Article Notes
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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. ↩
- Very few ASA 4 (5%) patients were enrolled.
- Only volatile-maintenance anaesthesia was studied not propofol/TIVA.
- We can draw no conclusion regarding the consequences of extreme-depth (ie. BIS << 35).
- The actual depth difference between the BIS-35 and BIS-50 groups was not as much as perhaps ideal: mean BIS 39 vs 47 respectively...
- Atracurium – 1 in 22,500
- Rocuronium – 1 in 2,500
- Suxamethonium – 1 in 2,000
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It would also be feasible for recording, analysis and reporting to occur entirely at the bedside on a smartphone. ↩
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.
What’s all the fuss?
Significant observational evidence suggested an association between mortality and deep anaesthesia, in particular a 2017 meta-analysis. However it has been suspected that anaesthetic depth may merely be a surrogate marker for intraoperative hypotension, a well-established risk factor for post-operative mortality and morbidity.
With this large RCT, the Balanced Anaesthesia Study Group has shown that deep general anaesthesia is not associated with an increase 1-year mortality.
What did they do?
The researchers conducted an ambitious, large (6,644 patients), multi-center, randomised controlled trial. Patients aged ≥60 years undergoing major surgery (expected ≥2h surgery and ≥2d hospital stay) were randomised to receive volatile general anaesthesia targeting BIS 50 or BIS 35.
To minimise intra-operative blood pressure as a confounder, anaesthetists were required to specify a target MAP before BIS-group allocation.
They found...
Not only was there no mortality difference between the BIS 50 and BIS 35 groups, there were also no major or moderate morbidity differences, or difference in recovery or length of stay. BIS targets were adequately achieved, though not perfect, and MAP was clinically similar for both groups.
Context is everything
This is about as high-quality as a large, modern study looking at longer-term outcomes can get. It is widely applicable to most populations and common general anaesthetic scenarios, except for a few important caveats:
Final thought
...there was (only) one case of awareness in the light-depth BIS 50 group, despite 39% of patients receiving volatile < 0.7 MAC.
Australia and New Zealand both experience an unusually high incidence of perioperative anaphylaxis, particularly to neuromuscular blocking drugs. The opioid-based anti-tussive pholcodine has been implicated in increasing population hypersensitivity to muscle relaxants.
Although historically difficult to identify accurate denominator numbers for incidence calculations, more recent data shows that the anaphylaxis risk for rocuronium is particularly high in Australia & New Zealand and may in fact be roughly comparable to the local risk of suxamethonium anaphylaxis, at 1 in 2,000-3,000 exposures.
Rocuronium also has a higher risk of anaphylaxis than it’s aminosteroid-sibling vecuronium, and up to a ten-times greater risk than the benzylisoquinolinium atracurium (~1 in 22,500, depending on population). Cisatracurium demonstrates the lowest incidence of anaphylaxis (~1 in 50,000).
Additionally, as sugammadex appears as a new anaphylaxis cause the potential for a rocuronium-sugammadex combination having an even higher risk of anaphylaxis than suxamethonium needs to be considered.
This retrospective, observational cohort study over 6 years from Auckland, New Zealand identified a 10 fold higher incidence of anaphylaxis for rocuronium than for atracurium.
Also of note, the rate of anaphylaxis to rocuronium was similar to that for suxamethonium.
Anaphylaxis incidence for the three muscle relaxants were approximately:
Why is this important?
Despite growth of regional and non-opioid analgesic options, opioids remain the mainstain of peri-operative management of moderate to severe pain. IV patient-controlled analgesia (PCA) is a safe, common and reliable delivery mechanism.
What did they do?
Dinges et al. performed a network meta-analysis of 63 studies covering 16 different PCA opioids, comparing side-effects at equianalgesic doses. Morphine was used as the baseline comparator.
And they found?
Although there were some small difference in the incidence of nausea & vomiting (fentanyl having lowest N&V risk, buprenorphine highest) and pruritus (nalbuphine, butorphanol, methadone, and pethidine/meperidine resulting in least pruritis), there were significant differences for sedation and satisfaction.
Pethidine/meperidine, fentanyl & oxymorphone showed the lowest sedation scores, although respiratory depression events were too infrequent to show differences. Oxycodone, alfentanil, remifentanil, fentanyl & pethidine/meperidine resulted in the highest patient satisfaction and tramadol was the least satisfying.
Take-home message
Although some PCA-opioids perform better than others in small ways, overall side-effect profiled are very similar and comparably safe. Oxycodone, alfentanil and remifentanil however result in significantly higher patient satisfaction.
The big picture...
Rather than focusing on the small differences among opioids, there is almost certainly more to be gained by a disciplined, multi-modal analgesic focus that reduces opioid use and thus side-effects.
What’s so interesting?
De Carvalho and co. show that pre-operative voice analysis can be predictive of difficult laryngoscopy.
I’d never thought about that...
The authors describe how different frequency components and acoustic qualities of the voice are, at least partly, determined by the shape and size of different anatomical areas of the vocal tract. By analysing the most intense frequencies (voice formants) within the voice spectrum they were able to correlate components with difficult laryngoscopy, namely Cormack & Lehane grade 3 or 4.
The practicalities
During pre-anaesthetic assessment, 467 elective general surgical patients were asked to pronounce each of the five vowels, corresponding to base phonemes. This was recorded on a smartphone and then later processed and analysed on a laptop computer.1
They found...
A model using voice ‘formants’ could reliably predict difficult laryngoscopy with a ROC-AUC of 0.761 (ie. 76% probability that it correctly classifies a patient as difficult or not). When combined with the modified Mallampati this improved to 92%.
The big picture
While interesting, it’s worth remembering that using voice formants (76%) did not perform as well as modified Mallampati alone (87%), and that this performance is also surprisingly much better than those from the most recent Cochrane meta-analysis (2018) of bedside airway assessment. Over 133 studies the Cochrane review reported a summary sensitivity of only 53% and specificity of 80% for the modified Mallampati (vs 100% and 75% respectively for this study).
Although this is an interesting and novel new test, it’s just not that simple... Screening for an uncommon outcome using tests with imperfect sensitivity and specificity is already problematic, but doubly so when we are not always certain which outcome we should be screening for (laryngoscopy, intubation, ventilation, oxygenation...).
As an airway screening test, voice analysis is both different and also more of the same.
The authors suggest a possible revision of anaesthesia consent, such as:
"You may receive medications during your anesthetic that could interfere with the effectiveness of oral contraceptives. If you are using oral contraceptives, consider alternative methods of birth control for 7 days following your anesthetic." This disclosure would cover potential interactions with sugammadex, antibiotics, and other medications.
Note the authors: “So long as neostigmine and glycopyrrolate are available and not prohibitively expensive, we should make a point in our practice to not use sugammadex for rocuronium reversal in women of childbearing age in situations where neostigmine and glycopyrrolate will have equal effectiveness.”
Why?
Although often used to manage chronic pain acutely, the longer-term benefits of ketamine infusions remain uncertain. Despite this there has been significant growth in using ketamine infusions to treat chronic pain, rationalised by ketamine’s expected effect to reduce central sensitisation.
What?
This meta-analysis identified a small benefit for up to two weeks after a ketamine infusion, although little evidence of longer-term benefit. There appears to be a dose-response effect, suggesting greater efficacy with high-dose ketamine infusions.
The underlying problem...
Most research on ketamine infusions focuses on perioperative analgesia. Trials invetsigating ketamine infusions for chronic pain are universally small, lack standardisation and are often low quality.
This meta-analysis unfortunately does not add clarity to the question of whether ketamine infusions have long-term benefit in chronic pain syndromes. Clinicians will continue to need to judge indication on a case-by-case basis...