Nmba Flashcards
What is the structure of succinylcholine?
2 joined Ach molecules
What is the dosage of succinylcholine ?
1-1.5 mg/kg
What is the intubating dose of suc if you use a defasciculating dose of roc?
1.5-2 mg/kg
What is the defasciculating dose of roc?
0.03mg/kg
How is succinylcholine metabolized?
By pseudocholinesterases
How long can paralysis last in someone homozygous for pseudocholinesterase deficiency?
3-8 hours
How can you tell if they have pseudocholinesterase deficiency?
Dibucaine inhibits normal pseudocholinesterase by 80% but only 20% in abnormal
What drug prolongs neuromuscular blockade?
Cyclosporine (has solvent polyethoxylated castor oil) Aminoglycosides Tetracyclines Polymixin Clindamycin
What drug prolongs the action of succinylcholine?
Echothiophate
How does Echothiophate prolong succinylcholine ?
By inhibiting pseudocholinesterase
Can cause 95% decrease in plasma butyrylcholinesterase for 4-6 weeks after stopping the drug
What is Echothiophate?
A topical eye medication for glaucoma- an acetylcholinesterase inhibitor
How do all neuromuscular blocking agents work?
They are quaternary ammonium compounds with a positively charged nitrogen that has an affinity for the nicotinic receptors
What is a phase I block?
When a depolarizing muscle blocker is bound to Ach receptors the perijunctional voltage gated Na channels close after a certain amount of time so you get the initial excitation (propagation of signal via the sodium channels and then release of calcium from the sarcoplasmic reticulum) and then the sodium channel closes again. The endplate cannot repolarize while the muscle blocker is bound to the Ach receptors
How do nondepolarizing muscle relaxants work?
Competitive antagonism
They do not produce a conformational change for ion channel opening
What are the two subunits on the neuromuscular Ach receptors that bind acetylcholine?
Two identical alpha subunits
How many binding sites have to be occupied by acetylcholine to elicit a conformational change?
The 2 alpha subunits
What is the difference in the fetal form of Ach receptor?
It has a gamma unit instead of epsilon
Low channel conductance
What happens in conditions of chronically decreased acetylcholine release?
More expression of the extrajudicial all Ach receptor.
Why do states with more extrajunctional receptors have prolonged blockade with depolarizing muscle relaxants?
Because there are more receptors being depolarized
What is the sensitivity of neuromuscular blockade in myasthenia gravis.
A resistance to depolarizing relaxants (because there are fewer receptors)
Increased sensitivity to nondepolarizing relaxants (only takes one subunit to bind to cause muscle relaxation)
What are other ways of causing neuromuscular blockade?
Channel blockade
What drugs may cause channel blockade?
Neostigmine
Antibiotics
Cocaine
Quinidine
What is sugammadex
A cyclodextrin that binds tightly in a 1:1 ratio with steroidal nondepolarizing agents (roc, vec)
How much current should a peripheral nerve monitor be able to create for muscle contraction?
50 mA across 1000 ohm load
How long is the stimulus of a peripheral nerve monitor?
200 nanoseconds
What is the train of four stimulation?
Four successive 200 nanosecond stimuli in 2 seconds
What happens to the train of four as the block increases?
Train of four decreases
How much block do you after disappearance of the fourth twitch (3)?
75%
How much block do you have after disappearance of the third twitch? (Two twitches)
80%
How much block do you have with disappearance of the second twitch?
90%
How much block does clinical relaxation require?
75-95% so 1-3 twitches
What is tetany a test of?
Neuromuscular function
What is double burst more sensitive than?
More sensitive than train of four for fade
What does 5 second tetany indicate?
Adequate but not full reversal
What muscles recover faster than adductor pollicis?
Diaphragm
Rectus abdominis
Laryngeal adductors
Orbicularis ocular
What is tetany
A sustained stimulus 50-100 Hz usually lasting 5 seconds
What is fade indicative of?
A nondepolarizing block (phase 2 block)
What does the absence of fade indicate?
Adequate clinical recovery
What is fade due to?
Prejunctional effect of NMBs that reduces the amount of acetylcholine available for release (the higher the calcium influx, the more quanta of Ach released - nondepolarizing agents don’t allow for influx)
What is posttetanic potentiation?
The ability of theta if stimulation to increase the evoked response to a subsequent twitch during a partial nondepolarizing block
Why is post-tetanic potentiation possible?
Transient increase in Ach mobilization due to tetany
What is the lipid solubility of succinylcholine
Low
How does succinylcholine stop working?
It diffuses away from the membrane and gets broken done by pseudocholinesterase
What does hypothermia due to succinylcholine metabolism?
Decreases the rate of its hydrolysis so prolongs its action
In what conditions are there reduced levels of pseudocholinesterase?
Pregnancy
Liver disease
Renal failure
What is dibucaine
A local anesthetic that inhibits normal pseudocholinesterase by 80%
Why is dibucaine used to test for pseudocholinesterase deficiency?
Because abnormal pseudocholinesterase is only inhibited 20% by dibucaine as opposed to normal which is 80%
What is a normal dibucaine number?
80
How long will a heterozygote of pseudocholinesterase deficiency have a block from succinylcholine
20-30 minutes
How long will a homozygous of pseudocholinesterase deficiency have a block from succinylcholine
4-8 hours
How do acetylcholinesterase inhibitors prolong depolarizing blockade?
- Inhibit acetylcholinesterase so that more acetylcholine is in the junction causing more polarization
- Reduce hydrolysis of succinylcholine by inhibiting pseudocholinesterase
How do nondepolarizing agents antagonize a phase 1 block?
They occupy some acetylcholine receptors
Why do children require higher doses of succinylcholine?
Because they have a larger extra cellular space than adults and succinylcholine is not lipid soluble
Why isn’t succinylcholine used in children?
May cause a systole in children with undiagnosed myopathies or prolonged paralysis
Where does succinylcholine work?
At ALL acetylcholine receptors
What are the CV effects of succinylcholine in children?
Profound bradycardia
What are the CV effects of low dose succinylcholine in an adult?
Negative chronograph and inotropy due to stimulation of parasympathetic ganglia to SA node
What are the CV effects of high dose succinylcholine in an adult?
Increased heart rate and contractility
Increased catecholamines
Due to SNS stimulation in Heart
What may happen to heart rate in an adult after second dose of succinylcholine?
Bradycardia due to succinylmonocholine (hydrolyzed succinylcholine) sensitization of muscarinic cholinergic receptors in the heart
How long after a spinal cord or burn injury can you use succinylcholine before it becomes unsafe?
24 hours
Why is using succinylcholine unsafe in burn or spinal cord patients?
Because of hyperkalemia cardiac arrest refractory to treatment
When is the risk of hyperkalemia the highest after injury?
7-10 days
How do you prevent myalgia from succinylcholine?
Pretreatment with 0.06 mg/kg - 0.1 mg/kg of or uranium
How do you treat myalgias
NSAID
How does succinylcholine increase intraocular pressure?
Extra ocular muscles have more motor end-plates on each cell
What is a premonitory sign of malignant hyperthermia?
Increased tone of the masseter muscle preventing malignant hyperthermia
Can you give succinylcholine to someone with NMS
Yes
What does succinylcholine do to CBF?
Increases it
What does succinylcholine do to ICP?
Increases it
Is succinylcholine contraindicated in patients with hig ICP?
No
How can increased ICP with succinylcholine be avoided?
Pretreatment with rocuronium and lidocaine
Hyperventilating
Which nondepolarizing muscle relaxant is vagolytic?
Pancuronium
What kind of nondepolarizing agents cause histamine release ?
Benzylisoquinolones (atracurium, gantacurium)
What is the purpose of a priming dose?
To produce intubating conditions within 60-90 seconds
What is the dose of a priming dose?
10-15% of the usual intubating dose
How much do volatile agents decrease nondepolarizing dosage requirements?
By at least 15%
Do the newer nondepolarizing agents affect the autonomic systems?
No
Which nondepolarizing agents are metabolized significantly by the liver?
Pancuronium and vecuronium
Which 2 nondepolarizing agents are excreted via the biliary system?
Roc and vec
Which 2 nondepolarizing agents have prolonged effect in liver failure?
Pancuronium and rocuronium
Which nondepolarizing agents are excreted by the kidney?
Pancuronium
Vecuronium
Doxacurium
Pipecurium
How does hypothermia prolong blockade?
By decreasing metabolism and excretion
How does respiratory acidosis affect nondepolarizing blockade?
Prolongs it and antagonizes its reversal
How does hypermagnesemia affect nondepolarizing blockade?
Prolongs it because mg competes with calcium at the motor end plate
How does hypokalemia and hypocalcemia affect nondepolarizing blockade?
Increases the block
What is special about vec in the pediatric population?
Longer acting in neonate X
Which nondepolarizing agent is not prolonged in the elderly?
Cisatracurium
What do you have to do to the dosage of nondepolarizing agents in the obese population?
Increase by 20% of lean body weight
What kind of nondepolarizing agent is atracurium?
Benzylisoquinolone
How is atracurium metabolized?
Ester hydrolysis and spontaneous chemical breakdown (Hoffman elimination)
What is the intubating dose of atracurium?
0.5mg/kg
What are the side effects of atracurium?
Bronchospasm
Transient drop in SVR and increase in CO
Seizure (laudanosine toxicity)
Anaphylaxis (acrylate immune activation)
What is laudanosine toxicity?
It is a tertiary amine that is a breakdown product of atracurium which causes CNS excitation
What happens to atracurium if you run it with lidocaine or thiopental?
It will precipitate as a free acid because those are bases
What is acrylate?
Metabolite of atracurium that can cause anaphylaxis
What is cisatracurium?
A stereoisomers of atracurium that is 4 times more potent
How is cisatracurium metabolized?
Hoffman elimination only
What is the intubating dose of cisatracurium?
0.1-0.15 mg/kg within 2 minutes
What does pancuronium look like?
Steroid ring with two modified Ach molecules
It resembles Ach enough to bind the nicotinic receptor but not activate it
How is pancuronium metabolized?
By the liver
How is pancuronium excreted?
Renally
What is the induction dose of pancuronium?
.08-.12 mg/kg
What are the side effects of pancuronium?
Vagolytic - tachycardia
SNS stimulation - HTN
Arrhythmias due increased catecholamines and decreased uptake
What drugs should pancuronium not be used with and why?
Halothane and TCAs because of ventricular arrhythmias
What allergy should you avoid using pancuronium with?
Bromide
How long does pancuronium last?
60-120 minutes
How is vecuronium metabolized?
Liver a little
But then excreted in biliary and renal systems
What is vecuronium linked to in ICU?
Polyneuropathy from prolonged blockade
What is the intubating dose of vecuronium?
0.08-0.12 mg/kg
What is interesting about women and men with vecuronium?
Women are 30% more sensitive than men (greater and longer blockade) same with roc and pan
What changes about the dosage of vec in the anhepatic phase of liver transplantation?
They are reduced
How is rocuronium metabolized?
It’s not
How is roc eliminate?
Primarily by liver through the biliary system
What conditions prolong roc?
Liver disease
Pregnancy
What kind of nondepolarizing agents are pan, roc, and vec?
Steroids
What is the intubating dose of rocuronium?
0.6-1.2 mg/kg
What is gantacurium?
A nondepolarizing agent that has a ultra short duration of action and comes in a powder
How is gantacurium metabolized?
Ester hydrolysis
Cysteine adduction
What ion is responsible for neuron depolarization?
Sodium influx
What does sodium influx into a neuron lead to in the nerve terminal?
Calcium influx in the nerve terminal
What does influx of calcium do at the nerve terminal?
Facilitates the release of Ach molecules out of the presynaptic nerve into the NMJ
What do the Ach molecules in the NMJ do?
Bind nicotinic Ach receptors on the motor end plate which depolarizers the muscle
What is the titanic fade due to?
Blockade of pre-junctional receptors
Due to blocking of the positive feedback system (normally release more acetylcholine in response to stimulation, but cannot when blocked by NMB)
How should succinylcholine be dosed?
Using TBW
How should NMBs be dosed?
IBW or LBW
How much reversal should be given for a phase II block from succinylcholine?
0.03 mg/kg
Why must the minimum amount of neostigmine be used to reverse a patient with pseudocholinesterase deficiency?
Because neostigmine inhibits pseudocholinesterase as well and at higher doses will do this which will prolong blockade cause by succinylcholine and acetylcholinesterase inhibition
What does phenytoin do to NMBs?
Enhances the blockade if acute
Chronically reduces duration of blockade action
What does a phase II block mean?
Means the postjunctional membrane has become repolarized, but it is desensitized to acetylcholine
How would you reverse succinylcholine apnea in a patient with abnormal pseudocholinesterase?
Low dose neostigmine after phase II blocks occurs
- low dose because neostigmine preferentially inhibits acetylcholinesterase, but higher dose inhibits pseudocholinesterase which would impair metabolism of sux even further
What is the dosage of sugammadex for routine reversal?
2 mg/kg of actual body weight
How much sugammadex for no twitches?
4 mg/kg
What is the dosage of sugammadex for immediate reversal aft RSI dose of roc?
16 mg/kg
What is the advantage of double burst stimulation of train of four?
It allows better tactile and visual assessment of neuromuscular blockade
What are the clinical signs of a TOF ratio greater than 0.7?
Head lift greater than 5 seconds Leg lift Hand grip Tidal volume of 15-20ml/kg Effective cough Negative inspiratory pressure of -25 cmH2O
What side effect of succinylcholine cannot be blunted with a defasciculating dose of roc?
Increased IOP
How much does IOP increase with succinylcholine?
5-15 mm Hg
What does carbamazepine do to P450?
Induces it so it may cause decrease NMB by vec, roc
How do amino glycosides prolong the NMB?
Inhibit the release of acetylcholine from alpha motor neurons
How does clindamycin prolong NMB?
Prevents prejunctionsl release of Ach and decreases postjunctional nicotinic Ach receptors to Ach
How do tetracyclines prolong NMB?
Postjunctional inhibitor
How does cyclophosphamide affect NMB?
It is a pseudocholinesterase inhibitor so causes prolonged apnea after succinylcholine administration
How long do the anti-pseudocholinesterase activities of cyclophosphamide last?
3-4 weeks after administration
Which volatile augments NMB the most?
Desflurane
What drugs potentiate NMBs?
Aminoglycosides Tetracyclines Clindamycin Lincomycin Polymixin Volatile Lithium Anticonvulsant
Which volatile potentiates NMB the most?
Desflurane
How is gantacurium metabolized?
Ester hydrolysis
How is gantacurium inactivated?
By L-cysteine which replaces a chlorine atom
Which NMB has an active metabolite?
Vecuronium
Metabolite = 3-desacetyl and has 80% activity, can accumulate in renal disease
