General about NMBA & Succ Flashcards
Benefits of NMBA
Improve surgical conditions, allow for CV/Neuro/transplants, facilitate ETT.
Risks of NMBA
No analgesis or anesthetic properties
Describe the nicotinic acetylcholine receptor
5 subunit complex with 2 alpha, 1 beta, 1 delta & 1 gamma subunit
What happens when ACh binds and where does it bind on the nACHR
It binds to the alpha subunits, creates a conformational change & the channel opwns
ED50 of NMBA
50% depression of twitch tension in the nACHR
What does succinylcholine do the nACHR
binds to the nACHR, causes the conformational change, but does not allow any further action potential to be generated by desensitizing the nACHR, inactivating the VGNaC & NMJ, & increases K permeability in the surrounding membrane
Prejunctional nicotinic receptors & ACh
Have a positive feedback role in making ACh available to the nACHR when needed, involved in mobilization (not release of) ACh
Prejunctional muscarinic receptors & ACh
Involved in facilitation and inhibition of the release of ACh through modulation of Ca influx
How do nondepolarizers affect prejunctional nicotinic & muscarinic receptors
Blockade of nicotinic will affect availability of ACh when needed fast (TOF) - may explain fade, do not appear to block muscarinic
Where do NMBAs block fastest, deepest, and wear off fastest from?
Blocks centrally located (larynx, diaphragm) fastest, blocks peripheral deeper, wears off quickest from central. (If twitch shows paralyzed at adductor pollicis, likely not going to respond to intubation.
What are all NMBAs related to?
Acetylcholine - they are all quaternary ammonium compounds
How do NMBAs attach to the nACHR and what does that mean for the rest of the body?
They have positive charges that mimic the quaternary nitrogen atom of ACh.. this means they can also affect other nACHR sites (autonomic ganglia, SNS, PNS, prejunctional nicotinic/muscarinic receptors)
Depolarizing relaxant(s)
Succinylcholine
How does succ work?
2 ACh molecules connected by ester bond, mimics action of ACh by binding to the alpha subunits (at both nicotinic & muscarinic receptors) & holds the channel open which does not allow any further depolarizations
ED95 of Succ
0.3 mg/kg-0.63 mg/kg
Typical dose of succ
1 mg/kg (“Newer: 0.5-0.6 mg/kg)
How quickly does succ act & recover?
45- 60 seconds, get recovery in 8-15 minutes with 1 mg/kg dose
How is succ metabolized?
Butrylcholinesterase - to succinylmonocholine (also a weaker NMBA, metabolized slowly to succinic acid & choline)& choline… only about 10% of the succ dose reaches the NMJ.
How is the action of succ terminated?
Diffusion away from the NMJ back into circuation
What effects the level of metabolism of succ?
Liver disease, age, malnutrition, pregnancy, burns, oral contraceptives, MAOIs, ecothiphate, cytotoxic drugs, neoplasms, anticholinesterases, tetrahydroaminacrine, hexafluorenium, metoclopramide –> less Butrylcholinesterase activity (longest lasting from these things has been 23 minutes)
Dibucaine test
Drug inhibits action of normal Butrylcholinesterase by about 80%, it does not measure the concentration of the enzyme or the efficiency of the enzyme – Determines QUALITY not quantity (the greater the percentage indicates normal pseudocholinesterase)
What the dibucaine numbers mean
How much dibucaine inhibits Butrylcholinesterase activity… 70-80 - succ lasts the normal amount of time, 50-60 (heterozygous atypical BCE)- succ lasts about 50-100% longer = 15-30 minutes, 20-30 (homozygous atypical BCE) - succ can last 4-24 hours)
What does it mean if the dibucaine number is low?
The BCE is atypical and will not metabolize succ well
Succ CV Side Effects & explanations
- -Effects nicotinic receptors on sympathetic & parasympathetic ganglia & muscarinic receptors in sinus node
- Bradycardia (stimulation of cardiac muscarinic receptors in sinus node) particularly bad in patients with a lot of vagal tone (peds) or 2nd dose about 5 minutes after 1st, can give atropine
- Negative inotropic
- High dose = tachycardia
- Dysrhythmias- junctional (nodal) due to stimulation of muscarinic receptors in sinus node, AV pacemaker takes over momentarily
- Circulating catecholamines increase 4fold & potassium increase may lead to ventricular dysrhythmias (along with other compounding effects - hypoxia, hypercapnia, ETT, surgery)
Succ & hyperkalemia
Causes a 0.5 mEq/L increase from the potassium movement out of the cells- **even more is release in patients with hypovolemia, metabolic acidosis, intra-abdominal infections >1 week, increase in extrajunctional receptors (hemiplegia, paraplegia, muscular dystrophies, Guillain-Barre, burns)
Treatment for severe rapid onset hyperkalemia
Hyperventilate, 1-2 mg CaCl, 50 mL D50W IV + 10 units Insulin (or kids 1 mL/kg D50W + 0.15 U/kg insulin), BiCarb 1 mEq/kg
Succ & IOP
Open anterior chamber eye injury- succ is contraindicated. Increases IOP within 1 min, peaks 2-4 min, subsides in 6 min. If patient becomes light and starts moving during eye surgery - do NOT give succ (may result in extrusion of eye contents = blindness)
Succ & Intra-gastric Pressure
Increases potentially above 28 cm H2O (will vomit)- may increase aspiration risk especially in pregnancy, ascites, bowel obstruction, hiatal hernia. Does not happen in children & infants
Succ & ICP
Increases, no clinical significance
What side effects can predosing nondepolarizing NMBAs before succ help?
IOP, ICP,
Succ & myalgia
More frequent in minor surgery, women & ambulatory patients, unsure of what it is related to
Succ & masseter spasm
Due to exaggerated contraction of the NMJ in the jaw (not related to MH)
Succ & MH
Potentially the worst agent to trigger MH
Dantrolene administration
Initial dose 2 mg/kg, repeat 2 mg/kg up to 10 mg/kg if required to stop MH
How do you know when dantrolene has worked?
Clinical response - decrease in temp, end-tidal CO2
When can MH occur?
Anytime! No prior family history needed, multiple unremarkable anesthetics (even succ), during maintenance or postop)
Succ & phase II block
Acts like non-depolarizing blockade a NMJ, TOF will show a fade pattern, if TOF is < 0.4 and it has been 20-30 minutes since admin, reversal may be attempted but extubation not attempted until TOF is 0.9
Succ & neostigmine
If neostigmine has been given to reverse nondepolarizing agent, and you give succ, it will last 30-60 minutes from baseline
What conditions are resistant to succ?
Myasthenia gravis (fewer receptors to work with)
