Hope you guys enjoyed the case. Here is the discussion and hopefully some useful take home concepts.
This case illustrated a number of key acute and chronic pain concepts that all GP anaesthetists should consider when anaesthetising an opioid tolerant chronic pain patient, namely opioid induced hyperalgesia (OIH), central sensitization (wind up) and pre-emptive analgesia.
In this case, our patient did not receive adequate perioperative analgesia or pre-emptive analgesia based on his chronic pain and opioid dependent background. He was left in distress for a period of time in which his pain became unmanageable (wind up) and remained so for 16 hours. It seemingly became non-responsive (OIH) to opioids but rotation to a new opioid, a background infusion of a NMDA antagonist and the use of a regional technique helped immensely.
Opioid induced Hyperalgesia
Opioid induced hyperalgesia is a paradoxical response to opioids in which patient receiving opioids have an enhanced response to painful stimuli resulting in hyperalgesia. This results from the upregulation of pronociceptive pathways in the central and peripheral nervous system.
Acute OIH occurs in various settings, most commonly post operatively in the opioid dependent patient but also in low dose and maintenance dose regimes. OIH is distinct from tolerance in that tolerance is reduced effectiveness of an opioid at a receptor over time.
NMDA receptor activation is important in the development of OIH. Antagonism of this receptor has been shown to reduce progression and improve post operative pain especially in opioid dependent patients (Wu + Macintyre + Huxtable et al).
Using an opioid PCA in opioid tolerant patients allows consumption and background requirements to be monitored. A basal infusion equivalent to the patient’s usual daily opioid use should be considered or given orally as tolerated.
Ketamine has been shown to reduce OIH in the post-operative setting (Vadivelu + Huxtable + Macintyre et al). There is evidence that subanaesthetic doses (0.1-0.2mg/kg) of ketamine provides excellent analgesia in opioid dependent patients and prevents opioid induced hyperalgesia in patients consuming high doses of opioid for postoperative relief. (Macintyre et al + Vadivelu et al).
Opioid rotation is the practice switching from one opioid to another to improve analgesia and reduce side effects (OIH in this case). This concept is based on the premise that individual opioids act differently on different opioid receptors and that tolerance between them is likely to be incomplete.
Practically this is preformed by using opioid equivalence charts and commencing with 50% of the equivalent dose and titrating up. (Huxtable)
Methadone together with its mu-receptor agonism has weak antagonistic properties on the NMDA receptor thereby playing a small role in OIH.
Wind up (central sensitization)
Post-operative pain results from peripheral nociception (primary hyperalgesia) from tissue injury and resultant central nociception (secondary hyperalgesia) in the spinal cord.
Any continuous barrage of activity to the spinal chord leads to central sensitization. Perioperatively this is related to periods of inadequate analgesia, extensive surgery or infection (Shipton).
As this central sensitization continues from the noxious stimuli, this maintains secondary hyperalgesia, amplifies post operative pain and contributes to chronic pain. Central sensitization will manifest clinically as hyperalgesia (increased pain sensitivity) and allodynia (pain in response to a previously non-painful stimulus) (Macintyre et al).
NMDA receptor activation plays a key role in central sensitization. Medications such as Gabapentin, Pregabalin and Ketamine have been found to improve post operative pain and thought to reduce the progression to chronic pain.
Using Ketamine at subanaesthetic doses (0.1-0.2mg/kg) antagonizes the NMDA receptor and produces an antihyperalgesic, antiallodynic and anti-tolerance effect. It is useful in pain associated with central sensitization such as severe acute pain and opioid resistant pain.
Pregabalin is a safe and well tolerated and helps to reduce perioperative opioid consumption. It has been shown to decrease the incidence in the progression to chronic pain. Gabapentin similarly has been shown to prevent chronic post surgical pain syndromes (Shipton).
Pre-emptive & Preventative Analgesia
Pre-emptive analgesia is treatment that is initiated before the surgical procedure in order to reduce peripheral and central sensitization. This in effect helps to reduce post operative pain and prevent chronic pain development (Dahl)
Preventive analgesia is simply the well thought out provision of analgesia within the postoperative period and persistence of treatment beyond the expected duration and aims to minimize central sensitisation (Macintyre et al)
Ketamine modulates central sensitization caused by incision and tissue damage and can be used perioperatively to antagonize this (Vadivelu).
Preoperative pregabalin is opioid sparing and improves post operative pain scores. It is a useful adjuvant and anti-hyperalgesic agent used in a multimodal regime.
Prevention of Withdrawal
Inadequate opioid supplementations in the post operative period can lead to withdrawal characterized by excitatory autonomic symptoms. The onset will depend on the individual opioid’s duration of action (Macintyre et al).
Opioid tolerant patients should firstly be identified preoperatively and continue their preadmission opioid regimes with appropriate route substitutions as clinically directed.
Heavily weighted non-opioid regimes should be used with caution as opioid tolerant patient due their risk of withdrawal (e.g.: pure non opioid regime or tramadol as a sole opioid).
If withdrawal is suspected, Clondine can be used orally and intravenously to aid in the symptomatic management.
Preoperatively identify opioid tolerant and chronic pain patients and make a peri/post operative analgesia plan
Always replace a patient’s preoperative opioid use in the post-surgical period
Consider preventative analgesics such as Ketamine, Pregabalin and Gabapentin to prevent central sensitization and subsequently wind up pain.
Consider an opioid rotation in patients who respond poorly to an opioid regime or with escalating requirements
Reverse analgesic ladder on recovery with background opiate titration
Hope this helps. Let me know what you think.
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