Kost IV anesthesia

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Barbiturates, benzodiazepines, and hypnotics

Which compound has a pH of 10-11 and why?

Barbiturates, due to the inclusion of sodium carbonate which prevents precipitation of free acids by atmospheric carbon dioxide

How do barbiturates work?

They bind to GABA receptors and reduce neuronal activity

Which drug gives dissociative anesthesia?

Ketamine

Which drug class has a naturally occurring ring structure?

Opioids

Which receptor gives the most respiratory depression?

Mu2

Where does Ketamine work?

Old theory: functionally dissociates thalamocortical and limbic systems
New theory: binds noncompetitively to the phencyclidine recognition site on the NMDA receptor (inhibiting activation of the receptor)

How is barbituric acid formed?

Condensation of urea and malonic acid

Which barbiturate has the shortest duration of action?

methohexital (Brevital)

Which class of drug is used in ECT and why?

Barbiturates, because they lower the seizure threshold

What are the steps in treating intra-arterial injection of barbiturates?

1. LEAVE THE IV IN!
2. Remove any restrictive garments (on the patient)
3. Inject papaverine or procaine to inhibit smooth muscle spasm
4. Heparinize unless contraindicated
5. If necessary, perform sympathetic block of brachial plexus and/or stellate ganglion to relieve pain and dilate collateral circulation

What are two things that can adversely affect rectal barbiturate administration?

1. Evacuation
2. Incorrect catheter placement, leading to inadequate absorption

Which class of drugs has an antianalgesic effect and how can the anesthetist counteract this?

Barbiturates, supplement with fentanyl

What effects do barbiturates have on the CNS?

Decreased ICP, decreased CBF, decreased CMRO2

What effects do barbiturates have on the CV system?

Transient reduction in CO, increase in HR, hypotension secondary to vasodilation

Is histamine released upon administration of pentothal?

Yes

Is histamine released upon administration of methohexital?

No

How do barbiturates affect the respiratory system?

Decreased ventilatory response to hypercarbia and hypoxemia, decreased minute volume and tidal volume (all dose dependent)

What is an absolute contraindication to use of barbiturates?

Acute intermittent porphyria

How do barbiturates exacerbate acute intermittent porphyria?

They stimulate the activity of a mitochondrial enzyme which accelerates the production of heme

What is the induction dose for thiopental?

3-5mg/kg IV

What is the induction dose for methohexital?

1-1.5mg/kg IV

You're in the OR and your patient begins to seize. What is the first drug you can grab?

Midazolam (0.1mg/kg IV for suppression of seizure activity)

How is midazolam buffered in the bottle?

Its benzene ring is open in the bottle, making it water soluble with a pH of 3.5. In the body the ring closes and the drug becomes lipid soluble.

What six properties do benzodiazepines have?

Hypnotic, sedative, anxiolytic, muscle relaxant (at higher doses), amnestic (anterograde), anticonvulsant

What is the mechanism of action of benzodiazepines?

Bind to alpha subunit of GABA receptor, enhancing inhibitory effect of GABA (inhibition is due to increased influx of chloride ions into the cell, increasing the polarization of the nerve cell so ability to promote a signal is decreased)

What drug has propylene glycol as a suspension?

Diazepam

How protein-bound are benzodiazepines? Who needs caution with administration?

90-98% protein bound, leaving 2-10% free drug. Use caution with debilitated patients with low plasma proteins.

Which factor impacts the rate of biotransformation most?

Patient age. The older the patient, the less drug needed. 30 is the peak of physiological function. :(

Which population needs the most caution when administering benzodiazepines and why?

Elderly, because benzos are dependent on hepatic microsomal enzyme activity, hepatic blood flow, protein binding, and lipid solubility. Elderly patients have slow drug absorption, decreased plasma protein, decreased hepatic blood flow, decreased metabolism, decreased CO, and decreased circulation time (??? this was in his slide... doesn't he mean INcreased circ time?)

Does midazolam create active metabolites?

No

Does diazepam create active metabolites?

Yes, demethylation yields oxazepam, which is pharmacologically active.

Benzodiazepines have long half-lives. Why is this important?

It's important to consider for elderly patients, as well as for dosing intervals.

How are benzos metabolized and excreted?

Metabolized by conjugation and excreted in the urine.

What effect does enterohepatic circulation have on diazepam?

Produces a secondary peak in plasma concentration within 6-12 hours

What effects do benzos have on the CNS?

Dose-related decrease in CBF, ICP, and CMRO2, and increase in seizure threshold.

How do benzos affect the respiratory system?

Dose-related decrease in hypoxic drive/response to CO2, decreased ventilation (higher doses)

How do benzos affect the CV system?

No actual CV effect, but a decrease in HR and BP may occur due to anxiolysis

What is the induction dose for midazolam?

0.1-0.3mg/kg IV

What is the induction dose for lorazepam?

0.1mg/kg IV

What is the induction dose for diazepam?

0.3-0.5mg/kg IV

What is the reversal agent for benzodiazepines?

romazicon (Flumenazil)

What is the half-life of romazicon?

41-79 minutes. Clinical duration of action is about 20 minutes

What is the problem when you combine the half-life of romazicon with the half-life of benzos?

Sedation can return. Patient should be monitored for 120 minutes after giving romazicon.

What is a common side effect of romazicon?

Nausea and vomiting

What is the dose for romazicon?

0.2mg, repeat as needed. Max single dose = 1mg

Which medication is a dissociative?

Ketamine

What is the induction dose for ketamine?

1-2mg/kg IV or 4-6mg/kg IM

Agree or disagree?: Ketamine interacts with GABA receptors

Disagree

Agree or disagree?: Ketamine is a NMDA receptor agonist

Disagree. It's a NMDA receptor antagonist

How is ketamine metabolized?

The hepatic microsomal enzyme is responsible for the biotransformation of ketamine.

Does ketamine form an active metabolite?

Yes, ketamine is demethylated into norketamine, which is 20-30% pharmacologically active

How does ketamine affect the CNS?

Produces profound analgesia, a dissociative state of amnesia, and a cataleptic state (eyes open, pupils reactive to light, corneal reflexes intact, lacrimation and blinking)

Agree or disagree?: Ketamine increases CBF?

Agree, but only transiently. Increases by 60-80%, and returns to normal in 20-30 minutes

What effects does ketamine have on the CV system?

It is an all-around circulatory stimulant: increases BP, CO, HR, CVP, myocardial contractility, and myocardial O2 consumption.

What causes the transient changes in CV after a dose of ketamine?

Sympathetic nervous system stimulation

Ketamine is contraindicated in which patients?

CHF, CAD, uncontrolled HTN, neuro, cerebral aneurysms.

What patients are the exception to the ketamine CV rule?

Those who are catecholamine depleted (then ketamine will act as a myocardial depressant)

What respiratory side effects are associated with ketamine?

Minor and/or transient decrease in tidal volume (accentuated with larger doses or concomitant opioid), increased salivation

Can a person anesthetized with ketamine protect their own airway?

Theoretically, yes. Ketamine preserves the laryngeal, pharyngeal, cough, sneeze, and swallow reflexes

What is the induction dose of etomidate?

0.2-0.3mg/kg IV

How does etomidate work?

Depresses the RAS and mimics the inhibitory effects of GABA, producing a hypnotic CNS effect

What is the chemical structure of etomidate?

It is an imidazole derivative

Agree or disagree?: Etomidate is water soluble?

Disagree, it is lipid soluble and results in extensive redistribution to organs and tissues after one minute

How is etomidate metabolized?

By hepatic microsomal enzymes and produces plasma esterases via hydrolysis, resulting in inactive metabolites

How is etomidate excreted?

Mostly in the kidneys, 10% bile and 13% feces

Does etomidate have analgesic properties?

No, due to its inability to block afferent pain stimulus to the thalamus

What does etomidate do to CBF and CMRO2?

Decreases both, it is a potent cerebral vasoconstrictor

_________ ________ is a distinct disadvantage of etomidate which produces ________ ________

Excitatory phenomenon; muscle tremors

Agree or disagree?: Etomidate produces profound CV changes with normal doses. With higher doses?

Disagree. Changes to HR, SV, and CO are minimal. With higher doses, significant decrease in BP and CO occur.

Does etomidate produce histamine release?

No

What effect does etomidate have on respiration?

Dose dependent respiratory depression, including increased RR, decreased MV, apnea followed by hyperventilation

What medication is associated with adrenocortical suppression?

Etomidate

Which enzyme is inhibited by etomidate?

11 beta hydroxylase

What is the induction dose for propofol?

1.5-2.5mg/kg IV

What is the mechanism of action of propofol?

It mimics GABA's inhibitory effect

Propofol is structurally related to ________

alkylphenols

When a patient has an egg allergy on their chart, can you give propofol?

Yes, because allergy is usually to the egg protein (egg white), and propofol contains egg phosphatide (yolk)

What are two ways to minimize the pain of propofol injection?

1. Use a large vein (like the antecubital)
2. Pretreat with lidocaine 1% 1mL IV

Agree or disagree?: You can mix lidocaine with propofol in the same syringe to minimize injection pain.

Disagree. This can result in coalescence of oil droplets, destabilizing the propofol.

How long is propofol good for after drawing it out of the vial?

Six hours, as long as sterile technique was used

Ideally, propofol should be pushed at a rate of ___________

40mg in 10 seconds for healthy patients, 20mg in 10 seconds for elderly patients

Agree or disagree?: Propofol is a great choice for induction in pediatrics under three years old, pregnancy, labor and delivery, and lactating ladies

Disagree. While propofol can be used for induction over three years of age and maintenance over 2 months of age, it is not recommended for the other populations listed due to transfer to fetus/infant through blood/breast milk.

My patient woke up after like eight minutes after I gave a bolus of propofol. Why?

Propofol rapidly redistributes from the central compartment to the peripheral compartment, decreasing the plasma concentration in 8-10 minutes.

My patient woke up with a wicked hangover. Is it because I gave him propofol?

No, propofol has less hangover effect compared to other agents secondary to high plasma clearance

The pharmacokinetics of propofol are affected by _______________

Age, debilitating conditions, cardiac compromise, and weight

Propofol is metabolized via _________

conjugation in the liver to inactive metabolites

Describe the effects of propofol on the CNS

Decreases CMRO2, CBF, ICP, and CPP, making it a good choice for neuro anesthesia

What is CPP?

Cerebral perfusion pressure (MAP-ICP)

Describe the effects of propofol on the CV system?

Decreases MAP, SBP, SVR, and CO due to negative inotropic properties (up for debate), causes arterial and venous vasodilation, and inhibits normal baroreceptor responses, making it a bad choice for cardiac anesthesia (but it's still the best thing we have)

What is a rare cardiac complication of propofol?

Bradycardia that is refractory to atropine

What effects does propofol have on respiration?

More respiratory depression than is seen with pentothal, can cause apnea, more depression of upper airway reflexes than is seen with pentothal, minimal bronchial tone alteration (good for asthmatics)

Generic propofol contains what bacterial retardant, and why is it bad?

Metabisulfate, which can trigger an asthma attack

Can brand name Diprivan cause an asthma attack?

No, because it contains a non-sulfite preservative

What makes propofol a good antiemetic?

It possesses antidopaminergic qualities, which depress the CRTZ, decrease glutamate and aspartate in the olfactory cortex, and reduces serotonin concentrations in the area postrema

Your patient is vomiting, but you've already given them propofol, zofran, and decadron. What else can you try?

Reglan, because their stomach may be full of blood

Propofol infusion syndrome causes what muscle-wasting condition? How long does it take?

Rhabdomyolysis, after a propofol infusion lasting 3-4 days

What are the three conditions that propofol infusion syndrome causes?

Myocardial failure, metabolic acidosis, and rhabdomyolysis

What is thought to cause propofol infusion syndrome?

Large lipid load associated with prolonged infusion

What is the chemical structure of Precedex, and to which other drug is it related?

Imidazole derivative; etomidate

Agree or disagree?: Precedex is FDA approved for anesthesia

Disagree. This is an "off-label" use. Only approved for short term use in ventilated ICU patients.

Is Precedex faster or slower than propofol in terms of onset and offset?

Slower

Why do we care about Precedex? What's so great about it?

Produces a more "natural" sleep state than other sedatives, produces less respiratory depression, and produces only moderate changes in SVR and HR

What is the induction dose for Precedex?

Trick question! There is none. Not approved for anesthesia.

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