Exam 3 Flashcards
influences of age on the PK of volatiles
↓ lean body mass (muscle mas)
↑ fat mass = ↑ Vd for drugs (especially for more fat soluble)- in certain compartments
↓ clearance if pulmonary exchange is impaired
↑ time constraints due to lower cardiac output
Boyle’s Law
Given a constant temperature….
Pressure and volume of gas are inversely proportional
Fick’s Diffusion Law
Once the molecules get to the alveoli, they move around randomly and begin to diffuse into the pulmonary capillary
Diffusion depends on:
Partial pressure gradient of the gas
Solubility of the gas (diffusion)
Thickness of the membrane
Carbon dioxide vs oxygen molecular wt and solubility
Carbon dioxide, molecular wt 44 g
Oxygen, molecular wt 32 g
co2 is more soluble
Graham’s Law of Effusion
Process by which molecules diffuse through pores and channels without colliding
Smaller molecules effuse faster dependent on solubility (diffusion)
Alveolar pressure an indicator of:
Depth of anesthesia
Recovery from anesthesia- if brain is greater than amount to alveoli – waking up / loosing gas from vessel rich group to alveolis.
Solubility
A ratio of how the inhaled anesthetic distributes between 2 compartments at equilibrium (when partial pressures are equal)
***the relative capacity of each compartment to hold volatile
temperature dependent
Blood gas partition coefficient for Halothane
2.54
Blood gas partition coefficient for Enflurane
1.90
Blood gas partition coefficient for isoflurane
1.46
Blood gas partition coefficient for nitrous oxide
0.46
Blood gas partition coefficient for desflurane
0.42
Blood gas partition coefficient for sevo
0.69
des color
blue
sevo color
yellow
iso color
purple
halothane color
red
MAC: Minimum alveolar concentration:
“the concentration at 1 atm that prevents skeletal muscle movement in response to supramaximal, painful stimulation in 50% of patients”
partial pressure/ percentage of volatile anesthetic we will give.
MACawake
(0.3-0.5 MAC)
presumes that all we are giving is 1.3 mac when we turn the mac off and we let them wake up when they get to 0.3-0.5 = wake up.
MACBAR
(1.7-2.0 MAC)
blunts autonomic responses. If we had 2 mac of des on board w/ no pain and we intubated you, hr wouldnt respond, no sns response at mac bar. But will be very hypotensive. Mac bar = not used.
nitrous mac
104%
halothane mac
0.75%
mac enflurane
1.63%
mac iso
1.17%
mac des
6.6%
mac values based on
Based on 30-55y/o average; 37 degrees C; 760mmHg pressure (1 ATM)
sevo mac
1.8%
Factors that alter MAC
Biggest…
Body temperature
Age…6% per decade
MAC peaks at 1 y/o
Increases in MAC
Hyperthermia
Excess pheomelanin (redhead) production
Drug-induced increase in catecholamine levels
Hypernatremia
Decreases in MAC
Hypothermia
Preoperative medication, intraoperative opioids
Alpha-2 agonists
Acute alcohol ingestion
Pregnancy
Post partum (early…12-72 hours)
Lidocaine
PaO2 <38 mm Hg
Mean BP < 40mm Hg
Cardiopulmonary bypass
Hyponatremia
No change in MAC
Chronic alcohol abuse
Gender
Duration of anesthesia
PaCO2 15-95 mm Hg
PaO2 > 38 mm Hg
Blood pressure > 40 mm Hg
Hyper/hypokalemia
Thyroid gland dysfunction
(Spinal) Immobility by
Depress excitatory AMPA and NMDA (glutamate receptors)
Enhance inhibitory glycine
Act on sodium channels
Loss of consciousness by
Inhibitory transmission of GABA
Potentiation of glycine activation in brainstem
Henry’s Law
”the amount of dissolved gas in a liquid is proportional to its partial pressure above the liquid”
Vapor pressure halothane
243 torr
vapor pressure enflurane
175 torr
iso vapor pressure
238 torr
sevo generic name
ultane
desflurane generic name
suprane
isoflurane generic name
forane
Sevo vapor pressure
157 torr
des vapor pressure
669 torr
Things that affect Anesthetic machine to alveoli- boyls law
Inspired partial pressure
Alveolar ventilation- faster = more inhaled gas we take in
Anesthetic breathing system (is there a lot of re-breathing?)
FRC
Things that affect pressure gradient alveoli to blood
Blood: gas partition coefficient- Different for every gas
Cardiac output
A-v partial pressure difference
Things that influence Partial pressure gradient of arterial blood to brain
Brain: blood partition coefficient
Cerebral blood flow (depends on CO)
a-v partial pressure difference
The impact of PI on the rate of rise of PA
The higher the PI (of a volatile) the more rapidly PA approaches PI
“Over pressurization”
Way to force extreme contraction gradient on the vaporizer to the patient get asleep in a couple breaths= large increases in inspired pressure.
A large increase in PI
1 vital capacity breath of high concentration Sevoflurane (7%)
loss of eyelash reflex= ready to intubate
Second gas effect
nitrous + VAA
High volume of N2O uptake into pulmonary capillary concentrates alveolis = increased VAA partial pressure
Nitrous diffuses into
air-filled cavity
Up to 10L in the 1st 10-15 minutes
Compliant walls
Non-compliant walls
cases we dont give nitrous to
bowel case, ear or eye cases, pntx
if temperature of the blood increase…..
solubility of the drug increases
Low blood solubility……
Minimal amounts must be dissolved; PA/Pa is rapid; induction is rapid
High blood solubility…..
Large amounts must be dissolved: PA/Pa is slow; induction prolonged
When does emergence begin?
When PI is zero (inhaled agent is turned off)
Muscle/fat maybe not at equilibrium
Muscle/fat continue to take up anesthetic (helps decrease PA and PBr)
1.3 mac
the concentration at 1 atm that prevents skeletal muscle movement in response to supramaximal, painful stimulation in 99% of patients
Vapor Pressure
Pressure at which vapor, and liquid are at equilibrium
Splitting ratio
how big the whole is/ sending to pass through vaporizer
Large splitting ration = sending more
0 splitting ration = not dividing at all
high flow
FGF exceeds minute ventilation
MOA that vaa on relaxing airway smm
Block voltage-gated Ca++
Deplete Ca++ in SR= no bronchodilation
Require intact epithelium; inflammatory processes, epithelial damage alters
VAA With bronchospasm with R/f and meds
Risk factors: COPD, cough response with ETT, age <10, URI
Sevoflurane > Isoflurane at causing bronchodilation
Desflurane may worsen especially in smokers due to pungency/irritation
Respiratory resistance comparison meds
thiopental and des more than halothane, sevo or iso
vaa nm effects
Dose-dependent skeletal muscle relaxation
Potentiate depolarizing and non-depolarizing NMBDs
nAch receptors at NMJ
Enhance glycine (inhibitory nt) at spinal cord
Nitrous oxide has no relaxant effect on skeletal muscles
VAA on cmro2 and cerebral activity
mac to get there
mac for burst supp and silence
⬇️ CMRO2 and cerebral activity
Begins approx 0.4 MAC as wakefulness changes to unconsciousness
1.5 MAC: burst suppression
2 MAC: electrical silence
Isoflurane=sevoflurane=desflurane
vaa on cbf, mac necessary. meds that affect and how
Dose dependent ;
⬆️ CBF due decreased cerebral vascular resistance
May increase ICP
Onset > 0.6 MAC
Occurs within minutes despite lack of BP change
Isoflurane= Desflurane
Sevoflurane less vasodilatory effect
Nitrous potent vasodilator (but give < 1MAC)
Halothane worst
vaa effect on Autoregulation at what mac
Halothane lost by 0.5 MAC
Sevo preserves to 1 MAC
Iso and Des lost 0.5-1.5 MAC
vaa on Respiratory depression mac for apnea
Dose-dependent ↑ rate, ↓ Vt
Apnea (1.5-2.0 MAC)
Type I: hepatotoxicity
20% of patients
1-2 weeks after exposure
Direct toxic effect or free radical effect???
Nausea, lethargy, fever
Type II: hepatotoxicity
Less common
Immune-mediated response against hepatocytes: eosinophilia, fever
Prior exposure
High mortality: acute hepatitis, hepatic necrosis
1 month after exposure
mivacurium reversal
reverses from plasma cholinesterase
Depolarizing action
Mimics the action of acetylcholine
Non-depolarizing Action
Interferes with the action of acetylcholine
Depolarizing meds
succinylcholine (Anectine)
Long acting non depolarizing
Pancuronium (Pavulon)
short acting non depolarizing
mivacrium (mivacron)
Intermediate acting non depolarizing
Atracurium (Tracrium)
Vecuronium (norcuron)
Rocuronium (zemuron)
Cisatracrium (nimbex)
Chemical Classification for pancuronium (pavulon)
Aminosteroid
Chemical Classification for atracurium
Benzylisoquinolone
Chemical Classification Vecuronium
Aminosteroid
Chemical Classification rocuronium
aminosteroid
Chemical Classification
cisatracurium
Benzylisoquinoline
Chemical Classification
mivacruium
Benzylisoquinoline
ED95 for NMBD
Equal Potency: dose necessary to produced 95% suppression of single twitch
In the presence of nitrous/barbiturate/opioid anesthesia—–GA.
Adductor pollicis muscle-
palm nerve that causes the thumb to adduct
NMB block depends on….
of postsynaptic Ach receptors
number of presynaptic Ach containing vesicles released
# of postsynaptic Ach receptors. Fewer R than what we have ach released?
Blood flow to area
Drug potency
Orbicularis oculi reflects
facial nerve stimulation
More closely reflects diaphragm and laryngeal muscle blockade
Underestimate residual paralysis
Adductor pollicis indicates
Poor indictor of laryngeal relaxation
Good indicator of peripheral recovery.
Look for extubation
Gold standard for recovery
Distal electrode
black
proximal electrode
red
Ulnar nerve side of arm
pinky side, closer to midline
Defasciculating dose
give 20% of normal intubating dose early / primer/
small dose as primer prior to intubating dose, pt still somewhat awake but they are still somewhat awake and if you give defasciculating dose = still have side effects ; blurred vision, feeling weak/ can’t take a deep breath
tell them; will get sleepy, blurry eye, droopy eyeballs, encourage them to close their eyes.
helps keeping them from being anxious.
Patient symptoms to nmb
Loss of visual focus
Mandibular muscle weakness
Ptosis
Diplopia
Dysphagia
Increased hearing acuity; encourage quiet environment.
Single twitch and use
Usually 1 Hz/second decreasing to 0.1 Hz q 10 seconds
Continuously/ gtt
Onset of block = fade with each stimulus
Double Burst
3 short bursts followed by 3 short bursts; pause in between
Use 50 Hz (supramaximal current)- more strength/ power
Developed to improve detection of residual block
Fade in 2nd response vs 1st
Qualitatively better than TO4
Train of Four (TOF)
4 stimuli at 2 Hz in ½ second
Reflects events at presynaptic membrane
TOF Ratio
Prior to NMBD:
4/4 twitches…TOFR 1
TOF Ratio
After administration
return of 4 twitches
Amplitude of 4th twitch to 1st twitch
If amplitude of 4th 50% of 1st…. TOFR 0.5
Experienced anesthetists’ unable to detect fade TOFR > 0.4 (40%)
Tetanic stimulation
Very rapid, 50 Hz for 5 seconds
Tetanic stimulation depolarizing block
Sustained muscle response
Tetanic stimulation non-depolarizing block
Non-sustained response; fade
Phase II block with Succs
Fade with tetanic stimulation related to
Presynaptic depletion of Ach or inhibition of release
Frequency and length of stimulation
Post-tetanicstimulation
Single twitch 3 seconds after tetanic stimulation
Occurs d/t accumulation of calcium during “tetany”
Excess calcium stimulates Ach release
no response to Post-tetanicstimulation
= intense blockade
Block is really strong and wont be unparalyzed.
stimulation for reversing someone
TOF -> tetany and post tetanic stimulation.
Earlier response = more spontaneous reversal we have.
twitches are what type of measurement
qualitative not quantitative
What breaks down succ
butyrylcholinesterase (plasma cholinesterase)
Purpose of Ache
hydrolysis of Ach
breaks down to acetic acid and choline
resting membrane potential for post synaptic cleft of nmj
-90 mv
Maintained by sodium/potassium
nAChRs directly opposite
Pentameric unit of nachr
2-alphas, beta, delta, gamma
Transmembrane pore
If Ach binds to nachr subunit
Conformational change
Pores open, sodium/calcium/potassium flow
If NMBD binds to nachr subunit
No conformational change
No ion flow
Probability of binding d/t concentration of NMBD vs Ach
sch on nachr
*Sch only requires binding at 1 alpha subunit
Other alpha either Sch or Ach
Channel remains open longer
Can leave 1 receptor and attach to other nAChRs till hydrolyzed….fasiculations
Dose of sch
1 mg/kg IV
Onset of sch
30-60 seconds; don’t ventilate after giving
Duration of action of sch
3-5 min
Hydrolysis of sch
Hydrolysis is slower than Ach
Sustained opening of receptor ion channels
Leakage of potassium ions = 0.5 mEq/liter serum increase
Dialysis patients? Safe if dialyzed recent. Check K+ before giving
Depolarization called
phase 1 block
Phase I block characteristics
⬇️ contraction height to single twitch stimulation
⬇️ amplitude to continuous stimulation
TOF ratio > 0.7; don’t have a fade and no change from first to last twitch
Absence of post-tetanic facilitation; same amplitude
Skeletal muscle fasciculations
Phase II block typical
Responses typical of non-depolarizing NMBD
Can be antagonized by anti-cholinesterase drug
other causes of phase 2 block
SCh dose 2-4 mg/kg
Lack of/poorly functioning pseudocholinesterase
Relative “overdose”….phase 1 transition to phase 2 characteristics ; desensitization
butyrylcholinesterase
Synthesized in liver
Terminated by diffusion out of NMJ into plasma
Succinylmonocholine (less potent) and choline
Pseudocholinesterase activity affected by….
-Decreased hepatic production (⬇️ 75% before apparent)
-Drug-induced decreases (Neostigmine, Reglan, chemo, insectides)
-Genetically atypical; less quality of functioning pseudocholinesterase.
-Chronic diseases (renal): ↓ activity (quality of function)
-Pregnancy (high estrogen levels): ↓activity
-Obese: ↑ activity of plasma cholinesterase. If giving in real life; give sux then based on actual body wt not ideal body wt because obesity increase hydrolysis ability. Get rid of sux faster.
Dibucaine-related variant
Get Dibucaine level
Reflects quality not quantity of enzyme
20: SCh 1mg/kg lasts 3 hours
Dibucaine
-Amide local anesthetic
-Inhibits breakdown of butyrylcholinesterase
-% inhibition = dibucaine number
normal dibucaine level
80 or above = normal breakdown
Side effects of SCh
Cardiac dysrhythmias (SB, JR, Sinus arrest)
Hyperkalemia
Myalgia
Myoglobinuria
Masseter spasm
⬆️ intragastric pressure
⬆️ intraocular pressure
⬆️ intracranial pressure
Pretreatment with non-depolarizing NMBD
Myoglobinuria from sch
Damage to skeletal muscles
Especially pediatrics
Usually found later to have MH or muscular dystrophy
Deuchenees.
No sux to peds
Actions at cardiac muscarinic, cholinergic receptors
with sch
Mimics action of ACh
Most likely on 2nd dose, 5 minutes post 1st
Due to metabolites: succinylmonocholine and choline
Sch Actions at ANS ganglia
⬆️ Heart rate and blood pressure
Mimics action of Ach
Usually occurs with large doses
Hyperkalemia occurs in….
Patients with extrajunctional sites
Unrecognized muscular dystrophy (Duchenne’s)
Unhealed 3rd degree burns
Denervation of skeletal muscles (atrophy)
Skeletal muscle trauma
Upper motor neuron lesions
Myalgia with sch
Young adults
Neck, back, abdomen
Phayngitis
Confused with pharyngitis d/t intubation
Muscle aches from muscle twitching
Intraocular pressure from sch
Maximum increase 2-4 minutes after administration
-Lasts 5-10 minutes
-MOA unknown
-Contraction of EOM and globe distortion
-Resistance to outflow of aqueous humor and dilation of vessels
sch Contraindicated in open anterior chamber injury
Efficacy of pre-curarization controversial
Intracranial pressure with sch
In patients with intracranial tumors or CHI
Not consistently observed in studies
Attenuated by hyperventilation prior to SCh
Co2 decreases = cerebral blood flow decreases/constrict= decrease ICP
RSI not ventilated
Sustained skeletal muscle contraction with sch
Incomplete jaw relaxation/masseter muscle spasm
Muscles contract and don’t relax
Spasm = cant intubate-> wait for sux to wear off
Inadequate dosage given (children)
Early indicator of Malignant Hyperthermia
Malignant hyperthermia signs
Muscle destruction
Hyperkalemia
Acidosis
Dysrhythmia
Renal failure
DIC
Hereditary rhabdomyolysis associated with anesthetics
Triggers for MH
ALL volatile anesthetics
Succinylcholine
MOA of MH
Mutations in skeletal muscle calcium release
Ryanodine receptor (RyR1)
Ca release of SR
50-70% of MH patients
Native Americans
Skeletal muscle caffeine contracture testing
Muscle biopsy
Symptoms of MH
Acute increased skeletal muscle metabolism
Increased oxygen consumption
Lactate formation
Heat production
Rhabdomyolysis
↑ ETCO2
↑ temp 1 degree C/5 minutes
Arrhythmias
Skeletal muscle rigidity
Treatment of MH
Agent; stop triggering agent, adnimister non triggering anesthetics, ask for help, ask for MH cart
Breathing- hyperventilate w/ 100% oxygen
C= cooling if pt is >102.2
D=dantrolene, continous Rapid IV push
Dantrolene dose
2mg/kg IV
Repeat doses until symptoms subside or 10mg/kg IV
Dantrolene moa
Inhibits calcium release into SR
By affecting the ryanodine receptor
Dantrolene metabolization
Metabolized in liver
5-hydroxydantrolene
Muscle relaxant properties
50% c/o weakness…grip strength
careful with; Verapamil, Cardizem->Cardiovascular collapse
Dantrolene side effects
Most common
Weakness
Phlebitis
Respiratory failure
Gastrointestinal upset
Less common
Confusion
Dizziness
Drowsiness
Myasthenia Gravis
Autoimmune disease
Antibodies against Ach receptor
↓ Ach receptors
Increasing weakness/fatigue
Diplopia
Ptosis
Extremity and respiratory muscle weakness
Tx with cholinesterase inhibitors
Care for MG
Resistant to Sch… 1.5-2.0 mg/kg
fewer receptors….ED95 2.5 times higher
pt should go first case
Lambert-Eton
Autoimmune disease
Small-cell lung cancer
Antibodies against calcium channels
Decreases release of Ach pre-junctionally
Increased sensitivity
Depolarizers
Non-depolarizers
give less; 20% of normal dose.
“autonomic margin of safety”
Difference between dose that produces blockade (ED95) and dose that creates circulatory effects
Same dose for pancuronium
Very different dose for vec, roc, cis
Volatiles that cause dose dependent enhancement of NMBD
Desflurane>Sevoflurane>Isoflurane
Onset as early as 30 minutes
loop DiureticsCorticosteroidsMetocloproideLAs
w/ nmd
Enhances or prolong blockade;
↑ acetylcholine release
Depression of cholinesterase activity
Depression of nerve conduction
Magnesium on non depol and sch and moa
Enhances blockade
MOA (for non-depolarizers);
Decreases prejunctional release of Ach
Decreases sensitivity to postjunctional membranes
Ephedrine prior to non-depolarizers
Decreases onset time d/t⬆️ CO and skeletal muscle flow
Esmolol prior to induction
Delays onset
Hypothermia on ndmb and moa
Even mild hypothermia
Vecuronium, Pancuronium (doubles the duration)
MOA; Temperature slowing of hepatic enzyme activity
Atracurium/Cisatracurium metabolism
MOA: temperature and ph dependent elimination processes
Hoffman elimination
Ester hydrolysis
Burns on ndmb and moa
Resistance
Begins approx. 10 days post injury
Declines after 60 days
30% BSA or >
May be offset by using 1.2 mg/kg dose of Rocuronium– use more ?
MOA???
Altered affinity of nAChRs?
Not related to altered density (# of receptors)
Stroke of ndmb and moa
paretic arm; Resistance compared to unaffected side
Unaffected side; Resistance compared to normal patients
MOA; Proliferation of extrajunctional nAChRs
Allergic reactions
Succinylcholine more likely
Pavulon, Vecuronium, Rocuronium < Succinylcholine
Cisatracurium least likely
cross-sensitivity with quaternary ammonia
Gender effect on ndmb
Women more sensitive
Need 22% less (vecuronium)- less muscle
Need 30% less (rocuronium)
duration of block greater in women
Intubating Dose for Pancuronium(Pavulon)
0.1 mg/kg
Onset for pancuronium
3-5 min
duration of pavulon
60-90 minutes
Metabolism of pavulon
80% eliminated unchanged in urine
renal failure with pavulon
30-50% decreased plasma clearance
10-40% deasacetylpancuronium metabolite ½ as active (by liver)
liver disease with pavulon
Increased VD
Larger initial dose is needed
Prolonged elimination ½ time
Pavulon cv effects
↑ HR, MAP, CO
d/t vagal blockade
Mostly at SA node
BP increase d/t HR
d/t SNS activation
Release of NE presynaptically
Blockade of NE reuptake
Compared with Long Acting NMBDs intermediate acting…..
Similar onset of maximum blockade (except high dose roc)
Approximately 1/3 duration of action
Minimal/absent cardiovascular effects
Antagonized by anticholinesterase drugs approx 20 min.
Vecuronium(Norcuron) dose onset duration
Intubating Dose: 0.1 mg/kg
Onset: 3-5 minutes
Duration: 20-35 minutes
Vec metabolism
Hepatic metabolism
Principle organ of elimination
3-desacetylvecuronium 50-80% as potent (but rapidly converted to metabolite with 1/10 the effects)
Renal excretion
Approx 30% appears unchanged (*70% metabolized in liver)
Renal dysfunction
Elimination ½ time prolonged
the cumulative effect of vec
Repeated doses or infusion: cumulative effects
vec metabolism for OB
Increased clearance in 3rd trimester (progesterone)
Prolonged duration early postpartum (give IBW)
Vec on elderly
Decreased volume of distribution (less muscle mass)
Decreased plasma clearance (less hepatic flow)
Single dose mechanics unchanged
Delayed recovery with infusions
Respiratory acidosis
Following NMBD
prolongs blockade
Activity inversely proportional to bound drug…acidosis decreases the bound amount
Change in ionization at receptor increases attachment time
Concern postop with hypoventilation
Rocuronium(Zemuron) dose onset duration
intubation: 0.6 mg/kg or
RSI; 1.2 mg/kg (parrallel onset of sch)
Onset: 3-5 minutes; 1-2 minutes (with sux)
Duration: 20-35 minutes
Metabolism for roc
Excreted unchanged in bile
Longer duration of action in liver failure and elderly
d/t decreased clearance and an increased Vd
10-30% renal excretion
Only marginally affected in renal failure
Cisatracurium(Nimbex), dose, onset, duration
Intubating Dose: 0.1 mg/kg
Onset: 3-5 minutes
Duration of action 20-35 minutes
Metabolism of nimbex
Recovery from infusion NOT affected by time
Degradation
Hoffman elimination (ph and temperature dependent)
Doesn’t use non-specific plasma cholinesterases as much as Atracurium
nimbex in obese
Duration of action prolonged IF dosed at actual body weight
d/t Vd
Mivacurium(Mivacron) dose onset duration
Intubating Dose: 0.15 mg/kg
Onset: 2-3 minutes
Conditions less desirable
Duration of action: 12-20 minutes
nimbex metabolism
Cleared by plasma cholinesterase
nimbex histamine release
> 3 x ED95… transient MAP drop
More common with rapid, large doses
MAP drop more in HTN pts than non-HTN pts
Dose succ based on….
actual body wt
resistance
harder to block / need more to get effect
