EXAM 2 Flashcards
General anesthesia is a state of drug induced _____
unconsciousness
What does the vessel rich group include?
What % of our CO does it get?
Brain, heart, kidney, liver
75%
What does the muscle group include?
What % of our CO does it get?
Skeletal muscle and skin
18%
What % of our CO does fat get?
5%
What does the vessel poor group include?
What % of our CO does it get?
Bone, tendon, cartilage, hair, nails
2%
What are the 5 components of general anesthesia?
Hypnosis
Analgesia
Muscle relaxation
Sympatholysis
Amnesia
(A MASH)
According to Doctor Castillo what is the first stage of general anesthesia called?
analgesia
According to Doctor Castillo what is the second stage of general anesthesia called?
delirium
most dangerous stage
According to Doctor Castillo what is the third stage of general anesthesia called?
surgical anesthesia
According to Doctor Castillo what is the fourth stage of general anesthesia called?
medullary paralysis
*pt is over sedated**
These are our 4 protective airway reflexes
Sneezing
Coughing
Swallowing
Gagging
Stage 1 begins with _______ and ends with ______
initiation of an anesthetic agent and ends with the loss of consciousness
What is the lightest level of anesthesia?
stage 1
How are our 4 protective airway reflexes impacted in stage 1?
They’re still present! Not impacted
How are our 4 protective airway reflexes impacted in stage 2?
They are diminished
How are our 4 protective airway reflexes impacted in stage 3?
They are absent
How is sensory and mentation impacted during stage 1?
Depression
Patients pass through stage 2 within ___ to ___ seconds. Max of ___ seconds
5-15, 30 seconds max
Why is it important to pay attention to the EKG/SPO2 monitor during stage 2? What does it tell you?
pulse ox or EKG tone – it will increase due to excitation!!!! then HR goes back down after stage 2 is done
According to Castillo, Stage 2 starts with ______ to the onset of _______ _____ of vital signs
loss of consciousness, automatic rhythmicity
In modern day, patients pass through stage 2 quicker than they used to. Why?
Anesthetic agents are more rapid than ether and the use of short acting barbiturates.
What are dysconjugate ocular movements?
What stage do you see it in?
Eyes moving in different directions Stage 2
(in reality we won’t see it because their eyes are taped shut)
Why do we not intubate in stage 2?
-Potential for passive or active emesis
-Laryngospasms can occur due to hyper-excitability to stimuli
This stage is characterized by the absence of response to surgical incision and depression in all elements of nervous system function
Stage 3
In stage 4, what 2 things are absent?
-Spontaneous respiration
-All reflexes
(Importantly: Medullary cardiac reflexes)
What is the medullary cardiac reflex?
A series of autonomic responses that regulate the HR and BP in response to changes in blood pressure and oxygen levels from the medulla oblongata
Characteristics of the pulse during stage 4?
Weak and irregular
Stage 2 is more prolonged during _____ than _____
emergence than induction
Because Inhalation induction takes longer than total IV anesthesia (TIVA). Patients will be in stage 2 up to ___minutes
15
all phases occur longer in inhalation induction compared to IV
This barbiturate used to be the most common but is not used in the USA anymore because of _____
thiopental; it is used for lethal injection
What is the gold standard induction drug?
Barbiturates
we do not use them anymore but it used for comparison
Barbiturate mechanism of action
potentiate GABA a channel activity; directly mimics GABA
What receptors do barbiturates act on? (4 total)
-GABAa
-Glutamate
-Adenosine
-Neuronal nicotinic acetylcholine
How do barbiturates impact cerebral vessels?
They are cerebral vasoconstrictors
Do barbiturates have an analgesic component?
NO
How do barbiturates impact CBF and CMRO2? By what % are they affected?
They decrease it, 55%
Why are barbiturates good for reducing the incidence of CVA?
Barbiturates decreases CBF and CMRO2 up to 55% - this decreases the risk of CVA/stroke b/c we are reducing metabolism of brain
When using IV induction medications CBF and CMRO2 are ______ (coupled or non-coupled?).
When using inhalation agents CBF and CMRO2 are ______ (coupled or non-coupled?).
IV - Coupled
Inhalation - Uncoupled
Babiturate onset
Rapid; 30 seconds
With a prolonged infusion of barbiturates, there is a _____ context-sensitive half-time
lengthy
How many minutes does it take for barbiturates to be equal in the skeletal muscle and plasma?
15 minutes
Barbituates are dosed on _____ body weight
lean / ideal body weight
Why are barbiturates dosed on ideal body weight?
Fat acts as a reservoir for the drug and acts like an IV bag which will redose the patient and have a cumulative effect
Where are Barbiturates metabolized? What % metabolism occurs here?
hepatocytes, 99%
How are Barbiturates excreted?
Renally
How is elimination half time of Barbiturates impacted in pediatric patients?
elimination half time is shorter
What % of Barbiturates is bound to albumin?
Why do we care?
70-85%
This acts as another reservoir because the drug can detach and produce effects again
What is the effect on redistribution if the drug has a high protein binding capacity?
It has a longer duration of action
With Barbiturates, the non-ionized lipid soluble drug favors: acidosis or alkalosis?
acidosis
With Barbiturates, the ionized less lipid soluble drug favors: acidosis or alkalosis?
alkalosis
Although Barbiturates are only marketed as racemic mixtures, it is important to know the ___ isomer is more potent than the ____ isomer
S (-) is more potent than R (+)
Name the three oxybarbiturates
- Methohexital
- Phenobarbital
- Pentobarbital
Name the two thiobarbiturates
- Thiopental
- Thiamylal
Which Barbiturate is used in conjunction with electroconvulsive therapy?
Methohexital
This drug is also known as truth serum
Thiopental
With thiopental, after 30 minutes only ___% in brain because of _____
10%, rapid redistribution
Thiopental (sodium pentothal) dose
4-5 mg/kg IV
Which has a longer elimination half time: thiopental or methohexital?
Thiopental
What is the fat/blood partition coefficient of thiopental? Is this high or low?
11; HIGH
This describes the distribution of a given agent at equilibrium between two substances at the same temperature, pressure and volume
Partition coefficient
The blood is considered a pharmacologically ____ reservoir in regards to the blood-gas coefficient
inactive
This describes the distribution of an anesthetic between blood and gas at the same partial pressure
blood-gas coefficient
A _____ blood-gas coefficient correlates with higher solubility of anesthetic in blood and thus ____ the rate of induction
higher, slows
Why does methohextial have a shorter duration of action than Pentothal?
Because methohexital has a lower lipid solubility than Pentothal
Other name for methohextial
brevital
At a normal pH ___% of methohextial is non-ionized
76%
At a normal pH ___% of Pentothal is non-ionized
61%
In comparison to oxybarbiturates, thiobarbiturates are ___ lipid soluble and have greater ______ potency
more, hypnotic
Why is it that the greater the ratio of fat to body weight, the less is the blood volume (ml/kg)?
Adipose tissue has decreased blood supply (its a vessel poor group)
What is excitatory phenomena?
Myoclonus, hiccough (hiccups lol)
True or false: methohextial is associated with excitatory phenomena
true
Methohextital (breivital) dose IV
1.5 mg/kg IV
Methohextital (breivital) dose rectal
20-30 mg/kg
How does Methohextital (breivital) impact the seizure threshold.
What surgery is this relevant to?
It lowers the threshold; more prone to having seizures
Induces seizures in patients undergoing temporal lobe resection
Methohextital (breivital) decreased seizure duration ___ - ___ % in ECT patients compared to etomidate
35-45%
Since barbiturates cause histamine release, what 2 things do we worry about?
Hypotension
Anaphylactoid response
Which barbiturate may have an anaphylactic response with previous exposure?
Thiopental
Caution administering barbiturates to patients with a lack of this response?
Baroreceptor
What is the dose dependent ventilatory response to barbiturates?
- The more we give, the more depressed the ventilatory centers get.
- The medullary and pontine are LESS sensitive to CO2; this leads to slow frequency and decreased tidal volume.
- Takes longer to return to spontaneous ventilation.
What happens immediately if you give barbiturates through an arterial line?
- Immediate, intense vasoconstriction and excruciating pain that radiates down the artery
What are the consequences if you give barbiturates down an arterial line?
- Pain
- Obscure of distal arterial pulses
- Blanching and cyanosis
- Gangrene and permanent nerve damage
If you give barbiturates down an arterial line, how do you treat it?
Injecting vasodilators; lidocaine or papaverine
What is Somatosensory evoked potential (SSEP)?
SSEP monitoring is a neurophysiological technique that assesses the function of the nervous system. It’s used during surgery to detect changes in nerve conduction and prevent neurological injury.
What is the desired drug for SSEP monitoring?
Barbiturates
Barbiturates induce enzymes after ___ to ___ days of infusion and may persist for __ days
2 to 7
persist for 30 days
How do barbiturates impact RBF and GFR? Why?
They can cause a modest, transient decrease. Probably due to hypotension!
*Try to infuse crystalloids to prevent this**
What class is propofol?
GABA agonist
Full name of GABA
Gamma aminobutyric acid
Induction dose of propofol
1.5-2.5 mg/kg IV
Conscious sedation dose of propofol
25-100 mcg/kg/min
Maintenance dose of propofol
100-300 mcg/kg/min
How many mcg in 1 mg?
1000 mcg = 1 mg
How quickly does a rapid injection of propofol produce unconsciousness?
30 seconds
What 3 components make up 1% propofol
- Soybean oil (10%)
- Glycerol (2.25%)
- Purified egg phosphatide (lecithin) - (1.2%)
Is lecithin egg yolk or egg white?
Egg yolk!
1% propofol concentration
10 mg/ml
2% propofol concentration
20 mg/mL
3 disadvantages of the propofol mixture
-supports bacterial growth
-increased plasma triglycerides
-pain on injection (because of soybean oil)
Which commercial preparation of propofol causes dyesthia?
Aquavan
This is the burning sensation in genitals, especially in females
Which component of propofol makes it isotonic like the blood?
Glycerol
What causes immobility from propofol anesthesia?
It’s action on the brain! It is NOT caused by drug induced spinal cord depression
Does propofol cause drug induced spinal cord depression
NO
What receptor does propofol hit (besides GABA) to contribute to its hypnosis effect?
Glycine
With propofol, what occurs first: hepatic first pass or pulmonary first pass?
Pulmonary
What hepatic enzyme metabolizes propofol?
CP450
Propofol elimination half time
0.5 - 1.5 hours
Propofol context-sensitive half-time (8 hour infusions)
40 minutes
Propofol volume of distribution
3.5-4.5 L/kg
How does propofol impact systemic BP and HR?
decreases them
What organ mainly metabolizes propofol
Liver
Etomidate elimination half time
2-5 hours
Etomidate volume of distribution
2.2-4.5 L/kg
Etomidate clearance
10-20 mL/kg/min
Propofol clearance
30-60 ml/kg/min
How does etomidate impact systemic BP and HR?
No change or decreased BP
No change on HR
Ketamine elimination half time
2-3 hours
Ketamine volume of distribution
2.5-3.5 L/kg
Ketamine clearance
16-18 ml/kg/min
How does ketamine impact systemic BP and HR?
Both are increased
Does propofol cross the placenta?
Yes, worry about fetal ion trapping so be careful with pregnant patients
What is the blackbox warning for propofol pertaining to?
Caution with pediatric patients
What is the induction drug of choice?
Propofol
Why do children require a higher dose of propofol?
Presumably reflecting they have a larger central distribution volume and higher clearance rate
Why do the elderly require a lower dose of propofol?
As a result of them having a smaller central distribution volume and decreased clearance rate
At what propofol blood level is there unconsciousness upon induction?
2-6 mcg/mL
Awakening without CNS effects is characteristic of propofol. Awakening typically occurs at plasma propofol concentrations of ___ to ____
1.0 -1.5 mcg/mL
What two benefits of propofol make it suited for ambulatory conscious sedation?
-Prompt recovery without residual sedation
-Low incidence of PONV
Propofol has ____ and ____ and _____ properties. However, at low doses we may need to supplement with ____ or ____ medications.
Analgesic and amnestic and anticonvulsant
Opiods or midazolam
Propofol is more effective than zofran in these two types of N/V
CINV (chemo induced)
PONV
How does propofol help with nausea and vomiting (MOA)?
depresses subcortical pathways and has a direct depressant effect on the vomiting center.
Propofol sub hypnotic dose
What is this good for?
10 to 15 mg IV followed by 10 µg/kg/minute
CINV and PONV
Dose of propofol to get anti-pruritic effects.
Why may patients experience pruritic?
Anti-pruritic effects:
10 mg IV
D/T neuraxial opioids exciting spinal cord or cholestasis
Propofol anti-convulsant dose
Anti-convulsant: 1 mg/kg IV
Why is propofol good for asthmatic patients
It has bronchodilator abilities
Does propofol trigger malignant hyperthermia?
no
This induction drug has potent antioxidant properties
propofol
How does propofol impact:
CBF
CMRO2
ICP
Decreases CBF
Decreases CMRO2
Decreases ICP
What is the CMRG? What is it related to?
Cerebral metabolic rate of glucose
CMRO2 (basically the same thing)
How does propofol impact Autoregulation r/t CBF and PaCO2?
They are maintained
How does propofol impact SSEP? What is the exception to this?
It does not impact it. This makes it great for neuro cases.
Exception: Unless volatiles or nitrous added
What are the excitatory movements propofol can cause?
Myoclonus
On an EEG, what do delta waves indicate? Theta waves? Alpha waves?
Delta waves: deep sleep *what we want for surgical anesthesia**
Theta - light sleep
Alpha waves – awake
Which decreases SBP more: thiopental or propofol?
What is the MOA of this?
Propofol
- Inhibition of SNS…vascular smooth muscle relaxation… ↓ SVR
- Decreases intracellular calcium
Why does propofol cause bradycardia?
-Decreases SNS response by reducing vagal tone; has direct effect on muscarinic receptor
-May depress baroreceptor reflexes– so no compensatory increase in HR
With this drug, profound bradycardia and asystole can be found with healthy adult patients and children
Propofol
Explain what is happening in this image
The HR response to IV atropine is impacted in patients receiving propofol. The decreases in HR cannot be overcome by larger doses of atropine which suggests propofol may decrease SNS activity.
You may have to give a beta agonist for propofol induced bradycardia!
How does propofol impact veniltation?
It produces dose dependent depression of ventilation. Apnea can occur as well.
How is hypoxic pulmonary vasoconstriction response impacted by administration of propofol?
It remains intact
What can counteract the ventilatory depressant effects of propofol?
Painful surgical stimulation
Why does propofol cause green urine?
Does this mean renal function is impacted?
Due to the phenols
No impact on renal function
Why does propofol cause cloudy urine?
Does this mean renal function is impacted?
-uric acid crystallization
-No alteration in renal function.
How does propofol impact intraocular pressure (IOP)?
Platelet aggregation?
Decreases IOP
Inhibits platelet aggregation
What is another name for propofol infusion syndrome?
lactic acidosis
With what doses / time period do you see Propofol Infusion Syndrome (Lactic Acidosis)?
High dose infusions of >75 µg/kg/min longer than 24H
What do we see with pediatric patients who have Propofol Infusion Syndrome (Lactic Acidosis)?
Severe, refractory, and fatal bradycardia in children
Signs and symptoms of Propofol Infusion Syndrome?
Diagnosis?
- Lactic acidosis
-Brady-dysrhythmias
-Rhabdomyolysis
Dx: ABG and serum lactate concentrations
Can you reverse Propofol Infusion Syndrome (Lactic Acidosis)?
Yes, in the early stage
The only carboxylated imidazole-containing compound for induction
etomidate
Etomidate is water soluble at an ______ pH and lipid soluble at _____ pH; weak ____ (acid or base?)
acidic, physiologic
It is a weak base
Etomidate is made up of 35% ________. This is why it burns on injection.
Propylene glycol
Only induction drug with direct systemic absorption in oral mucosa that bypasses hepatic metabolism
Etomidate
Etomidate causes excitatory effects that manifest as _____
myoclonus
What is the biggest indicator of onset of action
Lipid solubility is biggest indicator of onset of action!!!!
More lipid soluble = faster onset of action
Why is etomidate great for pediatric patients?
Because it has direct systemic absorption in oral mucosa that bypasses hepatic metabolism
When drug is given orally, first pass from liver metabolism usually eliminates ___% of drug
50%
Etomidate MOA
In/directly open Cl- Channels of GABAA receptors
Cell Hyperpolarization
Etomidate onset
Onset: 1-minute s/p IV injection
Etomidate is __% albumin bound
76%
Etomidate clearance: __x faster than Thiopental
We experience prompt awakening due to what property of etomidate?
5x faster
It is highly lipid soluble!
this is due to the redistribution from the brain to inactive tissue sites
How is etomidate metabolized?
Hydrolysis through hepatic microsomal enzymes & plasma esterases
Etomidate Elimination: __% in urine & __% - ___% in bile.
85%
10-13%
Etomidate half time
T ½: 2 - 5 hours
Etomidate peak time
2 minutes
Standard induction dose of etomidate
Dose: 0.3 mg/kg IV
What type of patients is etomidate the best for?
Unstable Cardiovascular System
-Especially with little or no cardiac reserve
Do patients experience hangover or cumulative drug effect with etomidate?
No
True or false: Etomidate has analgesic effects
FALSE
We need to give opioids during induction (direct laryngoscopy and tracheal intubation)
The incidence of myoclonus from etomidate can be decreased by doing what?
Prior administration of an opioid (such as fentanyl) or benzos
How much fentanyl would you give prior to etomidate to prevent myoclonus
Fentanyl: 1 to 2 µg/kg IV
Involuntary myoclonic movements:
___ to ___% Etomidate > ____% after Thiopental, ___% after Methohexital, ___% after propofol
50% to 80% Etomidate > 17% after Thiopental, 13% after Methohexital, 6% after propofol
This is an alteration in balance of inhibitory and excitatory influences on the thalamocortical tract.
Involuntary Myoclonic Movements
Caution using etomidate in patients who have a history of ____. Why?
seizures
May activate seizure foci
Etomidate causes ______ ____ by producing a dose dependent inhibition of the conversion of cholesterol to cortisol
Adrenocortical Suppression
Etomidate enzyme inhibition of 11-B-hydroxylase last for __ to __ hours after induction dose
4-8
Explain why we care about this graph
Etomidate, but not thiopental is associated with decrease in the plasma concentrations of cortisol
Etomidate ______ CBF and CMRO2 ___ to ___%
Decreases, 35% to 45%
Etomidate is a potent direct cerebral _____
What does this mean for ICP?
vasoconstrictor
↓ ICP
Etomidate has similar EEG changes (Thiopental) except more frequent _____ spikes
excitatory
Why do you not use etomidate in nerve surgery?
May increase amplitude of SSEP, gives us false positives
With an induction dose of 0.3 mg/kg of etomidate, how is CO/HR/SV impacted?
What about with a dose of 0.45 mg/kg IV?
It is not impacted, however SVR drops.
0.45: Significant decreases in systemic blood pressure and CO occur
True or false: etomidate releases histamine
false
Rapid IV injection to etomidate will cause this impact on the respiratory rate
apnea
all induction drugs besides ketamine do this by the way
Which of the following has a greater impact on depressing ventilation: etomidate or propofol/barbiturates?
Propofol/barbiturates
Why do patients who receive etomidate come back breathing earlier?
Stimulates CO2 medullary centers– so they come back breathing earlier
Which induction drug may be useful when maintaining spontaneous ventilation is desirable
etomidate
What else is ketamine called?
Angel dust or PCP
What kind of anesthesia does ketamine provide?
Dissociative
You walk in the room, your patients eyes are open with a slow systemic gaze. They are non communicative but awake. What drug are they most likely on?
Are they amnesic? Analgesic?
Ketamine
Yes!
Yes! It is intense analgesia
When giving ketamine, hypertonus may occur. Why is this a concern?
It can lead to rhabdomylosis
2 advantages of ketamine over Propofol and Etomidate
-No pain @ injection.
-Profound analgesia at subanesthetic doses
2 disadvantages of ketamine
Disadvantages:
Emergence delirium
Abuse potential
What preservative is with ketamine?
Why is this good?
Preservative: Benzethonium Chloride
Communicative effects: increases analgesia
What isomer of ketamine is used for therapy resistant depression?
S(+) ketamine (esketamine)
Which form of ketamine has cocaine like effects: S isomer, R isomer, or racemic?
Racemic
Which isomer of ketamine has: More intense analgesia, lower incidence of emergence reactions, and less salivation?
S isomer
Ketamine receptors?
Binds noncompetitively to N-methyl-D-aspartate (NMDA) receptors.
Inhibits activation of NMDA receptors by glutamate and decreases the presynaptic release of glutamate.
Most abundant excitatory neurotransmitter in CNS
glutamate
____ is an obligatory co-agonist of glutamate
Glycine
What other receptor sites does ketamine impact?
-opioid (µ, δ, and κ; weak σ),
-monoaminergic
-muscarinic
-voltage-sensitive sodium
-L-type calcium channels
-Neuronal nicotinic acetylcholine receptors which helps produce analgesic effects
(LVN MOM)
Ketamine has a weak action at this type of receptor
GABA A
What opioid receptor is weak
Weak opioid site is sigma (σ)
Ketamine has a rapid onset of action (similar to Thiopental)
The peak plasma concentrations @ _ minute(s) after IV & __ min(s) (IM)
1 minute IV
5 minutes IM
Ketamine has a:
____ (Short or long) duration of action
Duration: __ to ___ mins
___ to ___ min to return to full orientation.
Short duration of action
10 – 20 mins
60-90 min to return to full orientation.
Is ketamine highly, moderate or minimally lipid soluble?
Compare it to thiopental
Highly
5-10x more
Is ketamine significantly plasma bound?
No
What is ketamines vD?
3L/min
Ketamine elimination half-time
2 to 3 hours
Ketamine has a ____ (high or low) hepatic clearance rate of ___ L/min
high, 1L / min
What enzyme metabolizes ketamine?
CYP450
Ketamine active metabolite?
How potent is it in comparison to ketamine?
Norketamine
1/3 – 1/5 potency
Ketamine excretion organ
Excretion: Kidneys
What patient population develops a tolerance to ketamine?
Burn patients
Ketamine dose for induction:
IV
IM
PO
0.5 - 1.5 mg/kg IV
4 - 8 mg/kg IM
10 mg/kg PO
Ketamine dose for maintenance
IV
IM
0.2 - 0.5 mg/kg IV analgesia
4 - 8 mg/kg IM
Ketamine subanesthetic (analgesic dose)
0.2 - 0.5 mg/kg IV
4 prong approach on pain for ketamine:
Voltage channels
Nicotinic receptors
Active metabolite
Preservative
^ These things contribute to analgesia
Ketamine dose post Op Sedation and Analgesia
1 - 2 mg/kg/hour (pediatric cardiac surgery)
Ketamine dose Neuraxial Analgesia
Concentration in how much saline?
Where can I give?
30 mgs Epidural
5 - 50 mg in 3 mLs of saline Intrathecal/Spinal/Subarachnoid
Why do you give robinul before ketamine?
Ketamine induces salivary secretions
Ketamine induction LOC effect time IV and IM
30 secs – 1 min (IV)
2 to 5 mins (IM)
Why do we induce with ketamine in hypovolemic patients?
Ketamine stimulates the SNS
Why is ketamine good for patients with asthma?
Bronchodilator properties and no histamine release
Can I give ketamine to a patient who has a hx of MH?
Yes
Induction Coronary artery disease ‘cocktail’:
-Coronary artery disease ‘cocktail’:
-Diazepam 0.5 mg/kg IV
-Ketamine 0.5 mg/kg IV
Continuous Ketamine infusion: 15 to 30 µg/kg/minute IV
How does ketamine impact ICP?
Increases it
Caution in ketamine with patients who have pulmonary HTN. Why?
It may increase it up to 44%
Why would an eye surgeon look at you like you were an idiot after you gave ketamine to their patient?
It causes nystagmus which is not great for eye procedures
Ketamine is a potent cerebral _____
vasodilator
How does ketamine impact CBF and CMRO2
↑ CBF by 60% (because it is a potent vasodilator); also increases CMRO (glucose also)
How does ketamine impact the EEG? Seizure threshold?
Increases Excitatory activity in EEG
Does not alter seizure threshold.
Ketamine can cause increased amplitude with SSEP → this can be reduced by administering _____
can reduced by N20
How does ketamine impact the CV system?
-Resemble SNS stimulation: Increases …
sBP, PAP, HR, CO, MRO2
-Increases plasma Epi & Norepinephrine levels
How can you blunt the SNS CV effects of ketamine
Blunted by pre-med with benzos or inhaled anesthetics & N20
You have an unexpected drop in sBP and CO with ketamine. What can cause this?
Depeleted catecholamine stores
If you have a drop in HR / BP due to ketamine. What is the drug of choice, why?
Epinephrine
The bradycardia is due to depleted catecholamines. Atropine will not work.
How is ventilatory response to CO2 impacted by ketamine?
Ventilatory response to C02 is maintained
With ketamine PaCO2 is unlikely to increase more than __ mmHg.
3
Ketamine impact on: upper airway skeletal muscle tone and reflexes
They maintained & intact.
Is emergence delirium an adverse reaction?
No, just a side effect
What percentage of patients experience emergence delirium?
5% to 30% of patients
(Psychedelic effects)
How long do the Psychedelic effects last after ketamine?
Morbid & vivid dreams (in color) and hallucinations up to 24H
How to prevent emergence delirium? 2 options
**-Benzodiazepine IV (5 minutes prior)
**-Also could give alpha 2 agonist; Clonidine and Dexmedetomidine
How does ketamine effect non-depolarizing muscle relaxing drugs?
Enhances
How? InIhibits cytosolic free calcium concentration
How does ketamine impact succ?
Prolongs apnea from Succinylcholine by Inhibiting plasma cholinesterases
Drug interactions:
Ketamine + Volatile anesthetic (Iso/Sevo/Des):
Hypotension
Obstructive Sleep Apnea and Ketamine risks and benefits:
**Risks:
**Psychiatric Effects, SNS activation, hypersalivation
Obstructive Sleep Apnea and Ketamine
**Benefits:
**Upper airway preservation (if appropriate dose) and ventilatory function (as long as subanesthetic doses)
Which induction agent has the highest analgesic properties:
-Propofol
-Ketamine
-Thiopental
-Etomidate
Ketamine!
What is Ketafol?
Ketamine + Prop mixed in a syringe
Why is ketafol mixture bad?
Propofol is not a chiral compound and Ketamine is, its not stable.
Propofol + lidocaine mixed in a syringe can create ____
lipid bubbles which causes risk of PE’s
We used to only be able to draw up our drugs 1 hour before surgery, but now we can draw up our drugs __ hours before case
4
What are the two components of pain?
Sensory-discriminative and motivational affective
What two ascending tracts are involved with the sensory-discriminative component of pain?
Where are they located?
Spinothalamic
Trigeminothalamic tracts
Located in the cerebral cortex
What does the sensory-discriminative component of pain tell us?
Perception of the quality of pain (ex: pricking, burning, aching), the location and intensity as well as duration.
Motivational-affective responses to painful stimuli include (4 things)
- Attention and arousal
- Somatic and autonomic reflexes→ ex. Touching something hot
- Endocrine responses
- Emotional changes
Nociception definition
The experience of pain with a series of complex neurophysiologic processes
Four distinct components of nociception:
- Transduction
- Transmission
- Interpretation
- Modulation (PNS and CNS)
What is Increased pain sensations to normally painful stimuli?
Hyperalgesia
Most common reason for people to go to doctor
Pain
What are the steps (starting with trauma to tissue) to pain perception
Trauma, transduction, transmission, modulation and perception
What part of the spinal cord is in charge of modulation?
Dorsal horn
What part of pain perception involves: Nerve/electrical impulses/signals start at the nerve endings?
Transduction
What part of pain perception involves: Travel of nerve/electrical impulses to the nerve body connecting to the dorsal horn of the spinal cord.
Transmission
What part of pain perception involves: Process of altering (inhibitory/excitatory) pain transmission mechanisms at the dorsal horn to the PNS and CNS.
Modulation
What part of pain perception involves: Thalamus acting as the central relay station for incoming pain signals & the primary somatosensory cortex serving for interpretation/discrimination of specific sensory stimuli.
Perception
These types of anesthetic drugs work on peripheral nociceptors and impact transduction (transduction of mechanical, chemical and thermal stimuli into an action potential)
LA and NSAIDs
This type of anesthetic works on pain transmission of action potentials via A delta and C fibers
LA
These anesthetic drugs work at the level of the spinal cord and impact modulation of afferent signals in the dorsal horn and production of reflex reactions
LA, opiods, ketamine and alpha 2 agonists
These anesthetic drugs work at the level of the brain and affect perception (activation of descending inhibitory pain pathways and memory)
Opioids, alpha 2 agonists, general anesthetics
Where does the modulation of pain impulses occur?
A. Thalamus
B. Dorsal Horn
C. Cortex
D. CNS
B. Dorsal horn
C FIBERS:
Myelinated or unmyelinated?
Fast or Slow pain?
- Unmyelinated
- Slow pain
Which type of fibers would transmit information about burning pain from heat and pain from sustained pressure.
C fibers
A FIBERS
myelinated or unmyelinated?
Fast or slow?
Myelinated
Fast
What are type II fibers?
A delta (Aδ) fibers with lower conduction velocity
What are type I fibers?
Aβ & Aδ fibers
This type of nociceptor is responsive to heat, mechanical and chemical stimuli
Type I: Aβ & Aδ fibers
What are our peptides?
- Substance P
- Calcitonin
- Bradykinin [1st released]
- CGRP
What are our chemical mediators?
- Peptides (Substance P, Calcitonin, Bradykinin [1st released], CGRP)
- Eicosanoids
- Lipids (Prostaglandins, Thromboxanes, Leukotrienes, Endocannabinoids)
- Neutrophins
- Cytokines
- Chemokines
- Extracellular proteases and protons
(PEEL CNC)
______ Hyperalgesia occurs at the original site of injury from heat and mechanical injury and ____ Hyperalgesia occurs at uninjured skin surrounding the injury (only from mechanical stimuli).
Primary, secondary
What are some examples of things that decrease pain threshold?
-Being an infant
-No sleep
-Anxiety
-Hangovers
-Stress
-Not eating
Relay center for nociceptive & other sensory activity.
Spinal dorsal horn
What part of the dorsal horn are the main target for afferent C fibers? What are their other names?
Lamina I (marginal layer) and Lamina II (substantia gelatinosa)
Myelinated fibers innervating muscles and viscera terminate in laminae ___, ____ to ___ and the ___ horn
Lamina I, IV to VII, ventral horn
Pg #689 of textbook
These two laminae express the neurokinin 1 receptor (NK1) and are heavily innervated by substance P containing afferents.
III and IV
This is important for spinal / epidural anesthesia
Gate theory: A neurologic “gate” in the spinal ___ horn.
dorsal
With the gate theory, when the gate is open: pain is projected to _________ regions via ____ and ___ fibers
supraspinal brain regions
A delta and C fibers
With the gate theory, when the gate is closed: pain is not felt with simultaneous ______ impulses via _____ fibers which deliver information about ___ and ___
inhibitory
Aβ fibers (large diameter, myelinated: faster) deliver information about pressure and touch (rubbing)
Which parts of the brain are involved with perception of motivational-affective pain components.
Limbic cortex and thalamus
This part of the CNS depresses or facilitates the integration of pain info in the spinal dorsal horn.
Periaqueductal gray – rostral ventromedial medulla (PAG-RVM) system
Tissue injury and/or damaged cells release ____.
Give some examples
neuromdoulators
Substance P
Glutamate
CGRP
NMDA
AMPA
BDNF
Cytokines
An excitatory impulse mediator:
a. GABA
b. Glycine
c. Glutamate
d. Norepinephrine
Glutamate
These 5 neuromodulators deal with excitatory impulses
- Glutamate
- Calcitonin
- Aspartate
- Neuropeptide Y
- Substance P
(G CANS)
These 5 neuromodulators deal with inhibitory impulses
- Dopamine
- Enkephalin
- Norepinephrine
- GABA
- Glycine
Ascending Pathways of Nociceptive Information
- Spinothalamic
- Spinomedullary
- Spinobulbar
- Spinohypothalamic
Thalamus and cerebellum are a part of ___brain
hind
Somatosensory I and II are part of the ___ brain
forebrain
Where do the Supra-Spinal Modulation
Descending Inhibitory Tracts originate?
Periaqueductal gray
What are the three neurotransmitters involved with the descending inhibitory complex?
Neurotransmitters:
Endorphins, enkephalins, serotonin
PAG-RVM system works on these type of receptors
µ, κ, δ opioid receptors
Where does the pain impulse originate if it is pertaining to the descending inhibitory tract?
PAG-RVM
Chronic pain: > ___ to ___ months: persists beyond tissue healing
3 to 6
This type of pain is characterized by a reduced nociceptive threshold and persists in the absence of a stimulis and is refractory to traditional anaglesics
Neuropathic
This type of pain is diffuse & poorly localized (referred to somatic sites: muscle & skin)
Visceral
A variety of painful conditions following injury in a region with impairment of sensory, motor, and autonomic systems
Spontaneous pain, allodynia, hyperalgesia, edema, autonomic abnormalities, active and passive movement disorders, and trophic changes of skin & SQ tissues.
Complex Regional Pain Syndromes
Pain perception at ___ weeks of gestation
23
With patients in pain, they may have pulmonary effects such as splinting. What is this?
Respiratory splinting is defined as reduced inspiratory effort as a result of sharp pain upon inspiration. This can result in atelectasis post-operatively.
GI / GU resopnse to pain
-Enhanced sympathetic tone:↑ sphincter tone, and ↓ motility
-Ileus
-Urinary retention
-Hypersecretion of acid
-Stress ulceration
-Aspiration
**-N/V
**-Abdominal distention b/c of decreased peristalsis
In reponse to pain, your body _____ (increases or decreases) catabolic hormones and _____ (increases or decreases) anabolic hormones
Increases catabolic and decreases anabolic
Are the following catabolic or anabolic hormones:
Catecholamines
Cortisol
Glucagon
Catabolic
Are the following catabolic or anabolic hormones:
Insulin and testosterone
Anabolic
Pain / stress related hematologic Response
Hypercoagulability; increased risk for clots
When you are under pain / stress, you may have a negative nitrogen balance. What does this mean for your blood pH?
Acidosis may occur
Which opiod is the gold standard?
Morphine
What plant do opiods originate from?
Opiates from Papaver somniferum aka Opion aka poppy juice (350 BC)
Are opioids endogenous or exogenous?
ALL are Exogenous (synthethic and nonsynthetic)
What structure are: Morphine, Codeine, & Thebaine
Phenanthrenes
What structure catergory is: Papaverine & Noscapine
Benzylisoquinoline
Which Opioid receptor subtype is responsible for dysphoria?
Kappa
Which opioid receptor subtype is responsible for the hallucinogenic effects and decreased GI sensations?
Delta
Which opioid receptor subtype is responsible for majority of effects ex. Analgesia, euphoria, sedation, respiratory depression and constipation
Mu
Are opioids agonists or antagonists?
Agonists
How do opioids cause pre synpathic inhibition of acetylcholine, dopamine, norepinephrine, Substance P?
- Increased K+ conductance (hyperpolarization)
- Ca+ channel inactivation
- Decreased neurotransmission
- Pain modulators or anti-nociceptive
Where are opioid receptors located in the brain?
Periaqueductal gray (PAG), rostral ventral medulla (RVM), locus ceruleus & hypothalamus
Which receptor produces physical dependence?
Mu 1 or Mu 2
Mu2
What two opioid receptor subtypes deal with constipation, ventilatory depression and physical dependence?
Mu 2 and delta
These two opioid receptor subtypes deal with euphoria, low abuse potential and miosis
Mu 1 and kappa
These two opioid receptor subtypes deal with urinary retention
Mu1 and delta
Which opioid receptor subtype deals with bradycardia and hypothermia?
Mu 1
Which opioid receptor subtype deals with diuresis?
Kappa
Agonists of Mu1 and Mu2
-Endorphins
-Morphine
-Synthetic opioids
Agonists of kappa
Dynorphins
Agonists of delta
enkephalins
Antagonists of ALL opioid receptor subtypes
Naloxone, naltrexone and nalmefene
CV side effects of opioids
-Bradycardia
-Hypotension
-Decrease venous return and CO
-Possible histamine release
This drug class is cardioprotective from myocardial ischemia
Opioids
This drug can reverse antagonize ventilatory depression but not analgesia from opioids
Physostigmine
Normal deadspace
2 mL/ kg
Skeletal thoracic (chest wall) & abdominal muscle rigidity caused by opioids can be treated with
Narcan or muscle relaxants
True or false: large doses of opioids can cause myoclonus
True
Rank from least to greatest to prevelance of oddi spasm with the following meds:
Morphine, Demerol, Fentanyl
Least: Morphine 53%
Moderate: Demerol 61%
Greatest: Fentanyl 99%
How do you differentiate between a heart attack and a sphincter spasm caused by opioids?
Give naloxone; if pain persists it may be an MI!
Why do opioids cause vomiting?
Direct stimulation of CTZ and increased GI secretions and delayed GI emptying
Why do you avoid opioids in an ERCP?
Avoid opioids in ERCP b/c of sphincter spasm – if its spasms they can’t get in there to do procedure – fentanyl is biggest culprit, then morphine and meperidine
Why do you give glucagon to patients on opioids?
- glucagon increases gastric emptying (warning: diarrhea)
- Treatment for Oddi spasms
- 2 mg IV
GU effects opioids
Urinary urgency
Opioids side effects cutaneous
Cutaneous: histamine release → flushed face, neck, & upper chest.
Opioid effects on the neonate
Placenta: neonate depression; dependence (chronic)
How long does it take to develop a tolerance to morphine?
Morphine: 25 days
The development of the requirement for increased drug doses (usually 2 to 3 weeks).
Tolerance
Why do people develop a tolerance to opioids?
Downregulation: opioid receptors on the cell membrane surfaces become gradually desensitized by reduced transcription & subsequent decreases in numbers of opioid receptors.
Withdrawal from which of the following opioids has the longest onset and lasts the longest:
-Methadone
-Demerol and Fentanyl
-Morphine and Heroin
Methadone
Withdrawal from which of the following opioids has the quickest onset lasts the shortest:
-Methadone
-Demerol and Fentanyl
-Morphine and Heroin
Demerol and Fentanyl
True or false:
Higher doses of intra op opioids lead to less post op pain
False; they lead to greater post op pain
Morphine intra op dose
1-10 mg IV
Morphine post op dose
5-20 mg
Morphine onset
10-20 min
Morphine duration
4-5 hours
Fentanyl intraop
1.5-3 mcg/kg IV
Fentanyl onset
30-60 seconds
Fentanyl duration
1-1.5 hours
Sufentanil intraop
0.3-1 mcg/kg IV
Remifentanil duration
6-8 minutes
Sufentanil duration
1-1.5 hours
Sufentanil infusion
Infusion: 0.5 to 1 µg/kg/hr IV
Remifentanil intra op
Load: 0.5-1 mcg/kg over 1 minute
Remifentanil, Sufentanil and Fentanyl onset
30-60 seconds
Remifentanil infusion
0.125-0.375 mcg/kg/min
Meperidine post op dose for shivering
12.5 mg
Both meperidine and hydromorphone have an onset of ___ to ___ minutes and a duration of __ to __ hours
Onset: 5-15 minutes
Duration: 2-4 hours
Naloxone dose
40-80 mcg
Naloxone onset and duration
Onset: 1-5
Duration: 30 minutes
Morphine active metabolites
Morphine-6-glucuronide: active analgesic
Morphine peak
IV:
IM:
IV: 15-30 minutes
IM: 45-90 min
Morphine onset for IV/IM
10-20 minutes
This agonist drug has a PO Hepatic 1st Pass: 25%.
No first pass uptake in lungs
Morphine
Demerol MOA
-Mu and kappa receptor agonist
-Alpha 2 agonist
What % of demerol is affected by Hepatic 1st pass?
80%
Where is meperidine metabolized?
Metabolites?
Hepatic
Normeperidine
How protein bound is meperidine?
60%
Meperidine E1/2 time
3 to 5 hours
35 hours with renal failure “
Other options besides demerol for post op shivering
Physostigmine and alpha 2 agonists (clonidine)
Side effects of demerol
tachycardia & mydriasis with dry mouth, (-) inotropy, serotonin syndrome (MAOIs & TCAs), impaired ventilation, crosses placenta
This opioid reaches its Blood:Brain Effect-Site Equilibration: 6.4 minutes→ very quick!
Fentanyl
Fentanyl lung first pass effect %
75%
This organs act as reservoirs and also have an effect on drug metabolism
Lungs
Principal metabolite of fentanyl
Metabolite: Norfentanyl
Fentanyl has a ____ volume of distribution
Large
How soon after you give a IV bolus dose of fentanyl is 80% gone?
IV bolus dose(<5 mins 80% is gone)
→ first goes to highly vascular tissues
Rank the context sensitive half time of the following drugs from longest to shortest:
-Fentanyl
-Remifentanil
-Sufentanil
-Alfentanil
Longest:
Fentanyl
Alfentanil
Sufentanil
Remifentanil (shortest)
Fentanyl dose for Analgesia:
1 to 2 µg/kg IV
Fentanyl dose for adjunct with inhaled anesthetics:
2 to 20 µg/kg IV
Fentanyl dose
Surgical Anesthesia (solo):
50 to 150 µg/kg IV
Fentanyl dose intrathecal
Intrathecal: 25 µg
Fentanyl dose transmucosal
Transmucosal (Oral): 5 to 20 µg/kg
Fentanyl dose pediatrics 2-8 years old
15 to 20 µg/kg PO 45 minutes prior
Fentanyl dose transdermal:
75 to 100 µg (18 hours steady delivery)
__ mg of PO fentanyl = __ mg of IV morphine
1 mg of PO Fentanyl = 5 mgs of IV Morphine
Fentanyl CV S/E
Large doses: no histamine release, depressed carotid sinus baroreceptor reflex
NO significant bradycardia
decreased BP & cardiac output
How does fentanyl impact the CNS?
-Seizure like activity
-Modest increase in ICP (6 to 9 mmHg)
This is 5-12x more potent than fentanyl
Sufentanil
Sufentanil has ___% lung first pass uptake
60%
Sufentanil ____% bound to alpha 1 acid glycoprotein
92.5
How is sufentanil excreted?
Excretion: renal and fecal (caution in chronic renal failure)
Does sufentanil bind to albumin or alpha 1 acid glycoprotein?
alpha 1 acid glycoprotein
Sufentanil analgesic dose
Analgesia: 0.1 to 0.4 µg/kg IV
Sufentanil induction dose
Induction: 18.9 µg/kg IV
Sufentanil CV effects
- Bradycardia
Alfentanil is ___ less potent than fentanyl (1976)
1/5th
Alfentanil onset
1.4 minutes > fentanyl & sufentanil
How does cirrhosis impact the E 1/2 time of alfentanil
Prolongs it
What is abnormal about alfentanil lipid solubility
90% nonionized at normal pH →so lower lipid solubility but has good Vd
Alfentanil metabolite
Noralfentanil
Alfentanil dose for Induction laryngoscopy:
15 to 30 µg/kg IV (90 seconds prior)
Alfentanil dose for induction alone:
Induction alone: 150 to 300 µg/kg IV
Maintenance dose of alfentanil with inhaled anesthethics
Maintenance: 25 to 150 µg/kg/hour IV with inhaled anesthetics
What happens if you give alfentanil to parkinsons patients
acute dystonia
Remifentanil
Selective ___ opioid agonist
µ(mu)
This opioid agonist is 15 to 20 times as potent as alfentanil (same as fentanyl)
Remifentanil
How is remifentanil metabolized?
Hydrolysis by nonspecific plasma and tissue esterases
Which opioid agonist has:
Brief action, rapid onset and offset (15 mins)
Precise and rapid titratable effect
Lack of accumulation
Rapid recovery when discontinued
Remifentanil
Do you dose remifentanil on actual body weight or IBW
IBW
Peak effect site of remifentanil
30-60 sec
Remifentnil clearance
Clearance: 3L/min (8x more rapid > alfentanil)
Remifentanil Elimination half-time
6.3 minutes (99.8%)
How long does it take to reach steady state with remifentanil infusion
10 minutes
Is remifentanil impacted by renal or hepatic disease?
No, metabolized by tissue esterases
remifentanil induction dose
0.5-1 mcg/kg over 30 to 60 seconds
Maintenance dose of remifentanil
0.25 to 1 µg/kg IV or 0.005 to 2 µg/kg/min IV
Before stopping remifentanil, you want to give ____________
longer-acting opioid
Diluadid is __x more potent than morphine
5x
Diluadid dose and how often to redose
Dose 0.5 mg IV → 1 to 4 mgs total
Re-dose every 4 hours
Why does codeine not have an IV form?
no IV b/c of histamine induced hypotension
Codeine e1/2 time
Elimination half time: 3 to 3.5 hours
Codeine dose for cough suppression:
Cough suppressant: 15 mgs
Codeine dose for analgesia
60 mgs
Codeine 120 mgs = __ mgs of Morphine
10
Which is more potent, codeine or morphine
Codeine
Tramadol information:
Potency:
Receptor:
PO dose:
Interaction:
Tramadol
5 -10x less (morphine)
µ with weak κ & δ
PO: 3 mg/kg
Interacts with Coumadin
Of the following drugs:
Morphine
Meperidine
Fentanyl
Sufentanil
Alfentanil
Remifentanil
Which one has the greatest protein binding?
The least?
Greatest: Sufentanil
Lowest: Morphine
Of the following drugs:
Morphine
Meperidine
Fentanyl
Sufentanil
Alfentanil
Remifentanil
Which one has the greatest clearance?
The least?
Greatest: Remifentanil
Lowest: Alfentanil
Of the following drugs:
Morphine
Meperidine
Fentanyl
Sufentanil
Alfentanil
Remifentanil
Which one has the greatest VD?
The least?
Greatest: Fentanyl
Lowest: Alfentanil
Of the following drugs:
Morphine
Meperidine
Fentanyl
Sufentanil
Alfentanil
Remifentanil
Which one has the longest E1/2 time?
The shortest?
Longest: Fentanyl
Shortest:Remifentanil
Of the following drugs:
Morphine
Meperidine
Fentanyl
Sufentanil
Alfentanil
Remifentanil
Which one has the longest context sensitive half time?
The shortest?
Longest: Fentanyl
Shortest:Remifentanil
Of the following drugs:
Morphine
Meperidine
Fentanyl
Sufentanil
Alfentanil
Remifentanil
Which one has the longest effect side (blood brain) equilibirum time?
The shortest?
Longest: Fentanyl
Shortest:Remifentanil
Which of the following pharmacokinetic variables best describes onset of action?
A. Effect site equilibrium
B. Protein binding
C. Elimination half time
D. Pk
A
Which volatile and IV anesthetics favor bronchodilation the most?
A. Halothane and versed
B.Propofol and Isoflurance
C. Sevoflurane and ketamine
B. Propofol and iso
Which volatile and IV anesthetics favor bronchodilation the least:
A.Propofol and Isoflurance
B. Sevoflurane and ketamine
C. Halothane and versed
C
