SS25 Induction Drugs (Barbs & Propofol) (Exam 2) Flashcards
(100 cards)
1
Q
What is MAC?
A
- Monitored Anesthesia Care
- Also known as Conscious sedation or Procedural Sedation
- Combo of sedatives & analgesics to depress LOC for patient’s to be able to tolerate unpleasant procedures & surgeons to perform effectively
2
Q
What are the 5 components of General Anesthesia (GA)?
(MAASH)
A
- Hypnosis, analgesia, muscle relaxation, sympatholysis, amnesia
High dose Propofol has all of these
3
Q
What organs utilize the most blood supply?
What organs utilize the least?
What organs are in between these two groups?
A
- Vessel-rich group = 75% CO (brain, heart, liver, kidneys)
- Skeletal muscles & skin = 18% CO
- Fat = 5% CO
- Vessel poor group (Bone, tendons, cartilage, skin, hair, nails) = 2% CO
4
Q
T/F: All anesthetics go to vessel-rich group.
A
- True (esp. induction)
- A part of 75% CO
5
Q
When the drug is administered via CVC, does it travel through cardiopulmonary circuit or systemic circuit first?
A
- cardiopulmonary circuit
6
Q
What are the stages of general anesthesia (GA)?
A
- Stage 1: Analgesia
- Stage 2: Delirium
- Stage 3: Surgical Anesthesia
- Stage 4: Medullary paralysis (of ALL reflexes (CNS/CV), severe hypotension, death)
7
Q
Describe Stage 1: Anesthesia
A
- Begins with initiation of an anesthetic agent and ends with LOC
- Lightest level of anesthesia
- sensory and mental depression
- able to open their eyes on command, breathe normal, maintain reflexes, tolerate mild stimuli
8
Q
If stage 1 anesthesia is maintained, what is it called?
A
- Conscious sedation
9
Q
What are the four upper airway reflexes are we suppressing during stage 1 anesthesia?
A
- Sneezing, Coughing, Swallowing, and Gagging
10
Q
During induction, when would one most likely see laryngospasm?
A
- Stage 2
- danger zone; violent/ exaggerated responses
- Starts with LOC to the onset of automatic rhythmicity of VS
-CV instability excitement, dysconjugate ocular movements, emesis - rapid stage!
11
Q
What population may have a prolonged stage 2 and why?
A
- Pedis
- Inhaled induction takes longer for LOC and autonomicity
12
Q
During emergence, when would one most likely need to be re-intubated?
A
- Stage 2
13
Q
Which stage would we like to extubate in?
A
Stage 1: Able to protect airway
14
Q
Characteristics of Stage 3:
A
- Absence of response to surgical incision
- depression of all 5 GA components of nervous system (MAASH)
15
Q
What is the mechanism of action of barbiturates?
A
- Potentiate (increase) GABA-a channel activity (directly mimics) causing Cl⁻ influx & cellular hyperpolarization
16
Q
Do barbiturates have analgesic effects?
A
- No, will have to add multimodal or opioid
17
Q
What other receptors do Barbiturates act on?
A
- Glutamate
- adenosine
- n-Ach
18
Q
- What do barbiturates do to CBF & CMRO₂ ?
- How is this accomplished?
A
- ↓ CBF & ↓ CMRO₂ by 55% via cerebral vasoconstriction (coupled)
19
Q
What drug class is represented by the figure below?
-What is the clinical significance of graph?
A
- Barbiturates (Thiopental)
- Rapid re-distribution from brain to other tissues
- VRG→ muscle group → fat → VPG
20
Q
Barbiturates:
- Onset
- Reversal gradient:
- What can cause the drug to re-enter circulation?
A
- Onset: 30 secs & rapid awakening d/t rapid uptake
-
Reversal of gradient
-At 5 mis: 50% total dose gone
-At 30 mins: 10% of total dose remaining - Lengthy context-sensitive half-time (d/t fat “reservoir” accumulation)
21
Q
- What’s the initial site of redistribution from VRG?
- Considerations?
A
- Skeletal Muscle = Lean tissues (18% CO)
- Considerations: shock patient (decreased perfusion) and elderly (decreased muscle mass)
22
Q
Barbs: When is equilibrium between plasma concentrations & skeletal muscle concentrations reached?
A
- Equilibrium at 15 mins
23
Q
Where is the main reservoir for barbiturates?
What does this mean clinically?
A
- Fat (5%): Drug reservoir; can re-dose or cause cumulative effect
- Must dose per IBW or lean body weight
24
Q
Barbiturates: Thiopental
- Metabolism?
- Excretion?
A
- Metabolism: Hepatic 99%
- Excretion: Renal
25
Barbiturates: Protein bound (in a percentage).
- Clinical significance?
- **70 - 85% Albumin bound**
- Able to re-bind to Albumin carrier and re-enter VRG (ie: brain) = re-hypnosis
26
T/F: In pedis, the E1/2 is prolonged with barbiturate use
- False
- **shorter**
27
What's the effect on redistribution if the drug has a high protein binding capacity?
- Longer duration of action d/t context- sensitive half-time
28
What are the characteristics of a **non-ionized** barbiturate?
- Favors Fat - **Lipophilic**
- Favors **acidosis**
- Readily crosses BBB
29
What are the characteristics of an **ionized** barbiturate?
- Hater = **Lipophobic**
- Favors **alkalosis**
30
Why might barbiturates be considered cerebro-protective?
- Barbs = ↓CBF & ↓CMRO₂ 55%
31
Regarding barbiturates, are S-isomers or R-isomers more potent?
Which is used clinically?
- **S-isomer** barbiturates are **more potent**
- Trick question! **Racemic mixtures are only ones used**
32
How would one differentiate thiobarbiturates vs oxybarbiturates?
- Thiobarbiturates: **thio**pental, **thia**mylal.
- O**x**ybarbiturates: methohe**x**ital (current ECT treatment), phenobarbital, pentobarbital.
33
Thiobarbiturates result from the replacement of Oxybarbiturate's oxygen with a _____ atom.
- How does this effect solubility and potency?
- Sulfur atom
- Higher lipid solubility
- **greater hypnotic** potency
34
Thiopental (Sodium Pentothal):
- Dose?
- E1/2 compared to methohexital?
- Fat/blood coefficient?
- 4 - 5 mg/kg IV
- E1/2: Longer than methohexital (Thiopental is more lipid soluble)
- 11→ indicates longer duration of action (use IBW)
35
The greater the ratio of fat to body weight, the less is the blood volume (ml/kg). Why?
- Adipose/fat tissue has reduced blood supply
36
How much Thiopental is present in the brain 30 mins post-administration?
- Why?
- Only **10%**
- **Rapid redistribution**, skeletal muscles, & decrease doses in shock elderly
37
What does a partition coefficient describe?
- What are the 2 types?
- The distribution of a drug at equilibrium between two substances that have the same temp, pressure, and volume.
- **Blood:gas** and **Fat:blood**
38
What is the blood-gas coefficient?
- The distribution of an anesthetic between blood and gas at the same partial pressure.
39
What would a high blood-gas coefficient indicate?
- Correlates with a higher solubility of anesthetic in blood → **slower induction time**
-The blood basically acts as a pharmacologically inactive reservoir (drug wants to stay in blood)
- Inhalant agents
40
_____ agents have fat to blood coefficients.
- Induction agents
41
Which is more lipid soluble, Thiopental or Methohexital?
- Why?
- Thiopental
- Sulfur atom → lipid soluble & greater hypnotic potency
42
At a normal pH, _____% of methohexital is non-ionized.
At a normal pH, ____% of Thiopental is non-ionized.
What does this mean in regards to induction for comparing these drugs?
- 76%
- 61%
- Methohexital **for induction** has a faster metabolism and recovery due to its increased lipid-solubility.
43
Which barbiturate causes excitatory phenomena of **m**yoclonus and **h**iccups?
**M**etho**h**exital
44
How would methohexital infusions differ from induction?
**Very lipid-soluble** so:
- Induction: **clears quickly**
- Infusion: **persists from infusion**
45
Methohexital:
- IV dose?
-Rectal (PR) dose?
- IV Dose: 1.5 mg/kg
- PR dose: 20 - 30 mg/kg
46
What is the seizure profile of Methohexital?
- Decreases seizure threshold→ induces seizure (ie: 1out 3 patients during temporal lobe resection)
- Decrease duration of seizure by 35 - 45% in ECT therapy compared to Etomidate
47
What CV side effects would occur with Thiopental 5 mg/kg administration in a normovolemic patient?
- Transient SBP **decrease** of 10-20mmHg
- Transient HR **increase** of 15-20 bpm (compensation)
48
Barbiturates (Thiopental) blunts _____ response.
- CV considerations?
- Baroreceptor response
- Caution for **Hypovolemia, CHF, & β-blockade**
49
Thiopental can have a __________ response due to __________ release coupled with previous exposure to the drug.
- anaphylactoid ; histamine
50
Barbiturates: Ventilation SE
- Dose-dependent **medullary & pontine** centers respiratory depression
(Less sensitive to CO₂ levels)
- Delayed return to spontaneous ventilation (slow frequency (RR) and decreased tidal volume (shallow breathing)
- Stage 4 territory = over anesthetized
51
What would occur with accidental arterial administration of a barbiturate?
What is the treatment?
- Immediate, limb-threatening vasoconstriction
- obscures distal arterial pulses → permanent nerve damage risk
- Tx: **Vasodilators** Lido or Papaverine
52
What type of IntraOp monitoring would prefer barbiturates?
- Why?
- SSEP (Somatosensory Evoked Potential) monitoring
- desired use of barbs over volatiles b/c volatiles suppress sensory output which would cause SSEP not to work
53
When would CYP450 enzyme **induction** be seen with a barbiturate infusion?
How long could it last?
- What drugs would be affected?
- 2-7 days post-infusion
- Could last up to 30 days
- **Accelerates** metabolism of anticoags, phenytoin, TCAs, digoxin, corticosteroids, bile salts and Vit K → may need supplementation
54
Barbiturates: Renal SE
- Transient ↓RBF and ↓GFR
- May need IV fluids
55
For Propofol, what are the doses for:
1. Induction
2. Conscious sedation
3. Maintenance
4. Anticonvulsant
5. Sub-hypnotic
6. Anti-pruritic
1. Induction = 1.5 - 2.5 **mg**/kg IV
2. Conscious sedation = 25 - 100 **mcg**/kg/min
3. Maintenance = 100 - 300 **mcg**/kg/min
4. Anticonvulsant: 1**mg**/kg IV
5. Sub-hypnotic (N/V): 10 -15 **mg**/kg, followed by 10 **mcg**/kg/min
6. Anti-pruritic: 10 **mg** IV
- **Tip**: maintenance has highest dose range for Prop
56
Pediatric dose for Propofol?
- Why?
- Require higher dose
- **Larger central distribution volume, Higher clearance rate**, Higher metabolism
57
Propofol:
- How long should I push IV injection?
- Onset
- Duration
- E1/2
- Potency compared to barbiturates
- Rapid (<15 secs)
- 30 secs
- Duration: very short acting
- E1/2: **0.5 - 1.5 hrs**
- Equipotent to barbs
58
What is the most common concentration of a 1% solution Propofol?
- 10 mg/mL
59
What are Propofol clinical uses?
- Induction (1% soln)
- Continuous IV infusion
1. Prop only
2. **TIVA - Total/Balanced IV Anesthesia**
3. ICU: 2% soln used to ↓ lipid use
4. Status Epileptics
60
What are the following characteristics of propofol:
- Elimination ½ time.
- Volume of distribution
- Clearance (mL/kg/min)
- E ½ time = 0.5 - 1.5 hrs
- Context sensitive half-time: 40 mins (8- hr infusions)
- **Vd = 3.5 - 4.5 L/kg**
- **Clearance = 30 - 60 mL/kg/min**
61
What are the inactive ingredients in propofol?
- Why is one particularly important? (Think allergies)
- 1.2% **Lecithin (from egg yolks)** → Anaphylaxis with egg allergy
- 2.25% glycerol
- 10% soybean oil
- **Tip**: typically if allergy to egg yolk, NOT given; allergy to **egg white = OKAY to give**
62
What are the disadvantages of propofol's inactive ingredient composition?
- ↑ bacterial growth (**6 hrs** of use from spike; green discoloration)
- ↑ plasma triglycerides with prolonged infusions
- Pain on injection
63
Differentiate Commercial Prop preps: Ampofol, Aquavan, Non-lipid Cyclodextrins.
- Ampofol: low-lipid, no preservative, high pain on inject
- **Aquavan**: prodrug with less injection pain but not used often b/c causes **dysesthesia** (burning sensation esp. women genitals) an **slower onset, larger Vd, and high potency**
- Non-lipid w/ Cyclodextrins (Solubilizing Agent): in trials; study shows even higher injection pain
64
Prop MOA (2)
- Selective modulator of GABA-a that increases Cl⁻ conductance → postsynaptichyper polarization
- Potentiates Glycerine → partial hypnotic effect
65
How does propofol cause immobility through spinal cord-depression?
- Trick question! Immobility from propofol is **not** from drug-induced spinal cord depression.
## Footnote
* Side bars:
* Volatiles alter spinal motor function
* Spinal motor neuron excitability measured by H reflexes
66
What are the clearance characteristics of propofol?
- cleared intravascularly NOT from body
- The clearance of propofol from plasma (lung first pass uptake) **exceeds** hepatic blood flow
- Tissue uptake > CYP450
67
- What metabolizes propofol?
- What are the metabolites?
- CYP450 and UGT1A9
- Water-soluble sulfate and glucuronic acid metabolites
68
- What is the context-sensitive half-time of propofol?
- Is this a relatively Low or High context-sensitive (CS) half-time?
- 40 minutes (for an 8 hours infusion)
- Very Low CS ½ time.
69
Differentiate blood pressure and heart rate changes that occur with propofol vs thiopental.
- Propofol: ↓BP & ↓HR
- Thiopental: ↓BP & ↑HR
70
Does propofol cross the placenta?
- What are the consequences of this?
- Yes but is rapidly cleared from neonatal circulation.
- Beaware of **ion** trapping
71
Do cirrhosis and renal dysfunction have significant effects on propofol metabolism?
- Cirrhosis: No, similar awakening time with alcoholic and normal patient
- Renal dysfunction: No influence on prop clearance via IV
72
What drug is the induction drug of choice?
Dose?
- Propofol
- 1/5 - 2.5 mg/kg IV
73
What is the induction dose of propofol in adults? Children?
- Adults: 1.5-2.5 mg/kg IV
- Pediatrics: higher doses due to larger central volume and clearance rate.
74
What is the induction dose of propofol in the elderly?
- 25 - 50% lower than regular adult dose
75
What **plasma** propofol levels would correlate with unconsciousness on induction?
What about awakening?
- Unconsciousness: **2 - 6 μg/mL**
- Awakening: **1 - 1.5 μg/mL**
76
What is the conscious sedation dose of propofol?
- 25 - 100 mcg/kg/min IV
77
What are the characteristics of propofol in the context of conscious sedation?
- **Anticonvulsant** use
- DOC for **brief GI procedures**
- ICU patients on MV postop
- ↓ risk of PONV
- Prompt recovery w/ low residual sedation
- Minimal analgesia and amnestic properties (adjunct opioid or multimodal)
- Midazolam or opioids as adjuncts.
78
What is the sub-hypnotic dosing for propofol?
- 10 - 15 mg IV, followed by 10 mcg/kg/min
79
- What are the anti-emetic properties of propofol?
- MOA?
- Which dose would you give?
- More effective than ondansetron; CIMV, PONV
- MOA: Depresses subcortical pathways & direct depression of vomiting center
- Give sub-hypnotic dose (10 - 15 mg IV, followed by 10 mcg/kg/min)
80
What is the anti-pruritic dosing of propofol?
- 10 mg IV
- Pruritus secondary to neuraxial opioids or cholestasis
81
What is the anti-convulsant dosing of propofol?
- 1mg/kg IV
82
List "other" category benefits of propofol?
- **Bronchodilator**
- Anti-emetic
- Anti-pruritic
- Anti-convulsant
- Low dose analgesia
- Potent Antioxidant
- Does **not** trigger MH
83
Explain figure.
Respiratory resistance after tracheal intubation the least after Propofol induction and most with Etomidate
84
Propofol: CNS effects:
- **DECREASED** **↓** CMRO₂, **↓**CBF, and **↓**ICP
- **↓** CPP (support MAP)
- **Myoclonus** can occur. Does **NOT produce seizures tho**
85
T/F: Auto-regulation of CBF and PaCO2 are maintained.
- What term describes the relationship?
- True
- CBF and PaCO2 is coupled
86
**T/F**: Propofol EEG changes similar to Isoflurane.
- False; **Prop EEG similar to Thiopental**
87
EEG waves one word descriptions per lecture:
Alpha
Beta
Delta
Gamma
Theta
- Alpha: awake
- Beta: Concentration
- Delta: Deep Sleep
- Gamma: Thinking/Testing
- Theta: Light Sleep
88
Does Propofol cause SSEP suppression?
- No
- **Exceptions**: Nitrous or volatiles added
89
Which would decrease blood pressure more, thiopental or propofol?
* Propofol
- Decreased SBP greater than Thiopental
90
What is the mechanism for propofol-induced hypotension?
* What conditions will these effects be exaggerated?
- SNS inhibition → **vascular smooth muscle relaxation** = ↓SVR
- ↓ ICF Ca⁺⁺ = ↓ contractility
- Hypovolemia, elderly, and LV compromise
91
How is propofol-induced hypotension from induction usually counteracted?
- Intubation **(laryngoscopy stimulation**)
92
Mechanisms of bradycardia with propofol administration:
- ↓SNS response by direct effect on muscaranic receptors
- Baroreceptor reflex
depression
- Profound bradycardia & asystole (documented even in healthy patient)
93
Propofol black box warning in pediatrics?
- Profound bradycardia (fatal)
- Pre-medicate pedis with Glycopyrolate
94
Propofol: Pulm effects
How does this change with opioids?
- What intraOp technique can counteract negative effects?
- **Dose-dependent** ventilation depression (apnea)
(**painful surgical stimulation by surgeon counteracts**)
- **Synergistic with opioids** (increased risk)
- Hypoxic pulmonary vasoconstriction reflex remains **intact**
95
Propofol: Hepatic/Renal effects
- LFTs/ creatinine are normal
- Hepatocellular injury
- Propofol Infusion Syndrome
96
What is Propofol Infusion Syndrome?
- What dose is associated w/ syndrome?
- **Lactic acidosis** thought to occur from poisoning of electron transport chain and impaired oxidation of fatty acids.
- High doses > 75 mcg/kg/min longer than 24 hrs
97
Propofol infusion syndrome: - - S&S?
- Diagnostics?
- Is it reversible?
- Late stage complication?
- Urine changes, **lactic acidosis, brady-dysrhythmias, rhabdomyolysis**
- ABG & Lactic
- Reversible in early stages
- Late stage = CV Shock (ECMO)
- **severe, refractory bradycardia in KIDS**
98
What relatively benign condition(s) can occur from prolonged propofol infusions?
Why does this happen?
- Urine: Green (phenols) and/or cloudy (uric acid crystals)
- **No alterations in renal function**
99
What is the worst side effect in children who have propofol infusion syndrome?
- Severe, refractory, fatal bradycardia
100
Propofol: Other organ effects
- Injection pain (10% of patients (give Lido prior and/or use larger vein)
- ↓ IOP (benefit for trendelenburg position)
- PLT aggregation inhibition (insignificant clotting risk)
- Allergic reactions (ie: lecithin)
- Prolonged myoclonus (sleep w/ involuntary movement)
- Abuse/misuse (15% in HCWs)
