Lecture 6 Induction: Etomidate and Ketamine Test 2 Flashcards
Even though Methohexital (Brevital) has a higher non-ionized component (76%) at normal pH than pentothal (61%). Why does Methohexital have a lower lipid solubility than pentothal?
Oxybarbitruates (Methohexital) have oxygen at the second position. Replacement of the oxygen with sulfur atom results in the corresponding thiobarbiturates (Pentothal) which are much more lipid soluble and have greater potency.
Basically, percent ionization can not be the sole factor to determine solubility. In this example, chemical structure determines lipid solubility.
When giving a highly lipid-soluble drug, why would a lower dose be administered to someone with a high fat-to-bodyweight ratio (obese patient and geriatrics)?
People with low body fat will have a smaller volume of distribution as there is not significant about of fat for the drug to distribute to, so they will require less bc there will be no drug stored in a non-existent body fat.
When there is a high fat-to-bodyweight there will be less blood volume to kilogram ratio. For this reason, it is important to administer certain drugs by ideal body weight.
Just think less lean muscle, lower drug dose.
Etomidate is the only (chemical structure) __________ __________-containing compound.
What does that mean?
carboxylated imidazole
This means that etomidate is water-soluble at an acidic pH and lipid-soluble at physiological pH (7.4).
Due to etomidate using 35% ______________ as a carrier agent, there will be pain at the injection site and venous irritation.
propylene glycol
Make sure to use lidocaine before to numb the internal structures of the vein (excluding cardiac patients)
What musculoskeletal SE does Etomidate have a high incidence of _________.
myoclonus
(Make sure to not mistake the myoclonus for the patient being awake, giving more etomidate will increase myoclonus.)
Myoclonus is the most significant adverse side effect of etomidate.
Etomidate is the only induction drug with direct systemic absorption in the oral mucosa that bypasses ___________.
Hepatic Metabolism
The percentage of the active drug does not decrease if given PO due to bypassing hepatic metabolism.
What is the mechanism of action of Etomidate?
Selective modulator of GABA-Alpha receptors.
What percent of etomidate is bound to albumin?
76%
Remember: drugs bound to albumin are inactive. The free-floating drugs are the ones that are active.
Etomidate has a large Vd, resulting in a clearance that is _______ times faster than thiopental. What does this mean for the patient?
5 times faster
Prompt awakening with Etomidate.
The large Vd/clearance of etomidate counteracts the 76% binding capacity to albumin (counteracts the fact that theres is so much free unbound drug)
How is Etomidate metabolized?
Hydrolysis by hepatic microsomal enzymes and plasma esterases.
What is the elimination half-time for Etomidate?
Percent of Etomidate eliminated in the urine and bile?
2-5 hours
85% eliminated in the urine
10-13% eliminated in the bile
What is the dose of etomidate?
What is the onset time?
Range: 0.2 to 0.4 mg/kg IV
Onset: 1 minute
For clinical use, etomidate is a great alternative to _______or _____ for IV induction of anesthesia.
Propofol or Barbiturates
Etomidate also has no hangover or cumulative drug effects, unlike pentothal and thiopental.
Etomidate is best suited for what type of patients for induction?
Unstable Cardiovascular patients, especially the ones with little or no cardiac reserves.
What are the analgesic effects of etomidate?
There is no analgesic effects
Opioids are used with etomidate during direct laryngoscopy and tracheal intubation.
What can be given to attenuate the myoclonic effects of etomidate prior to administration?
Opioids (*Fentanyl 1 to 2 mcg/kg) or BZD
What is the incidence rate of myoclonus with etomidate?
50-80%
Caution use in patients with seizure history
Etomidate causes myoclonus due to alteration in the balance of inhibitory and excitatory influences on the ________ tract.
Thalamocortical Tract
Fentanyl concentration: 50 mcg/mL .
Patient’s weight is 100 kg.
Administer 1 mcg/kg to attenuate myoclonus, how many ml will you administer?
2 mL
How does etomidate affect adrenocortical response?
Etomidate will cause adrenocortical suppression.
(Dose-dependent inhibition of the conversion of cholesterol to cortisol, decrease stress response)
What will be the physiological result and complication of adrenocortical suppression from etomidate?
Enzyme inhibition will last between _____ to _____ hours after the initial dose.
Blocks stress response - inhibits conversition of cholesterol to cortisol
Severe hypotension
Longer Mechanical Ventilation hours
4 to 8 hours after the initial dose of etomidate
When might we need to keep our cortical response intact and might have to consider an alternative besides etomidate?
When dealing with septic or hemorrhagic patients
What does this graph tell you?
Etomidate is associated with a decrease in the plasma concentration of cortisol.
CNS side effects of etomidate include a decrease in ______ and ______. By how much?
Decrease in Cerebral Blood Flow (CBF) and Cerebral Metabolic Rate of O2 (CMRO2).
CBF and CMRO2 decrease by 35% to 45%
Like most of our barbiturates (thiopental), etomidate is a potent direct cerebral _________.
What does this do to ICP?
Vasoconstrictor
Decrease ICP
Compare EEG changes between Thiopental and Etomidate.
Etomidate will have more frequent excitatory spikes because it lowers the seizure threshold.
Etomidate may activate seizure foci and augment the amplitude of Somatosensory Evoked Potential (SSEP)….more labile monitoring.
What are the CV effects of Etomidate?
Most CV stable induction agent with minimal changes in HR, contractility, SV, and CO
Mild decrease in MAP d/t decrease in SVR.
No intra-arterial damage and no histamine release.
Etomidate can cause sudden hypotension with hypovolemia
What are the respiratory side effects of etomidate?
Less ventilation depressant than barbiturates, d/t rapid clearance.
Rapid injection will lead to apnea.
Decrease Vt is offset by a compensatory increase in RR (Transient, will last 3-5 mins).
What is the formula for minute ventilation?
Tidal Volume x Respiratory Rate
Etomidate _________the CO2 drive through the stimulation process.
preserves
Ketamine is a derivative of _______.
Why is this drug used for induction?
Phencyclidine (PCP) Angel Dust
Ketamine is used for its amnestic and intense analgesic properties.
Describe the dissociative anesthesia of Ketamine (Hint: sloth)
Signs & Sx:
The patient will resemble being in a cataleptic state (dazed) in which eyes are open with a slow nystagmic gaze.
Signs & Sx: uncommunicative, but wakefulness is present; hypertonus and purposeful skeletal muscle movements.
It’s like talking to a sloth.
What advantages does ketamine have over propofol and etomidate?
No pain on injection. (Lipid emulsion not required.)
Profound analgesia at subanesthetic doses.
What are the 2 disadvantages of ketamine discussed in PPT?
Frequent emergence delirium.
Abuse potential.
What is the preservative of ketamine?
Benzethonium Chloride
Describe S(+) Ketamine:
_______-handed optical isomer
More Intense Analgesia:
___x greater than racemic ketamine
___x greater than R(-) ketamine
_______ metabolism and recovery
_______ salivation
________ incidence of emergence
Describe S(+) Ketamine:
Left-handed optical isomer
More Intense Analgesia:
2x greater than racemic ketamine
4x greater than R(-) ketamine
Faster metabolism and recovery
Less salivation
Lower incidence of emergence
Racemic Ketamine inhibits the uptake of __________ back into postganglionic sympathetic nerve endings.
Use ketamine with caution in these types of patients:______________
Catecholamines
(this will result in a cocaine-like effect)
A-fib, Coronary Artery Disease, SVT, Hx of V-fib, Hx of MI
Patients that receive racemic ketamine will have less ________ and ________.
Less fatigue
Less cognitive impairment
MOA of Ketamine
Binds noncompetitively to N-methyl-D-aspartate (NMDA) receptor.
This will inhibit the activation of the NMDA receptors caused by glutamate and decreases the presynaptic release of glutamate.
Ketamine will also bind to opioid receptors (mu, delta, kappa) and weak bind to sigma receptors. analgesic effects
Ketamine will have weak actions at GABA-A receptors
Others: Monoaminergic, muscarinic, volatage-sensitive sodium, L-type calcium, & and neuronal nicotinic AChR
Ketamine
Onset time of action:
Duration of action:
Lipid Solubility:
Vd:
Ketamine
Onset time of action: Peak plasma concentration at 1 minute (IV). 5 minutes for IM (pediatric patients).
Duration of action: 10-20 minutes
Lipid Solubility: High (5x to 10x than Thiopental). (goes to the brain, does not bind with albumin, distributed to the tissues)
Vd: Large Vd (3L/kg), elimination half-time 2-3 hours
What is the hepatic clearance rate of ketamine?
1L/min
How is ketamine metabolized?
What is its metabolite, active or nonactive?
How is ketamine excreted?
Hepatic CYP450 enzymes
Norketamine, active, one-third potency, prolonged analgesia
Excreted through the kidneys
With ketamine, there is increased tolerance and potential for abuse/dependence with _____ patients.
burn
What is the induction dose of ketamine IV and IM.
IV induction dose: 0.5 - 1.5 mg/kg
IM induction dose: 4 - 8 mg/kg
What is the maintenance dose of ketamine IV and IM.
IV maintenance dose: 0.2 - 0.5 mg/kg
IM maintenance dose: 4 - 8 mg/kg
What is the subanesthetic dose (analgesic dose) of ketamine IV?
0.2 - 0.5 mg/kg IV
What is the post-op sedation/analgesia dose of ketamine (pediatric cardiac surgery)?
1 - 2 mg/kg/hr
What is the neuraxial analgesia dose of ketamine epidural and spinal (to include intrathecal/subarachnoic)?
Epidural: 30 mg mixed in a drip
Spinal: 5 - 50 mg/mL saline
Ketamine can induce ________. Therefore, the maintenance of pharyngeal and laryngeal reflexes (coughing/laryngospasm) is crucial.
What can be given to mitigate this?
salivary secretions
Glycopyrrolate (0.2 mg)
Glycopyrrolate acts as an anticholinergic or antimuscarinic agent. Its mechanism of action (MOA) involves blocking the action of acetylcholine at muscarinic receptors in the body. These receptors are found in various tissues and organs, including the salivary glands, bronchial tubes, and the gastrointestinal tract. By inhibiting the action of acetylcholine, glycopyrrolate reduces secretions (such as saliva and mucus), decreases the acidity of gastric secretions, slows the gut motility, and can help in dilating the airways.
What is the time for loss of consciousness (LOC) for ketamine?
Time to return to consciousness (ROC)?
Full consciousness?
How long does amnesia persist after ROC?
LOC: 30-60 seconds (IV); 2-5 minutes (IM)
ROC: 10 - 20 minutes
Full Consciousness: 60 - 90 minutes
Persistence of amnesia after ROC: 60 - 90 minutes
What are the clinical uses of ketamine?
Great for acutely hypovolemic patients (SNS effect)
Great for asthmatic (bronchodilator),
MH
Pediatric induction
Burn dressing changes, debridement, skin graft.
Reversal of opioid tolerance.
Improve Psych disorder.
Restless Leg Syndrome.
What are the 3 components of the coronary artery disease cocktail?
Diazepam (valium) 0.5mg/kg IV
Ketamine 0.5mg/kg IV
Continuous Ketamine infusion 15-30 mcg/kg/min IV
What patients do you want to avoid giving ketamine to?
Pulmonary: Systemic/Pulmonary HTN
Neuro: Increase ICP
Increase SNS effect from ketamine
CNS side effects of ketamine:
Potent cerebral ___________.
Can increase CBF by ____%
CNS side effects of ketamine:
Potent cerebral vasodilator.
Can increase CBF by 60%
There will be no further increase of ICP with what IV dose of ketamine?
0.5 to 2 mg/kg IV
Does ketamine’s excitatory activity in EEG alter seizure threshold?
No
But there is still a risk for myoclonus
Ketamine will increase amplitude with Somatosensory Evoked Potential (SSEP). This can be reduced with what?
Nitrous
CV effects of ketamine:
Resembles _______ stimulation.
SNS
There will be an increase in SBP, PAP, HR, CO, and MRO2.
Increase plasma Epi, and NE levels (prevents reuptake of catecholamines by the preganglionic neuron)
How can the CV effects of ketamine be mitigated?
Premedicate with BZD, inhaled anesthetics, or nitrous
Ketamine can result in unexpected drops in SBP and CO d/t _______.
Depleted catecholamines stores
Ephedrine will not help b/c it is an indirect vasoconstrictor. Give a director vasoconstrictor (phenylephrine) instead.
Respiratory effects of ketamine:
No significant depression on ________.
Ventilatory response to CO2 is ________.
PaCO2 is unlikely to increase more than _______.
Respiratory-wise __________ and ________ are maintained and intact.
_________ salivary secretions.
_________ bronchodilator activity.
_________ histamine release.
Respiratory effects of ketamine:
No significant depression on ventilation.
Ventilatory response to CO2 is maintained.
PaCO2 is unlikely to increase more than 3mm Hg.
Upper airway skeletal muscle tone and reflexes are maintained and intact.
Increase salivary secretions.
Increase bronchodilator activity.
No histamine release.
5 to 30% of patients on ketamine will have ________.
Signs/Sx:
Psychedelic Effects (Emergence Delirium)
S/Sx: Visual, auditory, proprioceptive, and confusional illusion, delirium, vivid dreams up to 24 hours.
How does ketamine cause emergence delirium?
How do you mitigate emergence delirium?
Depression of the inferior colliculus and medial geniculate nucleus (responsible for separating reality and fantasy)
Mitigate by giving BZD 5 minutes prior to ketamine administration.
What are two drugs to give prior to ketamine?
Glycopyrrolate (for increased salivary secretions)
Versed (mitigate SNS symptoms?)
Other side effects of ketamine include inhibition of _______. Can induce bleeding.
Inhibits ______ which can enhance nondepolarizing NMBD.
Inhibits _____ which will prolong apnea from Succinylcholine.
Other side effects of ketamine include inhibition of platelet aggregation. Can induce bleeding.
Inhibits cytosolic free calcium concentration which can enhance NMBD.
Inhibits plasma cholinesterase which will prolong apnea from Succinylcholine.
Drug interactions with ketamine.
Volatile anesthetics:
NDNMB:
Succinylcholine:
Drug interactions with ketamine.
Volatile anesthetics: Hypotension
NDNMB: Enhanced
Succinylcholine: Prolonged
OSA and Ketamine
Risk:
Benefits:
OSA and Ketamine
Risk: Psych effects, SNS activation, hypersalivation
Benefits: Upper airway preservation and ventilatory function, bronchodilator effect.
What is Ketafol?
Ketamine and Propofol
Best practice is to separate your meds, don’t mix.
What is the immediate use rule for single-dose medication?
Meds that are sterilely compounded must be used in one hour.
USP 797: Now extended to 4 hours as of Nove 1, 2023
