Non-depolarizing neuromuscular blockers (exert their effect through competitive antagonism ofnicotinic acetylcholine receptors): All blockers ending in _-ium.
Depolarizing neuromuscular blockers (exert their effect through activation and persistent depolarization of post-synaptic acetylcholine receptors): Succinylcholine
Choice of which neuromuscular blocker to use depends on several factors:
Whether rapid sequence intubation is required (will usually use succinylcholine for fast onset/offset or double dose rocuronium for fast onset).
Whether there are contraindications to succinylcholine (e.g hyperkalemia, prolonged immobility, burns).
Whether nerve monitoring will be required during the surgery. In cases requiring recurrent nerve monitoring neuromuscular blockers are not given.
For emergency paralysis (e.g. laryngospasm), succinylcholine is typically use because of its immediate onset (~30 sec).
In renal of hepatic cases, cisatracurium may be useful as it is degraded by plasma esterases and Hoffman elimination.
Certain diseases are resistant to non-depolarizing NMBA (e.g. Guillain-Barre, Burns, Spinal Cord Injury, CVA, prolonged immobility).
Specific Drug Selection Guidelines (UNC):
Pancuronium
Cisatracurium
70 years old
Vecuronium
Mivacurium
Rocuronium
d-tubocurarine
The following drugs have not been deemed to have clinical value our operating room:
Rapidly metabolized by pseudocholinesterases (Duration ~ 10 min) (as opposed to hepatic metabolism, which takes longer).
Phase 1 is the depolarizing phase where muscle fibers are depolarized and fasiculations occur.
Phase 2 is the desensitizing phase in which the muscle is no longer responsive to acetylcholine released by motor neurons. At this point, full neuromuscular block has been achieved.
Side Effects:
Prevention of side effects:
Myalgias and increased ICP might be prevented with a defasciulating dose of rocuronium (0.03 mg/kg 3 minutes prior to sux). This will NOT prevent hyperkalemia or increased intraocular pressure.
Succinylcholine: Risk of hyperkalemic arrhythmias/arrest, bradycardia (due to stimulation of muscarinic receptors in sino-atrial node). Eliminated by pseudocholinesterase.
For the other neuromuscular blockers, cardiovascular effects (if present) are normally due to histamine release. Specific effects and elimination patterns are below;
Drug | Potency* | ED95
(mg/kg) |
Duration
ED95 (min) |
Cardiovascular Effects | Elimination |
Pancuronium | 1 | 0.07 | ~60 | ↑HR, ↓BP | 60% kidney 40% liver |
Gallamine | 0.025 | 2.8 | ~60 | ↑HR, ↓BP | 100% kidney |
Curare | 0.14 | 0.5 | ~60 | Histamine release ¯↓BP,
ganglionic blockade |
40% kidney 60% liver |
Metocurine | 0.25 | 0.28 | ~60 | 1/3 histamine of curare ¯↓BP,
ganglionic block |
60-90% kidney |
Vecuronium | 0.9 | 0.056 | ~25 | None | 50% liver 20% kidney |
Atracurium | 0.25 | 0.26 | ~25-30 | 1/3 histamine of curare ¯↓BP | Nonspecific plasma esterases,
Hoffmann elimination |
Mivacurium | 0.875 | 0.08 | ~19 | similar to atracurium | Hydrolysis: plasma cholinesterase |
Doxacurium | 2.3 | 0.03 | ~60 | minimal ¯↓BP | ~50% kidney |
Pipecuronium | 1.4 | 0.05 | ~60 | None | 75% kidney |
Rocuronium | 0.23 | 0.3 | ~25-30 | None, ? ↑HR | ~ 50% liver ~ 20% kidney |
Cisatracurium | 1.4 | 0.05 | ~25-30 | None | Hoffmann elimination |
Drug | Potency* | ED95
(mg/kg) |
Duration
ED95 (min) |
Cardiovascular Effects | Elimination |
Pancuronium | 1 | 0.07 | ~60 | ↑HR, ↓BP | 60% kidney 40% liver |
Gallamine | 0.025 | 2.8 | ~60 | ↑HR, ↓BP | 100% kidney |
Curare | 0.14 | 0.5 | ~60 | Histamine release ¯↓BP,
ganglionic blockade |
40% kidney 60% liver |
Metocurine | 0.25 | 0.28 | ~60 | 1/3 histamine of curare ¯↓BP,
ganglionic block |
60-90% kidney |
Vecuronium | 0.9 | 0.056 | ~25 | None | 50% liver 20% kidney |
Atracurium | 0.25 | 0.26 | ~25-30 | 1/3 histamine of curare ¯↓BP | Nonspecific plasma esterases,
Hoffmann elimination |
Mivacurium | 0.875 | 0.08 | ~19 | similar to atracurium | Hydrolysis: plasma cholinesterase |
Doxacurium | 2.3 | 0.03 | ~60 | minimal ¯↓BP | ~50% kidney |
Pipecuronium | 1.4 | 0.05 | ~60 | None | 75% kidney |
Rocuronium | 0.23 | 0.3 | ~25-30 | None, ? ↑HR | ~ 50% liver ~ 20% kidney |
Cisatracurium | 1.4 | 0.05 | ~25-30 | None | Hoffmann elimination |
Surgical relaxation can be achieved when a patient has 2-3 twitches.
Different muscle groups respond differently to blockade.
(Most resistant to most sensitive): Vocal cords > diaphragm > currogator supercilii (muscle controlling the eyebrow) > abdominal muscles > adductor pollicis > pharyngeal muscles > extraocular muscles.
Anticholinesterase "reversal agents" indirectly increase the amount of Ach in the NMJ by inhibiting acetylcholinesterase.
Anticholinesterases cause vagal side effects (bradycardia, GI stimulation, bronchospasm) by increasing ACh activity at parasympathetic muscarinic receptors. Anticholinergics should always be co-administered.
Neostigmine (40-50 mcg/kg) with glycopyrolate (20% of neostigmine dose) most commonly used. Ceiling effect (Do not give >70 mcg/kg of neostigmine). Pyridostigmine and Edrophonium can also be used.
Pair anticholinesterase and anticholinergics based on speeds of onset.
Unlike the above drugs, Physostigmine crosses the BBB and can be used to treat central anticholinergic syndrome/atropine toxicity.
In these cases, a laryngneal tracheal anesthetic (LTA, usually 4% Lidocaine) is administered directly on the vocal cords to relax the vocal cords and allow the endotracheal tube to enter.
Succinylcholine resembles two adjoined Acetylcholine molecules. It causes persistent depolarization of muscles by attaching to ACh receptors on the motor end plate.
Competitive antagonism of post-synaptic acetylcholine receptors.