Case 20 - Depolarizing Neuromuscular Blockade

Question 1

DDx for healthy patients whose vital signs are stable but not waking up after GENA

Answer 1

Assuming stable and appropriate BP, HR, SaO2, core temp, and EtCO2

• 1) anesthetic drugs, 2) metabolic disturbances, 3) neurological problems, 4) toxins
  1) anesthetic drugs
• opioids, BZD, inhaled anesthetics, neuromusclar blocking agents, ketamine.
• Patient opioid naive and received to much narcotic?
• Was long acting NMBD accidentally given at the end?
• Synergistic effects of multiple agents resulting in apnea and unconsciousness?

2) Metabolic

• hyponatremia (ex: TURP)
• hypoglycemia (ex: insulin in fasting patient)
• hypocalcemia (ex: multiple blood product transfusion)

3) Neurologic

• prolonged hypotension and hypoperfusion can lead to global cerebral ischemia
  
  • cuff position (ex: cuff on calf in sitting position)
• Post-op craniotomy c/b cerebral bleed? -> CT?

4) pre-existing toxin use?

Question 2

Normal neuromuscular transmission

Answer 2

• action potential of a motor neuron depolarizes to its terminal, at which point influx of calcium ions causes vesiciles containing AcH to release into neuromuscular junction.
• AcH crosses synaptic cleft to bind to nicotonic cholinergic receptors, which produces conformational change and allows sodium and calicum ions to flow into the muscle cell, gneerating an end plate potential.
• Enough binding of AcH to its receptors will cause the motor end plate to depolarzie, thus producing an action potential which is proprageted along the muscle fiber –> contraction of muscle (myosin and tropomyosin)

Question 3

MOA of Succinylcholine

Answer 3

• Structure similar to two AcH molecules bound together
• agonist at nicotinic cholinergic receptor at motor endplate –> produces muscle action potential and muscle fasciculations
• not inhihibited by acetylcholinesterases, therefore as long as sux remains in synaptic cleft, it will continue to depolarize motor end plate and cause muscle blockade
• actions terminated by diffusion about of NMJ into systemic circulation, and metabolized by psuedocholinesterases.

Question 4

Sux terminated?

Answer 4

• rapidly metabolized by pseudocholinesteras
• sux enters NMJ, and then diffuses away from NMJ (termination of action) into plasma, where it becomes metabolized
• DOA is 5-10 minutes

Question 5

Low Plasma Psuedocholinesterase

Answer 5

• Pregnancy, renal failure, hepatic failure, even some chemotherapeutic medicaitons
• Heterozygous psuedocholinesterase deficiency
  
  • 20 to 30 minutes prolong duration
• homozygous pseudocholin deficiency
  
  • as much as up to 8 hours –> patients must remain sedated, intubated, supported with mech ventilation until drug has been metabolized by other pathways.

Question 6

Benefits of Sux

Answer 6

• Rapid Onset of Action (30-45s)
• Provides reliable and predictable skeletal muscle relaxation
• optimum relaxation for laryngoscopy (extremely important for adeuate laryngoscopy views)
• Quick ON and OFF (important for difficult intubation and ventilation - offers greatest likelihood patient will recover sponatenous ventilation before hypoxemia ensues)

Question 7

Hazards with Sux

Answer 7

1) Severe Hyperkalemia

• normal patients K+ increase by 0.5 mEq/L after intubating dose
• Spinal cord injuries, sepsis, burns, prolonged immoblization lead to upregulation of extrajunctional nicotinic cholinergic receptors

2) Hyperkalemic Cardiac Arrest
* young kids with undiagnosed myopathy
3) MH Trigger
4) Masseter muscle spasm
5) Myalgias
6) increased intraocular and intracranial pressures
7) phase II neuromuscular blockade
* (Prolong administration or high doses can lead to actions similar to NDMB)

Question 8

Contraindications to Sux

Answer 8

• allergy to sux
• known/suspected MH
• Anything that upregulates extrajunctional nicotinic receptors (burn, stroke > 72 hrs old, prolonged immobolizaiton, crush injury, burn > 24-48 hrs old, sepsis, spinal cord transection)
• Muscular dystrophy
• MS, ALS
• Rhabdomyolysis
• pre-existing hyperkalemia

Question 9

Best and Safest Drugs for RSI&I

Answer 9

• Rapid sequence induction and intubation = expeditious tracheal intubation in order to prevent and protect from gastric aspiration
• Two main drugs - Sux and Roc

Question 10

Pros and Cons of Sux and Roc for RSI&I

Answer 10

Sux

Pro

• rapid on and off
• adequate intubating conditions
• short DOA
  
  • allows possiblity of early return to spont ventilation in difficult to intubate and ventilate situations

Con

• hazard effects (hyperkalemia, MH, myalgia, increase IOP and ICP,
• ? increased risk of Intragastric pressure)

Roc

Pro

• well tolerated, not as much hazard effects as Sux

Con

• intbuating dose is 1.2 mg/kg (4 x ED95 dose)
  
  • high dose prevents antagonism of blockade for at least 30-60 min, should the patient be difficult to ventilate or intubate, there is no chance of recovery of spont vent

​IF sux is contraindicated, and patient appears to be difficult to ventilate (including via supraglottic airway), this may be an indication for awake FOB or awake trach