SS25 Induction Drugs (Etomidate & Ketamine) (Exam 2) Flashcards
In general, thiobarbiturates are much more _____ soluble and have a greater _______ than oxybarbiturates.
What atom do thiobarbiturates have in lieu of an oxygen in the second position (like oxybarbiturates)?
- Lipid; potency
- Sulfur
- Goal: Surgical stimulation at peak time
- Study table
What is unique about Etomidate’s organic chemical structure?
It is the only carboxylated imidazole containing compound.
Etomidate:
- water-soluble vs lipid-soluble?
- Is it a weak acid or weak base?
- H₂O-soluble at acidic pH.
- Lipid-soluble at physiologic pH
- weak base
What percentage of etomidate is propylene glycol? What is the result of this?
- 35% propylene glycol resulting in pain on injection.
What additional route can Etomidate be given?
- Clinical significance?
- Sub-lingual
- Only drug with direct systemic absorption in oral mucosa that bypasses hepatic metabolism
- great for pediatrics
Why does etomidate have a low incidence of myoclonus?
- Trick Question! Etomidate has a high incidence of myoclonus, just like all other induction agents.
Etomidate MOA?
Indirect & Direct opening of Cl⎺ channels of GABA-a receptors → hyperpolarization
Etomidate;
- Onset?
- Peak?
- Protein bound percent & which protein?
- E1/2?
- Onset: 1 minute
- Peak: 2 min
- 76% Albumin bound
- E1/2: 2- 5 hrs
Etomidate:
- Vd
- Clearance? Compared to Thiopental?
- What is the result of this clearance?
- Large Vd (2.2 - 3.5 L/kg)
- CL: 10 - 20 mL/kg/min
- 5x faster than Thiopental = prompt awakening
- No hangover or accumulative drug efffect
Etomidate:
- Metabolism?
- Elimination?
- Metabolism: Hydrolysis via CYP450 & plasma esterases
- Elimination: Urine 85% & Bile 10 - 13%
What is the induction dosage range for etomidate?
- 0.3 mg/kg
What is the best use for etomidate?
- Induction for unstable cardiac patients (patients with no cardiac reserve; low EF/ low LVEDP)
What needs to be used concurrently with etomidate when performing a laryngoscopy? Why?
- Need Opioid, Etomidate has NO analgesic effects.
What is Etomidate’s most common side effect?
- How often does this occur?
-Risk factors (3) per lecture?
- Involuntary Myoclonic Movements (Thalamocortical Tract)
- 50 - 80% of Etomidate administrations (highest of all the induction drugs)
- Seizure history, vaping, cannabis use
What should be administered with etomidate to prevent involuntary myoclonic movements?
- Fentanyl 1-2 mcg/kg IV
- Opioids and benzos both help lessen occurence
Etomidate has a dose dependent inhibition of the conversion of cholesterol to _________.
- What is this condition termed as?
- What does this mean clinically?
- Cortisol
- Adrenalcortical Suppression with prolonged use: inhibits stress = catecholamines depletion
- Prolonged mechanical ventilation, severe hypotension
- More common with continuous use vs. induction dose
What can you give to pre-medicate if patient is increased risk for Adrenalcortical Suppression?
- Solumedrol or Prednisone
How long does adrenocortical suppression with etomidate last?
- What two pathologies do you want to avoid the use of Etomidate in?
- 4 - 8 hrs
- Sepsis & hemorrhage (anything where you need an intact cortisol response)
Compare Etomidate and Thiopental to plasma cortisol levels.
- Compared to Thiopental, Etomidate will lower plasma cortisol concentrations greatly.
T/F: Etomidate is a direct cerebral vasoconstrictor.
- False!
- Etomidate is a Direct Cerebral Vasoconstrictor
What effects does Etomidate have on CNS?
- Direct Cerebral Vasoconstrictor
- Decreases ↓CBF & ↓CMRO₂ by 35- 45%
- ↓ICP
(Prop and Thiopental does this as well)
Etomidate:
- EEG compared to Thiopental?
- Can Etomidate induce seizures?
- Is SSEP amplitude increased or decreased affected? How does this effect the monitoring?
- Similar EEG to Thiopental but more frequent excitatory spikes
- May activate seizure foci
- Increases SSEP amplitude; can cause false positive imopulse (signal may not detect nerve is in danger of being cut during neuro sx)
Etomidate CV effects:
- Most cardioprotective
- Minimal changes in HR, SV, SVR, CO, contractility,
- Decreased PAP
- Mild decrease in MAP
- No intra-arterial damage
(Remember: Thiopental causes Gangrene)
Though Etomidate is great for cardiac patients, what condition can result in significant hypotension if not treated prior to induction?
- Hypovolemia
- Esp. high dose induction (0.45 m/kg IV)
Histamine-induced hypotension via Etomidate is prevented by what med?
- Trick question! Etomidate does NOT release histamine.
Etomidate: Pulm effects
- No change in minute ventilation
- Transient increases RR q 3 - 5 mins offsets Vt decreases (compensatory)
- Less ventilation depression than barbiturates
- Rapid IV produces apnea
- Stimulates CO₂ medullary centers → emerge breathing earlier (avoids CO2 narcosis)
(Etomidate not as lipid soluble as barbs)
(MV = Vt x RR)
Ketamine:
- Derivative?
- What type of anesthesia does it produce?
- Phencyclidine derivative (PCP; “angel dust”)
- Dissociative anesthesia
Ketamine:
- Primary receptor type?
- What 2 components of GA does Ketamine provide?
- NMDA receptor antagonist
-Amnestic and intense analgesic properties
Ketamine: dissociative anesthesia S&S
- Zonked state: “Eyes open but no one’s home”
- Non-communicative but awake
- Hypertonus & purposeful skeletal muscle movements
- Cataleptic state (slow nystagmic gaze)
Hypertonus = Risk for Rhabdo!
-Also, maintain safety (restraints, etc.)
What are ketamine’s 2 advantages over Propofol & Etomidate?
- No pain at injection (no propylene glycol)
- Profound analgesia at subanesthetic doses.
What are the 2 disadvantages of ketamine?
- Emergence delirium (Dissociation)
- Abuse potential (PCP)
What is Benzethonium Chloride? What is it’s relevance?
- Ketamine preservative that adds to its effect
- Inhibits ACh receptors
Differentiate S (+) Ketamine, R (-) Ketamine, & Racemic mixtures,
- S (+) Ketamine (left-handed isomer)
1. More intense analgesia = 2x > Racemic; and 4x > R (-)
2. ↑metabolism & recovery
3. Less salivation
4. ↓ incidence of emergence rxns - Racemic
1. Inhibits Catecholamine uptake back into postganglionic sympathetic nerve endings (cocaine-like effect)
2. Less fatigue
3. Less cognitive impairment
R (-) Ketamine - R handed optical isomer
Ketamine: MOA?
- Non-competitive inhibition of NMDA (N-methyl-D-aspartate) receptors and decreases pre-synaptic release of glutamate
Glutamate most abundant excitatory neurotransmitter in CNS
- Glycine = obligatory co-agonist
Ketamine: Secondary receptor sites? (A lot)
- Opioid (μ, δ, κ & weak σ)
- Weak GABA-a -sedation effects
- Muscaranic: Anticholinergic properties = increase salivation, emergence delirium, bronchodilation, sympathomimetic)
- MOA: antinociceptive; may activate descending inhibitory pathway
- VG Na channels- local anesthetics effects
Others: n-Ach, L-type Ca channels, MOA
Ketamine:
- Onset?
- Peak? (IV & IM)
- Onset: Similar to Thiopental (rapid)
- Peak IV: 30 sec - 1 min
- Peak IM: 2 - 5 min (mostly for pediatric patients)
Ketamine: Induction DOAs
- Loss of consciousness (onset)
- ROC (return of consciousness)
- Full consciousness:
- Amnesia persists after ROC
- LOC (onset): 30 secs - 1 min
- ROC: 10 - 20 mins
- Full consciousness: 60 - 90 mins
- Amnesia persists after ROC: 60 - 90 mins (won’t remember the drive home postop)
Ketamine:
- Protein bound percent?
- Lipid solubility?
- CL?
- What is the result of this?
- Vd?
- E1/2?
- PPB = Trick Question! NOT plasma bound
- Highly lipid soluble (5-10x greater than thiopental)
- CL: high CL from brainto tissues
- Vd = 3 L/kg (LARGE)
- E ½ = 2 - 3 hours
Ketamine:
- Clearance:
- Metabolism:
- Excretion:
- Clearance: high hepatic clearance (1 L/min)
- Metabolism: CYP450
- Excretion: Kidneys
What is the primary metabolite of ketamine?
- Significance?
- Norketamine: active metabolite (⅓-⅕ potency and prolonged analgesia
In what patient population is ketamine tolerance most often seen?
- Burn patients: Abuse & dependence potential
Ketamine Induction dose:
- IV
- IM
-PO
- IV: 0.5 - 1.5 mg/kg
- IM: 4 - 8 mg/kg
- PO: 10 mg/kg
Ketamine Maintenance dose: IV & IM
- IV: 0.2 - 0.5 mg/kg for analgesia
- IM: 4 - 8 mg/kg
IM dose same for Induction & Maintenance;
IV dose same as regular analgesic dose
Ketamine: Subanesthetic/ analgesic dose:
- IV: 0.2 - 0.5 mg/kg
Ketamine: Postop sedation & analgesia
- What type of sx is this dose used in?
- 1 - 2 mg/kg/hr
- Pediatric cardiac sx
Ketamine:
- Neuraxial epidural
- Spinal/ Intrathecal
- Epidural: 30 mg
-Spinal: 5 - 50 mg in 3 cc of saline
Intrathecal/spinal/subarachnoid
Ketamine is a potent sialagogue.
- Clinical significance?
- Excessive secretions during intubation
- Watch for coughing/ laryngospasm
What first line drug do you use to treat ketamine-induced salivary secretions?
- Dose?
- Other drugs options?
- First line: Glycopyrrolate: 0.2 mg
- Atropine, Scopaline (emergence delirium)
Ketamine: Clinical uses (8)
- Include rationale for each
- Acutely hypovolemic patients - stimulates SNS
- Asthmatics & MH patients - bronchodilator
- Pediatric induction - difficult to manage
- Cardiac sx - CAD cocktail - prevent iscemia
- Burn & skin dressings/ procedures
- Reversal of opioid tolerance
- Psych dx (OCD, PTSD, Depression)
- Restless Leg Syndriome (10mg/kg PO)
OTHER PEDI CHOICES: NASAL PRECEDEX, PO VERSED
Bonus: What volatiles and IV anesthetics induce bronchodilatory properties?
SHIPMK
- Sevo
- Halothane
- Isoflurane
- Propofol
- Midazolam
- Ketamine
- Why would we use a CAD cocktail?
- What’s the ingredients?
- Help avoid cardiac event; synergisticaly reduces risk of dysrhythmias during sx
- Diazepam 0.5 mg/kg IV
- Ketamine 0.5 mg/kg IV
- Continuous Ketamine IV infusion: 15 - 30 mcg/kg/min
When would you do an IM induction of a patient?
- What’s the IM dose again?
- Uncooperative and difficult to manage patients; not just kids
- 4 - 8 mg/kg IM
When do we avoid Ketamine us?
- Systemic/ Pulmonary HTN - (increase up to 44%)
- ↑ICP - Ketamine is potent cerebral vasodilator
Explain mechanism of Ketamine on ICP.
- Potent cerebral vasodilator
- ↑ICP via ↑CBF by 60%
- ↑CMRO₂ & ↑ glucose
At what dose of Ketamine will the ICP plateau?
- 0.5 - 2mg/kg IV
Start low
Due to Ketamine’s increased excitatory EEG activity, how much does seizure potential increase with administration?
- Trick question. No increase in seizure potential with ketamine
- Myoclonus may occur
Outlier: Etomidate alters sz threshold
Ketamine increases SSEP amplitude. This may be reduced by _________ gas use.
- Nitrous
Ketamine: CV effects
How can CV effects be blunted?
- SNS stimulation ( ↑ in SBP, PAP, HR, CO, CMRO₂,)
- ↑Epi & NE
- Blunted via pre-med with benzo’s, inhaled anesthetics, or nitrous gas
You just gave Ketamine and you patient’s BP and CO dropped significantly (marked hypotension).
- What happened?
- How do you treat it?
- Most sympathetic drug
- Depleted catecholamine stores
- Give Epi - direct acting, non-selective
- direct myocardial depressant
- No histamine release
Etomidate: most CV stable
Ketamine: Pulm effects
- No depression of ventilation with CO₂ response maintained.
- ↑ salivary excretions
- Intact upper airway tone & reflexes.
- Bronchodilator + no histamine release.
Good for pulm patient, with healthy heart
Ketamine-induced emergence delirium S&S:
- Psychedelic effects (5-30% of patients)
- Visual, auditory, proprioceptive illusions
- Morbid & vivid dreams in color/hallucinations up to 24 hours
- Not an adverse reaction
Ketamine-induced emergence delirium MOA:
- Depression of inferior colliculus & medial geniculate nucleus
Ketamine-induced emergence delirium prevention
- IV benzo 5 mins prior
- Clonidine or Precedex
Ketamine other systems effects :
- Inhibit cytosolic free [Ca] = Enhances non-depolarizing NMBAs (ie: Rocuronium)
- Inhibit plasma cholisterases = Prolong apnea from Succinylcholine
- PLT aggregation inhibition (low significane)
Ketamine: Most common drug interactions
- Volatiles (Iso, Sevo, Des) → hypotension
- Non-depolarizing NMBAs → enhanced
- Succinylcholine → prolonged
What are the risks and benefits of Ketamine use in OSA?
- Benefits: Preservation of Upper airway reflexes (on subanesthetic doses) & Ventilatory function
- Risks: Psych effects, SNS activation, hypersalivation
Bronchodilator
Which induction agent has the highest analgesic properties?
- Ketamine
Ketafol
- Ketafol = Propofol & Ketamine mixture
- Not approved FDA but facility trumps FDA
- **Propofol is NOT chiral = unstable **
- Not recommended to mix Prop with any drug
- Prop + Lido (lipid bubbles = PE)
- Prop + Succ (BBW peds) - some facilities approved; Pre-treat Glycopyrolate
Sterile Prep USP 797
- Sterile compounding
-Immediate use rule: Single dose meds - Able to draw up within 4 hrs pre-op (new)
- PPE
- Aseptic
