FRCA Notes

Rebound Pain Following Regional Anaesthesia

Resources

  • Rebound pain is an adverse effect of regional anaesthesia, most apparent after single-shot peripheral nerve blocks
  • It is common, with a reported incidence of 35 - 62% depending on the patient and surgical cohort examined

  • Rebound pain lacks a formal definition, but has several characteristic qualities

  • An acute, transient post-operative pain distinct from post-surgical pain
  • Ensues following dissipation of a peripheral nerve block
  • Frequently onsets at night, probably relating to the timing of the block and the expected duration of action
  • Pain at rest and on movement
  • Variable quality, typically 'burning' and sometimes hyperalgesic but not otherwise a neuropathic pain e.g. lacks allodynia
  • Duration of severest pain is for 2 - 6hrs but then abates
  • Clinically significant (in either its intensity or its impact on patient psychology, recovery or ADLs)
  • Typically necessitates an increase in analgesic consumption


Patient Factors Surgical Factors Anaesthetic Factors
Pre-operative pain, especially nocturnal pain Day-case surgery Denser sensory block e.g. brachial plexus or sciatic nerve block
Younger age (<60yrs) Severe post-operative pain e.g. bone surgery Single shot block
Female gender Upper limb surgery Lack of IV steroid use
Severe anxiety Foot/ankle surgery


Induced hyperalgesia

  • Hyperalgesia to heat stimuli occurs as a consequence of surgical trauma, even without regional anaesthesia
    • There is a spectrum of post-incisional primary hyperalgesia which can last up to 7 days post-operatively
    • Secondary hyperalgesia occurs in the uninjured tissue surrounding the site of trauma due to sensitisation by mediators such as CGRP, COX, PGEs, cytokines, interleukins and neurotrophins

  • It is unclear if rebound pain is:
    • Merely a consequence of unmasking the expected post-surgical nociceptive response in the absence of adequate analgesia
    • An exaggerated nociceptive response (partially) induced by the use of regional anaesthesia i.e. hyperalgesia
  • Some animal studies suggest peripheral nerve block can induce hyperalgesia, but how clinically significant these findings are in relation to human patients is unclear

Altered pain perception

  • Peripheral nerve blockade inhibits central sensitisation to pain by preventing upregulation of activity/responsiveness of neurons in the dorsal horns
  • However, it does not affect peripheral sensitisation, where the above effects will occur if systemic analgesia isn't taken
  • There is therefore a hyperalgesic area at the site of injury, from which nociceptive input becomes apparent as the block resolves, leading to rebound pain
  • The inhibition of central sensitisation, however, helps uncouple the relationship between rebound pain and chronic post-surgical pain

Pro-nociceptive effects of local anaesthetic

  • Local anaesthetics have themselves been shown to alter neuronal function in various animal and lab models, via:
    • Axonal demyelination and Wallerian degeneration, causing early-phase peripheral nerve injury
    • Disruption of mitochondrial membrane potentials, starting a cascade which involves cytochrome C release, caspase activation and cell apoptosis, ultimately causing neuro- and cyto-toxicity
    • Directly increase COX-2 gene expression and PGE2 production at the site of local anaesthetic infiltration
  • The relevance of these neurotoxic and pro-inflammatory effects are unclear; if there was structural neural tissue damage one would expect the pain to last longer than rebound pain does

  • The difference in pain trajectory for those who receive peripheral nerve blockade is accounted for by the termination of the nerve block, leading to an unmasking of the nociceptive response and a sudden increase in pain score

Peripheral nerve blockade vs. GA alone

  • Differences in peak pain score and opioid consumption between those who do or don't receive peripheral nerve block is variable
  • Multiple studies demonstrate those who receive peripheral nerve block have:
    • Lower cumulative opioid consumption for the first 12hrs (i.e. as block is still working)
    • Increased pain scores at 12-24hrs (i.e. rebound pain)
    • Similar pain scores after 24hrs
    • Lower or similar cumulative opioid consumption after 24-48hrs (i.e. after block offset)
    • Higher patient satisfaction at 24hrs

Why the difference?

  • Patients without nerve block have carefully titrated analgesia in PACU, which is maintained following discharge
  • Conversely, patients with nerve blocks receive little-to-no analgesia in PACU and are ready for discharge sooner, but may not have received systemic multi-modal analgesics by the time the block offsets

  • Cognitive factors
    • The 'contrast effect' bias
      • A stimulus is perceived as more intense when it is contrasted with a prior, lower intensity stimulus
      • Therefore the appearance of pain as the block wears off, after a period of relative comfort, may make rebound pain feel more intense
    • Placebo analgesia
      • Patients who are primed to expect good analgesia demonstrate decrease pain perception and cerebral activity in response to noxious stimulus
      • Patients who have peripheral nerve block are advised they can expect excellent post-operative analgesia
      • If they are not warned about rebound pain, their expectations may not be met and the disappointment can bias them towards reporting higher pain scores

Patient satisfaction

  • Use of regional anaesthesia increases patient satisfaction owing to:
    • Avoidance of GA
    • Effective post-operative analgesia + reduced opioid requirements
    • Reduced PONV
    • Superior recovery profile inc. shorter time to discharge
  • Despite rebound pain, patients still report high satisfaction and a preference for a similar technique in future
  • Even if patients describe increased pain scores after block resolution, satisfaction is still high and similar to those who didn't receive regional anaesthesia

Chronic post-surgical pain

  • No evidence to suggest rebound pain predisposes to chronic post-surgical pain
  • Regional anaesthesia may reduce the incidence of chronic post-surgical pain after some surgeries (e.g. breast surgery, caesarean section)

Healthcare costs

  • Rebound pain is implicated in higher rates of unanticipated healthcare resource utilisation compared to those who didn’t undergo regional anaesthesia
  • This finding is not consistent, with some studies showing lower rates of unplanned admissions, re-admissions or emergency department visits following peripheral nerve block

Pre-operative education/counselling

  • Educate patient on expected (finite) duration of analgesia and anticipated pain levels once it wears off
  • Patient should be informed to take analgesia regularly even during ongoing sensory blockade in anticipation of block offset
  • Use written or multimedia materials to help improved compliance and reduce uncertain

Adjuncts

  • Dexamethasone can reduce rebound pain, particularly if given perineurally (although this is an off-license use)
    • NNT 2.8
    • Variably efficacious; 23 - 42% received no preventative effect from dexamethasone with respect to rebound pain
    • Higher doses may be more efficacious for those at high risk of rebound pain

  • Other agents have been promising but not yet proven to reduce rebound pain:
    • Liposomal bupivacaine, although evidence does not demonstrate superiority over conventional local anaesthetics nor an effect on rebound pain
    • Buprenorphine, but only at doses >300μg

Multi-modal analgesic regimens

  • No consistent evidence that they reduce rebound pain
  • Should still be used routinely as part of good practice for perioperative pain management
  • Tend to include:
    • Paracetamol
    • NSAID
    • Oral opioid

Catheter techniques

  • Extending the duration of sensory blockade by inserting a nerve catheter and providing continuous local anaesthetic infusion:
    • Allows more time for healing/resolution of the inflammatory process
    • Leads to a less precipitous offset of sensory blockade
    • Preserves all the early benefit of a single shot block but largely abolishes rebound pain
    • Delays and attenuates the peak in pain score
  • Catheter-based techniques are, however, not without issues e.g. failure, more intense logistical set-up etc.