IV Agents Flashcards
What are the rapidly acting IV-induction agents?
Propofol
Sodium Thiopentone
Etomidate
Ketamine
What are the slower-acting IV inducting agents?
Benzodiazepines (e.g. diazepam, midazolam)
Neuroleptics (e.g. droperidol)
Large-dose opioids (e.g. fentanyl)
Advantages of IV induction?
- Rapid onset of action
- Smooth induction with rapid transfer through stage II
- More pleasant for patient
- “Pollution” free
Disadvantages of IV induction?
- Venepuncture required
- Easy to overdose
- No removal of drugs via the lungs (once its in, its in)
- Sudden loss of normal protective mechanisms and often apnoea
MoA of IV induction agents (excluding Ketamine)?
Not fully understood. Modulate GABA (inhibitory NT) neuronal transmission, thereby interfering with transmembrane electrical activity.
MoA of Ketamine?
An opioid receptor agonist
Antagonises NMDA receptor
Metabolism and excretion of IV induction agents?
These lipid-soluble drugs are metabolised in the liver to inactive water-soluble metabolites, then excreted in urine.
TIVA stands for?
Total Intravenous Anaesthesia
The 2 drugs used for TIVA?
Propofol
Ketamine
TCI stands for?
Target Controlled Infusion
Indications for TIVA?
Risk of hyperthermia
Severe PONV
Day-case surgery
TIVA dosing with Propofol?
Initial bolus: 1mg/kg
Infusion:
10mg/kg/hr (10 minutes)
8mg/kg/hr (10minutes)
6mg/kg/hr thereafter
("10-8-6" regimen)Physical properties of Propofol?
1% propofol preparation (10 mg/kg) in a fat emulsion
Fat emulsion can act as a culture medium
Ampoule should be used within 6 hours of opening
Also available as 2% solution for infusion
Often stings on insertion
Pharmacokinetics of Propofol?
Clearance > hepatic flow
Highly fat soluble and sequesters in fat following long infusions
Rapid decrease in Propofol concentration upon stopping of infusion (regardless of infusion duration)
Dosing of Propofol for induction?
Adults: 1,5-2,5 mg/kg
Infants and young children: 2,5-3,0 mg/kg
Elderly: less than adult
Dosing of Propofol for sedation?
1,5-3,0 mg/kg/hr
CNS effects of Propofol?
Rapid LOC and rapid recovery Minimal impairment of psychomotor function Less hangover effect than other agents Low incidence of excitatory phenomena No antanalgesia Antipruritic
CVS effects of Propofol?
Less compensatory tachycardia than other agents
Reduced SVR (systemic vascular resistance)
Greater hypotensive effect than other agents
Respiratory effects of Propofol?
Respiratory depression
High incidence apnoea
Depressed laryngeal reflexes (good for LMA insertion)
No histamine release (safe in asthmatics)
GIT effects of Propofol?
Anti-emetic properties
Metabolic effects of Propofol?
PRIS (Propofol infusion syndrome)
Characteristics of PRIS?
Rare
Lipemia, metabolic acidosis, CMO, CF, skeletal myopathy and death
Doses of 5 mg/kg/hr >48 hours
Indications for Propofol?
Induction agent of choice for porphyria
Good agent for asthmatics (no histamine release)
Suited for day-case anesthetics
Contraindications for Propofol?
Heart failure
Hypovolaemia
Fixed CO (aortic stenosis/ mitral stenosis/HOCM)
(Caution in the elderly)
Physical properties of Sodium Thiopentone?
Barbiturate (anti-convulsant)]
Yellow, amorphous powder that can be dissolved in H20/saline
Alkaline solution (pH 10,5)
Must not be mixed with low pH solutions (i.e. glucose, muscle relaxants) as barbiturates will precipitate
Stinky
Mix 500 mg ampoule with 20 ml saline = 25 mg/ml (2,5%)
Solution stable for 24-48 hours
Dosing of Thiopentone?
Adults: 3-5 mg/kg
Children: 5-6 mg/kg
CNS effects of Thiopentone?
Smooth LOC (within 30s) Recovery 5-10min Small doses may cause antanalgesia Good anti-convulsant Used in treatment of status epilepticus (brain protection: decreased cerebral metabolic rate of O2 consumption and decreased ICP)
CVS effects of Thiopentone?
↓ CO 10-20% (peripheral vaso-dilatation, negative inotropic effect, ↓ central catecholamine release)
Exaggerated in CF, hypovolaemia, fixed CO etc.
Respiratory effects of Thiopentone?
POTENT depression of respiratory centre
Laryngeal reflexes NOT depressed until deep (early instrumentation may result in laryngospasm)
Histamine release (not suited for asthmatics)
Local effects of Thiopentone?
Extreme irritant to local tissues (beware extra-vascular and intra-arterial injections)
Prevention and treatment of an intra-arterial injection of Thiopentone?
Prevent:
Avoid veins next to known arteries
2,5% (NOT 5%) and test dose
Treat spasm: Leave cannula in artery and inject Papaverine 40-80mg in 10-20ml saline Sympathetic block (vasodilates) Anti-coagulation (thrombus) Analgesia
Absolute and relative contraindications to Thiopentone?
Absolute:
Porphyria
Known allergy to Thiopentone
Relative: CF Hypovolaemia Fixed CO Asthma
Physical properties of Etomidate?
Imidazole derivative
pH 8,1 (alkaline)
1 ml ampoules with 2 mg/ml of drug dissolved in water with 35% propylene glycol
May be mixed with saline or water to make 1 mg/ml solution
Also available in fat emulsion (not to be confused with propofol)
Burns on insertion
Dosing of Etomidate?
0,2-0,3 mg/kg
CNS effects of Etomidate?
Rapid onset
Rapid recovery (6-8min)
High incidence of involuntary movement and myoclonus
CVS effects of Etomidate?
Very stable
May cause marked bradycardia with synthetic opioids and suxamethonium
Respiratory effects of Etomidate?
Little respiratory depression
No histamine release
GIT effects of Etomidate?
High incidence of PONV (“vomidate”)
Anti-emetic recommended
Endocrine effects of Etomidate?
Inhibits cortisol and aldosterone synthesis in the adrenal cortex (one dose suppresses adrenal function 5-8h)
Physical properties of Ketamine?
Acidic solution Suitable for IV, IM or oral 1% and 10% solutions available Stable in solution Long shelf life
Pharmacokinetics of Ketamine?
When surgical anaesthesia terminated, 50-60% drug still remains in body in active form
Main metabolite has weak hypnotic properties
(Causes complete analgesia with superficial sleep)
Dosing of Ketamine?
Induction:
IV: 1-2mg/kg (onset 30-60s, lasts 5-15min)
IM: 5-10mg/kg (onset 3-8min, lasts 10-30min)
Maintenance: 0,5mg/kg IV (incremental boluses) OR 1-4mg/kg/hr (infusion)
Analgesia: 0,2-0,4mg/kg IV/2-4mg/kg IM, followed by infusion of 0,2-0,2mg/kg/hr
CNS effects of Ketamine?
IV induction 90s Complete analgesia and amnesia Involuntary movements not uncommon Increases ICP and intra-ocular pressure Psychic reactions during recovery (can be reduced by concurrent administration of benzodiazepines or opioids)
CVS effects of Ketamine?
Sympathomimetic effect ↑HR ↑BP ↑CO
Direct stimulation of central catecholamine release
A direct myocardial depressant that may be unmasked if catecholamine stores are depleted
Respiratory effects of Ketamine?
Minimal respiratory depression
Pharyngeal reflexes preserved and good airway control (do not need to instrument)
Bronchodilation
No histamine release
Increased bronchial and salivary secretions (administration of a drying agent recommended)
GIT effects of Ketamine?
PONV relatively common
Uterine effects of Ketamine?
May cause uterine contractions in first trimester
Indications for Ketamine?
Poor risk surgical patients Paediatric surgery Burns patients Short procedures Analgesia Anaesthesia in sub-optimal conditions (“field work”) Treatment of status asthmaticus
Contraindications for Ketamine?
CVS disorders Raised ICP Cerebral aneurysms Open eye injuries Increased intraocular pressure Psyche patients Epileptics Thyrotoxicosis Full stomach Early pregnancy Tricylclic antidepressants
Pharmacokinetics of Midazolam?
Rapidly absorbed after oral or IM administration
Metabolites have little clinical significance
High clearance
Short elimination half-life
Accumulation less likely to occur than Diazepam, and may be administered as a continuous infusion
Dosing of Midazolam?
Premed (30-60 min pre-op): 7,5-15,0 mg orally
Induction: 0,1-0,3 mg/kg IV
CNS effects of benzodiazepines?
Slower induction Good anterograde amnesia Low incidence of excitatory phenomena Anticonvulsant Disorientation after a prolonged period in the elderly
CVS effects of benzodiazepines?
Stable
Slight fall in BP
Small transient increased HR
What is Flumazenil?
Benzodiazepine antagonist
Indications for Flumazenil?
Termination of GA induced/maintained with benzo’s
Reversal of benzo sedation
Reversal of benzo OD
Diagnostic measure in unconsciousness of unknown origin
Dosing of Flumazenil?
0,2 mg IV
A second dose of 0,1 mg may be injected after 60s and repeated every 60s up to a total dosage of 1 mg
