Intravenous induction agents in Anesthesia

Intravenous anesthesia agents

1. Intravenous
Anaesthetic Agents
4
th
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
“true induction agents”
Slower-acting
•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 GABA
A 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 48-72 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
•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
Pharmacokinetics
•Extra-hepatic metabolism
•++ lipid-soluble
•Rapid plasma clearance
•Unique, therefore versatile
Uses
•Induction
•Maintenance (TIVA)
•Sedation

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

14. •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
•Yellow powder
–Mix with H
2O or N/Sal
•pH 10.5
–precipitates
•Strength 2.5% (25mg/ml)
•Solution stable for 24-48
hours
Dose
•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
–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
•10 ml ampoules (2mg/ml)
Dose
•0.2-0.3mg/kg
Pharmacokinetics
•Rapid recovery
•Repeated doses are not
cumulative
–But not used for infusions
because of adrenocortical
suppression

24. Organ effects of ETOMIDATE
•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
•Respiratory
–Minimal respiratory
depression
–No histamine release
•Least likely to cause
analphylaxis
•GIT
–Severe PONV!
–“VOMIDATE”
•Endocrine
–Inhibition of steroid
synthesis

25. KETAMINE

26. KETAMINE
Physical Properties
•Solutions
–1% (10mg/ml)
–5% (50mg/ml)
–10% (100mg/ml)
•Long-shelf half life
•No pain on injection
Doses
•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:
–0.2-0.4mg/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
–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
1
st
trimester

30. KETAMINE
Indications
•Sick and unstable adults and
children
•Burns surgery
–Debridement
–Change of dressings
•Short diagnostic procedures
•Analgesia
•Field anaesthesia
•Status asthmaticus
Contra-indications
•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
Physical Properties
•preparations
–5 mg ampoules (1mg/ml)
–15mg ampoules (5mg/ml)
•Look identical so be careful
when checking
–Tablets available
Pharmacokinetcs
•Short duration of action
Dose
•Premed: 0.5mg/kg
–Adults 7.5-15mg orally
–Works within 30 min
–Kids – amx 7.5mg/kg
•Induction: 0.1-0.3mg/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 55-140sec
–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
–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