IV Anesthetics Flashcards
Propofol MOA
GABA-A
Directly stimulates GABA A and potentiates the actions of endogenous GABA
Propofol onset
30-60 seconds (one circulation time)
Propofol duration
5-15 min
Propofol induction dose
1-2.5 mg/kg IV bolus
Propofol maintenance of gen anesthesia dose
100-300 mcg/kg/min (when only TIVA)
Ketamine induction dose
1-4.5 mg/kg IV lasts 5-10 min
Etomidate induction dose
0.2-0.4 mg/kg
Dex loading dose
1mcg/kg over 10 minutes
Ketamine IM dose
4-8 mg/kg lasts 12-25 min
Ketamine sedation dose
0.1-0.5 mg/kg IV
Ketamine dose for chronic pain
0.1-0.3 mg/kg/hr
Ketamine depression dose
0.5 mg/kg over 30-40 minutes
Flumazenil dose for benzo reversal
0.2 mg
Remimazolam dose for adult induction
5mg over 1 minute
Remimazolam dose for adult maintenance
After 2 minutes of loading, 2.5 mg over 15 seconds prn
Midazolam induction dose
0.1-0.2 mg/kg over 30 to 60 seconds
Midazolam adult sedation dose
0.25 -2.5 mg
Propofol sedation dose
25-75 mcg/kg/min (or 10-20 mg)
Propofol sedation bolus dose
1-2 ml
Propofol antiemetic dose
10-15 mcg/kg/min
Mechanism of action of Barbiturates
Potentiating GABA A channel activity.
(also work on glutamate, adenosine, and neuronal nicotinic ACh receptors)
Increase affinity of GABA for it’s binding site, thereby increasing the duration of GABA A activated opening of chloride channels.
MOA of Barbiturates at higher doses
Mimic action of GABA by directly activating GABA A receptors
Type of metabolism of barbiturates
Hepatic, mostly oxidation, EXCEPT phenobarbitol.
Increases production of porphyrins
Elimination of phenobarbitol
Unchanged via renal excretion
Important considerations for induction dose of thiopental
Age, weight, and MOST importantly, cardiac output
Barbiturate used for anticonvulsant therapy
Methohexital - has decreased anticonvulsant effect
CNS effects of barbiturates
Dose-dependent CNS depression
Decreased CMRO2 and CBF
Decreased ICP
Decreased EEG activity
NO analgesia
Respiratory effects of barbiturates
HIstamine release - SEVERE
Resp Depression
Dose-Dependent depression of medullary and pontine ventilatory centers
Laryngeal and cough reflexes not depressed until large doses
CV effects of thiopental
5mg/kg IV produces 10-20mm decrease in BD.
Due to vasodilation but also depression of medullary vasomotor center and decreased SNS outflow.
Offset by compensatory 15-20 bpm increase in HR
Induction dose Methohexital
1-1.5 mg/kg
What is propofol used for
sedation, induction, maintenance of anesthesia
2, 6-diisopropyl phenol
Propofol
pH and pKa of diprivan
7-8.5
11
pH of generic Propofol
4.5-6.4
hours prop syringe is good for
hours prop tubing is good for
6
12
Propofol antipruritic dose
10 mg
What type of transmitter is GABA
inhibitory
What happens when GABA A receptors are activated
Transmembrane chloride conductance increases
Reason why you can use propofol when monitoring evoked potentials
Spinal motor neuron excitability is not altered
Propofol - time to awakening is dependent on what
dose and patients (5-15 min)
Prop distribution half life
2-4 minutes
Prop elimination half life
1-5 hours
Propfol % protein binding
98%
Two IV agents that are not highly protein bound
Etomidate - 75%
Ketamine - 12%
What is context sensitive half time and what does it depend on?
The time needed for the pasma levels of a drug to drop by 50% after stopping the infusion.
Depends of duration for which an infusion has been run
Does Propofol have analgesic properties?
NO
CNS effects of propofol
Decreased CMRO2
Decreased cerebral blood flow
Decreased cerebral blood volume
Decreased ICP
Decreased Intraocular pressure
Large doses cause burst suppression on EEG
CV effects of propofol
Decreased BP - transient and within 10 minutes of induction.
Decreased CO, CI, stroke volume index, SVR, sympathetic tone
What does of prop reduces SBP by 25-40%
induction dose of 2-2.5 mg/kg
What factors make CV effects of Prop more pronounced
Elderly
ASA > 3
Baseline MAP <70
Given with high doses of fentanyl (synergistic)
Respiratory effects of Prop
Dose-dependent resp depression
Decreased Tidal Volume
Apnea
Decreased sensitivity to CO2
Minimal bronchodilation
Other properties of Propofol
Anti-emetic
Antipruritic
Pain on injection
Easily passes placental barrier
Green urine - phenols
Cloudy urine - uric acid
What propofol does NOT do
Does not:
Enhance neuro-muscular blockade
Trigger MH
Affect corticosteroid synthesis
Normally affect hepatic or renal function
What are the allergic components of propofol
Phenyl nucleus
Disopropyl side chain (rare)
In lipid emulsion formulations - Lecithin (egg yolk)
Generic - Metabisulfite or benzyl alcohol preservative
Clinical characteristics of PRIS
-Impaired systemic microcirculation with tissue hypoperfusion and hypoxia
EKG changes (arrhythmias, wide QRS)*
Severe Metabolic Acidosis *
Refractory bradycardia -requires pacing
Hypotension
Hyperlipidemia
Renal failure
Rhabdo
Fever
Hyperkalemia
Hypoxia
Hepatic disturbances
Risk factors for PRIS
Long-term high dose infusions of propofol
Dose > 5mg/kg per hour
Duration >48 hours
ICU setting
High-fat low-carb intake (keto)
Inborn errors of mitochondrial fatty acid oxidation
Concomitant catecholamine infusion/steroid
Management of PRIS
D/C propofol
Sedate with versed or precedex
Supportive measures
Cardiac pacing
NO established guidelines
Success of tx r/t earlier diagnosis
IV anesthetic with hypnotic but not analgesic properties and with minimal hemodynamic effects
Etomidate
Etomidate is _______ soluble at an acidic pH and _______ soluble at physiologic pH
water soluble at acidic
lipid soluble at physiologic
MOA of Etomidate
Single isomer (stereoisomer)
Anesthetic effect resides in the R+ isomer
Relatively selective as a modulator of GABA A receptors
Onset of etomidate
100 seconds
DOA of etomidate
Usually 5-15 minutes
Depends on redistribution to inactive tissue sites
Metabolism of etomidate
Hepatic by ester hydrolosis to inactive metabolites, then excreted in urine and biles.
Initial distribution half life of etomidate
2.7 minutes
Redistribution half life of etomidate
29 minutes
elimination half life of etomidate
2.9 - 5.3 hours
CNS effects of etomidate
Dose-dependent CNS depression within one arm-brain circulation-hypnotic via GABA.
NO analgesia
CBF and CMRO2 decreased
ICP decreased (but no change in MAP so CPP stays the same)
Myoclonia
IOP Decreased
CV effects of etomidate
PRIMARY advantage is hemodynamic stability in modestly debiliated patients.
No change in HR, PAP, CI, SVR, and SBP (unless pt has aortic or mitral valve disease)
NO effect on SNS/baroreceptor
How does etomidate mediate increased BP
Acts as agonist at a2B-adrenoceptors
Respiratory effects of etomidate
Dose-dependent decrease in tidal volume, but RESP RATE INCREASES.
Decreased ventilatory response to CO2.
Brief periods of apnea.
Little effect on bronchial tone
NO histamine release
Etomidate’s mechanism of adrenocortical suppression
Dose dependent inhibition of the conversion of cholesterol to cortisol.
Inhibits 11 b-hydroxylase.
Lasts 8-12 hours after SINGLE induction dose.
Primary advantage of etomidate
Hemodynamic stability in modestly debilitated patients
When is etomidate contraindicated
Known sensitivity
Adrenal suppression
Acute porphyrias
enzyme inhibited by etomidate
11beta hydroxylase
Etomidate effect on nausea/vomiting
increases
Fade is observed with which type of NMBDs
Nondepolarizing
What causes fade during TOF stimulation
Antagonism of the presynaptic nicotinic receptors by nondepolarizing NMBDs
At rest, is the inside of the cell generally positive or negative
Negative
What drugs are metabolized by pseudocholinesterase
Succ, mivacurium, and ester local anesthetics
Primary location of acetycholinesterase
Neuromuscular junction
Primary location of pseudocholinesterase
Plasma
Treatment for hyperkalemia that stabilizes the myocardium
IV calcium
Treatment for hyperkalemia that shifts potassium into the cell
Glucose + insulin
Sodium bicarb
Hyperventilation
Albuterol
Treatment for kyperkalemia that promotes K elimination
Lasix
Volume resuscitation
Hemodialysis
Hemofiltration
Benzylisoquinolinium nondepolarizing drugs
Atracurium
Cisatracurium
Mivacurium
Aminosteroid nondepolarizing drugs
Rocuronium
Vecuronium
Pancuronium
What is Hofmann elimination dependent on
Normal blood pH and temperature
NMBDs that don’t produce an active metabolite
Rocuronium
Mivacurium
NMBDs that produce active metabolite Laudanosine
Atracurium
Cisatracurium
Metabolism of Atracurium
Plasma: Hofmann and ester hydrolysis
Metabolism of Cisatracurium
Plasma: hofmann elimination
Metabolism of Mivacurium
Plasma: Pseudocholinesterase
Metabolism of Rocuronium
None: Undergoes biliary excretion
Metabolism of Vecuronium
Liver
Metabolism of Pancuronium
Liver
85% eliminated from kidneys
Which NMBDs release histamine
Succ
Atracurium
Mivacurium
Hofmann elimination is faster with
Alkalosis and hyperthermia
Hofmann elimination is slower with
Acidosis and hypothermia
Reversal agent of diazepam, midazolam, and lorazepam
Flumazenil - selective antagonist
Desired effects of benzos
Anxiolysis and anterograde amnesia, sedation, hypnosis, and anticonvulsant
MOA of Benzos
Agonist action at benzodiazepine receptor binding sites on the GABA A receptor throughout the CNS
How does the GABA A receptor exert its action
Modulating chloride channels
Is midaz lipid soluble or water soluble in vivo/blood
Lipid at pH >4
Which effect of midazolam greater, amnestic or sedative
Amnestic
Does midazolam cross the placenta
Yes
How are benzos metabolized
Selectively metabolized by hepatic cytochrome P450 to single dominant ACTIVE metabolite
CNS effects of benzos
Dose-dependent CNS depression
Anticonvulsant effects, amnesia, muscle-relaxing properties
Not all antiemetic (midaz is antiemetic)
Reduce CMRO2 and CBF at higher doses
Dose-related anterograde amnesia
NO ANALGESIA
CV effect of benzos
Sedation dose= minimal effects
*unless elderly, cv disease, or given with opioids
Induction dose= decrease in SBP and SVR
Resp effects of benzos
Dose-dependent depression
Midazolam is MOST respiratory depressing
Most common adverse effects of benzos
Unexpected respiratory depression and over-sedation
Avoid in patients with porphyria
Sedation dose of Midazolam
Onset
Peak
Duration
IV: 0.25-2.5 mg
Onset: 30-60 seconds
Peak: 5 minutes
Duration: 15-80 minutes
Induction dose of Midazolam
0.1-0.2 mg/kg IV over 30-60 seconds
Remimazolam metabolism
Rapid via nonspecific tissue esterases to an inactive carboxylic acid
Remimazolam Dose for adults
5mg IV over 1 minutes
Remimazolam dose for ASA 3-4 adults
2.5 - 5mg IV over 1 minutes
Remimazolam maintenance dose
After AT LEAST 2 minutes, 2.5 mg over 15 seconds
Remimazolam preparation
Powder needs reconstituted
20 mg vial
8ml NSS = 2.5 mg/ml
10ml NSS = 2 mg /ml
For infusion, reconstitute to 1 mg/ml
Remimazolam Onset
1-1.5 minutes
Peak sedation 3-3.5 minutes
Remimazolam Duration
11-14 minutes
Initial dose of flumazenil
0.2 mg IV
Onset of flumazenil
2 minutes
DOA of flumazenil
30-60 minutes
Subsequent dosing of flumazenil
0.1 mg IV at 60 second intervals
When should flumazenil not be given
For patients being treated with antiepileptic drugs for control of seizure activity
MOA of flumazenil
Competative Benzo receptor antagonist
Effects of ketamine
Dissociative Anesthesia
Amnesia
Intense analgesia
Retains protective reflexes
Eyes remain open with slow nystagmus
MOA of ketamine
Antagonism at NMDA receptors in brain
Dissociates thalamus (sensory) from limbic system (awareness)
Direct inhibition of cytokines in blood
Inhibit TNF-a and interluken 6
Ketamine’s primary site of analgesic action
Thalamo-neocortical system
When is the NMDA receptor activated
When glutamine and glycine bind to it
How does ketamine work on the NMDA receptor
Deactivates. Decreases presynaptic release of glutamate
Metabolism of Ketamine
Extensively by hepatic microsomal enzymes. Demethylation by P450 to form active metabolite Norketamine.
<4% unchanged in urine.
<5% fecal excretion
What is elimination of ketamine dependent upon
Hepatic blood flow. High hepatic extraction.
Onset of ketamine
3-5 minutes
Ketamine elimination half life
2-3 hours
CNS effects of Ketamine
Cerebral dilator
Increases CBF and CMRO2
Emergence delirium
Can increase CBF up to 60%
Nystagmus, Increased IOP
Increased EEG activity
CV effects of Ketamine
Stimulant
Increases BP, HR, Contractility, CO, CVP via centrally mediated sympathetic stimulation
Increased myocardial O2 consumption
Ketamine not used for patients with:
Increased ICP
Recent MI or severe heart disease
Respiratory effects of Ketamine
Minor and short duration
Reflexes and tone remain intact
Central response to CO2 maintained
Increases pulm compliance and decreases resistance
NO histamine release
ONLY active bronchodilating IV induction agent
Increases secretions
IV induction drug of choice for active asthma/wheezing for urgent surgery
Ketamine
Dexmedetomidine class
highly selective alpha 2 agonist.
Targets high density of alpha 2 receptors in the pontine locus ceruleus
Primary effects of Dex
sedation, analgesia, anxiolysis, reduced postop shivering and agitation, CV sympatholytic actions
What class of alpha 2 agonist is Dex
Imidazolines
MOA of Dex
Stimulates a2 receptors resulting in decreased catecholamine release.
Activates sleep pathways
Analgesic effects at the dorsal horn of spinal cord
Metabolism of Dex
Rapid hepatic involving conjugation, n-methylation, and hydroxylation.
Metabolites excreted in urine and bile.
No active metabolites
Onset of Dex
10-20 minutes after loading dose
DOA of Dex
10-30 minutes after infusion stopped
Loading dose for Dex
1 mcg/kg over 10 minutes
Maintenance dose of Dex
0.2-0.7 mcg/kg iv infusion
CNS effects of Dex
Does not interfere with electrophysiologic monitoring.
No change in CMRO2.
CBF decreased due to vasoconstriction.
Reduces postop agitation and delirium.
CV effects of Dex
Hypotension and bradycardia
Transient hypertension with rapid loading dose.
NO direct effect on contractility
Reduces myocardial O2 demand
Transient profound HTN with glyco
Resp effects of Dex
Respirations maintained
Responsiveness to CO2 is normal
Airway patency and reflexes present or slightly diminished
Decrease airway reactivity in pts with COPD or Asthma
