Developments in TIVA 2014 Barcelona 2 - EuroSIVARemimazolam 4. Remimazolam 5....
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Developments in Intravenous Anaesthesia What is new in 2013
Transcript of Developments in TIVA 2014 Barcelona 2 - EuroSIVARemimazolam 4. Remimazolam 5....
Developments in Intravenous Anaesthesia
What is new in 2013
Agenda
Advances in pharmacology
New insights in physiology
Improved drug delivery
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Advances in pharmacology
PK, PD and more
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Remimazolam
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Remimazolam
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Orexins and dynamic effect site
6Zhang LN et al, Anesth Analg 2012;115:789-‐96
Hypothalamic orexinergic neurons play a critical role in the promotion and maintenance of wakefulness in mammals. Previous studies have demonstrated that activities of orexinergic neurons were inhibited by isoflurane and sevoflurane, and microinjection of orexin facilitated the emergence from volatile anesthesia. In this study we first examined the hypothesis that the activity of orexin neurons is inhibited by propofol anesthesia. Moreover, the role of the orexinergic signals in basal forebrain in regulating the anesthesia–arousal cycle of propofol anesthesia is also elucidated.
Orexins and dynamic effect site
CONCLUSION: Activity of orexinergic neurons is inhibited by propofol anesthesia, and the orexin signals in basal forebrain are involved in anesthesia–arousal regulation from propofol anesthesia.
7Zhang LN et al, Anesth Analg 2012;115:789-‐96
Allometric scaling in PK
8Caldwell GW et al, Eur J Drug Met Pharmacokin 2004;29:133-‐43
Allometric scaling in PK
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“Allometry is the study of the rela2onship of body size to shape, anatomy, physiology and finally behaviour, first outlined by O<o Snell in 1892”
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New insights in physiology
ModulaWng the peri-‐operaWve
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Propofol anaesthesia reduces postoperaWve PONV
Cheng S et al. Anesth Analg 2008;106:264-‐9
Nausea Vomiting
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Propofol anaesthesia reduces postoperaWve pain
Numerical analogue scale and morphine consumption
Cheng S et al. Anesth Analg 2008;106:264-‐913
Does propofol induce analgesia?
14Takechi K et al, Anesth Analg 2013;116:932-‐8
• Propofol inhibits WDR neuron responses to noxious sWmulaWon
• Reduces anWhyperalgesic effect
• Mechanism of acWon ? (endocannabinoids, pGABA A receptors)
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Does propofol induce analgesia?
Takechi K et al, Anesth Analg 2013;116:932-‐8
Remifentanil-‐induced hyperalgesia is dependent on hypnoWc agent
• Sevoflurane anaesthesia with high-‐dose remifentanil induces RIH compared with low-‐dose remifentanil.
• Propofol anaesthesia does not induce RIH regardless of remifentanil dose/concentraWon
• Propofol maintenance provides beeer analgesia with regard to RIH than sevoflurane.
Shin S-‐W et al. Br J Anaesth 2010; 105:661-‐7.16
Remifentanil-‐induced hyperalgesia is dependent on hypnoWc agent
Shin S-‐W et al. Br J Anaesth 2010; 105:661-‐7.17
HepaWc blood flow
Meierhenrich R et al. Anaesthesia 2010;65:1085-‐93
“Propofol anaesthesia is associated with significant greater hepatic blood flow than desflurane anaesthesia.”
Desflurane Propofol
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AeenuaWon of inflammatory response during CABG
Propofol aeenuates free-‐radical mediated lipid peroxidaWon and systemic inflammaWon in paWents with impaired myocardial funcWon
Corcoran TB et al. Br J Anaesth 2006;97:825-‐3119
Remifentanil and cardioprotecWon
• Remifentanil precondiWoning protects against ischaemic injury in the intact rat heart (Zhang Y at al. Anesthesiology 2004)
• Remifentanil precondiWoning confers cardioprotecWon via cardiac κ-‐ and δ-‐opioid receptors (Zhang Y et al. Anesthesiology 2005)
• Remifentanil precondiWoning confers delayed cardioprotecWon in the rat (Br J Anaesth 2007)
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Improved drug delivery
Technology moves on
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Closed loop TIVA
22Hemmerling TW et al. Br J Anaesth 2013;110:1031-‐9.
Closed loop TIVA
23Hemmerling TW et al. Br J Anaesth 2013;110:1031-‐9.
Impact of Closed-‐loop systems
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“An automated controller strikingly frees the anesthesiologist from manual interven2on to
adjust drug delivery.”
Dussaussoy C et al. J Clin Monit Comput 2013;.
PATIENT CO
VARIATES
SMART integraWon of TCI models
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ADULT
ELDERLY
CHILD
OBESE
MODEL D
ATA BA
SE
USER
Advisory Systems
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Navigator (GE)
Smart Pilot (Draeger)
Coming soon on
Conclusion:
Of the recovery domains measured using the Postoperative Quality of Recovery Scale, only nociception (pain or nausea) contributed to incomplete satisfaction.
Royes CF et al. Eur J Anaesthesiol 2013; 30:106-‐10. 28
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VolaWle anaestheWcs ause the same changes in the brain as those seen with Alzheimer's Disease
• Neurofibrillary tangles
• Amyloid Plaques
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“In conclusion, the current results suggest that propofol and thiopental are relatively safe with respect to the formation of Aβ assembly because they have direct and indirect inhibitory effects on Aβ fibrillogenesis.”
Yamamoto N et al. Anesthesiology 2013; 118:1408-‐16.
Summary
Advances in pharmacology
New insights in physiology
Improved drug delivery
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Thank You
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