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Intravenous Anaesthetic Agents

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Presentation on theme: "Intravenous Anaesthetic Agents"— Presentation transcript:

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

28

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


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