Article Notes
- Ultra-low dose intrathecal (≤50 mcg) or epidural (≤1 mg) morphine in low-risk women does not require extra respiratory monitoring.
- Low dose intrathecal (50-150 mcg) or epidural (1-3 mg) morphine in low-risk women should have respiratory rate and sedation monitored every 2h for the first 12h.
- Women with significant comorbities, sedation risk factors or if receiving higher morphine doses should be monitored as per ASA/ASRA guidelines.
- Low-dose intrathecal (50-150 mcg) or epidural (1-3 mg) morphine provides the best balance between analgesia and minimising side effects.
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Buprenorphine is also a kappa and delta receptor antagonist, a weak partial NOP/Nociceptin receptor agonist, and has potent local anaesthetic effects. It behaves as a full agonist for analgesia in the opioid-naive, but a partial agonist for respiratory depression. ↩
This consensus statement from the Society for Obstetric Anesthesia and Perinatology (SOAP) provides post-operative monitoring guidelines for women receiving neuraxial morphine for cesarean section analgesia.
The context
Neuraxial morphine is a widely used and effective technique for managing post-cesarean pain in the first 24 hours. However because of morphine’s low-lipid solubility, the risk of delayed repsiratory depression has required frequent respiratory monitoring in this first 24 hour period.
The SOAP task force aimed to balance opioid safety needs while avoiding excessive respiratory monitoring in new mothers. Existing ASA/ASRA guidelines were considered by many obstetric anesthesiologists to be too rigorous when applied to the healthy post-natal population, both because of their lower risk of respiratory depression and even greater need to minimize sleep interruptions.
“The SOAP Task Force members strongly agree that neuraxial morphine should be the preferred method for postcesarean delivery analgesia in healthy women.”
The recommendations
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The paper’s full-text goes into more detail covering the evidence for the safety and efficacy of neuraxial morphine, the incidence of respiratory depression, respiratory monitoring techniques and duration, optimal dosing and analgesic regimes.
The title of this paper is pretty vague and possibly even misleading: “unexpectedly unfavorable outcomes”...? Generally ‘outcome’ is used in service to something broader and longer-term, such as procedural success, long-term comfort, time to discharge, or functional recovery.
A more appropriate and descriptive title would have been: “Remifentanil for abdominal surgery is associated with worse analgesia and more PONV in the PACU.” 👍
Although we know that OIH and AOT are issues for remifentanil and may explain the PACU analgesia differences observed in this study, it’s also possible that worse PACU pain scores occur because anesthetists/anesthesiologists have not adequately transitioned from short-acting to longer-acting analgesics at the end of the case.
That is, the findings may represent inadequate pre-emergence analgesia because of the complexity of managing pharmacokinetic transitions, rather than a direct pharmacodynamic effect of remifentanil...
My money is still on this being acute hyperalgesia and tolerance, but keep an open mind...
What’s the relevance?
Remifentanil’s ultrashort-acting kinetics have driven its growth as a reliable technique for maintaining intraoperative analgesia. It is now one of the most widely used synthetic opioids in anesthesia.
However these unique pharmacological characteristics are associated with both Opioid Induced Hyperalgesia and Acute Opioid Tolerance, and possibly increase the risk of chronic pain after surgery.
Details:
Niedermayer and team performed a large, multicenter, propensity-matched observational study of remifentanil use during intra-abdominal surgery, and its association with postoperative pain in the PACU. Importantly the patients receiving epidural analgesia in addition to TIVA GA were also included. Volatile GA was excluded.
Among 16,420 patients meeting inclusion criteria, 3,652 GA/TIVA patients received remifentanil and were matched to 3,318 controls, and 829 GA/epi received remifentanil, being matched to 631 controls. Mean remifentanil infusions rates were 0.11 and 0.13 mcg/kg/min for non-EA and EA groups respectively.
They showed:
Among GA-only patients, remifentanil was associated with higher PACU pain scores (both on arrival and discharge), greater analgesic requirements and more PONV – however there was no decrease of either time-to-extubation or PACU discharge.
Interestingly, the epidural analgesia cohort also showed higher PACU pain scores when receiving remifentanil.
The rapid nociceptive changes due to remifentil are well known, however real clincial consequences remain unclear. This large observational study highlights the detrimental analgesic effects of remifentanil in the most immediate post-op period, reminding anesthetists and anesthesiologists that gold-standard intraoperative analgesia may come at a cost.
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Explore collected articles answering: Is remifentanil associated with Opioid Induced Hyperalgesia and Acute Opioid Tolerance?
Why is this important?
Buprenorphine (Subutex, Tamgesic, Suboxone, Norspan) is a partial opioid agonist with high mu-receptor affinity, though limited by a ceiling effect. Because of its favourable safety profile it is used for opioid dependence, chronic and, increasingly, acute pain.1
Patients historically often have regular buprenorphine (BUP) ceased post-operatively when needing opioid analgesia. It was assumed that because of it’s high mu-receptor affinity, BUP blocks the efficacy of additional opioid analgesics. In reality, ceasing buprenorphine creates more complexity and may precipitate acute withdrawal.
Be smart
Haber, DeFries & Martin point out that despite the high receptor affinity of BUP, there are still additional receptors remaining for full-agonist opioids to bind and activate. This is supported by the literature (Kornfeld 2010 & Harrison 2018). Even in the post-operative period buprenorphine can be easily continued, although with patients sometimes needing higher doses of acute opioid analgesics (Goel 2019 & Hansen 2016).
“Temporarily discontinuing buprenorphine introduces unnecessary complexity to a hospitalization, places the patient at risk of exacerbation of pain, opioid withdrawal...“
Bottom-line
If buprenorphine is regularly being taken then it should not be ceased for hospital admission. Additional short-acting opioids can be added if needed. Doses required may be higher, but this is primarily due to opioid tolerance rather than receptor competition with BUP. Alternatively, a maintenance BUP dose can be split into 3-4 divided doses and/or increased to cover acute analgesic needs.