Neuromuscular Blocking Flashcards
Choline Hydrolysis
Acetylcholinesterase (“true” cholinesterase)
VS.
Butyrylcholinesterase (plasma cholinesterase)
PChe - pseudocholinesterase
Synthesized in liver
Succinylcholine hydrolysis in plasma
Muscle Relaxation Onset
Eye muscles > extremities > trunk > abdominal muscles > diaphragm
Neuromuscular Function Clinical Tests
TOF Tetanus Post-tetanic count Single twitch Double-burst suppression
Train of Four
Most widely used
Four separate stimuli every 0.5sec at 2Hz
T1-T4 comparison
Non-depolarizing onset = fade
4 twitches 75-80% receptors can still be blocked
Zero twitches = 100% blocked
Tetany
Continuous electrical stimulation for 5sec at 50-100Hz
Reliable for detecting fade
Sustained contraction w/out fade = paralysis unlikely
Post-Tetanic Count
Tetany followed in 3sec by single twitch stimulations
Higher the count (>8) less intense the block
Single Twitch
Single twitch at 0.1-1Hz for 0.1-0.2sec
Determine when 100% paralysis present
Double-Burst Suppression
Seems to improve ability to detect residual paralysis
Evaluate 2 rather than 4 twitches
Extubation Conditions
5 second head life
Generate peak negative inspiratory pressure 20-30cm H2O
Neuromuscular Blocking Structure
Quaternary ammoniums = ionized
Low Vd - does not cross blood-brain or placenta
Structurally r/t ACh
Primarily synthetic alkaloids
Non-Depolarizing Blockade
Decrease in twitch tension (strength)
Fade during repetitive stimulation
Post-tetanic potentiation
Fade
Concentration
Twitch depression results from blocking post-synaptic nicotinic ACh receptors
Post-tetanic or TOF fade results from blocking PRE-synaptic nAChR ↓ACh released
Depolarizing Blockade
Phase 1 often preceded by muscle fasciculation
Decrease in twitch tension
NO fade during repetitive stimulation
NO post-tetanic potentiation
Phase 2 not commonly seen
Repeated or long-term administration
Doses >6mg/kg
Inhibit pre-synaptic nAChR
Succinylcholine
ONLY depolarizing NMBD
Two ACh molecules linked by acetate methyl groups
Intubating conditions w/in 60sec
Duration 4-5min
Recovery to 90% muscle strength 9-13min (offset)
Short action d/t rapid hydrolysis by butyrylcholinesterase
Butyrylcholinesterase (PChE)
Psuedocholinesterase
Metabolized in liver & found in plasma
Genetic variations prolong effects d/t unable to metabolize succinylcholine
Dibucaine
Local anesthetic than inhibits typical PChE
Number indicates cholinesterase quality NOT quantity
80 = 80% PChE enzyme inhibited
Dibucaine Number
Normal genotype >70 Heterogenous for atypical gene = 40-60 → Prolongs block 1.5-2x longer Homogenous for atypical gene < 30 → Block prolonged 4-8hrs (unable to extubate) → Overnight ICU admission
Succinylcholine SE
Bradycardia, junctional rhythm, sinus arrest
Ventricular dysrhythmias, tachycardia, ↑ BP d/t autonomic ganglia stimulation
Hyperkalemia - severe in burn, abdominal infections, metabolic acidosis, closed head injury, & nAChR upregulation
Myoglobinuria - damage to skeletal muscle (especially in pediatric patients MD or malignant hyperthermia susceptible)
↑ intraocular pressure NOT commonly used in eye surgery
↑ gastric and lower esophageal pressures (↑ gastric contents)
↑ ICP r/t head injury
Masseter spasm (early indicator) - KNOWN TRIGGER for malignant hyperthermia
Myalgias - prominent in neck, back, & abdomen skeletal muscle
Elderly: Slower onset d/t ↓ circulation & reduced PChE levels
Pediatrics: Avoided in patients <5yo, Duchenne muscular dystrophy, cardiac arrest d/t hyperkalemic rhabdomyolysis
Malignant Hyperthermia
Pharmacogenetic disorder triggered by volatile anesthetics, succinylcholine, & stress
Ryanodine receptor gene mutation (chromosome 19)
S/S: ↑ CO2 production (1st sign), muscle rigidity, ↑ peak airway pressure, ↓ TV, metabolic acidosis, ↑ temp (late sign)
Succinylcholine Dose
Intubation 1mg/kg based on ideal body weight
Non-Depolarizing NMBDs Classifications
*Steroidal - Pancuronium, Vecuronium, & Rocuronium
Most common
Benzylisoquinoliniums - Atracurium & Cisatracurium
Atracurium
Benzylisoquinoliniums
Intermediate onset & action
Ester hydrolysis & spontaneous degradation
-Hoffmann elimination
Metabolite: Laudanosine (tertiary amine) implicated in convulsions
HISTAMINE RELEASE
Atracurium Dose
Intubation 0.5mg/kg
Cisatracurium
Benzylisoquinoliniums Atracurium cis-isomer Intermediate onset & action Metabolism - Hoffmann elimination NO histamine release Acceptable option for liver and/or renal failure
Cisatracurium Dose
Intubation 0.1mg/kg
Mivacurium
Only available short-acting non-depolarizing drug available
Not used in the USA (only Europe)
Metabolized by butyrylcholinesterase in plasma
Histamine release possible
Mivacurium Dose
Intubation 0.15mg/kg
Pancuronium
Steroidal
Potent long-acting NMBD
Vagolytic (maintain HR & BP) and butyrylcholinesterase properties
Clearance via kidney
Small amount de-acetylated by liver
3-OH metabolite accumulation responsible for block prolongation
Pancuronium Dose
Intubation 0.08mg/kg (most potent steroidal NMBD)
Pancuronium Onset
SLOWEST
Onset time to maximum block 2.9min
Vecuronium
Steroidal
Intermediate-acting (as compared to Pancuronium) NMBD
Essentially Pancuronium w/out quaternized methyl group - slight potency decrease, loss vagolytic properties, molecular instability (shorter duration), ↑ lipid solubility
Metabolized primarily by liver
3-OH metabolite 80% neuromuscular potency
Vecuronium Dose
Intubation 0.1mg/kg
Vecuronium Onset
Onset time to maximum block 2.4min
Rocuronium
Steroidal
Intermediate-acting NMBD
Metabolized primarily by liver
Approximately 30% excreted in urine
Rocuronium Dose
Intubation 0.6mg/kg (least potent steroidal NMBD)
6x less potent than Vecuronium
Rocuronium Onset
FASTEST
Onset time to maximum block 1.7min
Steroidal Compounds
Acetyl ester facilitates interaction w/ nAChR
No conformational change
Essential that 1/2 nitrogen atoms quaternized
Pancuronium, Vecuronium, Rocuroniuam
Liver & renal impact
NMBD Potency
Increase: Inhalation agents, antibiotics, hypothermia, Magnesium sulfate (Ca2+ antagonist), local anesthetics, Quinidine (anti-arrythmic)
Decrease: Chronic anticonvulsant administration, hyperparathyroidism, hypercalcemia
INVERSE relationship w/ onset
Low potency = quick onset
NMBDs Adverse Effects
Autonomic - block nicotinic receptors w/in SNS & PSNS → bradycardia & hypotension
Histamine - flushing, hypotension, reflex tachycardia, bronchospasm, ↑ HR, ↓ SVR
Usually short duration (1-5min)
Pre-treat w/ H1 & H2 blockers to ↓ CV effects
Respiratory r/t histamine release in patients w/ reactive airway disease ↑ airway resistance & bronchospasm
Allergic reactions - cross reactivity b/w NMBDs & food, cosmetics, disinfectants, industrial materials
Roc & Succ most common cause (also ↑ prevalence/administration)
Treatment: 100% FiO2, IV epi, intubation, fluid admin (crystalloid vs. colloid), sympathomimetic drugs (pressers)
NMBD Reversal
Acetylhcholinesterase hydrolyzes ACh - reversal dependent on ACh vs. NMBD concentration at NMJ AChE inhibitors (Neostigmine, Edrophonium, Pyridostigmine) - antagonize residual effects, accelerate recovery, cause ACh build-up to compete w/ residual NMBD Antagonism depends on blockage depth when reversal attempted, inhibitor chosen, dose, spontaneous clearance rate, & anesthesia choice/depth
Neostigmine
Ceiling effect - once reached additional doses have no effect
Maximum block depth antagonist corresponds to 4th twitch return
Cannot antagonize profound or deep blockade levels
Administering more inhibitor can have detrimental effects
Neostigmine Dose
40-80mcg/kg
Maximum dose 6mg
Edrophonium Dose
1-1.5mg/kg
Based on block %
Twitches number, strength, & fade
ACh Inhibitor SE
Cardiovascular: Muscarinic effects MUST be blocked by anticholinergic
Pulmonary: Bronchoconstriction (↑ airway resistance & ↑ salivation)
GI: ↑ bowel motility w/ no effect on PONV incidence
Effects reduced by co-administration w/ anticholinergics
Glycopyrrolate +
NEOSTIGMINE Similar onset times *Match dosages* Small w/ small Moderate w/ moderate Large w/ large MAX w/ MAX
Glycopyrrolate Dose
5-10mcg/kg
200mcg per 1mg Neostigmine OR
0.4mg per 2mg Neostigmine
Atropine +
EDROPHONIUM
Similar onset times
Match dosages
Atropine Dose
7-10mcg/kg OR 0.01mg/kg
Only True Objective NMBD Monitoring
Qualitative monitoring Need 4/4 twitches to assess % fade from 1st to last twitch TOF >0.9 (90%) Less than 0.9 associated w/ difficulty speaking & swallowing, visual disturbances, & aspiration risk
Sugammadex
Modified gamma-cyclodextrin
Aminosteroid-induced reversal (Roc, Vec, & Panc)
Selective relaxant-binding
NO effect on acetylcholinesterase - not r/t ratio
Attaches in plasma to encapsulate NMBD therefore unable to work (inactivates)
Also encapsulates progesterone - birth control ineffective for 1wk
Ineffective against succinylcholine & benzylisoquinoliniums
Possible allergic reactions or bleeding
Sugammadex Dose
Based on TOF response
TOF >2 = 2mg/kg
1-2 = 4mg/kg
0 = 8-16mg/kg
