Depolarizing NMB

Question 1

What is the typical dose of succinylcholine for RSI?

Answer 1

1mg/kg

Question 2

What is the duration of apnea with succinylcholine?

Answer 2

3-4 minutes

Question 3

How long dose it take for 90% of muscle strength to return following use of succinylcholine?

Answer 3

9-13 minutes

Question 4

What is the structure and mechanism of action of succinylcholine?

Answer 4

Structure: resembles 2 acetylcholine molecules

MOA: binds to and depolarizes postsynaptic and extrajunctional NICOTINIC acetylcholine receptors

Question 5

How is succinylcholine broken down?

Answer 5

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.

Question 6

What is the mechanism for succinylcholine altering serum [K]?

Answer 6

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]

Question 7

What are the characteristics of a phase 1 block?

Answer 7

1. Decreased twitch amplitude
2. Sustained (but diminished) response to (tetanic) stimulation
3. Similar decreases of ALL twitches in the train-of-four (ratio >0.7)
4. NO post-tetanic potentiation
5. Augmentation by anticholinesterase drugs

Question 8

What are the characteristics of a phase 2 block?

Answer 8

1. tetanic fade
2. post-tetanic facilitation
3. TOF ratio 5mg/kg IV or given over period of 30+ minutes

Question 9

How much of the original dose of succinylcholine actually reaches the NMJ?

Answer 9

~10% as it is broken down so quickly

Question 10

How is NMB by succinylcholine terminated?

Answer 10

diffusion away from the NMJ into extracellular fluid (no plasma cholinesterase is present at NMJ)

Question 11

What drugs and co-morbidities decrease cholinesterase activity –> prolong NMB with succinylcholine?

Answer 11

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

Question 12

What does the dibucaine number indicate?

Answer 12

QUALITY of plasma cholinesterase (ability to metabolize succinylcholine) = not the quantity of enzyme circulating in plasma

Question 13

What is the mutation for atypical butyrylcholinesterase?

How common is the deficiency?

Answer 13

single point mutation at nucleotide 209 (GAT to GGT)

1:3200 - 1:5000
more common in Persian Jews or Native Alaskan

Question 14

What is dibucaine?

Answer 14

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.

Question 15

What are the side effects/abnormal responses to succinylcholine?

Answer 15

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.

Question 16

What type of patients are more susceptible to hyperkalemia with succinylcholine?

Answer 16

burns
crush injuries
severe metabolic hypovolemic acidosis
upper motor neuron lesions
prolonged immobility
myopathies

Question 17

What are the cardiovascular effects of succinylcholine? What receptors are responsible for these effects?

Answer 17

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

Question 18

What might happen if you give a second dose of succinylcholine, especially in infants?

Answer 18

bradycardia and potentially sinus arrest

Question 19

What is the effect of cholinesterase inhibitors on depolarizing blockade?

Answer 19

Prolong blockade

1. inhibition of acetylcholinesterase –> acetylcholine accumulates at receptor
2. inhibition of butyrylcholinesterase –> prevents hydrolysis of such

Question 20

what other factors can prolong blockade by succinylcholine?

Answer 20

Hypothermia
abnormal levels of enzymes
atypical enzymes

Question 21

What are the contraindications for using succinylcholine?

Answer 21

1. personal/family history of malignant hyperthermia
2. personal/ family history of prolonged apnea after surgery
3. burn patients (24-48 hrs after –> 2 years after the skin healed)
4. upper motor neuron lesions (stroke, brain tumors, spinal cord tumors)
5. prolonged immobility
6. severe hypovolemic metabolic acidosis
7. myopathies
8. history of anaphylactic reactions to succinylcholine

Question 22

How long does NMB typically last with a dibucaine number of 50?

Answer 22

20-30minutes

Heterozygous atypical

Question 23

How long does NMB typically last with a dibucaine number of 20?

Answer 23

1-3 hours

Question 24

How does Sux affect autonomic ganglia and cardiac receptors?

Answer 24

Stimulates autonomic and cardiac muscarinic receptors

• Kids with higher symp tone –> Brady
• Adults with higher para tone –> tachy
• Brady with second dose of sux

Question 25

What are the side effects of Dantrolene and which is most common?

Answer 25

Most common = weakness N/V, blurred vision 300mg Mannitol/20mg Dantrolene --> DIURESIS Stop when core reaches 38deg to prevent hypothermia