1 / 10

Your Anaesthetic Should be Apologetic: Anaesthetic Actions That You Don't Want

Your Anaesthetic Should be Apologetic: Anaesthetic Actions That You Don't Want. Jason T Maynes, PhD/MD Departments of Anaesthesia and Molecular Structure and Function “Three things should be considered: problems, theorems and applications.” Gotfrield Leibniz.

vega
Download Presentation

Your Anaesthetic Should be Apologetic: Anaesthetic Actions That You Don't Want

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Your Anaesthetic Should be Apologetic: Anaesthetic Actions That You Don't Want Jason T Maynes, PhD/MD Departments of Anaesthesia and Molecular Structure and Function “Three things should be considered: problems, theorems and applications.” Gotfrield Leibniz

  2. Why do we care about blood pressure? • What happens to the body with no blood pressure? • Loss of oxygen, glucose, removal of waste • Metabolic failure -> loss of energy, cell integrity • Mitochondrial failure • Lack of blood pressure -> mitochondrial failure • Vessel rich group: brain, heart, liver, kidney

  3. Patient Monitoring HR (CO, tissue perfusion) BP (CO, tissue perfusion) PAP (oxygenation) CVP (?Fluid status) SvO2 (metabolic supply/demand) SaO2 (blood oxygenation) CO/CI (tissue oxygenation) EtCO2 (metabolic waste) Neuro: BIS/EEG/rSO2(NIRS)

  4. Low/No Blood Pressure Local Tissue Perfusion Local Nutrient Extraction Drugs/Anaesthesia Pharmacokinetics/dynamics Surgical Stress Mitochondrial Failure Pharmacogenomics Developmental Stage Short term outcomes – Wound infection, hospital Length of stay, recovery times, PICU admission Long term outcomes – ?can my pt still win a Nobel Morbidity and Mortality

  5. Common Anaesthetics (Isoflurane, versed, nitrous) cause widespread neurodegeneration Anaesthesia in the developing brain causes cognitive, behavioral and developmental abN -age < 4 yrs, >1 anaesthetic

  6. Mitochondrial Mechanisms to Produce Lasting Cellular Dysfunction Hepatocyte/Epithelial Culture 1 hr exposure to clinically relevant concentrations of Anaesthetics 0.5,1,1.5 MAC isoflurane 10,25,50 uMPropofol 10,20,50 uMLidocaine Image Mitochondria With dyes – high throughput fluorescent microscopy

  7. Anaesthesia Exposure

  8. Isoflurane Sevoflurane Propofol Lidocaine Etomidate Ketamine Morphine Versed Mitochondrial Morphology Changes Mitochondrial Dysfunction and membrane potential loss Mitochondrial DNA Damage – LASTING CHANGE Mitochondrial DNA Damage in vivo model for neurodegeneration, Dr. G. Stratmann UCSF – anaesthesia, Alzheimer’s, Parkinson’s

  9. Mitigate the Damage Anaesthetic neurotoxicity, post-op recovery times, Sx inflammation, wound healing, POCD Screen small molecule libraries for compounds that may attenuate the damage and identify stress pathways involved (~20 000 molecules) Identify proteins that may be involved, solve their structure by X-ray crystallography and identify activators/inhibitors Express the protein in bacteria/insect cells/mammalian cells, crystallize it, shoot it with a high energy X-ray beam, solve the structure

More Related