Anesthesia and analgesia
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Anesthesia and analgesia · Oct 2019
Polymodal Mechanism for TWIK-Related K+ Channel Inhibition by Local Anesthetic.
Local anesthetics cause reversible block of pain and robustly inhibit TWIK-related K channel (TREK-1) currents. Before local anesthesia onset, injection of local anesthetics can cause unwanted transient pain. TREK-1 is an anesthetic-sensitive potassium channel that when inhibited produces pain. A disordered C-terminal loop of TREK-1 is thought to contribute to anesthetic sensitivity, but the molecular basis for TREK-1 inhibition by local anesthetics is unknown. Phospholipase D2 (PLD2) is an enzyme that produces phosphatidic acid (PA) required for TREK-1 activation and also binds to the channel's C terminus. ⋯ We propose a mechanism of TREK-1 inhibition comprised of (1) primarily indirect PLD2-dependent inhibition of lipid catalysis and (2) limited direct inhibition for select local anesthetics through partial open pore block. The inhibition through PLD2 explains how the C terminus can regulate the channel despite being devoid of structure and putative binding sites for local anesthetics.
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Anesthesia and analgesia · Oct 2019
Effects of Dexmedetomidine on Myocardial Repolarization in Children Undergoing General Anesthesia: A Randomized Controlled Trial.
Dexmedetomidine is a highly selective α2-adrenergic agonist, which is increasingly used in pediatric anesthesia and intensive care. Potential adverse effects that have not been rigorously evaluated in children include its effects on myocardial repolarization, which is important given that the drug is listed as a possible risk factor for torsades de pointes. We investigated the effect of 3 different doses of dexmedetomidine on myocardial repolarization and transmural dispersion in children undergoing elective surgery with total IV anesthesia. ⋯ Of the bolus doses of dexmedetomidine studied, none had an effect on Tp-e and the dexmedetomidine 0.5 and 0.75 µg/kg doses shortened corrected QT intervals when measured at 1 minute after dexmedetomidine bolus injection during total IV anesthesia. There is no evidence for an increased risk of torsades de pointes in this context.
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Anesthesia and analgesia · Oct 2019
Comparative Study Observational StudyDistinguished Service Awards in Anesthesiology Specialty Societies: Analysis of Gender Differences.
The authors queried 9 anesthesiology societies to examine Distinguished Service Award recipients over time by gender. Of the 211 total Distinguished Service Awards given by all 9 societies, women received 25 (11.8%). ⋯ Low levels of awardees stand in contrast to the increasing number of women in the academic pipeline. The authors recommend that societies collect gender membership data and study their award processes from nomination to selection.
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Anesthesia and analgesia · Oct 2019
Meta AnalysisSide Effect Rates of Opioids in Equianalgesic Doses Via Intravenous Patient-Controlled Analgesia: A Systematic Review and Network Meta-analysis.
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.
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