Neuromuscular Blocking Agents

1. Motor neuron action potential → Ca²⁺ influx at nerve terminal
2. Vesicles fuse and release acetylcholine (ACh)
3. ACh diffuses across synapse → binds α-subunits of nicotinic receptors
4. Both α-subunits must bind ACh → channel opens → Na⁺/Ca²⁺ in, K⁺ out → end-plate depolarization → muscle contraction

NMBAs interrupt this at the receptor (depolarizing or competitive antagonist).

• Structure: two ACh molecules joined by a methyl group
• Mechanism: nAChR agonist → prolonged depolarization → flaccid paralysis
• Intubating dose: 1–1.5 mg/kg IV (1.5–2 mg/kg if defasciculating dose given); IM 3–4 mg/kg
• Onset: 30–60 s; Duration: ~10 min
• Metabolism: plasma pseudocholinesterase (butyrylcholinesterase)

Pseudocholinesterase deficiency - Heterozygous (~1/480): block extended 50–100% - Homozygous (~1/3200): block 4–8 h - Dibucaine number: % of normal pseudocholinesterase inhibited by dibucaine. Normal 80, hetero 50, homo 20.

Hyperkalemia risk (upregulated junctional/extrajunctional AChR): - Burn injury > 24–48 hours old - Muscular dystrophy (Duchenne), myotonias - Prolonged immobility (ICU, paraplegia) - Upper motor neuron disease (stroke, MS, GBS, spinal cord injury, tumor)

Other: - Personal or family history of malignant hyperthermia - Open globe / anterior chamber injury (transient ↑ IOP)

Normal induction dose ↑ K⁺ by ~0.5 mEq/L in healthy patients. Up to 5–10 mEq/L spikes can occur in susceptible patients → cardiac arrest.

Normokalemic ESRD is NOT a contraindication.

• Fasciculations (mitigate with defasciculating dose of rocuronium 0.03 mg/kg, 3 min before sux)
• Myalgia (worse in young women, athletes, ambulatory patients)
• Bradycardia — especially in children and with repeat dosing. Pretreat peds with atropine 0.02 mg/kg.
• Tachycardia in adults
• Anaphylaxis (~1:5,000–10,000)
• Trismus (premonitory sign for MH)
• ↑ intragastric, ↑ IOP, ↑ ICP

Mechanism: competitive inhibition of nAChR. Also blocks presynaptic nAChR → "fade" on TOF.

Two structural classes: 1. Benzylisoquinolinium ("-urium"): cisatracurium, atracurium, mivacurium, d-tubocurarine. More likely to release histamine. 2. Aminosteroid ("-onium"): rocuronium, vecuronium, pancuronium. Vagolytic (pancuronium > roc > vec).

Intubating dose ≈ 2× ED95. Larger dose speeds onset but lengthens duration.

Train-of-four (TOF): four supramaximal stimuli q 0.5 s. - TOF count 4 → ~75% receptors blocked - TOF count 3 → ~80% - TOF count 2 → ~85% - TOF count 1 → ~90% - TOF count 0 → ~100% - TOF ratio (4th/1st twitch) ≥ 0.9 → adequate recovery

Post-tetanic count (PTC): for deep block (TOF 0). 50 Hz tetanus → 1-Hz twitches. - PTC 1–2 → very deep; PTC > 8–10 → returning toward TOF 1

Sites: adductor pollicis (gold standard); facial nerve / orbicularis oculi resists block (overestimates recovery).

Variability of muscle blockade (most resistant → most sensitive): vocal cords > diaphragm > corrugator supercilii > orbicularis oculi > geniohyoid > adductor pollicis > pharyngeal muscles

• AChE inhibitor → ↑ ACh at NMJ → outcompetes non-depolarizers.
• Dose: 0.04–0.07 mg/kg IV (max ~5 mg).
• Co-administer glycopyrrolate 0.2 mg per 1 mg neostigmine (or atropine 0.4 mg per 1 mg) to prevent bradycardia.
• Ceiling effect — cannot reverse deep block (TOF count 0).
• Requires TOF ≥ 2 at minimum.
• Side effects: bradycardia, bronchospasm, ↑ secretions, PONV.

• γ-cyclodextrin that encapsulates rocuronium and vecuronium 1:1.
• Does NOT reverse benzylisoquinolinium agents (cisatracurium, atracurium).
• Dose by depth of block:
• Routine (TOF ≥ 2): 2 mg/kg
• Deep (PTC 1–2): 4 mg/kg
• Immediate after RSI dose of roc: 16 mg/kg
• Onset 1–3 min.
• Pharmacologic activity ~24 h — wait 24 h before re-administering rocuronium after 16 mg/kg dose, 5 min after 2–4 mg/kg.
• Side effects: bradycardia/arrest (rare), anaphylaxis (~0.3%), ↓ efficacy of hormonal contraception (counsel × 7 days).
• Renal excretion — caution if CrCl < 30.