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Induction agents Flashcards

1
Q

Classify intravenous induction agents

A

Rapidly acting (±30 s / 1 x arm-brain circulation time) 1. Propofol (1.5 - 2.5) (kids: 2.5 - 3 mg/kg) 2. Thiopentone (3 - 5) 3. Etomidate (0.1 - 0.3) 4. Ketamine (1 - 2) Slower acting 1. Benzodiazepines (adjunctive) - Midazolam - Diazepam - Lorazepam 2. Neuroleptic + opioid - Droperidol - Haloperidol 3. Large dose opioid - Fentanyl - Alfentanyl - Remifentanyl - Sufentanyl - Morphine

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2
Q

List 4 advantages of IV induction

A
  1. Rapid onset 2. Smooth induction: rapid transit through stage 2 anaesthesia (stage of excitement) 3. More pleasant for the patient (unpleasant odour VA) 4. Pollution free
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3
Q

List 4 disadvantages of IV induction

A
  1. Requires venipuncture 2. Overdose easy 3. No removal via lungs: Once in, its in (requires: redistribution, metabolism, excretion) 4. Apnoea: Sudden loss of normal protective mechanisms
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4
Q

Describe the mechanism of action of the IV induction agents

A

Not fully understood Modulate GABA mediated neural transmission –> interefering with transmembrane electrical activity. Ketamine: Opioid receptor agonist but works as an NMDA receptor antagonist

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5
Q

Describe the pharmacokinetic reason why a patient can awaken rapidly after IV induction

A

Redistribution of drug to tissues with poorer blood supply (muscle and fat). Drug initially active in tissues with rich blood supply (e.g. brain). Thereafter the drug re-distributes to tissues with poorer blood supply. Rapid awakening is NOT due to metabolism or excretion of the drug.

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6
Q

What should the patient be cautioned about after a GA with regard to the first 24 hours afterwards

A

Increased sensitivity to alcohol/analgaesia/sedatives for 24 hours Partake in no legally binding decisions for 24 hours after an anaesthetic

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7
Q

Briefly describe the metabolism and excretion of the IV induction agents and note when these process become important to the anaesthetist

A

Metabolism: Liver –> converted to water soluble metabolites. Excretion: KIdney - in urine The importance of excretion and metabolism terminating drug effect increases with HIGH PLASMA CONCENTRATIONS due to multiple doses or continuous IV infusion

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8
Q

What is the difference between TIVA and TCI

A

TCI = Target Controlled Infusion - The anaesthetist enters demographic information: Age, sex, height and weight - The anaesthetist sets and target concentration for the plasma or for the ‘effect site’ (brain). - A microprocessor within the TCI infusion pump uses the demographic information entered in an algorithm to calculate the required infusion rate required to achieve the set target concentration. - The infusion rate is based on an estimated drug concentration rather than a measured one. TIVA = Total IntraVenous Anaesthesia - An anaesthetic technique which uses IV agents only to induce and maintain anaesthesia. No inhalation agents are used. Syringe pumps designed to be accurate a very low flow rates are used. They usually have a library of agents pre-programmed. TIVA requires a dedicated and monitored IV line to avoid awakening and awareness.

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9
Q

What are the two main models used for TCI

A

Marsh and Schnider

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10
Q

Describe the physical properties of propofol

A

Highly lipophilic (crosses BBB)

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11
Q

Is propofol soluble in water? Is propofol fat emulsion soluble in water?

A

No. Propofol is fat soluble Propofol’s preparation asa fat emulsion is an aqueous solution.

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12
Q

Describe the Propofol’s presentation

A

Glass ampoule No refrigeration required Fat emulsion - Propofol 1% - Soy bean 10% - Egg phosphatide 1.2% - Glycerol 2.25%

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13
Q

How long after an ampoule of propofol is opened should it be discarded and why?

A

6 hours. It is a fat emulsion and may act as a culture medium

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14
Q

What concentration of propofol is usually used for long infusions

A

2% (20, 50 and 100 ml ampoules are available)

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15
Q

What is the incidence of pain on injection of propofol?

A

30 - 40%

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16
Q

Do patients with egg allergy react to propofol.

A

Not usually

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17
Q

What are the uses of propofol

A

Induction Maintenance Sedation

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18
Q

What is the induction, maintenance and sedation dose for propofol

A

Induction: 1 - 2 mg/kg Maintenance: - TCI: 4 - 8 ug/ml. - TIVA 6 -12 mg/kg/hr Sedation: - TCI: 0.1 - 2.5 ug/ml - TIVA: 1.5 - 3 mg/kg/hr

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19
Q

What is the protein binding of propofol

A

98%

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20
Q

What is the Volume of Distribution of propofol compared to the other rapid acting induction agents

A

Propofol: 4L/kg Ketamine: 3L/kg Etomidate: 3L/kg Thiopentone: 2.5 L/kg

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21
Q

How does propofol’s clearance compare to hepatic blood flow?

A

Exceeds it. This means that some degree of extra-hepatic metabolism occurs

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22
Q

Describe the metabolism of propofol

A

Mostly hepatic - 40% conjugated to glucoronide - 60% metabolized to quinol (glucoronide and sulfate) All metabolites are inactive and excreted in urine

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23
Q

Compare the clearance of propofol to that of the other induction agents and state the relevance of this

A

Propofol: 30 - 60 ml/kg/min Thipentone: 3.5 ml/kg/min Ketamine: 17 ml/kg/min Etomidate: 10 - 20 ml/kg/min Propofol has the highest clearance - plasma levels fall more rapidly than other IV agents following the initial distribution phase

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24
Q

What is the terminal elimination half life of propofol

A

5 - 12 hours

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25
What is the time to peak effect (TTPE) for propofol in kids, adults, elderly
Kids: 2.5 min Adults: 3 min Elderly: \> 3 min
26
Describe the effects of propofol on the CNS
1. Induction: rapid LOC and rapid recovery - ± 5 minutes 2. Sedation and drowsiness at lower doses 3. Complete recovery: ± 3 hours 4. Reduced hangover effect vs. barbiturates, benzo and VA 5. Low incidence of excitatory phenomena
27
Does propofol lower the pain threshold or have analgaesic effects
Does not lower the pain threshold (thiopentone) No analgaesic effects
28
Describe propofol's effects on the CVS
Decreased SVR (BP down) uncommon reflex tachycardia Decreased SNS (HR down) Decreased contractility (SV down)
29
Describe propofol's effects on RSP
RSP depression: apnoea Airway reflexes depressed: LMA ! NO histamine release
30
Describe propofol's effects on GIT
Antiemetic (even at sub-anaesthetic doses)
31
What is Propofol Infusion Syndrome (PRIS)
Fat overload syndrome --\> fat overload in blood, heart, muscle, kidney, liver, lungs Lipaemia Metabolic Acidosis Cardiomyopathy and cardiac failure Skeletal Myopathy Death Doses \> 5 mg/kg/hr or \> 48 hours Children are at greater risk
32
What can be done to reduce the burning pain associated with propofol administration
1. New formulation: "Lipuro" 2. Add 2% lidocaine (1 - 2 ml) 3. Use new IV line with \> 18G cannula 4. Mini bier's block (venous torniquet for 2 mins and inject lidocaine before propofol administration)
33
Does propofol cause pruritis
It is an antipruritic
34
How does propofol interact with opioids?
Significant synergistic interaction - Advantage: less propofol needed for desired effect - Disadvantage: Increased incidence of side effects
35
Which conditions is propofol specifically indicated
Porphyria Asthma Day case anaesthesia
36
Which conditions should an agent other than propofol be used
Caution in elderly Heart failure Hypovolaemia Fixed cardiac output
37
Draw propofol
38
Describe the presentation of Thiopentone
Yellow powder Dissolved in water or normal saline **MUST remain strongly alkaline (pH 10.5)** - prepared with NaCO3 so when mixed with H2O makes NaHCO3 - N2 instead of air to remove CO2 from releasing H ions when mixed with H2O DO NOT DILUTE WITH ACIDIC: GLUCOSE CONTAINING FLUIDS OR MUSCLE RELAXANTS
39
What is the preferred strength of Thiopentone
2.5% Higher concentrations cause local irritant effects
40
How many hours is Thiopentone stable for once mixed?
24 - 48 hours
41
Can thiopentone act as a culture medium for micro-organisms
Its is bacteriostatic due to alkaline pH 10.5
42
What is the induction dose of Thiopentone for adults and children
Children: 5 -6 mg/kg Adults: 3 - 5 mg/kg
43
What is the time to peak effect (TTPE) of thiopentone and how does this compare to the TTPE of propofol
2 minutes Propofol: 3 mins
44
What are the effects of Thiopentone on the CNS
## Footnote 1. Rapid LOC 30s without spontaneous movement/cough/hiccough 2. Recovery 5 - 10 min (vs propofol 5 min) 3. Anticonvulsant 4. Brain protection: - Decreased CMRO2 - Decreased ICP.
45
What are the effects of Thiopentone on the CVS
1. Decreased SVR 2. Decreased SV 3. **Sometimes: compensatory tachycardia**
46
What effects does thiopentone have on RSP
RSP depression, apnoea Laryngospasm Bronchospasm
47
Give three examples of fixed cardiac output states
1. Stenotic valvular lesions 2. Cardiac tamponade 3. Constrictive pericarditis
48
Does thiopentone cause histamine release Does propofol cause histamine release
Thiopentone: yes Propofol: no
49
Name 5 drugs that can precipitate an acute porphyric crisis
1. Thiopentone 2. Etomidate 3. Halothane 4. Lidocaine | Cocaine | Prilocaine 5. Diclofenac | Clonidine 6. Metoclopramide | Hyoscine | Ranitidine
50
Name 5 anaesthetic drugs safe in Porphyria
Propofol Fentanyl Morphine Isoflurane Paracetamol Dexamethasone Ondansetron
51
What effect does thiopentone have on the Renal/Hepatic and GIT
1. Depressed function but minimal clinical relevance
52
When does venous thrombosis occur with thiopentone administration and why. What happens when thiopentone is injected extra-vascularly What happens if thiopentone is injected intra-arterial
EXTREMELY IRRITANT TO TISSUEs Thrombosis: When a 5% solution is adminstered - this should never be done Extra-vascular: Slight pain to extensive local tissue sloughingand necrosis Intra-arterial: Plasma pH of 4 --\> rapid precipitation of solid crystals --\> blocking arterioles and capillaries of narrow diameter. This does not happen in the veins as thiopentone is diluted by venous tributaries. --\> ischaemia and necrosis
53
Describe the treatment of an intravascular thiopentone injection
1. Prevention - use veins not known to be adjacent to arteries 2. Use 2.5% (Not 5%) and give test dose 3. Treat spasm - Leave cannula in and give one of the following: *
54
Summarize the absolute and relative contraindications of Thiopentone
**Absolute** Porphyria Anaphylaxis **Relative** CVS disorder Asthma
55
Summarize the key differences between propofol and thiopentone
Propofol (1.5 - 2.5mg/kg) 1. Can be used for Induction, maintenance and sedation. Large Vd and rapid metabolism. (PRIS) 2. Rapid emergence (5 minutes) 3. TTPE: 3 mins 4. Less hangover 5. Minimal excitatory phenomena 6. Depress airway reflexes 7. Less compensatory tachycardia 8. No histamine release 9. Use in porphyria/asthma/day case Thiopentone (3 - 7 mg/kg) 1. Use: Induction, status epilepticus 2. Slower emergence (5 - 10 mins) 3. TTPE (2 mins) 4. More hangover 5. Antanalgaesia 6. Brain protection (ICP | CMRO2) 7. More compensatory tachycardia 8. Histamine release 9. Use in status epilepticus
56
Describe the presentations of etomidate
1. 10 ml ampoules 0.2% 2. Dissolved in water 3. Propylene glycol 35% 4. pH 8.1 5. Can mix with Saline/water to make 1% solution
57
What % of patient experience pain on injection and how is this mitigated
25 -50 % (vs propofol 30 - 40%) FAST injection Large bore cannula Add 20mg lidocaine
58
What is the dose and time to peak effect (TTPE) of etomidate
±2 min
59
How long does it take to recover from an induction dose of etomidate?
6 - 8 minutes
60
Can etomidate be used as an infusion
No - adrenal suppression
61
What effects does etomidate have on the CNS
Rapid LOC High incidence of involuntary movements and myoclonus - reduced by opioids and midazolam.
62
How does the quality of recovery of etomidate compare to other induction agents
Etomidate - good Propofol - good Thiopentone - hang over Ketamine - halluconations/dissociative state
63
What are the effects of etomidate on the CVS
Minimal When combined with synthetic opioids and sux --\> can cause bradycardia
64
What are the effects of etomidate on the RSP
Mild reduction RR and Vt (less than other agents) No histmine release - suitable for asthmatics
65
What are the effects of etomidate on GIT
Vomidate - high incidence of N and V
66
What are the effects of etomidate on the endocrine system
Inhibits cortisol and aldosterone synthesis in the adrenal cortex - One dose supresses adrenal function for 5 - 8 hours (little clinical significane in healthy patients) - Infusions in ICU were associated with increased mortality in septic patients
67
Summarize the unique aspects of etomidate
1. Adrenal cortical supression (1 x dose --\> 5 - 8 hrs) 2. Involuntary movements and myoclonus common (reduced with midazolam/opioids) 3. CVS stable (Rarely: brady with sux and synthetic opioids) 4. RSP depression minimal and NO histamine release 5. Vomidate
68
How is etomidate made
Imidazole derivative
69
How is ketamine made
Phencyclidine derivative
70
Describe the physical properties of ketamine
Acidic solution 10mg/ml or 100 mg/ml Stable in solution with long shelf life Non-irritant
71
Which is the only one of the induction agents that is a non-irritant
Ketamine
72
Describe the dose, onset and duration of action of ketamine for induction of anaesthesia via the IV and the IM route of administration
## Footnote IV Dose: 1 - 2 mg/kg Onset: 30 - 60 seconds Duration: 5 - 15 minutes IM Dose: 5 - 10 mg/kg Onset: 3 - 8 mins Duration: 10 - 30 minutes
73
Describe the dose of ketamine used for maintenance of anaesthesia by bolus dosing and infusion
## Footnote Bolus: - 0.5 mg/kg incremental boluses Infusion - 1 - 4 mg/kg/hr
74
Describe the analgaesic doses of ketamine for both IV and IM routes of administration
## Footnote IV - 0.2 - 0.4 mg/kg IM - 2 - 4 mg/kg Both followed by an infusion 0.2 - 0.3 mg/kg/hour
75
Describe 4 effects of ketamine on the CNS
## Footnote 1. **Dissociative anaesthetic**: complete analgaesia and amnesia but involuntary movements/nystagmus/hypertonus/vocalisation - EEG: dissociation between thalamus/limbic system/cerebral cortex 2. **RICP and RIOP** --\> no clear clinical significance plus ketamine exhibits some neuroprotective effects 3. **Psychotic reactions** in recovery: Rx with opioids and benzos and dark area 4. Potent **antidepressant** and inhibits active suicidal behaviour
76
Describe the effectsof ketamine on the CVS
1. Sympathomimmetic: Increase - HR, BP, SVR, CO 2. Dysrrhythmias uncommon - Release of central catecholamines - Direct myocardial depressant --\> unmasked when catecholamine stores are depleted.
77
Describe the effects of ketamine on the RSP
1. Minimal RSP depression 2. Preserved airway reflexes (but no protection from aspiration - full stomach) 3. Bronchodilation SNS and no Histamine release 4. Increased salivary and bronchial secretions (give glycopyrrolate)
78
Which of the four inductions agents cause histamine release and is therefore contraindicated in Asthma
Thiopentone
79
Describe the effect of ketamine on GIT
N and V is relatively common
80
What is the effect of ketamine on the uterus
May cause uterine contractions in the first TM of pregnancy
81
List 8 uses for ketamine
1. High risk surgical patients 2. Paediatric surgery 3. Short procedures (diagnostic/surgical) 4. Analgaesia 5. Trauma 'field-work' 6. Status asthmaticus 7. Psychiatry for refractory depression (alternative to ECT)
82
What are the contraindications to ketamine
1. CVS disease (HPT | IHD | Aneurysm | HF) 2. Epilepsy 3. Thyrotoxicosis 4. Oral/airway surgery when airway reflexes need to be supressed 5. Early pregnancy 6. Pts on TCAs --\> interaction causes HPT and dysrhythmias
83
Name a drug with significant drug interactions with ketamine
Tricyclic antidepressants
84
Differentiate the physical properties and preparations of diazepam and midazolam
## Footnote Diazepam (tablets and supp available) - Insoluble in water (5mg/ml) Midazolam (tablets available) - Water soluble - pH dependent ring opening phenomenon (pH 7.4 ring closes --\> highly lipid soluble) - Preparations: 1mg/ml in 5ml and 5mg/ml in 3 ml
85
Describe the pharmacokinetics of diazepam and midazolam
Diazepam - Poor IM absorption - Rapid oral absorption - Long elimination half life - Active metabolites and accumulation - don't infuse Midazolam - Rapidly absorbed oral and IM - Short elimination half life - No active metabolites and no accumulation - maybe infused.
86
Describe the premedication, induction and sedation doses for Diazepam and Midazolam
## Footnote Premedication (1 hour pre-op) - Diazepam: 5 - 10 mg PO - Midazolam: 7.5 - 15mg PO Induction (significant inter-individual variation in dose) - Diazepam: 0.1 - 0.6 mg/kg IV - Midazolam: 0.1 - 0.3 mg/kg IV Sedation - Midazolam: 0.1 mg/kg IV (elderly and sick patients much less)
87
Describe the effects of midazolam on the CNS
## Footnote 1. Slow onset: 1 - 2.5 mins and variable 2. Good anterograde amnesia 3. Low incidence irritable airways 4. Anticonvulsant 5. Lower dose VA for maintenance 6. Elderly: long period of disorientation 7. Unsuitable for day case surgery
88
Describe the effects of midazolam on the CVS
## Footnote 1. Small decrease BP (like in sleep) 2. Transient slight increase HR
89
Describe the effects of midazolam on the RSP
1. Small dose - ok 2. Large dose --\> apnoea esp. with opioids 3. No Histamine release
90
Describe th effect of midazolam on the GIT
Low incidence N and V
91
Are benzodiazepines suitable for Caesarian Section and why?
NO 1. Hypotonia (Ux) 2. Hypothermia 3. RSP depression neonate 4. Mothers full stomach (RSI not possible)
92
How does flumazenil work?
Competitive antagonism at the benzodiazepine receptor
93
What are the indications for flumazenil
1. Termination of GA induced and maintained by benzos 2. Reversal of benzo sedation in short diagnostic and therapeutic procedures 3. Reversal of benzo overdose 4. Diagnostic measures in unconsciousness of unknown origin
94
What is the onset, duration of action and dose of Flumazenil
## Footnote Dose: 0.2 mg IV (followed by 0.1 mg every 1 min until total dose of 1mg) Onset: 5 minutes Duration: 1 - 3.5 hours
95
How should induction agents be administered?
Titrated to effect (except in RSI) Inject 25% of calculated dose and observe: LOC, RSP, CVS response.
96
How do mg/kg doses vary with the extremes of age
Neonate: lower Infant/children: higher Elderly: lower
97
What does rapidity of onset depend on for drugs
1. Nature of drug 2. Speed of injection 3. Central Vd 4. Cardiac output
98
Rank the time to recovery from fastest to slowest for the induction agents
Fastest 1. Propofol 2. Etomidate 3. Thiopentone 4. Midazolam 5. Ketamine 6. Diazepam Slowest
99

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