Your SlideShare is downloading. ×
Intravenous Anaesthetics (Intro)
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×

Introducing the official SlideShare app

Stunning, full-screen experience for iPhone and Android

Text the download link to your phone

Standard text messaging rates apply

Intravenous Anaesthetics (Intro)

4,037
views

Published on

Published in: Health & Medicine

0 Comments
4 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
4,037
On Slideshare
0
From Embeds
0
Number of Embeds
1
Actions
Shares
0
Downloads
151
Comments
0
Likes
4
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide

Transcript

  • 1. Intravenous Anaesthetics Craigavon Area Hospital CT1 Education Series (Intro) Dr. Andrew Ferguson
  • 2. Overview
    • Mechanisms of action
    • Pharmacological principles
    • Individual agent overviews
    • Pharmacokinetics
    • Induction characteristics
    • Organ effects
    Dr. Andrew Ferguson
  • 3. How do they work?
    • Major inhibitory neuro-transmitter in the CNS = GABA
    • Active GABA receptor => Cl - influx => hyperpolarisation
    • Propofol & barbiturates slow GABA/receptor dissociation
    • Benzodiazepines increase GABA to receptor coupling
    • Ketamine acts at NMDA receptor
    • These effects lead to sedative & hypnotic effects
    Dr. Andrew Ferguson
  • 4. Pharmacodynamics
    • Increasing dose => sedation => hypnosis
    • All iv anaesthetics affect other organ systems
      • Potential for respiratory depression
      • Potential for CVS depression
      • Potential for altered CBF/ICP
    • Hypovolaemia => severe haemodynamic effects seen due to decreased blood pool
      • Use lower doses!
    Dr. Andrew Ferguson
  • 5. Distribution & Elimination Dr. Andrew Ferguson
  • 6. Single-injection Kinetics Dr. Andrew Ferguson
  • 7. Context-sensitive Half-Time
    • Time required for central compartment blood concentration to fall by half as a function of the duration of an infusion (of variable rate designed to maintain steady state)
    Dr. Andrew Ferguson
  • 8. Schema for Discussing Drugs
    • Chemistry
        • Structure & structure-activity relationship
        • Physical properties
    • Mode of action
    • Organ effects
        • CVS
        • RS
        • CNS
        • GIT etc.
    • Pharmacokinetics
        • Distribution
        • Metabolism
        • Elimination
    • Side-effects
    • Clinical Use
    Dr. Andrew Ferguson
  • 9. Propofol
    • Very widespread use...know inside out!
      • 2,6-diisopropylphenol
      • Emulsion with 10% soybean oil , 2.25% glycerol and 1.2% lecithin (egg yolk phosphatide - ? allergen)
      • Injection pain (up to 65%) decreased by lidocaine
      • Induction dose higher in kids, lower in elderly
      • Metabolised in liver & ? lungs
      • Wake-up due to redistribution, not metabolism
      • Significant vasodilatation & baroreceptor inhibitor
      • Antiemetic
      • Suppresses laryngeal reflexes
    Dr. Andrew Ferguson
  • 10. Etomidate
    • Imidazole derivative, D-(+) isomer
    • Poorly soluble in H 2 O => propylene glycol used
    • Wake-up due to redistribution
    • Metabolised by ester hydrolysis to inactives
    • Minimal haemodynamic effects, short half-life
    • High incidence of PONV (35-40%)
    • May activate seizure foci, myoclonus in 50%
    • Adrenocortical suppression
        • dose-dependent 11  -hydroxylase inhibition
        • lasts 4-12 hrs after single dose (much longer in critically ill)
    Dr. Andrew Ferguson
  • 11. Ketamine
    • Phencyclidine derivative
    • Racemic mixture: S -isomer fewer adverse effects
    • Effects
      • Significant analgesia at sub-anaesthetic doses
      • “ Dissociative anaesthesia” - cataleptic state
      • Blocks NMDA receptor (NOT GABA A active)
      • Vivid dreams or hallucinations during recovery
      • EEG changes cannot be used to gauge depth
      • More stable haemodynamics in unstable patients
      • Less diminution of airway reflexes (less, not none!!)
    Dr. Andrew Ferguson
  • 12. Benzodiazepines
    • iv prep: midazolam, diazepam, lorazepam
    • Midazolam has imidazole ring
        • ring protonated => water soluble at acid pH
        • In body, ring unprotonated => lipid soluble
        • solubility NOT due to opening of benzo ring at low pH
        • At pH 4 only 9% of MDZ rings are open (75% at pH 2)
    • Bind specific site between  +  subunits of GABA A receptor
    • Hepatic metabolism
    • Vasodilatation with MDZ > Diazepam
    Dr. Andrew Ferguson
  • 13. Thiopental
    • Thiobarbiturate
        • Sodium salt + anhdrous NaHCO 3 => pH 10-11
        • Precipitates with acidic drugs e.g. NMBs
        • Extravascular injection => pain + tissue injury
        • Intra-arterial injection => crystals + ischaemia
    • Dose dependent CNS depression
        • Decrease CBF, ICP, CMRO 2 , seizure activity
    • Less BP fall at induction than propofol
        • Compensatory heart rate increase offsets vasodilatation effects
        • Caution in hypovolaemia, tamponade, IHD, heart failure
    • Wake-up due to redistribution
    Dr. Andrew Ferguson
  • 14. Dr. Andrew Ferguson Management of intra-arterial injection of Thiopental Stop injection but leave needle or cannula in place Dilute with immediate injection of saline Give intra-arterial LA + vasodilator
      • Lidocaine 50mg (5 ml of 1% solution)
      • Phenoxybenzamine (  blocker) 0.5 mg bolus or 50-200  g/minute infusion
    Consider systemic papaverine 40-80 mg Consider sympathetic blockade (stellate ganglion or brachial plexus block) Start iv heparin infusion Consider intra-arterial hydrocortisone Postpone non-urgent surgery Liaise with vascular surgeon
  • 15. Single dose pharmacokinetics Dr. Andrew Ferguson Drug Redistribution T1/2 (min) Protein binding % VdSS l/kg Clearance ml/kg/min Elimination T1/2 (hrs) Thiopental 2-4 85 2.5 3.3 11 Methohexital 5-6 85 2.2 11 4 Propofol 2-4 98 2-10 20-30 4-23 Midazolam 7-15 94 1.1-1.7 6.4-11 1.7-2.6 Diazepam 10-15 98 0.7-1.7 0.2-0.5 20-50 Lorazepam 3-10 98 0.8-1.3 0.8-1.8 11-22 Etomidate 2-4 75 2.5-4.5 18-25 2.9-5.3 Ketamine 11-16 12 2.5-3.5 12-17 2-4
  • 16. Induction Characteristics Dr. Andrew Ferguson Drug Induction dose (mg/kg) Onset (secs) Duration (mins) Excitation Injection pain Heart rate BP Thiopental 3-6 <30 5-10 + 0/+ + - Methohexital 1-3 <30 5-10 ++ + ++ - Propofol 1.5-2.5 15-45 5-10 + ++ 0/- -- Midazolam 0.2-0.4 30-90 10-30 0 0 0 0/- Diazepam 0.3-0.6 45-90 15-30 0 +/+++ 0 0/- Lorazepam 0.03-0.06 60-120 60-120 0 ++ 0 0/- Etomidate 0.2-0.3 15-45 3-12 +++ +++ 0 0 Ketamine 1-2 45-60 10-20 + 0 ++ ++
  • 17. CNS effects of IV anaesthetics CMRO 2 = cerebral metabolic rate for oxygen CBF = cerebral blood flow CPP = cerebral perfusion pressure ICP = intracranial pressure Dr. Andrew Ferguson Drug CMRO 2 CBF CPP ICP Anticonvulsant Thiopental -- -- + -- Yes Methohexital -- -- + -- No Propofol -- -- - - Yes Etomidate -- -- + -- No Benzodiazepines - + 0 - Yes Ketamine + ++ + + No
  • 18. CVS Effects of IV Anaesthetics Dr. Andrew Ferguson Drug MAP HR CO Contractility SVR Venous dilatation Thiopental - + - - + ++ Methohexital - ++ - - + + Propofol -- - - - -- ++ Etomidate 0 0 0 0 0 0 Diazepam 0/- + 0 0 -/0 + Midazolam 0/- + 0/- 0 -/0 + Ketamine ++ ++ + + + 0
  • 19. RS Effects of IV Anaesthetics Dr. Andrew Ferguson Drug Ventilation Respiratory rate CO 2 response Hypoxia response Propofol --- -- --/--- Thiopental -- - -- Ketamine Unchanged Unchanged Unchanged ? Midazolam Unchanged Unchanged - - Etomidate - - -
  • 20. Dr. Andrew Ferguson Propofol Thiopental Midazolam Ketamine Etomidate SBP Decrease Decrease 0/Decrease Increase Decrease Heart rate 0/Decrease Increase Unchanged Increase Decrease SVR Decrease Decrease Unchanged/Decrease Increase Decrease Ventilation Decrease Decrease Unchanged Unchanged Unchanged Resp rate Decrease Decrease Unchanged Unchanged Unchanged CO 2 response Decrease Decrease Unchanged Unchanged Unchanged CBF Decrease Decrease Unchanged Unchanged/Increase Unchanged CMRO 2 Decrease Decrease Unchanged Unchanged/increase Unchanged/Decrease ICP Decrease Decrease Unchanged Unchanged/Increase Unchanged Anticonvulsant Yes? Yes Yes Unclear Anxiolysis No No Yes No Yes? Analgesia No No No Yes No? Emergence delirium No No No Yes No N&V Decrease Unchanged Unchanged Increase Increase Adrenal suppression No No Yes? No No