Article Notes
- 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
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.
Daniel Jolley
Pholcodine, rocuronium and suxamethonium, showing common tertiary/quaternary ammonium epitopes.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.
Daniel Jolley
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:
Daniel Jolley
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.
Daniel Jolley