Depolarizing NMB Flashcards
What is the typical dose of succinylcholine for RSI?
1mg/kg
What is the duration of apnea with succinylcholine?
3-4 minutes
How long dose it take for 90% of muscle strength to return following use of succinylcholine?
9-13 minutes
What is the structure and mechanism of action of succinylcholine?
Structure: resembles 2 acetylcholine molecules
MOA: binds to and depolarizes postsynaptic and extrajunctional NICOTINIC acetylcholine receptors
How is succinylcholine broken down?
butyrylcholinesterase produced by liver (formerly called pseudocholinesterase) in plasma –> remains at the endplate much longer than acetylcholine –> ceases to respond to stimulus (desensitization)
succinylcholine –> succinylmonocholine + choline –> succinic acid + choline.
What is the mechanism for succinylcholine altering serum [K]?
sustained opening of end-plate receptor ion channels is assoc w/ leakage of K from the interior –> average 0.5-1 mEq/L increase of serum [K]
What are the characteristics of a phase 1 block?
- Decreased twitch amplitude
- Sustained (but diminished) response to (tetanic) stimulation
- Similar decreases of ALL twitches in the train-of-four (ratio >0.7)
- NO post-tetanic potentiation
- Augmentation by anticholinesterase drugs
What are the characteristics of a phase 2 block?
- tetanic fade
- post-tetanic facilitation
- TOF ratio 5mg/kg IV or given over period of 30+ minutes
How much of the original dose of succinylcholine actually reaches the NMJ?
~10% as it is broken down so quickly
How is NMB by succinylcholine terminated?
diffusion away from the NMJ into extracellular fluid (no plasma cholinesterase is present at NMJ)
What drugs and co-morbidities decrease cholinesterase activity –> prolong NMB with succinylcholine?
Anti-cholinesterase drugs
- echothiophate
- nitrogen mustard
- cyclophosphamide
- neostigmine
- organophosphate (malathion)
Old age liver disease/biliary cirrhosis (less plasma cholinesterase produced) pregnancy uremia/renal failure malnutrition burns and oral contraceptive or esmolol use
What does the dibucaine number indicate?
QUALITY of plasma cholinesterase (ability to metabolize succinylcholine) = not the quantity of enzyme circulating in plasma
What is the mutation for atypical butyrylcholinesterase?
How common is the deficiency?
single point mutation at nucleotide 209 (GAT to GGT)
1:3200 - 1:5000
more common in Persian Jews or Native Alaskan
What is dibucaine?
amide local anesthetic that inhibits normal plasma butyrylcholinesterase activity by 80% (dibucaine # of 70-80)
Inhibits the atypical enzyme by about 20% in homozygotes and by 50% in heterozygotes.
What are the side effects/abnormal responses to succinylcholine?
malignant hyperthermia
hyperkalemia
prolonged neuromuscular blockade
bradycardia
masseter muscle spasm (1% - can signal MH - up to 50% are susceptible)
increased intraocular pressures (7-10mmHg)
anaphylaxis.
What type of patients are more susceptible to hyperkalemia with succinylcholine?
burns crush injuries severe metabolic hypovolemic acidosis upper motor neuron lesions prolonged immobility myopathies
What are the cardiovascular effects of succinylcholine? What receptors are responsible for these effects?
sinus bradycardia
junctional rhythms
ventricular tachycardia
Due to STIMULATION of autonomic cholinergic receptors
- muscarinic receptors in the sinus node
- nicotinic receptors in sympathetic and parasympathetic ganglia
What might happen if you give a second dose of succinylcholine, especially in infants?
bradycardia and potentially sinus arrest
What is the effect of cholinesterase inhibitors on depolarizing blockade?
Prolong blockade
- inhibition of acetylcholinesterase –> acetylcholine accumulates at receptor
- inhibition of butyrylcholinesterase –> prevents hydrolysis of such
what other factors can prolong blockade by succinylcholine?
Hypothermia
abnormal levels of enzymes
atypical enzymes
What are the contraindications for using succinylcholine?
- personal/family history of malignant hyperthermia
- personal/ family history of prolonged apnea after surgery
- burn patients (24-48 hrs after –> 2 years after the skin healed)
- upper motor neuron lesions (stroke, brain tumors, spinal cord tumors)
- prolonged immobility
- severe hypovolemic metabolic acidosis
- myopathies
- history of anaphylactic reactions to succinylcholine
How long does NMB typically last with a dibucaine number of 50?
20-30minutes
Heterozygous atypical
How long does NMB typically last with a dibucaine number of 20?
1-3 hours
How does Sux affect autonomic ganglia and cardiac receptors?
Stimulates autonomic and cardiac muscarinic receptors
- Kids with higher symp tone –> Brady
- Adults with higher para tone –> tachy
- Brady with second dose of sux
What are the side effects of Dantrolene and which is most common?
Most common = weakness
N/V, blurred vision
300mg Mannitol/20mg Dantrolene –> DIURESIS
Stop when core reaches 38deg to prevent hypothermia
