1. Intravenous Anaesthetic Agents
4th year MBChB
Anaesthesia Tutorial

2. Classification
True induction agents produce loss of consciousness within one arm-brain circulation time
Approximately 30 seconds

3. Classification Rapidly –Acting Slower-acting “true induction agents”
Thiopentone
Etomidate
Propofol
Ketamine
Benzodiazepines
Neuroleptic-anaesthetics
Opioids

4. Advantages of IV Induction
Rapid onset of action
More pleasant & acceptable for the patient
Pollution free
Low incidence of side-effects
Smooth induction with rapid transfer through stage 2

5. Stages of anaesthesia

6. Disadvantages Need IV access
It is easy to give too much .... Side-effects
No removal of drug via the lungs as with inhalationals
Recovery requires
Redistribution
Metabolism
Excretion
Sudden loss of normal protective reflexes

7. Mechanism of Action
Most sedative hypnotics exert their effect via the inhibitory GABAA receptors
GABA – γ (gamma)-aminobutyric acid
Increased chloride conductance → hyperpolarisation → neuronal inhibition
Some inhibit the release of glutamate, an excitatory amino acid, in brain
Not clearly understood

8. Pharmacokinetics
The onset of action depends on the drug reaching the effect site (the brain) by crossing the BBB
Arm-brain circulation time is determined by
Speed of injection
Lipid solubility
Protein binding
Blood flow to brain
Recovery is determined by
Redistribution from vessel-rich to vessel-poor organs (brain → muscle etc)
Metabolism and excretion

9. Redistribution
Following IV Induction, the patient will wake up after a few minutes due to REDISTRIBUTION of the drug from brain to other tissues that are less well perfused
Rapid awakening is not due to metabolism or excretion
Low concentrations of the drug will remain in the brain
This impairs concentration and higher functioning
Recommended not to drive or make important decisions for hours post anaesthesia

10. Characteristics of an Ideal IV Induction Agent
Smooth and rapid onset
Rapid recovery
No pain on injection
Minimal side-effects
No toxicity

11. PROPOFOL

12. PROPOFOL Physical properties Pharmacokinetics 1% = 10mg/ml
2,6 di-isopropylphenol
Preparation:
10% soya bean oil
1.2% egg phosphatitide
From egg lecithin (yolk)
2.25% glycerol
Fat emulsion
Culture medium
Use within 6 hours of opening
Multiple amp sizes
20ml, 50ml or 100ml
1% or 2%
1% = 10mg/ml
Extra-hepatic metabolism
++ lipid-soluble
Rapid plasma clearance
Unique, therefore versatile
Uses
Induction
Maintenance (TIVA)
Sedation

13. Pharmacodynamics of PROPOFOL
Doses
Organ Effects
Induction:
Adults: 2 – 2.5 mg/kg
Elderly: 1 – 1.5 mg/kg
Children: 2.5 – 3 mg/kg
CNS
CVS
Respiratory
GIT
Metabolic

14. Inhibits laryngeal reflexes
CNS
rapid LOC + recovery
Less hangover effect than other induction agents or gases
No real excitatory effects
No antalgesia, infact very slight analgesic effect
Antipruritic
Pain on injection!!
CVS
Dose-related CVS depression
↓ed SVR
↓ed BP
Slight ↑ HR
Respiratory
Dose-dependent depression
Apnoea on induction close to 100%
Inhibits laryngeal reflexes
No histamine release
GIT
Anti-emetic
Metabolic
Propofol infusion syndrome (PRIS)
Lipaemia
Metabolic acidosis
Cardiomyopathy and shock
Skeletal myopathy
death

15. PROPOFOL Most commonly used Ideal for these specific scenarios
TIVA
Conscious sedation
Asthma
Porphyria
History of PONV
History of Malignant Hyperthermia
Use with caution !!
Elderly
Cardiac failure
Hypovolaemia
Fixed cardiac output
Aortic / Mitral stenosis
HOCM

16. THIOPENTONE

17. THIOPENTONE Physical properties Dose Yellow powder pH 10.5
Mix with H2O or N/Sal
pH 10.5
precipitates
Strength 2.5% (25mg/ml)
Solution stable for hours
Induction:
Adults: 3 – 5mg/kg
Children: 5-6mg/kg
Caution in elderly

18. Organ Effects of THIOPENTONE
CNS
LOC in 30sec
Classically described for RSI
Smooth, no reflex movements or coughing
Antalgesia
Anti-convulsant
Used in treatment of STATUS EPILEPTICUS
Neuroprotective
↓CMRO2
↓ ICP\
No pain on injection
CVS
↓ C.O. (10 – 20%)
Vasodilatation
negative inotropy
↓ central catecholamines
Compensatory ↑HR
Exaggerated response with
Elderly
Cardiac failure
Fixed cardiac output
Hypovolaemia
ACIDOSIS

19. What do Pearl Harbour and Thiopentone have to do with each other?

20. Respiratory Renal, Hepatic, GIT Local Effects Dose-dependent apnoea
No depression of laryngeal reflexes
Histamine release
Renal, Hepatic, GIT
No real issues
Local Effects
Irritant to tissues
Venous thrombosis with 5% solutions
Intra-arterial injection is a disaster
Precipitation of solid crystals of thiopentone in arteries due to blood pH of 7.4
Acute ischaemia of limb

21. Contra-indications for THIOPENTONE
Absolute:
Porphyria
Known allergy (rare)
Relative:
Asthma (Theoretical - It has been used in many asthmatics without problems)
Cardiovascular instability

22. ETOMIDATE

23. ETOMIDATE Physical Properties Dose Pharmacokinetics
10 ml ampoules (2mg/ml)
mg/kg
Pharmacokinetics
Rapid recovery
Repeated doses are not cumulative
But not used for infusions because of adrenocortical suppression

24. Organ effects of ETOMIDATE
Respiratory
Minimal respiratory depression
No histamine release
Least likely to cause analphylaxis
GIT
Severe PONV!
“VOMIDATE”
Endocrine
Inhibition of steroid synthesis
CNS
Rapid LOC
Myoclonus and involuntary movements
Reduced by concurrent opiate and benzodiazepine use
Pain on injection
CVS
Most stable
Little change in BP or HR

25. KETAMINE

26. KETAMINE Physical Properties Doses Solutions Long-shelf half life
1% (10mg/ml)
5% (50mg/ml)
10% (100mg/ml)
Long-shelf half life
No pain on injection
iv, im or oral
Induction:
1-2mg/kg iv
onset 30-60s
Lasts 5-15 min
5-10mg/kg im
Onset 3-8min
Lasts 10-30min
Analgesia:
mg/kg iv

27. Organ Effects of KETAMINE
CNS
Dissociative anaesthetic
Complete analgesia with superficial sleep
↑ed ICP and IOP
Psychic reactions:
Hallucinations and emergence delirium
Less in kids, males, elderly, long procedures and repeated administration
Worse if pt stimulated on awakening
CVS
Sympathetic stimulant centrally
↑ HR
↑ BP
↑ C.O.
↑ SVR
But...
Direct myocardial depressant
Not arrhythmogenic

29. Respiratory GIT Uterus Increased salivation and bronchial secretions
Minimal or no respiratory depression
Preserved pharyngeal reflexes
Maintains airway
Do not need to intubate or insert LMA
Bronchodilator
Sympathetic stimulation
Safe in asthma (no histamine release)
Last line treatment of status asthmaticus
Increased salivation and bronchial secretions
Use anti-sialogogue (anticholinergic like atropine or glycopyrrolate)
GIT
PONV
Uterus
Uterine contractions in 1st trimester

30. KETAMINE Indications Contra-indications
Sick and unstable adults and children
Burns surgery
Debridement
Change of dressings
Short diagnostic procedures
Analgesia
Field anaesthesia
Status asthmaticus
CVS diseases
IHD, hypertension, AAA, CCF
↑ed ICP
↑ed IOP and “open eye”
Psychiatric patients
Epileptics
Thyrotoxicosis
Full stomach
Early pregnancy

31. Problems with KETAMINE
Drug of abuse: Special K, Vitamin K, Ket, K

32. BENZODIAZEPINES Sedatives Also act on the GABA receptors
Used mainly as premedication and intra-operative sedation in anaesthesia
Rarely used as induction agents
Premeds:
Lorazepam, temazepam, diazepam, midazolam
Sedation:
midazolam

33. MIDAZOLAM

34. MIDAZOLAM Pharmacokinetcs Physical Properties Dose
preparations
5 mg ampoules (1mg/ml)
15mg ampoules (5mg/ml)
Look identical so be careful when checking
Tablets available
Short duration of action
Dose
Premed: 0.5mg/kg
Adults mg orally
Works within 30 min
Kids – amx 7.5mg/kg
Induction: mg/kg
Sedation: 0.1mg/kg
Less with elderly

35. Organ Effects of MIDAZOLAM
CNS
Induction does not occur within 1 arm-rain circulation time
Takes sec
Anterograde amnesia
Anxiolysis
Sedation
Prolonged recovery
CVS
Stable
Often used in cardiac surgery
Respiratory
Little effect
GIT
Low incidence PONV
Uterus
Crosses placenta and cause floppy neonate

36. FLUMAZENIL
Specific benzodiazepine antagonist
Dose: 0.2mg iv

37. TIVA TIVA = Total Intravenous Anaesthesia Indications Benefits
Ideal: PROPOFOL
Ketamine
Indications
Risk of malignant hyperthermia
Severe PONV in prior case
Day-case surgery
Cheaper than gases
Benefits
Rapid wake-up
No PONV
Requirements
Infusion pumps

38. Practical Points on IV Induction
Reduce pain on injection
Iv lignocaine 10-20mg in syringe
New big drip
Titrate to effect..... You can always give more
Less in elderly .... More in children