Case Studies of Neuromuscular Blocking Agents

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Case Studies of Neuromuscular Blocking Agents

• Jay Horrow, MD, MS
• Professor and Chair, Anesthesiology
• Professor of Physiology Pharmacology
• Professor of Epidemiology Biostatistics

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Mini-Review

• ACh receptor 5 subunits
• 2-?, ?, ?, ?.
• Immature ? replaces ?.
• Extrajunctional ? replaces ?.
• 2 ACh molecules needed one for each ? receptor.

From Morgan GE Clinical Anesthesiology, p. 207
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Mini-Review - continued

• Depolarizing Block
• Upper gate open Lower gate closes
• Agonist
• Nondepolarizing Blk
• Upper gate closed
• Receptors with ? resistant to non-depolarizing
  block
• Need bind to only 1 ? subunit
• Competitive antagonists

From Morgan GE Clinical Anesthesiology, p. 208
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Nicotinic Receptors

• C6 hexamethonium autonomic ganglia
• C10 decamethonium NM junction
• Decamethonium
• Long-acting depolarizer
• No longer in clinical use
• 100 renal excretion

From Morgan GE Clinical Anesthesiology, p. 206
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Monitoring Neuromuscular Block

• Twitch monitor
• Nondepolarizers
• TRAIN of 4
• 2 Hz, 200ms wide
• Adductor pollicis
• v.
• Orbicularis oculi

From Morgan GE Clinical Anesthesiology, p. 208
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Succinylcholine

• Autonomic Perturbations HR, BP
• Fasciculations / Muscle Pain
• ? intragastric pressure
• ? intracranial pressure
• Hyperkalemia ?K in blood
• Typically 0.5 mEq/L increase after 1 mg/kg IV
• Denervation (7-10d) massive K increase
• ? intraocular pressure
• Masseter Rigidity / Malignant Hyperthermia

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Why use Succinylcholine?

• Its quick! (onset AND offset)
• full stomach
• GERD
• Aspiration pneumonia DEATH
• Nothing else is quite as quick
• Intubation is easier in horses than humans

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Clinical Challenge 1

• 4 yr old, penetrating injury to L eye (pencil)
• Happened at a birthday party
• Lots of cake and ice cream
• Emergency surgery remove pencil,irrigate eye,
  repair lacerated globe.
• Question Should we use succinylcholine to secure
  his airway?

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Competing Risks

• Full stomach
• What is risk of regurgitation?
• What is risk of aspiration if he regurgitates?
• Can we mitigate risk? Maybe Cricoid
  pressure(N.B. No EBM to support/refute benefit)
• How bad is 2nd best option to SCh?
• Rocuronium 1.2 mg/kg 60-90s v. 30-60s
• Lasts longer (60 min) so what?

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Nondepolarizing Relaxants

• By duration of action

Withdrawn unacceptable incidence of
bronchospasm
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Nondepolarizing Relaxants

• By route of elimination

N.B. correlation of renal elimination with long
duration of action
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Nondepolarizing Relaxants

• By side effect

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Clinical Challenge 2

• 23 yo trauma victim, severe burns, hip pin
• Changes in NMJ receptors
• ? growth factor signaling ? ? subunits
• Extrajunctional immature receptors multiply
• Begins about 24 h after injury and lasts
• Succinylcholine ? massive increase K
• Nondepolarizers ? resistance
• Clinical solution?

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Clinical Challenge 3

• 40 yr old man with chronic renal failure
• Dialysis dependent, acute appendicitis
• CRF ? increased Vd ? larger dose
• loading dose mg Vd mL ? Cpss mg/mL

From Millers Anesthesia, 6th ed, p506
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Clinical Challenge 3

• 40 yr old man with chronic renal failure
• Dialysis dependent, acute appendicitis
• CRF ? increased Vd ? larger dose
• loading dose mg Vd mL ? Cpss mg/mL

From Millers Anesthesia, 6th ed, p506
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Clinical Challenge 4

• 27 yr old pregnant woman at term
• Pre-eclampsia ?BP, proteinuria
• Fetal distress ? STAT Caesarean section
• BTW receiving IV MgSO4.
• PRIORITY Get the baby out!

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Challenge 4 Solutions

• Regional anesthesia
• Increased risk with intravascular volume shift
• Must be skilled time is of the essence
• General anesthesia
• Intubation all relaxants are prolonged
• Mg2 competes with Ca2 pre-synaptically
• Decreased release of ACh from terminal
• So what?

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Clinical Challenge 5

• 58 yr old man, acute coronary syndrome
• Not amenable to stenting ? CABG
• Tachycardia is most serious threat to life
• But need to maintain cardiac output (HR?SV)
• Anesthetic (fentanyl) ? bradycardia
• Solution balance the side-effects.

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Mini-review (continued) Anticholinesterases

• Reverse neuromuscular blockade
• Law of mass action overwhelm with ACh
• But ACh receptors are everywhere
• Solution give muscarinic blocker also.
• Bradycardia bronchospasm hypermotility
  salivation
• Which first?

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Mini-review (continued) Anticholinesterases

• Reverse neuromuscular blockade
• Edrophonium
• Neostigmine
• Pyridostigmine
• Physostigmine

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The Future of Reversal Agents?

• Cysteine adducts chlorofumarates
• Condensation product with cysteine
• t1/2 ? 1-2 min
• 5-10 mg/kg reverses 100 block in 1-2 min
• Cyclodextrins cocoons for steroid relaxants
• Sugammadex as chelator for rocuronium
• Reversal within 2-3 min

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Clinical Challenge 6

• 20 yr old man had sports hernia repair
• Obstructed airway ? pulmonary edema
• Requires urgent reintubation
• Received neostigmine 3 mg iv, 15 min ago
• Use succinylcholine?

• Choices
• No relaxant will we succeed?
• Non-depolarizer need larger dose?
• Succinylcholine accept slow offset?