Exam 2 - Etomidate and Ketamine Flashcards by Brandon Simpson

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.

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Etomidate is a weak ____ the and only (chemical structure) ____ -containing compound.

What does that mean?

base; carboxylated imidazole

This means that etomidate is water-soluble at an acidic pH and lipid-soluble at physiological pH (7.4).

similar to midazolam

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Due to etomidate containing 35% ____ as a carrier agent, there will be pain at the injection site and venous irritation.

propylene glycol

Textbook says now formulated with lipids so it doesn’t burn

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Etomidate has 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.

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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.

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What is Etomidate’s MOA?

Directly and Indirectly opens Cl- channels of GABA_A receptors

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What is the onset time for etomidate?

1 minute IV

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What percent of etomidate is bound to albumin?
How does this effect drug duration?

76%

In general, highly protein bound drugs have prolonged duration of action.

Remember: drugs bound to albumin are inactive. The free-floating drugs are the ones that are active.

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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 of etomidate counteracts the 76% binding capacity to albumin

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How is Etomidate metabolized?

Hydrolysis by hepatic microsomal enzymes and plasma esterases.

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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

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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.

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Etomidate is best suited for what type of patients for induction?

Unstable Cardiovascular patients, especially the ones with little or no cardiac reserves.

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What are the analgesic effects of etomidate?

There is no analgesic effects

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What is the primary side effect seen with etomidate?
How can this be mitigated?
What patients would we use caution with because of this?

Involuntary myclonic movements
Pre-administering opiods (fentanyl 1-2 mcg/kg IV) or benzos
History of seizures

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Rank these drugs from highest incidence of myoclonus to least:
Propofol, thiopental, methohexital, and etomidate

Etomidate (50-80%)
Thiopental (17%)
Methohexital (13%)
Propofol (6 %)

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Fentanyl 50 mcg/mL is available and your patient weighs 75 kg. You want to adminster 1 mcg/kg to attenuate myclonus. How many mLs will you administer?

1.5 mL

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How does etomidate cause adrenocortical suppression?
What side effects will this cause?

Through dose-dependent inhibition of the conversion of cholesterol to cortisol… inhibiting the stress response.
Severe hypotension, increased time for MV, enzyme inhibition lasting 4-8 hours

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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

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What does this graph tell you?

Etomidate is associated with a decrease in the plasma concentration of cortisol.

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CNS side effects of etomidate include a decrease in ______ and ________.

Decrease in Cerebral Blood Flow (CBF) and Cerebral Metabolic Rate of O2 (CMRO2).

CBF and CMRO2 decrease by 35% to 45%

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Like most of our barbiturates (thiopental), etomidate is a potent direct cerebral _________.

What does this do to ICP?

Vasoconstrictor

Decrease ICP

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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.

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What are the CV effects of Etomidate?

Most CV stable induction agent with minimal changes in HR, SV, CO, and contractility.
Decreases PAP
Mild decrease in MAP d/t decrease in SVR.
No intra-arterial damage and no histamine release.

Etomidate can cause sudden hypotension with hypovolemia with high induction doses

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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 medullary centers.

stimulates

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. 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.

What advantages does ketamine have over propofol and etomidate?

* No pain on injection. * Profound analgesia at subanesthetic doses.

What are the disadvantages of ketamine?

Frequent emergence delirium. Abuse potential.

What is the preservative of ketamine? What is the significance of this?

* Benzethonium Chloride * This preservative inhibits nicotinic acetylcholine receptors, which will helps increase analgesic effects

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. This causes ____ effect.

* Catecholamines * Cocaine-like (increases SNS effects)

Patients that receive racemic ketamine will have less ____ and ____ .

Less fatigue Less cognitive impairment

MOA of Ketamine (3)

1. Binds noncompetitively to **N-methyl-D-aspartate (NMDA)** receptor. This will inhibit the activation of the NMDA receptors by glutamate and decrease the presynaptic release of glutamate. 2. Ketamine will also bind to opioid receptors (mu, delta, kappa) and weak bind to sigma receptors. *analgesic effects* 3. Ketamine will have weak actions at GABA-A receptors

Ketamine Onset of action: Duration of action: Lipid Solubility: Vd:

Onset 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?

The hepatic enzyme, cytochrome P450. 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, IM, PO.

IV: 0.5 - 1.5 mg/kg IM: 4 - 8 mg/kg PO: 10 mg/kg

What is the maintenance dose of ketamine IV and IM.

IV: 0.2 - 0.5 mg/kg IM: 4 - 8 mg/kg

What is the analgesic (subanesthetic) dose of ketamine IV?

0.2 - 0.5 mg/kg IV

What is the post-op sedation and analgesia dose of ketamine (pediatric surgery)?

1 - 2 mg/kg/hr

What is the neuraxial analgesia dose of ketamine epidural and spinal?

Epidural: 30 mg Spinal: 5 - 50 mg in 3 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

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) Great for asthmatic and MH patients (bronchodilator) Pediatric induction (IM) Burn dressing changes, debridement, skin graft. Reversal of opioid tolerance. Improve Psych disorder. Restless Leg Syndrome.

Ketamine is available in 25mg/mL vials. How much diluent should be used to obtain a concentration of 5 mg/mL?

4 mL (total of 5 mL)

What are the components of the coronary artery disease cocktail?

Diazepam 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?

* Systemic/Pulmonary HTN * Increase ICP

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 SNS stimulation. There will be an increase in SBP, PAP, HR, CO, and MRO2. Increase plasma Epi and NE levels.

How can the CV effects of ketamine be mitigated?

Premedicate with BZD or inhaled anesthetics or nitrous

Ketamine can result in unexpected drops in SBP and CO d/t _______.

Depleted catecholamines stores Needs to be treated with exogenous catecholamines - not ephedrine or atropine.

Respiratory effects of ketamine: No significant depression on ____ . Ventilatory response to CO2 is ____ . PaCO2 is unlikely to increase more than ____ . Upper airway ____ 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 Mitigate by giving BZD 5 minutes prior to ketamine administration.

Other side effects of ketamine include inhibition of ____ . Can induce bleeding. Decreases ____ 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: NDMB: Succinylcholine:

Drug interactions with ketamine. Volatile anesthetics: Hypotension NDMB: Enhanced Succinylcholine: Prolonged

OSA and Ketamine Risks: Benefits:

OSA and Ketamine Risks: Psych effects, SNS activation, hypersalivation Benefits: Upper airway preservation and ventilatory function, bronchodilator effect.

What is Ketafol?

Ketamine and Propofol *Propofol, unlike thiopental, etomidate, and ketamine, is not a chiral compound. The mixing of propofol with any other drug is not recommended,*

What is the immediate use rule for single-dose medication?

Meds that are sterilely compounded must be used in 4 hours.