Although rare (~1 in 10,000 via NAP6 although varies by region) perioperative anaphylaxis is likely under-reported.
“Cyclodextrin is frequently used in foods and cosmetics because it can change the physical properties of various compounds by their encapsulation within the cyclic structure. The average person is thought to ingest about 4 g of gamma-cyclodextrin per day from food. ... even people who have never received sugammadex may be sensitised by food and cosmetics.” (Mertes 2019)
Hairdressers demonstrate increased IgE sensitisation to neuromuscular blocking drugs due to occupational exposure to quaternary ammonium ion compounds.
“Patients suffering from anaphylaxis to succinylcholine crossreact with cis-atracurium in 10% of cases and with rocuronium in 20% of cases. Cross-sensitivity is most frequently observed with rocuronium and less frequently with cis-atracurium.”
Life-threatening anaphylaxis occured in approximately 1 in 10,000 anaesthetics (NAP6 UK).
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.
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.”
- 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.
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.
Fit and healthy women receiving low-dose intrathecal (50-150 mcg) or epidural (1-3 mg) morphine for cesarean section analgesia should have respiratory rate and sedation monitored second-hourly for the first 12 hours.
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.
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.
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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