicity in elderly and those with renal failure
• Codeine
  • Not a reliable analgesic and produces more nausea, vomiting and dysphoria than other opioids
  • Requires conversion to active metabolites codeine-6-glucuronide and morphine
  • Slow metabolisers
    • 10% of population is deficient in these enzymes with inadequate analgesic response
    • 7% of Caucasians and up to 20% of Africans
  • Ultrametabolisers (at risk of opioid toxicity)
    • 1-4% of Western Europeans
    • 7-10% of southern Europeans
    • 5-30% of Africans
    • 20% of Arabs
  • Case reports of infant deaths of mothers breastfeeding on codeine and hypermetabolising
  • Standard PO dose of 30-60mg produces minimal analgesic effect above that of paracetamol or NSAID’s

Opioid analgesics

• Tramadol
  • Binds at mu-receptors (low affinity) and weakly inhibits noradrenaline and serotonin reuptake leading to central opioid analgesic effect
  • Less effective than paracetamol + codeine
  • Significant euphoric effects help establish dependency
  • Side effects include dizziness, nausea, constipation and headache
    • Also hypoglycaemia in overdose (usually just need 10% glucose infusion for <24 hours)
    • Hyponatraemia, serotonin toxicity
  • Can induce serotonin syndrome, agitation and seizures (CI if known seizure disorder)
  • Produces false-positive phencyclidine UDS
• Pruritis, urinary retention, confusion and respiratory depression are more common with IV, transmucosal and epidural administration than PO
• Adjuncts
  • No evidence for pre-treatment with antiemetics to enhance analgesic effect, reduce amount of opioid or prevent side effects
  • Symptomatic therapy may be required however

Opioids

• Methadone
  • Half-life 15-60 hours
  • Prolonged QT in overdose
  • Potent respiratory depressant at 6-8 hours after administration

Opioid analgesics

• Transdermal formulations are not useful for acute pain management
• If patients have these on, best to remove on arrival to ED and titrate acute opioid dosing to effect 
  • Prevents combinatorial complications
• Opioid agonists/antagonists
  • Claimed to produce a ceiling on respiratory depression
  • Not clear if ceiling on analgesia also exists
  • Should be used with extreme caution in those with opioid addiction as can lead to withdrawal symptoms

Equipotent opioids

Ketamine

• Phencyclidine derivative analgesia and dissociative anaesthesia
• Minimal respiratory supression
• Low-dose (subdissociative) infusions are effective in combination with opioids for severe pain
  • 0.15-0.4mg/kg IV over 10 minutes followed by infusion 0.1-0.2mg/kg/hr (2-10mg/hr) if required
• 0.3mg/kg provides equivalent analgesia to 0.1mg/kg morphine
• Useful in trauma patients for opioid sparing and acute neuropathic pain
• Adverse effects
  • Hypersalivation
  • Re-emergence phenomena (typically if >1.5mg/kg IV induction dose used)

Nitrous oxide

• Fast-onset, short-acting analgesic and sedative
• Nausea and vomiting side effects
• Contraindicated if altered mental status, head injury, suspected pneumothorax or perforated abdominal viscous
• Severe pulmonary disease may alter respiratory elimination of drug

Neuropathic pain

• Long-acting opioids, cyclic antidepressants, SNRI and anticonvulsants are the most effective therapy for acute neuropathic pain
• Close primary care follow-up is crucial to allow ongoing titration of agents
• Amitryptilline/nortryptiline 0.1mg/kg PO nocte increased over 2-3 weeks
  • 0.5-2mg/kg per day is typical effective dose (max 150mg/day)
  • Chronic pain
• Carbamazepine 100mg BD; increased 100-200mg per day
  • 200-400mg BD (max 1200mg per day) is usual effective dose
  • Trigeminal neuralgia
• Duloxetine 30mg mane increased after 1 week
  • 60mg mane (max 120mg per day) is usual effective dose
  • Especially useful for diabetic neuropathy
• Gabapentin 300mg mane increased by up to 300mg per day
  • 300-1200mg TDS per day (maximum 3600mg per day) usual effective dose
• Pregabalin 50mg TDS increased over one week
  • 150mg BD to 100mg TDS per day (max 600mg per day) is usual effective dose

Topical medications

• Can provide pain relief with reduced systemic drug absorption and lower risk of adverse effects
• Topical NSAID’s are effective for acute soft tissue injuries and chronic joint pain from osteoarthritis
• Topical lignocaine effective for postherpetic neuralgia and diabetic neuropathy
• Topical capsaicin has variable benefits and seems to require regular use for prolonged pain relief
  • Single 60-min application of high-dose (8%) is effective for post-herpetic neuralgia but requires professional application and removal to prevent side effects
• Adverse effects
  • Local burning (capsaicin)
  • Menthol/methyl salicylate preparations in NSAID’s can also cause burns

Topical agents

• AnGel better than EMLA for venepuncture
• No agents aside from sucrose relieve pain of capillary sampling
• LMX4 probably as good as AnGel
• Sucrose 24% 0.25mL up to 1mL total for up to 2mo

Special populations

• Hypotension is infrequent and is usually due to histamine release and is short-acting
• Elderly
  • More than one source of pain often
  • At risk of drug-drug and drug-disease interactions
  • Opioid-naïve elderly patient suffer higher peak and longer duration of pain relief
  • More sensitive to sedation, respiratory depression and cognitive impairment
  • Half dose compared to younger patients
• Addiction and dependence
  • Dependence requires 4-6 weeks of daily dosing while addiction can occur after a single dose of heroin
  • Err on the side of acute pain control
  • Dependence and addiction occur in 1/3 of chronic opioid therapy
  • Unknown what the rate is for acute <2 weeks courses from ED
  • ED’s are NOT where most cases of opioid addiction/dependence arise but are seen as perpetuators
  • The Drug Abuse Screening Test may provide a more objective means of screening for addiction
  • In reality, distinguishing between oligoanalgesia and addiction requires repeated assessments over time and is almost impossible in the ED setting
• Renal impairment
  • Active opioid metabolites such as norpropoxyphene, norpethidine, morphine-6-glucuronide and dihydrocodeine are all renally excreted
  • Hydromorphone and fentanyl are preferred
• Hepatic dysfunction
  • Mild dysfunction has little effect on opioid metabolism
  • If severe dysfunction, titration with low doses minimises the risk of overdose
• Respiratory insufficiency
  • Particularly vulnerable to opioids and nitrous oxide
  • Careful monitoring is key
  • Ketamine may be a useful adjunct in this scenario
• Drug interactions
  • Anxiolytics/antipsychotics/TCA’s may synergistically cause respiratory depression/sedation

Specific situations

• Abdominal pain
  • Early IV opioids does not affect accuracy of evaluation, diagnosis or management
  • Reduction in pain does NOT indicate improvement in pathophysiology
• Migraine
  • Opioid use has lost favour as mechanistic agents are considered more effective
  • Promethazine, chlorpromazine and prochlorperazine are highly successful
    • Tempered by EPSE (up to 45%) and occasional intense dysphoria
  • Paracetamol, high-dose aspirin/NSAID’s and triptans also very useful
• Trauma
  • Judicious use of opioids is key
  • Fentanyl bolus then infusion may be the opioid of choice due to haemodynamic stability
  • Regional analgesia is encouraged
  • NSAID’s should not be used due to risk of excessive bleeding from platelet dysfunction, stress ulcers and potential for acute renal failure in volume deplete patient

Disposition

• Persistent pain after ED discharge is common
• Rarely are patients admitted just for pain relief
• Prescriptions for long-acting agents are usually avoided upon ED discharge but are useful for special patient groups e.g. cancer patients in whom short-acting agents are not effective
• Patients should be counselled to take regular doses or when pain first begins rather than waiting for peak
• Prescribe only a few days worth as if pain persists, need primary care follow-up
• If opioids prescribed to the elderly or the opioid-naïve, home observation by a responsible adult is crucial so that adverse effects are recognised
• Instruct to avoid making important decisions while medications and to avoid driving, operating machinery, working at heights and provide advice for constipation
• Educate about securing opioids and prescriptions as 85% of prescription opioid misuse by adolescents come from parents medication cabinet

Last Updated on August 30, 2024 by Andrew Crofton