Neuromuscular blockers

Neuromuscular blockers:

Other
Background	Train of four
Pharmacokinetic Profiles
Drugs
Atracurium (Tracrium ® )	Cisatracurium (Nimbex ® )
doxacurium (Nuromax ® )	mivacurium (Mivacron ® )
pancuronium (Pavulon ® )	Rocuronium (Zemuron ® )
Succinylcholine	vecuronium (Norcuron ® )

Background

Overview: Neuromuscular blocking agents are used in the ICU setting for 3 reasons: (1) to eliminate spontaneous breathing and promote mechanical ventilation (eg eliminate urge to fight the vent. (2) Cause a pharmacologic restraint so patients do not harm themselves. (3) To decrease oxygen consumption.

Train of four:

Whenever a paralytic agent is used, the Train of Four is the test used to measure the degree of neuromuscular blockade. A peripheral nerve stimulator is used. Do a baseline measurement before paralytic agent is started to determine current necessary to obtain twitch. 20 mA may be enough for the patient. Complete and document until TOF to 2/4.

Instructions

1. Attach 2 electrodes along the course of the ulnar nerve. (Temporal may be used.)
2. Connect the lead to the peripheral nerve stimulator by inserting the jacks into the Proximal (red) and Distal (black) output jacks. Connect the other end to the patient electrodes.
3. Turn the stimulator on. Select the current necessary (usually 20) for that patient to twitch when the stimuli is applied.
4. Press TOF once. It will deliver a train of four pulses where each is 0.5 seconds apart. Do NOT use the other buttons on the stimulator!
5. Count the number of twitches the patient had out of four (0/4, 1/4, 2/4, 3/4, 4/4.) Adjust the medication as ordered. Goal is 1/4 to 2/4 twitches.

Atracurium (Tracrium ® )

May be given undiluted by IV bolus.
Dosing (Adults): initially 0.4 to 0.5 mg/kg IV bolus, followed by 0.08 to 0.1 mg/kg every 20 to 45 minutes after initial dose.
Continuous infusion: initially 0.4 to 0.5 mg IV bolus, followed by 9 to 10 mcg/kg/min. Maintenance infusion rates of 5 to 9 mcg/kg/min are usually adequate. (Range: 2 to 15 mcg/kg/min).

Toxic metabolite (laudanosine) may accumulate in renal failure.

[Supplied: 50 mg/5 ml ; 100 mg/10ml vial]

Cisatracurium (Nimbex ® )

Dosing (Adults):
Intermittent: initial dose: 0.15 to 0.2 mg/kg IV bolus followed by 0.03 mg/kg IV every 40 to 60 minutes.
Continuous infusion: 0.15 to 0.2 mg/kg IV bolus followed by 1 to 3 mcg/kg/min. The average infusion rate for long term use in the ICU is @ 3 mcg/kg/min (range: 0.5 to 10.2 mcg/kg/min). In some cases, re-administration of the bolus dose may be req'd while titrating. Dosage reductions are not required in renal or hepatic failure.

Drug of choice in the following cases: (1) hemodynamically significant increases in HR (eg >20%) while paralyzed with pancuronium or MAP>110. (2) Concurrent corticosteroid administration (>72hrs) (3) Significant renal dysfunction (CRCL < 30 ml/min) (4)History of asthma or bronchospasm.

doxacurium (Nuromax ® )

Dosing (Adults): (usual)
Anesthesia adjunct: initial, 0.05 mg/kg and 0.08 mg/kg IV to provide neuromuscular block for an average 100 min and 160 min, respectively. Maintenance, 0.005 mg/kg and 0.01 mg/kg IV to provide neuromuscular blockage for an average of 30 min and 45 min, respectively.
Endotracheal intubation: 0.05 mg/kg IV. Endotracheal intubation: (with succinylcholine) initial, 0.025 mg/kg IV.

[ Supplied: 1 mg/ml Solution]

mivacurium (Mivacron ® )

Short-acting arizing neuromuscular blocking agent.
Dosing (Adults)
Endotracheal intubation: 0.15 mg/kg IV bolus. For extended neuromuscular block, IV average infusion rates of 6 to 7 mcg/kg/min are used. Recovery from muscular paralysis occurs within 15 to 30 minutes.

pancuronium (Pavulon ® )

Non-depolarizing skeletal muscle blocker--competes with acetylcholine at the neuromuscular junction.
Dosing (Adults)
Intermittent dosing: 0.1 to 0.2 mg/kg (usually 0.1) every 1 to 3 hours (range: 0.04 to 0.2 mg/kg).
Continuous infusion: Loading dose: 0.04 to 0.10 mg/kg , followed by 1 to 1.7 mcg/kg/min or 0.06 to 0.1 mg/kg/hr

Rocuronium (Zemuron ® )

Dosing (Adults) (usual): Intubation(rapid sequence intubation): initial, 0.6-1.2 mg/kg IV. tracheal intubation: initial, 0.6 mg/kg IV. Maintenance, 0.1-0.2 mg/kg IV repeated as needed.
Maintenance (continuous IV infusion): 0.01-0.012 mg/kg/minute.
Skeletal muscle relaxation: initial, 0.6 mg/kg IV. Maintenance: 0.1-0.2 mg/kg IV repeated as needed. Alternatively: maintenance (continuous IV infusion): 0.01-0.012 mg/kg/minute

Succinylcholine

Depolarizing skeletal muscle blocker. Indications: procedures of short duration such as endotracheal intubation.
Dosing (Adults):
Intermittent: 0.6 mg/kg (0.3 to 1.1) over 10-30 seconds, up to 150mg total dose. Maintenance: 0.04 to 0.07 mg/kg every 5-10 minutes as needed.
Continuous infusion: 2.5 mg/min (0.5 to 10 mg/min).
D Dilute to 1-2 mg/ml.

vecuronium (Norcuron ® )

Dosing (Adults)
Intermittent dosing: initially 0.08 to 0.1 mg/kg IBW IV bolus. (Higher initial doses-up to 0.3 mg/kg-may be used for rapid onset. Maintenance: 0.01 to 0.015 mg/kg every 25 to 45 minutes as needed.

Continuous infusion: initial IV bolus (0.08 to 0.3 mg/kg), followed by (after 20-40min), 1 mcg/kg/min infusion (usual range: 0.8 to 1.2 mcg/kg/min).

Dosage reductions are not req'd in renal failure.

Pharmacokinetic Profiles

Neuromuscular Blocking Agents
Agent	Onset of action	Duration of action	ED_{90-95* (mg/kg)}
Short Acting
Mivacurium (Mivacron)	2.5 min	15 - 20 min	0.07
Rapacuronium (Raplon)	Mean: 90 seconds (35 - 219 sec)	Mean: 15 min (6 - 30 min)	1.03
Rocuronium (Zemeron)	1 - 3 min	31 min (15 - 85 min)	0.3
Succinylcholine	30 - 60 seconds	5 - 8 min	0.3
Intermediate acting
Atracurium (Tracrium)	2.5 - 5 min	20 - 45 min	0.2
Cisatracurium (Nimbex)	2 - 3 min	30 - 40 min	0.05
Pancuronium (Pavulon)	2 - 3 min	60 - 90 min	0.06
Vecuronium (Norcuron)	2 - 3 min	25 - 40 min	0.05
Long Acting
Doxacurium (Nuromax)	6 min (2.5 - 13)	100 min (39 - 232)	0.025
Pipecuronium (Arduan)	2.5 - 5 min	75 min (35 - 175)	0.07
Tubocurarine	3 - 5 min	70 - 90 min	0.05

ED_{90-95 =
Dose required to produce 90-95% suppression of muscle response}

Disclaimer

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David F. McAuley, Pharm.D., R.Ph. GlobalRPh Inc.

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